AU2023214349A1

AU2023214349A1 - CD19 compositions and methods for immunotherapy

Info

Publication number: AU2023214349A1
Application number: AU2023214349A
Authority: AU
Inventors: Vijaya BALAKRISHNAN; Michael Joseph BRISKIN; Brian DOLINSKI; Kutlu Goksu ELPEK; Tucker EZELL; Scott Francis HELLER; Nicole KOSMIDER; Abhishek KULKARNI; Dan Jun LI; Michelle Lynn OLS; Dexue Sun; Vipin Suri
Original assignee: Obsidian Therapeutics Inc
Current assignee: Obsidian Therapeutics Inc
Priority date: 2017-03-03
Filing date: 2023-08-11
Publication date: 2023-08-31
Also published as: SG10202001869VA; JP2023164900A; JP7341900B2; WO2018161017A1; AU2018227583B2; CN110831961A; EP3589646A1; KR20200010181A; JP2020511529A; AU2018227583A1; EP3589646A4; CA3055202A1; SG11201907922PA; KR102746901B1; CN110831961B

Abstract

The present invention provides biocircuit systems, effector modules and compositions for cancer immunotherapy. Methods for inducing anti-cancer immune responses in a subject are also provided.

Description

CD19 COMPOSITIONS AND METHODS FOR IMMUNOTHERAPY

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to the US Provisional Patent Application No. 62/466,601, filed on March 3, 2017 entitled Compositions and Methods for Immunotherapy and the US Provisional Patent Application No. 62/484,052, filed on April 11, 2017 entitled Anti CD19 compositions and methods for immunotherapy, the contents of each of which are herein incorporated by reference in their entirety. This is a divisional of Australian Patent Application No. 2018227583, the entire contents of which are incorporated herein by reference SEQUENCE LISTING

[0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 2095_1201PCTSL.txt, created on March 2, 2018, which is 2,116,001 bytes in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety. FIELD OF THE INVENTION

[0003] The present invention relates to compositions and methods for immunotherapy. Provided in the present invention include polypeptides of biocircuit systems, effector modules, stimulus response elements (SREs) and immunotherapeutic agents, polynucleotides encoding the same, vectors and cells containing the polypeptides and/or polynucleotides for use in cancer immunotherapy. In one embodiment, the compositions comprise destabilizing domains (DDs) which tune protein stability. BACKGROUND OF THE INVENTION

[0004] Cancer immunotherapy aims to eradicate cancer cells by rejuvenating the tumoricidal functions of tumor-reactive immune cells, predominantly T cells. Strategies of cancer immunotherapy including the recent development of checkpoint blockade, adoptive cell transfer (ACT) and cancer vaccines which can increase the anti-tumor immune effector cells have produced remarkable results in several tumors.

[0005] The impact of host anti-tumor immunity and cancer immunotherapy is impeded by three major hurdles: 1) low number of tumor antigen-specific T cells due to clonal deletion; 2) poor activation of innate immune cells and accumulation of tolerogenic antigen-presenting cells in the tumor microenvironment; and 3) formation of an immunosuppressive tumor microenvironment. Particularly, in solid tumors the therapeutic efficacy of immunotherapeutic regimens remains unsatisfactory due to lack of an effective an anti-tumor response in the immunosuppressive tumor microenvironment. Tumor cells often induce immune tolerance or suppression and such tolerance is acquired because even truly foreign tumor antigens will become tolerated. Such tolerance is also active and dominant because cancer vaccines and adoptive transfer of pre-activated immune effector cells (e.g., T cells), are subject to suppression by inhibitory factors in the tumor microenvironment (TME).

[0006] In addition, administration of engineered T cells could result in on/off target toxicities as well as a cytokine release syndrome (reviewed by Tey Clin. Transl. Immunol., 2014, 3: e17 10.1038).

[0007] Development of a tunable switch that can turn on or off the transgenic immunotherapeutic agent expression is needed in case of adverse events. For example, adoptive cell therapies may have a very long and an indefinite half-life. Since toxicity can be progressive, a safety switch is desired to eliminate the infused cells. Systems and methods that can tune the transgenic protein level and expression window with high flexibility can enhance therapeutic benefit, and reduce potential side effects.

[0008] To develop regulatable therapeutic agents for disease therapy, in particular cancer immunotherapy, the present invention provides biocircuit systems to control the expression of immunotherapeutic agents. The biocircuit system comprises a stimulus and at least one effector module that responds to the stimulus. The effector module may include a stimulus response element (SRE) that binds and is responsive to a stimulus and an immunotherapeutic agent operably linked to the SRE. In one example, a SRE is a destabilizing domain (DD) which is destabilized in the absence of its specific ligand and can be stabilized by binding to its specific ligand. SUMMARY OF THE INVENTION

[0009] The present invention provides compositions and methods for immunotherapy. The compositions relate to tunable systems and agents that induce anti-cancer immune responses in a cell or in a subject. The tunable system and agent may be a biocircuit system comprising at least one effector module that is responsive to at least one stimulus. The biocircuit system may be, but is not limited to, a destabilizing domain (DD) biocircuit system, a dimerization biocircuit system, a receptor biocircuit system, and a cell biocircuit system. These systems are further taught in co owned U.S. Provisional Patent Application No. 62/320,864 filed April 11, 2016, 62/466,596 filed March 3, 2017 and the International Publication W02017/180587 (the contents of each of which are herein incorporated by reference in their entirety).

[0010] In some embodiments, the composition for inducing an immune response may comprise an effector module. In some embodiments, the effector module may comprise a stimulus response element (SRE) operably linked to at least one payload. In one aspect, the payload may be an immunotherapeutic agent.

[0011] In some embodiments, the immunotherapeutic agent maybe selected from, but is not limited to a chimeric antigen receptor (CAR) and an antibody.

[0012] In one aspect, the SRE of the composition may be responsive to or interact with at least one stimulus.

[0013] In some embodiments, the SRE may comprise a destabilizing domain (DD). The DD may be derived from a parent protein or from a mutant protein having one, two, there, or more amino acid mutations compared to the parent protein. In some embodiments, the parent protein may be selected from, but is not limited to, human protein FKBP, comprising the amino acid sequence of SEQ ID NO. 3; human DHFR (hDHFR), comprising the amino acid sequence of SEQ ID NO. 2; E. Coli DHFR, comprising the amino acid sequence of SEQ ID NO. 1; PDE5, comprising the amino acid sequence of SEQ ID NO. 4; PPAR, gamma comprising the amino acid sequence of SEQ ID NO. 5; CA2, comprising the amino acid sequence of SEQ ID NO. 6; or NQO2, comprising the amino acid sequence of SEQ ID NO. 7.

[0014] In one aspect, the parent protein is hDHFR and the DD comprises a mutant protein. The mutant protein may comprise a single mutation and may be selected from, but not limited to hDHFR (117V), hDHFR (F59S), hDHFR (N65D), hDHFR (K81R), hDHFR (A107V), hDHFR (Y1221), hDHFR (N127Y), hDHFR (M1401), hDHFR (K185E), hDHFR (N186D), and hDHFR (M1401), hDHFR (Amino acid 2-187 of WT; N127Y), hDHFR (Amino acid 2-187 of WT; 117V), hDHFR (Amino acid 2-187 of WT; Y1221), and hDHFR (Amino acid 2-187 of WT; KI85E). In some embodiments, the mutant protein may comprise two mutations and may be selected from, but not limited to, hDHFR (C7R, Y163C), hDHFR (A1OV, H88Y), hDHFR (Q36K, Y1221), hDHFR (M53T, R1381), hDHFR (T57A, 172A), hDHFR (E63G, 1176F), hDHFR (G21T, Y1221), hDHFR (L74N, Y1221), hDHFR (V75F, Y1221), hDHFR (L94A, T147A), DHFR (V121A, Y221), hDHFR (Y1221, A125F), hDHFR (H131R, E144G), hDHFR (T137R, F143L), hDHFR (Y178H, E18IG), and hDHFR (Y183H, K185E), hDHFR (E162G, 1176F) hDHFR (Amino acid 2-187 of WT; 117V, Y1221), hDHFR (Amino acid 2-187 of WT; Y1221, M1401), hDHFR (Amino acid 2-187 of WT; N127Y, Y1221), hDHFR (Amino acid 2-187 of WT; E162G, 1176F), and hDHFR (Amino acid 2-187 of WT; H131R, E144G), and hDHFR

(Amino acid 2-187 of WT; Y1221, A125F). In some embodiments, the mutant may comprise three mutations and the mutant may be selected from hDHFR (V9A, S93R, P150L), hDHFR (18V, K133E, Y163C), hDHFR (L23S, V121A, Y157C), hDHFR (K19E, F89L, E181G), hDHFR (Q36F, N65F, Y 1221), hDHFR (G54R, M140V, S168C), hDHFR (V110A, V136M, K177R), hDHFR (Q36F, Y1221, A125F), hDHFR (N49D, F59S, D153G), and hDHFR (G21E, 172V, 1176T), hDHFR (Amino acid 2-187 of WT; Q36F, Y1221, A125F), hDHFR (Amino acid 2-187 of WT; Y1221, H131R, E144G), hDHFR (Amino acid 2-187 of WT; E31D, F32M, VI161), and hDHFR (Amino acid 2-187 of WT; Q36F, N65F, Y1221). In some embodiments, the mutant may comprise four or more mutations and the mutant may be selected from hDHFR (V2A, R33G, Q36R, L100P, K185R), hDHFR (Amino acid 2-187 of WT; D22S, F32M, R33S, Q36S, N65S), hDHFR (117N, L98S, K99R, M112T, E151G, E162G, E172G), hDHFR (G16S, 117V, F89L, D96G, K123E, M140V, D146G, K156R), hDHFR (K81R, K99R, L100P, E102G, N108D, K123R, H128R, D142G, F180L, K185E), hDHFR (R138G, D142G, F143S, K156R, K158E, E162G, V166A, K177E, Y178C, K185E, N186S), hDHFR (N14S, P24S, F35L, M53T, K56E, R92G, S93G, N127S, H128Y, F135L, F143S, L159P, L160P, E173A, F180L), hDHFR (F35L, R37G, N65A, L68S, K69E, R71G, L80P, K99G, GI17D, L132P,1139V, M1401, D142G, D146G, E173G, D187G), hDHFR (L28P, N30H, M38V, V44A, L68S, N73G, R78G, A97T, K99R, A107T, K109R, DII1N, L134P, F135V, T147A, 1152V, K158R, E172G, V182A, E184R), hDHFR (V2A, 117V, N30D, E31G, Q36R, F59S, K69E, 172T, H88Y, F89L, N108D, K109E, V110A, I115V, Y122D, L132P, F135S, M140V, E144G, T147A, Y157C, V170A, K174R, N186S), hDHFR (L100P, E102G, Q103R, P104S, E105G, N108D, VI13A, WI14R, Y122C, M1261, N127R, H128Y, L132P, F135P, 1139T, F148S, F149L, 1152V, D153A, D169G, V170A, 1176A, K177R, V182A, K185R, N186S), and hDHFR (A1OT, Q13R, N14S, N20D, P24S, N30S, M38T, T40A, K47R, N49S, K56R, 6IT, K64R, K69R, 172A, R78G, E82G, F89L, D96G, N108D, M112V, W114R, Y122D, K123E, 1139V, Q141R, D142G, F148L, E151G, E155G, Y157R, Q171R, Y183C, E184G, K185del, D187N).

[0015] In one aspect, the stimulus of the SRE maybe Trimethoprim orMethotrexate.

[0016] In some embodiments, the immunotherapeutic agent of the effector module is a chimeric antigen receptor (CAR). The chimeric antigen may comprise an extracellular target moiety; a transmembrane domain; an intracellular signaling domain; and optionally, one or more co-stimulatory domains.

[0017] In one aspect, the CAR may be selected from, but is not limited to a standard CAR, a split CAR, an off-switch CAR, an on-switch CAR, a first-generation CAR, a second-generation CAR, a third-generation CAR, or a fourth-generation CAR.

[0018] In some embodiments, the extracellular target moiety of the CAR maybe selected from, but is not limited to an Ig NAR, a Fab fragment, a Fab' fragment, a F(ab)'2 fragment, a F(ab)'3 fragment, an Fv, a single chain variable fragment (scFv), a bis-scFv, a (scFv)2, a minibody, a diabody, a triabody, a tetrabody, an intrabody, a disulfide stabilized Fv protein (dsFv), a unibody, a nanobody, and an antigen binding region derived from an antibody that may specifically bind to any of a protein of interest, a ligand, a receptor, a receptor fragment or a peptide aptamer.

[0019] In one aspect, the extracellular target moiety may be an scFv derived from an antibody. In one aspect, the scFv may specifically bind to a CD19 antigen

[0020] In one aspect, the scFv of the CAR maybe a CD19 scFv. In some embodiments, the CD19 scFv may comprise a heavy chain variable region having an amino acid sequence independently selected from the group consisting of SEQ ID NO: 49-80, and a light chain variable region having an amino acid sequence independently selected from the group consisting of any of SEQ ID NOs: 81-122. In some embodiments, the CD19 scFv may comprise an amino acid sequence selected from the group consisting of any of SEQ ID NOs: 123-267 and 624.

[0021] In some embodiments, the intracellular signaling domain of the CAR may be a signaling domain derived from T cell receptor CD3zeta. In some embodiments, the intracellular signaling domain may be selected from a cell surface molecule selected from the group consisting of FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d. In one aspect, the CAR may include a co-stimulatory domain. In some embodiments, the co-stimulatory domain may be selected from the group consisting of 2B4, HVEM, ICOS, LAG3, DAP1O, DAP12, CD27, CD28,4-1BB (CD137), OX40 (CD134), CD30, CD40, ICOS (CD278), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte function-associated antigen-i (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3.

[0022] (b) the co-stimulatory domain is present and is selected from the group consisting of 2B4, HVEM, ICOS, LAG3, DAP1O, DAP12, CD27, CD28,4-1BB (CD137), OX40 (CD134), CD30, CD40, ICOS (CD278), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte function-associated antigen-i (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3.

[0023] In some embodiments, the intracellular signaling domain of the CAR may be a T cell receptor CD3zeta signaling domain, which may comprise the amino acid sequence of SEQ ID NO: 339.

[0024] In some embodiments, T cell receptor CD3zeta signaling domain of the CAR, comprising the amino acid sequence of SEQ ID NO: 626 may further comprise at least one co stimulatory domain. The co-stimulatory domain may comprise an amino acid sequence of SEQ ID NOs: 268-374.

[0025] In one embodiment, the transmembrane domain of the CAR may be derived from a transmembrane region of an alpha, beta or zeta chain of a T-cell receptor. In one aspect, the transmembrane domain may be derived from the CD3 epsilon chain of a T-cell receptor. In one embodiment, the transmembrane domain may be derived from a molecule selected from CD4, CD5, CD8, CD8a, CD9, CD16, CD22, CD33, CD28, CD37, CD45, CD64, CD80, CD86, CD148, DAP 10, EpoRI, GITR, LAG3, ICOS, Her2, OX40 (CD134),4-1BB (CD137), CD152, CD154, PD-1, or CTLA-4. In another embodiment, the transmembrane domain may be derived from an immunoglobulin selected from IgG, IgD, IgG4, and an IgG4 Fc region. In one aspect, the transmembrane domain may comprise an amino acid sequence selected from the group consisting of any of SEQ ID NOs: 375-425 and 897-907.

[0026] In some embodiments, the CAR of the effector module may further comprise a hinge region near the transmembrane domain. In one aspect, the hinge region may comprise an amino acid sequence selected from the group consisting of any of SEQ ID NOs: 426-504.

[0027] In some embodiments, the immunotherapeutic agent may be an antibody that is specifically immunoreactive to an antigen selected from a tumor specific antigen (TSA), a tumor associated antigen (TAA), or an antigenic epitope.

[0028] In one aspect, the antigen may be an antigenic epitope. In some embodiments, the antigenic epitope may be CD19.

[0029] In some embodiments, the antibody may comprise a heavy chain variable region having an amino acid sequence independently selected from the group consisting of any of SEQ ID NOs: 49-80 and a light chain variable region having an amino acid sequence independently selected from the group consisting of any of SEQ ID NOs: 81-122. In one aspect, the antibody may comprise an amino acid sequence selected from the group consisting of any of SEQ ID NOs: 123-267 and 624.

[0030] In one aspect, the first effector module may comprise the amino acid sequence of any of SEQ ID NO: 635-649, 1005-1010, 1015-1018 and 1215-1231.

[0031] In some embodiments, the first SRE of the effector module may stabilize the immunotherapeutic agent by a stabilization ratio of 1 or more, wherein the stabilization ratio may comprise the ratio of expression, function or level of the immunotherapeutic agent in the presence of the stimulus to the expression, function or level of the immunotherapeutic agent in the absence of the stimulus.

[0032] In some embodiments, the SRE may destabilize the immunotherapeutic agent by a destabilization ratio between 0, and 0.09, wherein the destabilization ratio may comprise the ratio of expression, function or level of the immunotherapeutic agent in the absence of the stimulus specific to the SRE to the expression, function or level of the immunotherapeutic agent that is expressed constitutively, and in the absence of the stimulus specific to the SRE.

[0033] The present invention also provides polynucleotides comprising the compositions of the invention.

[0034] In one aspect, the polynucleotides may be a DNA or RNA molecule. In one aspect, the polynucleotides may comprise spatiotemporally selected codons. In one aspect, the polynucleotides of the invention may be a DNA molecule. In some embodiments, the polynucleotides may be an RNA molecule. In one aspect, the RNA molecule may be a messenger molecule. In some embodiments, the RNA molecule may be chemically modified.

[0035] In some embodiments, the polynucleotides may further comprise, at least one additional feature selected from, but not limited to, a promoter, a linker, a signal peptide, a tag, a cleavage site and a targeting peptide.

[0036] The present invention also provides vectors comprising polynucleotides described herein. In one aspect, the vector may be a viral vector. In some embodiments, the viral vector may be a retroviral vector, a lentiviral vector, a gamma retroviral vector, a recombinant AAV vector, an adeno viral vector, and an oncolytic viral vector.

[0037] The present invention also provides immune cells for adoptive cell transfer (ACT) which may express the compositions of the invention, the polynucleotides described herein. In one aspect, the immune cells may be infected or transfected with the vectors described herein. The immune cells for ACT may be selected from, but not limited to a CD8+ T cell, a CD4+ T cell, a helper T cell, a natural killer (NK) cell, a NKT cell, a cytotoxic T lymphocyte (CTL), a tumor infiltrating lymphocyte (TIL), a memory T cell, a regulatory T (Treg) cell, a cytokine induced killer (CIK) cell, a dendritic cell, a human embryonic stem cell, a mesenchymal stem cell, a hematopoietic stem cell, or a mixture thereof.

[0038] In some embodiments, the immune cells may be autologous, allogeneic, syngeneic, or xenogeneic in relation to a particular individual subject.

[0039] In some embodiments, the immune cell may further express a composition comprising a second effector module, said second effector module comprising a second SRE linked to a second immunotherapeutic agent. In one aspect, the second immunotherapeutic agent may be selected from a cytokine, and a cytokine- cytokine receptor fusion.

[0040] In one aspect, the second immunotherapeutic agent may be a cytokine. In one aspect, the cytokine may be IL12 or IL15.

[0041] In one aspect, the second immunotherapeutic agent may be a cytokine- cytokine receptor fusion polypeptide.

[0042] In some embodiments, the cytokine-cytokine receptor fusion polypeptide may be selected from, but is not limited to a IL12-IL12 receptor fusion polypeptide, a IL15-IL15 receptor fusion polypeptide, and a IL15-IL15 receptor sushi domain fusion polypeptide.

[0043] The present invention provides methods for reducing a tumor volume or burden in a subject comprising contacting the subject with the immune cells of the invention. Also provided herein, is a method for inducing an anti-tumor immune response in a subject, comprising administering the immune cells of the system to the subject.

[0044] The present invention also provides methods for enhancing the expansion and/or survival of immune cells, comprising contacting the immune cells with the compositions of the invention, the polynucleotides of the invention, and/or the vectors of the invention.

[0045] Also provided herein, is a method for inducing an immune response in a subject, administering the compositions of the invention, the polynucleotides of the invention, and/or the immune cells of the invention to the subject.

[0046] The present invention also provides a method of identifying a domain of a CD19 antigen which will not bind the FMC63 antibody (FMC63-distinct CD19 binding domain). The method may comprise (a) preparing a composition comprising a CD19 antigen, (b) contacting the composition in (a) with saturating levels of FMC63 antibody, (c) contacting the composition of step (b) with one or more selected members of a library of potential CD19 binders; and (d) identifying a binding domain on the CD19 antigen based on the differential binding of the selected members of the library of CD19 binders compared to the binding of FMC63. In some embodiments, the binding domains of the library may be generated using phage display techniques with the CD19 antigen as the seed sequence. In one aspect, the binding domain may be selected from a Fab fragment, a Fab' fragment, a F(ab)'2 fragment, a F(ab)'3 fragment, Fv, a single chain variable fragment (scFv), a bis-scFv, a (scFv)2, a minibody, a diabody, a triabody, a tetrabody, a disulfide stabilized Fv protein (dsFv), a unibody, a nanobody, or an antigen binding region of an antibody, and an antibody fragment. In one aspect, the CD19 antigen may be selected from a whole or a portion of a human CD19 antigen, and a whole or a portion of a Rhesus CD19 antigen.

[0047] The present invention also provides chimeric antigen receptors that may comprise the FMC63-distinct CD19 binding domain obtained according to the methods described herein. Also, provided herein is a stimulus response element (SRE) operably linked to the chimeric antigen receptors that include the FMC63-distinct CD19 binding domain.

[0048] In some embodiments, the effector module comprises a stimulus response element (SRE) and at least one payload comprising a protein of interest (POI).

[0049] In some embodiments, the SRE may be a destabilizing domain (DD). In some examples, the DD is a mutant domain derived from a protein such as FKBP (FK506 binding protein), E. coli DHFR (Dihydrofolate reductase) (ecDHFR), human DHFR (hDHFR), or any protein of interest. In this context, the biocircuit system is a DD biocircuit system.

[0050] The payload may be any immunotherapeutic agent used for cancer immunotherapy such as a chimeric agent receptor (CAR) such as CD19 CAR that targets any molecule of tumor cells, an antibody, an antigen binding domain or combination of antigen binding domains, a cytokine such as IL12, IL15 or IL15/IL15Ra fusion, or any agent that can induce an immune response. The SRE and payload may be operably linked through one or more linkers and the positions of components may vary within the effector module.

[0051] In some embodiments, the effector module may further comprise of one or more additional features such as linker sequences (with specific sequences and lengths), cleavage sites, regulatory elements (that regulate expression of the protein of interest such as microRNA targeting sites), signal sequences that lead the effector module to a specific cellular or subcellular location, penetrating sequences, or tags and biomarkers for tracking the effector module.

[0052] In some embodiments, the DD may stabilize the immunotherapeutic agent with a stabilization ratio of at least one in the presence of the stimulus. According to the present invention, the DD may destabilize the immunotherapeutic agent in the absence of ligand with a destabilization ratio between 0, and 0.99.

[0053] The invention provides isolated biocircuit polypeptides, effector modules, stimulus response elements (SREs) and payloads, as well as polynucleotides encoding any of the foregoing; vectors comprising polynucleotides of the invention; and cells expressing polypeptides, polynucleotides and vectors of the invention. The polypeptides, polynucleotides, viral vectors and cells are useful for inducing anti-tumor immune responses in a subject.

[0054] In some embodiments, the vector of the invention is a viral vector. The viral vector may include, but is not limited to a retroviral vector, an adenoviral vector, an adeno-associated viral vector, or a lentiviral vector.

[0055] In some embodiments, the vector of the invention may be a non-viral vector, such as a nanoparticles and liposomes.

[0056] The present invention also provides immune cells engineered to include one or more polypeptides, polynucleotides, or vectors of the present invention. The cells may be immune effector cells, including T cells such as cytotoxic T cells, helper T cells, memory T cells, regulatory T cells, natural killer (NK) cells, NK T cells, cytokine-induced killer (CIK) cells, cytotoxic T lymphocytes (CTLs), and tumor infiltrating lymphocytes (TILs). The engineered cell may be used for adoptive cell transfer for treating a disease (e.g., a cancer).

[0057] The present invention also provides methods for inducing immune responses in a subject using the compositions of the invention. Also provided are methods for reducing a tumor burden in a subject using the compositions of the invention.

[0058] Also provided herein are methods for identifying FMC63-distinct binding domains and using CD19 antigens in which the FMC63 binding epitope is masked or absent. In some embodiments, the FMC63 binding domain may be included in the payloads and effector modules of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] Figure 1 shows an overview diagram of a biocircuit system of the invention. The biocircuit comprises a stimulus and at least one effector module responsive to a stimulus, where the response to the stimulus produces a signal or outcome. The effector module comprises at least one stimulus response element (SRE) and one payload.

[0060] Figure 2 shows representative effector modules carrying one payload. The signal sequence (SS), SRE and payload may be located or positioned in various arrangements without

(A to F) or with (G to Z, and AA to DD) a cleavage site. An optional linker may be inserted between each component of the effector module.

[0061] Figure 3 shows representative effector modules carrying two payloads without a cleavage site. The two payloads may be either directly linked to each other or separated.

[0062] Figure 4 shows representative effector modules carrying two payloads with a cleavage site. In one embodiment, an SS is positioned at the N-terminus of the construct, while other components: SRE, two payloads and the cleavage site may be located at different positions (A to L). In another embodiment, the cleavage site is positioned at the N-terminus of the construct (M to X). An optional linker may be inserted between each component of the effector module.

[0063] Figure 5 shows effector modules of the invention carrying two payloads, where an SRE is positioned at the N-terminus of the construct (A to L), while SS, two payloads and the cleavage site can be in any configuration. An optional linker may be inserted between each component of the effector module.

[0064] Figure 6 shows effector modules of the invention carrying two payloads, where either the two payloads (A to F) or one of the two payloads (G to X) is positioned at the N-terminus of the construct (A to L), while SS, SRE and the cleavage site can be in any configuration. An optional linker may be inserted between each component of the effector module.

[0065] Figure 7 depicts representative configurations of the stimulus and effector module within a biocircuit system. A trans-membrane effector module is activated either by a free stimulus (Figure 7A) or a membrane bound stimulus (Figure 7B) which binds to SRE. The response to the stimulus causes the cleavage of the intracellular signal/payload, which activates down-stream effector/payload.

[0066] Figure 8 depicts a dual stimulus-dual presenter biocircuit system, where two bound stimuli (A and B) from two different presenters (e.g., different cells) bind to two different effector modules in a single receiver (e.g., another single cell) simultaneously and create a dual signal to downstream payloads.

[0067] Figure 9 depicts a dual stimulus-single presenter biocircuit system, where two bound stimuli (A and B) from the same presenter (e.g., a single cell) bind to two different effector modules in another single cell simultaneously and create a dual-signal.

[0068] Figure 10 depicts a single-stimulus-bridged receiver biocircuit system. In this configuration, a bound stimulus (A) binds to an effector module in the bridge cell and creates a signal to activate a payload which is a stimulus (B) for another effector module in the final receiver (e.g., another cell).

[0069] Figure 11 depicts a single stimulus-single receiver biocircuit system, wherein the single receiver contains the two effector modules which are sequentially activated by a single stimulus.

[0070] Figure 12 depicts a biocircuit system which requires a dual activation. In this embodiment, one stimulus must bind the transmembrane effector module first to prime the receiver cell being activated by the other stimulus. The receiver only activates when it senses both stimuli (B).

[0071] Figure 13 depicts a standard effector module of a chimeric antigen receptor (CAR) system which comprises an antigen binding domain as an SRE, and signaling domain(s) as payload.

[0072] Figure 14 depicts the structure design of a regulatable CAR system, where the trans membrane effector modules comprise antigen binding domains sensing an antigen and a first switch domain and the intracellular module comprises a second switch domain and signaling domains. A stimulus (e.g., a dimerization small molecule) can dimerize the first and second switch domains and assemble an activated CAR system.

[0073] Figure 15 shows schematic representation of CAR systems having one (A) or two (B and C) SREs incorporated into the effector module.

[0074] Figure 16 depicts a split CAR design to control T cell activation by a dual stimulus (e.g., an antigen and small molecule). Figure 16A shows normal T cell activation which entails a dual activation of TCR and co-stimulatory receptor. The regular CAR design (Figure 16B) combines the antigen recognition domain with TCR signaling motif and co-stimulatory motif in a single molecule. The split CAR system separates the components of the regular CAR into two separate effector modules which can be reassembled when a heterodimerizing small molecule (stimulus) is present.

[0075] Figure 17 depicts the positive and negative regulation of CAR engineered T cell activation. The absence or presence of a second stimulus can negatively (A) or positively (B) control T cell activation.

[0076] Figure 18 shows schematic representation of gated activation of CAR engineered T cells. If a normal cell that has no stimulus (e.g., an antigen) (Figure 18A) or an antigen that cannot bind to the trans-membrane effector module (Figure18B), or only an antigen that activates the trans-membrane effector module and primes the receiver T cell to express the second effector

(Fig 18C), the receiver T cell remains inactive. When both stimuli (e.g. two antigens) that bind the trans-membrane effector module and the primed effector, are present on the presenter cell (e.g. a cancer cell), the T cell is activated (Figure 18D).

[0077] Figure 19A is a bar graph depicting IL12 levels in the various dilutions of media derived from cells expressing DD-IL12. Figure 19B is a bar graph depicting the Shield-i dose responsive induction of DD- IL12. Figure 19C depicts plasma IL12 levels in mice implanted with SKOV3 cells. Figure 19D depicts plasma IL12 levels in mice in response to different Shield-i dosing regimens.

[0078] Figure 20A is a western blot of IL15 protein levels in 293 cells. Figure 20B and 20C are histograms depicting surface expression of IL15 and IL15Ra. Figure 20 D is a western blot of IL15 and hDHFR in HCT116 cells.

[0079] Figure 21A and Figure 21B are western blots of depicting the protein levels of CD3 Zeta of the DD- CD19 CAR construct and actin. Figure 21C shows the expression of CD19 chimeric antigen receptors in a western blot using 4-1BB antibody. Figure 21D is a bar graph depicting the surface expression of CD19 CAR.

[0080] Figure 22 denotes the frequency of IFNgamma positive T cells.

[0081] Figure 23A depicts IFN gamma production in T cells. Figure 23B depicts T cell expansion with IL15/IL15Ra treatment. Figure 23C is a dot plot depicting percentage human cells after in vivo cell transfer. Figure 23D is scatter plot depicting CD4+/CD8+ T cells.

[0082] Figure 24A depicts T cell subpopulations expressing CD19 CAR. Figure 28B depicts cell death caused by CD19 CAR expressing T cells.

[0083] Figure 25A is a bar graph depicting IL15Ra positive cells with 24 hour TMP treatment. Figure 25B is a bar graph depicting IL15Ra positive cells with 48 hour TMP treatment. Figure 25C is a bar graph depicting IL15Ra positive cells in response to varying concentrations of TMP.

[0084] Figure 26 is a western blot of IL15Ra protein levels in HCT116 cells.

[0085] Figure 27A represents percentage of human T cells blood with respect to mouse T cells. Figure 27B represents the number of T cells in blood. Figure 27C represents ratio of CD4 to CD8 cells in the blood. Figure 27D represents the percentage of IL15Ra positive CD4 and CD8 T cells in the blood.

[0086] Figure 28A depicts the expansion of T cells in response to cytokine treatment. Figure 28B, Figure 28C and Figure 28D depict the frequency of IFN gamma positive cells with IL12 treatment.

[0087] Figure 29 is a bar graph representing the effect of promoters on transgene expression.

[0088] Figure 30A shows the expression of CD19 in parental K562 cells and K562-CD19 cells. Figure 30B shows the proliferation of K562 cells cocultured with T cells expressing DD regulated CAR constructs, in the presence or absence of ligand. Figure 30C shows the area of target cells killed by T cells expressing DD regulated CAR constructs, in the presence of ligand.

[0089] Figure 31A shows IFNgamma concentration. Figure 31B shows IL2 concentration.

[0090] Figure 32A provides the final IL12 concentration for each of the four groups tested. Figure 32B shows that IL12 is detectable in kidney and Figure 32C shows that IL12 is detectable in tumor.

[0091] Figure 33A shows the regulation of IL12 over 24 hours. Figure 33B shows the regulation in the plasma and Figure 33C shows the detection of flexi-IL12 in the kidneys.

[0092] Figure 34A shows that restimulation increased the expression of IL12. Figure 34B and Figure 34C show that ligand increased production of IL12.

[0093] Figure 35A shows the concentration-dependent induction of IL12 secretion of IL12 secretion from primary human T cells. Figure 35B shows the time course induction of IL12 secretion from primary human T cells.

[0094] Figure 36A shows the dose response of Aquashield-Induced DD-IL12 regulation in vivo. Figure 36B shows that plasma levels of IL12 remain high in animals transplanted with constitutive IL12 transduced T cells.

[0095] Figure 37A and 37B show the expression of IL12 in vivo over 7 days. Figure 37C and 37D show the expression of IL12 in vivo over 11 days. Figure 37E shows the Geometric MFI (GeoMFI) of Granzyme B (GrB) after 7 days in CD8+ T cells. Figure 37F shows the GeoMFI of Perforin at day 7 in CD8+ T cells.

[0096] Figure 38A shows the regulation of IL12 with PGK and EFl a promoters and FKBP domains. Figure 38B shows the relative expression of IL12.

[0097] Figure 39 depicts the kinetics of IL15Ra surface expression on CD4 T cells after TMP treatment.

[0098] Figure 40 represents a western blot of IL15-IL15Ra protein in HCT116 tumors from mice treated with TMP for 17 days in xenograft assays.

[0099] Figure 41 is a graph of the results of the MSD assay of IL15 protein levels in HEK293 cells.

[00100] Figure 42A provides FACS plots showing the expression of membrane bound IL15 after a dose response study of TMP. Figure 42B is two graphs showing the dose and time of exposure of TMP in vitro influences membrane bound IL15 expression.

[00101] Figures 43A- 43C show the regulation of membrane bound IL15 using IL15 (Figure 43A), IL15Ra (Figure 43B), or IL15/ILI5Ra double ++ staining (Figure 43C). Figure 43D shows FACS plots of the expression of IL15. Figure 43E is a graph of the regulation of IL15 in blood and Figure 43F is a graph of the plasma TMP levels.

[00102] Figure 44 represents the regulation of membrane bound IL15 with PO or IP dosing of TMP. DETAILED DESCRIPTION OF THE INVENTION

[00103] The details of one or more embodiments of the invention are set forth in the accompanying description below. Although any materials and methods similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred materials and methods are now described. Other features, objects and advantages of the invention will be apparent from the description. In the description, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the case of conflict, the present description will control. I. INTRODUCTION

[00104] Cancer immunotherapy aims' at the induction or restoration of the reactivity of the immune system towards cancer. Significant advances in immunotherapy research have led to the development of various strategies which may broadly be classified into active immunotherapy and passive immunotherapy. In general, these strategies may be utilized to directly kill cancer cells or to counter the immunosuppressive tumor microenvironment. Active immunotherapy aims at induction of an endogenous, long-lasting tumor-antigen specific immune response. The response can further be enhanced by non-specific stimulation of immune response modifiers such as cytokines. In contrast, passive immunotherapy includes approaches where immune effector molecules such as tumor-antigen specific cytotoxic T cells or antibodies are administered to the host. This approach is short lived and requires multiple applications.

[00105] Despite significant advances, the efficacy of current immunotherapy strategies is limited by associated toxicities. These are often related to the narrow therapeutic window associated with immunotherapy, which in part, emerges from the need to push therapy dose to the edge of potentially fatal toxicity to get a clinically meaningful treatment effect. Further, dose expands in vivo since adoptively transferred immune cells continue to proliferate within the patient, often unpredictably.

[00106] A major risk involved in immunotherapy is the on-target but off tumor side effects resulting from T-cell activation in response to normal tissue expression of the tumor associated antigen (TAA). Clinical trials utilizing T cells expressing T-cell receptor against specific TAA reported skin rash, colitis and hearing loss in response to immunotherapy.

[00107] Immunotherapy may also produce on target, on-tumor toxicities that emerge when tumor cells are killed in response to the immunotherapy. The adverse effects include tumor lysis syndrome, cytokine release syndrome and the related macrophage activation syndrome. Importantly, these adverse effects may occur during the destruction of tumors, and thus even a successful on-tumor immunotherapy might result in toxicity. Approaches to regulatably control immunotherapy are thus highly desirable since they have the potential to reduce toxicity and maximize efficacy.

[00108] The present invention provides systems, compositions, immunotherapeutic agents and methods for cancer immunotherapy. These compositions provide tunable regulation of gene expression and function in immunotherapy. The present invention also provides biocircuit systems, effector modules, stimulus response elements (SREs) and payloads, as well as polynucleotides encoding any of the foregoing. In one aspect, the systems, compositions, immunotherapeutic agents and other components of the invention can be controlled by a separately added stimulus, which provides a significant flexibility to regulate cancer immunotherapy. Further, the systems, compositions and the methods of the present invention may also be combined with therapeutic agents such as chemotherapeutic agents, small molecules, gene therapy, and antibodies.

[00109] The tunable nature of the systems and compositions of the invention has the potential to improve the potency and duration of the efficacy of immunotherapies. Reversibly silencing the biological activity of adoptively transferred cells using compositions of the present invention allows maximizing the potential of cell therapy without irretrievably killing and terminating the therapy.

[00110] The present invention provides methods for fine tuning of immunotherapy after administration to patients. This in turn improves the safety and efficacy of immunotherapy and increases the subject population that may benefit from immunotherapy. II. COMPOSITIONS OF THE INVENTION

[00111] According to the present invention, biocircuit systems are provided which comprise, at their core, at least one effector module system. Such effector module systems comprise at least one effector module having associated, or integral therewith, one or more stimulus response elements (SREs). The overall architecture of a biocircuit system of the invention is illustrated in Figure 1. In general, a stimulus response element (SRE) may be operably linked to a payload construct which could be any protein of interest (POI) (e.g., an immunotherapeutic agent), to form an effector module. The SRE, when activated by a particular stimulus, e.g., a small molecule, can produce a signal or outcome, to regulate transcription and/or protein levels of the linked payload either up or down by perpetuating a stabilizing signal or destabilizing signal, or any other types of regulation. A much-detailed description of a biocircuit system can be found in U.S. Provisional Patent Application No. 62/320,864 filed April 11, 2016 or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587 (the contents of each of which are herein incorporated by reference in their entirety). In accordance with the present invention, biocircuit systems, effector modules, SREs and components that tune expression levels and activities of any agents used for immunotherapy are provided.

[00112] As used herein, a "biocircuit" or "biocircuit system" is defined as a circuit within or useful in biologic systems comprising a stimulus and at least one effector module responsive to a stimulus, where the response to the stimulus produces at least one signal or outcome within, between, as an indicator of, or on a biologic system. Biologic systems are generally understood to be any cell, tissue, organ, organ system or organism, whether animal, plant, fungi, bacterial, or viral. It is also understood that biocircuits may be artificial circuits which employ the stimuli or effector modules taught by the present invention and effect signals or outcomes in acellular environments such as with diagnostic, reporter systems, devices, assays or kits. The artificial circuits may be associated with one or more electronic, magnetic, or radioactive components or parts.

[00113] In accordance with the present invention, abiocircuit system maybe a destabilizing domain (DD) biocircuit system, a dimerization biocircuit system, a receptor biocircuit system, and a cell biocircuit system. Any of these systems may act as a signal to any other of these biocircuit systems. Effector modules and SREs for immunotherapy

[00114] In accordance with the present invention, biocircuit systems, effector modules, SREs, and components that tune expression levels and activities of any agents used for immunotherapy are provided. As non-limiting examples, an immunotherapeutic agent may be an antibody and fragments and variants thereof, a cancer specific T cell receptor (TCR) and variants thereof, an anti-tumor specific chimeric antigen receptor (CAR), a chimeric switch receptor, an inhibitor of a co-inhibitory receptor or ligand, an agonist of a co-stimulatory receptor and ligand, a cytokine, chemokine, a cytokine receptor, a chemokine receptor, a soluble growth factor, a metabolic factor, a suicide gene, a homing receptor, or any agent that induces an immune response in a cell and a subject.

[00115] As stated, the biocircuits of the invention include at least one effector module as a component of an effector module system. As used herein, an "effector module" is a single or multi-component construct or complex comprising at least (a) one or more stimulus response elements (i.e. proteins of interest (POIs). As used herein a "stimulus response element (SRE)" is a component of an effector module which is joined, attached, linked to or associated with one or more payloads of the effector module and in some instances, is responsible for the responsive nature of the effector module to one or more stimuli. As used herein, the "responsive" nature of an SRE to a stimulus may be characterized by a covalent or non-covalent interaction, a direct or indirect association or a structural or chemical reaction to the stimulus. Further, the response of any SRE to a stimulus may be a matter of degree or kind. The response may be a partial response. The response may be a reversible response. The response may ultimately lead to a regulated signal or output. Such output signal may be of a relative nature to the stimulus, e.g., producing a modulatory effect of between 1% and 100% or a factored increase or decrease such as 2-fold, 3-fold, 4-fold, 5-fold, 10-fold or more.

[00116] In some embodiments, the present invention provides methods for modulating protein expression, function or level. In some aspects, the modulation of protein expression, function or level refers to modulation of expression, function or level by at least about 20%, such as by at least about 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95% and 100%, or at least 20-30%, 20 40%, 20-50%, 20-60%, 20-70%, 20-80%, 20-90%, 20-95%, 20-100%, 30-40%, 30-50%, 30 60%, 30-70%, 30-80%, 30-90%, 30-95%, 30-100%, 40-50%, 40-60%, 40-70%, 40-80%, 40

90%, 40-95%, 40-100%, 50-60%, 50-70%, 50-80%, 50-90%, 50-95%, 50-100%, 60-70%, 60 80%, 60-90%, 60-95%, 60-100%, 70-80%, 70-90%, 70-95%, 70-100%, 80-90%, 80-95%, 80 100%,90-95%,90-100% or 95-100%.

[00117] In some embodiments, the present invention provides methods for modulating protein, expression, function or level by measuring the stabilization ratio and destabilization ratio. As used herein, the stabilization ratio may be defined as the ratio of expression, function or level of a protein of interest in response to the stimulus to the expression, function or level of the protein of interest in the absence of the stimulus specific to the SRE. In some aspects, the stabilization ratio is at least 1, such as by at least 1-10, 1-20, 1 -30, 1-40, 1-50, 1- 60, 1-70, 1-80, 1- 90, 1-100, 20-30,20-40,20-50,20-60,20-70,20-80,20-90,20-95,20-100,30-40,30-50,30-60,30-70,30 80,30-90,30-95,30-100,40-50,40-60,40-70,40-80,40-90,40-95,40-100,50-60,50-70,50 80,50-90,50-95,50-100,60-70,60-80,60-90,60-95,60-100,70-80,70-90,70-95,70-100,80 90, 80-95, 80-100, 90-95, 90-100 or 95-100. As used herein, the destabilization ratio may be defined as the ratio of expression, function or level of a protein of interest in the absence of the stimulus specific to the effector module to the expression, function or level of the protein of interest, that is expressed constitutively and in the absence of the stimulus specific to the SRE. As used herein "constitutively" refers to the expression, function or level of a protein of interest that is not linked to an SRE, and is therefore expressed both in the presence and absence of the stimulus. In some aspects, the destabilization ratio is at least 0, such as by at least 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or at least, 0-0.1, 0-0.2, 0 -0.3, 0-0.4, 0-0.5, 0-0.6, 0-0.7, 0-0.8, 0-0.9, 0.1-0.2, 0.1 -0.3, 0.1-0.4, 0.1-0.5, 0.1-0.6, 0.1-0.7, 0.1-0.8, 0.1-0.9, 0.2 -0.3, 0.2-0.4, 0.2-0.5, 0.2 0.6, 0.2-0.7, 0.2-0.8, 0.2-0.9, 0.3-0.4, 0.3-0.5, 0.3-0.6, 0.3-0.7, 0.3-0.8, 0.3-0.9, 0.4-0.5, 0.4-0.6, 0.4-0.7, 0.4-0.8, 0.4-0.9, 0.5-0.6, 0.5-0.7, 0.5-0.8, 0.5-0.9, 0.6-0.7, 0.6-0.8, 0.6-0.9,0.7-0.8, 0.7 0.9 or 0.8-0.9.

[00118] In some embodiments, the stimulus of the present invention maybe ultrasound stimulation. In some embodiments, the SREs of the present invention may derived from mechanosensitive proteins. In one embodiment, the SRE of the present invention may be the mechanically sensitive ion channel, Piezo1.

[00119] Expression of the payload of interest in such instances is tuned by providing focused ultrasound stimulation. In other embodiments, the SREs of the present invention may be derived from calcium biosensors, and the stimulus of the present invention may calcium. The calcium may be generated by the ultrasound induced mechanical stimulation of mechanosensitive ion channels. The ultrasound activation of the ion channel causes a calcium influx thereby generating the stimulus. In one embodiment, the mechanosensitive ion channel is Piezo 1. Mechanosensors may be advantageous to use since they provide spatial control to a specific location in the body.

[00120] The SRE of the effector module may be selected from, but is not limited to, a peptide, peptide complex, peptide-protein complex, protein, fusion protein, protein complex, protein protein complex. The SRE may comprise one or more regions derived from any natural or mutated protein, or antibody. In this aspect, the SRE is an element, when responding to a stimulus, can tune intracellular localization, intramolecular activation, and/or degradation of payloads.

[00121] In some embodiments, effector modules of the present invention may comprise additional features that facilitate the expression and regulation of the effector module, such as one or more signal sequences (SSs), one or more cleavage and/or processing sites, one or more targeting and/or penetrating peptides, one or more tags, and/or one or more linkers. Additionally, effector modules of the present invention may further comprise other regulatory moieties such as inducible promoters, enhancer sequences, microRNA sites, and/or microRNA targeting sites. Each aspect or tuned modality may bring to the effector module or biocircuit a differentially tuned feature. For example, an SRE may represent a destabilizing domain, while mutations in the protein payload may alter its cleavage sites or dimerization properties or half-life and the inclusion of one or more microRNA or microRNA binding site may impart cellular detargeting or trafficking features. Consequently, the present invention embraces biocircuits which are multifactorial in their tenability. Such biocircuits may be engineered to contain one, two, three, four or more tuned features.

[00122] In some embodiments, effector modules of the present invention may include one or more degrons to tune expression. As used herein, a "degron" refers to a minimal sequence within a protein that is sufficient for the recognition and the degradation by the proteolytic system. An important property of degrons is that they are transferrable, that is, appending a degron to a sequence confers degradation upon the sequence. In some embodiments, the degron may be appended to the destabilizing domains, the payload or both. Incorporation of the degron within the effector module of the invention, confers additional protein instabilityto the effector module and may be used to minimize basal expression. In some embodiments, the degron may be an N degron, a phospho degron, a heat inducible degron, a photosensitive degron, an oxygen dependent degron. As a non-limiting example, the degron may be an Ornithine decarboxylase degron as described by Takeuchi et al. (Takeuchi J et al. (2008). Biochem J. 2008 Mar 1;410(2):401-7; the contents of which are incorporated by reference in their entirety). Other examples of degrons useful in the present invention include degrons described in International patent publication Nos. W02017004022, W02016210343, and W02011062962; the contents of each of which are incorporated by reference in their entirety.

[00123] As shown in Figure 2, representative effector module embodiments comprising one payload, i.e. one immunotherapeutic agent are illustrated. Each components of the effector module may be located or positioned in various arrangements without (A to F) or with (G to Z, and AA to DD) a cleavage site. An optional linker may be inserted between each component of the effector module.

[00124] Figures 3 to 6 illustrate representative effector module embodiments comprising two payloads, i.e. two immunotherapeutic agents. In some aspects, more than two immunotherapeutic agents (payloads) may be included in the effector module under the regulation of the same SRE (e.g., the same DD). The two or more agents may be either directly linked to each other or separated (Figure 3). The SRE may be positioned at the N-terminus of the construct, or the C-terminus of the construct, or in the internal location.

[00125] In some aspects, the two or more immunotherapeutic agents may be the same type such as two antibodies, or different types such as a CAR construct and a cytokine IL12. Biocircuits and components utilizing such effector molecules are given in Figures 7-12.

[00126] In some embodiments, biocircuits of the invention may be modified to reduce their immunogenicity. Immunogenicity is the result of a complex series of responses to a substance that is perceived as foreign and may include the production of neutralizing and non-neutralizing antibodies, formation of immune complexes, complement activation, mast cell activation, inflammation, hypersensitivity responses, and anaphylaxis. Several factors can contribute to protein immunogenicity, including, but not limited to protein sequence, route and frequency of administration and patient population. In a preferred embodiment, protein engineering may be used to reduce the immunogenicity of the compositions of the invention. In some embodiments, modifications to reduce immunogenicity may include modifications that reduce binding of the processed peptides derived from the parent sequence to MHC proteins. For example, amino acid modifications may be engineered such that there are no or a minimal of number of immune epitopes that are predicted to bind with high affinity, to any prevalent MHC alleles. Several methods of identifying MHC binding epitopes of known protein sequences are known in the art and may be used to score epitopes in the compositions of the present invention. Such methods are disclosed in US Patent Publication No. US 20020119492, US20040230380, and US 20060148009; the contents of each of which are incorporated by reference in their entirety.

[00127] Epitope identification and subsequent sequence modification may be applied to reduce immunogenicity. The identification of immunogenic epitopes may be achieved either physically or computationally. Physical methods of epitope identification may include, for example, mass spectrometry and tissue culture/cellular techniques. Computational approaches that utilize information obtained on antigen processing, loading and display, structural and/or proteomic data toward identifying non-self-peptides that may result from antigen processing, and that are likely to have good binding characteristics in the groove of the MHC may also be utilized. One or more mutations may be introduced into the biocircuits of the invention directing the expression of the protein, to maintain its functionality while simultaneously rendering the identified epitope less or non-immunogenic.

[00128] In some embodiments, protein modifications engineered into the structure of the compositions of the invention to interfere with antigen processing and peptide loading such as glycosylation and PEGylation, may also be useful in the present invention. Compositions of the invention may also be engineered to include non-classical amino acid sidechains to design less immunogenic compositions. Any of the methods discussed in International Patent Publication No. W02005051975 for reducing immunogenicity may be useful in the present invention (the contents of which are incorporated by reference in their entirety).

[00129] In one embodiment, patients may also be stratified according to the immunogenic peptides presented by their immune cells and may be utilized as a parameter to determine suitable patient cohorts that may therapeutically benefit for the compositions of the invention.

[00130] In some embodiments, reduced immunogenicity may be achieved by limiting immuproteasome processing. The proteasome is an important cellular protease that is found in two forms: the constitutive proteasome, which is expressed in all cell types and which contains active e.g. catalytic subunits and the immunoproteasome that is expressed in cell of the hematopoietic lineage, and which contains different active subunits termed low molecular weight proteins (LMP) namely LMP-2, LMP- 7 and LMP-10. Immunoproteasomes exhibit altered peptidase activities and cleavage site preferences that result in more efficient liberation of many MHC class I epitopes. A well described function of the immunoproteasome is to generate peptides with hydrophobic C terminus that can be processed to fit in the groove of MHC class I molecules. Deol P et al. have shown that immunoproteasomes may lead to a frequent cleavage of specific peptide bonds and thereby to a faster appearance of a certain peptide on the surface of the antigen presenting cells; and enhanced peptide quantities (Deol P et al. (2007) JImmunol 178 (12) 7557-7562; the contents of which are incorporated herein reference in its entirety). This study indicates that reduced immunoproteasome processing may be accompanied by reduced immunogenicity. In some embodiments, immunogenicity of the compositions of the invention may be reduced by modifying the sequence encoding the compositions of the invention to prevent immunoproteasome processing. Biocircuits of the present invention may also be combined with immunoproteasome-selective inhibitors to achieve the same effects. Examples of inhibitors useful in the present invention include UK-101 (Bli selective compound), IPSI-001, ONX 0914 (PR-957), and PR-924 (IPSI).

1. Destabilizing domains (DDs)

[00131] In some embodiments, biocircuit systems, effector modules, and compositions of the present invention relate to post-translational regulation of protein (payload) function anti-tumor immune responses of immunotherapeutic agents. In one embodiment, the SRE is a stabilizing/destabilizing domain (DD). The presence, absence or an amount of a small molecule ligand that binds to or interacts with the DD, can, upon such binding or interaction modulate the stability of the payload(s) and consequently the function of the payload. Depending on the degree of binding and/or interaction the altered function of the payload may vary, hence providing a "tuning" of the payload function.

[00132] In some embodiments, destabilizing domains described herein or known in the art may be used as SREs in the biocircuit systems of the present invention in association with any of the immunotherapeutic agents (payloads) taught herein. Destabilizing domains (DDs) are small protein domains that can be appended to a target protein of interest. DDs render the attached protein of interest unstable in the absence of a DD-binding ligand such that the protein is rapidly degraded by the ubiquitin-proteasome system of the cell (Stankunas, K., et al., Mol. Cell, 2003, 12: 1615-1624; Banaszynski, et al., Cell; 2006, 126(5): 995-1004; reviewed in Banaszynski, L.A., and Wandless, T.J. Chem. Biol.; 2006, 13:11-21 and Rakhit R et al., Chem Biol. 2014; 21(9):1238-1252). However, when a specific small molecule ligand binds its intended DD as a ligand binding partner, the instability is reversed and protein function is restored. The conditional nature of DD stability allows a rapid and non-perturbing switch from stable protein to unstable substrate for degradation. Moreover, its dependency on the concentration of its ligand further provides tunable control of degradation rates.

[00133] In some embodiments, the desired characteristics of the DDs may include, but are not limited to, low protein levels in the absence of a ligand of the DD (i.e. low basal stability), large dynamic range, robust and predictable dose-response behavior, and rapid kinetics of degradation. DDs that bind to a desired ligand but not endogenous molecules may be preferred.

[00134] Several protein domains with destabilizing properties and their paired small molecules have been identified and used to control protein expression, including FKBP/shield-1 system (Egeler et al., JBiol. Chem. 2011, 286(36): 32328-31336; the contents of which are incorporated herein by reference in their entirety), ecDHFR and its ligand trimethoprim (TMP); estrogen receptor domains which can be regulated by several estrogen receptor antagonists (Miyazaki et al., JAm Chem. Soc., 2012, 134(9): 3942-3945; the contents of which are incorporated by reference herein in their entirety); and fluorescent destabilizing domain (FDD) derived from bilirubin-inducible fluorescent protein, UnaG and its cognate ligand bilirubin (BR) (Navarro et al., A CS Chem Biol., 2016, June 6; the contents of which are incorporated herein by reference in their entirety).

[00135] Known DDs also include those described in U.S. Pat. NO. 8,173,792 and U.S. Pat. NO. 8,530,636, the contents of which are each incorporated herein by reference in their entirety.

[00136] In some embodiments, the DDs of the present invention may be derived from some known sequences that have been approved to be capable of post-translational regulation of proteins. For example, Xiong et al., have demonstrated that the non-catalytic N-terminal domain (54-residues) of ACS7 (1-aminocyclopropane-1-carboxylate synthase) in Arabidopsis, when fused to the p-glucuronidase (GUS) reporter, can significantly decrease the accumulation of the GUS fusion protein (Xiong et al., J Exp. Bot., 2014, 65(15): 4397-4408). Xiong et al. further demonstrated that both exogenous 1-aminocyclopropane-1-carboxylic acid (ACC) treatment and salt can rescue the levels of accumulation of the ACS N-terminal and GUS fusion protein. The ACS N-terminus mediates the regulation of ACS7 stability through the ubiquitin-26S proteasome pathway.

[00137] Another non-limiting example is the stability control region (SCR, residues 97-118) of Tropomyosin (Tm), which controls protein stability. A destabilizing mutation L1I1A, and a stabilizing mutation A109L dramatically affect Tropomyosin protein dynamics (Kirwan and Hodges, J Biol. Chem., 2014, 289: 4356-4366). Such sequences can be screened for ligands that bind them and regulate their stability. The identified sequence and ligand pairs may be used as components of the present invention.

[001381 In some embodiments, the DDs of the present invention may be developed from known proteins. Regions or portions or domains of wild type proteins may be utilized as SREs/DDs in whole or in part. They may be combined or rearranged to create new peptides, proteins, regions or domains of which any may be used as SREs/DDs or the starting point for the design of further SREs and/or DDs.

[00139] Ligands such as small molecules that are well known to bind candidate proteins can be tested for their regulation in protein responses. The small molecules may be clinically approved to be safe and have appropriate pharmaceutical kinetics and distribution. In some embodiments, the stimulus is a ligand of a destabilizing domain (DD), for example, a small molecule that binds a destabilizing domain and stabilizes the POI fused to the destabilizing domain. In some embodiments, ligands, DDs and SREs of the present invention, include without limitation, any of those taught in Tables 2-4 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety. Some examples of the proteins that may be used to develop DDs and their ligands are listed in Table 1. Table 1: Proteins and their binding ligands Protein Protein Sequence Protein Ligands SEQ ID NO.: E. coli MISLIAALAVDRVIGMENAMPWNLPADL 1 Methotrexate Dihydrofolate AWFKRNTLNKPVIMGRHTWESIGRPLPGR (MTX) reductase KNIILSSQPGTDDRVTWVKSVDEAIAACG Trimethoprim (ecDHFR) DVPEIMVIGGGRVYEQFLPKAQKLYLTHI (TMP) (Uniprot ID: DAEVEGDTHFPDYEPDDWESVFSEFHDA POABQ4) DAQNSHSYCFEILERR Human MVGSLNCIVAVSQNMGIGKNGDLPWPPL 2 Methotrexate Dihydrofolate RNEFRYFQRMTTTSSVEGKQNLVIMGKK (MTX) reductase TWFSIPEKNRPLKGRINLVLSRELKEPPQG Trimethoprim (hDHFR) AHFLSRSLDDALKLTEQPELANKVDMVW (TMP) (Uniprot ID: IVGGSSVYKEAMNHPGHLKLFVTRIMQDF P00374) ESDTFFPEIDLEKYKLLPEYPGVLSDVQEE KGIKYKFEVYEKND FK506 binding GVQVETISPGDGRTFPKRGQTCVVHYTG 3 Shield-1 protein (FKBP) MLEDGKKFDSSRDRNKPFKFMLGKQEVI (Uniprot ID: RGWEEGVAQMSVGQRAKLTISPDYAYGA P62942) TGHPGIIPPHATLVFDVELLKLE Phosphodiesteras MEETRELQSLAAAVVPSAQTLKITDFSFS 4 Sildenafil; e 5 (PDE5), DFELSDLETALCTIRMFTDLNLVQNFQMK Vardenafil; ligand binding HEVLCRWILSVKKNYRKNVAYHNWRHA Tadalafil domain (Uniprot FNTAQCMFAALKAGKIQNKLTDLEILALL ID: Uniprot ID IAALSHDLDHRGVNNSYIQRSEHPLAQLY 076074) CHSIMEHHHFDQCLMILNSPGNQILSGLSI EEYKTTLKIIKQAILATDLALYIKRRGEFFE LIRKNQFNLEDPHQKELFLAMLMTACDLS AITKPWPIQQRIAELVATEFFDQGDRERKE LNIEPTDLMNREKKNKIPSMQVGFIDAICL QLYEALTHVSEDCFPLLDGCRKNRQKWQ ALAEQQ PPAR gamma, SVEAVQEITEYAKSIPGFVNLDLNDQVTL 5 Posiglitazone ligand binding LKYGVHEIIYTMLASLMNKDGVLISEGQG Pioglitazone domain (Uniprot FMTREFLKSLRKPFGDFMEPKFEFAVKFN ID: P37231; ALELDDSDLAIFIAVIILSGDRPGLLNVKPI amino acids 317- EDIQDNLLQALELQLKLNHPESSQLFAKL 505) LQKMTDLRQIVTEHVQLLQVIKKTETDMS LHPLLQEIYKDLY Carbonic MSHHWGYGKHNGPEHWHKDFPIAKGER 6 Celecoxib anhydrase 11 QSPVDIDTHTAKYDPSLKPLSVSYDQATS Acetazolamide (CA2) (Uniprot LRILNNGHAFNVEFDDSQDKAVLKGGPL ID: P00918) DGTYRLIQFHFHWGSLDGQGSEHTVDKK KYAAELHLVHWNTKYGDFGKAVQQPDG LAVLGIFLKVGSAKPGLQKVVDVLDSIKT KGKSADFTNFDPRGLLPESLDYWTYPGSL TTPPLLECVTWIVLKEPISVSSEQVLKFRK LNFNGEGEPEELMVDNWRPAQPLKNRQI KASFK NRH: Quinone MAGKKVLIVYAHQEPKSFNGSLKNVAVD 7 Imatinib oxidoreductase 2 ELSRQGCTVTVSDLYAMNLEPRATDKDIT Melatonin (NQO2) (Uniprot GTLSNPEVFNYGVETHEAYKQRSLASDIT ID: P16083) DEQKKVREADLVIFQFPLYWFSVPAILKG WMDRVLCQGFAFDIPGFYDSGLLQGKLA LLSVTTGGTAEMYTKTGVNGDSRYFLWP LQHGTLHFCGFKVLAPQISFAPEIASEEER KGMVAAWSQRLQTIWKEEPIPCTAHWHF GQ

[00140] In some embodiments, DDs of the invention may be FKBP DD or ecDHFR DDs such as those listed in Table 2. The position of the mutated amino acid listed in Table 2 is relative to the ecDHFR (Uniprot ID: POABQ4) of SEQ ID NO. 1 for ecDHFR DDs and relative to FKBP (Uniprot ID: P62942) of SEQ ID NO. 3 for FKBP DDs. Table 2: ecDHFR DDs and FKBP DDs DD Sequence SEQ ID NO: ecDHFR MISLIAALAVDYVIGMENAMPWNLPADLAWFKRNTL 8 (R12Y, NKPVIMGRHTWESIGRPLPGRKNIILSSQPGTDDRVTW Y1001) VKSVDEAIAACGDVPEIMVIGGGRVIEQFLPKAQKLY LTHIDAEVEGDTHFPDYEPDDWESVFSEFHDADAQNS HSYCFEILERR ecDHFR ISLIAALAVDYVIGMENAMPWNLPADLAWFKRNTLN 9 (Amino acid KPVIMGRHTWESIGRPLPGRKNIILSSQPGTDDRVTWV 2-159 of WT) KSVDEAIAACGDVPEIMVIGGGRVIEQFLPKAQKLYLT

(R12Y, HIDAEVEGDTHFPDYEPDDWESVFSEFHDADAQNSHS Y1001) YCFEILERR

ecDHFR ISLIAALAVDHVIGMENAMPWNLPADLAWFKRNTLN 10 (Amino acid KPVIMGRHTWESIGRPLPGRKNIILSSQPGTDDRVTWV 2-159 of WT) KSVDEAIAACGDVPEIMVIGGGRVYEQFLPKAQKLYL (R12H, THIDAEVEGDTHFPDYKPDDWESVFSEFHDADAQNSH E129K) SYCFEILERR FKBP (F36V, GVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKV 11 L106P) DSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRA KLTISPDYAYGATGHPGIIPPHATLVFDVELLKPE FKBP (E31G, GVQVETISPGDGRTFPKRGQTCVVHYTGMLGDGKKV 12 F36V, R71G, DSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQGA K105E) KLTISPDYAYGATGHPGIIPPHATLVFDVELLELE

[00141] Inventors of the present invention have tested and identified several candidate human proteins that may be used to develop destabilizing domains. As show in Table 2, these candidates

include human DHFR (hDHFR), PDE5 (phosphodiesterase 5), PPAR gamma (peroxisome proliferator-activated receptor gamma), CA2 (Carbonic anhydrase II) and NQO2 (NRH: Quinone oxidoreductase 2). Candidate destabilizing domain sequence identified from protein domains of these proteins (as a template) may be mutated to generate libraries of mutants based on the template candidate domain sequence. Mutagenesis strategies used to generate DD libraries may include site-directed mutagenesis e.g. by using structure guided information; or random

mutagenesis e.g. using error-prone PCR, or a combination of both. In some embodiments, destabilizing domains identified using random mutagenesis may be used to identify structural

properties of the candidate DDs that may be required for destabilization, which may then be used to further generate libraries of mutations using site directed mutagenesis.

[00142] In some embodiments, novel DDs derived from E.coli DHFR (ecDHFR) may comprise amino acids 2-159 of the wild type ecDHFR sequence. This may be referred to as an MIdel mutation.

[00143] In some embodiments, novel DDs derived from ecDHFR may comprise amino acids 2 159 of the wild type ecDHFR sequence (also referred to as an MIdel mutation), and may include one, two, three, four, five or more mutations including, but not limited to, MIdel, R12Y, R12H, Y100I, and E129K.

[00144] In some embodiments, novel DDs derived from FKBP may comprise amino acids 2 107 of the wild type FKBP sequence. This may be referred to as an M del mutation.

[00145] In some embodiments, novel DDs derived from FKBP may comprise amino acids 2 107 of the wild type FBKP sequence (also referred to as an Ml del mutation), and may include one, two, three, four, five or more mutations including, but not limited to, Mldel, E31G, F36V, R71G, K105E, and L106P.

[00146] In some embodiments, DD mutant libraries may be screened for mutations with altered, preferably higher binding affinity to the ligand, as compared to the wild type protein. DD libraries may also be screened using two or more ligands and DD mutations that are stabilized by some ligands but not others may be preferentially selected. DD mutations that bind preferentially to the ligand compared to a naturally occurring protein may also be selected. Such methods may be used to optimize ligand selection and ligand binding affinity of the DD. Additionally, such approaches can be used to minimize deleterious effects caused by off-target ligand binding.

[00147] In some embodiments, suitable DDs may be identified by screening mutant libraries using barcodes. Such methods may be used to detect, identify and quantify individual mutant clones within the heterogeneous mutant library. Each DD mutant within the library may have distinct barcode sequences (with respect to each other). In other instances, the polynucleotides can also have different barcode sequences with respect to 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleic acid bases. Each DD mutant within the library may also comprise a plurality of barcode sequences. When used in plurality may be used such that each barcode is unique to any other barcode. Alternatively, each barcode used may not be unique, but the combination of barcodes used may create a unique sequence that can be individually tracked. The barcode sequence may be placed upstream of the SRE, downstream of the SRE, or in some instances may be placed within the SRE. DD mutants may be identified by barcodes using sequencing approaches such as Sanger sequencing, and next generation sequencing, but also by polymerase chain reaction and quantitative polymerase chain reaction. In some embodiments, polymerase chain reaction primers that amplify a different size product for each barcode may be used to identify each barcode on an agarose gel. In other instances, each barcode may have a unique quantitative polymerase chain reaction probe sequence that enables targeted amplification of each barcode.

[00148] In some embodiments, DDs of the invention may be derived from human dihydrofolate reductase (hDHFR). hDHFR is a small (18 kDa) enzyme that catalyzes the reduction of dihydrofolate and plays a vital role in variety of anabolic pathway. Dihydrofolate reductase (DHFR) is an essential enzyme that converts 7,8-dihydrofolate (DHF) to 5,6,7,8, tetrahydrofolate (THF) in the presence of nicotinamide adenine dihydrogen phosphate (NADPH). Anti-folate drugs such as methotrexate (MTX), a structural analogue of folic acid, which bind to DHFR more strongly than the natural substrate DHF, interferes with folate metabolism, mainly by inhibition of dihydrofolate reductase, resulting in the suppression of purine and pyrimidine precursor synthesis. Other inhibitors of hDHFR such as folate, TQD, Trimethoprim (TMP), epigallocatechin gallate (EGCG) and ECG (epicatechin gallate) can also bind to hDHFR mutants and regulates its stability.In one aspect of the invention, the DDs of the invention may be hDHFR mutants including the single mutation hDHFR (Y1221), hDHFR (K81R), hDHFR (F59S), hDHFR (117V), hDHFR (N65D), hDHFR (A107V), hDHFR (N127Y), hDHFR (K185E), hDHFR (N186D), and hDHFR (M1401); double mutations: hDHFR (M53T, R1381), hDHFR (V75F, Y1221), hDHFR (A125F, Y1221), hDHFR (L74N, Y1221), hDHFR (L94A, T147A), hDHFR (G21T, Y1221), hDHFR (V121A, Y1221), hDHFR (Q36K, Y1221), hDHFR (C7R, Y163C),hDHFR (Y178H, E18IG), hDHFR (A1OV, H88Y), hDHFR (T137R, F143L), hDHFR (E63G, 1176F), hDHFR (T57A, 172A), hDHFR (H131R, E144G), and hDHFR (Y183H, K185E); and triple mutations: hDHFR (Q36F, N65F, Y1221), hDHFR (G21E,172V, 1176T), hDHFR (18V, K133E, Y163C), hDHFR (V9A, S93R, P150L), hDHFR (K19E, F89L, E181G), hDHFR (G54R, M140V, S168C), hDHFR (L23S, V121A, Y157C), hDHFR (V110A, V136M, K177R), and hDHFR (N49D, F59S, D153G).

[00149] In one embodiment, the stimulus is a small molecule that binds to a SRE to post translationally regulate protein levels. In one aspect, DHFR ligands: trimethoprim (TMP) and methotrexate (MTX) are used to stabilize hDHFR mutants. The hDHFR based destabilizing domains are listed in Table 3. The position of the mutated amino acid listed in Table 3 is relative to the human DHFR (Uniprot ID: P00374) of SEQ ID NO. 2 for human DHFR. In Table 3, "del" means that the mutation is the deletion of the amino acid at that position relative to the wild type sequence.

Table 3: Human DHFR mutants and novel destabilizing domains

Mutants Amino acid Sequence SEQ ID NO hDHFR (117V) MVGSLNCIVAVSQNMGVGKNGDLPWPPLRNEFRYFQR 13 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (F59S) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 14 MTTTSSVEGKQNLVIMGKKTWSSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (N65D) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 15 MTTTSSVEGKQNLVIMGKKTWFSIPEKDRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW

IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR(K81R) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 16 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELREPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (A107V) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 17 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELVNKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Y1221) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 18 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (N127Y) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 19 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMYHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (M1401) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 20 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIIQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (K185E) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 21 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEEND hDHFR(Ni86D) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 22 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKDD hDHFR (C7R, Y163C) MVGSLNRIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 23 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPECPGVLSDVQEEKGIKYKFEVYEKND hDHFR (AlOV, H88Y) MVGSLNCIVVVSQNMGIGKNGDLPWPPLRNEFRYFQR 24 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAYFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Q36K, Y1221) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFKR 25 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (M53T, R1381) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 26 MTTTSSVEGKQNLVITGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTIIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (T57A, 172A) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 27 MTTTSSVEGKQNLVIMGKKAWFSIPEKNRPLKGRANLV LSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMV WIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEI DLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (E63G, 1176F) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 28 MTTTSSVEGKQNLVIMGKKTWFSIPGKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGFKYKFEVYEKND hDHFR (G21T, Y1221) MVGSLNCIVAVSQNMGIGKNTDLPWPPLRNEFRYFQRM 29 TTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLS RELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (L74N, Y1221) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 30 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINNVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (V75F, Y1221) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 31 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLFL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (L94A, T147A) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 32 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSADDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDAFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND DHFR (V121A, Y221) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 33 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSAIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Y1221, A125F) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 34 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVIKEFMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (H131R, E144G) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 35 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGRLKLFVTRIMQDFGSDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (T137R, F143L) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 36 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVRRIMQDLESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Y178H, E181G) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 37 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKHKFGVYEKND hDHFR (Y183H, K185E) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 38 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL

SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVHEEND hDHFR (V9A, S93R, P150L) MVGSLNCIAAVSQNMGIGKNGDLPWPPLRNEFRYFQR 39 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRRLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFLEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (18V, K133E, Y163C) MVGSLNCVVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 40 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLELFVTRIMQDFESDTFFPEID LEKYKLLPECPGVLSDVQEEKGIKYKFEVYEKND hDHFR (L23S, V121A, Y157C) MVGSLNCIVAVSQNMGIGKNGDSPWPPLRNEFRYFQR 41 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSAYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKCKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (K9E, F89L, E181G) MVGSLNCIVAVSQNMGIGENGDLPWPPLRNEFRYFQRM 42 TTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLS RELKEPPQGAHLLSRSLDDALKLTEQPELANKVDMVWI VGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFGVYEKND hDHFR (Q36F, N65F, Y1221) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFFRM 43 TTTSSVEGKQNLVIMGKKTWFSIPEKFRPLKGRINLVLS RELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (G54R, M140V, S168C) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 44 MTTTSSVEGKQNLVIMRKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIVQDFESDTFFPEIDL EKYKLLPEYPGVLCDVQEEKGIKYKFEVYEKND hDHFR (V110A, V136M, K177R) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 45 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKADMVW IVGGSSVYKEAMNHPGHLKLFMTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIRYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFFRMT 46 Q36F, Y1221, A125F) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEFMNHPGHLKLFVTRIMQDFESDTFFPEIDLEK YKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (N49D, F59S, D153G) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 47 MTTTSSVEGKQDLVIMGKKTWSSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIG LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (G21E, 172V, 1176T) MVGSLNCIVAVSQNMGIGKNEDLPWPPLRNEFRYFQRM 48 TTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRVNLVLS RELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGTKYKFEVYEKND hDHFR loopO, E102G, Q103R, MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 871 P104S, E105G, N108D, Vi13A, MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL W114R, Y122C, M1261, N127R, SRELKEPPQGAHFLSRSLDDALKPTGRSGLADKVDMAR H128Y, L132P, F135P, 1139T,

F148S, F149L, 1152V, D153A, IVGGSSVCKEAIRYPGHPKLPVTRTMQDFESDTSLPEVA D169G, V170A, 1176A, K177R, LEKYKLLPEYPGVLSGAQEEKGARYKFEAYERSD V182A, K185R, N186S) hDHFR (V2A, R33G, Q36R, MAGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFGYFRR 872 L100P, K185R) MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKPTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVYERND hDHFR (G16S, 117V, F89L, MVGSLNCIVAVSQNMSVGKNGDLPWPPLRNEFRYFQR 873 D96G, K123E, M140V, D146G, MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL K156R) SRELKEPPQGAHLLSRSLDGALKLTEQPELANKVDMVW IVGGSSVYEEAMNHPGHLKLFVTRIVQDFESGTFFPEIDL ERYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (F35L, R37G, N65A, MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYLQG 874 L68S, K69E, R71G, L80P, K99G, MTTTSSVEGKQNLVIMGKKTWFSIPEKARPSEGGINLVL G117D, L132P, 1139V, M1401, SREPKEPPQGAHFLSRSLDDALGLTEQPELANKVDMVW D142G, D146G, E173G, D187G) IVDGSSVYKEAMNHPGHPKLFVTRVIQGFESGTFFPEIDL EKYKLLPEYPGVLSDVQEGKGIKYKFEVYEKNG hDHFR (117N, L98S, K99R, MVGSLNCIVAVSQNMGNGKNGDLPWPPLRNEFRYFQR 875 M112T, E151G, E162G, E172G) MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDASRLTEQPELANKVDTVWI VGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPGIDL EKYKLLPGYPGVLSDVQGEKGIKYKFEVYEKND hDHFR (Ri38G, D142G, F143S, MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 876 K156R, K158E, E162G, V166A, MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL K177E, Y178C, K185E, N186S) SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTGIMQGSESDTFFPEID LERYELLPGYPGALSDVQEEKGIECKFEVYEESD hDHFR (K81R, K99R, L100P, MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 877 E102G, N108D, K123R, H128R, MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL D142G, F180L, K185E) SRELREPPQGAHFLSRSLDDALRPTGQPELADKVDMVW IVGGSSVYREAMNRPGHLKLFVTRIMQGFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKLEVYEEND hDHFR (N14S, P24S, F35L, MVGSLNCIVAVSQSMGIGKNGDLSWPPLRNEFRYLQRM 878 M53T, K56E, R92G, S93G, TTTSSVEGKQNLVITGKETWFSIPEKNRPLKGRINLVLSR N127S, H128Y, F135L, F143S, ELKEPPQGAHFLSGGLDDALKLTEQPELANKVDMVWIV L159P,L160P,E173A,F180L) GGSSVYKEAMSYPGHLKLLVTRIMQDSESDTFFPEIDLE KYKPPPEYPGVLSDVQEAKGIKYKLEVYEKND hDHFR (V2A, 117V, N30D, MAGSLNCIVAVSQNMGVGKNGDLPWPPLRDGFRYFRR 879 E31G, Q36R, F59S, K69E, 172T, MTTTSSVEGKQNLVIMGKKTWSSIPEKNRPLEGRTNLV H88Y, F89L, N108D, K109E, LSRELKEPPQGAYLLSRSLDDALKLTEQPELADEAGMV Vi10A, 1115V, Y122D, L132P, WVVGGSSVDKEAMNHPGHPKLSVTRIVQDFGSDAFFPE F135S, M140V, E144G, T147A, IDLEKCKLLPEYPGVLSDAQEERGIKYKFEVYEKSD Y157C, V170A, K174R, N186S) hDHFR (L28P, N30H, M38V, MVGSLNCIVAVSQNMGIGKNGDLPWPPPRHEFRYFQRV 880 V44A, L68S, N73G, R78G, A97T, TTTSSAEGKQNLVIMGKKTWFSIPEKNRPSKGRIGLVLS K99R,A107T,K109R,D111N, GELKEPPQGAHFLSRSLDDTLRLTEQPELTNRVNMVWI L134P, F135V, T147A, 1152V, VGGSSVYKEAMNHPGHLRPVVTRIMQDFESDAFFPEVD K158R, E172G, V182A, E184R) LEKYRLLPEYPGVLSDVQGEKGIKYKFEAYRKND hDHFR (A10T, Q13R, N14S, MVGSLNCIVTVSRSMGIGKDGDLSWPPLRSEFRYFQRTT 881 N20D, P24S, N30S, M38T, T40A, ATSSVEGRQSLVIMGKRTWFSTPERNRPLRGRANLVLS K47R, N49S, K56R, 161T, K64R, GELKGPPQGAHLLSRSLDGALKLTEQPELADKVDVVRI K69R, 172A, R78G, E82G, F89L, VGGSSVDEEAMNHPGHLKLFVTRVMRGFESDTLFPGID D96G, N108D, M112V, Wi14R, LGKRKLLPEYPGVLSDVREEKGIKYKLEVCGNN Y122D, K123E, 1139V, Q141R, D142G,F148L,E151G,E155G,

Y157R, Q171R, Y183C, E184G, K185del, D187N) hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGVGKNGDLPWPPLRNEFRYFQRM 882 117V, Y1221) TTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLS RELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 883 Y1221, M1401) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEAMNHPGHLKLFVTRI1QDFESDTFFPEIDLEK YKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 884 N127Y, Y1221) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEAMYHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 885 Y1221, H131R, E144G) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEAMNHPGRLKLFVTRIMQDFGSDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGSLPWPPLRNEMSYFSRMT 886 D22S, F32M, R33S, Q36S, N65S) TTSSVEGKQNLVIMGKKTWFSIPEKSRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNDMRYFQRM 887 E31D, F32M, Vi161) TTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLS RELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW11 GGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 888 E162G, 1176F) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPGYPGVLSDVQEEKGFKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 889 K185E) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEEND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 890 Y1221, A125F) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEFMNHPGHLKLFVTRIMQDFESDTFFPEIDLEK YKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFFRMT 891 Q36F, N65F, Y1221) TTSSVEGKQNLVIMGKKTWFSIPEKFRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 892 N127Y) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMYHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 893 H131R, E144G) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMNHPGRLKLFVTRIMQDFGSDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGVGKNGDLPWPPLRNEFRYFQRM 894 117V) TTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLS RELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDL EKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMT 895 Y1221) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (E162G, 1176F) MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 896 MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVL SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVW IVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPGYPGVLSDVQEEKGFKYKFEVYEKND hDHFR (Amino acid 2-187 of WT; VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFKRMT 981 Q36K, Y1221) TTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSR ELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLE KYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND

[00150] In some embodiments, DD mutations that do not inhibit ligand binding may be preferentially selected. In some embodiments, ligand binding may be improved by mutation of residues in DHFR. Amino acid positions selected for mutation include aspartic acid at position 22 of SEQ ID NO. 2, glutamic acid at position 31 of SEQ ID NO. 2; phenyl alanine at position 32 of SEQ ID NO. 2; arginine at position 33 of SEQ ID NO. 2; glutamine at position 36 of SEQ ID NO. 2; asparagine at position 65 of SEQ ID NO. 2; and valine at position 115 of SEQ ID NO. 2. In some embodiments, one or more of the following mutations may be utilized in the DDs of the present invention to improve TMP binding, including but not limited to, D22S, E3ID, F32M, R33S, Q36S, N65S, and VI161. The position of the mutated amino acids is relative to the wildtype human DHFR (Uniprot ID: P00374) of SEQ ID NO. 2.

[00151] In some embodiments, novel DDs derived from human DHFR may include one, two, three, four, five or more mutations including, but not limited to, MIdel, V2A, C7R,18V, V9A, A10T, A1OV, Q13R, N14S, G16S, 117N, 117V, K19E, N20D, G21T, G21E, D22S, L23S, P24S, L28P, N30D, N30H, N30S, E31G, E31D, F32M, R33G, R33S, F35L, Q36R, Q36S, Q36K, Q36F, R37G, M38V, M38T, T40A, V44A, K47R, N49S, N49D, M53T, G54R, K56E, K56R, T57A, F59S, 6IT, K64R, N65A, N65S, N65D, N65F, L68S, K69E, K69R, R71G,172T, 172A, 172V, N73G, L74N, V75F, R78G, L80P, K81R, E82G, H88Y, F89L, R92G, S93G, S93R, L94A, D96G, A97T, L98S, K99G, K99R, LIOOP, E102G, Q103R, P104S, E105G, A107T, A107V,

N108D, K109E, K109R, V11OA, DI1N, M112T, M112V, V113A, W114R, 1115V, 1115L, VI161, GI17D, V121A, Y122C, Y22D, Y1221, K123R, K123E, A125F, M1261, N127R, N127S, N127Y, H128R, H128Y, H131R, L132P, K133E, L134P, F135P, F135L, F135S, F135V, V136M, T137R, R138G, R1381,1139T, 1139V, M1401, M140V, Q141R, D142G, F143S, F143L, E144G, D146G, T147A, F148S, F148L, F149L, P150L, E151G, 1152V, D153A, D153G, E155G, K156R, Y157R, Y157C, K158E, K158R, L159P, L160P, E162G, Y163C, V166A, S168C, D169G, V170A, Q171R, E172G, E173G, E173A, K174R, 1176A, 1176F, 1176T, K177E, K177R, Y178C, Y178H, F180L, E181G, V182A, Y183C, Y183H, E184R, E184G, K185R, K185del, K185E, N186S, N186D, D187G, and D187N.

[00152] In some embodiments, novel DDs derived from human DHFR may comprise amino acids 2-187 of the wild type human DHFR sequence. This may be referred to as an MIdel mutation.

[00153] In some embodiments, novel DDs derived from human DHFR may comprise amino acids 2-187 of the wild type human DHFR sequence (also referred to as an Mldel mutation), and may include one, two, three, four, five or more mutations including, but not limited to, MIdel, V2A, C7R, 18V, V9A, A1OT, A1OV, Q13R, N14S, G16S, 117N, 117V, K19E, N20D, G21T, G21E, D22S, L23S, P24S, L28P, N3OD, N30H, N30S, E31G, E31D, F32M, R33G, R33S, F35L, Q36R, Q36S, Q36K, Q36F, R37G, M38V, M38T, T40A, V44A, K47R, N49S, N49D, M53T, G54R, K56E, K56R, T57A, F59S, 6IT, K64R, N65A, N65S, N65D, N65F, L68S, K69E, K69R, R71G, 172T, 172A, 172V, N73G, L74N, V75F, R78G, L80P, K81R, E82G, H88Y, F89L, R92G, S93G, S93R, L94A, D96G, A97T, L98S, K99G, K99R, L100P, E102G, Q103R, P104S, E105G, A107T, A107V, N108D, K109E, K109R, V110A, D111N, M112T, M112V, VI13A, WI14R, I115V, I115L, V161, G17D, V121A, Y22C, Y22D, Y1221, K123R, K123E, A125F, M1261, N127R, N127S, N127Y, H128R, H128Y, H131R, L132P, K133E, L134P, F135P, F135L, F135S, F135V, V136M, T137R, R138G, R1381,1139T, 1139V, M1401, M140V, Q141R, D142G, F143S, F143L, E144G, D146G, T147A, F148S, F148L, F149L, P150L, E151G, 1152V, D153A, D153G, E155G, K156R, Y157R, Y157C, K158E, K158R, L159P, L160P, E162G, Y163C, V166A, S168C, D169G, V170A, Q171R, E172G, E173G, E173A, K174R,1176A, 1176F, 1176T, K177E, K177R, Y178C, Y178H, F180L, E181G, V182A, Y183C, Y183H, E184R, E184G, K185R, K185del, K185E, N186S, N186D, D187G, and D187N.

2. Payloads: Immunotherapeutic agents

[00154] In some embodiments, payloads of the present invention maybe immunotherapeutic agents that induce immune responses in an organism. The immunotherapeutic agent may be, but is not limited to, an antibody and fragments and variants thereof, a chimeric antigen receptor (CAR), a chimeric switch receptor, a cytokine, chemokine, a cytokine receptor, a chemokine receptor, a cytokine-cytokine receptor fusion polypeptide, or any agent that induces an immune response. In one embodiment, the immunotherapeutic agent induces an anti-cancer immune response in a cell, or in a subject. Antibodies

[00155] In some embodiments, antibodies, fragments and variants thereof are payloads of the present invention.

[00156] In some embodiments, antibodies of the present invention, include without limitation, any of those taught in Table 5 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety. Antibody fragments and variants

[00157] In some embodiments, antibody fragments and variants may comprise antigen binding regions from intact antibodies. Examples of antibody fragments and variants may include, but are not limited to Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules such as single chain variable fragment (scFv); and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen binding fragments, called "Fab" fragments, each with a single antigen-binding site. Also produced is a residual "Fc" fragment, whose name reflects its ability to crystallize readily. Pepsin treatment yields an F(ab')2 fragment that has two antigen-binding sites and is still capable of cross-linking with the antigen. Pharmaceutical compositions, biocircuits, biocircuit components, effector modules including their SREs or payloads of the present invention may comprise one or more of these fragments.

[00158] For the purposes herein, an "antibody" may comprise a heavy and light variable domain as well as an Fc region. As used herein, the term "native antibody" usually refers to a heterotetrameric glycoprotein of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Genes encoding antibody heavy and light chains are known and segments making up each have been well characterized and described (Matsuda et al., The JournalofExperimentalMedicine. 1998, 188(11): 2151-62 and Li et al., Blood, 2004, 103(12): 4602-4609; the content of each of which are herein incorporated by reference in their entirety). Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain.

[00159] As used herein, the term "variable domain" refers to specific antibody domains found on both the antibody heavy and light chains that differ extensively in sequence among antibodies and are used in the binding and specificity of each particular antibody for its particular antigen. Variable domains comprise hypervariable regions. As used herein, the term "hypervariable region" refers to a region within a variable domain comprising amino acid residues responsible for antigen binding. The amino acids present within the hypervariable regions determine the structure of the complementarity determining regions (CDRs) that become part of the antigen binding site of the antibody. As used herein, the term "CDR" refers to a region of an antibody comprising a structure that is complimentary to its target antigen or epitope. Other portions of the variable domain, not interacting with the antigen, are referred to as framework (FW) regions. The antigen-binding site (also known as the antigen combining site or paratope) comprises the amino acid residues necessary to interact with a particular antigen. The exact residues making up the antigen-binding site are typically elucidated by co-crystallography with bound antigen, however computational assessments based on comparisons with other antibodies can also be used (Strohl, W.R. Therapeutic Antibody Engineering. Woodhead Publishing, Philadelphia PA. 2012. Ch. 3, p47-54, the contents of which are herein incorporated by reference in their entirety). Determining residues that make up CDRs may include the use of numbering schemes including, but not limited to, those taught by Kabat (Wu et al., JEM, 1970, 132(2):211-250 and Johnson et al., Nucleic Acids Res. 2000, 28(1): 214-218, the contents of each of which are herein incorporated by reference in their entirety), Chothia (Chothia and Lesk, J. Mol. Biol. 1987, 196, 901, Chothia et al., Nature, 1989, 342, 877, and Al-Lazikani et al., J Mol. Biol. 1997, 273(4): 927-948, the contents of each of which are herein incorporated by reference in their entirety),

Lefranc (Lefranc et al., Immunome Res. 2005, 1:3) and Honegger (Honegger and Pluckthun, J Mol. Biol. 2001, 309(3): 657-70, the contents of which are herein incorporated by reference in their entirety).

[00160] VH and VL domains have three CDRs each. VL CDRs are referred to herein as CDR LI, CDR-L2 and CDR-L3, in order of occurrence when moving from N- to C- terminus along the variable domain polypeptide. VH CDRs are referred to herein as CDR-H1, CDR-H2 and CDR-H3, in order of occurrence when moving from N- to C- terminus along the variable domain polypeptide. Each of CDRs has favored canonical structures with the exception of the CDR-H3, which comprises amino acid sequences that may be highly variable in sequence and length between antibodies resulting in a variety of three-dimensional structures in antigen-binding domains (Nikoloudis, et al., PeerJ. 2014, 2: e456). In some cases, CDR-H3s may be analyzed among a panel of related antibodies to assess antibody diversity. Various methods of determining CDR sequences are known in the art and may be applied to known antibody sequences (Strohl, W.R. Therapeutic Antibody Engineering. Woodhead Publishing, Philadelphia PA. 2012. Ch. 3, p47-54, the contents of which are herein incorporated by reference in their entirety).

[00161] As used herein, the term "Fv" refers to an antibody fragment comprising the minimum fragment on an antibody needed to form a complete antigen-binding site. These regions consist of a dimer of one heavy chain and one light chain variable domain in tight, non-covalent association. Fv fragments can be generated by proteolytic cleavage, but are largely unstable. Recombinant methods are known in the art for generating stable Fv fragments, typically through insertion of a flexible linker between the light chain variable domain and the heavy chain variable domain (to form a single chain Fv (scFv)) or through the introduction of a disulfide bridge between heavy and light chain variable domains (Strohl, W.R. Therapeutic Antibody Engineering. Woodhead Publishing, Philadelphia PA. 2012. Ch. 3, p46-47, the contents of which are herein incorporated by reference in their entirety).

[00162] As used herein, the term "light chain" refers to a component of an antibody from any vertebrate species assigned to one of two clearly distinct types, called kappa and lambda based on amino acid sequences of constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains, antibodies can be assigned to different classes. There are five major classes of intact antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGI, IgG2, IgG3, IgG4, IgA, and IgA2.

[00163] As used herein, the term "single chain Fv" or "scFv" refers to a fusion protein of VH and VL antibody domains, wherein these domains are linked together into a single polypeptide chain by a flexible peptide linker. In some embodiments, the Fv polypeptide linker enables the scFv to form the desired structure for antigen binding. In some embodiments, scFvs are utilized in conjunction with phage display, yeast display or other display methods where they may be expressed in association with a surface member (e.g. phage coat protein) and used in the identification of high affinity peptides for a given antigen.

[00164] Using molecular genetics, two scFvs can be engineered in tandem into a single polypeptide, separated by a linker domain, called a "tandem scFv" (tascFv). Construction of a tascFv with genes for two different scFvs yields a "bispecific single-chain variable fragments" (bis-scFvs). Only two tascFvs have been developed clinically by commercial firms; both are bispecific agents in active early phase development by Micromet for oncologic indications, and are described as "Bispecific T-cell Engagers (BiTE)." Blinatumomab is an anti-CD19/anti-CD3 bispecific tascFv that potentiates T-cell responses to B-cell non-Hodgkin lymphoma in Phase 2. MT110 is an anti-EP-CAM/anti-CD3 bispecific tascFv that potentiates T-cell responses to solid tumors in Phase 1. Bispecific, tetravalent "TandAbs" are also being researched by Affimed (Nelson, A. L., MAbs., 2010, Jan-Feb; 2(1):77-83). maxibodies (bivalent scFv fused to the amino terminus of the Fc (CH2-CH3 domains) of IgG may also be included.

[00165] As used herein, the term "bispecific antibody" refers to an antibody capable of binding two different antigens. Such antibodies typically comprise regions from at least two different antibodies. Bispecific antibodies may include any of those described in Riethmuller, G. Cancer Immunity. 2012, 12:12-18, Marvin et al., 2005. Acta PharmacologicaSinica. 2005, 26(6): 649 658 and Schaefer et al., PNAS. 2011, 108(27):11187-11192, the contents of each of which are herein incorporated by reference in their entirety.

[00166] As used herein, the term "diabody" refers to a small antibody fragment with two antigen-binding sites. Diabodies are functional bispecific single-chain antibodies (bscAb). Diabodies comprise a heavy chain variable domain VH connected to a light chain variable domain VL in the same polypeptide chain. By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al. (Hollinger,

P. et al., "Diabodies": Small bivalent and bispecific antibody fragments. PNAS, 1993. 90: 6444 6448); the contents of each of which are incorporated herein by reference in their entirety.

[00167] The term "intrabody" refers to a form of antibody that is not secreted from a cell in which it is produced, but instead targets one or more intracellular proteins. Intrabodies may be used to affect a multitude of cellular processes including, but not limited to intracellular trafficking, transcription, translation, metabolic processes, proliferative signaling and cell division. In some embodiments, methods of the present invention may include intrabody-based therapies. In some such embodiments, variable domain sequences and/or CDR sequences disclosed herein may be incorporated into one or more constructs for intrabody-based therapy.

[00168] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous cells (or clones), i.e., the individual antibodies comprising the population are identical and/or bind the same epitope, except for possible variants that may arise during production of the monoclonal antibodies, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen.

[00169] The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. The monoclonal antibodies herein include "chimeric" antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies.

[00170] As used herein, the term "humanized antibody" refers to a chimeric antibody comprising a minimal portion from one or more non-human (e.g., murine) antibody source(s) with the remainder derived from one or more human immunoglobulin sources. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from the hypervariable region from an antibody of the recipient are replaced by residues from the hypervariable region from an antibody of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and/or capacity. In one embodiment, the antibody may be a humanized full-length antibody. As a non-limiting example, the antibody may have been humanized using the methods taught in US Patent Publication NO. US20130303399, the contents of which are herein incorporated by reference in its entirety.

[00171] As used herein, the term "antibody variant" refers to a modified antibody (in relation to a native or starting antibody) or a biomolecule resembling a native or starting antibody in structure and/or function (e.g., an antibody mimetic). Antibody variants may be altered in their amino acid sequence, composition or structure as compared to a native antibody. Antibody variants may include, but are not limited to, antibodies with altered isotypes (e.g., IgA, IgD, IgE, IgGI, IgG2, IgG3, IgG4, or IgM), humanized variants, optimized variants, multispecific antibody variants (e.g., bispecific variants), and antibody fragments.

[00172] In some embodiments, pharmaceutical compositions, biocircuits, biocircuit components, effector modules including their SREs or payloads of the present invention may be antibody mimetics. As used herein, the term "antibody mimetic" refers to any molecule which mimics the function or effect of an antibody and which binds specifically and with high affinity to their molecular targets. In some embodiments, antibody mimetics may be monobodies, designed to incorporate the fibronectin type III domain (Fn3) as a protein scaffold (US 6,673,901; US 6,348,584). In some embodiments, antibody mimetics may be those known in the art including, but are not limited to affibody molecules, affilins, affitins, anticalins, avimers, Centyrins, DARPINSTM, Fynomers and Kunitz and domain peptides. In other embodiments, antibody mimetics may include one or more non-peptide regions.

[00173] In one embodiment, the antibody may comprise a modified Fc region. As a non limiting example, the modified Fc region may be made by the methods or may be any of the regions described in US Patent Publication NO. US20150065690, the contents of which are herein incorporated by reference in its entirety.

[00174] In some embodiments, payloads of the invention may encode multispecific antibodies that bind more than one epitope. As used herein, the terms "multibody" or "multispecific antibody" refer to an antibody wherein two or more variable regions bind to different epitopes. The epitopes may be on the same or different targets. In one embodiment, the multispecific antibody may be generated and optimized by the methods described in International Patent Publication NO. WO2011109726 and US Patent Publication NO. US20150252119, the contents of which each of which are herein incorporated by reference in their entirety. These antibodies are able to bind to multiple antigens with high specificity and high affinity.

[00175] In certain embodiments, a multi-specific antibody is a "bispecific antibody" which recognizes two different epitopes on the same or different antigens. In one aspect, bispecific antibodies are capable of binding two different antigens. Such antibodies typically comprise antigen-binding regions from at least two different antibodies. For example, a bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein composed of fragments of two different monoclonal antibodies, thus allowing the BsAb to bind to two different types of antigen. Bispecific antibody frameworks may include any of those described in Riethmuller, G., 2012. Cancer Immunity, 2012, 12:12-18; Marvin et al., Acta Pharmacologica Sinica. 2005, 26(6):649-658; and Schaefer et al., PNAS. 2011, 108(27): 11187-11192, the contents of each of which are herein incorporated by reference in their entirety. New generations of BsMAb, called "trifunctional bispecific" antibodies, have been developed. These consist of two heavy and two light chains, one each from two different antibodies, where the two Fab regions (the arms) are directed against two antigens, and the Fc region (the foot) comprises the two heavy chains and forms the third binding site.

[00176] In some embodiments, payloads may encode antibodies comprising a single antigen binding domain. These molecules are extremely small, with molecular weights approximately one-tenth of those observed for full-sized mAbs. Further antibodies may include "nanobodies" derived from the antigen-binding variable heavy chain regions (VHHs) of heavy chain antibodies found in camels and llamas, which lack light chains (Nelson, A. L., MAbs.2010. Jan-Feb; 2(1):77-83).

[00177] In some embodiments, the antibody may be "miniaturized". Among the best examples of mAb miniaturization are the small modular immunopharmaceuticals (SMIPs) from Trubion Pharmaceuticals. These molecules, which can be monovalent or bivalent, are recombinant single chain molecules containing one VL, one VH antigen-binding domain, and one or two constant "effector" domains, all connected by linker domains. Presumably, such a molecule might offer the advantages of increased tissue or tumor penetration claimed by fragments while retaining the immune effector functions conferred by constant domains. At least three "miniaturized" SMIPs have entered clinical development. TRU-015, an anti-CD20 SMIP developed in collaboration with Wyeth, is the most advanced project, having progressed to Phase 2 for rheumatoid arthritis (RA). Earlier attempts in systemic lupus erythrematosus (SLE) and B cell lymphomas were ultimately discontinued. Trubion and Facet Biotechnology are collaborating in the development of TRU-016, an anti-CD37 SMIP, for the treatment of CLL and other lymphoid neoplasias, a project that has reached Phase 2. Wyeth has licensed the anti-CD20 SMIP SBI-087 for the treatment of autoimmune diseases, including RA, SLE and possibly multiple sclerosis, although these projects remain in the earliest stages of clinical testing. (Nelson, A. L., MAbs, 2010. Jan Feb; 2(1):77-83).

[00178] On example of miniaturized antibodies is called "unibody" in which the hinge region has been removed from IgG4 molecules. While IgG4 molecules are unstable and can exchange light-heavy chain heterodimers with one another, deletion of the hinge region prevents heavy chain-heavy chain pairing entirely, leaving highly specific monovalent light/heavy heterodimers, while retaining the Fc region to ensure stability and half-life in vivo. This configuration may minimize the risk of immune activation or oncogenic growth, as IgG4 interacts poorly with FcRs and monovalent unibodies fail to promote intracellular signaling complex formation (see, e.g., Nelson, A. L., MAbs, 2010. Jan-Feb; 2(1):77-83).

[00179] In some embodiments, payloads of the invention may encode single-domain antibodies (sdAbs, or nanobodies) which are antibody fragment consisting of a single monomeric variable antibody domain. Like a whole antibody, it is able to bind selectively to a specific antigen. In one aspect, a sdAb may be a "Camel Ig or "camelid VHH". As used herein, the term "camel Ig" refers to the smallest known antigen-binding unit of a heavy chain antibody (Koch-No lte, et al, FASEB J., 2007, 21: 3490- 3498). A "heavy chain antibody" or a "camelid antibody" refers to an antibody that contains two VH domains and no light chains (Riechmann L. et al, J Immunol. Methods, 1999, 231: 25-38; International patent publication NOs. WO1994/04678 and W01994/025591; and U.S. Patent No. 6,005,079). In another aspect, a sdAb may be a "immunoglobulin new antigen receptor" (IgNAR). As used herein, the term "immunoglobulin new antigen receptor" refers to class of antibodies from the shark immune repertoire that consist of homodimers of one variable new antigen receptor (VNAR) domain and five constant new antigen receptor (CNAR) domains. IgNARs represent some of the smallest known immunoglobulin-based protein scaffolds and are highly stable and possess efficient binding characteristics. The inherent stability can be attributed to both (i) the underlying Ig scaffold, which presents a considerable number of charged and hydrophilic surface exposed residues compared to the conventional antibody VH and VL domains found in murine antibodies; and (ii) stabilizing structural features in the complementary determining region (CDR) loops including inter-loop disulphide bridges, and patterns of intra-loop hydrogen bonds.

[00180] In some embodiments, payloads of the invention may encode intrabodies. Intrabodies are a form of antibody that is not secreted from a cell in which it is produced, but instead targets one or more intracellular proteins. Intrabodies are expressed and function intracellularly, and may be used to affect a multitude of cellular processes including, but not limited to intracellular trafficking, transcription, translation, metabolic processes, proliferative signaling and cell division. In some embodiments, methods described herein include intrabody-based therapies. In some such embodiments, variable domain sequences and/or CDR sequences disclosed herein are incorporated into one or more constructs for intrabody-based therapy. For example, intrabodies may target one or more glycated intracellular proteins or may modulate the interaction between one or more glycated intracellular proteins and an alternative protein.

[00181] The intracellular expression of intrabodies in different compartments of mammalian cells allows blocking or modulation of the function of endogenous molecules (Biocca, et al., EMBO J. 1990, 9: 101-108; Colby et al., Proc. Nat. Acad. Sci. U.S.A. 2004, 101: 17616-17621). Intrabodies can alter protein folding, protein-protein, protein-DNA, protein-RNA interactions and protein modification. They can induce a phenotypic knockout and work as neutralizing agents by direct binding to the target antigen, by diverting its intracellular trafficking or by inhibiting its association with binding partners. With high specificity and affinity to target antigens, intrabodies have advantages to block certain binding interactions of a particular target molecule, while sparing others.

[00182] Sequences from donor antibodies may be used to develop intrabodies. Intrabodies are often recombinantly expressed as single domain fragments such as isolated VH and VL domains or as a single chain variable fragment (scFv) antibody within the cell. For example, intrabodies are often expressed as a single polypeptide to form a single chain antibody comprising the variable domains of the heavy and light chains joined by a flexible linker polypeptide. Intrabodies typically lack disulfide bonds and are capable of modulating the expression or activity of target genes through their specific binding activity. Single chain intrabodies are often expressed from a recombinant nucleic acid molecule and engineered to be retained intracellularly (e.g., retained in the cytoplasm, endoplasmic reticulum, or periplasm). Intrabodies may be produced using methods known in the art, such as those disclosed and reviewed in: (Marasco et al., PNAS, 1993, 90: 7889-7893; Chen et al., Hum. Gene Ther. 1994, 5:595-601; Chen et al., 1994, PNAS, 91: 5932-5936; Maciejewski et al., 1995, Nature Med., 1: 667-673; Marasco, 1995, Immunotech, 1: 1-19; Mhashilkar, et al., 1995, EMBO J. 14: 1542-51; Chen et al., 1996, Hum.

Gene Therap., 7: 1515-1525; Marasco, Gene Ther. 4:11-15, 1997; Rondon and Marasco, 1997, Annu. Rev. Microbiol. 51:257-283; Cohen, et al., 1998, Oncogene 17:2445-56; Proba et al., 1998, J. Mol. Biol. 275:245-253; Cohen et al., 1998, Oncogene 17:2445-2456; Hassanzadeh, et al., 1998, FEBS Lett. 437:81-6; Richardson et al., 1998, Gene Ther. 5:635-44; Ohage and Steipe, 1999, J. Mol. Biol. 291:1119-1128; Ohage et al., 1999, J. Mol. Biol. 291:1129-1134; Wirtz and Steipe, 1999, Protein Sci. 8:2245-2250; Zhu et al., 1999, J. Immunol. Methods 231:207-222; Arafat et al., 2000, Cancer Gene Ther. 7:1250-6; der Maur et al., 2002, J. Biol. Chem. 277:45075-85; Mhashilkar et al., 2002, Gene Ther. 9:307-19; and Wheeler et al., 2003, FASEB J. 17: 1733-5; and references cited therein).

[00183] In some aspects, payloads of the invention may encode biosynthetic antibodies as described in U.S. Patent No. 5,091,513, the contents of which are herein incorporated by reference in their entirety. Such antibody may include one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic VH and VL dimers, 2) VH VL or VL-VH single chains wherein the VH and VL are attached by a polypeptide linker, or 3) individuals VH or VL domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The biosynthetic antibodies may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the biosynthetic antibodies, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.

[00184] In some embodiments, payloads may encode antibodies with antibody acceptor frameworks taught in U.S. Patent No. 8,399,625. Such antibody acceptor frameworks may be particularly well suited accepting CDRs from an antibody of interest.

[00185] In one embodiment, the antibody may be a conditionally active biologic protein. An antibody may be used to generate a conditionally active biologic protein which are reversibly or irreversibly inactivated at the wild type normal physiological conditions as well as to such conditionally active biologic proteins and uses of such conditional active biologic proteins are provided. Such methods and conditionally active proteins are taught in, for example, International Publication No. W02015175375 and W02016036916 and US Patent Publication No. US20140378660, the contents of each of which are incorporated herein by reference in their entirety.

Antibody preparations

[00186] The preparation of antibodies, whether monoclonal or polyclonal, is known in the art. Techniques for the production of antibodies are well known in the art and described, e.g. in Harlow and Lane "Antibodies, A Laboratory Manual", Cold Spring Harbor Laboratory Press, 1988; Harlow and Lane "Using Antibodies: A Laboratory Manual" Cold Spring Harbor Laboratory Press, 1999 and "Therapeutic Antibody Engineering: Current and Future Advances Driving the Strongest Growth Area in the Pharmaceutical Industry" Woodhead Publishing, 2012.

[00187] The antibodies and fragments and variants thereof as described herein can be produced using recombinant polynucleotides. In one embodiment, the polynucleotides have a modular design to encode at least one of the antibodies, fragments or variants thereof. As a non-limiting example, the polynucleotide construct may encode any of the following designs: (1) the heavy chain of an antibody, (2) the light chain of an antibody, (3) the heavy and light chain of the antibody, (4) the heavy chain and light chain separated by a linker, (5) the VH1, CHI, CH2, CH3 domains, a linker and the light chain or (6) the VH1, CHI, CH2, CH3 domains, VL region, and the light chain. Any of these designs may also comprise optional linkers between any domain and/or region. The polynucleotides of the present invention may be engineered to produce any standard class of immunoglobulins using an antibody described herein or any of its component parts as a starting molecule.

[00188] Recombinant antibody fragments may also be isolated from phage antibody libraries using techniques well known in the art and described in e.g. Clackson et al., 1991, Nature 352: 624-628; Marks et al., 1991, J. Mol. Biol. 222: 581-597. Recombinant antibody fragments may be derived from large phage antibody libraries generated by recombination in bacteria (Sblattero and Bradbury, 2000, Nature Biotechnology 18:75-80; the contents of which are incorporated herein by reference in its entirety). Antibodies used for immunotherapy

[00189] In some embodiments, payloads of the present invention may be antibodies, fragments and variants thereof which are specific to tumor specific antigens (TSAs) and tumor associated antigens (TAAs). Antibodies circulate throughout the body until they find and attach to the TSA/TAA. Once attached, they recruit other parts of the immune system, increasing ADCC (antibody dependent cell-mediated cytotoxicity) and ADCP (antibody dependent cell-mediated phagocytosis) to destroy tumor cells. As used herein, the term "tumor specific antigen (TSA)" means an antigenic substance produced in tumor cells, which can trigger an anti-tumor immune response in a host organism. In one embodiment, a TSA may be a tumor neoantigen. The tumor antigen specific antibody mediates complement-dependent cytotoxic response against tumor cells expressing the same antigen.

[00190] In some embodiments, the tumor specific antigens (TSAs), tumor associated antigens (TAAs), pathogen associated antigens, or fragments thereof can be expressed as a peptide or as an intact protein or portion thereof. The intact protein or a portion thereof can be native or mutagenized. Antigens associated with cancers or virus-induced cancers as described herein are well-known in the art. Such a TSA or TAA may be previously associated with a cancer or may be identified by any method known in the art.

[00191] In one embodiment, the antigen is CD19, a B-cell surface protein expressed throughout B-cell development. CD19 is a well-known B cell surface molecule, which upon B cell receptor activation enhances B-cell antigen receptor induced signaling and expansion of B cell populations. CD19 is broadly expressed in both normal and neoplastic B cells. Malignancies derived from B cells such as chronic lymphocytic leukemia, acute lymphocytic leukemia and many non-Hodgkin lymphomas frequently retain CD19 expression. This near universal expression and specificity for a single cell lineage has made CD19 an attractive target for immunotherapies. Human CD19 has 14 exons wherein exon 1-4 encode the extracellular portion of the CD19, exon 5 encodes the transmembrane portion of CD19 and exons 6-14 encode the cytoplasmic tail.

[00192] In one embodiment, payloads of the present invention may be antibodies, fragments and variants thereof which are specific to CD19 antigen.

[00193] In one embodiment, the payload of the invention may be a FMC63 antibody, antibody fragment of variant. FMC63 is an IgG2a mouse monoclonal antibody clone specific to the CD19 antigen that reacts with CD19 antigen on cells of the B cell lineage. The epitope of CD19 recognized by the FMC63 antibody is in exon 2 (Sotillo et al (2015) Cancer Discov ;5(12):1282 95; the contents of which are incorporated by reference in their entirety). In some embodiments, the payload of the invention may be other CD19 monoclonal antibody clones including but not limited to 4G7, SJ25C1, CVID3/429, CVID3/155, HIB19, and J3-119.

[00194] In some embodiments, the payloads of the present invention may include variable heavy chain and variable light chain comprising the amino acid sequences selected from those in Table 4.

Table 4: Variable Heavy and Light Chain Sequences

Tarjjet Antibody SEQ ID Source chain NO CD19 VH 49 SEQ ID NO: 28 in W216168773A3 CD19 VH 50 SEQ ID NO: 29 in W2016168773A3 CD19 VH 51 SEQ ID NO: 32 in W2016168773A3 CD19 VH 52 SEQ ID NO: 33 in W2016168773A3 CD19 VH 53 SEQ ID NO: 34 in W2016168773A3 CD19 VH 54 SEQ ID NO: 35 in W2016168773A3 CD19 VH 55 SEQ ID NO: 51in W216187349A1 CD19 VH 56 SEQ IDNO: 20 inUS20160039942 CD19 VH 57 SEQ ID NO. 1in W2014184143 CD19 VH 58 SEQ IDNO. 5in US20160145337A1 CD19 VH 59 SEQ IDNO: 15 inUS20160319020 CD19 VH 60 SEQ IDNO: 166 inUS20160152723 CD19 VH 61 SEQ IDNO: 167 inUS20160152723 CD19 VH 62 SEQ IDNO: 168 inUS20160152723 CD19 VH 63 SEQ IDNO: 17 inEP3057991A1 CD19 VH 64 SEQ IDNO: 172 inUS20160152723 CD19 VH 65 SEQ IDNO: 176 inUS20160152723 CD19 VH 66 SEQ IDNO: 177 inUS20160152723 CD19 VH 67 SEQ IDNO: 181 inUS20160152723 CD19 VH 68 SEQ IDNO: 183 inUS20160152723 CD19 VH 69 SEQ IDNO: 184 inUS20160152723 CD19 VH 70 SEQ IDNO: 185 inUS20160152723 CD19 VH 71 SEQ IDNO: 62 inUS20160152723 CD19 VH 72 SEQ ID NO: 62in W2016097231 CD19 VH 73 SEQ ID NO. 12in W2016134284 CD19 VH 74 SEQ ID NO: 111 in US20160333114A1 CD19 VH 75 SEQ IDNO: 113 inUS20160333114A1 CD19 VH 76 SEQ IDNO: 33 inEP3057994A1 CD19 VH 77 SEQ IDNO: 34 inEP3057994A1 CD19 VH 78 SEQ ID NO: 35 inEP3057994A1 CD19 VH 79 SEQ ID NO. 53in W2016120216 CD19 VH 80 SEQ ID NO. 55in W02016120216 CD19 VK 81 SEQ ID NO: 13 inUS20160319020 CD19 VK 82 SEQ ID NO: 6in US20160319020 CD19 VL 83 SEQ ID NO: 27 in W2016168773A3 CD19 VL 84 SEQ ID NO: 31 in W2016168773A3 CD19 VL 85 SEQ ID NO: 49 in W2016187349A1 CD19 VL 86 SEQ ID NO. 11in W02016134284 CD19 VL 87 SEQ IDNO. 194 inUS20140134142A1 CD19 VL 88 SEQ ID NO. 54in W2016120216

CD19 VL 89 SEQ ID NO. 56 in W02016120216 CD19 VL 90 SEQ ID NO: 13 in US20160152723 CD19 VL 91 SEQ ID NO: 14 in US20160152723 CD19 VL 92 SEQ ID NO: 15 in US20160152723 CD19 VL 93 SEQ ID NO: 16 in US20160152723 CD19 VL 94 SEQ ID NO: 17 in US20160152723 CD19 VL 95 SEQ ID NO: 186 in US20160152723 CD19 VL 96 SEQ ID NO: 187 in US20160152723 CD19 VL 97 SEQ ID NO: 188 US20160152723 CD19 VL 98 SEQ ID NO: 189 in US20160152723 CD19 VL 99 SEQ ID NO: 192 in US20160152723 CD19 VL 100 SEQ ID NO: 196 in US20160152723 CD19 VL 101 SEQ ID NO: 197 in US20160152723 CD19 VL 102 SEQ ID NO: 198 in US20160152723 CD19 VL 103 SEQ ID NO: 199 in US20160152723 CD19 VL 104 SEQ ID NO: 200 in US20160152723 CD19 VL 105 SEQ ID NO: 201 in US20160152723 CD19 VL 106 SEQ ID NO: 202 in US20160152723 CD19 VL 107 SEQ ID NO: 203 in US20160152723 CD19 VL 108 SEQ ID NO: 204 in US20160152723 CD19 VL 109 SEQ ID NO: 205 in US20160152723 CD19 VL 110 SEQ ID NO: 22 in US20160039942 CD19 VL 111 SEQ ID NO: 63 in WO2016097231 CD19 VL 112 SEQ ID NO: 64 in US20160152723 CD19 VL 113 SEQ ID NO: 66 in US20160152723 CD19 VL 114 SEQ ID NO: 67 in US20160152723 CD19 VL 115 SEQ ID NO: 68 in US20160152723 CD19 VL 116 SEQ ID NO: 69 in US20160152723 CD19 VL 117 SEQ ID NO: 70 in US20160152723 CD19 VL 118 SEQ ID NO: 71 in US20160152723 CD19 VL 119 SEQ ID NO: 91 in US20160152723 CD19 VL 120 SEQ ID NO. 3 in US20160145337A1 CD19 VL 121 SEQ ID NO: 112 in US20160333114A1 CD19 VL 122 SEQ ID NO: 114 in US20160333114A1

[00195] A tumor specific antigen (TSA) maybe a tumor neoantigen. A neoantigen is a mutated antigen that is only expressed by tumor cells because of genetic mutations or alterations in transcription which alter protein coding sequences, therefore creating novel, foreign antigens. The genetic changes result from genetic substitution, insertion, deletion or any other genetic changes of a native cognate protein (i.e. a molecule that is expressed in normal cells). In the context of CD19, neoantigens such as a transcript variant of CD19 lacking exon 2 or lacking exon 5-6 or both have been described (see International patent publication No. W02016061368; the contents of which are incorporated herein by reference in their entirety). Since FMC63 binding epitope is in exon 2, CD19 neoantigen lacking exon 2 is not recognized by FMC63 antibody. Thus, in some embodiments, payloads of the invention may include FMC63-distinct antibodies, or fragments thereof. As used herein "FMC63-distinct" refers, to an antibody or fragment thereof that is immunologically specific and binds to an epitope of the CD19 antigen that is different or unlike the epitope of CD19 antigen that is bound by FMC63. In some instances, antibodies of the invention may include CD19 antibodies, antibody fragments or variants that recognize CD19 neoantigens including the CD19 neoantigen lacking exon2. In one embodiment, the antibody or fragment thereof is immunologically specific to the CD19 encoded by exon 1, 3 and/or 4. In one example, the antibody or fragment thereof is specific to the epitope that bridges the portion of CD19 encoded by exon 1 and the portion of CD19 encoded by exon 3.

[00196] Chimeric antigen receptors (CARs)

[00197] In some embodiments, payloads of the present invention maybe a chimeric antigen receptors (CARs) which when transduced into immune cells (e.g., T cells and NK cells), can re direct the immune cells against the target (e.g., a tumor cell) which expresses a molecule recognized by the extracellular target moiety of the CAR.

[00198] As used herein, the term "chimeric antigen receptor (CAR)" refers to a synthetic receptor that mimics TCR on the surface of T cells. In general, a CAR is composed of an extracellular targeting domain, a transmembrane domain/region and an intracellular signaling/activation domain. In a standard CAR receptor, the components: the extracellular targeting domain, transmembrane domain and intracellular signaling/activation domain, are linearly constructed as a single fusion protein. The extracellular region comprises a targeting domain/moiety (e.g., a scFv) that recognizes a specific tumor antigen or other tumor cell-surface molecules. The intracellular region may contain a signaling domain of TCR complex (e.g., the signal region of CD3(), and/or one or more costimulatory signaling domains, such as those from CD28, 4-1BB (CD137) and OX-40 (CD134). For example, a "first-generation CAR" only has the CD3Q signaling domain. In an effort to augment T-cell persistence and proliferation, costimulatory intracellular domains are added, giving rise to second generation CARs having a CD3(signal domain plus one costimulatory signaling domain, and third generation CARs having CD3Q signal domain plus two or more costimulatory signaling domains. A CAR, when expressed by a T cell, endows the T cell with antigen specificity determined by the extracellular targeting moiety of the CAR. Recently, it is also desirable to add one or more elements such as homing and suicide genes to develop a more competent and safer architecture of CAR, so called the fourth-generation CAR.

[00199] In some embodiments, the extracellular targeting domain is joined through the hinge (also called space domain or spacer) and transmembrane regions to an intracellular signaling domain. The hinge connects the extracellular targeting domain to the transmembrane domain which transverses the cell membrane and connects to the intracellular signaling domain. The hinge may need to be varied to optimize the potency of CAR transformed cells toward cancer cells due to the size of the target protein where the targeting moiety binds, and the size and affinity of the targeting domain itself. Upon recognition and binding of the targeting moiety to the target cell, the intracellular signaling domain leads to an activation signal to the CAR T cell, which is further amplified by the "second signal" from one or more intracellular costimulatory domains. The CAR T cell, once activated, can destroy the target cell.

[00200] In some embodiments, the CAR of the present invention may be split into two parts, each part is linked a dimerizing domain, such that an input that triggers the dimerization promotes assembly of the intact functional receptor. Wu and Lim recently reported a split CAR in which the extracellular CD19 binding domain and the intracellular signaling element are separated and linked to the FKBP domain and the FRB* (T2089L mutant of FKBP-rapamycin binding) domain that heterodimerize in the presence of the rapamycin analog AP21967. The split receptor is assembled in the presence of AP21967 and together with the specific antigen binding, activates T cells (Wu et al., Science, 2015, 625(6258): aab4077).

[00201] In some embodiments, the CAR of the present invention may be designed as an inducible CAR. Sakemura et al recently reported the incorporation of a Tet-On inducible system to the CD19 CAR construct. The CD19 CAR is activated only in the presence of doxycycline (Dox). Sakemura reported that Tet-CD19CAR T cells in the presence of Dox were equivalently cytotoxic against CD19' cell lines and had equivalent cytokine production and proliferation upon CD19 stimulation, compared with conventional CD19CAR T cells (Sakemura et al., Cancer Immuno. Res., 2016, Jun 21, Epub ahead of print). In one example, this Tet-CAR may be the payload of the effector module under the control of SREs (e.g., DDs) of the invention. The dual systems provide more flexibility to turn-on and off of the CAR expression in transduced T cells.

[00202] According to the present invention, the payload of the present invention may be a first generation CAR, or a second-generation CAR, or a third-generation CAR, or a fourth-generation CAR. Representative effector module embodiments comprising CAR constructs are illustrated in Figures 13-18. In some embodiments, the payload of the present invention may be a full CAR construct composed of the extracellular domain, the hinge and transmembrane domain and the intracellular signaling region. In other embodiments, the payload of the present invention may be a component of the full CAR construct including an extracellular targeting moiety, a hinge region, a transmembrane domain, an intracellular signaling domain, one or more co-stimulatory domain, and other additional elements that improve CAR architecture and functionality including but not limited to a leader sequence, a homing element and a safety switch, or the combination of such components.

[00203] CARs regulated by biocircuits and compositions of the present invention are tunable and thereby offer several advantages. The reversible on-off switch mechanism allows management of acute toxicity caused by excessive CAR-T cell expansion. Pulsatile CAR expression using SREs of the present invention may be achieved by cycling ligand level. The ligand conferred regulation of the CAR may be effective in offsetting tumor escape induced by antigen loss, avoiding functional exhaustion caused by tonic signaling due to chronic antigen exposure and improving the persistence of CAR expressing cells in vivo.

[00204] In some embodiments, biocircuits and compositions of the invention may be utilized to down regulate CAR expression to limit on target on tissue toxicity caused by tumor lysis syndrome. Down regulating the expression of the CARs of the present invention following anti tumor efficacy may prevent (1) On target off tumor toxicity caused by antigen expression in normal tissue, (2) antigen independent activation in vivo.

[00205] In one embodiment, selection of a CAR with a lower affinity may provide more T cell signaling and less toxicity. Extracellulartargetingdomain/moiety

[00206] In accordance with the invention, the extracellular target moiety of a CAR may be any agent that recognizes and binds to a given target molecule, for example, a neoantigen on tumor cells, with high specificity and affinity. The target moiety may be an antibody and variants thereof that specifically binds to a target molecule on tumor cells, or a peptide aptamer selected from a random sequence pool based on its ability to bind to the target molecule on tumor cells, or a variant or fragment thereof that can bind to the target molecule on tumor cells, or an antigen recognition domain from native T- cell receptor (TCR) (e.g. CD4 extracellular domain to recognize HIV infected cells), or exotic recognition components such as a linked cytokine that leads to recognition of target cells bearing the cytokine receptor, or a natural ligand of a receptor.

[00207] In some embodiments, the targeting domain of a CAR may be a Ig NAR, a Fab fragment, a Fab' fragment, a F(ab)'2 fragment, a F(ab)'3 fragment, Fv, a single chain variable fragment (scFv), a bis-scFv, a (scFv)2, a minibody, a diabody, a triabody, a tetrabody, a disulfide stabilized Fv protein (dsFv), a unitbody, a nanobody, or an antigen binding region derived from an antibody that specifically recognizes a target molecule, for example a tumor specific antigen (TSA). In one embodiment, the targeting moiety is a scFv antibody. The scFv domain, when it is expressed on the surface of a CAR T cell and subsequently binds to a target protein on a cancer cell, is able to maintain the CAR T cell in proximity to the cancer cell and to trigger the activation of the T cell. A sFv can be generated using routine recombinant DNA technology techniques and is discussed in the present invention.

[002081 In one embodiment, the targeting moiety of the CAR may recognize CD19. CD19 is a well-known B cell surface molecule, which upon B cell receptor activation enhances B-cell antigen receptor induced signaling and expansion of B cell populations. CD19 is broadly expressed in both normal and neoplastic B cells. Malignancies derived from B cells such as chronic lymphocytic leukemia, acute lymphocytic leukemia and many non-Hodgkin lymphomas frequently retain CD19 expression. This near universal expression and specificity for a single cell lineage has made CD19 an attractive target for immunotherapies. Human CD19 has 14 exons wherein exon 1-4 encode the extracellular portion of the CD19, exon 5 encodes the transmembrane portion of CD19 and exons 6-14 encode the cytoplasmic tail. In one embodiment, the targeting moiety may comprise scFvs derived from the variable regions of the FMC63 antibody. FMC63 is an IgG2a mouse monoclonal antibody clone specific to the CD19 antigen that reacts with CD19 antigen on cells of the B lineage. The epitope of CD19 recognized by the FMC63 antibody is in exon 2 (Sotillo et al (2015) Cancer Discov;5(12):1282-95; the contents of which are incorporated by reference in their entirety). In some embodiments, the targeting moiety of the CAR may be derived from the variable regions of other CD19 monoclonal antibody clones including but not limited to 4G7, SJ25C1, CVID3/429, CVID3/155, HIB19, and J3-119.

[00209] In some embodiments, the targeting moiety of a CAR may recognize a tumor specific antigen (TSA), for example a cancer neoantigen that is only expressed by tumor cells because of genetic mutations or alterations in transcription which alter protein coding sequences, therefore creating novel, foreign antigens. The genetic changes result from genetic substitution, insertion, deletion or any other genetic changes of a native cognate protein (i.e. a molecule that is expressed in normal cells). In the context of CD19, TSAs may include a transcript variant of human CD19 lacking exon 2 or lacking exon 5-6 or both (see International patent publication No. W02016061368; the contents of which are incorporated herein by reference in their entirety). Since FMC63 binding epitope is in exon 2, CD19 lacking exon 2 is not recognized by FMC63 antibody. Thus, in some embodiments, the targeting moiety of the CAR may be an FMC63-distinct scFV. As used herein "FMC63-distinct" refers, to an antibody, scFv or a fragment thereof that is immunologically specific and binds to an epitope of the CD19 antigen that is different or unlike the epitope of CD19 antigen that is bound by FMC63. In some instances, targeting moiety may recognize a CD19 antigen lacking exon2. In one embodiment, the targeting moiety recognizes a fragment of CD19 encoded by exon 1, 3 and/or 4. In one example, the targeting moiety recognizes the epitope that bridges the portion of CD19 encoded by exon 1 and the portion of CD19 encoded by exon 3.

[00210] In some embodiments, the targeting moieties of the present invention may be scFv comprising the amino acid sequences in Table 5. Table 5: scFv sequences Target Description SEQ ID Source NO CD19 scFv 123 SEQ ID NO. 53 in EP3083671A1 CD19 scFv 124 SEQ ID NO. 54 in EP3083671A1 CD19 scFv 125 SEQ ID NO. 1 in WO2015157252 CD19 scFv 126 SEQ ID NO. 10 in WO2015157252 CD19 scFv 127 SEQ ID NO. 10 in WO2016033570 CD19 scFv 128 SEQ ID NO. 11 in WO2015157252 CD19 scFv 129 SEQ ID NO. 12 in WO2015157252 CD19 scFv 130 SEQ ID NO. 2 in WO2015157252 CD19 scFv 131 SEQ ID NO. 2 in WO2016033570 CD19 scFv 132 SEQ ID NO. 206 in WO2016033570 CD19 scFv 133 SEQ ID NO. 207 in WO2016033570 CD19 scFv 134 SEQ ID NO. 208 in WO2016033570 CD19 scFv 135 SEQ ID NO. 209 in WO2016033570 CD19 scFv 136 SEQ ID NO. 210 in WO2016033570 CD19 scFv 137 SEQ ID NO. 211 in WO2016033570 CD19 scFv 138 SEQ ID NO. 213 in WO2016033570 CD19 scFv 139 SEQ ID NO. 214 in WO2016033570 CD19 scFv 140 SEQ ID NO. 215 in WO2016033570 CD19 scFv 141 SEQ ID NO. 216 in WO2016033570 CD19 scFv 142 SEQ ID NO. 217 in WO2016033570 CD19 scFv 143 SEQ ID NO. 218 in WO2016033570 CD19 scFv 144 SEQ ID NO. 219 in WO2016033570

CD19 scFv 145 SEQ ID NO. 220 in W02016033570 CD19 scFv 146 SEQ ID NO. 221 in W02016033570 CD19 scFv 147 SEQ ID NO. 222 in W02016033570 CD19 scFv 148 SEQ ID NO. 223 in W02016033570 CD19 scFv 149 SEQ ID NO. 224 inM02016033570 CD19 scFv 150 SEQ ID NO. 225 in W02016033570 CD19 scFv 151 SEQ ID NO. 3in W02015157252 CD19 scFv 152 SEQ ID NO. 4in W02015157252 CD19 scFv 153 SEQ ID NO. 4in W02016033570 CD19 scFv 154 SEQ ID NO. 45 inW02016033570 CD19 scFv 155 SEQ ID NO. 47 inW02016033570 CD19 scFv 156 SEQ ID NO. 49 inW02016033570 CD19 scFv 157 SEQ ID NO. 5in W2015155341A1 CD19 scFv 158 SEQ ID NO. 5in W02015157252 CD19 scFv 159 SEQ ID NO. 51 inW02016033570 CD19 scFv 160 SEQ ID NO. 53 inW02016033570 CD19 scFv 161 SEQ ID NO. 55 inW02016033570 CD19 scFv 162 SEQ ID NO. 57 inW02016033570 CD19 scFv 163 SEQ ID NO. 59 inW02015157252 CD19 scFv 164 SEQ ID NO. 59 inW02016033570 CD19 scFv 165 SEQ ID NO. 6in W02015157252 CD19 scFv 166 SEQ ID NO. 6in W02016033570 CD19 scFv 167 SEQ ID NO. 7in W02014184143 CD19 scFv 168 SEQ ID NO. 7in W02015157252 CD19 scFv 169 SEQ ID NO. 8in W02015157252 CD19 scFv 170 SEQ ID NO. 8in W02016033570 CD19 scFv 171 SEQ ID NO. 87 inW02016033570 CD19 scFv 172 SEQ ID NO. 9in W02015157252 CD19 scFv 173 SEQ ID NO.9 in W02016139487 CD19 scFv 174 SEQ IDNO. 10 inUS20160152723 CD19 scFv 175 SEQ IDNO. 2in US20160152723 CD19 scFv 176 SEQ IDNO. 206 inUS20160152723 CD19 scFv 177 SEQ IDNO. 207 inUS20160152723 CD19 scFv 178 SEQ IDNO. 208 inUS20160152723 CD19 scFv 179 SEQ IDNO. 209 inUS20160152723 CD19 scFv 180 SEQ IDNO. 210 inUS20160152723 CD19 scFv 181 SEQ ID NO. 211 in US20160152723 CD19 scFv 182 SEQ IDNO. 212 inUS20160152723 CD19 scFv 183 SEQ ID NO. 213 in US20160152723 CD19 scFv 184 SEQ IDNO. 214 inUS20160152723 CD19 scFv 185 SEQ IDNO. 215 inUS20160152723 CD19 scFv 186 SEQ IDNO. 216 inUS20160152723 CD19 scFv 187 SEQ IDNO. 217 inUS20160152723 CD19 scFv 188 SEQ IDNO. 218 inUS20160152723 CD19 scFv 189 SEQ IDNO. 219 inUS20160152723 CD19 scFv 190 SEQ IDNO. 220 inUS20160152723 CD19 scFv 191 SEQ ID NO. 221 in US20160152723 CD19 scFv 192 SEQ IDNO. 222 inUS20160152723 CD19 scFv 193 SEQ ID NO. 223 in US20160152723 CD19 scFv 194 SEQ IDNO. 224 inUS20160152723 CD19 scFv 195 SEQ IDNO. 225 inUS20160152723 CD19 scFv 196 SEQ IDNO. 32 inEP308369 1A2 CD19 scFv 197 SEQ IDNO. 35 inEP3083691A2 CD19 scFv 198 SEQ IDNO. 38 inEP3083691A2 CD19 scFv 199 SEQ IDNO. 4in US20160152723

CD19 scFv 200 SEQ IDNO. 45in U20160152723 CD19 scFv 201 SEQ IDNO. 47 inUS20160152723 CD19 scFv 202 SEQ IDNO. 49in U20160152723 CD19 scFv 203 SEQ IDNO. 51 inUS20160152723 CD19 scFv 204 SEQ IDNO. 53 inUS20160152723 CD19 scFv 205 SEQ IDNO. 55 inUS20160152723 CD19 scFv 206 SEQ IDNO. 57 inUS20160152723 CD19 scFv 207 SEQ IDNO. 59 inUS20160152723 CD19 scFv 208 SEQ IDNO. 6in U20160152723 CD19 scFv 209 SEQ IDNO. 8in U20160152723 CD19 scFv 210 SEQ IDNO. 87 inUS20160152723 CD19 scFv 211 SEQ IDNO. 89 inUS20160152723 CD19 scFv 212 SEQ ID NO. 39in W2016109410 CD19 scFv 213 SEQ IDNO. 37 inEP3083671A1 CD19 scFv 214 SEQ ID NO. 174 in W02016115482 CD19 scFv 215 SEQ ID NO. 20in W2012079000 CD19 scFv 216 SEQ ID NO. 32in W2015092024 CD19 scFv 217 SEQ ID NO. 33in W2015092024A2 CD19 scFv 218 SEQ ID NO. 35in W2015092024A2 CD19 scFv 219 SEQ ID NO. 38 in W2015092024A2 CD19 scFv 220 SEQ ID NO. 40in W2016109410 CD19 scFv 221 SEQ ID NO. 41in W2016109410 CD19 scFv 222 SEQ ID NO. 42in W2016109410 CD19 scFv 223 SEQ ID NO. 43in W2016109410 CD19 scFv 224 SEQ ID NO. 44in W2016109410 CD19 scFv 225 SEQ ID NO. 45in W2016109410 CD19 scFv 226 SEQ ID NO. 46in W2016109410 CD19 scFv 227 SEQ ID NO. 47in W2016109410 CD19 scFv 228 SEQ ID NO. 48in W2016109410 CD19 scFv 229 SEQ ID NO. 49in W2016109410 CD19 scFv 230 SEQ ID NO. 5in W2015155341A1 CD19 scFv 231 SEQ ID NO. 50in W2016109410 CD19 scFv 232 SEQ ID NO. 51in W2016109410 CD19 scFv 233 SEQ ID NO. 7in US20160145337A1 CD19 scFv 234 SEQ ID NO. 9in US20160145337A1 CD19 scFv 235 SEQ ID NO.20 in US9499629B2 CD19 scFv 236 SEQ ID NO.6 in W2015155341A1 CD19 scFv 237 SEQ ID NO.73 in W02016164580 CD19 scFv 238 SEQ ID NO. 10 US20160152723 CD19 scFv 239 SEQ IDNO. 2in US20160152723 CD19 scFv 240 SEQ IDNO. 206 inUS20160152723 CD19 scFv 241 SEQ ID NO. 207 in US20160152723 CD19 scFv 242 SEQ IDNO. 209 inUS20160152723 CD19 scFv 243 SEQ ID NO. 210 in U20160152723 CD19 scFv 244 SEQ IDNO. 212in U20160152723 CD19 scFv 245 SEQ IDNO. 216in U20160152723 CD19 scFv 246 SEQ IDNO. 218in U20160152723 CD19 scFv 247 SEQ IDNO. 219in U20160152723 CD19 scFv 248 SEQ IDNO. 220in U20160152723 CD19 scFv 249 SEQ IDNO. 221in U20160152723 CD19 scFv 250 SEQ IDNO. 222in U20160152723 CD19 scFv 251 SEQ IDNO. 223in U20160152723 CD19 scFv 252 SEQ ID NO. 224 in US20160152723 CD19 scFv 253 SEQ ID NO. 225 in US20160152723 CD19 scFv 254 SEQ IDNO. 4in U20160152723

CD19 scFv 255 SEQ ID NO. 45 in US20160152723 CD19 scFv 256 SEQ ID NO. 47 in US20160152723 CD19 scFv 257 SEQ ID NO. 49 in US20160152723 CD19 scFv 258 SEQ ID NO. 51 in US20160152723 CD19 scFv 259 SEQ ID NO. 53 in US20160152723 CD19 scFv 260 SEQ ID NO. 55 in US20160152723 CD19 scFv 261 SEQ ID NO. 57 in US20160152723 CD19 scFv 262 SEQ ID NO. 59 in US20160152723 CD19 scFv 263 SEQ ID NO. 6 in US20160152723 CD19 scFv 264 SEQ ID NO. 8 in US20160152723 CD19 scFv 265 SEQ ID NO. 87 in US20160152723 CD19 scFv 266 SEQ ID NO. 89 in US20160152723 CD19 scFv 267 SEQ ID NO. 5 in W02016055551

Intracellularsignaling domains

[00211] The intracellular domain of a CAR fusion polypeptide, after binding to its target molecule, transmits a signal to the immune effector cell, activating at least one of the normal effector functions of immune effector cells, including cytolytic activity (e.g., cytokine secretion) or helper activity. Therefore, the intracellular domain comprises an "intracellular signaling domain" of a T cell receptor (TCR).

[00212] In some aspects, the entire intracellular signaling domain can be employed. In other aspects, a truncated portion of the intracellular signaling domain may be used in place of the intact chain as long as it transduces the effector function signal.

[00213] In some embodiments, the intracellular signaling domain of the present invention may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs (ITAMs). Examples of ITAM containing cytoplasmic signaling sequences include those derived from TCR CD3zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d. In one example, the intracellular signaling domain is a CD3 zeta (CD3() signaling domain.

[00214] In some embodiments, the intracellular region of the present invention further comprises one or more costimulatory signaling domains which provide additional signals to the immune effector cells. These costimulatory signaling domains, in combination with the signaling domain can further improve expansion, activation, memory, persistence, and tumor-eradicating efficiency of CAR engineered immune cells (e.g., CAR T cells). In some cases, the costimulatory signaling region contains 1, 2, 3, or 4 cytoplasmic domains of one or more intracellular signaling and /or costimulatory molecules. The costimulatory signaling domain may be the intracellular/cytoplasmic domain of a costimulatory molecule, including but not limited to CD2, CD7, CD27, CD28,4-1BB (CD137), OX40 (CD134), CD30, CD40, ICOS (CD278), GITR

(glucocorticoid-induced tumor necrosis factor receptor), LFA-1 (lymphocyte function-associated antigen- 1), LIGHT, NKG2C, B7-H3. In one example, the costimulatory signaling domain is derived from the cytoplasmic domain of CD28. In another example, the costimulatory signaling domain is derived from the cytoplasmic domain of 4-1BB (CD137). In another example, the co stimulatory signaling domain may be an intracellular domain of GITR as taught in U.S. Pat. NO.: 9, 175, 308; the contents of which are incorporated herein by reference in its entirety.

[00215] In some embodiments, the intracellular region of the present invention may comprise a functional signaling domain from a protein selected from the group consisting of an MHC class I molecule, a TNF receptor protein, an immunoglobulin-like protein, a cytokine receptor, an integrin, a signaling lymphocytic activation protein (SLAM) such as CD48, CD229, 2B4, CD84, NTB-A, CRACC, BLAME,CD2F-10, SLAMF6, SLAMF7, an activating NK cell receptor, BTLA, a Toll ligand receptor, OX40, CD2, CD7, CD27, CD28, CD30, CD40, CDS, ICAM-1, LFA-1 (CD11a/CD18),4-1BB (CD137), B7-H3, CDS, ICAM-1, ICOS (CD278), GITR, BAFFR, LIGHT, HVEM (LIGHTR), SLAMF7, NKp80 (KLRFI), NKp44, NKp30, NKp46, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, IL15Ra, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD1Id, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, NKG2D, NKG2C, NKD2C SLP76, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAMI, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMFI, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, CD270 (HVEM), GADS, SLP-76, PAG/Cbp, CD19a, a ligand that specifically binds with CD83, DAP 10, TRIM, ZAP70, Killer immunoglobulin receptors (KIRs) such as KIR2DL1, KIR2DL2/L3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1/S1, KIR3DL2, KIR3DL3, and KIR2DP1; lectin related NK cell receptors such as Ly49, Ly49A, and Ly49C.

[00216] In some embodiments, the intracellular signaling domain of the present invention may contain signaling domains derived from JAK-STAT. In other embodiments, the intracellular signaling domain of the present invention may contain signaling domains derived from DAP-12 (Death associated protein 12) (Topfer et al., Immunol., 2015, 194: 3201-3212; and Wang et al., Cancer Immunol., 2015, 3: 815-826). DAP-12 is a key signal transduction receptor in NK cells. The activating signals mediated by DAP-12 play important roles in triggering NK cell cytotoxicity responses toward certain tumor cells and virally infected cells. The cytoplasmic domain of DAP12 contains an Immunoreceptor Tyrosine-based Activation Motif (ITAM). Accordingly, a CAR containing a DAP12-derived signaling domain may be used for adoptive transfer of NK cells.

[00217] In some embodiments, T cells engineered with two or more CARs incorporating distinct co-stimulatory domains and regulated by distinct DD may be used to provide kinetic control of downstream signaling.

[00218] In some embodiments, the intracellular domain of the present invention may comprise amino acid sequences of Table 6.

Table 6: Intracellular signaling and co-stimulatory domains Description Amino Acid Sequence Amino Acid SEQ ID 2B4 co-stimulatory WRRKRKEKQSETSPKEFLTIYEDVKDLKTRRNHEQEQTFP 268 domain GGGSTIYSMIQSQSSAPTSQEPAYTLYSLIQPSRKSGSRKRN HSPSFNSTIYEVIGKSQPKAQNPARLSRKELENFDVYS CD27 co-stimulatory HQRRKYRSNKGESPVEPAEPCRYSCPREEEGSTIPIQEDYR 269 domain KPEPACSP CD272 (BTLA1) co- RRHQGKQNELSDTAGREINLVDAHLKSEQTEASTRQNSQ 270 stimulatory domain VLLSETGIYDNDPDLCFRMQEGSEVYSNPCLEENKPGVYA SLNHSVIGPNSRLARNVKEAPTEYASICVRS CD272 (BTLA1) co- CCLRRHQGKQNELSDTAGREINLVDAHLKSEQTEASTRQ 271 stimulatory domain NSQVLLSETGIYDNDPDLCFRMQEGSEVYSNPCLEENKPG IVYASLNHSVIGPNSRLARNVKEAPTEYASICVRS CD28 co-stimulatory FWVLVVVGGVLACYSLLVTVAFIIFWV 272 CD28 co-stimulatory KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGC 273 domain EL CD28 co-stimulatory FWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDF 274 domain AAYRS CD28 co-stimulatory RSKRSRGGHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAY 275 domain RS CD28 co-stimulatory RSKRSRGGHSDYIVINMTPRRPGPTRKHYQPYAPPRDFAA 276 domain YRS CD28 co-stimulatory MLRLLLALNLFPSIQVTGNKILVKQSPMLVAYDNAVNLSC 277 signaling region KYSYNLFSREFRASLHKGLDSAVEVCVVYGNYSQQLQVY SKTGFNCDGKLGNESVTFYLQNLYVNQTDIYFCKIEVMYP PPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVG GVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPG PTRKHYQPYAPPRDFAAYRS CD30 co-stimulatory RRACRKRIRQKLHLCYPVQTSQPKLELVDSRPRRSSTQLR 278 domain SGASVTEPVAEERGLMSQPLMETCHSVGAAYLESLPLQD ASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVG

TVKAELPEGRGLAGPAEPELEEELEADHTPHYPEQETEPPL GSCSDVMLSVEEEGKEDPLPTAASGK CD30 co-stimulatory RRACRKRIRQKLHLCYPVQTSQPKLELVDSRPRRSSTQLR 279 domain SGASVTEPVAEERGLMSQPLMETCHSVGAAYLESLPLQD ASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVG TVKAELPEGRGLAGPAEPELEEELEADHTPHYPEQETEPPL GSCSDVMLSVEEEGKEDPLPTAASGK GITR co-stimulatory HIWQLRSQCMWPRETQLLLEVPPSTEDARSCQFPEEERGE 280 domain RSAEEKGRLGDLWV HVEM co-stimulatory CVKRRKPRGDVVKVIVSVQRKRQEAEGEATVIEALQAPP 281 domain DVTTVAVEETIPSFTGRSPNH ICOS co-stimulatory TKKKYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL 282 domain ICOS co-stimulatory CWLTKKKYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL 283 signaling domain LAG-3 co-stimulatory HLWRRQWRPRRFSALEQGIHPPQAQSKIEELEQEPEPEPEP 284 region EPEPEPEPEPEQL OX40 co-stimulatory ALYLLRRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLA 285 domain KI OX40 co-stimulatory RRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKI 286 domain 4-1BB intracellular KRGRKKLLYIFKQPFMRPVQTIQEEDGCSCRFPEEEEGGCE 287 domain L 4-1BB signaling KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGY 288 domain EL 4-1BB-CD3Zeta TGTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG 289 intracellular domain LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSAD APAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG KPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKG HDGLYQGLSTATKDTYDALHMQALPPR 4-1BB-Z endodomain KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGC 290 fusion ELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDK RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIG MKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD127 intracellular KRIKPIVWPSLPDHKKTLEHLCKKPRKNLNVSFNPESFLDC 291 domain QIHRVDDIQARDEVEGFLQDTFPQQLEESEKQRLGGDVQS PNCPSEDVVITPESFGRDSSLTCLAGNVSACDAPILSSSRSL DCRESGKNGPHVYQDLLLSLGTTNSTLPPPFSLQSGILTLN PVAQGQPILTSLGSNQEEAYVTMSSFYQNQ CD137 intracellular RFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEE 292 domain EEGGCEL CD148 intracellular RKKRKDAKNNEVSFSQIKPKKSKLIRVENFEAYFKKQQAD 293 domain SNCGFAEEYEDLKLVGISQPKYAAELAENRGKNRYNNVL PYDISRVKLSVQTHSTDDYINANYMPGYHSKKDFIATQGP LPNTLKDFWRMVWEKNVYAIIMLTKCVEQGRTKCEEYW PSKQAQDYGDITVAMTSEIVLPEWTIRDFTVKNIQTSESHP LRQFHFTSWPDHGVPDTTDLLINFRYLVRDYMKQSPPESPI LVHCSAGVGRTGTFIAIDRLIYQIENENTVDVYGIVYDLR MHRPLMVQTEDQYVFLNQCVLDIVRSQKDSKVDLIYQNT TAMTIYENLAPVTTFGKTNGYIA CD27 intracellular QRRKYRSNKGESPVEPAEPCHYSCPREEEGSTIPIQEDYRK 294 domain PEPACSP CD28 intracellular FAAYRS 295 domain CD28 signaling chain FWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDY 296 MNMTPRRPGPTRKHYQPYAPPRDFAAYRS

CD28 signaling domain RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAY 297 RS CD28 signaling domain SKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYR 298 S CD28 signaling domain IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFW 299 VLVVVGGVLACYSLLVTVAFIIFWRSKRSRLLHSDYMNM TPRRPGPTRKHYQPYAPPRDFAAYRS CD28,4-1BB, and/or RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAY 300 CD3( signaling domain RSRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFP EEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRRE EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMA EAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPR CD28/CD3C AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSK 301 PFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDY MNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADA PAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGK PRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH DGLYQGLSTATKDTYDALHMQALPPR CD28-0XZ intracellular RSKRSRLLHSDYNMTPRRPGPTRKHYQPYAPPRDFAAYRS 302 domain RDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKIRVKFS RSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDP EMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR CD28-4-1BB MFWVLVVVGGVLACYSLLVTVAFIIFWVKRGRKKLLYIF 303 intracellular domain KQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL CD28-4-1BB IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFW 304 intracellular domain VLVVVGGVLACYSLLVTVAFIIFWVKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCEL CD28-CD3 Zeta RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAY 305 intracellular domain RSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDK RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIG MKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD28-CD3Zeta KRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS 306 intracellular domain RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 delta chain MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSIT 307 intracellular signaling WVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDK domain ESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALGV FCFAGHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYS HLGGNWARNK CD3 delta chain MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSIT 308 intracellular signaling WVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDK domain ESTVQVHYRTADTQALLRNDQVYQPLRDRDDAQYSHLG GNWARNK CD3 delta chain DQVYQPLRDRDDAQYSHLGGN 309 intracellular signaling domain CD3 delta intracellular MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSIT 310 domain WVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDK ESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALGV FCFAGHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYS HLGGNWARNK CD3 delta intracellular MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSIT 311 domain WVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDK

ESTVQVHYRTADTQALLRNDQVYQPLRDRDDAQYSHLG GNWARNK CD3 delta intracellular DQVYQPLRDRDDAQYSHLGGN 312 domain CD3 epsilon MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKV 313 intracellular domain SISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDE DHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVC ENCMEMDVMSVATIVIVDICITGGLLLLVYYWSKNRKAK AKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRD LYSGLNQRRI CD3 epsilon NPDYEPIRKGQRDLYSGLNQR 314 intracellular domain CD3 gamma MEQGKGLAVLILAIILLQGTLAQSIKGNHLVKVYDYQEDG 315 intracellular domain SVLLTCDAEAKNITWFKDGKMIGFLTEDKKKWNLGSNAK DPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGF LFAEIVSIFVLAVGVYFIAGQDGVRQSRASDKQTLLPNDQ LYQPLKDREDDQYSHLQGNQLRRN, CD3 gamma DQLYQPLKDREDDQYSHLQGN 316 intracellular domain CD3 gamma DQLYQPLKDREDDQYSHLQGN 317 intracellular domain CD3 gamma MEQGKGLAVLILAIILLQGTLAQSIKGNHLVKVYDYQEDG 318 intracellular domain SVLLTCDAEAKNITWFKDGKMIGFLTEDKKKWNLGSNAK DPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGF LFAEIVSIFVLAVGVYFIAGQDGVRQSRASDKQTLLPNDQ LYQPLKDREDDQYSHLQGNQLRRN CD3 zeta intracellular MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFI 319 domain YGVILTALFLRVKFSRSADAPAYQQGQNQLYNELNLGRR EEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKM AEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALH MQALPPR CD3 zeta intracellular MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFI 320 domain YGVILTALFLRVKFSRSADAPAYQQGQNQLYNELNLGRR EEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDAL HMQALPPR CD3 zeta intracellular MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFI 321 domain YGVILTALFLRVKFSRSADAPAYQQGQNQLYNELNLGRR EEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDAL HMQALPPR CD3 zeta intracellular NQLYNELNLGRREEYDVLDKR 322 domain CD3 zeta domain 2 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 323 (NM_000734.3) RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular DGLYQGLSTATKDTYDALHMQ 324 domain CD3 zeta intracellular RVKFSRSAEPPAYQQGQNQLYNELNLGRREEYDVLDKRR 325 domain GRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 326 domain RGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIG MKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDK 327 domain RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIG MKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR

CD3 zeta intracellular RVKFSRSADAPAYQQGEYDVLDKRRGRDPEMGGKPRRK 328 domain NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLY QGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RVKFSRSADAPAYQQGQNQLYNELNLGRREEVDVLDKR 329 domain RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular MIPAVVLLLLLLVEQAAALGEPQLCYILDAILFLVGIVLTL 330 domain LVCRLKIQVRKAAITSYEKSRVKFSRSADAPAYQQGQNQL YNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL YNELQKDKMAEAVSEIGMKGERRRGKGHDGLYQGLSTA TKDTYDALHMQALPPR CD3 zeta intracellular LRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 331 domain RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 332 domain RGRDPEMGGKPQRRKNPQEGLY CD3 zeta intracellular LRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 333 domain RGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIG MKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDK 334 domain RRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIG MKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular NQLYNELNLGRREEYDVLDKR 335 domain CD3 zeta intracellular EGLYNELQKDKMAEAYSEIGMK 336 domain CD3 zeta intracellular DGLYQGLSTATKDTYDALHMQ 337 domain CD3 zeta intracellular RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 338 domain RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKR 339 domain RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CD3 zeta intracellular RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKR 340 domain RGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALP CD3 zeta intracellular DPKLCYLLDGILFIYGVILTALFLRVKFSRSADAPAYQQGQ 341 domain NQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNP QEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQG LSTATKDTYDALHMQALPPR CD3 zeta intracellular MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFI 342 domain YGVILTALFLRVKFSRSADAPAYQQGQNQLYNELNLGRR EEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKM AEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALH MQALPPR CD40 intracellular RSRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKI 343 domain CD79A intracellular MPGGPGVLQALPATIFLLFLLSAVYLGPGCQALWMHKVP 344 domain ASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWP PEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQEGNESYQQ SCGTYLRVRQPPPRPFLDMGEGTKNRIITAEGIILLFCAVVP GTLLLFRKRWQNEKLGLDAGDEYEDENLYEGLNLDDCS MYEDISRGLQGTYQDVGSLNIGDVQLEKP CD79A intracellular MPGGPGVLQALPATIFLLFLLSAVYLGPGCQALWMHKVP 345 domain ASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWP PEFLGPGEDPNEPPPRPFLDMGEGTKNRIITAEGIILLFCAV

VPGTLLLFRKRWQNEKLGLDAGDEYEDENLYEGLNLDDC SMYEDISRGLQGTYQDVGSLNIGDVQLEKP CD79A intracellular MPGGPGVLQALPATIFLLFLLSAVYLGPGCQALWMHKVP 346 domain ASLMVSLGEDAHFQCPHNSSNNANVTWWRVLHGNYTWP PEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQEGNESYQQ SCGTYLRVRQPPPRPFLDMGEGTKNRIITAEGIILLFCAVVP GTLLLFRKRWQNEKLGLDAGDEYEDENLYEGLNLDDCS MYEDISRGLQGTYQDVGSLNIGDVQLEKP CD79A intracellular ENLYEGLNLDDCSMYEDISRG 347 domain CD8 intracellular FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAG 348 domain GAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHR NR CD8 intracellular FVPVFLPAKPITTPAPRPPTPAPTIASQPLSLRPEACRPAAG 349 domain GAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHR NR CD8a intracellular PTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGL 350 domain DFACDI CTLA4 intracellular AVSLSKMLKKRSPLTTGVFVKMAPTEAECEKQFQPYFIPI 351 domain N CTLA4 intracellular AVSLSKMLKKRSPLTTGVYMNMTPRRPECEKQFQPYAPP 352 domain RDFAAYRS DAP10 intracellular RPRRSPAQDGKVYINMPGRG 353 domain DAP12 intracellular MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSP 354 domain GVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEAAT RKQRITETESPYQELQGQRSDVYSDLNTQRPYYK DAP12 intracellular MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSP 355 domain GVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEATR KQRITETESPYQELQGQRSDVYSDLNTQRPYYK DAP12 intracellular MGGLEPCSRLLLLPLLLAVSDCSCSTVSPGVLAGIVMGDL 356 domain VLTVLIALAVYFLGRLVPRGRGAAEAATRKQRITETESPY QELQGQRSDVYSDLNTQRPYYK DAP12 intracellular MGGLEPCSRLLLLPLLLAVSDCSCSTVSPGVLAGIVMGDL 357 domain VLTVLIALAVYFLGRLVPRGRGAAEATRKQRITETESPYQ ELQGQRSDVYSDLNTQRPYYK DAP12 intracellular MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSP 358 domain GVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEAAT RKQRITETESPYQELQGQRSDVYSDLNTQRPYYK DAP12 intracellular MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSP 359 domain GVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEATR KQRITETESPYQELQGQRSDVYSDLNTQRPYYK; DAP12 intracellular MGGLEPCSRLLLLPLLLAVSDCSCSTVSPGVLAGIVMGDL 360 domain VLTVLIALAVYFLGRLVPRGRGAAEAATRKQRITETESPY QELQGQRSDVYSDLNTQRPYYK DAP12 intracellular MGGLEPCSRLLLLPLLLAVSDCSCSTVSPGVLAGIVMGDL 361 domain VLTVLIALAVYFLGRLVPRGRGAAEATRKQRITETESPYQ ELQGQRSDVYSDLNTQRPYYK DAP12 intracellular ESPYQELQGQRSDVYSDLNTQ 362 domain DAP12 intracellular ESPYQELQGQRSDVYSDLNTQ 363 domain GITR intracellular RSQCMWPRETQLLLEVPPSTEDARSCQFPEEERGERSAEE 364 domain KGRLGDLWV ICOS intracellular TKKKYSSSVHDPNGEFMFMRAVNTAKKSRLTDVTL 365 domain

IL15Ra intracellular KSRQTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL 366 domain OX40-CD3 Zeta RRDQRLPPDAHKPPGGGSFRTPIQEEQADAHSTLAKIRVK 367 intracellular domain FSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR ZAP70 intracellular MPDPAAHLPFFYGSISRAEAEEHLKLAGMADGLFLLRQCL 368 domain RSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGP AELCEFYSRDPDGLPCNLRKPCNRPSGLEPQPGVFDCLRD AMVRDYVRQTWKLEGEALEQAIISQAPQVEKLIATTAHE RMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTY ALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEY LKLKADGLIYCLKEACPNSSASNASGAAAPTLPAHPSTLT HPQRRIDTLNSDGYTPEPARITSPDKPRPMPMDTSVYESPY SDPEELKDKKLFLKRDNLLIADIELGCGNFGSVRQGVYRM RKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYI VRLIGVCQAEALMLVMEMAGGGPLHKFLVGKREEIPVSN VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA KISDFGLSKALGADDSYYTARSAGKWPLKWYAPECINFR KFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFI EQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQ RMRACYYSLASKVEGPPGSTQKAEAACA CD28 intracellular MLRLLLALNLFPSIQVTGNKILVKQSPMLVAYDNAVNLSC 369 domain KYSYNLFSREFRASLHKGLDSAVEVCVVYGNYSQQLQVY SKTGFNCDGKLGNESVTFYLQNLYVNQTDIYFCKIEVMYP PPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVG GVLACYSLLVTVAFIIFWVR 4-1BB intracellular MGNSCYNIVATLLLVLNFERTRSLQDPCSNCPAGTFCDNN 370 domain RNQICSPCPPNSFSSAGGQRTCDICRQCKGVFRTRKECSST SNAECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKD CCFGTFNDQKRGICRPWTNCSLDGKSVLVNGTKERDVVC GPSPADLSPGASSVTPPAPAREPGHSPQIISFFLALTSTALLF LLFFLTLRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDG Fc epsilon Receptor I MIPAVVLLLLLLVEQAAALGEPQLCYILDAILFLYGIVLTL 371 gamma chain LYCRLKIQVRKAAITSYEKSDGVYTGLSTRNQETYETLKH intracellular domain EKPPQ Fc epsilon Receptor I DGVYTGLSTRNQETYETLKHE 372 gamma chain intracellular domain Fc epsilon Receptor I DPKLCYILDAILFLYGIVLTLLYCRLKIQVRKAAITSYEKSD 373 gamma chain GVYTGLSTRNQETYETLKHEKPPQ intracellular domain Fc epsilon Receptor I DGVYTGLSTRNQETYETLKHE 374 gamma chain intracellular domain

Transmembranedomains

[00219] In some embodiments, the CAR of the present invention may comprise a transmembrane domain. As used herein, the term "Transmembrane domain (TM)" refers broadly to an amino acid sequence of about 15 residues in length which spans the plasma membrane. More preferably, a transmembrane domain includes at least 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 amino acid residues and spans the plasma membrane. In some embodiments, the transmembrane domain of the present invention may be derived either from a natural or from a synthetic source. The transmembrane domain of a CAR may be derived from any naturally membrane-bound or transmembrane protein. For example, the transmembrane region may be derived from (i.e. comprise at least the transmembrane region(s) of) the alpha, beta or zeta chain of the T-cell receptor, CD3 epsilon, CD4, CD5, CD8, CD8a, CD9, CD16, CD22, CD33, CD28, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD152, or CD154.

[00220] Alternatively, the transmembrane domain of the present invention may be synthetic. In some aspects, the synthetic sequence may comprise predominantly hydrophobic residues such as leucine and valine.

[00221] In some embodiments, the transmembrane domain of the present invention may be selected from the group consisting of a CD8a transmembrane domain, a CD4 transmembrane domain, a CD 28 transmembrane domain, a CTLA-4 transmembrane domain, a PD-I transmembrane domain, and a human IgG4 Fc region. As non-limiting examples, the transmembrane domain may be a CTLA-4 transmembrane domain comprising the amino acid sequences of SEQ ID NOs.: 1-5 of International Patent Publication NO.: WO2014/100385; and a PD-i transmembrane domain comprising the amino acid sequences of SEQ ID NOs.: 6-8 of International Patent Publication NO.: WO2014100385; the contents of each of which are incorporated herein by reference in their entirety.

[00222] In some embodiments, the CAR of the present invention may comprise an optional hinge region (also called spacer). A hinge sequence is a short sequence of amino acids that facilitates flexibility of the extracellular targeting domain that moves the target binding domain away from the effector cell surface to enable proper cell/cell contact, target binding and effector cell activation (Patel et al., Gene Therapy, 1999; 6: 412-419). The hinge sequence may be positioned between the targeting moiety and the transmembrane domain. The hinge sequence can be any suitable sequence derived or obtained from any suitable molecule. The hinge sequence may be derived from all or part of an immunoglobulin (e.g., IgG1, IgG2, IgG3, IgG4) hinge region, i.e., the sequence that falls between the CHI and CH2 domains of an immunoglobulin, e.g., an IgG4 Fc hinge, the extracellular regions of type 1 membrane proteins such as CD8a CD4, CD28 and CD7, which may be a wild type sequence or a derivative. Some hinge regions include an immunoglobulin CH3 domain or both a CH3 domain and a CH2 domain. In certain embodiments, the hinge region may be modified from an IgGI, IgG2, IgG3, or IgG4 that includes one or more amino acid residues, for example, 1, 2, 3, 4 or 5 residues, substituted with an amino acid residue different from that present in an unmodified hinge. Table 7 provides various transmembrane regions that can be used in the CARs described herein. Table 7: Transmembrane domains Transmembrane domain Amino Acid Sequence SEQ ID NO. CD8 Transmembrane TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF 375 domain ACDI 2B4 Transmembrane FLVIIVILSALFLGTLACFCV 424 domain 4-1BB Transmembrane IISFFLALTSTALLFLLFFLTLRFSVVKRGR 376 domain 4-1BB Transmembrane IISFFLALTSTALLFLLFFLTLRFSVV 377 domain CD134 (OX40) VAAILGLGLVLGLLGPLAILLALYLL 378 Transmembrane domain CD148 Transmembrane AVFGCIFGALVIVTVGGFIFWRKKRKDAKNNEVSFSQIKPK 379 and intracellular domain KSKLIRVENFEAYFKKQQADSNCGFAEEYEDLKLVGISQPK YAAELAENRGKNRYNNVLPYDISRVKLSVQTHSTDDYINA NYMPGYHSKKDFIATQGPLPNTLKDFWRMVWEKNVYAII MLTKCVEQGRTKCEEYWPSKQAQDYGDITVAMTSEIVLPE VVTIRDFTVKNIQTSESHPLRQFHFTSWPDHGVPDTTDLLIN FRYLVRDYMKQSPPESPILVHCSAGVGRTGTFIAIDRLIYQI ENENTVDVYGIVYDLRMHRPLMVQTEDQYVFLNQCVLDI VRSQKDSKVDLIYQNTTAMTIYENLAPVTTFGKTNGYIA CD148 Transmembrane AVFGCIFGALVIVTVGGFIFW 380 domain CD2 Transmembrane KEITNALETWGALGQDINLDIPSFQMSDDIDDIKWEKTSDK 381 domain KKIAQFRKEKETFKEKDTYKLFKNGTLKIKHLKTDDQDIYK VSIYDTKGKNVLEKIFDLKIQERVSKPKISWTCINTTLTCEV MNGTDPELNLYQDGKHLKLSQRVITHKWTTSLSAKFKCTA GNKVSKESSVEPVSCPEKGLD CD28 Transmembrane and IEVMYPPPYLDNEKSNGTITHVKGKHLCPSPLFPGPSKPFW 382 intracellular domain VLVVVGGVLACYSLLVTVAHIFWVRSKRSRLLHSDYMNM TPRRPGPTRKHYQPYAPPRDFAAYRS CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWV 383 domain CD28 Transmembrane IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWV 384 domain LVVVGGVLACYSLLVTVAFIIFWV CD28 Transmembrane IFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRR 385 domain CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYM 386 domain NMTPRRPGPTRKHYQP YAPPRDFAAYRS CD28 Transmembrane MFWVLVVVGGVLACYSLLVTVAFIIFWV 387 domain CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFHFWV 388 domain CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYM 425 domain NMTPRRPGPTRKHYQAYAAARDFAAYRS CD28 Transmembrane IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWV 897 domain LWVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTP RRPGPTRKHYQPYAPPRDFAAYRS CD28 Transmembrane MFWVLVVVGGVLACYSGGVTVAFIIFWV 389 domain

CD28 Transmembrane WVLVVVGGVLACYSLLVTVAFIIFWV 390 domain CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWVR 898 domain CD28 Transmembrane PFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDY 391 domain MNMTPRRPGPTRKHYQPYAPPRDFAAYRS CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYM 392 domain and CD28 and NMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPA CD3 Zeta intracellular YQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRR domain KNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLY QGLSTATKDTYDALHMQALPPR CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYM 393 domain and CD28, OX40, NMTPRRPGPTRKHYQPYAPPRDFAAYRSRDQRLPPDAHKP and CD3 Zeta intracellular PGGGSFRTPIQEEQADAHSTLAKIRVKFSRSADAPAYQQGQ domain NQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQE GLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLST ATKDTYDALHMQALPPR CD28 Transmembrane FWVLVVVGGVLACYSLLVTVAFIIFWVRRVKFSRSADAPA 394 domain and CD3 Zeta YQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRR intracellular domain KNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLY QGLSTATKDTYDALHMQALPPR CD28 transmembrane-CD3 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP 395 zeta signaling domain FWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYM ("28z") NMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPA YQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRR KNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLY QGLSTATKDTYDALHMQALPPR CD3 zeta Transmembrane LCYLLDGILFIYGVILTALFLRV 396 domain CD3 zeta Transmembrane MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFIY 397 domain GVILTALFL CD3 zeta Transmembrane LCYLLDGILFIYGVILTALFL 398 domain CD4 Transmembrane ALIVLGGVAGLLLFIGLGIFFCVRC 399 domain CD4 Transmembrane MALIVLGGVAGLLLFIGLGIFF 400 domain CD45 Transmembrane and ALIAFLAFLIIVTSIALLVVLYKIYDLHKKRSCNLDEQQELV 401 intracellular domain ERDDEKQLMNVEPIHADILLETYKRKIADEGRLFLAEFQSIP RVFSKFPIKEARKPFNQNKNRYVDILPYDYNRVELSEINGD AGSNYINASYIDGFKEPRKYIAAQGPRDETVDDFWRMIWE QKATVIVMVTRCEEGNRNKCAEYWPSMEEGTRAFGDVVV KINQHKRCPDYIIQKLNIVNKKEKATGREVTHIQFTSWPDH GVPEDPHLLLKLRRRVNAFSNFFSGPIWHCSAGVGRTGTYI GIDAMLEGLEAENKVDVYGYVVKLRRQRCLMVQVEAQYI LIHQALVEYNQFGETEVNLSELHPYLHNMKKRDPPSEPSPL EAEFQRLPSYRSWRTQHIGNQEENKSKNRNSNVIPYDYNR VPLKHELEMSKESEHDSDESSDDDSDSEEPSKYINASFIMSY WKPEVMIAAQGPLKETIGDFWQMIFQRKVKVIVMLTELKH GDQEICAQYWGEGKQTYGDIEVDLKDTDKSSTYTLRVFEL RHSKRKDSRTVYQYQYTNWSVEQLPAEPKELISMIQWKQK LPQKNSSEGNKHHKSTPLLIHCRDGSQQTGIFCALLNLLES AETEEWDIFQWKALRKARPGMVSTFEQYQFLYDVIASTYP AQNGQVKKNNHQEDKIEFDNEVDKVKQDANCVNPLGAPE KLPEAKEQAEGSEPTSGTEGPEHSVNGPASPALNQGS CD62L Transmembrane PLFIPVAVMVTAFSGLAFIIWLA 402 domain

CD7 Transmembrane ALPAALAVISFLLGLGLGVACVLA 403 domain CD8 Transmembrane MALPVTALLLPLALLLHAARP 404 domain CD8 Transmembrane AAAFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPA 405 domain and CD28 AGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCN signaling domain HRNRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFA AYRSRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRF PEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRRE EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMA EAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ ALPPR CD8 transmembrane AAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR 406 domain-CD137 (4-1BB) GLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYI signaling domain and CD3 FKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSAD zeta signaling domain APAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG ("BBz") KPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH DGLYQGLSTATKDTYDALHMQALPPR CD8a Transmembrane FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGG 407 domain AVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRN CD8a Transmembrane IWAPLAGTCGVLLLSLVITLYC 408 domain CD8a Transmembrane IYIWAPLAGTCGVLLLSLVITLYC 409 domain CD8a Transmembrane IYIWAPLAGTCGVLLLSLVITLYCR 410 domain CD8a Transmembrane PTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 411 domain FACDIYIWAPLAGTCGVLLLSLVITLYCN CD8a Transmembrane IYIWAPLAGTCGVLLLSLVITLVCR 412 domain CD8a Transmembrane IYIWAPLAGTCGVLLLSLVIT 413 domain CD8a Transmembrane IYIWAPLAGTCGVLLLSLVITLY 414 domain CD8a Transmembrane TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAWTRGLDFAC 899 domain (NP 001139345.1) DIYIWAPLAGTCGVLLLSLVITLYCNHRNRRR CD8b Transmembrane LGLLVAGVLVLLVSLGVAIHLCC 900 domain DAP10 Transmembrane ILLAGLVAADAVASLLIVGAVFLCARR 901 domain EpoR Transmembrane APVGLVARLADESGHVVLRWLPPPETPMTSHIRYEVDVSA 415 domain GNGAGSVQRVEILEGRTECVLSNLRGRTRYTFAVRARMAE PSFGGFWSAWSEPVSLLTPSD FcERI a Transmembrane FFIPLLVVILFAVDTGLFISTQQQVTFLLKIKRTRKGFRLLNP 416 domain HPKPNPKNN FcERI a- Transmembrane MAPAMESPTLLCVALLFFAPDGVLAVPQKPKVSLNPPWNR 417 domain IFKGENVTLTCNGNNFFEVSSTKWFHNGSLSEETNSSLNIV NAKFEDSGEYKCQHQQVNESEPVYLEVFSDWLLLQASAEV VMEGQPLFLRCHGWRNWDVYKVIYYKDGEALKYWYENH NISITNATVEDSGTYYCTGKVWQLDYESEPLNITVIKAPRE KYWLQFFIPLLVVILFAVDTGLFISTQQQVTFLLKIKRTRKG FRLLNPHPKPNPKNN FcERI b- Transmembrane MDTESNRRANLALPQEPSSVPAFEVLEISPQEVSSGRLLKSA 418 region SSPPLHTWLTVLKKEQEFLGVTQILTAMICLCFGTVVCSVL DISHIEGDIFSSFKAGYPFWGAIFFSISGMLSIISERRNATYLV RGSLGANTASSIAGGTGITILIINLKKSLAYIHIHSCQKFFETK

CFMASFSTEIVVMMLFLTILGLGSAVSLTICGAGEELKGNK VPEDRVYEELNIYSATYSELEDPGEMSPPIDL FcERI g- Transmembrane MIPAVVLLLLLLVEQAAALGEPQLCYILDAILFLYGIVLTLL 419 region YCRLKIQVRKAAITSYEKSDGVYTGLSTRNQETYETLKHEK PPQ FeeRla Transmembrane DIFIPLLVVILFAVDTGLFISTQQQVTFLLKIKRTRKGFRLLN 420 domain PHPKPNPKNNR GITR Transmembrane PLGWLTVVLLAVAACVLLLTSAQLGLHIWQL 421 domain Her2 Transmembrane SIISAVVGILLVVVLGVVFGILII 422 domain Her2 Transmembrane CHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPS 423 domain GVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGC PAEQRASPLTSIISAVVGILLVVVLGVVFGILI ICOS Transmembrane FWLPIGCAAFVVVCILGCILI 902 domain IgG1Transmembrane EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTPE 903 domain VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGKKD LAG-3 Transmembrane LLFLILGVLSLLLLVTGAFGF 904 domain OX40 Transmembrane VAAILGLGLVLGLLGPLAILL 905 domain PD-1 Transmembrane VGWGGLLGSLVLLVWVLAVI 906 domain Transmembrane domain FWALVVVAGVLFCYGLLVTVALCVIWT 907

[00223] Hinge region sequences useful in the present invention are provided in Table 8A. Table 8A: Hinge regions Hinge Domain Amino Acid Sequence SEQID NO. Hinge DKTHT 426 Hinge CPPC 427 Hinge CPEPKSCDTPPPCPR 428 Hinge ELKTPLGDTTHT 429 Hinge KSCDKTHTCP 430 Hinge KCCVDCP 431 Hinge KYGPPCP 432 C233P Hinge VEPKSPDKTHTCPPCP 433 C233S Hinge LDPKSSDKTHTCPPCP 434 CD28 Hinge IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP 435 CD8a Hinge GGAVHTRGLDFA 436 CD8a Hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 437 FACD CD8a Hinge AKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR 438 GLDFACD

CD8a Hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 439 FACD CD8a Hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 440 FACD CD8a Hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 441 FACDEPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDT CD8a Hinge PAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT 442 RGLDFACDIY CD8a Hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 443 FACDIYIWAPLAGTCGVLLLSLVITLYC CD8a Hinge TTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF 444 ACD CD8a Hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 445 FACDIY Delta5 Hinge LDKTHTCPPCP 446 EpoR Hinge APVGLVARLADESGHVVLRWLPPPETPMTSHIRYEVDVS 447 AGNGAGSVQRVEILEGRTECVLSNLRGRTRYTFAVRARM AEPSFGGFWSAWSEPVSLLTPSD FCRI1a Hinge GLAVSTISSFFPPGYQ 448 FcyRl1a Hinge GLAVSTISSFFPPGYQ 449 Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 450 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFW AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH Hinge YVTVSSQDPAEPKSPDKTHTCPPCPAPELLGGPSVFLFPPK 451 PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKKDPK Hinge KPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG 452 LDFA Hinge LEPKSCDKTHTCPPCP 453 Hinge KPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG 454 LD Hinge EPKSCDKTHTCPPCP 455 Hinge ELKTPLGDTHTCPRCP 456 Hinge EPKSCDTPPPCPRCP 457 Hinge ESKYGPPCPSCP 458 Hinge ERKCCVECPPCP 459 Hinge (CH2- ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT 460 CH3) CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK Hinge (CH3) ESKYGPPCPPCPGQPREPQVYTLPPSQEEMTKNQVSLTCL 461 VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 462 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFW AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 463 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLHPSL PPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCEV SGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFWA WSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVSY VTDH IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 464 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMVVLEDQREVNTSGFAPARPPPQPGSTTFW AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH IgD Hinge ESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEE 465 KKKEKEKEEQEERETKTP IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 466 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFW AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 467 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFW AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 468 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFW AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH IgD Hinge RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGR 469 GGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAV QDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGV EEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPS LPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCE VSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFW

AWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVS YVTDH IgG1 (CH2CH3) AEPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIART 470 Hinge domain PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE QYNSTYRVVSVUTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKKD IgG1 (CH2CH3) AEPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIART 471 Hinge domain PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKKD IgG1 Hinge AEPKSPDKTHTCPPCPKDPK 472 IgG1 Hinge EPKSCDKTHTCPPCP 473 IgG1 Hinge EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTP 474 EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEVKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKKD IgG1 Hinge SVFLFPPKPKDTL 475 IgG1 Hinge EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTP 476 EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK IgG1 Hinge EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTP 477 EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKKDPK IgG1 Hinge VECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD 478 VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK IgG1 Hinge DPAEPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIA 479 (CH2CH3 RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR domain) EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKK IgG2 Hinge ERKCCVECPPCP 480 IgG3 Hinge ELKTPLGDTTHTCPRCP 481 IgG3 Hinge ELKTPLGDTHTCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPC 482 PRCPEPKSCDTPPPCPRCP IgG4 (CH2 and ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT 483 CH3) CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA

VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGKM IgG4 (CH2 and ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT 484 CH3) CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFQS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGKM IgG4 Hinge SPNMVPHAHHAQ 485 IgG4 Hinge GQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE 486 WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge ESKYGPPCPPCPGGGSSGGGSGGQPREPQVYTLPPSQEEM 487 TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYT QKSLSLSLGK IgG4 Hinge ESKYGPPCPSCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT 488 CVVVDVSQEDPEVQFNWYVDGVEVHQAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFVPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT 489 CVVVDVSQEDPEVQFNWYVDGVEVHQAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFVPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT 490 CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGKM IgG4 Hinge GAATCTAAGTACGGACCGCCCTGCCCCCCTTGCCCT 491 IgG4 Hinge ESKYGPPCPPCP 492 IgG4 Hinge ESKYGPPCPPCPGQPREPQVYTLPPSQEEMTKNQVSLTCL 493 VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT 494 CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT 495 CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge ESKYGPPCPPCP 496 IgG4 Hinge YGPPCPPCP 497 IgG4 Hinge KYGPPCPPCP 498 IgG4 Hinge EVVKYGPPCPPCP 499

IgG4 Hinge ESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT 500 CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDLSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGK IgG4 Hinge and ESKYGPPCPPCPGGGSSGGGSG 501 Linker IgGI Hinge EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTP 502 EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTIPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK IgGI Hinge EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTP 503 EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTIPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK IgGI Hinge EPKSPDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMIARTP 504 EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[002241 Hinge and transmembrane region sequences useful in the present invention are provided in Table 8B. Table 8B: Hinge and Transmembrane regions

Hinge Domain Amino Acid Sequence SEQ ID

CD8a Transmembrane TTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF 505 and Hinge ACDIYIWAPLAGTCGVLLLSLVITLYC CD8a Transmembrane DIQMTQSSSYLSVSLGGRVTITCKASDHINNWLAWYQQK 506 and Hinge PGNAPRLLISGATSLETGVPSRFSGSGSGKDYTLSITSLQTE DVATYYCQQYWSTPFTFGSGTKLEIKGGGGSGGGGSGGG GSQVQLKESGPGLVAPSQSLSITSTVSGFSLSRYSVHWVR QPPGKGLEWLGMIWGGGSTDYNSALKSRLSISKDNSKSQ VFLKMNSLQTDDTAMYYCARNEGDTTAGTWFAYWGQG TLVTVSS CD8a Transmembrane ALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLS 507 and Hinge LRPEACRPAAGGAVHTRGLD CD8a Transmembrane TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLD 508 and Hinge FACDIYIWAPLAGTCGVLLLSLVITLY CD8a Transmembrane KPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG 509 and Hinge LDFACDIYIWAPLAGTCGVLLLSLVITLY

[00225] In some embodiments, the CAR of the present invention may comprise one or more linkers between any of the domains of the CAR. The linker may be between 1-30 amino acids long. In this regard, the linker may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,

19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 amino acids in length. In other embodiments, the linker may be flexible.

[00226] In some embodiments, the components including the targeting moiety, transmembrane domain and intracellular signaling domains of the present invention may be constructed in a single fusion polypeptide. The fusion polypeptide may be the payload of an effector module of the invention. In some embodiments, more than one CAR fusion polypeptides may be included in an effector module, for example, two, three or more CARs may be included in the effector module under the control of a single SRE (e.g., a DD). Representative effector modules comprising the CAR payload are illustrated in Figures 2-6.

[00227] In some embodiments, the CAR sequences may be selected from Table 9. Table 9: CAR sequences Description SEQ ID Source NO CD19 CAR 510 SEQ ID NO: 12 in US9499629B2 CD19 CAR 511 SEQ ID NO: 24 in US20160333108A1 CD19 CAR 512 SEQ ID NO: 25 in US20160333108A1 CD19 CAR 513 SEQ ID NO: 26 in US20160333108A1 CD19 CAR 514 SEQ ID NO: 27 in US20160333108A1 CD19 CAR 515 SEQ ID NO: 1 in EP2997134A4 CD19 CAR 516 SEQ ID NO: 19 in EP3071687A1 CD19 CAR 517 SEQ ID NO: 20 in EP3071687A1 CD19 CAR 518 SEQ ID NO: 181 in W2016168773A3 CD19 CAR 519 SEQ ID NO: 2 in W2015157399A9 CD19 CAR 520 SEQ ID NO: 56 in W2016174409A1 CD19 CAR 521 SEQ ID NO: 62 in W2016174409A1 CD19 CAR 522 SEQ ID NO: 145 in WO2016179319A1 CD19 CAR 523 SEQ ID NO: 293 in US20160311907A1 CD19 CAR 524 SEQ ID NO: 294 in US20160311907A1 CD19 CAR 525 SEQ ID NO: 295 in US20160311907A1 CD19 CAR 526 SEQ ID NO: 296 in US20160311907A1 CD19 CAR 527 SEQ ID NO: 297 in US20160311907A1 CD19 CAR 528 SEQ ID NO: 298 in US20160311907A1 CD19 CAR 529 SEQ ID NO. 73 in WO2013176915A1 CD19 CAR 530 SEQ ID NO. 73 in WO2013176916A1 CD19 CAR 531 SEQ ID NO. 73 in US20130315884A1 CD19 CAR 532 SEQ ID NO. 73 in US20140134142A1 CD19 CAR 533 SEQ ID NO. 73 in US20150017136A1 CD19 CAR 534 SEQ ID NO. 73 in US20150203817A1 CD19 CAR 535 SEQ ID NO. 73 in US20160120905A1 CD19 CAR 536 SEQ ID NO. 73 in US20160120906A1 CD19 CAR 537 SEQ ID NO. 8 in W02015124715 CD19 CAR 538 SEQ ID NO. 5 in W02015124715 CD19 CAR 539 SEQ ID NO. 73 in W02014184744 CD19 CAR 540 SEQ ID NO. 73 in W02014184741 CD19 CAR 541 SEQ ID NO. 14 in US20160145337A1 CD19 CAR 542 SEQ ID NO. 15 in US20160145337A1 CD19 CAR 543 SEQ ID NO. 14 in W02014184143

CD19 CAR 544 SEQ ID NO. 15 in WO2014184143 CD19 CAR 545 SEQ ID NO. 15 in WO2015075175 CD19 CAR 546 SEQ ID NO. 16 in WO2015075175 CD19 CAR 547 SEQ ID NO. 16 in US20160145337A1 CD19 CAR 548 SEQ ID NO. 16 in WO2014184143 CD19 CAR 549 SEQ ID NO 12 in WO2012079000 CD19 CAR 550 SEQ ID NO.31 in WO2016164580 CD19 CAR 551 SEQ ID NO.32 in WO2016164580 CD19 CAR 552 SEQ ID NO.33 in WO2016164580 CD19 CAR 553 SEQ ID NO.34 in WO2016164580 CD19 CAR 554 SEQ ID NO.35 in WO2016164580 CD19 CAR 555 SEQ ID NO.36 in WO2016164580 CD19 CAR 556 SEQ ID NO.37 in WO2016164580 CD19 CAR 557 SEQ ID NO.38 in W02016164580 CD19 CAR 558 SEQ ID NO.39 in W02016164580 CD19 CAR 559 SEQ ID NO.40 in W02016164580 CD19 CAR 560 SEQ ID NO.41 in WO2016164580 CD19 CAR 561 SEQ ID NO.42 in WO2016164580 CD19 CAR 562 SEQ ID NO.58 in W02016164580 CD19 CAR 563 SEQ ID NO: 14 in US20160296563A1 CD19 CAR 564 SEQ ID NO: 15 in US20160296563A1 CD19 CAR 565 SEQ ID NO.31 in W02015157252 CD19 CAR 566 SEQ ID NO.32 in W02015157252 CD19 CAR 567 SEQ ID NO.33 in W02015157252 CD19 CAR 568 SEQ ID NO.34 in W02015157252 CD19 CAR 569 SEQ ID NO.35 in W02015157252 CD19 CAR 570 SEQ ID NO.36 in W02015157252 CD19 CAR 571 SEQ ID NO.37 in W02015157252 CD19 CAR 572 SEQ ID NO.38 in W02015157252 CD19 CAR 573 SEQ ID NO.39 in W02015157252 CD19 CAR 574 SEQ ID NO.40 in W02015157252 CD19 CAR 575 SEQ ID NO.41 in W02015157252 CD19 CAR 576 SEQ ID NO.42 in W02015157252 CD19 CAR 577 SEQ ID NO. 14 in W02016139487 CD19 CAR 578 SEQ ID NO.15 in W02016139487 CD19 CAR 579 SEQ ID NO: 53 in US20160250258A1 CD19 CAR 580 SEQ ID NO: 54 in US20160250258A1 CD19 CAR 581 SEQ ID NO: 55 in US20160250258A1 CD19 CAR 582 SEQ ID NO: 56 in US20160250258A1 CD19 CAR 583 SEQ ID NO: 57 in US20160250258A1 CD19 CAR 584 SEQ ID NO: 58 in US20160250258A1 CD19 CAR 585 SEQ ID NO. 1 in W02015187528 CD19 CAR 586 SEQ ID NO. 2 in W02015187528 CD19 CAR 587 SEQ ID NO. 3 in W02015187528 CD19 CAR 588 SEQ ID NO. 4 in W02015187528 CD19 CAR 589 SEQ ID NO. 5 in W02015187528 CD19 CAR 590 SEQ ID NO. 6 in W02015187528 CD19 CAR 591 SEQ ID NO. 7 in W02015187528 CD19 CAR 592 SEQ ID NO. 8 in W02015187528 CD19 CAR 593 SEQ ID NO. 9 in W02015187528 CD19 CAR 594 SEQ ID NO. 10 in W02015187528 CD19 CAR 595 SEQ ID NO. 11 in W02015187528 CD19 CAR 596 SEQ ID NO. 12 in W02015187528 CD19 CAR 597 SEQ ID NO. 13 in W02015187528 CD19 CAR 598 SEQ ID. NO. 31 in W02015157252

CD19 CAR 599 SEQ ID. NO. 32 in WO2015157252 CD19 CAR 600 SEQ ID. NO. 33 in W02015157252 CD19 CAR 601 SEQ ID. NO. 34 in W02015157252 CD19 CAR 602 SEQ ID. NO. 35 in W02015157252 CD19 CAR 603 SEQ ID. NO. 36 in WO2015157252 CD19 CAR 604 SEQ ID. NO. 37 in WO2015157252 CD19 CAR 605 SEQ ID. NO. 38 in W02015157252 CD19 CAR 606 SEQ ID. NO. 39 in W02015157252 CD19 CAR 607 SEQ ID. NO. 40 in W02015157252 CD19 CAR 608 SEQ ID. NO. 41 in W02015157252 CD19 CAR 609 SEQ ID. NO. 42 in W02015157252 CD19 CAR 610 SEQ ID. NO. 58 in W02015157252 CD19 CAR 611 SEQ ID NO. 31 in W02014153270 CD19 CAR 612 SEQ ID NO. 32 in W02014153270 CD19 CAR 613 SEQ ID NO. 33 in W02014153270 CD19 CAR 614 SEQ ID NO. 34 in W02014153270 CD19 CAR 615 SEQ ID NO. 35 in W02014153270 CD19 CAR 616 SEQ ID NO. 36 in W02014153270 CD19 CAR 617 SEQ ID NO. 37 in W02014153270 CD19 CAR 618 SEQ ID NO. 38 in W02014153270 CD19 CAR 619 SEQ ID NO. 39 in W02014153270 CD19 CAR 620 SEQ ID NO. 40 in W02014153270 CD19 CAR 621 SEQ ID NO. 41 in W02014153270 CD19 CAR 622 SEQ ID NO. 42 in W02014153270 CD19 CAR (Third generation) 623 SEQ ID NO.13 in W02016139487

[00228] In one embodiment of the present invention, the payload of the invention is a CD19 specific CAR targeting different B cell. In the context of the invention, an effector module may comprise a hDHFR DD, ecDHFR DD, or FKBP DD operably linked to a CD19 CAR fusion construct. In some instances, the promoter utilized to drive the expression of the effector module in the vector may be a CMV promoter or an EFla. The efficiency of the promoter in driving the expression of the same construct may be compared. For example, two constructs that differ only by their promoter, CMV (in OT-CD19N-001) or EFla promoter (in OT-CD19N-017) may be compared. The amino acid sequences of CD19 CAR constructs and its components are presented in Table 1Oa and Table 1Ob. The amino acid sequences in Table 1Oa and/or Table 1Ob may comprise a stop codon which is denoted in the table with a "*" at the end of the amino acid sequence. Table 10a: Sequences of components of CD19 CARs Description Amino Acid Sequence Amino Nucleic Acid SEQ Acid SEQ ID NO ID NO CD19 scFv DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNW 624 626,650 YQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTD 654 YSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEI TGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSL SVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIW

GSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVS S CD8c hinge--TM TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVH 625 627,655, TRGLDFACDIYIWAPLAGTCGVLLLSLVITLYC 982-984 CD8c hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVH 440 656-660 TRGLDFACD CD3 zeta signaling RVKFSRSADAPAYKQGQNQLYNELNLGRREEYD 339 661-665, domain VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDK 986 MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKD TYDALHMQALPPR 4-1BB (41BB) KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEE 273 666-670, intracellular signaling EEGGCEL 985 domain CD8a Transmembrane IYIWAPLAGTCGVLLLSLVITLYC 409 990,992 domain CD8c leader MALPVTALLLPLALLLHAARP 628 671-675 p40 signal sequence MCHQQLVISWFSLVFLASPLVA 719 736-744 p40 IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEE 723 632-634, DGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYT 752-761 CHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVK SSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSV ECQEDSACPAAEESLPIEVMVDAVHKLKYENYTS SFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDT WSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTS ATVICRKNASISVRAQDRYYSSSWSEWASVPCS p35 RNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKA 724 762-771, RQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELT 1012 KNESCLNSRETSFITNGSCLASRKTSFMMALCLSSI YEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKL CILLHAFRIRAVTIDRVMSYLNAS IL15 NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSC 785 794-797, KVTAMKCFLLELQVISLESGDASIHDTVENLIILAN 1001 NSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIV QMFINTS IL15Ra ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKR 803 812-813, KAGTSSLTECVLNKATNVAHWTTPSLKCIRDPAL 1003 VHQRPAPPSTVTTAGVTPQPESLSPSGKEPAASSPS SNNTAATTAAIVPGSQLMPSKSPSTGTTEISSHESS HGTPSQTTAKNWELTASASHQPPGVYPQGHSDTT VAISTSTVLLCGLSAVSLLACYLKSRQTPPLASVE MEAMEALPVTWGTSSRDEDLENCSHHL mCherry (M1L) LSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIE 1029 1030 GEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQ FMYGSKAYVKHPADIPDYLKLSFPEGFKWERVM NFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPS DGPVMQKKTMGWEASSERMYPEDGALKGEIKQR LKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNI KLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK IRES - 999 Linker (GGSGG) GGSGG 629 676-680 Linker (SG) SG - AGTGGA Linker ((G4S)3) GGGGSGGGGSGGGGS 720 910-915 Linker (GGSG) GGSG 822 823 Linker MLLLVTSLLLCELPHPAFLLIP 1031 1032

Linker (SG3-(SG4)3- SGGGSGGGGSGGGGSGGGGSGGGSLQ 802 811,916 SG3-SLQ) 920, 1002 Modified Furin ESRRVRRNKRSK 630 681-683 BamHI - GGATCC Spacer - 1000 HA Tag YPYDVPDYA 1024 1025-1027 FKBP (F36V, L106P) GVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGK 11 684-686, KVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMS 987,989 VGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVE LLKPE FKBP (E31G, F36V, GVQVETISPGDGRTFPKRGQTCVVHYTGMLGDG 12 688-691, R71G, K105E) KKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQM 994, 1013, SVGQGAKLTISPDYAYGATGHPGIIPPHATLVFDV 1028 ELLELE ecDHFR (Amino acid 2- ISLIAALAVDYVIGMENAMPWNLPADLAWFKRN 9 692,772, 159 of WT) (R12Y, TLNKPVIMGRHTWESIGRPLPGRKNIILSSQPGTDD 814,687, Y1001) RVTWVKSVDEAIAACGDVPEIMVIGGGRVIEQFLP 988,991 KAQKLYLTHIDAEVEGDTHFPDYEPDDWESVFSE FHDADAQNSHSYCFEILERR ecDHFR (Amino acid 2- ISLIAALAVDHVIGMENAMPWNLPADLAWFKRN 10 798,815, 159 of WT) (R12H, TLNKPVIMGRHTWESIGRPLPGRKNIILSSQPGTDD 993 E129K) RVTWVKSVDEAIAACGDVPEIMVIGGGRVYEQFL PKAQKLYLTHIDAEVEGDTHFPDYKPDDWESVFS EFHDADAQNSHSYCFEILERR hDHFR (Amino acid 2- VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 895 694,995 187 of WT; Y1221) QRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLK GRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQP ELANKVDMVWIVGGSSVIKEAMNHPGHLKLFVT RIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND hDHFR (Amino acid 2- VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 890 696,973, 187 of WT; Y1221, QRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLK 974,996 A125F) GRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQP ELANKVDMVWIVGGSSVIKEFMNHPGHLKLFVT RIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND hDHFR (Amino acid 2- VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 981 698,997 187 of WT; Q36K, KRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLK Y1221) GRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQP ELANKVDMVWIVGGSSVIKEAMNHPGHLKLFVT RIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND hDHFR (Q36F, N65F, VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 891 700,975, Y1221) FRMTTTSSVEGKQNLVIMGKKTWFSIPEKFRPLKG 976,998 RINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPE LANKVDMVWIVGGSSVIKEAMNHPGHLKLFVTRI MQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEK GIKYKFEVYEKND Description Amino Acid Sequence Amino Nucleic Acid SEQ Acid SEQ ID NO ID NO CD19 scFv DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNW 624 626,650 YQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTD 654 YSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEI TGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSL SVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIW GSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT_

DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVS S CD8c hinge--TM TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVH 625 627,655, TRGLDFACDIYIWAPLAGTCGVLLLSLVITLYC 982-984 CD8c hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVH 440 656-660 TRGLDFACD CD3 zeta signaling RVKFSRSADAPAYKQGQNQLYNELNLGRREEYD 339 661-665, domain VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDK 986 MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKD TYDALHMQALPPR 4-1BB (41BB) KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEE 273 666-670, intracellular signaling EEGGCEL 985 domain CD8a Transmembrane IYIWAPLAGTCGVLLLSLVITLYC 409 990,992 domain CD8c leader MALPVTALLLPLALLLHAARP 628 671-675 p40 signal sequence MCHQQLVISWFSLVFLASPLVA 719 736-744 p40 IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEE 723 632-634, DGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYT 752-761 CHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVK SSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSV ECQEDSACPAAEESLPIEVMVDAVHKLKYENYTS SFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDT WSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTS ATVICRKNASISVRAQDRYYSSSWSEWASVPCS p35 RNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKA 724 762-771, RQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELT 1012 KNESCLNSRETSFITNGSCLASRKTSFMMALCLSSI YEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKL CILLHAFRIRAVTIDRVMSYLNAS IL15 NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSC 785 794-797, KVTAMKCFLLELQVISLESGDASIHDTVENLIILAN 1001 NSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIV QMFINTS IL15Ra ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKR 803 812-813, KAGTSSLTECVLNKATNVAHWTTPSLKCIRDPAL 1003 VHQRPAPPSTVTTAGVTPQPESLSPSGKEPAASSPS SNNTAATTAAIVPGSQLMPSKSPSTGTTEISSHESS HGTPSQTTAKNWELTASASHQPPGVYPQGHSDTT VAISTSTVLLCGLSAVSLLACYLKSRQTPPLASVE MEAMEALPVTWGTSSRDEDLENCSHHL mCherry (M1L) LSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIE 1029 1030 GEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQ FMYGSKAYVKHPADIPDYLKLSFPEGFKWERVM NFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPS DGPVMQKKTMGWEASSERMYPEDGALKGEIKQR LKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNI KLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK IRES - 999 Linker (GGSGG) GGSGG 629 676-680 Linker (SG) SG - AGTGGA Linker ((G4S)3) GGGGSGGGGSGGGGS 720 910-915 Linker (GGSG) GGSG 822 823 Linker MLLLVTSLLLCELPHPAFLLIP 1031 1032

Linker (SG3-(SG4)3- SGGGSGGGGSGGGGSGGGGSGGGSLQ 802 811,916 SG3-SLQ) 920, 1002 Modified Furin ESRRVRRNKRSK 630 681-683 BamHI - GGATCC Spacer - 1000 HA Tag YPYDVPDYA 1024 1025-1027 FKBP (F36V, L106P) GVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGK 11 684-686, KVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMS 987,989 VGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVE LLKPE FKBP (E31G, F36V, GVQVETISPGDGRTFPKRGQTCVVHYTGMLGDG 12 688-691, R71G, K105E) KKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQM 994, 1013, SVGQGAKLTISPDYAYGATGHPGIIPPHATLVFDV 1028 ELLELE ecDHFR (Amino acid 2- ISLIAALAVDYVIGMENAMPWNLPADLAWFKRN 9 692,772, 159 of WT) (R12Y, TLNKPVIMGRHTWESIGRPLPGRKNIILSSQPGTDD 814,687, Y1001) RVTWVKSVDEAIAACGDVPEIMVIGGGRVIEQFLP 988,991 KAQKLYLTHIDAEVEGDTHFPDYEPDDWESVFSE FHDADAQNSHSYCFEILERR ecDHFR (Amino acid 2- ISLIAALAVDHVIGMENAMPWNLPADLAWFKRN 10 798,815, 159 of WT) (R12H, TLNKPVIMGRHTWESIGRPLPGRKNIILSSQPGTDD 993 E129K) RVTWVKSVDEAIAACGDVPEIMVIGGGRVYEQFL PKAQKLYLTHIDAEVEGDTHFPDYKPDDWESVFS EFHDADAQNSHSYCFEILERR hDHFR (Amino acid 2- VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 895 694,995 187 of WT; Y1221) QRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLK GRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQP ELANKVDMVWIVGGSSVIKEAMNHPGHLKLFVT RIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND hDHFR (Amino acid 2- VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 890 696,973, 187 of WT; Y1221, QRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLK 974,996 A125F) GRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQP ELANKVDMVWIVGGSSVIKEFMNHPGHLKLFVT RIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND hDHFR (Amino acid 2- VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 981 698,997 187 of WT; Q36K, KRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLK Y1221) GRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQP ELANKVDMVWIVGGSSVIKEAMNHPGHLKLFVT RIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND hDHFR (Q36F, N65F, VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYF 891 700,975, Y1221) FRMTTTSSVEGKQNLVIMGKKTWFSIPEKFRPLKG 976,998 RINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPE LANKVDMVWIVGGSSVIKEAMNHPGHLKLFVTRI MQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEK GIKYKFEVYEKND

Table 10b: Sequences of CD19 CARs Description Amino Acid Sequence Amino Nucleic Acid SEQ Acid SEQ ID NO ID NO OT-CD19 CAR-001 (OT- MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 635 701 CD19c-001) (CD8a LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI leader -CD19 scFV - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA

CD8a-Tm -41BB - TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG CD3zeta - stop) GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPR*

OT-CD19 CAR-002 (OT- MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 636 702 CD19c-002) (CD8a LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI leader - CD19 scFV - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA FKBP (F36V, L106P) - TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG CD8a-Tm - 41BB - GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD CD3zeta - stop) YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSGVQVETISPGDG RTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKP FKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIPPHATLVFDVELLKPETTTPAPRP PTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFA CDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLY IFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRV KFSRSADAPAYKQGQNQLYNELNLGRREEYDVL DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKM AEAYSEIGMKGERRRGKGHDGLYQGLSTATKDT YDALHMQALPPR*

OT-CD19 CAR-003 (OT- MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 637 703 CD19c-003) (CD8a LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI leader - CD19 scFV - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA ecDHFR - CD8a-Tm - TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG 41BB - CD3zeta - stop) GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSISLIAALAVDYVI GMENAMPWNLPADLAWFKRNTLNKPVIMGRHT WESIGRPLPGRKNIILSSQPGTDDRVTWVKSVDEA IAACGDVPEIMVIGGGRVIEQFLPKAQKLYLTHID AEVEGDTHFPDYEPDDWESVFSEFHDADAQNSHS YCFEILERRTTTPAPRPPTPAPTIASQPLSLRPEACR PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLS LVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQL YNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGH DGLYQGLSTATKDTYDALHMQALPPR*

OT-CD19 CAR-004 (OT- MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 638 704 CD19c-004) (CD8a LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI leader - CD19 scFV - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD8a Hinge - FKBP TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (F36V, L106P) -CD8a GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD

Transmembrane domain- YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS 41BB - CD3zeta - stop) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDGV QVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKV DSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVG QRAKLTISPDYAYGATGHPGIIPPHATLVFDVELL KPEIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLL YIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELR VKFSRSADAPAYKQGQNQLYNELNLGRREEYDV LDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKM AEAYSEIGMKGERRRGKGHDGLYQGLSTATKDT YDALHMQALPPR*

OT-CD19 CAR-005 (OT- MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 639 705 CD19c-005) (CD8a LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI leader - CD19 scFV - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD8a Hinge - ecDHFR TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (Amino acid 2-159 of GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD WT) (R12Y, Y1001) - YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS CD8a Transmembrane RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY domain -41BB -CD3zeta - YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP stop) TIASQPLSLRPEACRPAAGGAVHTRGLDFACDISLI AALAVDYVIGMENAMPWNLPADLAWFKRNTLN KPVIMGRHTWESIGRPLPGRKNIILSSQPGTDDRV TWVKSVDEAIAACGDVPEIMVIGGGRVIEQFLPK AQKLYLTHIDAEVEGDTHFPDYEPDDWESVFSEF HDADAQNSHSYCFEILERRIYIWAPLAGTCGVLLL SLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDG CSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRK NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKG HDGLYQGLSTATKDTYDALHMQALPPR*

OT-CD19c-006 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 640 706 leader-CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta -linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG) - ecDHFR GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (Amino acid 2-159 of YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS WT) (R12H, E129K) - RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY stop) YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGISLIAALAVDHVIGMENAMPWNL PADLAWFKRNTLNKPVIMGRHTWESIGRPLPGRK NIILSSQPGTDDRVTWVKSVDEAIAACGDVPEIMV IGGGRVYEQFLPKAQKLYLTHIDAEVEGDTHFPD YKPDDWESVFSEFHDADAQNSHSYCFEILERR*

OT-CD19c-007 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 641 707 leader - CD19 scFV- LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA

CD3zeta - linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG) -FKBP (E31G, GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD F36V, R71G, K105E) - YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS stop) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGGVQVETISPGDGRTFPKRGQTCV VHYTGMLGDGKKVDSSRDRNKPFKFMLGKQEVI RGWEEGVAQMSVGQGAKLTISPDYAYGATGHPG IIPPHATLVFDVELLELE*

OT-CD19c-008 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 642 708 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm -41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG)-hDHFR GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (Amino acid 2-187 of YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS WT; Y1221) - stop) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGVGSLNCIVAVSQNMGIGKNGDLP WPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKT WFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRS LDDALKLTEQPELANKVDMVWIVGGSSVIKEAM NHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLP EYPGVLSDVQEEKGIKYKFEVYEKND*

OT-CD19c-009 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 643 709 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta -linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG)-hDHFR GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (Amino acid 2-187 of YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS WT; Y1221, A125F) - RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY stop) YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGVGSLNCIVAVSQNMGIGKNGDLP WPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKT WFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRS LDDALKLTEQPELANKVDMVWIVGGSSVIKEFM

NHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLP EYPGVLSDVQEEKGIKYKFEVYEKND*

OT-CD19c-010 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 644 710 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG) -hDHFR GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (Amino acid 2-187 of YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS WT; Q36K, Y1221) - RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY stop) YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGVGSLNCIVAVSQNMGIGKNGDLP WPPLRNEFRYFKRMTTTSSVEGKQNLVIMGKKT WFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRS LDDALKLTEQPELANKVDMVWIVGGSSVIKEAM NHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLP EYPGVLSDVQEEKGIKYKFEVYEKND*

OT-CD19c-011 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 645 711 leader -CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta -linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG)-hDHFR GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (Amino acid 2-187 of YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS WT; Q36K,N65F, Y1221) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY -stop) YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGVGSLNCIVAVSQNMGIGKNGDLP WPPLRNEFRYFFRMTTTSSVEGKQNLVIMGKKTW FSIPEKFRPLKGRINLVLSRELKEPPQGAHFLSRSL DDALKLTEQPELANKVDMVWIVGGSSVIKEAMN HPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE YPGVLSDVQEEKGIKYKFEVYEKND*

OT-CD19n-012 (CD8a MALPVTALLLPLALLLHAARPSGGVQVETISPGDG 646 712 leader - Linker (SG)- RTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKP FKBP (F36V, L106P) - FKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD Furin Site -CD19 scFV - YAYGATGHPGIIPPHATLVFDVELLKPEESRRVRR CD8a-Tm - 41BB - NKRSKDIQMTQTTSSLSASLGDRVTISCRASQDIS CD3zeta - stop) KYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSG SGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFG GGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGL VAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLE WLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLK MNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQG TSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPA

AGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLV ITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSC RFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYN ELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQ EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDG LYQGLSTATKDTYDALHMQALPPR*

OT-CD19n-013 (CD8a MALPVTALLLPLALLLHAARPSGISLIAALAVDYVI 647 713 leader - Linker (SG)- GMENAMPWNLPADLAWFKRNTLNKPVIMGRHT ecDHFR (Amino acid 2- WESIGRPLPGRKNIILSSQPGTDDRVTWVKSVDEA 159 of WT) (R12Y, IAACGDVPEIMVIGGGRVIEQFLPKAQKLYLTHID Y1001) - Furin Site - AEVEGDTHFPDYEPDDWESVFSEFHDADAQNSHS CD19 scFV -CD8a-Tm - YCFEILERRESRRVRRNKRSKDIQMTQTTSSLSAS 41BB - CD3zeta - stop) LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPR*

OT-CD19n-014 (CD8a MALPVTALLLPLALLLHAARPSGVGSLNCIVAVSQ 648 714 leader - Linker (SG)- NMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGK hDHFR (Amino acid 2- QNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKE 187 of WT; Y1221, PPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV A125F) - Furin Site - GGSSVIKEFMNHPGHLKLFVTRIMQDFESDTFFPEI CD19 scFV - CD8a-Tm - DLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKN 41BB -CD3zeta - stop) DESRRVRRNKRSKDIQMTQTTSSLSASLGDRVTIS CRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQG NTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVK LQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIR QPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDN SKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYA MDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLS LRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGT CGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAY KQGQNQLYNELNLGRREEYDVLDKRRGRDPEMG GKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR

OT-CD19n-015 (CD8a MALPVTALLLPLALLLHAARPSGVGSLNCIVAVSQ 649 715 leader - Linker (SG)- NMGIGKNGDLPWPPLRNEFRYFKRMTTTSSVEGK hDHFR (Amino acid 2- QNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKE 187 of WT; Q36K, PPQGAHFLSRSLDDALKLTEQPELANKVDMVWIV Y1221) -Furin Site - GGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPE IDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKN DESRRVRRNKRSKDIQMTQTTSSLSASLGDRVTIS

CD19 scFV - CD8a-Tm - CRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS 41BB - CD3zeta -stop) GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQG NTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVK LQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIR QPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDN SKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYA MDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLS LRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGT CGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAY KQGQNQLYNELNLGRREEYDVLDKRRGRDPEMG GKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR

OT-CD19-056 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1005 1022 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - linker TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG (GGSGG)-hDHFR GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (Amino acid 2-187 of YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS WT; Y1221) -stop) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGGSGGVGSLNCIVAVSQNMGIGKNGDLP WPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKT WFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRS LDDALKLTEQPELANKVDMVWIVGGSSVIKEAM NHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLP EYPGVLSDVQEEKGIKYKFEVYEKND*

OT-CD19-057 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1006 1023 leader -CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - BamHI (GS)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG stop) GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGS*

OT-CD19-058 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1007 1033 leader -CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD

CD3zeta - p2A - BamHI YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS (GS)- stop) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGATNFSLLKQAGDVEENPGPGS*

OT-CD19-059 (CD8a MALPVTALLLPLALLLHAARPYPYDVPDYADIQM 1008 1034 leader - HA Tag - CD19 TQTTSSLSASLGDRVTISCRASQDISKYLNWYQQK scFV - CD8a-Tm - 41BB PDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTI - CD3zeta - BanH-l (GS)- SNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGG stop) GSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTC TVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSET TYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTA IYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTP APRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGC ELRVKFSRSADAPAYKQGQNQLYNELNLGRREE YDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQK DKMAEAYSEIGMKGERRRGKGHDGLYQGLSTAT KDTYDALHMQALPPRGS*

OT-CD19-060 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1009 1035 leader - CD19 scFV- LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm- 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - Linker (SG)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG Furin - BamHI (GS)- GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD stop) YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRSGESRRVRRNKRSKGS*

OT-CD19-063 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1010 1036 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - stop) TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE

IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPR*

OT-CD19-064 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1215-1231 1037 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - Linker (TR)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG HA Tag - FKBP (E31G, GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD F36V, R71G, K105E) - YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS stop-IRES- mCherry) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRTRYPYDVPDYAGVQVETISPGDGRTFPK RGQTCVVHYTGMLGDGKKVDSSRDRNKPFKFML GKQEVIRGWEEGVAQMSVGQGAKLTISPDYAYG ATGHPGIIPPHATLVFDVELLELE*MHRSAAAAT*I PPPPPLSLPPP*RYWPKPLGIRPVCVCLYVIFHHIAV FWQCEGPETWPCLLDEHS*GSFPSRQRNARSVEC REGSSSSGSFLKTNNVCSDPLQAAEPPTWRQVPLR PKATCIRYTCKGGTTPVPRCELDSCGKSQMALLK RIQQGAEGCPEGTPLYGI*SGASVHMLYMCLVEV KKTSRPPEPRGRGFPLKNTM11WPQP**ARARRIT WPSSRSSCASRCTWRAP*TATSSRSRARARAAPTR APRPPS*R*PRVAPCPSPGTSCPLSSCTAPRPT*STP PTSPTT*SCPSPRASSGSA**TSRTAAW*P*PRTPPC RTASSSTR*SCAAPTSPPTAP*CRRRPWAGRPPPSG CTPRTAP*RARSSRG*S*RTAATTTLRSRPPTRPRS PCSCPAPTTSTSSWTSPPTTRTTPSWNSTNAPRAA TPPAAWTSCTS*

OT-CD19-066 (CD8a MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1015 1039 leader - CD19 scFV - LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - Linker (GS)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG P2A peptide -mCherry GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (M1L) - stop) YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGSGATNFSLLKQAGDVEENPGPLSKGEE DNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGR PYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSK AYVKHPADIPDYLKLSFPEGFKWERVMNFEDGG VVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQ KKTMGWEASSERMYPEDGALKGEIKQRLKLKDG

GHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSH NEDYTIVEQYERAEGRHSTGGMDELYK*

OT-CAR19-IL15-001 MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1016 1040 (CD8a leader - CD19 LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI scFV -CD8a-Tm - 41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - Linker (GS)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG P2A - IL15 -Linker (SG3- GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (SG4)3-SG3-SLQ) - YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS IL15Ra - stop) RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGSGATNFSLLKQAGDVEENPGPNWVNVI SDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMK CFLLELQVISLESGDASIHDTVENLIILANNSLSSNG NVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS SGGGSGGGGSGGGGSGGGGSGGGSLQITCPPPMS VEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLT ECVLNKATNVAHWTTPSLKCIRDPALVHQRPAPP STVTTAGVTPQPESLSPSGKEPAASSPSSNNTAATT AAIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTT AKNWELTASASHQPPGVYPQGHSDTTVAISTSTV LLCGLSAVSLLACYLKSRQTPPLASVEMEAMEAL PVTWGTSSRDEDLENCSHHL*

OT-CAR19-IL15-002 MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1017 1041 (CD8a leader -CD19 LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI scFV -CD8a-Tm -41BB - YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA CD3zeta - Linker (GS)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG P2A - Linker GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD (MLLLVTSLLLCELPHP YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS AFLLIP) (SEQ ID NO: RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY 1031) - IL15 - Linker YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP (SG3-(SG4)3-SG3-SLQ) TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI - IL15Ra - stop) WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGSGATNFSLLKQAGDVEENPGPMLLLVT SLLLCELPHPAFLLIPNWVNVISDLKKIEDLIQSMH IDATLYTESDVHPSCKVTAMKCFLLELQVISLESG DASIHDTVENLIILANNSLSSNGNVTESGCKECEEL EEKNIKEFLQSFVHIVQMFINTSSGGGSGGGGSGG GGSGGGGSGGGSLQITCPPPMSVEHADIWVKSYS LYSRERYICNSGFKRKAGTSSLTECVLNKATNVA HWTTPSLKCIRDPALVHQRPAPPSTVTTAGVTPQP ESLSPSGKEPAASSPSSNNTAATTAAIVPGSQLMPS KSPSTGTTEISSHESSHGTPSQTTAKNWELTASAS HQPPGVYPQGHSDTTVAISTSTVLLCGLSAVSLLA

CYLKSRQTPPLASVEMEAMEALPVTWGTSSRDED LENCSHHL*

OT-CD19-IL15-006 MALPVTALLLPLALLLHAARPDIQMTQTTSSLSAS 1018 1042 (CD8a leader -CD19 LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLI scFV - CD8a-Tm - 41BB YHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA - CD3zeta - Linker (GS)- TYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSG P2A - IgE Leader - IL15 - GGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPD Linker (SG3-(SG4)3- YGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS SG3-SLQ) - IL15Ra - RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHY stop) YYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAP TIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYI WAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYKQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSE IGMKGERRRGKGHDGLYQGLSTATKDTYDALHM QALPPRGSGATNFSLLKQAGDVEENPGPMDWTW ILFLVAAATRVHSNWVNVISDLKKIEDLIQSMHID ATLYTESDVHPSCKVTAMKCFLLELQVISLESGDA SIHDTVENLIILANNSLSSNGNVTESGCKECEELEE KNIKEFLQSFVHIVQMFINTSSGGGSGGGGSGGGG SGGGGSGGGSLQITCPPPMSVEHADIWVKSYSLYS RERYICNSGFKRKAGTSSLTECVLNKATNVAHWT TPSLKCIRDPALVHQRPAPPSTVTTAGVTPQPESLS PSGKEPAASSPSSNNTAATTAAIVPGSQLMPSKSPS TGTTEISSHESSHGTPSQTTAKNWELTASASHQPP GVYPQGHSDTTVAISTSTVLLCGLSAVSLLACYLK SRQTPPLASVEMEAMEALPVTWGTSSRDEDLENC SHHL*

[00229] Constructs disclosed in Table 10 which are transcriptionally controlled by a CMV promoter, in some instances may be placed under the transcriptional control of a different promoter to test the role of promoters in CD19 CAR expression. In one embodiment, the CMV promoter may be replaced by an EFl a promoter. In one embodiment, the CMV promoter of the, OT-CD19-001 construct, may be replaced to generate OT-CD19N-017 construct, with a EFla promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-002 construct, may be replaced to generate OT-CD19N-O18 construct, with a EFla promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-003 construct, may be replaced to generate OT-CD19N-019 construct, with a EFla promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-004 construct, may be replaced to generate OT-CD19N-020 construct, with a EFla promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-005 construct, may be replaced to generate OT-CD19N-021 construct, with a EFl a promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-006 construct, may be replaced to generate OT

CD19N-022 construct, with a EFl a promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-007 construct, may be replaced to generate OT-CD19N-023 construct, with a EF la promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR-008 construct, may be replaced to generate OT-CD19N-024 construct, with a EFla promoter. In another embodiment, the CMV promoter of the CD19 CAR, OT-CD19 CAR 009 construct, may be replaced to generate OT-CD19N-025 construct, with a EFla promoter.

[00230] In one embodiment, the CAR construct comprises a CD19 scFV (e.g., CAT13.1E1O or FMC63), a CD8a spacer or transmembrane domain, and a 4-1BB and CD3Q endodomain. These constructs with CAT13.1E10 may have increased proliferation after stimulation in vitro, increased cytotoxicity against the CD19+ targets, and increased effector and target interactions as compared to constructs with FMC63.

[00231] In some embodiments, the payloads of the present invention maybe tuned using the catalytic domains of the E3 ubiquitin ligases. The catalytic domains of E3 ligases may be fused to an antibody or a fragment of the antibody. The payload is fused to the antigen recognized by the antibody or a fragment of the antibody that is fused to the E3 ligases catalytic domain. The E3 ligases useful in the present invention include, but are not limited to Ring E3 ligase, HECT E3 ligases and RBR E3 ligases. Any of the methods taught by Kanner SA et al. (2017) eLife; 6: e29744 may be useful in the present invention (the contents of which are incorporated by reference in their entirety).

[00232] In some embodiments, the payloads described herein, may be regulated by E3 ubiquitin ligases constructs. The E3 ligases constructs may comprise the catalytic domain of E3 ligases fused to an SRE and an antibody or a fragment of an antibody. The payloads are fused to the antigen recognized by the antibody or a fragment of an antibody, that is appended to the catalytic domain of E3 ligases. In the absence of the stimulus corresponding to the SRE, the E3 ubiquitin ligases constructs are destabilized, which in turn, allows the expression of the payloads fused to the antigen. In the presence of ligand corresponding to the SRE, the E3 ubiquitin ligases constructs are stabilized and available to bind to the antigen fused to the payloads. Binding of the E3 ligases constructs to the antigens, targets the protein for degradation. The E3 ubiquitin ligases constructs may be used to regulate any payload described herein, provided the payload is fused to an antigen recognized by the antibody or the fragment of the antibody in the E3 ubiquitin ligases construct. In some embodiments, the payload is a chimeric antigen receptor. The E3 ubiquitin ligases constructs may be used to design logic gates. In one embodiment, the E3 ubiquitin ligases constructs may be used to generate a NOT gate, wherein one ligand induces the expression of the payload, while another inhibits the expression of the payload. In some embodiments, the NOT gate may be generated using the E3 ubiquitin ligases constructs and by fusing the payloads-antigen fusion protein to a second a SRE that is distinct from the SRE in the E3 ubiquitin ligase construct.

[00233] In some embodiments, the payload of the invention may be any of the co-stimulatory molecules and/or intracellular domains described herein. In some embodiments, one or more co stimulatory molecules, each under the control of different SRE may be used in the present invention. SRE regulated co- stimulatory molecules may also be expressed in conjunction with a first generation CAR, a second generation CAR, a third generation CAR, a fourth generation, or any other CAR design described herein. Tandem CAR (TanCAR)

[00234] In some embodiments, the CAR of the present invention may be a tandem chimeric antigen receptor (TanCAR) which is able to target two, three, four, or more tumor specific antigens. In some aspects, The CAR is a bispecific TanCAR including two targeting domains which recognize two different TSAs on tumor cells. The bispecific CAR may be further defined as comprising an extracellular region comprising a targeting domain (e.g., an antigen recognition domain) specific for a first tumor antigen and a targeting domain (e.g., an antigen recognition domain) specific for a second tumor antigen. In other aspects, the CAR is a multispecific TanCAR that includes three or more targeting domains configured in a tandem arrangement. The space between the targeting domains in the TanCAR may be between about 5 and about 30 amino acids in length, for example, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30 amino acids. Split CAR

[00235] In some embodiments, the components including the targeting moiety, transmembrane domain and intracellular signaling domains of the present invention may be split into two or more parts such that it is dependent on multiple inputs that promote assembly of the intact functional receptor. In one embodiment, the split synthetic CAR system can be constructed in which the assembly of an activated CAR receptor is dependent on the binding of a ligand to the SRE (e.g. a small molecule) and a specific antigen to the targeting moiety. As a non-limiting example, the split CAR consists of two parts that assemble in a small molecule-dependent manner; one part of the receptor features an extracellular antigen binding domain (e.g. scFv) and the other part has the intracellular signaling domains, such as the CD3Q intracellular domain.

[00236] In other aspects, the split parts of the CAR system can be further modified to increase signal. In one example, the second part of cytoplasmic fragment may be anchored to the plasma membrane by incorporating a transmembrane domain (e.g., CD8a transmembrane domain) to the construct. An additional extracellular domain may also be added to the second part of the CAR system, for instance an extracellular domain that mediates homo-dimerization. These modifications may increase receptor output activity, i.e., T cell activation.

[00237] In some aspects, the two parts of the split CAR system contain heterodimerization domains that conditionally interact upon binding of a heterodimerizing small molecule. As such, the receptor components are assembled in the presence of the small molecule, to form an intact system which can then be activated by antigen engagement. Any known heterodimerizing components can be incorporated into a split CAR system. Other small molecule dependent heterodimerization domains may also be used, including, but not limited to, gibberellin-induced dimerization system (GID1-GAI), trimethoprim-SLF induced ecDHFR and FKBP dimerization (Czlapinski et al., JAm Chem Soc., 2008, 130(40): 13186-13187) and ABA (abscisic acid) induced dimerization of PP2C and PYL domains (Cutler et al., Annu Rev PlantBiol. 2010, 61: 651-679). The dual regulation using inducible assembly (e.g., ligand dependent dimerization) and degradation (e.g., destabilizing domain induced CAR degradation) of the split CAR system may provide more flexibility to control the activity of the CAR modified T cells. Switchable CAR

[00238] In some embodiments, the CAR of the invention may be a switchable CAR. Juillerat et al (Juilerat et al., Sci. Rep., 2016, 6: 18950; the contents of which are incorporated herein by reference in their entirety) recently reported controllable CARs that can be transiently switched on in response to a stimulus (e.g. a small molecule). In this CAR design, a system is directly integrated in the hinge domain that separate the scFv domain from the cell membrane domain in the CAR. Such system is possible to split or combine different key functions of a CAR such as activation and costimulation within different chains of a receptor complex, mimicking the complexity of the TCR native architecture. This integrated system can switch the scFv and antigen interaction between on/off states controlled by the absence/presence of the stimulus. Reversible CAR

[00239] In other embodiments, the CAR of the invention may be a reversible CAR system. In this CAR architecture, a LID domain (ligand-induced degradation) is incorporated into the CAR system. The CAR can be temporarily down-regulated by adding a ligand of the LID domain. The combination of LID and DD mediated regulation provides tunable control of continuingly activated CAR T cells, thereby reducing CAR mediated tissue toxicity. Activation-conditionalCAR

[00240] In some embodiments, payloads of the invention may be an activation-conditional chimeric antigen receptor, which is only expressed in an activated immune cell. The expression of the CAR may be coupled to activation conditional control region which refers to one or more nucleic acid sequences that induce the transcription and/or expression of a sequence e.g. a CAR under its control. Such activation conditional control regions may be promoters of genes that are upregulated during the activation of the immune effector cell e.g. IL2 promoter or NFAT binding sites. In some embodiments, activation of the immune cell may be achieved by a constitutively expressed CAR (International Publication No: W02016126608; the contents of which are incorporated herein by reference in their entirety). Cytokines, chemokines and other soluble factors

[00241] In accordance with the present invention, CARs of the present invention may be utilized along with other payloads of the present invention may be cytokines, chemokines, growth factors, and soluble proteins produced by immune cells, cancer cells and other cell types, which act as chemical communicators between cells and tissues within the body. These proteins mediate a wide range of physiological functions, from effects on cell growth, differentiation, migration and survival, to a number of effector activities. For example, activated T cells produce a variety of cytokines for cytotoxic function to eliminate tumor cells.

[00242] In some embodiments, payloads of the present invention may be cytokines, and fragments, variants, analogs and derivatives thereof, including but not limited to interleukins, tumor necrosis factors (TNFs), interferons (IFNs), TGF beta and chemokines. In some embodiments, payloads of the present invention may be cytokines that stimulate immune responses. In other embodiments, payloads of the invention may be antagonists of cytokines that negatively impact anti-cancer immune responses.

[00243] In some embodiments, payloads of the present invention may be cytokine receptors, recombinant receptors, variants, analogs and derivatives thereof; or signal components of cytokines.

[00244] In some embodiments, cytokines of the present invention may be utilized to improve expansion, survival, persistence, and potency of immune cells such as CD8+TEM, natural killer cells and tumor infiltrating lymphocytes (TIL) cells used for immunotherapy. In other embodiments, T cells engineered with two or more DD regulated cytokines are utilized to provide kinetic control of T cell activation and tumor microenvironment remodeling. In one aspect, the present invention provides biocircuits and compositions to minimize toxicity related to cytokine therapy. Despite its success in mitigating tumor burden, systemic cytokine therapy often results in the development of severe dose limiting side effects. Two factors contribute to the observed toxicity (a) Pleiotropism, wherein cytokines affect different cells types and sometimes produce opposing effects on the same cells depending on the context (b) Cytokines have short serum half-life and thus need to be administered at high doses to achieve therapeutic effects, which exacerbates the pleiotropic effects. In one aspect, cytokines of the present invention may be utilized to modulate cytokine expression in the event of adverse effects. In some embodiments, cytokines of the present invention may be designed to have prolonged life span or enhanced specificity to minimize toxicity.

[00245] In some embodiments, the payload of the present invention may be an interleukin (IL) cytokine. Interleukins (ILs) are a class of glycoproteins produced by leukocytes for regulating immune responses. As used herein, the term "interleukin (IL)" refers to an interleukin polypeptide from any species or source and includes the full-length protein as well as fragments or portions of the protein. In some aspects, the interleukin payload is selected from IL1, ILl alpha (also called hematopoietin-1), ILIbeta (catabolin), IL1 delta, ILlepsilon, ILl eta, IL1 zeta, interleukin-1family member 1to 11 (ILIFIto ILIF11), interleukin-1 homolog 1 to 4 (ILIHIto IL1H4), IL1 related protein 1 to 3 (ILIRPIto IL1RP3), IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9, IL1O, IL1OC, IL1OD, IL11, ILl1a, ILl1b, IL12, IL13, IL14, IL15, IL16, IL17, IL17A, 1117B, IL17C, IL17E, IL17F, IL18, IL19, IL20, IL20 like (IL20L), 1121, IL22, IL23, IL23A, IL23-p19, IL23-p40, IL24,1125, IL26, IL27, IL28A, IL28B, IL29, IL30, IL31, IL32, IL33, IL34, IL35, IL36 alpha, IL36 beta, IL36 gamma, IL36RN, IL37, IL37a, IL37b, IL37c, IL37d, IL37e and IL38. In other aspects, the payload of the present invention may be an interleukin receptor selected from CD121a, CDw12Ib, IL2Ra/CD25, IL2RP/CD122, IL2Ry/CD132, CDw31, CD124, CD131, CDw125, CD126, CD130, CD127, CDw210, IL8RA, IL11Ra, CD212, CD213al, CD213a2, IL14R, IL15Ra, CDw217, IL18Ra, IL18R, IL2Ra, and IL20R.

[00246] In one embodiment, the payload of the invention may comprise IL12. IL12 is a heterodimeric protein of two subunits (p35, p40) that is secreted by antigen presenting cells, such as macrophages and dendritic cells. IL12 is type 1 cytokine that acts on natural killer (NK) cells, macrophages, CD8' Cytotoxic T cells, and CD4' T helper cells through STAT4 pathway to induce IFN-y production in these effector immune cells (reviewed by Trinchieri G, Nat Rev Immunol. 2003; 3(2): 133-146). IL12 can promote the cytotoxic activity of NK cells and CD8' T cells, therefore has anti-tumor function. Intravenous injection of recombinant IL12 exhibited modest clinical efficacy in a handful of patients with advanced melanoma and renal cell carcinoma (Gollob et al., Clin. CancerRes. 2000; 6(5):1678-1692). IL12 has been used as an adjuvant to enhance cytotoxic immunity using a melanoma antigen vaccine, or using peptide pulsed peripheral blood mononuclear cells; and to promote NK cell activity in breast cancer with trastuzumab treatment. Local delivery of IL12 to the tumor microenvironment promotes tumor regression in several tumor models. These studies all indicate that locally increased IL12 level can promote anti-tumor immunity. One major obstacle of systemic or local administration of recombinant IL12 protein, or through oncolytic viral vectors is the severe side effects when IL12 is presented at high level. Developing a system that tightly controls IL12 level may provide a safe use of IL12 in cancer treatment.

[00247] It is understood in the art that certain gene and/or protein nomenclature for the same gene or protein may be inclusive or exclusive of punctuation such as a dash "-" or symbolic such as Greek letters. Whether these are included or excluded herein, the meaning is not meant to be changed as would be understood by one of skill in the art. For example, IL2, IL2 and IL 2 refer to the same interleukin. Likewise, TNFalpha, TNFa, TNF-alpha, TNF-a, TNF alpha and TNF a all refer to the same protein.

[00248] In one aspect, the effector module of the invention may be a DD-IL12 fusion polypeptide. This regulatable DD-IL12 fusion polypeptide may be directly used as an immunotherapeutic agent or be transduced into an immune effector cell (T cells and TIL cells) to generate modified T cells with greater in vivo expansion and survival capabilities for adoptive cell transfer. The need for harsh preconditioning regimens in current adoptive cell therapies may be minimized using regulated IL12 DD-IL12 may be utilized to modify tumor microenvironment and increase persistence in solid tumors that are currently refractory to tumor antigen targeted therapy. In some embodiments, CAR expressing T cells may be armored with DD regulated IL12 to relieve immunosuppression without systemic toxicity.

[00249] In some embodiments, the IL12 maybe a Flexi IL12, wherein both p35 and p40 subunits, are encoded by a single cDNA that produces a single chain polypeptide. The single chain polypeptide may be generated by placing p35 subunit at the N terminus or the c terminus of the single chain polypeptide. Similarly, the p40 subunit may be at the N terminus or C terminus of the single chain polypeptide. In some embodiments, the IL12 constructs of the invention may be placed under the transcriptional control of the CMV promoter (SEQ ID NO. 716), an EF la promoter (SEQ ID NO. 717, SEQ ID NO. 908) or a PGK promoter (SEQ ID NO. 718). Any portion of IL12 that retains one or more functions of full length or mature IL12 may be useful in the present invention. In some aspects, the DD-IL12 comprises the amino acid sequences listed in Table 11. The amino acid sequences in Table 11 may comprise a stop codon which is denoted in the table with a "*" at the end of the amino acid sequence. Table 11: DD-IL12 constructs Description Promoter Amino acid Sequence Amino Nucleic acid Acid SEQ ID SEQ ID NO NO p40 signal - MCHQQLVISWFSLVFLASPLVA 719 736-744 sequence Linker - GGSGG 629 679-680 Linker - GGGGSGGGGSGGGGS 720 910-915 Linker GS - GGATCC Spacer ATNFSLLKQAGDVEENPGP 745 746 Furin cleavage - SARNRQKRS 721 750 site Furin cleavage - ARNRQKRS 722 751 site Modified Furin - ESRRVRRNKRSK 630 681-683 P2A Cleavable - GATNFSLLKQAGDVEENPGP 925 926 Peptide p40 - IWELKKDVYVVELDWYPDAPGEMVVLTCD 723 752-761, TPEEDGITWTLDQSSEVLGSGKTLTIQVKEF 632-634 GDAGQYTCHKGGEVLSHSLLLLHKKEDGI WSTDILKDQKEPKNKTFLRCEAKNYSGRFT CWWLTTISTDLTFSVKSSRGSSDPQGVTCG AATLSAERVRGDNKEYEYSVECQEDSACP AAEESLPIEVMVDAVHKLKYENYTSSFFIRD IIKPDPPKNLQLKPLKNSRQVEVSWEYPDT WSTPHSYFSLTFCVQVQGKSKREKKDRVFT DKTSATVICRKNASISVRAQDRYYSSSWSE WASVPCS p40 (K217N) - IWELKKDVYVVELDWYPDAPGEMVVLTCD 747 748 TPEEDGITWTLDQSSEVLGSGKTLTIQVKEF GDAGQYTCHKGGEVLSHSLLLLHKKEDGI WSTDILKDQKEPKNKTFLRCEAKNYSGRFT CWWLTTISTDLTFSVKSSRGSSDPQGVTCG AATLSAERVRGDNKEYEYSVECQEDSACP AAEESLPIEVMVDAVHKLKYENYTSSFFIRD IIKPDPPNNLQLKPLKNSRQVEVSWEYPDT

WSTPHSYFSLTFCVQVQGKSKREKKDRVFT DKTSATVICRKNASISVRAQDRYYSSSWSE WASVPCS p35 - RNLPVATPDPGMFPCLHHSQNLLRAVSNM 724 762-771, LQKARQTLEFYPCTSEEIDHEDITKDKTSTV 1012 EACLPLELTKNESCLNSRETSFITNGSCLASR KTSFMMALCLSSIYEDLKMYQVEFKTMNA KLLMDPKRQIFLDQNMLAVIDELMQALNF NSETVPQKSSLEEPDFYKTKIKLCILLHAFRI RAVTIDRVMSYLNAS ecDHFR - ISLIAALAVDYVIGMENAMPWNLPADLAW 9 692,772, (Amino acid 2- FKRNTLNKPVIMGRHTWESIGRPLPGRKNII 814,687, 159 of WT) LSSQPGTDDRVTWVKSVDEAIAACGDVPEI 988,991 (R12Y, Y1001) MVIGGGRVIEQFLPKAQKLYLTHIDAEVEG DTHFPDYEPDDWESVFSEFHDADAQNSHSY CFEILERR FKBP (F36V, - GVQVETISPGDGRTFPKRGQTCVVHYTGML 11 684-686, L106P) EDGKKVDSSRDRNKPFKFMLGKQEVIRGW 987,989 EEGVAQMSVGQRAKLTISPDYAYGATGHP GIIPPHATLVFDVELLKPE FKBP (F36V, - GVQVETISPGDGRTFPKRGQTCVVHYTGML 12 688-691, E31G, R71G, GDGKKVDSSRDRNKPFKFMLGKQEVIRGW 994, 1013, K105E) EEGVAQMSVGQGAKLTISPDYAYGATGHP 1028 GIIPPHATLVFDVELLELE hDHFR - VGSLNCIVAVSQNMGIGKNGDLPWPPLRNE 46 773 (Amino acid 2- FRYFFRMTTTSSVEGKQNLVIMGKKTWFSI 187 of WT; PEKNRPLKGRINLVLSRELKEPPQGAHFLSR Q36F,Y1221, SLDDALKLTEQPELANKVDMVWIVGGSSVI A125F) KEFMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVY EKND hDHFR - VGSLNCIVAVSQNMGVGKNGDLPWPPLRN 894 979 (Amino acid 2- EFRYFQRMTTTSSVEGKQNLVIMGKKTWFS 187 of WT) IPEKNRPLKGRINLVLSRELKEPPQGAHFLS (117V) RSLDDALKLTEQPELANKVDMVWIVGGSS VYKEAMNHPGHLKLFVTRIMQDFESDTFFP EIDLEKYKLLPEYPGVLSDVQEEKGIKYKFE VYEKND hDHFR - VGSLNCIVAVSQNMGIGKNGDLPWPPLRNE 895 694,995 (Amino acid 2- FRYFQRMTTTSSVEGKQNLVIMGKKTWFSI 187 of WT) PEKNRPLKGRINLVLSRELKEPPQGAHFLSR (Y1221) SLDDALKLTEQPELANKVDMVWIVGGSSVI KEAMNHPGHLKLFVTRIMQDFESDTFFPEID LEKYKLLPEYPGVLSDVQEEKGIKYKFEVY EKND OT-IL12-001 CMV MCHQQLVISWFSLVFLASPLVAGVQVETISP 727 774 (p40 signal GDGRTFPKRGQTCVVHYTGMLEDGKKVDS sequence- SRDRNKPFKFMLGKQEVIRGWEEGVAQMS FKBP (F36V, VGQRAKLTISPDYAYGATGHPGIIPPHATLV L106P) - linker FDVELLKPEGGSGGIWELKKDVYVVELDW (GGSGG) - YPDAPGEMVVLTCDTPEEDGITWTLDQSSE p40 - linker2 VLGSGKTLTIQVKEFGDAGQYTCHKGGEVL (G4S)3 - p35- SHSLLLLHKKEDGIWSTDILKDQKEPKNKTF stop) LRCEAKNYSGRFTCWWLTTISTDLTFSVKS SRGSSDPQGVTCGAATLSAERVRGDNKEYE YSVECQEDSACPAAEESLPIEVMVDAVHKL KYENYTSSFFIRDIIKPDPPKNLQLKPLKNSR

QVEVSWEYPDTWSTPHSYFSLTFCVQVQG KSKREKKDRVFTDKTSATVICRKNASISVR AQDRYYSSSWSEWASVPCSGGGGSGGGGS GGGGSRNLPVATPDPGMFPCLHHSQNLLRA VSNMLQKARQTLEFYPCTSEEIDHEDITKDK TSTVEACLPLELTKNESCLNSRETSFITNGSC LASRKTSFMMALCLSSIYEDLKMYQVEFKT MNAKLLMDPKRQIFLDQNMLAVIDELMQA LNFNSETVPQKSSLEEPDFYKTKIKLCILLH AFRIRAVTIDRVMSYLNAS* OT-1L12-002 CMV MGVQVETISPGDGRTFPKRGQTCVVHYTG 728 775 (Met - FKBP MLEDGKKVDSSRDRNKPFKFMLGKQEVIR (F36V, L106P) GWEEGVAQMSVGQRAKLTISPDYAYGATG - linker HPGIIPPHATLVFDVELLKPEGGSGGMCHQ (GGSGG) - p40 QLVISWFSLVFLASPLVAIWELKKDVYVVE signal sequence LDWYPDAPGEMVVLTCDTPEEDGITWTLD - p40 - linker QSSEVLGSGKTLTIQVKEFGDAGQYTCHKG ((G4S)3) - p35 GEVLSHSLLLLHKKEDGIWSTDILKDQKEP - stop) KNKTFLRCEAKNYSGRFTCWWLTTISTDLT FSVKSSRGSSDPQGVTCGAATLSAERVRGD NKEYEYSVECQEDSACPAAEESLPIEVMVD AVHKLKYENYTSSFFIRDIIKPDPPKNLQLK PLKNSRQVEVSWEYPDTWSTPHSYFSLTFC VQVQGKSKREKKDRVFTDKTSATVICRKN ASISVRAQDRYYSSSWSEWASVPCSGGGGS GGGGSGGGGSRNLPVATPDPGMFPCLHHS QNLLRAVSNMLQKARQTLEFYPCTSEEIDH EDITKDKTSTVEACLPLELTKNESCLNSRET SFITNGSCLASRKTSFMMALCLSSIYEDLKM YQVEFKTMNAKLLMDPKRQIFLDQNMLAV IDELMQALNFNSETVPQKSSLEEPDFYKTKI KLCILLHAFRIRAVTIDRVMSYLNAS* OT-IL12-003 CMV MCHQQLVISWFSLVFLASPLVAGVQVETISP 729 776 (p40 signal GDGRTFPKRGQTCVVHYTGMLEDGKKVDS sequence- SRDRNKPFKFMLGKQEVIRGWEEGVAQMS FKBP (F36V, VGQRAKLTISPDYAYGATGHPGIIPPHATLV L106P)- furin FDVELLKPESARNRQKRSIWELKKDVYVVE (SARNRQKRS LDWYPDAPGEMVVLTCDTPEEDGITWTLD ) - p40- linker QSSEVLGSGKTLTIQVKEFGDAGQYTCHKG ((G4S)3)- p35 - GEVLSHSLLLLHKKEDGIWSTDILKDQKEP stop) KNKTFLRCEAKNYSGRFTCWWLTTISTDLT FSVKSSRGSSDPQGVTCGAATLSAERVRGD NKEYEYSVECQEDSACPAAEESLPIEVMVD AVHKLKYENYTSSFFIRDIIKPDPPKNLQLK PLKNSRQVEVSWEYPDTWSTPHSYFSLTFC VQVQGKSKREKKDRVFTDKTSATVICRKN ASISVRAQDRYYSSSWSEWASVPCSGGGGS GGGGSGGGGSRNLPVATPDPGMFPCLHHS QNLLRAVSNMLQKARQTLEFYPCTSEEIDH EDITKDKTSTVEACLPLELTKNESCLNSRET SFITNGSCLASRKTSFMMALCLSSIYEDLKM YQVEFKTMNAKLLMDPKRQIFLDQNMLAV IDELMQALNFNSETVPQKSSLEEPDFYKTKI KLCILLHAFRIRAVTIDRVMSYLNAS* OT-IL12-004 CMV MCHQQLVISWFSLVFLASPLVAIWELKKDV 730 777 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence - p40 WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT - linker CHKGGEVLSHSLLLLHKKEDGIWSTDILKD

((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - furin TDLTFSVKSSRGSSDPQGVTCGAATLSAER (ARNRQKRS) VRGDNKEYEYSVECQEDSACPAAEESLPIE - FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) -stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS ARNRQKRSGVQVETISPGDGRTFPKRGQTC VVHYTGMLGDGKKVDSSRDRNKPFKFML GKQEVIRGWEEGVAQMSVGQGAKLTISPD YAYGATGHPGIIPPHATLVFDVELLELE* OT-1L12-005 CMV MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-006 CMV MCHQQLVISWFSLVFLASPLVAIWELKKDV 732 779 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3)- p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - stop) TDLTFSVKSSRGSSDPQGVTCGAATLSAER VRGDNKEYEYSVECQEDSACPAAEESLPIE VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF

YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

* OT-1L12-007 CMV MCHQQLVISWFSLVFLASPLVAISLIAALAV 733 780 (p40signal DYVIGMENAMPWNLPADLAWFKRNTLNK sequence; PVIMGRHTWESIGRPLPGRKNIILSSQPGTD ecDHFR DRVTWVKSVDEAIAACGDVPEIMVIGGGR (Amino acid 2- VIEQFLPKAQKLYLTHIDAEVEGDTHFPDYE 159 of WT) PDDWESVFSEFHDADAQNSHSYCFEILERR (R12Y, 1001) - ESRRVRRNKRSKIWELKKDVYVVELDWYP furin site DAPGEMVVLTCDTPEEDGITWTLDQSSEVL (ESRRVRRNK GSGKTLTIQVKEFGDAGQYTCHKGGEVLSH RSK) - p40 - SLLLLHKKEDGIWSTDILKDQKEPKNKTFLR linker ((G4S)3) CEAKNYSGRFTCWWLTTISTDLTFSVKSSR - p35) GSSDPQGVTCGAATLSAERVRGDNKEYEY SVECQEDSACPAAEESLPIEVMVDAVHKLK YENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQ VEVSWEYPDTWSTPHSYFSLTFCVQVQGKS KREKKDRVFTDKTSATVICRKNASISVRAQ DRYYSSSWSEWASVPCSGGGGSGGGGSGG GGSRNLPVATPDPGMFPCLHHSQNLLRAVS NMLQKARQTLEFYPCTSEEIDHEDITKDKTS TVEACLPLELTKNESCLNSRETSFITNGSCL ASRKTSFMMALCLSSIYEDLKMYQVEFKT MNAKLLMDPKRQIFLDQNMLAVIDELMQA LNFNSETVPQKSSLEEPDFYKTKIKLCILLH AFRIRAVTIDRVMSYLNAS OT-1L12-008 CMV MCHQQLVISWFSLVFLASPLVAVGSLNCIV 734 781 (p40signal AVSQNMGIGKNGDLPWPPLRNEFRYFFRM sequence; TTTSSVEGKQNLVIMGKKTWFSIPEKNRPL hDHFR KGRINLVLSRELKEPPQGAHFLSRSLDDALK (Amino acid 2- LTEQPELANKVDMVWIVGGSSVIKEFMNHP 187 of WT) GHLKLFVTRIMQDFESDTFFPEIDLEKYKLL (Q36K, Y1221, PEYPGVLSDVQEEKGIKYKFEVYEKNDESR A125F) - furin RVRRNKRSKIWELKKDVYVVELDWYPDAP site GEMVVLTCDTPEEDGITWTLDQSSEVLGSG (ESRRVRRNK KTLTIQVKEFGDAGQYTCHKGGEVLSHSLL RSK)- p40 - LLHKKEDGIWSTDILKDQKEPKNKTFLRCE linker((G4S)3) AKNYSGRFTCWWLTTISTDLTFSVKSSRGS - p35) SDPQGVTCGAATLSAERVRGDNKEYEYSV ECQEDSACPAAEESLPIEVMVDAVHKLKYE NYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVE VSWEYPDTWSTPHSYFSLTFCVQVQGKSKR EKKDRVFTDKTSATVICRKNASISVRAQDR YYSSSWSEWASVPCSGGGGSGGGGSGGGG SRNLPVATPDPGMFPCLHHSQNLLRAVSNM LQKARQTLEFYPCTSEEIDHEDITKDKTSTV EACLPLELTKNESCLNSRETSFITNGSCLASR KTSFMMALCLSSIYEDLKMYQVEFKTMNA KLLMDPKRQIFLDQNMLAVIDELMQALNF NSETVPQKSSLEEPDFYKTKIKLCILLHAFRI RAVTIDRVMSYLNAS OT-1L12-009 CMV MCHQQLVISWFSLVFLASPLVAIWELKKDV 735 782 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT - linker CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - furin TDLTFSVKSSRGSSDPQGVTCGAATLSAER (ESRRVRRNK VRGDNKEYEYSVECQEDSACPAAEESLPIE

RSK)- FKBP VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN (E31G,F36V, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS R71G, K105E)- LTFCVQVQGKSKREKKDRVFTDKTSATVIC stop) RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS ESRRVRRNKRSKGVQVETISPGDGRTFPKR GQTCVVHYTGMLGDGKKVDSSRDRNKPFK FMLGKQEVIRGWEEGVAQMSVGQGAKLTI SPDYAYGATGHPGIIPPHATLVFDVELLELE *

OT-1L12-019 PGK MCHQQLVISWFSLVFLASPLVAIWELKKDV 732 779 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40- WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker((G4S)3)- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD p35-stop) QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS TDLTFSVKSSRGSSDPQGVTCGAATLSAER VRGDNKEYEYSVECQEDSACPAAEESLPIE VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS *

OT-1L12-020 EFla MCHQQLVISWFSLVFLASPLVAIWELKKDV 732 779 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40- WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker((G4S)3)- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD p35-stop) QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS TDLTFSVKSSRGSSDPQGVTCGAATLSAER VRGDNKEYEYSVECQEDSACPAAEESLPIE VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS *

OT-IL12-021 No promoter MCHQQLVISWFSLVFLASPLVAIWELKKDV 732 779 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40- WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT CHKGGEVLSHSLLLLHKKEDGIWSTDILKD linker((G4S)3)- QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS p35-stop) TDLTFSVKSSRGSSDPQGVTCGAATLSAER VRGDNKEYEYSVECQEDSACPAAEESLPIE VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS *

OT-1L12-022 PGK MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-023 EFla MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV

IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-024 No promoter MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-025 PGK MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-026 EFla MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL

HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-027 No promoter MCHQQLVISWFSLVFLASPLVAIWELKKDV 731 778 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 - WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT linker- CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - linker TDLTFSVKSSRGSSDPQGVTCGAATLSAER (GGSG) - VRGDNKEYEYSVECQEDSACPAAEESLPIE FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) - stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS GGSGGVQVETISPGDGRTFPKRGQTCVVHY TGMLGDGKKVDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQGAKLTISPDYAYGA TGHPGIIPPHATLVFDVELLELE* OT-1L12-028 PGK MCHQQLVISWFSLVFLASPLVAIWELKKDV 730 777 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence - p40 WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT - linker CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - furin TDLTFSVKSSRGSSDPQGVTCGAATLSAER (ARNRQKRS) VRGDNKEYEYSVECQEDSACPAAEESLPIE - FKBP (E31G, VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN F36V, R71G, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS K105E) -stop) LTFCVQVQGKSKREKKDRVFTDKTSATVIC RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS ARNRQKRSGVQVETISPGDGRTFPKRGQTC VVHYTGMLGDGKKVDSSRDRNKPFKFML GKQEVIRGWEEGVAQMSVGQGAKLTISPD YAYGATGHPGIIPPHATLVFDVELLELE* OT-1L12-029 EFla MCHQQLVISWFSLVFLASPLVAIWELKKDV 735 782 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT - linker CHKGGEVLSHSLLLLHKKEDGIWSTDILKD

((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - furin TDLTFSVKSSRGSSDPQGVTCGAATLSAER (ESRRVRRNK VRGDNKEYEYSVECQEDSACPAAEESLPIE RSK)- FKBP VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN (E31G,F36V, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS R71G, K105E)- LTFCVQVQGKSKREKKDRVFTDKTSATVIC stop) RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS ESRRVRRNKRSKGVQVETISPGDGRTFPKR GQTCVVHYTGMLGDGKKVDSSRDRNKPFK FMLGKQEVIRGWEEGVAQMSVGQGAKLTI SPDYAYGATGHPGIIPPHATLVFDVELLELE *

OT-IL12-030 No promoter MCHQQLVISWFSLVFLASPLVAIWELKKDV 735 782 (p40 signal YVVELDWYPDAPGEMVVLTCDTPEEDGIT sequence- p40 WTLDQSSEVLGSGKTLTIQVKEFGDAGQYT - linker CHKGGEVLSHSLLLLHKKEDGIWSTDILKD ((G4S)3) - p35 QKEPKNKTFLRCEAKNYSGRFTCWWLTTIS - furin TDLTFSVKSSRGSSDPQGVTCGAATLSAER (ESRRVRRNK VRGDNKEYEYSVECQEDSACPAAEESLPIE RSK)- FKBP VMVDAVHKLKYENYTSSFFIRDIIKPDPPKN (E31G,F36V, LQLKPLKNSRQVEVSWEYPDTWSTPHSYFS R71G, K105E)- LTFCVQVQGKSKREKKDRVFTDKTSATVIC stop) RKNASISVRAQDRYYSSSWSEWASVPCSGG GGSGGGGSGGGGSRNLPVATPDPGMFPCL HHSQNLLRAVSNMLQKARQTLEFYPCTSEE IDHEDITKDKTSTVEACLPLELTKNESCLNS RETSFITNGSCLASRKTSFMMALCLSSIYED LKMYQVEFKTMNAKLLMDPKRQIFLDQN MLAVIDELMQALNFNSETVPQKSSLEEPDF YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS ESRRVRRNKRSKGVQVETISPGDGRTFPKR GQTCVVHYTGMLGDGKKVDSSRDRNKPFK FMLGKQEVIRGWEEGVAQMSVGQGAKLTI SPDYAYGATGHPGIIPPHATLVFDVELLELE *

OT-IL12-046 EFla MCHQQLVISWFSLVFLASPLVAGVQVETISP 727 774 (p40 signal GDGRTFPKRGQTCVVHYTGMLEDGKKVDS sequence- SRDRNKPFKFMLGKQEVIRGWEEGVAQMS FKBP (F36V, VGQRAKLTISPDYAYGATGHPGIIPPHATLV L106P) - FDVELLKPEGGSGGIWELKKDVYVVELDW Linker YPDAPGEMVVLTCDTPEEDGITWTLDQSSE (GGSGG) - VLGSGKTLTIQVKEFGDAGQYTCHKGGEVL p40 - Linker SHSLLLLHKKEDGIWSTDILKDQKEPKNKTF ((G4S)3) - p35 LRCEAKNYSGRFTCWWLTTISTDLTFSVKSS - stop) RGSSDPQGVTCGAATLSAERVRGDNKEYE YSVECQEDSACPAAEESLPIEVMVDAVHKL KYENYTSSFFIRDIIKPDPPKNLQLKPLKNSR QVEVSWEYPDTWSTPHSYFSLTFCVQVQGK SKREKKDRVFTDKTSATVICRKNASISVRAQ DRYYSSSWSEWASVPCSGGGGSGGGGSGG GGSRNLPVATPDPGMFPCLHHSQNLLRAVS

NMLQKARQTLEFYPCTSEEIDHEDITKDKTS TVEACLPLELTKNESCLNSRETSFITNGSCLA SRKTSFMMALCLSSIYEDLKMYQVEFKTMN AKLLMDPKRQIFLDQNMLAVIDELMQALNF NSETVPQKSSLEEPDFYKTKIKLCILLHAFRI RAVTIDRVMSYLNAS*

[00250] In one embodiment, the payload of the invention may comprise IL15. Interleukin 15 is a potent immune stimulatory cytokine and an essential survival factor for T cells, and Natural Killer cells. Preclinical studies comparing IL2 and IL15, have shown than IL15 is associated with less toxicity than IL2. In some embodiments, the effector module of the invention may be a DD-IL15 fusion polypeptide. IL15 polypeptide may also be modified to increase its binding affinity for the IL15 receptor. For example, the asparagine may be replaced by aspartic acid at position 72 of IL15 (SEQ ID NO. 2 of US patent publication US20140134128A1; the contents of which are incorporated by reference in their entirety). In some embodiments, the IL15 constructs of the invention may be placed under the transcriptional control of the CMV promoter (SEQ ID NO. 716), an EF l a promoter (SEQ ID NO. 717, SEQ ID NO. 908) or a PGK promoter (SEQ ID NO. 718). In some aspects, the DD-IL15 comprises the amino acid sequences listed in Table 12. The amino acid sequences in Table 12 may comprise a stop codon which is denoted in the table with a "*" at the end of the amino acid sequence. Table 12: DD IL15 constructs Description/ Promoter Amino Acid Sequence Amino Nucleic Construct ID Acid SEQ Acid SEQ ID NO ID NO IL2 signal sequence - MYRMQLLSCIALSLALVTNS 783 788-791 IgE Leader - MDWTWILFLVAAATRVHS 801 810,930, 931 Linker - EFSTEF 784 792-793 Linker - GGSGG 629 676-680 HA Tag - YPYDVPDYA 1024 1025-1027 BamHI - GS - GGATCC P2A Cleavable - GATNFSLLKQAGDVEENPGP 925 926 Peptide mCherry (M1L) - LSKGEEDNMAIIKEFMRFKVHMEGSVNG 1029 1030 HEFEIEGEGEGRPYEGTQTAKLKVTKGGP LPFAWDILSPQFMYGSKAYVKHPADIPDY LKLSFPEGFKWERVMNFEDGGVVTVTQD SSLQDGEFIYKVKLRGTNFPSDGPVMQKK TMGWEASSERMYPEDGALKGEIKQRLKL KDGGHYDAEVKTTYKAKKPVQLPGAYN VNIKLDITSHNEDYTIVEQYERAEGRHSTG GMDELYK IL15 - NWVNVISDLKKIEDLIQSMHIDATLYTESD 785 794-797, VHPSCKVTAMKCFLLELQVISLESGDASIH 1001

DTVENLIILANNSLSSNGNVTESGCKECEE LEEKNIKEFLQSFVHIVQMFINTS* ecDHFR (Amino acid - ISLIAALAVDYVIGMENAMPWNLPADLA 9 692,772, 2-159 of WT) (R12Y, WFKRNTLNKPVIMGRHTWESIGRPLPGRK 814,687, Y1001) NIILSSQPGTDDRVTWVKSVDEAIAACGD 988,991 VPEIMVIGGGRVIEQFLPKAQKLYLTHIDA EVEGDTHFPDYEPDDWESVFSEFHDADA QNSHSYCFEILERR* hDHFR (Amino acid - VGSLNCIVAVSQNMGIGKNGDLPWPPLR 895 694,995 2-187 of WT) NEFRYFQRMTTTSSVEGKQNLVIMGKKT (Y1221) WFSIPEKNRPLKGRINLVLSRELKEPPQGA HFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVIKEAMNHPGHLKLFVTRIMQDFE SDTFFPEIDLEKYKLLPEYPGVLSDVQEEK GIKYKFEVYEKND OT-IL15-001 (IL2 CMV MYRMQLLSCIALSLALVTNSNWVNVISDL 786 799 signal sequence- KKIEDLIQSMHIDATLYTESDVHPSCKVTA IL15-stop) MKCFLLELQVISLESGDASIHDTVENLIILA NNSLSSNGNVTESGCKECEELEEKNIKEFL QSFVHIVQMFINTS* OT-1L15-002 (IL2 CMV MYRMQLLSCIALSLALVTNSEFSTEFISLIA 787 800 signal sequence- ALAVDYVIGMENAMPWNLPADLAWFKR linker[EFSTEF]- NTLNKPVIMGRHTWESIGRPLPGRKNIILS ecDHFR (amino acid SQPGTDDRVTWVKSVDEAIAACGDVPEI 2-159 of WT, R12Y, MVIGGGRVIEQFLPKAQKLYLTHIDAEVE 1001)- linker GDTHFPDYEPDDWESVFSEFHDADAQNS

[GGSGG]- IL15- HSYCFEILERRGGSGGNWVNVISDLKKIE stop) DLIQSMHIDATLYTESDVHPSCKVTAMKC FLLELQVISLESGDASIHDTVENLIILANNS LSSNGNVTESGCKECEELEEKNIKEFLQSF VHIVQMFINTS* OT-IL15-062 (IgE EF1a MDWTWILFLVAAATRVHSYPYDVPDYA 631 749 leader - HA Tag - NWVNVISDLKKIEDLIQSMHIDATLYTESD IL15 - BamHI (GS) - VHPSCKVTAMKCFLLELQVISLESGDASIH stop) DTVENLIILANNSLSSNGNVTESGCKECEE LEEKNIKEFLQSFVHIVQMFINTSGS* OT-1L15-132 (IgE EFla MDWTWILFLVAAATRVHSNWVNVISDLK 725 1055 leader -IL15 - KIEDLIQSMHIDATLYTESDVHPSCKVTA BamHI (GS) - P2A MKCFLLELQVISLESGDASIHDTVENLIILA cleavable peptide - NNSLSSNGNVTESGCKECEELEEKNIKEFL mCherry (M1L) - QSFVHIVQMFINTSGSGATNFSLLKQAGD stop) VEENPGPLSKGEEDNMAIIKEFMRFKVHM EGSVNGHEFEIEGEGEGRPYEGTQTAKLK VTKGGPLPFAWDILSPQFMYGSKAYVKH PADIPDYLKLSFPEGFKWERVMNFEDGGV VTVTQDSSLQDGEFIYKVKLRGTNFPSDG PVMQKKTMGWEASSERMYPEDGALKGEI KQRLKLKDGGHYDAEVKTTYKAKKPVQ LPGAYNVNIKLDITSHNEDYTIVEQYERAE GRHSTGGMDELYK* OT-IL15-134 (IgE EFla MDWTWILFLVAAATRVHSNWVNVISDLK 726 1056 leader -IL15 - Linker KIEDLIQSMHIDATLYTESDVHPSCKVTA (GS) - hDHFR (WT MKCFLLELQVISLESGDASIHDTVENLIILA 2-187, Y1221) - NNSLSSNGNVTESGCKECEELEEKNIKEFL BamHI (GS) - P2A QSFVHIVQMFINTSGSVGSLNCIVAVSQN cleavable peptide - MGIGKNGDLPWPPLRNEFRYFQRMTTTSS VEGKQNLVIMGKKTWFSIPEKNRPLKGRI mCherry (M1L) - NLVLSRELKEPPQGAHFLSRSLDDALKLT stop) EQPELANKVDMVWIVGGSSVIKEAMNHP GHLKLFVTRIMQDFESDTFFPEIDLEKYKL LPEYPGVLSDVQEEKGIKYKFEVYEKNDG SGATNFSLLKQAGDVEENPGPLSKGEEDN MAIIKEFMRFKVHMEGSVNGHEFEIEGEG EGRPYEGTQTAKLKVTKGGPLPFAWDILS PQFMYGSKAYVKHPADIPDYLKLSFPEGF KWERVMNFEDGGVVTVTQDSSLQDGEFI YKVKLRGTNFPSDGPVMQKKTMGWEAS SERMYPEDGALKGEIKQRLKLKDGGHYD AEVKTTYKAKKPVQLPGAYNVNIKLDITS HNEDYTIVEQYERAEGRHSTGGMDELYK

Description/ Promoter Amino Acid Sequence Amino Nucleic Construct ID Acid SEQ Acid SEQ ID NO ID NO IL2 signal sequence - MYRMQLLSCIALSLALVTNS 783 788-791 IgE Leader - MDWTWILFLVAAATRVHS 801 810,930, 931 Linker - EFSTEF 784 792-793 Linker - GGSGG 629 676-680 HA Tag - YPYDVPDYA 1024 1025-1027 BamHI - GS - GGATCC P2A Cleavable - GATNFSLLKQAGDVEENPGP 925 926 Peptide mCherry (M1L) - LSKGEEDNMAIIKEFMRFKVHMEGSVNG 1029 1030 HEFEIEGEGEGRPYEGTQTAKLKVTKGGP LPFAWDILSPQFMYGSKAYVKHPADIPDY LKLSFPEGFKWERVMNFEDGGVVTVTQD SSLQDGEFIYKVKLRGTNFPSDGPVMQKK TMGWEASSERMYPEDGALKGEIKQRLKL KDGGHYDAEVKTTYKAKKPVQLPGAYN VNIKLDITSHNEDYTIVEQYERAEGRHSTG GMDELYK IL15 - NWVNVISDLKKIEDLIQSMHIDATLYTESD 785 794-797, VHPSCKVTAMKCFLLELQVISLESGDASIH 1001 DTVENLIILANNSLSSNGNVTESGCKECEE LEEKNIKEFLQSFVHIVQMFINTS* ecDHFR (Amino acid - ISLIAALAVDYVIGMENAMPWNLPADLA 9 692,772, 2-159 of WT) (R12Y, WFKRNTLNKPVIMGRHTWESIGRPLPGRK 814,687, Y1001) NIILSSQPGTDDRVTWVKSVDEAIAACGD 988,991 VPEIMVIGGGRVIEQFLPKAQKLYLTHIDA EVEGDTHFPDYEPDDWESVFSEFHDADA QNSHSYCFEILERR* hDHFR (Amino acid - VGSLNCIVAVSQNMGIGKNGDLPWPPLR 895 694,995 2-187 of WT) NEFRYFQRMTTTSSVEGKQNLVIMGKKT (Y1221) WFSIPEKNRPLKGRINLVLSRELKEPPQGA HFLSRSLDDALKLTEQPELANKVDMVWI VGGSSVIKEAMNHPGHLKLFVTRIMQDFE SDTFFPEIDLEKYKLLPEYPGVLSDVQEEK GIKYKFEVYEKND OT-IL15-001 (IL2 CMV MYRMQLLSCIALSLALVTNSNWVNVISDL 786 799 signal sequence- KKIEDLIQSMHIDATLYTESDVHPSCKVTA IL15-stop) MKCFLLELQVISLESGDASIHDTVENLIILA NNSLSSNGNVTESGCKECEELEEKNIKEFL QSFVHIVQMFINTS*

OT-1L15-002 (IL2 CMV MYRMQLLSCIALSLALVTNSEFSTEFISLIA 787 800 signal sequence- ALAVDYVIGMENAMPWNLPADLAWFKR linker[EFSTEF]- NTLNKPVIMGRHTWESIGRPLPGRKNIILS ecDHFR (amino acid SQPGTDDRVTWVKSVDEAIAACGDVPEI 2-159 of WT, R12Y, MVIGGGRVIEQFLPKAQKLYLTHIDAEVE 1001)- linker GDTHFPDYEPDDWESVFSEFHDADAQNS

[GGSGG]- IL15- HSYCFEILERRGGSGGNWVNVISDLKKIE stop) DLIQSMHIDATLYTESDVHPSCKVTAMKC FLLELQVISLESGDASIHDTVENLIILANNS LSSNGNVTESGCKECEELEEKNIKEFLQSF VHIVQMFINTS* OT-IL15-062 (IgE EF1a MDWTWILFLVAAATRVHSYPYDVPDYA 631 749 leader - HA Tag - NWVNVISDLKKIEDLIQSMHIDATLYTESD IL15 - BamHI (GS) - VHPSCKVTAMKCFLLELQVISLESGDASIH stop) DTVENLIILANNSLSSNGNVTESGCKECEE LEEKNIKEFLQSFVHIVQMFINTSGS* OT-1L15-132 (IgE EFla MDWTWILFLVAAATRVHSNWVNVISDLK 725 1055 leader -IL15 - KIEDLIQSMHIDATLYTESDVHPSCKVTA BamHI (GS) - P2A MKCFLLELQVISLESGDASIHDTVENLIILA cleavable peptide - NNSLSSNGNVTESGCKECEELEEKNIKEFL mCherry (M1L) - QSFVHIVQMFINTSGSGATNFSLLKQAGD stop) VEENPGPLSKGEEDNMAIIKEFMRFKVHM EGSVNGHEFEIEGEGEGRPYEGTQTAKLK VTKGGPLPFAWDILSPQFMYGSKAYVKH PADIPDYLKLSFPEGFKWERVMNFEDGGV VTVTQDSSLQDGEFIYKVKLRGTNFPSDG PVMQKKTMGWEASSERMYPEDGALKGEI KQRLKLKDGGHYDAEVKTTYKAKKPVQ LPGAYNVNIKLDITSHNEDYTIVEQYERAE GRHSTGGMDELYK* OT-1L15-134 (IgE EFla MDWTWILFLVAAATRVHSNWVNVISDLK 726 1056 leader -IL15 - Linker KIEDLIQSMHIDATLYTESDVHPSCKVTA (GS) - hDHFR (WT MKCFLLELQVISLESGDASIHDTVENLIILA 2-187, Y1221) - NNSLSSNGNVTESGCKECEELEEKNIKEFL BamHI (GS) - P2A QSFVHIVQMFINTSGSVGSLNCIVAVSQN cleavable peptide - MGIGKNGDLPWPPLRNEFRYFQRMTTTSS mCherry (M1L) - VEGKQNLVIMGKKTWFSIPEKNRPLKGRI stop) NLVLSRELKEPPQGAHFLSRSLDDALKLT EQPELANKVDMVWIVGGSSVIKEAMNHP GHLKLFVTRIMQDFESDTFFPEIDLEKYKL LPEYPGVLSDVQEEKGIKYKFEVYEKNDG SGATNFSLLKQAGDVEENPGPLSKGEEDN MAIIKEFMRFKVHMEGSVNGHEFEIEGEG EGRPYEGTQTAKLKVTKGGPLPFAWDILS PQFMYGSKAYVKHPADIPDYLKLSFPEGF KWERVMNFEDGGVVTVTQDSSLQDGEFI YKVKLRGTNFPSDGPVMQKKTMGWEAS SERMYPEDGALKGEIKQRLKLKDGGHYD AEVKTTYKAKKPVQLPGAYNVNIKLDITS HNEDYTIVEQYERAEGRHSTGGMDELYK

[00251] A unique feature of IL15 mediated activation is the mechanism of trans-presentation in which IL15 is presented as a complex with the alpha subunit of IL15 receptor (IL15Ra) that binds to and activates membrane bound IL15 beta/gamma receptor, either on the same cell or a different cell. The IL15/IL15Ra complex is more effective in activating IL15 signaling, than IL15 by itself. Thus, in some embodiments, the effector module of the invention may include a DD-IL15/IL15Ra fusion polypeptide. In one embodiment, the payload may be IL15/IL15Ra fusion polypeptide described in US Patent Publication NO.: US20160158285A1 (the contents of which are incorporated herein by reference in their entirety). The IL15 receptor alpha comprises an extracellular domain called the sushi domain which contains most of the structural elements necessary for binding to IL15. Thus, in some embodiments, payload may be the IL15/IL15Ra sushi domain fusion polypeptide described in US Patent Publication NO.: US20090238791A1 (the contents of which are incorporated herein by reference in their entirety).

[00252] Regulated IL15/IL15Ra maybe used to promote expansion, survival and potency of CD8TEM cell populations without impacting regulatory T cells, NK cells and TIL cells. In one embodiment, DD-IL15/IL15Ra may be utilized to enhance CD19 directed T cell therapies in B cell leukemia and lymphomas. In one aspect, IL15/IL15Ra may be used as payload of the invention to reduce the need for pre-conditioning regimens in current CAR-T treatment paradigms.

[00253] The effector modules containing DD-IL15, DD-IL15/IL15Ra and/or DD-IL15/IL15Ra sushi domain may be designed to be secreted (using e.g. IL2 signal sequence) or membrane bound (using e.g. IgE or CD8a signal sequence).

[00254] In some aspects, the DD-IL115/IL15Ra comprises the amino acid sequences provided in Table 13a, 13b, and 13c. The amino acid sequences in Tables 13a, 13b and13c may comprise a stop codon which is denoted in the table with a "*" at the end of the amino acid sequence.

Table 13a: DD-IL15/IL15Ra construct sequences

Description/ Amino Acid Sequence Amino Acid Nucleic Acid Construct ID SEQ ID NO SEQ ID NO IgE leader MDWTWILFLVAAATRVHS 801 810,930,931 IL15RA Leader MAPRRARGCRTLGLPALLLLLLLRPPATRG 932 933 Linker (SG3- SGGGSGGGGSGGGGSGGGGSGGGSLQ 802 811, 916-920, (SG4)3-SG3-SLQ) 1002 Linker (SG3S) SGGGS 827 828,844,909 Linker SGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGS 921 923 (SG3(SG4)5SG3S) Linker SGGGSGGGGSGGGGSGGGGS 922 924 Linker GS - GGTTCC Linker SG AGCGGC Linker GSG GGATCCGG A or GGATCCGG T

Spacer 927-929, 1000, TCGCGAAT G, TCGCA IL15 NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVT 785 794-797, AMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSN 1001 GNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS* IL15Ra ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAG 803 812-813, TSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPA 1003 PPSTVTTAGVTPQPESLSPSGKEPAASSPSSNNTAATT AAIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTTAKN WELTASASHQPPGVYPQGHSDTTVAISTSTVLLCGLS AVSLLACYLKSRQTPPLASVEMEAMEALPVTWGTSS RDEDLENCSHHL* IL15Ra (31-205 of ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAG 1057 1058 Uniprot ID: TSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPA Q13261.1) PPSTVTTAGVTPQPESLSPSGKEPAASSPSSNNTAATTA AIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTTAKN WELTASASHQPPGVYPQGHSDTT mCherry MSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEG 1059 1060 EGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSK AYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVT VTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMG WEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVK TTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYE RAEGRHSTGGMDELYK* mCherry (M1L) LSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEG 1029 1030 EGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSK AYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVT VTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMG WEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVK TTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYE RAEGRHSTGGMDELYK HATag YPYDVPDYA 1024 1025-1027 Flag DYKDDDDK 1232 BamHI GS - GGATCC P2A Cleavable GATNFSLLKQAGDVEENPGP 925 926 Peptide ecDHFR (Amino ISLIAALAVDYVIGMENAMPWNLPADLAWFKRNTLN 9 692,772, acid 2-159 of WT KPVIMGRHTWESIGRPLPGRKNIILSSQPGTDDRVTWV 814,687, R12Y, Y1001) KSVDEAIAACGDVPEIMVIGGGRVIEQFLPKAQKLYLT 988,991 HIDAEVEGDTHFPDYEPDDWESVFSEFHDADAQNSHS YCFEILERR* ecDHFR (Amino ISLIAALAVDHVIGMENAMPWNLPADLAWFKRNTLN 10 798,815,993 acid 2-159 of WT KPVIMGRHTWESIGRPLPGRKNIILSSQPGTDDRVTWV R12H, E129K) KSVDEAIAACGDVPEIMVIGGGRVYEQFLPKAQKLYL THIDAEVEGDTHFPDYKPDDWESVFSEFHDADAQNS HSYCFEILERR* FKBP (E31G, GVQVETISPGDGRTFPKRGQTCVVHYTGMLGDGKKV 12 688-691,994, F36V, R71G, DSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQG 1013,1028 K105E) AKLTISPDYAYGATGHPGIIPPHATLVFDVELLELE* hDHFR (Amino VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 890 696,973, acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL 974,996 Y1221, A125F) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVIKEFMNHPGHLKLFVTRIMQDFESDTF FPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKN D* hDHFR (Amino VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFFRM 891 700,975, acid 2-187 of WT; TTTSSVEGKQNLVIMGKKTWFSIPEKFRPLKGRINLVL 976,998 Q36F, N65F, SRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMV Y1221) WIVGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTFFPE IDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND hDHFR (Amino VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 889 972 acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL K185E) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDT FFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEE ND* hDHFR (Amino VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 888 970-972 acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL E162G,1176F) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDT FFPEIDLEKYKLLPGYPGVLSDVQEEKGFKYKFEVYE KND* hDHFR (Amino VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 892 977 acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL N127Y) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVYKEAMYHPGHLKLFVTRIMQDFESDT FFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEK ND hDHFR (Amino VGSLNCIVAVSQNMGVGKNGDLPWPPLRNEFRYFQR 894 979 acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL 117V) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDT FFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEK ND hDHFR (Amino VGSLNCIVAVSQNMGVGKNGDLPWPPLRNEFRYFQR 882 969 acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL 117V, Y1221) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVIKEAMNHPGHLKLFVTRIMQDFESDTF FPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKN D hDHFR (Amino VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQR 893 978 acid 2-187 of WT; MTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINL H131R, E144G) VLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVD MVWIVGGSSVYKEAMNHPGRLKLFVTRIMQDFGSDT FFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEK ND

Table 13b: DD-IL15/IL15Ra constructs

Description Promoter Amino acid sequences Amino Acid Nucleic Acid SEQIDNO SEQIDNO OT-1L15-006 EFla MDWTWILFLVAAATRVHSNWVNVISDL 804 816 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence;IL15; AMKCFLLELQVISLESGDASIHDTVENLII linker1 (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)5-SG3); EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra; linker2 GGSGGGGSGGGSLQITCPPPMSVEHADI (GGSGG); WVKSYSLYSRERYICNSGFKRKAGTSSL ecDHFR (R12H, TECVLNKATNVAHWTTPSLKCIRDPALV E129K)) HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAIVPGSQLMPSKSP

STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGISLI AALAVDHVIGMENAMPWNLPADLAWF KRNTLNKPVIMGRHTWESIGRPLPGRKN IILSSQPGTDDRVTWVKSVDEAIAACGD VPEIMVIGGGRVYEQFLPKAQKLYLTHI DAEVEGDTHFPDYKPDDWESVFSEFHD ADAQNSHSYCFEILERR* OT-1L15-007 EFla MDWTWILFLVAAATRVHSNWVNVISDL 805 817 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence;IL15; AMKCFLLELQVISLESGDASIHDTVENLII linker1 (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)5-SG3); EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra; linker2 GGSGGGGSGGGSLQITCPPPMSVEHADI (GGSGG); WVKSYSLYSRERYICNSGFKRKAGTSSL FKBP TECVLNKATNVAHWTTPSLKCIRDPALV (E31G,F36V, HQRPAPPSTVTTAGVTPQPESLSPSGKEP R71G, K105E)) AASSPSSNNTAATTAAIVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGGVQ VETISPGDGRTFPKRGQTCVVHYTGMLG DGKKVDSSRDRNKPFKFMLGKQEVIRG WEEGVAQMSVGQGAKLTISPDYAYGAT GHPGIIPPHATLVFDVELLELE* OT-IL15-008 EFla MDWTWILFLVAAATRVHSNWVNVISDL 806 818 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence- IL15- AMKCFLLELQVISLESGDASIHDTVENLII linker (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)3-SG3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SLQ)-IL15Ra- GGSGGGGSGGGSLQITCPPPMSVEHADI stop) WVKSYSLYSRERYICNSGFKRKAGTSSL TECVLNKATNVAHWTTPSLKCIRDPALV HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAIVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHL* OT-1L15-009 EFla MDWTWILFLVAAATRVHSNWVNVISDL 807 819 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence- IL15- AMKCFLLELQVISLESGDASIHDTVENLII linker (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)3-SG3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SLQ)- IL15Ra- GGSGGGGSGGGSLQITCPPPMSVEHADI linker (SG)- WVKSYSLYSRERYICNSGFKRKAGTSSL ecDHFR (Amino TECVLNKATNVAHWTTPSLKCIRDPALV acid 2-159 of HQRPAPPSTVTTAGVTPQPESLSPSGKEP WT; R12Y, AASSPSSNNTAATTAAIVPGSQLMPSKSP Y1001)-stop) STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGISLI AALAVDYVIGMENAMPWNLPADLAWF KRNTLNKPVIMGRHTWESIGRPLPGRKN

IILSSQPGTDDRVTWVKSVDEAIAACGD VPEIMVIGGGRVIEQFLPKAQKLYLTHID AEVEGDTHFPDYEPDDWESVFSEFHDAD AQNSHSYCFEILERR* OT-IL15-010 EFla MDWTWILFLVAAATRVHSNWVNVISDL 808 820 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence- IL15- AMKCFLLELQVISLESGDASIHDTVENLII linker (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)3-SG3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SLQ)- IL15Ra- GGSGGGGSGGGSLQITCPPPMSVEHADI linker (SG)- WVKSYSLYSRERYICNSGFKRKAGTSSL hDHFR (Y1221, TECVLNKATNVAHWTTPSLKCIRDPALV A125F)-stop) HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAIVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGVGS LNCIVAVSQNMGIGKNGDLPWPPLRNEF RYFQRMTTTSSVEGKQNLVIMGKKTWF SIPEKNRPLKGRINLVLSRELKEPPQGAH FLSRSLDDALKLTEQPELANKVDMVWIV GGSSVIKEFMNHPGHLKLFVTRIMQDFE SDTFFPEIDLEKYKLLPEYPGVLSDVQEE KGIKYKFEVYEKND* OT-IL15-011 EFla MDWTWILFLVAAATRVHSNWVNVISDL 809 821 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence- IL15- AMKCFLLELQVISLESGDASIHDTVENLII linker (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)3-SG3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SLQ)- IL15Ra; GGSGGGGSGGGSLQITCPPPMSVEHADI linker (SG)- WVKSYSLYSRERYICNSGFKRKAGTSSL hDHFR (Amino TECVLNKATNVAHWTTPSLKCIRDPALV acid 2-187 of HQRPAPPSTVTTAGVTPQPESLSPSGKEP WT; Q36F, AASSPSSNNTAATTAAIVPGSQLMPSKSP N65F, Y1221)- STGTTEISSHESSHGTPSQTTAKNWELTA stop) SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGVGS LNCIVAVSQNMGIGKNGDLPWPPLRNEF RYFFRMTTTSSVEGKQNLVIMGKKTWFS IPEKFRPLKGRINLVLSRELKEPPQGAHFL SRSLDDALKLTEQPELANKVDMVWIVG GSSVIKEAMNHPGHLKLFVTRIMQDFES DTFFPEIDLEKYKLLPEYPGVLSDVQEEK GIKYKFEVYEKND* OT-1L15-017 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1061 1086 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence- IL15- AMKCFLLELQVISLESGDASIHDTVENLII linker (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)3-SG3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SLQ)- IL15Ra- GGSGGGGSGGGSLQITCPPPMSVEHADI linker (SG)- WVKSYSLYSRERYICNSGFKRKAGTSSL hDHFR (Amino TECVLNKATNVAHWTTPSLKCIRDPALV acid 2-187 of HQRPAPPSTVTTAGVTPQPESLSPSGKEP WT; K185E)- AASSPSSNNTAATTAAIVPGSQLMPSKSP stop) STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC

GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGVGS LNCIVAVSQNMGIGKNGDLPWPPLRNEF RYFQRMTTTSSVEGKQNLVIMGKKTWF SIPEKNRPLKGRINLVLSRELKEPPQGAH FLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMNHPGHLKLFVTRIMQDF ESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEEND* OT-1L15-018 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1062 1087 (IgEsignal KKIEDLIQSMHIDATLYTESDVHPSCKVT sequence- IL15- AMKCFLLELQVISLESGDASIHDTVENLII linker (SG3- LANNSLSSNGNVTESGCKECEELEEKNIK (SG4)3-SG3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SLQ)- IL15Ra- GGSGGGGSGGGSLQITCPPPMSVEHADI linker (SG)- WVKSYSLYSRERYICNSGFKRKAGTSSL hDHFR (Amino TECVLNKATNVAHWTTPSLKCIRDPALV acid 2-187 of HQRPAPPSTVTTAGVTPQPESLSPSGKEP WT; E162G, AASSPSSNNTAATTAAIVPGSQLMPSKSP 1176F)-stop) STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGVGS LNCIVAVSQNMGIGKNGDLPWPPLRNEF RYFQRMTTTSSVEGKQNLVIMGKKTWF SIPEKNRPLKGRINLVLSRELKEPPQGAH FLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMNHPGHLKLFVTRIMQDF ESDTFFPEIDLEKYKLLPGYPGVLSDVQE EKGFKYKFEVYEKND* OT-IL15-038 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1063 1088 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra - Linker GGSGGGGSGGGSLQITCPPPMSVEHADI (SG)- hDHFR WVKSYSLYSRERYICNSGFKRKAGTSSL (Amino acid 2- TECVLNKATNVAHWTTPSLKCIRDPALV 187 of WT; HQRPAPPSTVTTAGVTPQPESLSPSGKEP N127Y)-stop) AASSPSSNNTAATTAAIVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGVGS LNCIVAVSQNMGIGKNGDLPWPPLRNEF RYFQRMTTTSSVEGKQNLVIMGKKTWF SIPEKNRPLKGRINLVLSRELKEPPQGAH FLSRSLDDALKLTEQPELANKVDMVWIV GGSSVYKEAMYHPGHLKLFVTRIMQDF ESDTFFPEIDLEKYKLLPEYPGVLSDVQE EKGIKYKFEVYEKND* OT-IL15-051 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1064 1089 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - HA EFLQSFVHIVQMFINTSSGGGSGGGGSGG Tag - IL15Ra - GGSGGGGSGGGSLQYPYDVPDYAITCPP stop) PMSVEHADIWVKSYSLYSRERYICNSGF

KRKAGTSSLTECVLNKATNVAHWTTPSL KCIRDPALVHQRPAPPSTVTTAGVTPQPE SLSPSGKEPAASSPSSNNTAATTAAIVPG SQLMPSKSPSTGTTEISSHESSHGTPSQTT AKNWELTASASHQPPGVYPQGHSDTTV AISTSTVLLCGLSAVSLLACYLKSRQTPP LASVEMEAMEALPVTWGTSSRDEDLEN CSHHL* OT-1L15-053 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1066 1091 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3(SG4)5SG3 LANNSLSSNGNVTESGCKECEELEEKNIK S) - IL15Ra - EFLQSFVHIVQMFINTSSGGGSGGGGSGG Stop) GGSGGGGSGGGGSGGGGSGGGSITCPPP MSVEHADIWVKSYSLYSRERYICNSGFK RKAGTSSLTECVLNKATNVAHWTTPSLK CIRDPALVHQRPAPPSTVTTAGVTPQPES LSPSGKEPAASSPSSNNTAATTAAIVPGS QLMPSKSPSTGTTEISSHESSHGTPSQTTA KNWELTASASHQPPGVYPQGHSDTTVAI STSTVLLCGLSAVSLLACYLKSRQTPPLA SVEMEAMEALPVTWGTSSRDEDLENCS HHL* OT-IL15-054 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1067 1092 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3(SG4)3S) - LANNSLSSNGNVTESGCKECEELEEKNIK HA Tag - Linker EFLQSFVHIVQMFINTSSGGGSGGGGSGG (SG3S) - GGSGGGGSYPYDVPDYASGGGSITCPPP IL15Ra - Stop) MSVEHADIWVKSYSLYSRERYICNSGFK RKAGTSSLTECVLNKATNVAHWTTPSLK CIRDPALVHQRPAPPSTVTTAGVTPQPES LSPSGKEPAASSPSSNNTAATTAAIVPGS QLMPSKSPSTGTTEISSHESSHGTPSQTTA KNWELTASASHQPPGVYPQGHSDTTVAI STSTVLLCGLSAVSLLACYLKSRQTPPLA SVEMEAMEALPVTWGTSSRDEDLENCS HHL* OT-IL15-055 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1068 1093 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG) - IL15Ra - LANNSLSSNGNVTESGCKECEELEEKNIK Stop) EFLQSFVHIVQMFINTSSGITCPPPMSVEH ADIWVKSYSLYSRERYICNSGFKRKAGT SSLTECVLNKATNVAHWTTPSLKCIRDP ALVHQRPAPPSTVTTAGVTPQPESLSPSG KEPAASSPSSNNTAATTAAIVPGSQLMPS KSPSTGTTEISSHESSHGTPSQTTAKNWE LTASASHQPPGVYPQGHSDTTVAISTSTV LLCGLSAVSLLACYLKSRQTPPLASVEM EAMEALPVTWGTSSRDEDLENCSHHL* OT-IL15-060 EF1a MAPRRARGCRTLGLPALLLLLLLRPPAT 1069 1094 (IL15Ra signal RGNWVNVISDLKKIEDLIQSMHIDATLYT peptide - IL15 - ESDVHPSCKVTAMKCFLLELQVISLESG Linker (SG3- DASIHDTVENLIILANNSLSSNGNVTESG (SG4)3-SG3- CKECEELEEKNIKEFLQSFVHIVQMFINT SSGGGSGGGGSGGGGSGGGGSGGGSLQl

SLQ) - IL15Ra TCPPPMSVEHADIWVKSYSLYSRERYIC - stop) NSGFKRKAGTSSLTECVLNKATNVAHW TTPSLKCIRDPALVHQRPAPPSTVTTAGV TPQPESLSPSGKEPAASSPSSNNTAATTA AIVPGSQLMPSKSPSTGTTEISSHESSHGT PSQTTAKNWELTASASHQPPGVYPQGHS DTTVAISTSTVLLCGLSAVSLLACYLKSR QTPPLASVEMEAMEALPVTWGTSSRDE DLENCSHHL* OT-IL15-063 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1070 1095 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra - GGSGGGGSGGGSLQITCPPPMSVEHADI BamHI (GS) - WVKSYSLYSRERYICNSGFKRKAGTSSL stop) TECVLNKATNVAHWTTPSLKCIRDPALV HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDITTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLGS* OT-IL15-064 EFla MDWTWILFLVAAATRVHSNWVNVISDL 806 818 andOT-IL15- KKIEDLIQSMHIDATLYTESDVHPSCKVT 071 (IgE leader - AMKCFLLELQVISLESGDASIHDTVENLII IL15 - Linker LANNSLSSNGNVTESGCKECEELEEKNIK (SG3-(SG4)3- EFLQSFVHIVQMFINTSSGGGSGGGGSGG SG3-SLQ) - GGSGGGGSGGGSLQITCPPPMSVEHADI IL15Ra - stop) WVKSYSLYSRERYICNSGFKRKAGTSSL TECVLNKATNVAHWTTPSLKCIRDPALV HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDITTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHL* OT-1L15-066 EFla MDWTWILFLVAAATRVHSNWVNVISDL 807 819 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra- Linker GGSGGGGSGGGSLQITCPPPMSVEHADI (SG) ecDHFR WVKSYSLYSRERYICNSGFKRKAGTSSL (Amino acid 2- TECVLNKATNVAHWTTPSLKCIRDPALV 159 of WT, HQRPAPPSTVTTAGVTPQPESLSPSGKEP R12Y, Y1001) - AASSPSSNNTAATTAAVPGSQLMPSKSP stop) STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDITTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGISLI AALAVDYVIGMENAMPWNLPADLAWF KRNTLNKPVIMGRHTWESIGRPLPGRKN IILSSQPGTDDRVTWVKSVDEAIAACGD VPEIMVIGGGRVIEQFLPKAQKLYLTHID AEVEGDTHFPDYEPDDWESVFSEFHDAD AQNSHSYCFEILERR*

OT-1L15-067 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1071 1098 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra - Linker GGSGGGGSGGGSLQITCPPPMSVEHADI (SG) - ecDHFR WVKSYSLYSRERYICNSGFKRKAGTSSL (Amino acid 2- TECVLNKATNVAHWTTPSLKCIRDPALV 159 of WT, HQRPAPPSTVTTAGVTPQPESLSPSGKEP R12Y, Y1001) - AASSPSSNNTAATTAAIVPGSQLMPSKSP stop) STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSGISLI AALAVDYVIGMENAMPWNLPADLAWF KRNTLNKPVIMGRHTWESIGRPLPGRKN IILSSQPGTDDRVTWVKSVDEAIAACGD VPEIMVIGGGRVIEQFLPKAQKLYLTHID AEVEGDTHFPDYEPDDWESVFSEFHDAD AQNSHSYCFEILERR* OT-1L15-070 EFla MAPRRARGCRTLGLPALLLLLLLRPPAT 1072 1101 (IL15Ra signal RGNWVNVISDLKKIEDLIQSMHIDATLYT peptide - IL15 - ESDVHPSCKVTAMKCFLLELQVISLESG Linker (SG3- DASIHDTVENLIILANNSLSSNGNVTESG (SG4)3-SG3- CKECEELEEKNIKEFLQSFVHIVQMFINT SLQ) - IL15Ra SSGGGSGGGGSGGGGSGGGGSGGGSLQI - stop) TCPPPMSVEHADIWVKSYSLYSRERYIC NSGFKRKAGTSSLTECVLNKATNVAHW TTPSLKCIRDPALVHQRPAPPSTVTTAGV TPQPESLSPSGKEPAASSPSSNNTAATTA AIVPGSQLMPSKSPSTGTTEISSHESSHGT PSQTTAKNWELTASASHQPPGVYPQGHS DTTVAISTSTVLLCGLSAVSLLACYLKSR QTPPLASVEMEAMEALPVTWGTSSRDE DLENCSHHL* OT-IL15-072 EFla MDWTWILFLVAAATRVHSNWVNVISDL 806 1096 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra - stop) GGSGGGGSGGGSLQITCPPPMSVEHADI WVKSYSLYSRERYICNSGFKRKAGTSSL TECVLNKATNVAHWTTPSLKCIRDPALV HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDITTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHL* OT-1L15-089 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1074 1102 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT ecDHFR (Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-159 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT, R12Y, TAATTAAIVPGSQLMPSKSPSTGTTEISSH Y1001) - stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGISLIAALAVDY VIGMENAMPWNLPADLAWFKRNTLNKP VIMGRHTWESIGRPLPGRKNIILSSQPGT DDRVTWVKSVDEAIAACGDVPEIMVIGG GRVIEQFLPKAQKLYLTHIDAEVEGDTH FPDYEPDDWESVFSEFHDADAQNSHSYC FEILERR* OT-1L15-109 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1070 1095 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra - GGSGGGGSGGGSLQITCPPPMSVEHADI BamHI (GS) - WVKSYSLYSRERYICNSGFKRKAGTSSL stop) TECVLNKATNVAHWTTPSLKCIRDPALV HQRPAPPSTVTTAGVTPQPESLSPSGKEP AASSPSSNNTAATTAAIVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLGS* OT-IL15-110 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1075 1103 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY BamHI (GS) - SRERYICNSGFKRKAGTSSLTECVLNKAT stop) NVAHWTTPSLKCIRDPALVHQRPAPPST VTTAGVTPQPESLSPSGKEPAASSPSSNN TAATTAAIVPGSQLMPSKSPSTGTTEISSH ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGS* OT-IL15-114 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1076 1104 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY Linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT hDHFR (Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-187 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT; K185E) - TAATTAAIVPGSQLMPSKSPSTGTTEISSH stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGVGSLNCIVAV SQNMGIGKNGDLPWPPLRNEFRYFQRM TTTSSVEGKQNLVIMGKKTWFSIPEKNR

PLKGRINLVLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWIVGGSSVY KEAMNHPGHLKLFVTRIMQDFESDTFFP EIDLEKYKLLPEYPGVLSDVQEEKGIKYK FEVYEEND* OT-IL15-115 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1077 1105 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY Linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT hDHFR (Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-187 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT; E162G, TAATTAAIVPGSQLMPSKSPSTGTTEISSH 1176F) - stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGVGSLNCIVAV SQNMGIGKNGDLPWPPLRNEFRYFQRM TTTSSVEGKQNLVIMGKKTWFSIPEKNR PLKGRINLVLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWIVGGSSVY KEAMNHPGHLKLFVTRIMQDFESDTFFP EIDLEKYKLLPGYPGVLSDVQEEKGFKY KFEVYEKND* OT-IL15-116 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1078 1106 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY Linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT hDHFR (Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-187 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT; H131R, TAATTAAIVPGSQLMPSKSPSTGTTEISSH E144G) - stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGVGSLNCIVAV SQNMGIGKNGDLPWPPLRNEFRYFQRM TTTSSVEGKQNLVIMGKKTWFSIPEKNR PLKGRINLVLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWIVGGSSVY KEAMNHPGRLKLFVTRIMQDFGSDTFFP EIDLEKYKLLPEYPGVLSDVQEEKGIKYK FEVYEKND* OT-IL15-117 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1079 1107 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY Linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT hDHFR(Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-187 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT; 117V) - TAATTAAIVPGSQLMPSKSPSTGTTEISSH stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGVGSLNCIVAV SQNMGVGKNGDLPWPPLRNEFRYFQRM TTTSSVEGKQNLVIMGKKTWFSIPEKNR PLKGRINLVLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWIVGGSSVY KEAMNHPGHLKLFVTRIMQDFESDTFFP EIDLEKYKLLPEYPGVLSDVQEEKGIKYK FEVYEKND* OT-IL15-118 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1080 1108 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY Linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT hDHFR (Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-187 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT, N127Y) - TAATTAAIVPGSQLMPSKSPSTGTTEISSH stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGVGSLNCIVAV SQNMGIGKNGDLPWPPLRNEFRYFQRM TTTSSVEGKQNLVIMGKKTWFSIPEKNR PLKGRINLVLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWIVGGSSVY KEAMYHPGHLKLFVTRIMQDFESDTFFP EIDLEKYKLLPEYPGVLSDVQEEKGIKYK FEVYEKND* OT-IL15-119 EFla MDWTWILFLVAAATRVHSDYKDDDDK 1081 1109 (IgE leader - NWVNVISDLKKIEDLIQSMHIDATLYTES FLAG -IL15 - DVHPSCKVTAMKCFLLELQVISLESGDA Linker (SG3- SIHDTVENLIILANNSLSSNGNVTESGCK (SG4)3-SG3- ECEELEEKNIKEFLQSFVHIVQMFINTSSG SLQ) - HA Tag GGSGGGGSGGGGSGGGGSGGGSLQYPY - IL15Ra - DVPDYAITCPPPMSVEHADIWVKSYSLY Linker (GSG) - SRERYICNSGFKRKAGTSSLTECVLNKAT hDHFR (Amino NVAHWTTPSLKCIRDPALVHQRPAPPST acid 2-187 of VTTAGVTPQPESLSPSGKEPAASSPSSNN WT, 117V, TAATTAAIVPGSQLMPSKSPSTGTTEISSH Y1221) - stop) ESSHGTPSQTTAKNWELTASASHQPPGV YPQGHSDTTVAISTSTVLLCGLSAVSLLA CYLKSRQTPPLASVEMEAMEALPVTWG TSSRDEDLENCSHHLGSGVGSLNCIVAV SQNMGVGKNGDLPWPPLRNEFRYFQRM TTTSSVEGKQNLVIMGKKTWFSIPEKNR PLKGRINLVLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWIVGGSSVIK EAMNHPGHLKLFVTRIMQDFESDTFFPEI DLEKYKLLPEYPGVLSDVQEEKGIKYKF EVYEKND*

OT-1L15-128 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1082 1110 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra- Spacer GGSGGGGSGGGSLQITCPPPMSVEHADI - Flagx3 - WVKSYSLYSRERYICNSGFKRKAGTSSL Spacer - BamHI TECVLNKATNVAHWTTPSLKCIRDPALV (GS) - P2A HQRPAPPSTVTTAGVTPQPESLSPSGKEP cleavable peptide AASSPSSNNTAATTAAIVPGSQLMPSKSP - mCherry STGTTEISSHESSHGTPSQTTAKNWELTA (M1L) - stop) SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLSRMD YKDDDDKDYKDDDDKDYKDDDDKSRG SGATNFSLLKQAGDVEENPGPLSKGEED NMAIIKEFMRFKVHMEGSVNGHEFEIEG EGEGRPYEGTQTAKLKVTKGGPLPFAW DILSPQFMYGSKAYVKHPADIPDYLKLSF PEGFKWERVMNFEDGGVVTVTQDSSLQ DGEFIYKVKLRGTNFPSDGPVMQKKTM GWEASSERMYPEDGALKGEIKQRLKLK DGGHYDAEVKTTYKAKKPVQLPGAYN VNIKLDITSHNEDYTIVEQYERAEGRHST GGMDELYK* OT-IL15-129 EFla MDWTWILFLVAAATRVHSNWVNVISDL 1083 1111 (IgE leader - KKIEDLIQSMHIDATLYTESDVHPSCKVT IL15 - Linker AMKCFLLELQVISLESGDASIHDTVENLII (SG3-(SG4)3- LANNSLSSNGNVTESGCKECEELEEKNIK SG3-SLQ) - EFLQSFVHIVQMFINTSSGGGSGGGGSGG IL15Ra-BamHI GGSGGGGSGGGSLQITCPPPMSVEHADI (GS) - P2A WVKSYSLYSRERYICNSGFKRKAGTSSL cleavable peptide TECVLNKATNVAHWTTPSLKCIRDPALV - mCherry HQRPAPPSTVTTAGVTPQPESLSPSGKEP (MlL)-stop) AASSPSSNNTAATTAAIVPGSQLMPSKSP STGTTEISSHESSHGTPSQTTAKNWELTA SASHQPPGVYPQGHSDTTVAISTSTVLLC GLSAVSLLACYLKSRQTPPLASVEMEAM EALPVTWGTSSRDEDLENCSHHLGSGAT NFSLLKQAGDVEENPGPLSKGEEDNMAI IKEFMRFKVHMEGSVNGHEFEIEGEGEG RPYEGTQTAKLKVTKGGPLPFAWDILSP QFMYGSKAYVKHPADIPDYLKLSFPEGF KWERVMNFEDGGVVTVTQDSSLQDGEF IYKVKLRGTNFPSDGPVMQKKTMGWEA SSERMYPEDGALKGEIKQRLKLKDGGH YDAEVKTTYKAKKPVQLPGAYNVNIKL DITSHNEDYTIVEQYERAEGRHSTGGMD ELYK*

Table 13c: IL15/IL15Ra constructs

Construct Sequence Promoter Amino acid sequences Amino Nucleic Acid Description Description Acid SEQ ID NO/ SEQ ID Sequence NO

OT-IL15- Full EFla MDWTWILFLVAAATRVHSN 1114, 1120 122 (IgE construct WVNVISDLKKIEDLIQSMHID 1126 leader - ATLYTESDVHPSCKVTAMKC 1140 IL15 - FLLELQVISLESGDASIHDTVE linker (GS) NLIILANNSLSSNGNVTESGC - hDHFR KECEELEEKNIKEFLQSFVHIV (Amino acid QMFINTSGSVGSLNCIVAVSQ 2-187 of NMGIGKNGDLPWPPLRNEFR WT, Y1221) YFQRMTTTSSVEGKQNLVIM - stop - GKKTWFSIPEKNRPLKGRINL spacer - VLSRELKEPPQGAHFLSRSLD IRES- DALKLTEQPELANKVDMVWI spacer - VGGSSVIKEAMNHPGHLKLF mCherry - VTRIMQDFESDTFFPEIDLEKY stop) KLLPEYPGVLSDVQEEKGIKY KFEVYEKND*SR*YDSLEIPPL SLPPP*RYWPKPLGIRPVCVC LYVIFHHIAVFWQCEGPETWP CLLDEHS*GSFPSRQRNARSV ECREGSSSSGSFLKTNNVCSD PLQAAEPPTWRQVPLRPKAT CIRYTCKGGTTPVPRCELDSC GKSQMALLKRIQQGAEGCPE GTPLYGI*SGASVHMLYMCL VEVKKTSRPPEPRGRGFPLKN TMIIWPQP**ARARRITWPSSR SSCASRCTWRAP*TATSSRSR ARARAAPTRAPRPPS*R*PRV APCPSPGTSCPLSSCTAPRPT* STPPTSPTT*SCPSPRASSGSA* *TSRTAAW*P*PRTPPCRTASS STR*SCAAPTSPPTAP*CRRRP WAGRPPPSGCTPRTAP*RARS SRG*S*RTAATTTLRSRPPTRP RSPCSCPAPTTSTSSWTSPPTT RTTPSWNSTNAPRAATPPAA WTSCTS IgE leader- - MDWTWILFLVAAATRVHSN 1115 1121 IL15 - WVNVISDLKKIEDLIQSMHID linker (GS) ATLYTESDVHPSCKVTAMKC - hDHFR FLLELQVISLESGDASIHDTVE (Amino acid NLIILANNSLSSNGNVTESGC 2-187 of KECEELEEKNIKEFLQSFVHIV WT, Y1221) QMFINTSGSVGSLNCIVAVSQ - stop NMGIGKNGDLPWPPLRNEFR YFQRMTTTSSVEGKQNLVIM GKKTWFSIPEKNRPLKGRINL VLSRELKEPPQGAHFLSRSLD DALKLTEQPELANKVDMVWI VGGSSVIKEAMNHPGHLKLF VTRIMQDFESDTFFPEIDLEKY KLLPEYPGVLSDVQEEKGIKY KFEVYEKND* mCherry- - MSKGEEDNMAIIKEFMRFKV 1116 1122 stop HMEGSVNGHEFEIEGEGEGRP YEGTQTAKLKVTKGGPLPFA WDILSPQFMYGSKAYVKHPA DIPDYLKLSFPEGFKWERVM

NFEDGGVVTVTQDSSLQDGE FIYKVKLRGTNFPSDGPVMQ KKTMGWEASSERMYPEDGA LKGEIKQRLKLKDGGHYDAE VKTTYKAKKPVQLPGAYNV NIKLDITSHNEDYTIVEQYER AEGRHSTGGMDELYK* OT-IL15- Full EFla MDWTWILFLVAAATRVHSN 1117, 1123 123 and OT- construct WVNVISDLKKIEDLIQSMHID 1141 IL15- ATLYTESDVHPSCKVTAMKC 1149 127(IgE FLLELQVISLESGDASIHDTVE leader - NLIILANNSLSSNGNVTESGC IL15 - KECEELEEKNIKEFLQSFVHIV BamHI (GS) QMFINTSGS*NLDNTTH*RSR - stop - PSPSPPPNVTGRSRLE*GRCAF spacer - VYMLFSTILPSFGNVRARKPG IRES- PVFLTSIPRGLSPLAKGMQGL spacer - LNVVKEAVPLEAS*RQTTSVA mCherry - TLCRQRNPPPGDRCLCGQKP stop) RV*DTPAKAAQPQCHVVSWI VVERVKWLSSSVFNKGLKDA QKVPHCMGSDLGPRCTCFTC V*SRLKKRLGPPNHGDVVFL* KTR**YGHNHDEQGRGG*HG HHQGVHALQGAHGGLRERP RVRDRGRGRGPPLRGHPDRQ AEGDQGWPPALRLGHPVPSV HVRLQGLREAPRRHPRLLEA VLPRGLQVGARDELRGRRRG DRDPGLLPAGRRVHLQGEAA RHQLPLRRPRNAEEDHGLGG LLRADVPRGRRPEGRDQAEA EAEGRRPLRR*GQDHLQGQE ARAAARRLQRQHQVGHHLP QRGLHHRGTVRTRRGPPLHR RHGRAVQV IgE leader- - MDWTWILFLVAAATRVHSN 1118 1124 IL15 - WVNVISDLKKIEDLIQSMHID BamHI (GS) ATLYTESDVHPSCKVTAMKC - stop FLLELQVISLESGDASIHDTVE NLIILANNSLSSNGNVTESGC KECEELEEKNIKEFLQSFVHIV QMFINTSGS* mCherry- - MSKGEEDNMAIIKEFMRFKV 1119 1125 stop HMEGSVNGHEFEIEGEGEGRP YEGTQTAKLKVTKGGPLPFA WDILSPQFMYGSKAYVKHPA DIPDYLKLSFPEGFKWERVM NFEDGGVVTVTQDSSLQDGE FIYKVKLRGTNFPSDGPVMQ KKTMGWEASSERMYPEDGA LKGEIKQRLKLKDGGHYDAE VKTTYKAKKPVQLPGAYNV NIKLDITSHNEDYTIVEQYER AEGRHSTGGMDELYK*

[00255] In one embodiment, the payload of the present invention may comprise IL18. IL18 is a proinflammatory and immune regulatory cytokine that promotes IFN-y production by T and NK cells. IL18 belongs to the IL1 family. Secreted IL18 binds to a heterodimer receptor complex, consisting of IL18Ra and f-chains and initiates signal transduction. IL18 acts in concert with other cytokines to modulate immune system functions, including induction of IFN-y production, Th Responses, and NK cell activation in response to pathogen products. IL18 showed anti cancer effects in several tumors. Administration of recombinant IL18 protein or IL18 transgene induces melanoma or sarcoma regression through the activation of CD4' T and/or NK cell mediated responses (reviewed by Srivastava et al., Curr. Med. Chem., 2010, 17: 3353-3357). The combination of IL18 with other cytokines, such as IL12 or co-stimulatory molecules (e.g., CD80) increases IL18 anti-tumor effects. For example, IL18 and IL12A/B or CD80 genes have been integrated successfully in the genome of oncolytic viruses, with the aim to trigger synergistically T cell-mediated anti-tumor immune responses (Choi et al., Gene Ther., 2011, 18: 898-909). IL2/IL18 fusion proteins also display enhanced anti-tumor properties relative to either cytokine alone and low toxicity in preclinical models (Acres et al., Cancer Res., 2005, 65:9536 9546).

[00256] IL18 alone, or in combination of IL12 and IL15, activates NK cells. Preclinical studies have demonstrated that adoptively transferred IL12, IL15 and IL18 pre-activated NK cells display enhanced effector function against established tumors in vivo (Ni et al., JExp Med. 2012, 209: 2351-2365; and Romee et al., Blood. 2012,120:4751-4760). Human IL12/IL15/IL18 activated NK cells also display memory-like features and secrete more IFN-y in response to cytokines (e.g., low concentration of IL2). In one embodiment, the effector module of the present invention may be a DD-IL18 fusion polypeptide.

[00257] In one embodiment, the payload of the present invention may comprise IL21. IL21 is another pleiotropic type I cytokine that is produced mainly by T cells and natural killer T (NKT) cells. IL21 has diverse effects on a variety of cell types including but not limited to CD4' and CD8' T cells, B cells, macrophages, monocytes, and dendritic cells (DCs). The functional receptor for IL21 is composed of IL21 receptor (IL21R) and the common cytokine receptor gamma chain, which is also a subunit of the receptors for IL2, IL4, IL7, IL9 and IL15. Studies provide compelling evidence that IL21 is a promising immunotherapeutic agent for cancer immunotherapy. IL21 promotes maturation, enhances cytotoxicity, and induces production of IFN-y and perforin by NK cells. These effector functions inhibit the growth of B16 melanoma

(Kasaian et al., Immunity. 2002, 16(4):559-569; and Brady et al., JImmunol.2004, 172(4):2048 2058). IL21 together with IL15 expands antigen-specific CD8m T-cell numbers and their effector function, resulting in tumor regression (Zeng et al., JExp Med.2005, 201(1):139-148). IL21 may also be used to rejuvenate multiple immune effector cells in the tumor microenvironment. IL21 may also directly induce apoptosis in certain types of lymphoma such as diffuse large B-cell lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia cells, via activation of STAT3 or STAT1 signal pathway. IL21, alone or in combination with anti-CD20 mAb (rituximab) can activate NK cell-dependent cytotoxic effects. Interestingly, discovery of the immunosuppressive actions of IL21 suggests that this cytokine is a "double-edged sword"- IL21 stimulation may lead to either the induction or suppression of immune responses. Both stimulatory and suppressive effects of IL21 must be considered when using IL21-related immunotherapeutic agents. The level of IL21 needs to be tightly controlled by regulatory elements. In one aspect, the effector module of the present invention may be a DD-IL21 fusion polypeptide.

[00258] In some embodiments, payloads of the present invention may comprise type I interferons. Type I interferons (IFNs-I) are soluble proteins important for fighting viral infection in humans. IFNs-I include IFN-alpha subtypes (IFN- al, IFN- alb, IFN- alc), IFN-beta, IFN delta subtypes (IFN-delta 1, IFN-delta 2, IFN-delta 8), IFN-gamma, IFN-kappa, and IFN epsilon, IFN-lambda, IFN-omega, IFN-tau and IFN-zeta. IFN-a and IFN-j are the main IFN-I subtypes in immune responses. All subtypes of IFN-I signal through a unique heterodimeric receptor, interferon alpha receptor (IFNAR), composed of 2 subunits, IFNAR1 and IFNAR2. IFNR activation regulates the host response to viral infections and in adaptive immunity. Several signaling cascades can be activated by IFNR, including the Janus activated kinase-signal transducer and activation of transcription (JAK-STAT) pathway, the mitogen activated protein kinase (MAPK) pathway, the phosphoinositide 3-kinase (P13K) pathway, the v-crk sarcoma virus CT10 oncogene homolog (avian)-like (CRKL) pathway, and NF-KB cascade. It has long been established that type I IFNs directly inhibit the proliferation of tumor cells and virus infected cells, and increase MHC class I expression, enhancing antigen recognition. IFNs-I have also proven to be involved in immune system regulation. IFNs can either directly, through interferon receptor (IFNR), or indirectly by the induction of chemokines and cytokines, regulate the immune system. Type I IFNs enhance NK cell functions and promote survival of NK cells. Type I IFNs also affect monocytes, supporting the differentiation of monocytes into DC with high capacity for antigen presentation, and stimulate macrophage function and differentiation. Several studies also demonstrate that IFNs-I promote CD8' T cell survival and functions. In some instances, it may be desirable to tune the expression of Type I IFNs using biocircuits of the present invention to avoid immunosuppression caused by long-term treatment with IFNs.

[00259] New anticancer immunotherapies are being developed that use recombinant type I IFN proteins, type I IFN transgene, type I IFN-encoding vectors and type I IFN-expressing cells. For example, IFN-a has received approval for treatment of several neoplastic diseases, such as melanoma, RCC and multiple myeloma. Though type I IFNs are powerful tools to directly and indirectly modulate the functions of the immune system, side effects of systemic long-term treatments and lack of sufficiently high efficacy have dampened the interest of IFN-a for clinical use in oncology. It is believed that if IFN levels are tightly regulated at the malignant tissues, type I IFNs are likely more efficacious. Approaches for intermittent delivery are proposed according to the observation that intermittency at an optimized pace may help to avoid signaling desensitizing mechanisms (negative feedback mechanisms) induced by IFNs-I (i.e., because of SOCS1 induction) in the responding immune cells. In accordance with the present invention, the effector module may comprise a DD-IFN fusion polypeptide. The DD and its ligand control the expression of IFN to induce an antiviral and antitumor immune responses and in the meantime, to minimize the side effects caused by long-term exposure of IFN.

[00260] In some embodiments, payloads of the present invention may comprise members of tumor necrosis factor (TNF) superfamily. The term "TNF superfamily" as used herein refers to a group of cytokines that can induce apoptosis. Members of TNF family include TNF-alpha, TNF beta (also known as lymphotoxin-alpha (LT-a)), lymphotoxin-beta (LT-), CD40L(CD154), CD27L (CD70), CD30L(CD153), FASL(CD178),4-1BBL (CD137L), OX40L, TRAIL (TNF related apoptosis inducing ligand), APRIL (a proliferation-inducing ligand), TWEAK, TRANCE, TALL-1, GITRL, LIGHT and TNFSF1 to TNFSF20 (TNF ligand superfamily member 1 to 20). In one embodiment, the payload of the invention may be TNF-alpha. TNF alpha can cause cytolysis of tumor cells, and induce cell proliferation differentiation as well. In one aspect, the effector module of the present invention may comprise a DD-TNF alpha fusion polypeptide.

[00261] In some embodiments, payloads of the present invention may comprise inhibitory molecules that block inhibitory cytokines. The inhibitors may be blocking antibodies specific to an inhibitory cytokine, and antagonists against an inhibitory cytokine, or the like.

[00262] In some aspects, payloads of the present invention may comprise an inhibitor of a secondary cytokine IL35. IL35 belongs to the interleukin-12 (IL12) cytokine family, and is a heterodimer composed of the IL27 Pchain Ebi3 and the IL12 a chain p35. Secretion of bioactive IL35 has been described only in forkhead box protein 3 (Foxp3)* regulatory T cells (Tregs) (resting and activated Tregs). Unlike other membranes in the family, IL35 appears to function solely in an anti-inflammatory fashion by inhibiting effector T cell proliferation and perhaps other parameters (Collison et al., Nature, 2007, 450(7169): 566-569).

[00263] In some embodiments, payloads of the present invention may comprise inhibitors that block the transforming growth factor beta (TGF-) subtypes (TGF-1, TGF-2 and TGF-3). TGF-P is secreted by many cell types, including macrophages and is often complexed with two proteins LTBP and LAP. Serum proteinases such as plasmin catalyze the release of active TGF from the complex from the activated macrophages. It has been shown that an increase in expression of TGF-j correlates with the malignancy of many cancers. The immunosuppressive activity of TGF-P in the tumor microenvironment contributes to oncogenesis.

[00264] In some embodiments, payloads of the present invention may comprise inhibitors of IDO enzyme.

[00265] In some embodiments, payloads of the present invention may comprise chemokines and chemokine receptors. Chemokines are a family of secreted small cytokines, or signaling proteins that can induce directed chemotaxis in nearby responsive cells. The chemokine may be a SCY (small cytokine) selected from the group consisting of SCYAl-28 (CCL1-28), SCYB1-16 (CXCL1-16), SCYCl-2 (XCL1-2), SCYD-1 and SCYE-1; or a C chemokine selected from XCL1 and XCL2; or a CC chemokine selected from CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7,CCL8,CCL9,CCL1O,CCL11,CCL12,CCL13,CCL14,CCL15,CCL16,CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27 and CCL28; or a CXC chemokine selected from CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16 and CXCL17; or a CX3C chemokine CX3CL1. In some aspects, the chemokine receptor may be a receptor for the C chemokines including XCR1; or a receptor for the CC chemokines including CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9 and CCR1; or a receptor for the CXC chemokines including CXCR1, CXCR2, CXCR3, CXCR4 and CXCR5; or a CX3C chemokine receptor CX3CR1.

[00266] In some embodiments, payloads of the present invention may comprise other immunomodulators that play a critical role in immunotherapy, such as GM-CSF (Granulocyte macrophage colony stimulating factor), erythropoietin (EPO), MIP3a, monocyte chemotactic protein (MCP)-1, intracellular adhesion molecule (ICAM), macrophage colony stimulating factor (M-CSF), Interleukin-1 receptor activating kinase (iRAK-1), lactotransferrin, and granulocyte colony stimulating factor (G-CSF).

[00267] In some embodiments, the payload of the present invention may comprise Amphiregulin. Amphiregulin (AREG) is an EGF-like growth factor which binds to the EGFR receptor and enhances CD4+ regulatory T cells (Tregs) function. AREG promotes immune suppression in the tumor environment. Thus, in some embodiment, the payloads of the present invention may comprise Anhiregulin to dampen immune response during immunotherapy.

[00268] In some embodiments, payloads of the present invention may comprise fusion proteins wherein a cytokine, chemokine and/or other soluble factor may be fused to other biological molecules such as antibodies and or ligands for a receptor. Such fusion molecules may increase the half-life of the cytokines, reduce systemic toxicity, and increase local concentration of the cytokines at the tumor site. Fusion proteins containing two or more cytokines, chemokines and or other soluble factors may be utilized to obtain synergistic therapeutic benefits. In one embodiment, payload may be a GM-CSF/IL2 fusion protein. 3. Additional effector module features

[00269] The effector module of the present invention may further comprise a signal sequence which regulates the distribution of the payload of interest, a cleavage and/or processing feature which facilitate cleavage of the payload from the effector module construct, a targeting and/or penetrating signal which can regulate the cellular localization of the effector module, a tag, and/or one or more linker sequences which link different components of the effector module. Signalsequences

[00270] In addition to the SRE (e.g., DD) and payload region, effector modules of the invention may further comprise one or more signal sequences. Signal sequences (sometimes referred to as signal peptides, targeting signals, target peptides, localization sequences, transit peptides, leader sequences or leader peptides) direct proteins (e.g., the effector module of the present invention) to their designated cellular and/or extracellular locations. Protein signal sequences play a central role in the targeting and translocation of nearly all secreted proteins and many integral membrane proteins.

[00271] A signal sequence is a short (5-30 amino acids long) peptide present at the N-terminus of the majority of newly synthesized proteins that are destined towards a particular location. Signal sequences can be recognized by signal recognition particles (SRPs) and cleaved using type I and type II signal peptide peptidases. Signal sequences derived from human proteins can be incorporated as a regulatory module of the effector module to direct the effector module to a particular cellular and/or extracellular location. These signal sequences are experimentally verified and can be cleaved (Zhang et al., Protein Sci. 2004, 13:2819-2824).

[00272] In some embodiments, a signal sequence may be, although not necessarily, located at the N-terminus or C-terminus of the effector module, and may be, although not necessarily, cleaved off the desired effector module to yield a "mature" payload, i.e., an immunotherapeutic agent as discussed herein.

[00273] In some examples, a signal sequence may be a secreted signal sequence derived from a naturally secreted protein, and its variant thereof. In some instances, the secreted signal sequences may be cytokine signal sequences such as, but not limited to, IL2 signal sequence comprising amino acid of SEQ ID NO: 783, encoded by the nucleotide of SEQ ID NO: 788-791 and/or p40 signal sequence comprising the amino acid sequence of SEQ ID NO: 719, encoded by the nucleotide of SEQ ID NO: 736-744.

[00274] In some instances, signal sequences directing the payload of interest to the surface membrane of the target cell may be used. Expression of the payload on the surface of the target cell may be useful to limit the diffusion of the payload to non-target in vivo environments, thereby potentially improving the safety profile of the payloads. Additionally, the membrane presentation of the payload may allow for physiologically and qualitative signaling as well as stabilization and recycling of the payload for a longer half-life. Membrane sequences may be the endogenous signal sequence of the N terminal component of the payload of interest. Optionally, it may be desirable to exchange this sequence for a different signal sequence. Signal sequences may be selected based on their compatibility with the secretory pathway of the cell type of interest so that the payload is presented on the surface of the T cell. In some embodiments, the signal sequence may be IgE signal sequence comprising amino acid SEQ ID NO: 801 and nucleotide sequence of SEQ ID NO: 810, 930, or 931, CD8a signal sequence (also referred to as CD8a leader) comprising amino acid SEQ ID NO: 628 and nucleotide sequence of SEQ ID NO: 671-675, or ILI5Ra signal sequence (also referred to as IL5Ra leader) comprising amino acid SEQ ID NO: 932 and nucleotide sequence of SEQ ID NO: 933.

[00275] Other examples of signal sequences include, a variant may be a modified signal sequence discussed in U.S. Pat. NOs.: 8, 148, 494; 8,258,102; 9,133,265; 9,279,007; and U.S. patent application publication NO.: 20070141666; and International patent application publication NO.: WO1993018181; the contents of each of which are incorporated herein by reference in their entirety.

[00276] In other examples, a signal sequence may be a heterogeneous signal sequence from other organisms such as virus, yeast and bacteria, which can direct an effector module to a particular cellular site, such as a nucleus (e.g., EP 1209450). Other examples may include Aspartic Protease (NSP24) signal sequences from Trichoderma that can increase secretion of fused protein such as enzymes (e.g., U. S. Pat. NO.: 8,093,016 to Cervin and Kim), bacterial lipoprotein signal sequences (e.g., PCT application publication NO.: WO199109952 to Lau and Rioux), E.coli enterotoxin II signal peptides (e.g., U.S. Pat. NO.: 6,605,697 to Kwon et al.), E.coli secretion signal sequence (e.g., U.S. patent publication NO.: US2016090404 to Malley et al.), a lipase signal sequence from a methylotrophic yeast (e.g., U.S. Pat. NO.: 8,975,041), and signal peptides for DNases derived from Coryneform bacteria(e.g., U.S. Pat. NO.: 4,965,197); the contents of each of which are incorporated herein by reference in their entirety.

[00277] Signal sequences may also include nuclear localization signals (NLSs), nuclear export signals (NESs), polarized cell tubulo-vesicular structure localization signals (See, e.g., U.S. Pat. NO.: 8, 993,742; Cour et al., Nucleic Acids Res. 2003, 31(1): 393-396; the contents of each of which are incorporated herein by reference in their entirety),extracellular localization signals, signals to subcellular locations (e.g. lysosome, endoplasmic reticulum, golgi, mitochondria, plasma membrane and peroxisomes, etc.) (See, e.g., U.S. Pat. NO.: 7,396,811; and Negi et al., Database, 2015, 1-7; the contents of each of which are incorporated herein by reference in their entirety).

[00278] In some embodiments, signal sequences of the present invention, include without limitation, any of those taught in Table 6 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety. Cleavage sites

[00279] In some embodiments, the effector module comprises a cleavage and/or processing feature. The effector module of the present invention may include at least one protein cleavage signal/site. The protein cleavage signal/site may be located at the N-terminus, the C-terminus, at any space between the N- and the C- termini such as, but not limited to, half-way between the N and C-termini, between the N-terminus and the half-way point, between the half-way point and the C-terminus, and combinations thereof.

[00280] The effector module may include one or more cleavage signal(s)/site(s) of any proteinases. The proteinases may be a serine proteinase, a cysteine proteinase, an endopeptidase, a dipeptidase, a metalloproteinase, a glutamic proteinase, a threonine proteinase and an aspartic proteinase. In some aspects, the cleavage site may be a signal sequence of furin, actinidain, calpain-1, carboxypeptidase A, carboxypeptidase P, carboxypeptidase Y, caspase-1, caspase-2, caspase-3, caspase-4, caspase-5, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, cathepsin B, cathepsin C, cathepsin G, cathepsin H, cathepsin K, cathepsin L, cathepsin S, cathepsin V, clostripain, chymase, chymotrypsin, elastase, endoproteinase, enterokinase, factor Xa, formic acid, granzyme B, Matrix metallopeptidase-2, Matrix metallopeptidase-3, pepsin, proteinase K, SUMO protease, subtilisin, TEV protease, thermolysin, thrombin, trypsin and TAGZyme.

[00281] In one embodiment, the cleavage site is a furin cleavage site comprising the amino acid sequence SARNRQKRS (SEQ ID NO: 721), encoded by nucleotide sequence of SEQ ID NO: 750; or a revised furin cleavage site comprising the amino acid sequence ARNRQKRS (SEQ ID NO: 722), encoded by nucleotide sequence of SEQ ID NO: 751; or a modified furin site comprising the amino acid sequence ESRRVRRNKRSK (SEQ ID NO: 630), encoded by nucleotide sequence of SEQ ID NO: 681-683.

[00282] In some embodiments, cleavage sites of the present invention, include without limitation, any of those taught in Table 7 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication WO2017/180587, the contents of each of which are incorporated herein by reference in their entirety. Protein tags

[00283] In some embodiments, the effector module of the invention may comprise a protein tag. The protein tag may be used for detecting and monitoring the process of the effector module. The effector module may include one or more tags such as an epitope tag (e.g., a FLAG or hemagglutinin (HA) tag). A large number of protein tags may be used for the present effector modules. They include, but are not limited to, self-labeling polypeptide tags (e.g., haloalkane dehalogenase (halotag2 or halotag7), ACP tag, clip tag, MCP tag, snap tag), epitope tags (e.g., FLAG, HA, His, and Myc), fluorescent tags (e.g., green fluorescent protein (GFP), red fluorescent protein (RFP), yellow fluorescent protein (YFP), and its variants), bioluminescent tags (e.g. luciferase and its variants), affinity tags (e.g., maltose-binding protein (MBP) tag, glutathione-S-transferase (GST) tag), immunogenic affinity tags (e.g., protein A/G, IRS, AUl, AU5, glu-glu, KT3, S-tag, HSV, VSV-G, Xpress and V5), and other tags (e.g., biotin (small molecule), StrepTag (StreplI), SBP, biotin carboxyl carrier protein (BCCP), eXact, CBP, CYD, HPC, CBD intein-chitin binding domain, Trx, NorpA, and NusA.

[00284] In other embodiments, a tag may also be selected from those disclosed in U.S. Pat. NOs.: 8,999,897; 8,357,511; 7,094, 568; 5,011,912; 4,851,341; and 4,703,004; U.S patent application publication NOs.: US2013115635 and US2013012687; and International application publication NO.: W02013091661; the contents of each of which are incorporated herein by reference in their entirety.

[00285] In some aspects, a multiplicity of protein tags, either the same or different tags, may be used; each of the tags may be located at the same N- or C-terminus, whereas in other cases these tags may be located at each terminus.

[00286] In some embodiments, protein tags of the present invention, include without limitation, any of those taught in Table 8 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety. Targeting peptides

[00287] In some embodiments, the effector module of the invention may further comprise a targeting and/or penetrating peptide. Small targeting and/or penetrating peptides that selectively recognize cell surface markers (e.g. receptors, trans-membrane proteins, and extra-cellular matrix molecules) can be employed to target the effector module to the desired organs, tissues or cells. Short peptides (5-50 amino acid residues) synthesized in vitro and naturally occurring peptides, or analogs, variants, derivatives thereof, may be incorporated into the effector module for homing the effector module to the desired organs, tissues and cells, and/or subcellular locations inside the cells.

[00288] In some embodiments, a targeting sequence and/or penetrating peptide may be included in the effector module to drive the effector module to a target organ, or a tissue, or a cell (e.g., a cancer cell). In other embodiments, a targeting and/or penetrating peptide may direct the effector module to a specific subcellular location inside a cell.

[00289] A targeting peptide has any number of amino acids from about 6 to about 30 inclusive. The peptide may have 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 amino acids. Generally, a targeting peptide may have 25 or fewer amino acids, for example, 20 or fewer, for example 15 or fewer.

[00290] Exemplary targeting peptides may include, but are not limited to, those disclosed in the art, e.g., U.S. Pat. NOs.: 9,206,231; 9,110,059; 8,706,219; and 8,772,449; and U.S. application publication NOs.: 2016089447; 2016060296; 2016060314; 2016060312; 2016060311; 2016009772; 2016002613; 2015314011 and 2015166621; and International application publication NOs.: W02015179691 and W02015183044; the contents of each of which are incorporated herein by reference in their entirety.

[00291] In some embodiments, targeting peptides of the present invention, include without limitation, any of those taught in Table 9 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety. Linkers

[00292] In some embodiments, the effector module of the invention may further comprise a linker sequence. The linker region serves primarily as a spacer between two or more polypeptides within the effector module. The "linker" or "spacer", as used herein, refers to a molecule or group of molecules that connects two molecules, or two parts of a molecule such as two domains of a recombinant protein.

[00293] In some embodiments, "Linker" (L) or "linker domain" or "linker region" or "linker module" or "peptide linker" as used herein refers to an oligo- or polypeptide region of from about 1 to 100 amino acids in length, which links together any of the domains/regions of the effector module (also called peptide linker). The peptide linker may be 1-40 amino acids in length, or 2-30 amino acids in length, or 20-80 amino acids in length, or 50-100 amino acids in length. Linker length may also be optimized depending on the type of payload utilized and based on the crystal structure of the payload. In some instances, a shorter linker length may be preferably selected. In some aspects, the peptide linker is made up of amino acids linked together by peptide bonds, preferably from 1 to 20 amino acids linked by peptide bonds, wherein the amino acids are selected from the 20 naturally occurring amino acids: Glycine (G), Alanine (A), Valine (V), Leucine (L), Isoleucine (I), Serine (S), Cysteine (C), Threonine (T), Methionine (M), Proline (P), Phenylalanine (F), Tyrosine (Y), Tryptophan (W), Histidine (H), Lysine (K), Arginine (R), Aspartate (D), Glutamic acid (E), Asparagine (N), and Glutamine (Q). One or more of these amino acids may be glycosylated, as is understood by those in the art. In some aspects, amino acids of a peptide linker may be selected from Alanine (A), Glycine (G), Proline (P), Asparagine (R), Serine (S), Glutamine (Q) and Lysine (K).

[00294] In one example, an artificially designed peptide linker may preferably be composed of a polymer of flexible residues like Glycine (G) and Serine (S) so that the adjacent protein domains are free to move relative to one another. Longer linkers may be used when it is desirable to ensure that two adjacent domains do not interfere with one another. The choice of a particular linker sequence may concern if it affects biological activity, stability, folding, targeting and/or pharmacokinetic features of the fusion construct. Examples of peptide linkers include, but are not limited to: MH, SG, GGSG (SEQ ID NO: 822; encoded by the nucleotide sequence SEQ ID NO: 823), GGSGG (SEQ ID NO: 629; encoded by any of the nucleotide sequences SEQ ID NO: 676-680), GGSGGG (SEQ ID NO: 824; encoded by any of the nucleotide sequences SEQ ID NO: 825-826), SGGGS (SEQ ID NO: 827; encoded by the nucleotide sequence SEQ ID NO: 828, 844, 909), GGSGGGSGG (SEQ ID NO: 829; encoded by the nucleotide sequence SEQ ID NO: 830), GGGGG (SEQ ID NO: 831), GGGGS (SEQ ID NO: 832) or (GGGGS)n (n=1 (SEQ ID NO: 832), 2 (SEQ ID NO: 833), 3 (SEQ ID NO: 720, encoded by the nucleotide sequence SEQ ID NO: 910-915), 4 (SEQ ID NO: 834), 5 (SEQ ID NO: 835), or 6 (SEQ ID NO: 836)), SSSSG (SEQ ID NO: 837) or (SSSSG)n (n=1 (SEQ ID NO: 837), 2 (SEQ ID NO: 838), 3 (SEQ ID NO: 839), 4 (SEQ ID NO: 840), 5 (SEQ ID NO: 841), or 6 (SEQ ID NO: 842)), SGGGSGGGGSGGGGSGGGGSGGGSLQ (SEQ ID NO: 802; encoded by the nucleotide sequence SEQ ID NO: 811, 916-920, 1002), EFSTEF (SEQ ID NO: 784; encoded by any of the nucleotide sequences SEQ ID NO: 792-793), GKSSGSGSESKS (SEQ ID NO: 845), GGSTSGSGKSSEGKG (SEQ ID NO: 846), GSTSGSGKSSSEGSGSTKG (SEQ ID NO: 847), GSTSGSGKPGSGEGSTKG (SEQ ID NO: 848), VDYPYDVPDYALD (SEQ ID NO: 849; encoded by nucleotide sequence SEQ ID NO: 850), EGKSSGSGSESKEF (SEQ ID NO: 851), SGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGS (SEQ ID NO: 921; encoded by SEQ ID NO: 923 SGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 922; encoded by SEQ ID NO: 924), GS (encoded by GGTTCC), SG (encoded by AGCGGC), GSG (encoded by

GGATCCGGA or GGATCCGGT), or MLLLVTSLLLCELPHPAFLLIP (SEQ ID NO: 1031; encoded by SEQ ID NO: 1032).

[00295] In other examples, a peptide linker may be made up of a majority of amino acids that are sterically unhindered, such as Glycine (G) and Alanine (A). Exemplary linkers are polyglycines (such as (G)4 (SEQ ID NO: 1233), (G)5 (SEQ ID NO: 831), (G)8) (SEQ ID NO: 1234), poly(GA), and polyalanines. The linkers described herein are exemplary, and linkers that are much longer and which include other residues are contemplated by the present invention.

[00296] A linker sequence may be a natural linker derived from a multi-domain protein. A natural linker is a short peptide sequence that separates two different domains or motifs within a protein.

[00297] In some aspects, linkers may be flexible or rigid. In other aspects, linkers may be cleavable or non- cleavable. As used herein, the terms "cleavable linker domain or region" or "cleavable peptide linker" are used interchangeably. In some embodiments, the linker sequence may be cleaved enzymatically and/or chemically. Examples of enzymes (e.g., proteinase/peptidase) useful for cleaving the peptide linker include, but are not limited, to Arg-C proteinase, Asp-N endopeptidase, chymotrypsin, clostripain, enterokinase, Factor Xa, glutamyl endopeptidase, Granzyme B, Achromobacter proteinase I, pepsin, proline endopeptidase, proteinase K, Staphylococcal peptidase I, thermolysin, thrombin, trypsin, and members of the Caspase family of proteolytic enzymes (e.g. Caspases 1-10). Chemical sensitive cleavage sites may also be included in a linker sequence. Examples of chemical cleavage reagents include, but are not limited to, cyanogen bromide, which cleaves methionine residues; N-chloro succinimide, iodobenzoic acid or BNPS-skatole (2-(2-nitrophenylsulfenyl)-3-methylindole), which cleaves tryptophan residues; dilute acids, which cleave at aspartyl-prolyl bonds; and e aspartic acid proline acid cleavable recognition sites (i.e., a cleavable peptide linker comprising one or more D-P dipeptide moieties). The fusion module may include multiple regions encoding peptides of interest separated by one or more cleavable peptide linkers.

[00298] In other embodiments, a cleavable linker may be a "self-cleaving" linker peptide, such as 2A linkers (for example T2A), 2A-like linkers or functional equivalents thereof and combinations thereof. In some embodiments, the linkers include the picornaviral 2A-like linker, CHYSEL sequences of porcine teschovirus (P2A), Thosea asigna virus (T2A) or combinations, variants and functional equivalents thereof. Other linkers will be apparent to those skilled in the art and may be used in connection with alternate embodiments of the invention. In some embodiments, the biocircuits of the present invention may include 2A peptides. The 2A peptide is a sequence of about 20 amino acid residues from a virus that is recognized by a protease (2A peptidases) endogenous to the cell. The 2A peptide was identified among picornaviruses, a typical example of which is the Foot-and Mouth disease virus (Robertson BH, et. al., J Virol 1985, 54:651-660). 2A-like sequences have also been found in Picornaviridae like equine rhinitis A virus, as well as unrelated viruses such as porcine teschovirus-1 and the insect Thosea asigna virus (TaV). In such viruses, multiple proteins are derived from a large polyprotein encoded by an open reading frame. The 2A peptide mediates the co-translational cleavage of this polyprotein at a single site that forms the junction between the virus capsid and replication polyprotein domains. The 2A sequences contain the consensus motif D-V/I-E-X-N-P-G-P (SEQ ID NO: 1235). These sequences are thought to act co-translationally, preventing the formation of a normal peptide bond between the glycine and last proline, resulting in the ribosome skipping of the next codon (Donnelly ML et al. (2001). J Gen Virol, 82:1013-1025). After cleavage, the short peptide remains fused to the C -terminus of the protein upstream of the cleavage site, while the proline is added to the N-terminus of the protein downstream of the cleavage site. Of the 2A peptides identified to date, four have been widely used namely FMDV 2A (abbreviated herein as F2A); equine rhinitis A virus (ERAV) 2A (E2A); porcine teschovirus-1 2A (P2A) and Thoseaasignavirus 2A (T2A). In some embodiments, the 2A peptide sequences useful in the present invention are selected from SEQ ID NO.8-11 of International Patent Publication W02010042490, the contents of which are incorporated by reference in its entirety.

[00299] As a non-limiting example, the P2A cleavable peptide may be GATNFSLLKQAGDVEENPGP (SEQ ID NO: 925; encoded by SEQ ID NO: 926).

[00300] The linkers of the present invention may also be non-peptide linkers. For example, alkyl linkers such as -NH-(CH 2) a-C(O)-, wherein a=2-20 can be used. These alkyl linkers may further be substituted by any non-sterically hindering group such as lower alkyl (e.g., C-C6 )

lower acyl, halogen (e.g., Cl, Br), CN, NH 2 , phenyl, etc.

[00301] In some aspects, the linker may be an artificial linker from U.S. Pat. NOs.: 4,946,778; 5, 525, 491; 5,856,456; and International patent publication NOs.: W02012/083424; the contents of each of which are incorporated herein by reference in their entirety.

[00302] In some embodiments, linkers of the present invention, include without limitation, any of those taught in Table 11 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed

March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety.

[00303] In one embodiment, the linker may be a spacer region of one or more nucleotides. Non limiting examples of spacers are TCTAGATAATACGACTCACTAGAGATCC (SEQ ID NO: 927), TATGGCCACAACCATG (SEQ ID NO: 928), AATCTAGATAATACGACTCACTAGAGATCC (SEQ ID NO: 929), GCTTGCCACAACCCACAAGGAGACGACCTTCC (SEQ ID NO: 1000), TCGCGAATG, or TCGCGA.

[00304] In one embodiment, the linker may be a BamHI site. As a non-limiting example, the BamHI site has the amino acid sequence GS and/or the DNA sequence GGATCC. Embedded stimulus, signals and other regulatory features

[00305] In some embodiments, the effector module of the present invention may further comprise one or more microRNAs, microRNA binding sites, promotors and tunable elements. In one embodiment, microRNA may be used in support of the creation of tunable biocircuits. Each aspect or tuned modality may bring to the effector module or biocircuit a differentially tuned feature. For example, a destabilizing domain may alter cleavage sites or dimerization properties or half-life of the payload, and the inclusion of one or more microRNA or microRNA binding site may impart cellular detargeting or trafficking features. Consequently, the present invention embraces biocircuits which are multifactorial in their tenability. Such biocircuits and effector modules may be engineered to contain one, two, three, four or more tuned features.

[00306] In some embodiments, micro RNA sequences of the present invention, include without limitation, any of those taught in Table 13 of copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication WO2017/180587, the contents of each of which are incorporated herein by reference in their entirety.

[00307] In some embodiments, compositions of the invention may include optional proteasome adaptors. As used herein, the term "proteasome adaptor" refers to any nucleotide/ amino acid sequence that targets the appended payload for degradation. In some aspects, the adaptors target the payload for degradation directly thereby circumventing the need for ubiquitination reactions. Proteasome adaptors may be used in conjunction with destabilizing domains to reduce the basal expression of the payload. Exemplary proteasome adaptors include the UbL domain of Rad23 or hHR23b, HPV E7 which binds to both the target protein Rb and the S4 subunit of the proteasome with high affinity, which allows direct proteasome targeting, bypassing the ubiquitination machinery; the protein gankyrin which binds to Rb and the proteasome subunit S6. Polynucleotides

[00308] The term "polynucleotide" or "nucleic acid molecule" in its broadest sense, includes any compound and/or substance that comprise a polymer of nucleotides, e.g., linked nucleosides. These polymers are often referred to as polynucleotides. Exemplary nucleic acids or polynucleotides of the invention include, but are not limited to, ribonucleic acids (RNAs), deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs, including LNA having a P- D-ribo configuration, a-LNA having an a-L-ribo configuration (a diastereomer of LNA), 2'-amino-LNA having a 2'-amino functionalization, and 2'-amino- a-LNA having a 2'-amino functionalization) or hybrids thereof.

[00309] In some embodiments, polynucleotides of the invention may be a messenger RNA (mRNA) or any nucleic acid molecule and may or may not be chemically modified. In one aspect, the nucleic acid molecule is a mRNA. As used herein, the term "messenger RNA (mRNA)" refers to any polynucleotide which encodes a polypeptide of interest and which is capable of being translated to produce the encoded polypeptide of interest in vitro, in vivo, in situ or ex vivo.

[00310] Traditionally, the basic components of an mRNA molecule include at least a coding region, a 5'UTR, a 3'UTR, a 5' cap and a poly-A tail. Building on this wild type modular structure, the present invention expands the scope of functionality of traditional mRNA molecules by providing payload constructs which maintain a modular organization, but which comprise one or more structural and/or chemical modifications or alterations which impart useful properties to the polynucleotide, for example tenability of function. As used herein, a "structural" feature or modification is one in which two or more linked nucleosides are inserted, deleted, duplicated, inverted or randomized in a polynucleotide without significant chemical modification to the nucleosides themselves. Because chemical bonds will necessarily be broken and reformed to effect a structural modification, structural modifications are of a chemical nature and hence are chemical modifications. However, structural modifications will result in a different sequence of nucleotides. For example, the polynucleotide "ATCG" may be chemically modified to "AT-5meC-G". The same polynucleotide may be structurally modified from "ATCG" to

"ATCCCG". Here, the dinucleotide "CC" has been inserted, resulting in a structural modification to the polynucleotide.

[00311] In some embodiments, polynucleotides of the present invention may harbor 5'UTR sequences which play a role in translation initiation. 5'UTR sequences may include features such as Kozak sequences which are commonly known to be involved in the process by which the ribosome initiates translation of genes, Kozak sequences have the consensus XCCR(A/G) CCAUG, where R is a purine (adenine or guanine) three bases upstream of the start codon (AUG) and X is any nucleotide. In one embodiment, the Kozak sequence is ACCGCC. By engineering the features that are typically found in abundantly expressed genes of target cells or tissues, the stability and protein production of the polynucleotides of the invention can be enhanced.

[00312] Further provided are polynucleotides, which may contain an internal ribosome entry site (IRES) which play an important role in initiating protein synthesis in the absence of 5' cap structure in the polynucleotide. An IRES may act as the sole ribosome binding site, or may serve as one of the multiple binding sites. Polynucleotides of the invention containing more than one functional ribosome binding site may encode several peptides or polypeptides that are translated independently by the ribosomes giving rise to bicistronic and/or multicistronic nucleic acid molecules.

[00313] In some embodiments, polynucleotides encoding biocircuits, effector modules, SREs and payloads of interest such as immunotherapeutic agents may include from about 30 to about 100,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 1,000, from 30 to 1,500, from 30 to 3,000, from 30 to 5,000, from 30 to 7,000, from 30 to 10,000, from 30 to 25,000, from 30 to 50,000, from 30 to 70,000, from 100 to 250, from 100 to 500, from 100 to 1,000, from 100 to 1,500, from 100 to 3,000, from 100 to 5,000, from 100 to 7,000, from 100 to 10,000, from 100 to 25,000, from 100 to 50,000, from 100 to 70,000, from 100 to 100,000, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 3,000, from 500 to 5,000, from 500 to 7,000, from 500 to 10,000, from 500 to 25,000, from 500 to 50,000, from 500 to 70,000, from 500 to 100,000, from 1,000 to 1,500, from 1,000 to 2,000, from 1,000 to 3,000, from 1,000 to 5,000, from 1,000 to 7,000, from 1,000 to 10,000, from 1,000 to 25,000, from 1,000 to 50,000, from 1,000 to 70,000, from 1,000 to 100,000, from 1,500 to 3,000, from 1,500 to 5,000, from 1,500 to 7,000, from 1,500 to 10,000, from 1,500 to 25,000, from 1,500 to 50,000, from 1,500 to 70,000, from 1,500 to 100,000, from 2,000 to 3,000, from

2,000 to 5,000, from 2,000 to 7,000, from 2,000 to 10,000, from 2,000 to 25,000, from 2,000 to 50,000, from 2,000 to 70,000, and from 2,000 to 100,000 nucleotides). In some aspects, polynucleotides of the invention may include more than 10,000 nucleotides.

[00314] Regions of the polynucleotides which encode certain features such as cleavage sites, linkers, trafficking signals, tags or other features may range independently from 10-1,000 nucleotides in length (e.g., greater than 20, 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, and 900 nucleotides or at least 10, 15, 20, 25,30,35,40,45,50,55,60,70,80,90,100,120,140,160,180,200,250,300,350,400,450, 500, 600, 700, 800, 900, and 1,000 nucleotides).

[00315] In some embodiments, polynucleotides of the present invention may further comprise embedded regulatory moieties such as microRNA binding sites within the 3'UTR of nucleic acid molecules which when bind to microRNA molecules, down-regulate gene expression either by reducing nucleic acid molecule stability or by inhibiting translation. Conversely, for the purposes of the polynucleotides of the present invention, microRNA binding sites can be engineered out of (i.e. removed from) sequences in which they naturally occur in order to increase protein expression in specific tissues. For example, miR-142 and miR-146 binding sites may be removed to improve protein expression in the immune cells. In some embodiments, any of the encoded payloads may be may be regulated by an SRE and then combined with one or more regulatory sequences to generate a dual or multi-tuned effector module or biocircuit system.

[00316] In some embodiments, polynucleotides of the present invention may encode fragments, variants, derivatives of polypeptides of the inventions. In some aspects, the variant sequence may keep the same or a similar activity. Alternatively, the variant may have an altered activity (e.g., increased or decreased) relative to the start sequence. Generally, variants of a particular polynucleotide or polypeptide of the invention will have at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to that particular reference polynucleotide or polypeptide as determined by sequence alignment programs and parameters described herein and known to those skilled in the art. Such tools for alignment include those of the BLAST suite (Stephen et al., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res., 1997, 25:3389-3402.)

[00317] In some embodiments, polynucleotides of the present invention may be modified. As used herein, the terms "modified", or as appropriate, "modification" refers to chemical modification with respect to A, G, U (T in DNA) or C nucleotides. Modifications may be on the nucleoside base and/or sugar portion of the nucleosides which comprise the polynucleotide. In some embodiments, multiple modifications are included in the modified nucleic acid or in one or more individual nucleoside or nucleotide. For example, modifications to a nucleoside may include one or more modifications to the nucleobase and the sugar. Modifications to the polynucleotides of the present invention may include any of those taught in, for example, International Publication NO: WO2013052523, the contents of which are incorporated herein by reference in its entirety.

[00318] As described herein "nucleoside" is defined as a compound containing a sugar molecule (e.g., a pentose or ribose) or a derivative thereof in combination with an organic base (e.g., a purine or pyrimidine) or a derivative thereof (also referred to herein as "nucleobase"). As described herein, "nucleotide" is defined as a nucleoside including a phosphate group.

[00319] In some embodiments, the modification may be on the intemucleoside linkage (e.g., phosphate backbone). Herein, in the context of the polynucleotide backbone, the phrases "phosphate" and "phosphodiester" are used interchangeably. Backbone phosphate groups can be modified by replacing one or more of the oxygen atoms with a different substituent. Further, the modified nucleosides and nucleotides can include the wholesale replacement of an unmodified phosphate moiety with another intemucleoside linkage. Examples of modified phosphate groups include, but are not limited to, phosphorothioate, phosphoroselenates, boranophosphates, boranophosphate esters, hydrogen phosphonates, phosphoramidates, phosphorodiamidates, alkyl or aryl phosphonates, and phosphotriesters. Phosphorodithioates have both non-linking oxygens replaced by sulfur. The phosphate linker can also be modified by the replacement of a linking oxygen with nitrogen (bridged phosphoramidates), sulfur (bridged phosphorothioates), and carbon (bridged methylene-phosphonates). Other modifications which may be used are taught in, for example, International Application NO: W02013052523, the contents of which are incorporated herein by reference in their entirety.

[00320] Chemical modifications and/or substitution of the nucleotides or nucleobases of the polynucleotides of the invention which are useful in the present invention include any modified substitutes known in the art, for example, (±)1-(2-Hydroxypropyl)pseudouridine TP, (2R)-1-(2 Hydroxypropyl)pseudouridine TP, 1-(4-Methoxy-phenyl)pseudo-UTP,,2'-0-dimethyladenosine, 1,2'-O-dimethylguanosine, 1,2'-O-dimethylinosine, 1-Hexyl-pseudo-UTP, 1 Homoallylpseudouridine TP, 1-Hydroxymethylpseudouridine TP, 1-iso-propyl-pseudo-UTP, 1

Me-2-thio-pseudo-UTP, 1-Me-4-thio-pseudo-UTP, 1-Me-alpha-thio-pseudo-UTP, 1-Me-GTP, 2'-Amino-2'-deoxy-ATP, 2'-Amino-2'-deoxy-CTP, 2'-Amino-2'-deoxy-GTP, 2'-Amino-2' deoxy-UTP, 2'-Azido-2'-deoxy-ATP, tubercidine, under modified hydroxywybutosine, uridine 5-oxyacetic acid, uridine 5-oxyacetic acid methyl ester, wybutosine, wyosine, xanthine, Xanthosine-5'-TP, xylo-adenosine, zebularine, a-thio-adenosine, a-thio-cytidine, a-thio guanosine, and/or a-thio-uridine.

[00321] Polynucleotides of the present invention may comprise one or more of the modifications taught herein. Different sugar modifications, base modifications, nucleotide modifications, and/or internucleoside linkages (e.g., backbone structures) may exist at various positions in the polynucleotide of the invention. One of ordinary skill in the art will appreciate that the nucleotide analogs or other modification(s) may be located at any position(s) of a polynucleotide such that the function of the polynucleotide is not substantially decreased. A modification may also be a 5'or3'terminal modification. The polynucleotide may contain from about 1% to about 100% modified nucleotides (either in relation to overall nucleotide content, or in relation to one or more types of nucleotide, i.e. any one or more of A, G, U or C) or any intervening percentage (e.g., from 1% to 20%, from 1% to 25%, from 1% to 50%, from 1% to 6 0% , from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to 95%, from 10% to 2 0 %, 2 5 %, to from 10% to from 10% to 50%, from 10% to 60%, from 10% to 70%, from 10% 8 0 %, from 10% to 90%, from 10% to 95%, from 10% to 100%, from 20% to 25%, from 20% to 500%, from 20% to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20% to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from 50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%, from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to 100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90% to 9 5 %, from 90% to 100%, and from 95% to 100%).

[00322] In some embodiments, one or more codons of the polynucleotides of the present invention may be replaced with other codons encoding the native amino acid sequence to tune the expression of the SREs, through a process referred to as codon selection. Since mRNA codon, and tRNA anticodon pools tend to vary among organisms, cell types, sub cellular locations and over time, the codon selection described herein is a spatiotemporal (ST) codon selection.

[00323] In some embodiments of the invention, certain polynucleotide features may be codon optimized. Codon optimization refers to a process of modifying a nucleic acid sequence for enhanced expression in the host cell by replacing at least 1, 2, 3, 4, 5, 10, 15, 20, 25, 50 or more codons of the native sequence with codons that are most frequently used in the genes of that host cell while maintaining the native amino acid sequence. Codon usage may be measured using the Codon Adaptation Index (CAI) which measures the deviation of a coding polynucleotide sequence from a reference gene set. Codon usage tables are available at the Codon Usage Database (http://www.kazusa.or.jp/codon/) and the CAI can be calculated by EMBOSS CAI program (http://emboss.sourceforge.net/). Codon optimization methods are known in the art and may be useful in efforts to achieve one or more of several goals. These goals include to match codon frequencies in target and host organisms to ensure proper folding, bias nucleotide content to alter stability or reduce secondary structures, minimize tandem repeat codons or base runs that may impair gene construction or expression, customize transcriptional and translational control regions, insert or remove protein signaling sequences, remove/add post translation modification sites in encoded protein (e.g. glycosylation sites), add, remove or shuffle protein domains, insert or delete restriction sites, modify ribosome binding sites and degradation sites, to adjust translational rates to allow the various domains of the protein to fold properly, or to reduce or eliminate problem secondary structures within the polynucleotide. Codon optimization tools, algorithms and services are known in the art, and non-limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA), OptimumGene (GenScript, Piscataway, NJ), algorithms such as but not limited to, DNAWorks v3.2.3 and/or proprietary methods. In one embodiment, a polynucleotide sequence or portion thereof is codon optimized using optimization algorithms. Codon options for each amino acid are well-known in the art as are various species table for optimizing for expression in that particular species.

[00324] In some embodiments of the invention, certain polynucleotide features may be codon optimized. For example, a preferred region for codon optimization may be upstream (5') or downstream (3') to a region which encodes a polypeptide. These regions may be incorporated into the polynucleotide before and/or after codon optimization of the payload encoding region or open reading frame (ORF).

[00325] After optimization (if desired), the polynucleotide components are reconstituted and transformed into a vector such as, but not limited to, plasmids, viruses, cosmids, and artificial chromosomes.

[00326] Spatiotemporal codon selection may impact the expression of the polynucleotides of the invention, since codon composition determines the rate of translation of the mRNA species and its stability. For example, tRNA anticodons to optimized codons are abundant, and thus translation may be enhanced. In contrast, tRNA anticodons to less common codons are fewer and thus translation may proceed at a slower rate. Presnyak et al. have shown that the stability of an mRNA species is dependent on the codon content, and higher stability and thus higher protein expression may be achieved by utilizing optimized codons (Presnyak et al. (2015) Cell 160, 1111-1124; the contents of which are incorporated herein by reference in their entirety). Thus, in some embodiments, ST codon selection may include the selection of optimized codons to enhance the expression of the SRES, effector modules and biocircuits of the invention. In other embodiments, spatiotemporal codon selection may involve the selection of codons that are less commonly used in the genes of the host cell to decrease the expression of the compositions of the invention. The ratio of optimized codons to codons less commonly used in the genes of the host cell may also be varied to tune expression.

[00327] In some embodiments, certain regions of the polynucleotide may be preferred for codon selection. For example, a preferred region for codon selection may be upstream (5') or downstream (3') to a region which encodes a polypeptide. These regions may be incorporated into the polynucleotide before and/or after codon selection of the payload encoding region or open reading frame (ORF).

[00328] The stop codon of the polynucleotides of the present invention may be modified to include sequences and motifs to alter the expression levels of the SREs, payloads and effector modules of the present invention. Such sequences may be incorporated to induce stop codon readthrough, wherein the stop codon may specify amino acids e.g. selenocysteine or pyrrolysine. In other instances, stop codons may be skipped altogether to resume translation through an alternate open reading frame. Stop codon read through may be utilized to tune the expression of components of the effector modules at a specific ratio (e.g.as dictated by the stop codon context). Examples of preferred stop codon motifs include UGAN, UAAN, and UAGN, where N is either C or U. Polynucleotide modifications and manipulations can be accomplished by methods known in the art such as, but not limited to, site directed mutagenesis and recombinant technology. The resulting modified molecules may then be tested for activity using in vitro or in vivo assays such as those described herein or any other suitable screening assay known in the art.

[00329] In some embodiments, polynucleotides of the invention may comprise two or more effector module sequences, or two or more payloads of interest sequences, which are in a pattern such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than three times. In these patterns, each letter, A, B, or C represent a different effector module component.

[00330] In yet another embodiment, polynucleotides of the invention may comprise two or more effector module component sequences with each component having one or more SRE sequences (DD sequences), or two or more payload sequences. As a non-limiting example, the sequences may be in a pattern such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than three times in each of the regions. As another non-limiting example, the sequences may be in a pattern such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than three times across the entire polynucleotide. In these patterns, each letter, A, B, or C represent a different sequence or component.

[00331] According to the present invention, polynucleotides encoding distinct biocircuits, effector modules, SREs and payload constructs may be linked together through the3'-end using nucleotides which are modified at the 3'-terminus. Chemical conjugation may be used to control the stoichiometry of delivery into cells. Polynucleotides can be designed to be conjugated to other polynucleotides, dyes, intercalating agents (e.g. acridines), cross-linkers (e.g. psoralene, mitomycin C), porphyrins (TPPC4, texaphyrin, sapphyrin), polycyclic aromatic hydrocarbons (e.g., phenazine, dihydrophenazine), artificial endonucleases (e.g. EDTA), alkylating agents, phosphate, amino, mercapto, PEG (e.g., PEG-40K), MPEG, (MPEG) 2 , polyamino, alkyl, substituted alkyl, radiolabeled markers, enzymes, haptens (e.g. biotin), transport/absorption facilitators (e.g., aspirin, vitamin E, folic acid), synthetic ribonucleases, proteins, e.g., glycoproteins, or peptides, e.g., molecules having a specific affinity for a co-ligand, or antibodies e.g., an antibody, that binds to a specified cell type such as a cancer cell, endothelial cell, or bone cell, hormones and hormone receptors, non-peptidic species, such as lipids, lectins, carbohydrates, vitamins, cofactors, or a drug. As non-limiting examples, they may be conjugates with other immune conjugates.

[00332] In some embodiments, the compositions of the polynucleotides of the invention may generated by combining the various components of the effector modules using the Gibson assembly method. The Gibson assembly reaction consists of three isothermal reactions, each relying on a different enzymatic activity including a 5'exonuclease which generates long overhangs, a polymerase which fills in the gaps of the annealed single strand regions and a DNA ligase which seals the nicks of the annealed and filled-in gaps. Polymerase chain reactions are performed prior to Gibson assembly which may be used to generate PCR products with overlapping sequence. These methods can be repeated sequentially, to assemble larger and larger molecules. For example, the method can comprise repeating a method as above to join a second set of two or more DNA molecules of interest to one another, and then repeating the method again to join the first and second set DNA molecules of interest, and so on. At any stage during these multiple rounds of assembly, the assembled DNA can be amplified by transforming it into a suitable microorganism, or it can be amplified in vitro (e.g., with PCR).

[00333] In some embodiments, polynucleotides of the present invention may encode a fusion polypeptide comprising a destabilizing domain (DD) and at least one immunotherapeutic agent taught herein. The DD domain may be a FKBP mutant encoded by nucleotide sequence of SEQ ID NO: 684-686, 688-691, 987-989, 994, 1013, and/or 1028, an ecDHFR mutant encoded by nucleotide sequence of SEQ ID NO: 687, 692, 772, 798, 814-815, 988, 991, and/or 993, hDHFR mutant encoded by nucleotide sequence of SEQ ID NO: 693-700, 773, 852-857 and/or 934-980, and/or 995-998.

[00334] In some embodiments, the polynucleotides of the invention may encode effector modules comprising the CD19 CAR as the payload comprising the nucleotide sequence of SEQ ID NO: 701-715 and/or 1019-1042, or IL12 as the payload comprising the nucleotide sequence of SEQ ID NO. 774-782, or IL15 as the payload comprising the nucleotide sequence of SEQ ID NO: 749, 799-800, and/or 1055-1056, or IL15/ILI5Ra fusion polypeptide as the payload comprising the nucleotide sequence of SEQ ID NO: 816-821, 1086-1089, 1091-1095, 1098 1111, 1120, and/or 1123. Cells

[00335] In accordance with the present invention, cells genetically modified to express at least one biocircuit, SRE (e. g, DD), effector module and immunotherapeutic agent of the invention, are provided. Cells of the invention may include, without limitation, immune cells, stem cells and tumor cells. In some embodiments, immune cells are immune effector cells, including, but not limiting to, T cells such as CD8' T cells and CD4' T cells (e.g., Thl, Th2, Thl7, Foxp3+ cells), memory T cells such as T memory stem cells, central T memory cells, and effector memory T cells, terminally differentiated effector T cells, natural killer (NK) cells, NK T cells, tumor infiltrating lymphocytes (TILs), cytotoxic T lymphocytes (CTLs), regulatory T cells (Tregs), and dendritic cells (DCs), other immune cells that can elicit an effector function, or the mixture thereof. T cells may be Ta cells and Ty6 cells. In some embodiments, stem cells may be from human embryonic stem cells, mesenchymal stem cells, and neural stem cells. In some embodiments, T cells may be depleted endogenous T cell receptors (See US Pat. NOs.: 9, 273, 283; 9, 181, 527; and 9,028, 812; the contents of each of which are incorporated herein by reference in their entirety).

[00336] In some embodiments, cells of the invention may be autologous, allogeneic, syngeneic, or xenogeneic in relation to a particular individual subject.

[00337] In some embodiments, cells of the invention may be mammalian cells, particularly human cells. Cells of the invention may be primary cells or immortalized cell lines.

[00338] In some embodiments, cells of the invention may include expansion factors as payload to trigger proliferation and expansion of the cells. Exemplary payloads include RAS such as KRAS, NRAS, RRAS, RRAS2, MRAS, ERAS, and HRAS, DIRAS such as DIRAS1, DIRAS2, and DIRAS3, NKIRAS such as NKIRAS1, and NKIRAS2, RAL such as RALA, and RALB, RAP such as RAPlA, RAPIB, RAP2A, RAP2B, and RAP2C, RASD such as RASD1, and RASD2, RASL such as RASL1OA, RASLIOB, RASLI1A, RASL11B, and RASL12, REM such as REMI, and REM2, GEM, RERG, RERGL, and RRAD.

[00339] Engineered immune cells can be accomplished by transducing a cell compositions with a polypeptide of a biocircuit, an effector module, a SRE and/or a payload of interest (i.e., immunotherapeutic agent), or a polynucleotide encoding said polypeptide, or a vector comprising said polynucleotide. The vector may be a viral vector such as a lentiviral vector, a gamma-retroviral vector, a recombinant AAV, an adenoviral vector and an oncolytic viral vector. In other aspects, non-viral vectors for example, nanoparticles and liposomes may also be used. In some embodiments, immune cells of the invention are genetically modified to express at least one immunotherapeutic agent of the invention which is tunable using a stimulus. In some examples, two, three or more immunotherapeutic agents constructed in the same biocircuit and effector module are introduced into a cell. In other examples, two, three, or more biocircuits, effector modules, each of which comprises an immunotherapeutic agent, may be introduced into a cell.

[00340] In some embodiments, immune cells of the invention may be T cells modified to express an antigen-specific T cell receptor (TCR), or an antigen specific chimeric antigen receptor (CAR) taught herein (known as CAR T cells). Accordingly, at least one polynucleotide encoding a CAR system (or a TCR) described herein, or a vector comprising the polynucleotide is introduced into a T cell. The T cell expressing the CAR or TCR binds to a specific antigen via the extracellular targeting moiety of the CAR or TCR, thereby a signal via the intracellular signaling domain (s) is transmitted into the T cell, and as a result, the T cell is activated. The activated CAR T cell changes its behavior including release of a cytotoxic cytokine (e.g., a tumor necrosis factor, and lymphotoxin, etc.), improvement of a cell proliferation rate, change in a cell surface molecule, or the like. Such changes cause destruction of a target cell expressing the antigen recognized by the CAR or TCR. In addition, release of a cytokine or change in a cell surface molecule stimulates other immune cells, for example, a B cell, a dendritic cell, a NK cell, and a macrophage.

[00341] The CAR introduced into a T cell maybe a first-generation CAR including only the intracellular signaling domain from TCR CD3zeta, or a second-generation CAR including the intracellular signaling domain from TCR CD3zeta and a costimulatory signaling domain, or a third-generation CAR including the intracellular signaling domain from TCR CD3zeta and two or more costimulatory signaling domains, or a split CAR system, or an on/off switch CAR system. In one example, the expression of the CAR or TCR is controlled by a destabilizing domain (DD) such as a hDHFR mutant, in the effector module of the invention. The presence or absence of hDHFR binding ligand such as TMP is used to tune the CAR or TCR expression in transduced T cells or NK cells.

[00342] In some embodiments, CAR T cells of the invention may be further modified to express another one, two, three or more immunotherapeutic agents. The immunotherapeutic agents may be another CAR or TCR specific to a different target molecule; a cytokine such as IL2, IL12, IL15 and IL18, or a cytokine receptor such as IL15Ra; a chimeric switch receptor that converts an inhibitory signal to a stimulatory signal; a homing receptor that guides adoptively transferred cells to a target site such as the tumor tissue; an agent that optimizes the metabolism of the immune cell; or a safety switch gene (e.g., a suicide gene) that kills activated T cells when a severe event is observed after adoptive cell transfer or when the transferred immune cells are no longer needed. These molecules may be included in the same effector module or in separate effector modules.

[00343] In one embodiment, the CAR T cell (including TCR T cell) of the invention may be an "armed" CAR T cell which is transformed with an effector module comprising a CAR and an

effector module comprising a cytokine. The inducible or constitutively secrete active cytokines further armor CAR T cells to improve efficacy and persistence. In this context, such CAR T cell is also referred to as "armored CAR T cell". The "armor" molecule may be selected based on the tumor microenvironment and other elements of the innate and adaptive immune systems. In some embodiments, the molecule may be a stimulatory factor such as IL2, IL12, IL15, IL18, type I IFN, CD40L and 4-1BBL which have been shown to further enhance CAR T cell efficacy and persistence in the face of a hostile tumor microenvironment via different mechanisms (Yeku et al., Biochem Soc Trans., 2016, 44(2): 412-418).

[00344] In some aspects, the armed CAR T cell of the invention is modified to express a CD19 CAR and IL12. Such T cells, after CAR mediated activation in the tumor, release inducible IL12 which augments T-cell activation and attracts and activates innate immune cells to eliminate CD19-negative cancer cells.

[00345] In one embodiment, T cells of the invention may be modified to express an effector module comprising a CAR and an effector module comprising a suicide gene.

[00346] In one embodiment, the CAR T cell (including TCR T cell) of the invention may be transformed with effector modules comprising a cytokine and a safety switch gene (e.g., suicide gene). The suicide gene may be an inducible caspase such as caspase 9 which induces apoptosis, when activated by an extracellular stimulus of a biocircuit system. Such induced apoptosis eliminates transferred cell as required to decrease the risk of direct toxicity and uncontrolled cell proliferation.

[00347] In some embodiments, immune cells of the invention may be NK cells modified to express an antigen-specific T cell receptor (TCR), or an antigen specific chimeric antigen receptor (CAR) taught herein.

[00348] Natural killer (NK) cells are members of the innate lymphoid cell family and characterized in humans by expression of the phenotypic marker CD56 (neural cell adhesion molecule) in the absence of CD3 (T-cell co-receptor). NK cells are potent effector cells of the innate immune system which mediate cytotoxic attack without the requirement of prior antigen priming, forming the first line of defense against diseases including cancer malignancies and viral infection.

[00349] Several pre-clinical and clinical trials have demonstrated that adoptive transfer of NK cells is a promising treatment approach against cancers such as acute myeloid leukemia (Ruggeri et al., Science; 2002, 295: 2097-2100; and Geller et al., Immunotherapy, 2011, 3: 1445-1459). Adoptive transfer of NK cells expressing CAR such as DAP12-Based Activating CAR revealed improved eradication of tumor cells (Topfer et al., JImmunol. 2015; 194:3201-3212). NK cell engineered to express a CS-1 specific CAR also displayed enhanced cytolysis and interferon-y (IFN-) production in multiple myeloma (Chu et al., Leukemia, 2014, 28(4): 917-927).

[00350] NK cell activation is characterized by an array of receptors with activating and inhibitory functions. The important activation receptors on NK cells include CD94/NKG2C and NKG2D (the C-type lectin-like receptors), and the natural cytotoxicity receptors (NCR) NKp30, NKp44 and NKp46, which recognize ligands on tumor cells or virally infected cells. NK cell inhibition is essentially mediated by interactions of the polymorphic inhibitory killer cell immunoglobulin-like receptors (KIRs) with their cognate human-leukocyte-antigen (HLA) ligands via the alpha-i helix of the HLA molecule. The balance between signals that are generated from activating receptors and inhibitory receptors mainly determines the immediate cytotoxic activation.

[00351] NK cells may be isolated from peripheral blood mononuclear cells (PBMCs), or derived from human embryonic stem (ES) cells and induced pluripotent stem cells (iPSCs). The primary NK cells isolated from PBMCs may be further expanded for adoptive immunotherapy. Strategies and protocols useful for the expansion of NK cells may include interleukin 2 (IL2) stimulation and the use of autologous feeder cells, or the use of genetically modified allogeneic feeder cells. In some aspects, NK cells can be selectively expanded with a combination of stimulating ligands including IL15, IL21, IL2, 41BBL, IL12, IL18, MICA, 2B4, LFA-1, and BCM1/SLAMF2 (e.g., US patent publication NO: US20150190471).

[00352] Immune cells expressing effector modules comprising a CAR and/or other immunotherapeutic agents can be used as cancer immunotherapy. The immunotherapy comprises the cells expressing a CAR and/or other immunotherapeutic agents as an active ingredient, and may further comprise a suitable excipient. Examples of the excipient may include the aforementioned pharmaceutically acceptable excipients, including various cell culture media, and isotonic sodium chloride.

[00353] In some embodiments, cells of the present invention may be dendritic cells that are genetically modified to express the compositions of the invention. Such cells may be used as cancer vaccines.

Methods of CD19 antibody development and characterization

[00354] In some embodiments, the present invention provides methods of producing CD19 antibodies, antibody fragments or variants. Such methods may include the steps of: (1) preparing a composition with CD19, (2) contacting a library of antibodies or antibody fragments or variable with the composition, and (3) identifying one or more CD19 antibodies. Also, provided herein are methods for identifying FMC63-distinct CD19 antibodies, antibody fragments or variable.

[00355] In some embodiments, the present invention provides methods of identifying CD19 scFvs. Such methods may involve screening phagemid libraries for CD19 scFvs. Phagemid libraries expressing recombinant scFvs associated with the surface of bacteria or bacteriophages are useful in the present inventions. Phagemid libraries may be generated by PCR implication of the polynucleotides encoding the heavy chain and the kappa light chain of the immunoglobulin IgM and infecting Cre recombinase positive bacteria with the vectors containing the PCR products at a high multiplicity of infection (MOI). The high MOI results in bacteria containing multiple phagemids, each of which encodes a different VH and VL genes, which can be recombined by the Cre recombinase. The resulting library that may be generated by recombination is approximately 10 8 unique scFvs. In some instances, libraries of CD19 scFvs formatted into chimeric antigen receptor constructs may be screened to identify CD19scFvs useful in the present invention.

[00356] In some embodiments, scFvs immunologically specific to CD19 maybe identified using cells that ectopically express full length, a fragment or a portion of CD19. Cell lines with low endogenous CD19 expression may be selected for ectopic expression. In some embodiments, the CD19 may be a naturally occurring isoform of human CD19.

[00357] In some embodiments, fusion proteins comprising the extracellular domains of CD19 (i.e. exon 1- exon 4) fused to the Fc region of human IgGI(CD19sIg) are utilized to identify CD19 specific scFvs. Such fusion proteins have been described by Oliveira et al (2013) Journal of Translational Medicine 11:23; the contents of which are incorporated herein by reference in their entirety.

[00358] Also, provided herein are methods to identify FMC63-distinct scFvs, which include scFvs that are immunologically specific to and bind to an epitope of the CD19 antigen that is different or unlike the epitope of CD19 antigen that is bound by FMC63. In some embodiments, FMC63-distinct scFvs are identified by screening the scFv library with a complex consisting of human CD19 bound to FMC63. The CD19 of Rhesus macaque (Macacamulatta) herein referred to as Rhesus CD19, bears 88% homology to the human CD19. Despite this high degree of homology, the Rhesus CD19 is not recognized by FMC63, indicating that the FMC63 epitope is in the region of human CD19 that is non-homologous to Rhesus CD19. Thus, in some embodiments, Rhesus CD19 may be used to screen scFv libraries for FMC63-distinct scFvs. Mutations in the region of Rhesus CD19 that is non-homologous to the human CD19 have been previously utilized to identify residues of human CD19 that confer binding to FMC63 (Sommermeyer et al. (2017) Leukemia Feb 16. doi: 10.1038/leu.2017.57). In some embodiments, the mutational analysis described by Sommermeyer et al. may be utilized to design human CD19 mutants that are unable to bind to FMC63. Such mutants may include human CD19 (H218R, A237D, M243V, E244D, P250T) and human CD19 (H218R, A237D) and may be utilized to screen scFv libraries for FMC63-distinct scFvs. Sotillo et al have identified a splice variant of human CD19 lacking exon 2 in cancer patients (Sotillo et al. (2015) Cancer Discov. 2015 Dec;5(12):1282-95). The splice variant lacking exon 2 is not recognized by FMC63 and may also be used to screen scFv libraries for FMC63-distinct scFvs.

[00359] CD19 IgG fusion molecules generated by fusing the Fc region of human IgGI with the human CD19-complete extracellular domains, i.e., exons 1-4 (CD19sIgG1-4) or extracellular domains lacking exon 2, i.e., exons 1, 3 and 4 (CD19sIgG1,3,4) may also be utilized to screen scFv libraries for FMC63-distinct scFvs.

[00360] CD19 proteins, variants and mutants useful in the invention are provided in Table 14.

Table 14: CD19 proteins, variants and mutants

Description Sequence SEQ ID NO Human CD19, Isoform 1 MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLK 858 (NCBI Reference No. GTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIW NP_001171569.1) LFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARD MWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITA RPVLWHWLLRTGGWKVSAVTLAYLIFCLCSLVGILHLQR ALVLRRKRKRMTDPTRRFFKVTPPPGSGPQNQYGNVLSLP TPTSGLGRAQRWAAGLGGTAPSYGNPSSDVQADGALGSR SPPGVGPEEEEGEGYEEPDSEEDSEFYENDSNLGQDQLSQ DGSGYENPEDEPLGPEDEDSFSNAESYENEDEELTQPVAR TMDFLSPHGSAWDPSREATSLAGSQSYEDMRGILYAAPQ LRSIRGQPGPNHEEDADSYENMDNPDGPDPAWGGGGRM GTWSTR Human CD19, Isoform 2 MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLK 859 (NCBI Reference No. GTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIW NP_001761.3) LFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARD MWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITA RPVLWHWLLRTGGWKVSAVTLAYLIFCLCSLVGILHLQR ALVLRRKRKRMTDPTRRFFKVTPPPGSGPQNQYGNVLSLP

TPTSGLGRAQRWAAGLGGTAPSYGNPSSDVQADGALGSR SPPGVGPEEEEGEGYEEPDSEEDSEFYENDSNLGQDQLSQ DGSGYENPEDEPLGPEDEDSFSNAESYENEDEELTQPVAR TMDFLSPHGSAWDPSREATSLGSQSYEDMRGILYAAPQLR SIRGQPGPNHEEDADSYENMDNPDGPDPAWGGGGRMGT WSTR Rhesus CD19 MPPPCLLFFLLFLTPMEVRPQEPLVVKVEEGDNAVLQCLE 860 (Uniprot ID: F7F486) GTSDGPTQQLVWCRDSPFEPFLNLSLGLPGMGIRMGPLGI WLLIFNVSNQTGGFYLCQPGLPSEKAWQPGWTVSVEGSG ELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLNSSQLYV WAKDRPEMWEGEPVCGPPRDSLNQSLSQDLTMAPGSTL WLSCGVPPDSVSRGPLSWTHVRPKGPKSSLLSLELKDDRP DRDMWVVDTGLLLTRATAQDAGKYYCHRGNWTKSFYL EITARPALWHWLLRIGGWKVPAVTLTYLIFCLCSLVGILQ LQRALVLRRKRKRMTDPTRRFFKVTPPPGSGPQNQYGNV LSLPTPTSGLGRAQRWAAGLGGTAPSYGNPSSDVQVDGA VGSRSPPGAGPEEEEGEGYEEPDSEEGSEFYENDSNFGQD QLSQDGSGYENPEDEPLGPEDEDSFSNAESYENEDEELTQ PVARTMDFLSPHGSAWDPSREATSLGSQSYEDMRGLLYA APQLRTIRGQPGPNHEEDADSYENMDNPDGPDPAWGGGG RMGTWSAR Human CD19 (H218R, MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLK 861 A237D, M243V, E244D, GTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIW P250T) LFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS CGVPPDSVSRGPLSWTHVRPKGPKSLLSLELKDDRPDRD MWVVDTGLLLTRATAQDAGKYYCHRGNLTMSFHLEITA RPVLWHWLLRTGGWKVSAVTLAYLIFCLCSLVGILHLQR ALVLRRKRKRMTDPTRRFFKVTPPPGSGPQNQYGNVLSLP TPTSGLGRAQRWAAGLGGTAPSYGNPSSDVQADGALGSR SPPGVGPEEEEGEGYEEPDSEEDSEFYENDSNLGQDQLSQ DGSGYENPEDEPLGPEDEDSFSNAESYENEDEELTQPVAR TMDFLSPHGSAWDPSREATSLAGSQSYEDMRGILYAAPQ LRSIRGQPGPNHEEDADSYENMDNPDGPDPAWGGGGRM GTWSTR Human CD19 (H218R, MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLK 862 A237D) GTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIW LFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS CGVPPDSVSRGPLSWTHVRPKGPKSLLSLELKDDRPDRD MWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITA RPVLWHWLLRTGGWKVSAVTLAYLIFCLCSLVGILHLQR ALVLRRKRKRMTDPTRRFFKVTPPPGSGPQNQYGNVLSLP TPTSGLGRAQRWAAGLGGTAPSYGNPSSDVQADGALGSR SPPGVGPEEEEGEGYEEPDSEEDSEFYENDSNLGQDQLSQ DGSGYENPEDEPLGPEDEDSFSNAESYENEDEELTQPVAR TMDFLSPHGSAWDPSREATSLAGSQSYEDMRGILYAAPQ LRSIRGQPGPNHEEDADSYENMDNPDGPDPAWGGGGRM GTWSTR Human CD19 (Delta MPPPRLLFFLLFLTPMEVRPEEPLVVKVEGELFRWNVSDL 863 exon 2) GGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWE GEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVS RGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGL LLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLL RTGGWKVSAVTLAYLIFCLCSLVGILHLQRALVLRRKRKR

MTDPTRRFFKVTPPPGSGPQNQYGNVLSLPTPTSGLGRAQ RWAAGLGGTAPSYGNPSSDVQADGALGSRSPPGVGPEEE EGEGYEEPDSEEDSEFYENDSNLGQDQLSQDGSGYENPED EPLGPEDEDSFSNAESYENEDEELTQPVARTMDFLSPHGS AWDPSREATSLGSQSYEDMRGILYAAPQLRSIRGQPGPNH EEDADSYENMDNPDGPDPAWGGGGRMGTWSTR Human CD19 (Exon 1- MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLK 864 4) GTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIW LFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARD MWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITA RP Human CD19 (Exon MPPPRLLFFLLFLTPMEVRPEEPLVVKVEGELFRWNVSDL 865 1,3,4) GGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWE GEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVS RGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGL LLPRATAQDAGKYYCHRGNLTMSFHLEITARP

III. PHARMACEUTICAL COMPOSITIONS AND FORMULATIONS

[00361] The present invention further provides pharmaceutical compositions comprising one or more biocircuits, effector modules, SREs (e.g., DDs), stimuli and payloads of interest (i.e., immunotherapeutic agents), vectors, cells and other components of the invention, and optionally at least one pharmaceutically acceptable excipient or inert ingredient.

[00362] As used herein the term "pharmaceutical composition" refers to a preparation of biocircuits, SREs, stimuli and payloads of interest (i.e., immunotherapeutic agents), other components, vectors, cells and described herein, or pharmaceutically acceptable salts thereof, optionally with other chemical components such as physiologically suitable carriers and excipients. The pharmaceutical compositions of the invention comprise an effective amount of one or more active compositions of the invention. The preparation of a pharmaceutical composition that contains at least one composition of the present invention and/or an additional active ingredient will be known to those skilled in the art in light of the present disclosure, as exemplified by Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, incorporated herein by reference.

[00363] The term "excipient" or "inert ingredient" refers to an inactive substance added to a pharmaceutical composition and formulation to further facilitate administration of an active ingredient. For the purposes of the present disclosure, the phrase "active ingredient" generally refers to any one or more biocircuits, effector modules, SREs, stimuli and payloads of interest (i.e., immunotherapeutic agents), other components, vectors, and cells to be delivered as described herein. The phrases "pharmaceutically acceptable" refers to molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, such as, for example, a human, as appropriate.

[00364] In some embodiments, pharmaceutical compositions and formulations are administered to humans, human patients or subjects. Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to any other animal, e.g., to non-human animals, e.g. non-human mammals. Subjects to which administration of the pharmaceutical compositions is contemplated include, but are not limited to, non-human mammals, including agricultural animals such as cattle, horses, chickens and pigs, domestic animals such as cats, dogs, or research animals such as mice, rats, rabbits, dogs and non-human primates. It will be understood that, for human administration, preparations should meet sterility, pyrogenicity, general safety and purity standards as required by FDA Office of Biological Standards.

[00365] A pharmaceutical composition and formulation in accordance with the invention may be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. As used herein, a "unit dose" is discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage.

[00366] The compositions of the present invention may be formulated in any manner suitable for delivery. The formulation may be, but is not limited to, nanoparticles, poly (lactic-co glycolic acid) (PLGA) microspheres, lipidoids, lipoplex, liposome, polymers, carbohydrates (including simple sugars), cationic lipids and combinations thereof.

[00367] In one embodiment, the formulation is a nanoparticle which may comprise at least one lipid. The lipid may be selected from, but is not limited to, DLin-DMA, DLin-K-DMA, 98N12 5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG and PEGylated lipids. In another aspect, the lipid may be a cationic lipid such as, but not limited to, DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA and DODMA.

[00368] For polynucleotides of the invention, the formulation may be selected from any of those taught, for example, in International Application PCT/US2012/069610, the contents of which are incorporated herein by reference in its entirety.

[00369] Relative amounts of the active ingredient, the pharmaceutically acceptable excipient or inert ingredient, and/or any additional ingredients in a pharmaceutical composition in accordance with the invention will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1 and 100, e.g., between 0.5 and 50, between 1-30, between 5-80, at least 80 (w/w) active ingredient.

[00370] Efficacy of treatment or amelioration of disease can be assessed, for example by measuring disease progression, disease remission, symptom severity, reduction in pain, quality of life, dose of a medication required to sustain a treatment effect, level of a disease marker or any other measurable parameter appropriate for a given disease being treated or targeted for prevention. It is well within the ability of one skilled in the art to monitor efficacy of treatment or prevention by measuring any one of such parameters, or any combination of parameters. In connection with the administration of compositions of the present invention, "effective against" for example a cancer, indicates that administration in a clinically appropriate manner results in a beneficial effect for at least a statistically significant fraction of patients, such as an improvement of symptoms, a cure, a reduction in disease load, reduction in tumor mass or cell numbers, extension of life, improvement in quality of life, or other effect generally recognized as positive by medical doctors familiar with treating the particular type of cancer.

[00371] A treatment or preventive effect is evident when there is a statistically significant improvement in one or more parameters of disease status, or by a failure to worsen or to develop symptoms where they would otherwise be anticipated. As an example, a favorable change of at least 10 in a measurable parameter of disease, and preferably at least 20, 30, 40, 50 or more can be indicative of effective treatment. Efficacy for a given composition or formulation of the present invention can also be judged using an experimental animal model for the given disease as known in the art. When using an experimental animal model, efficacy of treatment is evidenced when a statistically significant change is observed. IV. APPLICATIONS

[00372] In one aspect of the present invention, methods for reducing a tumor volume or burden are provided. The methods comprise administering a pharmaceutically effective amount of a pharmaceutical composition comprising at least one biocircuit system, effector module, DD, and/or payload of interest (i.e., an immunotherapeutic agent), at least one vector, or cells to a subject having a tumor. The biocircuit system and effector module having any immunotherapeutic agent as described herein may be in forms of a polypeptide, or a polynucleotide such as mRNA, or a viral vector comprising the polynucleotide, or a cell modified to express the biocircuit, effector module, DD, and payload of interest (i.e., immunotherapeutic agent).

[00373] In another aspect of the present invention, methods for inducing an anti-tumor immune response in a subject are provided. The methods comprise administering a pharmaceutically effective amount of a pharmaceutical composition comprising at least one biocircuit system, effector module, DD, and/or payload of interest (i.e., an immunotherapeutic agent), at least one vector, or cells to a subject having a tumor. The biocircuit and effector module having any immunotherapeutic agent as described herein may be in forms of a polypeptide, or a polynucleotide such as mRNA, or a viral vector comprising the polynucleotide, or a cell modified to express the biocircuit, effector module, DD, and payload of interest (i.e., immunotherapeutic agent).

[00374] The methods, according to the present invention, may be adoptive cell transfer (ACT) using genetically engineered cells such as immune effector cells of the invention, cancer vaccines comprising biocircuit systems, effector modules, DDs, payloads of interest (i.e., immunotherapeutic agents) of the invention, or compositions that manipulate the tumor immunosuppressive microenvironment, or the combination thereof. These treatments may be further employed with other cancer treatment such as chemotherapy and radiotherapy. 1. Adoptive cell transfer (adoptive immunotherapy)

[00375] In some embodiments, cells which are genetically modified to express at least one biocircuit system, effector module, DD, and/or payload of interest (immunotherapeutic agent) may be used for adoptive cell therapy (ACT). As used herein, Adoptive cell transfer refers to the administration of immune cells (from autologous, allogenic or genetically modified hosts) with direct anticancer activity. ACT has shown promise in clinical application against malignant and infectious disease. For example, T cells genetically engineered to recognize CD19 have been used to treat follicular B cell lymphoma (Kochenderfer et al., Blood, 2010, 116:4099-4102; and Kochenderfer and Rosenberg, Nat Rev Clin Oncol., 2013, 10(5): 267-276) and ACT using autologous lymphocytes genetically-modified to express anti-tumor T cell receptors has been used to treat metastatic melanoma (Rosenberg and Dudley, Curr. Opin. Immunol. 2009, 21: 233 240).

[00376] According to the present invention, the biocircuits and systems may be used in the development and implementation of cell therapies such as adoptive cell therapy. Certain effector modules useful in cell therapy are given in Figures 7-12. The biocircuits, their components, effector modules and their SREs and payloads may be used in cell therapies to effect CAR therapies, in the manipulation or regulation of TILs, in allogeneic cell therapy, in combination T cell therapy with other treatment lines (e.g. radiation, cytokines), to encode engineered TCRs, or modified TCRs, or to enhance T cells other than TCRs (e.g. by introducing cytokine genes, genes for the checkpoint inhibitors PD1, CTLA4).

[00377] Provided herein are methods for use in adoptive cell therapy. The methods involve preconditioning a subject in need thereof, modulating immune cells with SRE, biocircuits and compositions of the present invention, administering to a subject, engineered immune cells expressing compositions of the invention and the successful engraftment of engineered cells within the subject.

[00378] In some embodiments, SREs, biocircuits and compositions of the present invention may be used to minimize preconditioning regimens associated with adoptive cell therapy. As used herein "preconditioning" refers to any therapeutic regimen administered to a subject to improve the outcome of adoptive cell therapy. Preconditioning strategies include, but are not limited to total body irradiation and/or lymphodepleting chemotherapy. Adoptive therapy clinical trials without preconditioning have failed to demonstrate any clinical benefit, indicating its importance in ACT. Yet, preconditioning is associated with significant toxicity and limits the subject cohort that is suitable for ACT. In some instances, immune cells for ACT may be engineered to express cytokines such as IL12 and IL15 as payload using SREs of the present invention to reduce the need for preconditioning (Pengram et al. (2012) Blood 119 (18): 4133 41; the contents of which are incorporated by reference in their entirety).

[00379] In some embodiments, immune cells for ACT may be dendritic cells, T cells such as CD8' T cells and CD4' T cells, natural killer (NK) cells, NK T cells, Cytotoxic T lymphocytes (CTLs), tumor infiltrating lymphocytes (TILs), lymphokine activated killer (LAK) cells, memory T cells, regulatory T cells (Tregs), helper T cells, cytokine-induced killer (CIK) cells, and any combination thereof. In other embodiments, immune stimulatory cells for ACT may be generated from embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC). In some embodiments, autologous or allogeneic immune cells are used for ACT.

[00380] In some embodiments, cells used for ACT may be T cells engineered to express CARs comprising an antigen-binding domain specific to an antigen on tumor cells of interest. In other embodiments, cells used for ACT may be NK cells engineered to express CARs comprising an antigen-binding domain specific to an antigen on tumor cells of interest. In addition to adoptive transfer of genetically modified T cells (e.g., CAR T cells) for immunotherapy, alternate types of CAR-expressing leukocytes, either alone, or in combination with CAR T cells may be used for adoptive immunotherapy. In one example, a mixture of T cells and NK cells may be used for ACT. The expression level of CARs in T cells and NK cells, according to the present invention, is tuned and controlled by a small molecule that binds to the DD(s) operably linked to the CAR in the effector module.

[00381] In some embodiments, the CARs of the present invention may be placed under the transcriptional control of the T cell receptor alpha constant (TRAC) locus in the T cells to achieve uniform CAR expression while enhancing T cell potency. The TRAC locus may be disrupted using the CRISPR/Cas 9, zinc finger nucleases (ZFNs), TALENs followed by the insertion of the CAR construct. Methods of engineering CAR constructs directed to the TRAC locus are described in Eyquem J. et al (2017) Nature.543(7643):113-117 (the contents of which are incorporated herein by reference in their entirety).

[00382] In some embodiments, NK cells engineered to express the present compositions may be used for ACT. NK cell activation induces perforin/granzyme-dependent apoptosis in target cells. NK cell activation also induces cytokine secretion such as IFN-y, TNF-a and GM-CSF. These cytokines enhance the phagocytic function of macrophages and their antimicrobial activity, and augment the adaptive immune response via up-regulation of antigen presentation by antigen presenting cells such as dendritic cells (DCs) (Reviewed by Vivier et al., Nat. Immunol., 2008, 9(5): 503-510).

[00383] Other examples of genetic modification may include the introduction of chimeric antigen receptors (CARs) and the down-regulation of inhibitory NK cell receptors such as NKG2A.

[00384] NK cells may also be genetically reprogrammed to circumvent NK cell inhibitory signals upon interaction with tumor cells. For example, using CRISPR, ZFN, or TALEN to genetically modify NK cells to silence their inhibitory receptors may enhance the anti-tumor capacity of NK cells.

[00385] Immune cells can be isolated and expanded ex vivo using a variety of methods known in the art. For example, methods of isolating and expanding cytotoxic T cells are described in U.S. Pat. NOs. 6,805,861 and 6,531, 451; US Patent Publication No.: US20160348072A1 and International Patent Publication NO: WO2016168595A1; the contents of each of which are incorporated herein by reference in their entirety. Isolation and expansion of NK cells is described in US Patent Publication NO.: US20150152387A1, U.S. Patent NO.: 7,435, 596; and Oyer, J.L. (2016). Cytotherapy.18(5):653-63; the contents of each of which are incorporated by reference herein in its entirety. Specifically, human primary NK cells may be expanded in the presence of feeder cells e.g. a myeloid cell line that has been genetically modified to express membrane bound IL15, IL21, IL12 and 4-1BBL.

[00386] In some instances, sub populations of immune cells may be enriched for ACT. Methods for immune cell enrichment are taught in International Patent Publication NO.: WO2015039100A1. In another example, T cells positive for B and T lymphocyte attenuator marker BTLA) may be used to enrich for T cells that are anti-cancer reactive as described in U.S. Pat. NO.: 9,512,401 (the content of each of which are incorporated herein by reference in their entirety).

[00387] In some embodiments, immune cells for ACT may be depleted of select sub populations to enhance T cell expansion. For example, immune cells may be depleted of Foxp3+ T lymphocytes to minimize the ant-tumor immune response using methods taught in US Patent Publication NO.: US 20160298081A1; the contents of which are incorporated by reference herein in their entirety.

[00388] In some embodiments, activation and expansion of T cells for ACT is achieved antigenic stimulation of a transiently expressed Chimeric Antigen Receptor (CAR) on the cell surface. Such activation methods are taught in International Patent NO.: WO2017015427, the content of which are incorporated herein by reference in their entirety.

[00389] In some embodiments, immune cells may be activated by antigens associated with antigen presenting cells (APCs). In some embodiments, the APCs may be dendritic cells, macrophages or B cells that antigen specific or nonspecific. The APCs may autologous or homologous in their organ. In some embodiments, the APCs may be artificial antigen presenting cells (aAPCs) such as cell based aAPCs or acellular aAPCs. Cell based aAPCs are may be selected from either genetically modified allogeneic cells such as human erythroleukemia cells or xenogeneic cells such as murine fibroblasts and Drosophila cells. Alternatively, the APCs maybe be acellular wherein the antigens or costimulatory domains are presented on synthetic surfaces such as latex beads, polystyrene beads, lipid vesicles or exosomes.

[00390] In some embodiments, cells of the invention, specifically T cells may be expanded using artificial cell platforms. In one embodiment, the mature T cells may be generated using artificial thymic organoids (ATOs) described by Seet CS et al. 2017. Nat Methods. 14, 521-530 (the contents of which are incorporated herein by reference in their entirety). ATOs are based on a stromal cell line expressing delta like canonical notch ligand (DLL1). In this method, stromal cells are aggregated with hematopoietic stem and progenitor cells by centrifugation and deployed on a cell culture insert at the air-fluid interface to generate organoid cultures. ATO-derived T cells exhibit naive phenotypes, a diverse T cell receptor (TCR) repertoire and TCR-dependent function.

[00391] In some embodiments, adoptive cell therapy is carried out by autologous transfer, wherein the cells are derived from a subject in need of a treatment and the cells, following isolation and processing are administered to the same subject. In other instances, ACT may involve allogenic transfer wherein the cells are isolated and/or prepared from a donor subject other than the recipient subject who ultimately receives cell therapy. The donor and recipient subject may be genetically identical, or similar or may express the same HLA class or subtype.

[00392] In some embodiments, the multiple immunotherapeutic agents introduced into the immune cells for ACT (e.g., T cells and NK cells) may be controlled by the same biocircuit system. In one example, a cytokine such as IL12 and a CAR construct such as CD19 CAR are linked to the same hDHFR destabilizing domain. The expression of IL12 and CD19 CAR is tuned using TMP simultaneously. In other embodiments, the multiple immunotherapeutic agents introduced into the immune cells for ACT (e.g., T cells and NK cells) may be controlled by different biocircuit systems. In one example, a cytokine such as IL12 and a CAR construct such as CD19 CAR are linked to different DDs in two separate effector modules, thereby can be tuned separately using different stimuli. In another example, a suicide gene and a CAR construct may be linked to two separate effector modules.

[00393] Following genetic modulation using SREs, biocircuits and compositions of the invention, cells are administered to the subject in need thereof. Methods for administration of cells for adoptive cell therapy are known and may be used in connection with the provided methods and compositions. For example, adoptive T cell therapy methods are described, e.g., in US Patent Application Publication No. 2003/0170238 to Gruenberg et al; US Patent No.

4,690,915 to Rosenberg; Rosenberg (2011) Nat Rev Clin Oncol. 8(10):577-85). See, e.g., Themeli et al. (2013) Nat Biotechnol. 31(10): 928-933; Tsukahara et al. (2013) Biochem Biophys Res Commun 438(1): 84-9; Davila et al. (2013) PLoS ONE 8(4): e61338; the contents of each of which are incorporated herein by reference in their entirety.

[00394] In some embodiments, immune cells for ACT may be modified to express one or more immunotherapeutic agents which facilitate immune cells activation, infiltration, expansion, survival and anti-tumor functions. The immunotherapeutic agents may be a second CAR or TCR specific to a different target molecule; a cytokine or a cytokine receptor; a chimeric switch receptor that converts an inhibitory signal to a stimulatory signal; a homing receptor that guides adoptively transferred cells to a target site such as the tumor tissue; an agent that optimizes the metabolism of the immune cell; or a safety switch gene (e.g., a suicide gene) that kills activated T cells when a severe event is observed after adoptive cell transfer or when the transferred immune cells are no-longer needed.

[00395] In some embodiments, immune cells used for adoptive cell transfer can be genetically manipulated to improve their persistence, cytotoxicity, tumor targeting capacity, and ability to home to disease sites in vivo, with the overall aim of further improving upon their capacity to kill tumors in cancer patients. One example is to introduce effector modules of the invention comprising cytokines such as gamma-cytokines (IL2 and IL15) into immune cells to promote immune cell proliferation and survival. Transduction of cytokine genes (e.g., gamma-cytokines IL2 and IL15) into cells will be able to propagate immune cells without addition of exogenous cytokines and cytokine expressing NK cells have enhanced tumor cytotoxicity.

[00396] In some embodiments, biocircuits, their components, SREs or effector modules may be utilized to prevent T cell exhaustion. As used herein, "T cell exhaustion" refers to the stepwise and progressive loss of T cell function caused by chronic T cell activation. T cell exhaustion is a major factor limiting the efficacy of antiviral and antitumor immunotherapies. Exhausted T cells have low proliferative and cytokine producing capabilities concurrent with high rates of apoptosis and high surface expression of multiple inhibitory receptors. T cell activation leading to exhaustion may occur either in the presence or absence of the antigen.

[00397] In some embodiments, the biocircuits, and their components may be utilized to prevent T cell exhaustion in the context of Chimeric Antigen Receptor - T cell therapy (CAR-T). In this context, exhaustion in some instances, may be caused by the oligomerization of the scFvs of the CAR on the cell surface which leads to continuous activation of the intracellular domains of the

CAR. As a non-limiting example, CARs of the present invention may include scFvs that are unable to oligomerize. As another non-limiting example, CARs that are rapidly internalized and re-expressed following antigen exposure may also be selected to prevent chronic scFv oligomerization on cell surface. In one embodiment, the framework region of the scFvs may be modified to prevent constitutive CAR signaling (Long et al. 2014. Cancer Research. 74(19) Si; the contents of which are incorporated by reference in their entirety). Tunable biocircuit systems of the present invention may also be used to regulate the surface expression of the CAR on the T cell surface to prevent chronic T cell activation. The CARs of the invention may also be engineered to minimize exhaustion. As a non-limiting example, the 41-BB signaling domain may be incorporated into CAR design to ameliorate T cell exhaustion. In some embodiments, any of the strategies disclosed by Long H A et al. may be utilized to prevent exhaustion (Long A H et al. (2015) Nature Medicine 21, 581-590; the contents of which are incorporated herein by reference in their entirety).

[00398] In some embodiments, the tunable nature of the biocircuits of the present invention may be utilized to reverse human T cell exhaustion observed with tonic CAR signaling. Reversibly silencing the biological activity of adoptively transferred cells using compositions of the present invention may be used to reverse tonic signaling which, in turn, may reinvigorate the T cells. Reversal of exhaustion may be measured by the downregulation of multiple inhibitory receptors associated with exhaustion.

[00399] In some embodiments, T cell metabolic pathways may be modified to diminish the susceptibility of T cells to exhaustion. Metabolic pathways may include, but are not limited to glycolysis, urea cycle, citric acid cycle, beta oxidation, fatty acid biosynthesis, pentose phosphate pathway, nucleotide biosynthesis, and glycogen metabolic pathways. As a non-limiting example, payloads that reduce the rate of glycolysis may be utilized to restrict or prevent T cell exhaustion (Long et al. Journal for Immunotherapy of Cancer 2013, 1(Suppl 1): P21; the contents of which are incorporated by reference in their entirety). In one embodiment, T cells of the present invention may be used in combination with inhibitors of glycolysis such as 2-deoxyglucose, and rapamycin.

[00400] In some embodiments, effector modules of the present invention, useful for immunotherapy may be placed under the transcriptional control of the T cell receptor alpha locus constant (TRAC) locus in the T cells. Eyquem et al. have shown that expression of the CAR from the TRAC locus prevents T cell exhaustion and the accelerated differentiation of T cells caused by excessive T cell activation (Eyquem J. et al (2017) Nature.543(7643):113-117; the contents of which are incorporated herein by reference in their entirety).

[00401] In some embodiments, payloads of the invention may be used in conjunction with antibodies or fragments that target T cell surface markers associated with T cell exhaustion. T cell surface markers associated with T cell exhaustion that may be used include, but are not limited to, CTLA-1, PD-1, TGIT, LAG-3, 2B4, BTLA, TIM3, VISTA, and CD96.

[00402] In one embodiment, the payload of the invention may be a CD276 CAR (with CD28, 4 IBB, and CD3 zeta intracellular domains), that does not show an upregulation of the markers associated with early T cell exhaustion (see International patent publication No. W02017044699; the contents of which are incorporated by reference in their entirety).

[00403] In some embodiments, the compositions of the present invention may be utilized to alter TIL (tumor infiltrating lymphocyte) populations in a subject. In one embodiment, any of the payloads described herein may be utilized to change the ratio of CD4 positive cells to CD8 positive populations. In some embodiments, TILs may be sorted ex vivo and engineered to express any of the cytokines described herein. Payloads of the invention may be used to expand CD4 and/or CD8 populations of TILs to enhance TIL mediated immune response. 2. Cancer vaccines

[00404] In some embodiments, biocircuits, effector modules, payloads of interest (immunotherapeutic agents), vectors, cells and compositions of the present invention may be used in conjunction with cancer vaccines.

[00405] In some embodiments, cancer vaccine may comprise peptides and/or proteins derived from tumor associated antigen (TAA). Such strategies may be utilized to evoke an immune response in a subject, which in some instances may be a cytotoxic T lymphocyte (CTL) response. Peptides used for cancer vaccines may also modified to match the mutation profile of a subject. For example, EGFR derived peptides with mutations matched to the mutations found in the subject in need of therapy have been successfully used in patients with lung cancer (Li F et al. (2016) Oncoimmunology. Oct 7;5(12): e1238539; the contents of which are incorporated herein by reference in their entirety).

[00406] In one embodiment, cancer vaccines of the present invention may superagonist altered peptide ligands (APL) derived from TAAs. These are mutant peptide ligands deviate from the native peptide sequence by one or more amino acids, which activate specific CTL clones more effectively than native epitopes. These alterations may allow the peptide to bind better to the restricting Class I MHC molecule or interact more favorably with the TCR of a given tumor specific CTL subset. APLs may be selected using methods taught in US Patent Publication NO.: US20160317633A1, the contents of which are incorporated herein by reference in their entirety. 3. Combination treatments

[00407] In some embodiments, it is desirable to combine compositions, vectors and cells of the invention for administration to a subject. Compositions of the invention comprising different immunotherapeutic agents may be used in combination for enhancement of immunotherapy.

[00408] In some embodiments, it is desirable to combine compositions of the invention with adjuvants, that can enhance the potency and longevity of antigen-specific immune responses. Adjuvants used as immunostimulants in combination therapy include biological molecules or delivery carriers that deliver antigens. As non-limiting examples, the compositions of the invention may be combined with biological adjuvants such as cytokines, Toll Like Receptors, bacterial toxins, and/or saponins. In other embodiments, the compositions of the present invention may be combined with delivery carriers. Exemplary delivery carriers include, polymer microspheres, immune stimulating complexes, emulsions (oil-in-water or water-in-oil), aluminum salts, liposomes or virosomes.

[00409] In some embodiments, immune effector cells modified to express biocircuits, effector modules, DDs and payloads of the invention may be combined with the biological adjuvants described herein. Dual regulation of CAR and cytokines and ligands to segregate the kinetic control of target-mediated activation from intrinsic cell T cell expansion. Such dual regulation also minimizes the need for pre-conditioning regimens in patients. As a non-limiting example, DD regulated CAR e.g. CD19 CAR may be combined with cytokines e.g. IL12 to enhance the anti-tumor efficacy of the CAR (Pegram H.J., et al. Tumor-targeted T cells modified to secrete IL12 eradicate systemic tumors without need for prior conditioning. Blood.2012;119:4133-41; the contents of each of which are incorporated herein by reference in their entirety). As another non-limiting example, Merchant et al. combined dendritic cell- based vaccinations with recombinant human IL7 to improve outcome in high-risk pediatric sarcomas patients (Merchant, M.S et. al. Adjuvant immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas. Clin Cancer Res. 2016. 22(13):3182-91; the contents of each of which are incorporated herein by reference in their entirety).

[00410] In some embodiments, immune effector cells modified to express one or more antigen specific TCRs or CARs may be combined with compositions of the invention comprising immunotherapeutic agents that convert the immunosuppressive tumor microenvironment.

[00411] In one aspect, effector immune cells modified to express CARs specific to different target molecules on the same cell may be combined. In another aspect, different immune cells modified to express the same CAR construct such as NK cells and T cells may be used in combination for a tumor treatment, for instance, a T cell modified to express a CD19 CAR may be combined with a NK cell modified to express the same CD19 CAR to treat B cell malignancy.

[00412] In other embodiments, immune cells modified to express CARs may be combined with checkpoint blockade agents.

[00413] In some embodiments, immune effector cells modified to expressed biocircuits, effector modules, DDs and payloads of the invention may be combined with cancer vaccines of the invention.

[00414] In some embodiments, methods of the invention may include combination of the compositions of the invention with other agents effective in the treatment of cancers, infection diseases and other immunodeficient disorders, such as anti-cancer agents. As used herein, the term "anti-cancer agent" refers to any agent which is capable of negatively affecting cancer in a subject, for example, by killing cancer cells, inducing apoptosis in cancer cells, reducing the growth rate of cancer cells, reducing the incidence or number of metastases, reducing tumor size, inhibiting tumor growth, reducing the blood supply to a tumor or cancer cells, promoting an immune response against cancer cells or a tumor, preventing or inhibiting the progression of cancer, or increasing the lifespan of a subject with cancer.

[00415] In some embodiments, anti-cancer agent or therapy may be a chemotherapeutic agent, or radiotherapy, immunotherapeutic agent, surgery, or any other therapeutic agent which, in combination with the present invention, improves the therapeutic efficacy of treatment.

[00416] In one embodiment, an effector module comprising a CD19 CAR maybe used in combination with amino pyrimidine derivatives such as the Burkit's tyrosine receptor kinase (BTK) inhibitor using methods taught in International Patent Application NO.: W02016164580, the contents of which are incorporated herein by reference in their entirety.

[00417] In some embodiments, compositions of the present invention may be used in combination with immunotherapeutics other than the inventive therapy described herein, such as antibodies specific to some target molecules on the surface of a tumor cell.

[00418] Exemplary chemotherapies include, without limitation, Acivicin; Aclarubicin; Acodazole hydrochloride; Acronine; Adozelesin; Aldesleukin; Altretamine; Ambomycin; Ametantrone acetate; Amsacrine; Anastrozole; Anthramycin; Asparaginase; Asperrin, Sulindac, Curcumin, alkylating agents including: Nitrogen mustards such as mechlor-ethamine, cyclophosphamide, ifosfamide, melphalan and chlorambucil; nitrosoureas such as carmustine (BC U), lomustine (CCNU), and semustine (methyl-CC U); thylenimines/methylmelamine such as thriethylenemelamine (TEM), triethylene, thiophosphoramide (thiotepa), hexamethylmelamine (HMM, altretamine); alkyl sulfonates such as busulfan; triazines such as dacarbazine (DTIC); antimetabolites including folic acid analogs such as methotrexate and trimetrexate, pyrrolidine analogs such as 5- fluorouracil, fluorodeoxyuridine, gemcitabine, cytosine arabinoside (AraC, cytarabine), 5-azacytidine, 2,2'- difluorodeoxycytidine, purine analogs such as 6-mercaptopurine, 6-thioguanine, azathioprine, 2'-deoxycoformycin (pentostatin), erythrohydroxynonyladenine (EHNA), fludarabine phosphate, and 2 chlorodeoxyadenosine (cladribine, 2- CdA); natural products including antimitotic drugs such as paclitaxel, vinca alkaloids including vinblastine (VLB), vincristine, and vinorelbine, taxotere, estramustine, and estramustine phosphate; epipodophylotoxins such as etoposide and teniposide; antibiotics, such as actimomycin D, daunomycin (rubidomycin), doxorubicin, mitoxantrone, idarubicin, bleomycins, plicamycin (mithramycin), mitomycinC, and actinomycin; enzymes such as L-asparaginase, cytokines such as interferon (IFN)-gamma, tumor necrosis factor (TNF) alpha, TNF-beta and GM-CSF, anti-angiogenic factors, such as angiostatin and endostatin, inhibitors of FGF or VEGF such as soluble forms of receptors for angiogenic factors, including soluble VGF/VEGF receptors, platinum coordination complexes such as cisplatin and carboplatin, anthracenediones such as mitoxantrone, substituted urea such as hydroxyurea, methylhydrazine derivatives including N- methylhydrazine (MIFf) and procarbazine, adrenocortical suppressants such as mitotane (o,p'-DDD) and aminoglutethimide; hormones and antagonists including adrenocorticosteroid antagonists such as prednisone and equivalents, dexamethasone and aminoglutethimide; progestin such as hydroxyprogesterone caproate, medroxyprogesterone acetate and megestrol acetate; estrogen such as diethylstilbestrol and ethinyl estradiol equivalents; antiestrogen such as tamoxifen; androgens including testosterone propionate and fluoxymesterone/equivalents; antiandrogens such as flutamide, gonadotropin releasing hormone analogs and leuprolide; non-steroidal antiandrogens such as flutamide; kinase inhibitors, histone deacetylase inhibitors, methylation inhibitors, proteasome inhibitors, monoclonal antibodies, oxidants, anti-oxidants, telomerase inhibitors, BH3 mimetics, ubiquitin ligase inhibitors, stat inhibitors and receptor tyrosin kinase inhibitors such as imatinib mesylate (marketed as Gleevac or Glivac) and erlotinib (an EGF receptor inhibitor) now marketed as Tarveca; anti-virals such as oseltamivir phosphate, Amphotericin B, and palivizumab; Sdi 1 mimetics; Semustine; Senescence derived inhibitor 1; Sparfosic acid; Spicamycin D; Spiromustine; Splenopentin; Spongistatin 1; Squalamine; Stipiamide; Stromelysin inhibitors; Sulfinosine; Superactive vasoactive intestinal peptide antagonist; Velaresol; Veramine; Verdins; Verteporfin; Vinorelbine; Vinxaltine; Vitaxin; Vorozole; Zanoterone; Zeniplatin; Zilascorb; and Zinostatin stimalamer; PI3K small-molecule inhibitor, GSK2636771; pan-PI3K inhibitor (BKM120); BRAF inhibitors. Vemurafenib (Zelboraf) and dabrafenib (Tafinlar); or any analog or derivative and variant of the foregoing.

[00419] Radiotherapeutic agents and factors include radiation and waves that induce DNA damage for example, y-irradiation, X-rays, UV-irradiation, microwaves, electronic emissions, radioisotopes, and the like. Therapy may be achieved by irradiating the localized tumor site with the above described forms of radiations. It is most likely that all of these factors effect a broad range of damage DNA, on the precursors of DNA, the replication and repair of DNA, and the assembly and maintenance of chromosomes. Dosage ranges for X-rays range from daily doses of 50 to 200 roentgens for prolonged periods of time (3 to 4 weeks), to single doses of 2000 to 6000 roentgens. Dosage ranges for radioisotopes vary widely, and depend on the half-life of the isotope, the strength and type of radiation emitted, and the uptake by the neoplastic cells.

[00420] In some embodiments, the chemotherapeutic agent may be an immunomodulatory agent such as lenalidomide (LEN). Recent studies have demonstrated that lenalidomide can enhance antitumor functions of CAR modified T cells (Otahal et al., Oncoimmunology, 2015, 5(4): el115940). Some examples of anti-tumor antibodies include tocilizumab, siltuximab.

[00421] Other agents maybe used in combination with compositions of the invention may also include, but not limited to, agents that affect the upregulation of cell surface receptors and their ligands such as Fas/Fas ligand, DR4 or DR5/TRAIL and GAP junctions, cytostatic and differentiation agents, inhibitors of cell adhesion such as focal adhesion kinase (FAKs) inhibitors and Lovastatin, or agents that increase the sensitivity of the hyper proliferative cells to apoptotic inducers such as the antibody C225.

[00422] The combinations may include administering the compositions of the invention and other agents at the same time or separately. Alternatively, the present immunotherapy may precede or follow the other agent/therapy by intervals ranging from minutes, days, weeks to months. 4. Diseases

[00423] Provided in the present invention is a method of reducing a tumor volume or burden in a subject in need, the method comprising introducing into the subject a composition of the invention.

[00424] The present invention also provides methods for treating a cancer in a subject, comprising administering to the subject an effective amount of an immune effector cell genetically modified to express at least one effector module of the invention. Cancer

[00425] Various cancers may be treated with pharmaceutical compositions, biocircuits, biocircuit components, effector modules including their SREs or payloads of the present invention. As used herein, the term "cancer" refers to any of various malignant neoplasms characterized by the proliferation of anaplastic cells that tend to invade surrounding tissue and metastasize to new body sites and also refers to the pathological condition characterized by such malignant neoplastic growths. Cancers may be tumors or hematological malignancies, and include but are not limited to, all types of lymphomas/leukemias, carcinomas and sarcomas, such as those cancers or tumors found in the anus, bladder, bile duct, bone, brain, breast, cervix, colon/rectum, endometrium, esophagus, eye, gallbladder, head and neck, liver, kidney, larynx, lung, mediastinum (chest), mouth, ovaries, pancreas, penis, prostate, skin, small intestine, stomach, spinal marrow, tailbone, testicles, thyroid and uterus.

[00426] Types of carcinomas which may be treated with the compositions of the present invention include, but are not limited to, papilloma/carcinoma, choriocarcinoma, endodermal sinus tumor, teratoma, adenoma/adenocarcinoma, melanoma, fibroma, lipoma, leiomyoma, rhabdomyoma, mesothelioma, angioma, osteoma, chondroma, glioma, lymphoma/leukemia, squamous cell carcinoma, small cell carcinoma, large cell undifferentiated carcinomas, basal cell carcinoma and sinonasal undifferentiated carcinoma.

[00427] Types of carcinomas which may be treated with the compositions of the present invention include, but are not limited to, soft tissue sarcoma such as alveolar soft part sarcoma, angiosarcoma, dermatofibrosarcoma, desmoid tumor, desmoplastic small round cell tumor, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, hemangiopericytoma, hemangiosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphosarcoma, malignant fibrous histiocytoma, neurofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, and Askin's tumor, Ewing's sarcoma (primitive neuroectodermal tumor), malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, and chondrosarcoma.

[00428] As a non-limiting example, the carcinoma which may be treated may be Acute granulocytic leukemia, Acute lymphocytic leukemia, Acute myelogenous leukemia, Adenocarcinoma, Adenosarcoma, Adrenal cancer, Adrenocortical carcinoma, Anal cancer, Anaplastic astrocytoma, Angiosarcoma, Appendix cancer, Astrocytoma, Basal cell carcinoma, B-Cell lymphoma ), Bile duct cancer, Bladder cancer, Bone cancer, Bowel cancer, Brain cancer, Brain stem glioma, Brain tumor, Breast cancer, Carcinoid tumors, Cervical cancer, Cholangiocarcinoma, Chondrosarcoma, Chronic lymphocytic leukemia, Chronic myelogenous leukemia, Colon cancer, Colorectal cancer, Craniopharyngioma, Cutaneous lymphoma, Cutaneous melanoma, Diffuse astrocytoma, Ductal carcinoma in situ, Endometrial cancer, Ependymoma, Epithelioid sarcoma, Esophageal cancer, Ewing sarcoma, Extrahepatic bile duct cancer, Eye cancer, Fallopian tube cancer, Fibrosarcoma, Gallbladder cancer, Gastric cancer, Gastrointestinal cancer, Gastrointestinal carcinoid cancer, Gastrointestinal stromal tumors, General, Germ cell tumor, Glioblastoma multiforme, Glioma, Hairy cell leukemia, Head and neck cancer, Hemangioendothelioma, Hodgkin lymphoma, Hodgkin's disease, Hodgkin's lymphoma, Hypopharyngeal cancer, Infiltrating ductal carcinoma, Infiltrating lobular carcinoma, Inflammatory breast cancer, Intestinal Cancer, Intrahepatic bile duct cancer, Invasive / infiltrating breast cancer, Islet cell cancer, Jaw cancer, Kaposi sarcoma, Kidney cancer, Laryngeal cancer, Leiomyosarcoma, Leptomeningeal metastases, Leukemia, Lip cancer, Liposarcoma, Liver cancer, Lobular carcinoma in situ, Low-grade astrocytoma, Lung cancer, Lymph node cancer, Lymphoma, Male breast cancer, Medullary carcinoma, Medulloblastoma, Melanoma, Meningioma, Merkel cell carcinoma, Mesenchymal chondrosarcoma, Mesenchymous, Mesothelioma, Metastatic breast cancer, Metastatic melanoma, Metastatic squamous neck cancer, Mixed gliomas, Mouth cancer, Mucinous carcinoma, Mucosal melanoma, Multiple myeloma, Nasal cavity cancer, Nasopharyngeal cancer, Neck cancer, Neuroblastoma, Neuroendocrine tumors, Non-Hodgkin lymphoma, Non-Hodgkin's lymphoma, Non-small cell lung cancer, Oat cell cancer, Ocular cancer, Ocular melanoma, Oligodendroglioma, Oral cancer, Oral cavity cancer, Oropharyngeal cancer, Osteogenic sarcoma, Osteosarcoma, Ovarian cancer, Ovarian epithelial cancer, Ovarian germ cell tumor, Ovarian primary peritoneal carcinoma, Ovarian sex cord stromal tumor, Paget's disease, Pancreatic cancer, Papillary carcinoma, Paranasal sinus cancer, Parathyroid cancer, Pelvic cancer, Penile cancer, Peripheral nerve cancer, Peritoneal cancer, Pharyngeal cancer, Pheochromocytoma, Pilocytic astrocytoma, Pineal region tumor, Pineoblastoma, Pituitary gland cancer, Primary central nervous system lymphoma, Prostate cancer, Rectal cancer, Renal cell cancer, Renal pelvis cancer, Rhabdomyosarcoma, Salivary gland cancer, Sarcoma, Sarcoma, bone, Sarcoma, soft tissue, Sarcoma, uterine, Sinus cancer, Skin cancer, Small cell lung cancer, Small intestine cancer, Soft tissue sarcoma, Spinal cancer, Spinal column cancer, Spinal cord cancer, Spinal tumor, Squamous cell carcinoma, Stomach cancer, Synovial sarcoma, T-cell lymphoma ), Testicular cancer, Throat cancer, Thymoma / thymic carcinoma, Thyroid cancer, Tongue cancer, Tonsil cancer, Transitional cell cancer, Transitional cell cancer, Transitional cell cancer, Triple negative breast cancer, Tubal cancer, Tubular carcinoma, Ureteral cancer, Ureteral cancer, Urethral cancer, Uterine adenocarcinoma, Uterine cancer, Uterine sarcoma, Vaginal cancer, and Vulvar cancer. Infectious diseases

[00429] In some embodiment, biocircuits of the invention may be used for the treatment of infectious diseases. Biocircuits of the invention may be introduced in cells suitable for adoptive cell transfer such as macrophages, dendritic cells, natural killer cells, and or T cells. Infectious diseases treated by the biocircuits of the invention may be diseases caused by viruses, bacteria, fungi, and/or parasites. IL15-IL15Ra payloads of the invention may be used to increase immune cell proliferation and/or persistence of the immune cells useful in treating infectious diseases.

[00430] "Infection diseases" herein refer to diseases caused by any pathogen or agent that infects mammalian cells, preferably human cells and causes a disease condition. Examples thereof include bacteria, yeast, fungi, protozoans, mycoplasma, viruses, prions, and parasites. Examples include those involved in (a) viral diseases such as, for example, diseases resulting from infection by an adenovirus, a herpesvirus (e.g., HSV-I, HSV-II, CMV, or VZV), a poxvirus (e-g-, an orthopoxvirus such as variola or vaccinia, or molluscum contagiosum), a picornavirus (e.g., rhinovirus or enterovirus), an orthomyxovirus (e.g., influenzavirus), a paramyxovirus (e.g., parainfluenza virus, mumps virus, measles virus, and respiratory syncytial virus (RSV)), a coronavirus (e.g., SARS), a papovavirus (e.g., papillomaviruses, such as those that cause genital warts, common warts, or plantar warts), a hepadnavirus (e.g., hepatitis B virus), a flavivirus (e.g., hepatitis C virus or Dengue virus), or a retrovirus (e.g., a lentivirus such as HIV); (b) bacterial diseases such as, for example, diseases resulting from infection by bacteria of, for example, the genus Escherichia, Enterobacter, Salmonella, Staphylococcus, Shigella, Listeria, Aerobacter, Helicobacter, Klebsiella, Proteus, Pseudomonas, Streptococcus, Chlamydia, Mycoplasma, Pneumococcus, Neisseria, Clostridium, Bacillus, Corynebacterium, Mycobacterium, Campylobacter, Vibrio, Serratia, Providencia, Chromobacterium, Brucella, Yersinia, Haemophilus, or Bordetella; (c) other infectious diseases, such chlamydia, fungal diseases including but not limited to candidiasis, aspergillosis, histoplasmosis, cryptococcal meningitis, parasitic diseases including but not limited to malaria, Pneumocystis camii pneumonia, leishmaniasis, cryptosporidiosis, toxoplasmosis, and trypanosome infection and prions that cause human disease such as Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann-Straiissler-Scheinker syndrome, Fatal Familial Insomnia and kuru. 5. Microbiome

[00431] Alterations in the composition of the microbiome may impact the action of anti-cancer therapies. A diverse community of symbiotic, commensal and pathogenic microorganisms exist in all environmentally exposed sites in the body and is herein referred to as the "Microbiome." Environmentally exposed sites of the body that may be inhabited by a microbiome include the skin, nasopharynx, the oral cavity, respiratory tract, gastrointestinal tract, and the reproductive tract.

[00432] In some embodiments, microbiome native or engineered with immunotherapeutic agents may be used to improve the efficacy of the anti-cancer immunotherapies. Methods of using microbiome to improve responsive to immunotherapeutic agents have been described by Sivan et al (Sivan A., et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-Li efficacy. Science 2015; 350:1084-9; the contents of which are incorporated herein by reference in their entirety). In one embodiment, protein, RNA and/or other biomolecules derived from the microbiome may be used as a payload to influence the efficacy of the anti-cancer immunotherapies. 6. Tools and agents for making therapeutics

[00433] Provided in the present invention are tools and agents that may be used in generating immunotherapeutics for reducing a tumor volume or burden in a subject in need. A considerable number of variables are involved in producing a therapeutic agent, such as structure of the payload, type of cells, method of gene transfers, method and time of ex vivo expansion, pre conditioning and the amount and type of tumor burden in the subject. Such parameters may be optimized using tools and agents described herein.

Cell lines

[00434] The present disclosure provides a mammalian cell that has been genetically modified with the compositions of the invention. Suitable mammalian cells include primary cells and immortalized cell lines. Suitable mammalian cell lines include, but are not limited to Human embryonic kidney cell line 293, fibroblast cell line NIH 3T3, human colorectal carcinoma cell line HCT116, ovarian carcinoma cell line SKOV-3, immortalized T cell lines (e.g. Jurkat cells and SupT1 cells), lymphoma cell line Raji cells, NALM-6 cells, K562 cells, HeLa cells, PC12 cells, HL-60 cells, NK cell lines (e.g. NKL, NK92, NK962, and YTS), and the like. In some instances, the cell is not an immortalized cell line, but instead a cell obtained from an individual and is herein referred to as a primary cell. For example, the cell is a T lymphocyte obtained from an individual. Other examples include, but are not limited to cytotoxic cells, stem cells, peripheral blood mononuclear cells or progenitor cells obtained from an individual. Tracking SREs, biocircuits and cell lines

[00435] In some embodiments, it may be desirable to track the compositions of the invention or the cells modified by the compositions of the invention. Tracking may be achieved by using reporter moieties, which, as used herein, refers to any protein capable of creating a detectable signal, in response to an input. Examples include alkaline phosphatase, p-galactosidase, chloramphenicol acetyltransferase, p-glucuronidase, peroxidase, p-lactamase, catalytic antibodies, bioluminescent proteins e.g. luciferase, and fluorescent proteins such as Green fluorescent protein (GFP).

[00436] Reporter moieties may be used to monitor the response of the DD upon addition of the ligand corresponding to the DD. In other instances, reporter moieties may be used to track cell survival, persistence, cell growth, and/or localization in vitro, in vivo, or ex vivo.

[00437] In some embodiments, the preferred reporter moiety may be luciferase proteins. In one embodiment, the reporter moiety is the Renilla luciferase (SEQ ID NO. 866, encoded by nucleic acid sequence of SEQ ID NO. 867), or a firefly luciferase (SEQ ID NO. 868, encoded by nucleic acid sequence of SEQ ID NO. 869). Animal models

[00438] The utility and efficacy of the compositions of the present invention may be tested in vivo animal models, preferably mouse models. Mouse models used to may be syngeneic mouse models wherein mouse cells are modified with compositions of the invention and tested in mice of the same genetic background. Examples include pMEL-1 and 4T1 mouse models.

Alternatively, xenograft models where human cells such as tumor cells and immune cells are introduced into immunodeficient mice may also be utilized in such studies. Immunodeficient mice used may be CByJ.Cg-Foxnn/J, B6;129S7-Rag'm m/J, B6.129S7-Rag1'm `/J, B6. CB17-Prkdcscid/SzJ, NOD.129S7(B6)-Rag'ImM m/J, NOD.Cg-RagIJM1mPrf1tm1SdZ/SZ, NOD.CB17-Prkdcscid/SzJ,NOD.Cg-PrkdcscdB2mt'unc/J,NOD-scid IL2Rgnun, Nude (nu) mice, SCID mice, NOD mice, RAG1/RAG2 mice, NOD-Scid mice, IL2rgnull mice, b2mnull mice, NOD-scid IL2rynull mice, NOD-scid-B2mnull mice, beige mouse, and HLA transgenic mice. Cellular assays

[00439] In some embodiments, the effectiveness of the compositions of the inventions as immunotherapeutic agents may be evaluated using cellular assays. Levels of expression and/or identity of the compositions of the invention may be determined according to any methods known in the art for identifying proteins and/or quantitating proteins levels. In some embodiments, such methods may include Western Blotting, flow cytometry, and immunoassays.

[00440] Provided herein are methods for functionally characterizing cells expressing SRE, biocircuits and compositions of the invention. In some embodiments, functional characterization is carried out in primary immune cells or immortalized immune cell lines and may be determined by expression of cell surface markers. Examples of cell surface markers for T cells include, but are not limited to, CD3, CD4, CD8, CD 14, CD20, CD1Ib, CD16, CD45 and HLA-DR, CD 69, CD28, CD44, IFNgamma. Markers for T cell exhaustion include PD1, TIM3, BTLA, CD160, 2B4, CD39, and LAG3. Examples of cell surface markers for antigen presenting cells include, but are not limited to, MHC class I, MHC ClassII, CD40, CD45,B7-1, B7-2, IFN-y receptor and IL2 receptor, ICAM-1 and/or Fcy receptor. Examples of cell surface markers for dendritic cells include, but are not limited to, MHC class I, MHC Class II,B7-2, CD18, CD29, CD31, CD43, CD44, CD45, CD54, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR and/or Dectin-1 and the like; while in some cases also having the absence of CD2, CD3, CD4, CD8, CD14, CD15, CD16, CD 19, CD20, CD56, and/or CD57. Examples of cell surface markers for NK cells include, but are not limited to, CCL3, CCL4, CCL5, CCR4, CXCR4, CXCR3, NKG2D, CD71, CD69, CCR5, Phospho JAK/STAT, phospho ERK, phospho p38/ MAPK, phospho AKT, phospho STAT3, Granulysin, Granzyme B, Granzyme K, IL1O, IL22, IFNg, LAP, Perforin, and TNFa.

V. DELIVERY MODALITIES AND/OR VECTORS Vectors

[00441] The present invention also provides vectors that package polynucleotides of the invention encoding biocircuits, effector modules, SREs (DDs) and payload constructs, and combinations thereof. Vectors of the present invention may also be used to deliver the packaged polynucleotides to a cell, a local tissue site or a subject. These vectors may be of any kind, including DNA vectors, RNA vectors, plasmids, viral vectors and particles. Viral vector technology is well known and described in Sambrook et al. (2001, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). Viruses, which are useful as vectors include, but are not limited to lentiviral vectors, adenoviral vectors, adeno-associated viral (AAV) vectors, herpes simplex viral vectors, retroviral vectors, oncolytic viruses, and the like.

[00442] In general, vectors contain an origin of replication functional in at least one organism, a promoter sequence and convenient restriction endonuclease site, and one or more selectable markers e.g. a drug resistance gene.

[00443] As used herein a promoter is defined as a DNA sequence recognized by transcription machinery of the cell, required to initiate specific transcription of the polynucleotide sequence of the present invention. Vectors can comprise native or non-native promoters operably linked to the polynucleotides of the invention. The promoters selected may be strong, weak, constitutive, inducible, tissue specific, development stage-specific, and/or organism specific. One example of a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of polynucleotide sequence that is operatively linked to it. Another example of a preferred promoter is Elongation Growth Factor-1. Alpha (EF-1. alpha). Other constitutive promoters may also be used, including, but not limited to simian virus 40 (SV40), mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV), long terminal repeat (LTR), promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter as well as human gene promoters including, but not limited to the phosphoglycerate kinase (PGK) promoter, actin promoter, the myosin promoter, the hemoglobin promoter, the Ubiquitin C (Ubc) promoter, the human U6 small nuclear protein promoter and the creatine kinase promoter. In some instances, inducible promoters such as but not limited to metallothionine promoter, glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter may be used. In some embodiments, the promoter may be selected from the SEQ ID NO.: 716-718.

[00444] In some embodiments, the optimal promoter may be selected based on its ability to achieve minimal expression of the SREs and payloads of the invention in the absence of the ligand and detectable expression in the presence of the ligand.

[00445] Additional promoter elements e.g. enhancers may be used to regulate the frequency of transcriptional initiation. Such regions may be located 10-100 base pairs upstream or downstream of the start site. In some instances, two or more promoter elements may be used to cooperatively or independently activate transcription.

[00446] In some embodiments, the recombinant expression vector may comprise regulatory sequences, such as transcription and translation initiation and termination codons, which are specific to the type of host cell into which the vector is to be introduced. 1. Lentiviral vectors

[00447] In some embodiments, lentiviral vectors/particles may be used as vehicles and delivery modalities. Lentiviruses are subgroup of the Retroviridae family of viruses, named because reverse transcription of viral RNA genomes to DNA is required before integration into the host genome. As such, the most important features of lentiviral vehicles/particles are the integration of their genetic material into the genome of a target/host cell. Some examples of lentivirus include the Human Immunodeficiency Viruses: HIV-1 and HIV-2, the Simian Immunodeficiency Virus (SIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), Jembrana Disease Virus (JDV), equine infectious anemia virus (EIAV), equine infectious anemia virus, visna-maedi and caprine arthritis encephalitis virus (CAEV).

[00448] Typically, lentiviral particles making up the gene delivery vehicle are replication defective on their own (also referred to as "self-inactivating"). Lentiviruses are able to infect both dividing and non-dividing cells by virtue of the entry mechanism through the intact host nuclear envelope (Naldini L et al., Curr. Opin. Biotechnol, 1998, 9: 457-463). Recombinant lentiviral vehicles/particles have been generated by multiply attenuating the HIV virulence genes, for example, the genes Env, Vif, Vpr, Vpu, Nef and Tat are deleted making the vector biologically safe. Correspondingly, lentiviral vehicles, for example, derived from HIV-/HIV-2 can mediate the efficient delivery, integration and long-term expression of transgenes into non dividing cells. As used herein, the term "recombinant" refers to a vector or other nucleic acid containing both lentiviral sequences and non-lentiviral retroviral sequences.

[00449] Lentiviral particles may be generated by co-expressing the virus packaging elements and the vector genome itself in a producer cell such as human HEK293T cells. These elements are usually provided in three (in second generation lentiviral systems) or four separate plasmids (in third generation lentiviral systems). The producer cells are co-transfected with plasmids that encode lentiviral components including the core (i.e. structural proteins) and enzymatic components of the virus, and the envelope protein(s) (referred to as the packaging systems), and a plasmid that encodes the genome including a foreign transgene, to be transferred to the target cell, the vehicle itself (also referred to as the transfer vector). In general, the plasmids or vectors are included in a producer cell line. The plasmids/vectors are introduced via transfection, transduction or infection into the producer cell line. Methods for transfection, transduction or infection are well known by those of skill in the art. As non-limiting example, the packaging and transfer constructs can be introduced into producer cell lines by calcium phosphate transfection, lipofection or electroporation, generally together with a dominant selectable marker, such as neo, DHFR, Gln synthetase or ADA, followed by selection in the presence of the appropriate drug and isolation of clones.

[00450] The producer cell produces recombinant viral particles that contain the foreign gene, for example, the effector module of the present invention. The recombinant viral particles are recovered from the culture media and titrated by standard methods used by those of skill in the art. The recombinant lentiviral vehicles can be used to infect target cells.

[00451] Cells that can be used to produce high-titer lentiviral particles may include, but are not limited to, HEK293T cells, 293G cells, STAR cells (Relander et al., Mol. Ther., 2005, 11: 452 459), FreeStyle T M 293 Expression System (ThermoFisher, Waltham, MA), and other HEK293T based producer cell lines (e.g., Stewart et al., Hum Gene Ther._2011, 22(3):357-369; Lee et al., Biotechnol Bioeng, 2012, 10996): 1551-1560; Throm et al., Blood. 2009, 113(21): 5104-5110; the contents of each of which are incorporated herein by reference in their entirety).

[00452] In some aspects, the envelope proteins may be heterologous envelop proteins from other viruses, such as the G protein of vesicular stomatitis virus (VSV G) or baculoviral gp64 envelop proteins. The VSV-G glycoprotein may especially be chosen among species classified in the vesiculovirus genus: Carajasvirus (CJSV), Chandipuravirus (CHPV), Cocal virus (COCV), Isfahan virus (ISFV), Maraba virus (MARAV), Piry virus (PIRYV), Vesicular stomatitis Alagoas virus (VSAV), Vesicular stomatitis Indiana virus (VSIV) and Vesicular stomatitis New Jersey virus (VSNJV) and/or stains provisionally classified in the vesiculovirus genus as Grass carp rhabdovirus,BeAn 157575 virus (BeAn 157575), Boteke virus (BTKV), Calchaquivirus (CQIV), Eel virus American (EVA), Gray Lodge virus (GLOV), Juronavirus (JURY), Klamath virus (KLAV), Kwatta virus (KWAV), La Joya virus (LJV), Malpais Spring virus (MSPV), Mount Elgon bat virus (MEBV), Perinetvirus (PERV), Pikefry rhabdovirus (PFRV), Porton virus (PORV), Radi virus (RADIV), Spring viremia ofcarp virus (SVCV), Tupaia virus (TUPV), Ulcerativedisease rhabdovirus (UDRV) and Yug Bogdanovac virus (YBV). The gp64 or other baculoviral env protein can be derived from Autographa calfornica nucleopolyhedrovirus (AcMNPV), Anagraphafalciferanuclear polyhedrosis virus, Bombyx mori nuclear polyhedrosis virus, Choristoneurafumiferananucleopolyhedrovirus, Orgyia pseudotsugata single capsid nuclear polyhedrosis virus, Epiphyaspostvittana nucleopolyhedrovirus, Hyphantria cunea nucleopolyhedrovirus, Galleria mellonella nuclear polyhedrosis virus, Dhori virus, Thogoto virus, Antheraeapemyi nucleopolyhedrovirus or Batken virus.

[00453] Additional elements provided in lentiviral particles may comprise retroviral LTR (long terminal repeat) at either 5' or 3' terminus, a retroviral export element, optionally a lentiviral reverse response element (RRE), a promoter or active portion thereof, and a locus control region (LCR) or active portion thereof. Other elements include central polypurine tract (cPPT) sequence to improve transduction efficiency in non-dividing cells, Woodchuck Hepatitis Virus (WHP) Posttranscriptional Regulatory Element (WPRE) which enhances the expression of the transgene, and increases titer. The effector module is linked to the vector.

[00454] Methods for generating recombinant lentiviral particles are discussed in the art, for example, U.S. Pat. NOs.: 8, 846, 385; 7,745, 179; 7,629,153; 7,575,924; 7,179, 903; and 6, 808, 905; the contents of each of which are incorporated herein by reference in their entirety.

[00455] Lentivirus vectors used may be selected from, but are not limited to pLVX, pLenti, pLenti6, pLJM1, FUGW, pWPXL, pWPI, pLenti CMV puro DEST, pLJM-EGFP, pULTRA, plnducer20, pHIV-EGFP, pCW57.1, pTRPE, pELPS, pRRL, and pLionlI.

[00456] Lentiviral vehicles known in the art may also be used (See, U.S. Pat. NOs. 9, 260, 725; 9,068,199; 9,023,646; 8,900,858; 8,748,169; 8,709,799; 8,420,104; 8,329,462; 8,076,106; 6,013,516; and 5,994,136; International Patent Publication NO.: W02012079000; the contents of each of which are incorporated herein by reference in their entirety).

2. Retroviral vectors (y-retroviral vectors)

[00457] In some embodiments, retroviral vectors may be used to package and deliver the biocircuits, biocircuit components, effector modules, SREs or payload constructs of the present invention. Retroviral vectors (RVs) allow the permanent integration of a transgene in target cells. In addition to lentiviral vectors based on complex HIV-1/2, retroviral vectors based on simple gamma-retroviruses have been widely used to deliver therapeutic genes and demonstrated clinically as one of the most efficient and powerful gene delivery systems capable of transducing a broad range of cell types. Example species of Gamma retroviruses include the murine leukemia viruses (MLVs) and the feline leukemia viruses (FeLV).

[00458] In some embodiments, gamma-retroviral vectors derived from a mammalian gamma retrovirus such as murine leukemia viruses (MLVs), are recombinant. The MLV families of gamma retroviruses include the ecotropic, amphotropic, xenotropic and polytropic subfamilies. Ecotropic viruses are able to infect only murine cells using mCAT-1 receptor. Examples of ecotropic viruses are Moloney MLV and AKV. Amphotropic viruses infect murine, human and other species through the Pit-2 receptor. One example of an amphotropic virus is the 4070A virus. Xenotropic and polytropic viruses utilize the same (Xprl) receptor, but differ in their species tropism. Xenotropic viruses such as NZB-9-1 infect human and other species but not murine species, whereas polytropic viruses such as focus-forming viruses (MCF) infect murine, human and other species.

[00459] Gamma-retroviral vectors may be produced in packaging cells by co-transfecting the cells with several plasmids including one encoding the retroviral structural and enzymatic (gag pol) polyprotein, one encoding the envelope (env) protein, and one encoding the vector mRNA comprising polynucleotide encoding the compositions of the present invention that is to be packaged in newly formed viral particles.

[00460] In some aspects, the recombinant gamma-retroviral vectors are pseudotyped with envelope proteins from other viruses. Envelope glycoproteins are incorporated in the outer lipid layer of the viral particles which can increase/alter the cell tropism. Exemplary envelop proteins include the gibbon ape leukemia virus envelope protein (GALV) or vesicular stomatitis virus G protein (VSV-G), or Simian endogenous retrovirus envelop protein, or Measles Virus H and F proteins, or Human immunodeficiency virus gp120 envelope protein, or cocal vesiculovirus envelop protein (See, e.g., U.S. application publication NO.: 2012/164118; the contents of which are incorporated herein by reference in its entirety). In other aspects, envelope glycoproteins may be genetically modified to incorporate targeting/binding ligands into gamma-retroviral vectors, binding ligands including, but not limited to, peptide ligands, single chain antibodies and growth factors (Waehler et al., Nat. Rev. Genet. 2007, 8(8):573-587; the contents of which are incorporated herein by reference in its entirety). These engineered glycoproteins can retarget vectors to cells expressing their corresponding target moieties. In other aspects, a "molecular bridge" may be introduced to direct vectors to specific cells. The molecular bridge has dual specificities: one end can recognize viral glycoproteins, and the other end can bind to the molecular determinant on the target cell. Such molecular bridges, for example ligand-receptor, avidin-biotin, and chemical conjugations, monoclonal antibodies and engineered fusogenic proteins, can direct the attachment of viral vectors to target cells for transduction (Yang et al., Biotechnol. Bioeng., 2008, 101(2): 357-368; and Maetzig et al., Viruses, 2011, 3, 677-713; the contents of each of which are incorporated herein by reference in their entirety).

[00461] In some embodiments, the recombinant gamma-retroviral vectors are self-inactivating (SIN) gammaretroviral vectors. The vectors are replication incompetent. SIN vectors may harbor a deletion within the 3' U3 region initially comprising enhancer/promoter activity. Furthermore, the 5' U3 region may be replaced with strong promoters (needed in the packaging cell line) derived from Cytomegalovirus or RSV, or an internal promoter of choice, and/or an enhancer element. The choice of the internal promoters may be made according to specific requirements of gene expression needed for a particular purpose of the invention.

[00462] In some embodiments, polynucleotides encoding the biocircuit, biocircuit components, effector module, SRE are inserted within the recombinant viral genome. The other components of the viral mRNA of a recombinant gamma-retroviral vector may be modified by insertion or removal of naturally occurring sequences (e.g., insertion of an IRES, insertion of a heterologous polynucleotide encoding a polypeptide or inhibitory nucleic acid of interest, shuffling of a more effective promoter from a different retrovirus or virus in place of the wild-type promoter and the like). In some examples, the recombinant gamma-retroviral vectors may comprise modified packaging signal, and/or primer binding site (PBS), and/or 5'-enhancer/promoter elements in the U3-region of the 5'- long terminal repeat (LTR), and/or 3'-SIN elements modified in the U3 region of the 3'-LTR. These modifications may increase the titers and the ability of infection.

[00463] Gamma retroviral vectors suitable for delivering biocircuit components, effector modules, SREs or payload constructs of the present invention may be selected from those disclosed in U.S. Pat. NOs.: 8,828,718; 7,585,676; 7,351,585; U.S. application publication NO.:

2007/048285; PCT application publication NOs.: W02010/113037; W02014/121005; W02015/056014; and EP Pat. NOs.: EP1757702; EP1757703 (the contents of each of which are incorporated herein by reference in their entirety). 3. Adeno-associated viral vectors (AAV)

[00464] In some embodiments, polynucleotides of present invention may be packaged into recombinant adeno-associated viral (rAAV) vectors. Such vectors or viral particles may be designed to utilize any of the known serotype capsids or combinations of serotype capsids. The serotype capsids may include capsids from any identified AAV serotypes and variants thereof, for example, AAV1, AAV2, AAV2G9, AAV3, AAV4, AAV4-4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12 and AAVrh10.

[00465] In one embodiment, the AAV serotype may be or have a sequence as described in United States Publication No. US20030138772, herein incorporated by reference in its entirety, such as, but not limited to, AAV1 (SEQ ID NO: 6 and 64 of US20030138772), AAV2 (SEQ ID NO: 7 and 70 of US20030138772), AAV3 (SEQ ID NO: 8 and 71 of US20030138772), AAV4 (SEQ ID NO: 63 of US20030138772), AAV5 (SEQ ID NO: 114 of US20030138772), AAV6 (SEQ ID NO: 65 of US20030138772), AAV7 (SEQ ID NO: 1-3 of US20030138772), AAV8 (SEQ ID NO: 4 and 95 of US20030138772), AAV9 (SEQ ID NO: 5 and 100 of US20030138772), AAV10(SEQ ID NO: 117 of US20030138772), AAV11 (SEQ ID NO: 118 of US20030138772), AAV12 (SEQ ID NO: 119 of US20030138772), AAVrh10 (amino acids 1 to 738 of SEQ ID NO: 81 of US20030138772) or variants thereof. Non-limiting examples of variants include SEQ ID NOs: 9, 27-45, 47-62, 66-69, 73-81, 84-94, 96, 97, 99, 101-113 of US20030138772, the contents of which are herein incorporated by reference in their entirety.

[00466] In one embodiment, the AAV serotype may have a sequence as described in Pulicherla et al. (Molecular Therapy, 2011, 19(6):1070-1078), U.S. Pat. NOs.: 6,156,303; 7,198,951; U.S. Patent Publication NOs.: US2015/0159173 and US2014/0359799; and International Patent Publication NOs.: W01998/011244, W02005/033321 and W02014/14422; the contents of each of which are incorporated herein by reference in their entirety.

[00467] AAV vectors include not only single stranded vectors but self-complementary AAV vectors (scAAVs). scAAV vectors contain DNA which anneals together to form double stranded vector genome. By skipping second strand synthesis, scAAVs allow for rapid expression in the cell.

[00468] The rAAV vectors may be manufactured by standard methods in the art such as by triple transfection, in sf9 insect cells or in suspension cell cultures of human cells such as HEK293 cells.

[00469] The biocircuits, biocircuit components, effector modules, SREs or payload constructs may be encoded in one or more viral genomes to be packaged in the AAV capsids taught herein.

[00470] Such vectors or viral genomes may also include, in addition to at least one or two ITRs (inverted terminal repeats), certain regulatory elements necessary for expression from the vector or viral genome. Such regulatory elements are well known in the art and include for example promoters, introns, spacers, stuffer sequences, and the like.

[00471] In some embodiments, more than one effector module or SRE (e.g. DD) may be encoded in a viral genome. 4. Oncolytic viral vector

[00472] In some embodiments, polynucleotides of present invention may be packaged into oncolytic viruses, such as vaccine viruses. Oncolytic vaccine viruses may include viral particles of a thymidine kinase (TK)-deficient, granulocyte macrophage (GM)-colony stimulating factor (CSF)-expressing, replication-competent vaccinia virus vector sufficient to induce oncolysis of cells in the tumor (e.g., US Pat. NO.: 9,226,977). 5. Messenger RNA (mRNA)

[00473] In some embodiments, the effector modules of the invention may be designed as a messenger RNA (mRNA). As used herein, the term "messenger RNA" (mRNA) refers to any polynucleotide which encodes a polypeptide of interest and which is capable of being translated to produce the encoded polypeptide of interest in vitro, in vivo, in situ or ex vivo. Such mRNA molecules may have the structural components or features of any of those taught in International Application number PCT/US2013/030062, the contents of which are incorporated herein by reference in its entirety.

[00474] Polynucleotides of the invention may also be designed as taught in, for example, Ribostem Limited in United Kingdom patent application serial number 0316089.2 filed on July 9, 2003 now abandoned, PCT application number PCT/GB2004/002981 filed on July 9, 2004 published as W02005005622, United States patent application national phase entry serial number 10/563,897 filed on June 8, 2006 published as US20060247195 now abandoned, and European patent application national phase entry serial number EP2004743322 filed on July 9, 2004 published as EP1646714 now withdrawn; Novozymes, Inc. in PCT application number

PCT/US2007/88060 filed on December 19, 2007 published as W02008140615, United States patent application national phase entry serial number 12/520,072 filed on July 2, 2009 published as US20100028943 and European patent application national phase entry serial number EP2007874376 filed on July 7, 2009 published as EP2104739; University of Rochester in PCT application number PCT/US2006/46120 filed on December 4, 2006 published as W02007064952 and United States patent application serial number 11/606,995 filed on December 1, 2006 published as US20070141030; BioNTech AG in European patent application serial number EP2007024312 filed December 14, 2007 now abandoned, PCT application number PCT/EP2008/01059 filed on December 12, 2008 published as W02009077134, European patent application national phase entry serial number EP2008861423 filed on June 2, 2010 published as EP2240572, United States patent application national phase entry serial number 12/,735,060 filed November 24, 2010 published as US20110065103, German patent application serial number DE 10 2005 046 490 filed September 28, 2005, PCT application PCT/EP2006/0448 filed September 28, 2006 published as W02007036366, national phase European patent EP1934345 published March, 21, 2012 and national phase US patent application serial number 11/992,638 filed August 14, 2009 published as 20100129877; Immune Disease Institute Inc. in United States patent application serial number 13/088,009 filed April 15, 2011 published as US20120046346 and PCT application PCT/US2011/32679 filed April 15, 2011 published as W020110130624; Shire Human Genetic Therapeutics in United States patent application serial number 12/957,340 filed on November 20, 2010 published as US20110244026; Sequitur Inc. in PCT application PCT/US1998/019492 filed on September 18, 1998 published as WO1999014346; The Scripps Research Institute in PCT application number PCT/US2010/00567 filed on February 24, 2010 published as W02010098861, and United States patent application national phase entry serial number 13/203,229 filed November 3, 2011 published as US20120053333; Ludwig Maximillians University in PCT application number PCT/EP2010/004681 filed on July 30, 2010 published as W02011012316; Cellscript Inc. in United States patent number 8,039,214 filed June 30, 2008 and granted October 18, 2011, United States patent application serial numbers 12/962,498 filed on December 7, 2010 published as US20110143436, 12/962,468 filed on December 7, 2010 published as US20110143397, 13/237,451 filed on September 20, 2011 published as US20120009649, and PCT applications PCT/US2010/59305 filed December 7, 2010 published as W02011071931 and PCT/US2010/59317 filed on December 7, 2010 published as W02011071936; The Trustees of the University of Pennsylvania in PCT application number PCT/US2006/32372 filed on August 21, 2006 published as WO2007024708, and United States patent application national phase entry serial number 11/990,646 filed on March 27, 2009 published as US20090286852; Curevac GMBH in German patent application serial numbers DE10 2001027 283.9 filed June 5, 2001, DE10 2001062 480.8 filed December 19, 2001, and DE 20 2006 051516 filed October 31, 2006 all abandoned, European patent numbers EP1392341 granted March 30, 2005 and EP1458410 granted January 2, 2008, PCT application numbers PCT/EP2002/06180 filed June 5, 2002 published as WO2002098443, PCT/EP2002/14577 filed on December 19, 2002 published as WO2003051401, PCT/EP2007/09469 filed on December 31, 2007 published as WO2008052770, PCT/EP2008/03033 filed on April 16, 2008 published as WO2009127230, PCT/EP2006/004784 filed on May 19, 2005 published as WO2006122828, PCT/EP2008/00081 filed on January 9, 2007 published as WO2008083949, and United States patent application serial numbers 10/729,830 filed on December 5, 2003 published as US20050032730, 10/870,110 filed on June 18, 2004 published as US20050059624, 11/914,945 filed on July 7, 2008 published as US20080267873, 12/446,912 filed on October 27, 2009 published as US2010047261 now abandoned, 12/522,214 filed on January 4, 2010 published as US20100189729, 12/787,566 filed on May 26, 2010 published as US20110077287, 12/787,755 filed on May 26, 2010 published as US20100239608, 13/185,119 filed on July 18, 2011 published as US20110269950, and 13/106,548 filed on May 12, 2011 published as US20110311472 all of which are herein incorporated by reference in their entirety.

[00475] In some embodiments, the effector modules may be designed as self-amplifying RNA. "Self-amplifying RNA" as used herein refers to RNA molecules that can replicate in the host resulting in the increase in the amount of the RNA and the protein encoded by the RNA. Such self-amplifying RNA may have structural features or components of any of those taught in International Patent Application Publication No. WO2011005799 (the contents of which are incorporated herein by reference in their entirety). VI. DOSING, DELIVERY AND ADMINISTRATIONS

[00476] The compositions of the invention may be delivered to a cell or a subject through one or more routes and modalities. The viral vectors containing one or more effector modules, SREs, immunotherapeutic agents and other components described herein may be used to deliver them to a cell and/or a subject. Other modalities may also be used such as mRNAs, plasmids, and as recombinant proteins.

1. Delivery to cells

[00477] In another aspect of the invention, polynucleotides encoding biocircuits, effector modules, SREs (e.g., DDs), payloads of interest (immunotherapeutic agents) and compositions of the invention and vectors comprising said polynucleotides may be introduced into cells such as immune effector cells.

[00478] In one aspect of the invention, polynucleotides encoding biocircuits, effector modules, SREs (e.g., DDs), payloads of interest (immunotherapeutic agents) and compositions of the invention, may be packaged into viral vectors or integrated into viral genomes allowing transient or stable expression of the polynucleotides. Preferable viral vectors are retroviral vectors including lentiviral vectors. In order to construct a retroviral vector, a polynucleotide molecule encoding a biocircuit, an effector module, a DD or a payload of interest (i.e. an immunotherapeutic agent) is inserted into the viral genome in the place of certain viral sequences to produce a virus that is replication-defective. The recombinant viral vector is then introduced into a packaging cell line containing the gag, pol, and env genes, but without the LTR and packaging components. The recombinant retroviral particles are secreted into the culture media, then collected, optionally concentrated, and used for gene transfer. Lentiviral vectors are especially preferred as they are capable of infecting both dividing and non-dividing cells.

[00479] Vectors may also be transferred to cells by non-viral methods by physical methods such as needles, electroporation, sonoporation, hyrdoporation; chemical carriers such as inorganic particles (e.g. calcium phosphate, silica, gold) and/or chemical methods. In some embodiments, synthetic or natural biodegradable agents may be used for delivery such as cationic lipids, lipid nano emulsions, nanoparticles, peptide based vectors, or polymer based vectors.

[00480] In some embodiments, the polypeptides of the invention may be delivered to the cell directly. In one embodiment, the polypeptides of the invention may be delivered using synthetic peptides comprising an endosomal leakage domain (ELD) fused to a cell penetration domain (CLD). The polypeptides of the invention are co introduced into the cell with the ELD-CLD synthetic peptide. ELDs facilitate the escape of proteins that are trapped in the endosome, into the cytosol. Such domains are derived proteins of microbial and viral origin and have been described in the art. CPDs allow the transport of proteins across the plasma membrane and have also been described in the art. The ELD-CLD fusion proteins synergistically increase the transduction efficiency when compared to the co-transduction with either domain alone. In some embodiments, a histidine rich domain may optionally be added to the shuttle construct as an additional method of allowing the escape of the cargo from the endosome into the cytosol. The shuttle may also include a cysteine residue at the N or C terminus to generate multimers of the fusion peptide. Multimers of the ELD-CLD fusion peptides generated by the addition of cysteine residue to the terminus of the peptide show even greater transduction efficiency when compared to the single fusion peptide constructs. The polypeptides of the invention may also be appended to appropriate localization signals to direct the cargo to the appropriate sub-cellular location e.g. nucleus. In some embodiments any of the ELDs, CLDs or the fusion ELD-CLD synthetic peptides taught in the International Patent Publication, W02016161516 and W02017175072 may be useful in the present invention (the contents of each of which are herein incorporated by reference in their entirety). 2. Dosing

[00481] The present invention provides methods comprising administering any one or more compositions for immunotherapy to a subject in need thereof. These may be administered to a subject using any amount and any route of administration effective for preventing or treating a clinical condition such as cancer, infection diseases and other immunodeficient diseases.

[00482] Compositions in accordance with the invention are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions of the present invention may be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective, or prophylactically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, previous or concurrent therapeutic interventions and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts.

[00483] Compositions of the invention may be used in varying doses to avoid T cell energy, prevent cytokine release syndrome and minimize toxicity associated with immunotherapy. For example, low doses of the compositions of the present invention may be used to initially treat patients with high tumor burden, while patients with low tumor burden may be treated with high and repeated doses of the compositions of the invention to ensure recognition of a minimal tumor antigen load. In another instance, the compositions of the present invention may be delivered in a pulsatile fashion to reduce tonic T cell signaling and enhance persistence in vivo. In some aspects, toxicity may be minimized by initially using low doses of the compositions of the invention, prior to administering high doses. Dosing may be modified if serum markers such as ferritin, serum C-reactive protein, IL6, IFN-y, and TNF-a are elevated.

[00484] In some embodiments, the neurotoxicity may be associated with CAR or TIL therapy. Such neurotoxicity may be associated CD19-CARs. Toxicity may be due to excessive T cell infiltration into the brain. In some embodiments, neurotoxicity may be alleviated by preventing the passage of T cells through the blood brain barrier. This can be achieved by the targeted gene deletion of the endogenous alpha-4 integrin inhibitors such as tysabri/natalizumab may also be useful in the present invention. 3. Administration

[00485] In some embodiments, the compositions for immunotherapy may be administered to cells ex vivo and subsequently administered to the subject. Immune cells can be isolated and expanded ex vivo using a variety of methods known in the art. For example, methods of isolating cytotoxic T cells are described in U.S. Pat. NOs. 6,805,861 and 6,531, 451; the contents of each of which are incorporated herein by reference in their entirety. Isolation of NK cells is described in U.S. Pat. NOs.: 7,435, 596; the contents of which are incorporated by reference herein in its entirety.

[00486] In some embodiments, compositions of the present invention, may be administered by any of the methods of administration taught in the copending commonly owned U.S. Provisional Patent Application No. 62/320,864 filed on 4/11/2016, or in US Provisional Application No. 62/466,596 filed March 3, 2017 and the International Publication W02017/180587, the contents of each of which are incorporated herein by reference in their entirety.

[00487] In some embodiments, depending upon the nature of the cells, the cells may be introduced into a host organism e.g. a mammal, in a wide variety of ways including by injection, transfusion, infusion, local instillation or implantation. In some aspects, the cells of the invention may be introduced at the site of the tumor. The number of cells that are employed will depend upon a number of circumstances, the purpose for the introduction, the lifetime of the cells, the protocol to be used, for example, the number of administrations, the ability of the cells to multiply, or the like. The cells may be in a physiologically-acceptable medium.

[00488] In some embodiments, the cells of the invention may be administrated in multiple doses to subjects having a disease or condition. The administrations generally effect an improvement in one or more symptoms of cancer or a clinical condition and/or treat or prevent cancer or clinical condition or symptom thereof.

[00489] In some embodiments, the compositions for immunotherapy may be administered in vivo. In some embodiments, polypeptides of the present invention comprising biocircuits, effector molecules, SREs, payloads of interest (immunotherapeutic agents) and compositions of the invention may be delivered in vivo to the subject. In vivo delivery of immunotherapeutic agents is well described in the art. For example, methods of delivery of cytokines are described in the E.P. Pat. No.: EP0930892 Al, the contents of which are incorporated herein by reference.

[00490] In one embodiment, the payloads of the present invention may be administered in conjunction with inhibitors of SHP-1 and/or SHP-2. The tyrosine-protein phosphatase SHP1 (also known as PTPN6) and SHP2 (also known as PTPN11) are involved in the Programmed Cell Death (PD1) inhibitory signaling pathway. The intracellular domain of PD1 contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). ITSM has been shown to recruit SHP-1 and 2. This generates negative costimulatory micro clusters that induce the dephosphorylation of the proximal TCR signaling molecules, thereby resulting in suppression of T cell activation, which can lead to T cell exhaustion. In one embodiment, inhibitors of SHP-1 and 2 may include expressing dominant negative versions of the proteins in T cells, TILs or other cell types to relieve exhaustion. Such mutants can bind to the endogenous, catalytically active proteins, and inhibit their function. In one embodiment, the dominant negative mutant of SHP-1 and/ or SHP-2 lack the phosphatase domain required for catalytic activity. In some embodiments, any of the dominant negative SHP 1 mutants taught Bergeron S et al. (2011). Endocrinology. 2011 Dec;152(12):4581-8.;Dustin JB et al. (1999) J Immunol. Mar 1;162(5):2717-24.; Berchtold S (1998) Mol Endocrinol. Apr;12(4):556-67 and Schram et al. (2012) Am J Physiol Heart Circ Physiol. 1;302(1):H231-43.; may be useful in the invention (the contents of each of which are incorporated by reference in their entirety). Routes of delivery

[00491] The pharmaceutical compositions, biocircuits, biocircuit components, effector modules including their SREs (e.g., DDs), payloads (i.e. immunotherapeutic agents), vectors and cells of the present invention may be administered by any route to achieve a therapeutically effective outcome.

[00492] These include, but are not limited to enteral (into the intestine), gastroenteral, epidural (into the dura matter), oral (by way of the mouth), transdermal, peridural, intracerebral (into the cerebrum), intracerebroventricular (into the cerebral ventricles), epicutaneous (application onto the skin), intradermal, (into the skin itself), subcutaneous (under the skin), nasal administration (through the nose), intravenous (into a vein), intravenous bolus, intravenous drip, intra-arterial (into an artery), intramuscular (into a muscle), intracranial (into the heart), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intraperitoneal, (infusion or injection into the peritoneum), intrasinal infusion, intravitreal, (through the eye), intravenous injection (into a pathologic cavity) intracavitary (into the base of the penis), intravaginal administration, intrauterine, extra-amniotic administration, transdermal (diffusion through the intact skin for systemic distribution), transmucosal (diffusion through a mucous membrane), transvaginal, insufflation (snorting), sublingual, sublabial, enema, eye drops (onto the conjunctiva), in ear drops, auricular (in or by way of the ear), buccal (directed toward the cheek), conjunctival, cutaneous, dental (to a tooth or teeth), electro-osmosis, endocervical, endosinusial, endotracheal, extracorporeal, hemodialysis, infiltration, interstitial, intra-abdominal, intra-amniotic, intra articular, intrabiliary, intrabronchial, intrabursal, intracartilaginous (within a cartilage), intracaudal (within the cauda equine), intracisternal (within the cisterna magna cerebellomedularis), intracorneal (within the comea), dental intracomal, intracoronary (within the coronary arteries), intracorporus cavemosum (within the dilatable spaces of the corporus cavemosa of the penis), intradiscal (within a disc), intraductal (within a duct of a gland), intraduodenal (within the duodenum), intradural (within or beneath the dura), intraepidermal (to the epidermis), intraesophageal (to the esophagus), intragastric (within the stomach), intragingival (within the gingivae), intraileal (within the distal portion of the small intestine), intralesional (within or introduced directly to a localized lesion), intraluminal (within a lumen of a tube), intralymphatic (within the lymph), intramedullary (within the marrow cavity of a bone), intrameningeal (within the meninges), intramyocardial (within the myocardium), intraocular (within the eye), intraovarian (within the ovary), intrapericardial (within the pericardium), intrapleural (within the pleura), intraprostatic (within the prostate gland), intrapulmonary (within the lungs or its bronchi), intrasinal (within the nasal or periorbital sinuses), intraspinal (within the vertebral column), intrasynovial (within the synovial cavity of a joint), intratendinous (within a tendon), intratesticular (within the testicle), intrathecal (within the cerebrospinal fluid at any level of the cerebrospinal axis), intrathoracic (within the thorax), intratubular (within the tubules of an organ), intratumor (within a tumor), intratympanic (within the aurus media), intravascular (within a vessel or vessels), intraventricular (within a ventricle), iontophoresis (by means of electric current where ions of soluble salts migrate into the tissues of the body), irrigation (to bathe or flush open wounds or body cavities), laryngeal (directly upon the larynx), nasogastric (through the nose and into the stomach), occlusive dressing technique (topical route administration which is then covered by a dressing which occludes the area), ophthalmic (to the external eye), oropharyngeal (directly to the mouth and pharynx), parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, respiratory (within the respiratory tract by inhaling orally or nasally for local or systemic effect), retrobulbar (behind the pons or behind the eyeball), intramyocardial (entering the myocardium), soft tissue, subarachnoid, subconjunctival, submucosal, topical, transplacental (through or across the placenta), transtracheal (through the wall of the trachea), transtympanic (across or through the tympanic cavity), ureteral (to the ureter), urethral (to the urethra), vaginal, caudal block, diagnostic, nerve block, biliary perfusion, cardiac perfusion, photopheresis or spinal. VII. DEFINITIONS

[00493] At various places in the present specification, features or functions of the compositions of the present disclosure are disclosed in groups or in ranges. It is specifically intended that the present disclosure include each and every individual sub combination of the members of such groups and ranges. The following is a non-limiting list of term definitions.

[00494] Activity: As used herein, the term "activity" refers to the condition in which things are happening or being done. Compositions of the invention may have activity and this activity may involve one or more biological events. In some embodiments, biological events may include cell signaling events. In some embodiments, biological events may include cell signaling events associated protein interactions with one or more corresponding proteins, receptors, small molecules or any of the biocircuit components described herein.

[00495] Adoptive cell therapy (ACT): The terms "Adoptive cell therapy" or "Adoptive cell transfer", as used herein, refer to a cell therapy involving in the transfer of cells into a patient, wherein cells may have originated from the patient, or from another individual, and are engineered (altered) before being transferred back into the patient. The therapeutic cells may be derived from the immune system, such as Immune effector cells: CD4+ T cell; CD8+ T cell, Natural Killer cell (NK cell); and B cells and tumor infiltrating lymphocytes (TILs) derived from the resected tumors. Most commonly transferred cells are autologous anti-tumor T cells after ex vivo expansion or manipulation. For example, autologous peripheral blood lymphocytes can be genetically engineered to recognize specific tumor antigens by expressing T-cell receptors (TCR) or chimeric antigen receptor (CAR).

[00496] Agent: As used herein, the term "agent" refers to a biological, pharmaceutical, or chemical compound. Non-limiting examples include simple or complex organic or inorganic molecule, a peptide, a protein, an oligonucleotide, an antibody, an antibody derivative, antibody fragment, a receptor, and soluble factor.

[00497] Agonist: the term "agonist" as used herein, refers to a compound that, in combination with a receptor, can produce a cellular response. An agonist may be a ligand that directly binds to the receptor. Alternatively, an agonist may combine with a receptor indirectly by, for example, (a) forming a complex with another molecule that directly binds to the receptor, or (b) otherwise resulting in the modification of another compound so that the other compound directly binds to the receptor. An agonist may be referred to as an agonist of a particular receptor or family of receptors, e.g., agonist of a co-stimulatory receptor.

[00498] Antagonist: the term "antagonist" as used herein refers to any agent that inhibits or reduces the biological activity of the target(s) it binds.

[00499] Antigen: the term "antigen" as used herein is defined as a molecule that provokes an immune response when it is introduced into a subject or produced by a subject such as tumor antigens which arise by the cancer development itself. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells such as cytotoxic T lymphocytes and T helper cells, or both. An antigen can be derived from organisms, subunits of proteins/antigens, killed or inactivated whole cells or lysates. In the context of the invention, the terms "antigens of interest" or "desired antigens" refers to those proteins and/or other biomolecules provided herein that are immunospecifically bound or interact with antibodies of the present invention and/or fragments, mutants, variants, and/or alterations thereof described herein. In some embodiments, antigens of interest may comprise any of the polypeptides or payloads or proteins described herein, or fragments or portions thereof.

[00500] Approximately: As used herein, the term "approximately" or "about," as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term "approximately" or "about" refers to a range of values that fall within 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100 of a possible value).

[00501] Associated with: As used herein, the terms "associated with," "conjugated ""linked," "attached," and "tethered," when used with respect to two or more moieties, mean that the moieties are physically associated or connected with one another, either directly or via one or more additional moieties that serve as linking agents, to form a structure that is sufficiently stable so that the moieties remain physically associated under the conditions in which the structure is used, e.g., physiological conditions. An "association" need not be strictly through direct covalent chemical bonding. It may also suggest ionic or hydrogen bonding or a hybridization based connectivity sufficiently stable such that the "associated" entities remain physically associated.

[00502] Autologous: the term "autologous" as used herein is meant to refer to any material derived from the same individual to which it is later to be re-introduced into the individual.

[00503] Barcode: the term "barcode" as used herein refers to polynucleotide or amino acid sequence that distinguishes one polynucleotide or amino acid from another.

[00504] Cancer: the term "cancer" as used herein refers a broad group of various diseases characterized by the uncontrolled growth of abnormal cells in the body. Unregulated cell division and growth results in the formation of malignant tumors that invade neighboring tissues ultimately metastasize to distant parts of the body through the lymphatic system or bloodstream.

[00505] Co-stimulatorymolecule: As used herein, in accordance with its meaning in immune T cell activation, refers to a group of immune cell surface receptor/ligands which engage between T cells and APCs and generate a stimulatory signal in T cells which combines with the stimulatory signal in T cells that results from T cell receptor (TCR) recognition of antigen/MHC complex (pMHC) on APCs

[00506] Cytokines: the term "cytokines", as used herein, refers to a family of small soluble factors with pleiotropic functions that are produced by many cell types that can influence and regulate the function of the immune system.

[00507] Delivery: the term "delivery" as used herein refers to the act or manner of delivering a compound, substance, entity, moiety, cargo or payload. A "delivery agent" refers to any agent which facilitates, at least in part, the in vivo delivery of one or more substances (including, but not limited to a compound and/or compositions of the present invention) to a cell, subject or other biological system cells.

[00508] Destabilized: As used herein, the term "destable," "destabilize," "destabilizing region" or "destabilizing domain" means a region or molecule that is less stable than a starting, reference, wild-type or native form of the same region or molecule.

[00509] Engineered: As used herein, embodiments of the invention are "engineered" when they are designed to have a feature or property, whether structural or chemical, that varies from a starting point, wild type or native molecule.

[00510] Expression: As used herein, "expression" of a nucleic acid sequence refers to one or more of the following events: (1) production of an RNA template from a DNA sequence (e.g., by transcription); (2) processing of an RNA transcript (e.g., by splicing, editing, 5' cap formation, and/or 3' end processing); (3) translation of an RNA into a polypeptide or protein; (4) folding of a polypeptide or protein; and (5) post-translational modification of a polypeptide or protein.

[00511] Feature: As used herein, a "feature" refers to a characteristic, a property, or a distinctive element.

[00512] Formulation:As used herein, a "formulation" includes at least a compound and/or composition of the present invention and a delivery agent.

[00513] Fragment: A "fragment," as used herein, refers to a portion. For example, fragments of proteins may comprise polypeptides obtained by digesting full-length protein. In some embodiments, a fragment of a protein includes at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17,18,19,20,25,30,35,40,45,50,55,60,65,70,75,80,85,90,95,100,150,200,250or more amino acids. In some embodiments, fragments of an antibody include portions of an antibody.

[00514] Functional:As used herein, a "functional" biological molecule is a biological entity with a structure and in a form in which it exhibits a property and/or activity by which it is characterized.

[00515] Immune cells: the term "an immune cell", as used herein, refers to any cell of the immune system that originates from a hematopoietic stem cell in the bone marrow, which gives rise to two major lineages, a myeloid progenitor cell (which give rise to myeloid cells such as monocytes, macrophages, dendritic cells, megakaryocytes and granulocytes) and a lymphoid progenitor cell (which give rise to lymphoid cells such as T cells, B cells and natural killer (NK) cells). Exemplary immune system cells include a CD4+ T cell, a CD8+ T cell, a CD4- CD8 double negative T cell, a T y6 cell, a Ta cell, a regulatory T cell, a natural killer cell, and a dendritic cell. Macrophages and dendritic cells may be referred to as "antigen presenting cells" or "APCs," which are specialized cells that can activate T cells when a major histocompatibility complex (MHC) receptor on the surface of the APC complexed with a peptide interacts with a TCR on the surface of a T cell.

[00516] Immunotherapy: the term "immunotherapy" as used herein, refers to a type of treatment of a disease by the induction or restoration of the reactivity of the immune system towards the disease.

[00517] Immunotherapeutic agent: the term "immunotherapeutic agent" as used herein, refers to the treatment of disease by the induction or restoration of the reactivity of the immune system towards the disease with a biological, pharmaceutical, or chemical compound.

[00518] In vitro: As used herein, the term "in vitro" refers to events that occur in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, in a Petri dish, etc., rather than within an organism (e.g., animal, plant, or microbe).

[00519] In vivo: As used herein, the term "in vivo" refers to events that occur within an organism (e.g., animal, plant, or microbe or cell or tissue thereof).

[00520] Linker: As used herein, a linker refers to a moiety that connects two or more domains, moieties or entities. In one embodiment, a linker may comprise 10 or more atoms. In a further embodiment, a linker may comprise a group of atoms, e.g., 10-1,000 atoms, and can be comprised of the atoms or groups such as, but not limited to, carbon, amino, alkylamino, oxygen, sulfur, sulfoxide, sulfonyl, carbonyl, and imine. In some embodiments, a linker may comprise one or more nucleic acids comprising one or more nucleotides. In some embodiments, the linker may comprise an amino acid, peptide, polypeptide or protein. In some embodiments, a moiety bound by a linker may include, but is not limited to an atom, a chemical group, a nucleoside, a nucleotide, a nucleobase, a sugar, a nucleic acid, an amino acid, a peptide, a polypeptide, a protein, a protein complex, a payload (e.g., a therapeutic agent). or a marker (including, but not limited to a chemical, fluorescent, radioactive or bioluminescent marker). The linker can be used for any useful purpose, such as to form multimers or conjugates, as well as to administer a payload, as described herein. Examples of chemical groups that can be incorporated into the linker include, but are not limited to, alkyl, alkenyl, alkynyl, amido, amino, ether, thioether, ester, alkylene, heteroalkylene, aryl, or heterocyclyl, each of which can be optionally substituted, as described herein. Examples of linkers include, but are not limited to, unsaturated alkanes, polyethylene glycols (e.g., ethylene or propylene glycol monomeric units, e.g., diethylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, tetraethylene glycol, or tetraethylene glycol), and dextran polymers, Other examples include, but are not limited to, cleavable moieties within the linker, such as, for example, a disulfide bond (-S-S-) or an azo bond (-N=N-), which can be cleaved using a reducing agent or photolysis. Non-limiting examples of a selectively cleavable bonds include an amido bond which may be cleaved for example by the use of tris(2 carboxyethyl) phosphine (TCEP), or other reducing agents, and/or photolysis, as well as an ester bond which may be cleaved for example by acidic or basic hydrolysis.

[00521] Checkpoint/factor: As used herein, a checkpoint factor is any moiety or molecule whose function acts at the junction of a process. For example, a checkpoint protein, ligand or receptor may function to stall or accelerate the cell cycle.

[00522] Metabolite: Metabolites are the intermediate products of metabolic reactions catalyzed by enzymes that naturally occur within cells. This term is usually used to describe small molecules, fragments of larger biomolecules or processed products.

[00523] Modified: As used herein, the term "modified" refers to a changed state or structure of a molecule or entity as compared with a parent or reference molecule or entity. Molecules may be modified in many ways including chemically, structurally, and functionally. In some embodiments, compounds and/or compositions of the present invention are modified by the introduction of non-natural amino acids.

[00524] Mutation: As used herein, the term "mutation" refers to a change and/or alteration. In some embodiments, mutations may be changes and/or alterations to proteins (including peptides and polypeptides) and/or nucleic acids (including polynucleic acids). In some embodiments, mutations comprise changes and/or alterations to a protein and/or nucleic acid sequence. Such changes and/or alterations may comprise the addition, substitution and or deletion of one or more amino acids (in the case of proteins and/or peptides) and/or nucleotides (in the case of nucleic acids and or polynucleic acids e.g., polynucleotides). In some embodiments, wherein mutations comprise the addition and/or substitution of amino acids and/or nucleotides, such additions and/or substitutions may comprise 1 or more amino acid and/or nucleotide residues and may include modified amino acids and/or nucleotides. The resulting construct, molecule or sequence of a mutation, change or alteration may be referred to herein as a mutant.

[00525] Neoantigen: the term "neoantigen", as used herein, refers to a tumor antigen that is present in tumor cells but not normal cells and do not induce deletion of their cognate antigen specific T cells in thymus (i.e., central tolerance). These tumor neoantigens may provide a "foreign" signal, similar to pathogens, to induce an effective immune response needed for cancer immunotherapy. A neoantigen may be restricted to a specific tumor. A neoantigen be a peptide/protein with a missense mutation (missense neoantigen), or a new peptide with long, completely novel stretches of amino acids from novel open reading frames (neoORFs). The neoORFs can be generated in some tumors by out-of-frame insertions or deletions (due to defects in DNA mismatch repair causing microsatellite instability), gene-fusion, read-through mutations in stop codons, or translation of improperly spliced RNA (e.g., Saeterdal et al., Proc Natl Acad Sci USA, 2001, 98: 13255-13260).

[00526] Off-target: As used herein, "off target" refers to any unintended effect on any one or more target, gene, cellular transcript, cell, and/or tissue.

[00527] Operably linked: As used herein, the phrase "operably linked" refers to a functional connection between two or more molecules, constructs, transcripts, entities, moieties or the like.

[00528] Payload or payload ofinterest (POI): the terms "payload" and "payload of interest (P01)", as used herein, are used interchangeable. A payload of interest (POI) refers to any protein or compound whose function is to be altered. In the context of the present invention, the POI is a component in the immune system, including both innate and adaptive immune systems. Payloads of interest may be a protein, a fusion construct encoding a fusion protein, or non coding gene, or variant and fragment thereof. Payload of interest may, when amino acid based, may be referred to as a protein of interest.

[00529] Pharmaceuticallyacceptable excipients: the term "pharmaceutically acceptable excipient," as used herein, refers to any ingredient other than active agents (e.g., as described herein) present in pharmaceutical compositions and having the properties of being substantially nontoxic and non-inflammatory in subjects. In some embodiments, pharmaceutically acceptable excipients are vehicles capable of suspending and/or dissolving active agents. Excipients may include, for example: antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (colors), emollients, emulsifiers, fillers (diluents), film formers or coatings, flavors, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, sorbents, suspending or dispersing agents, sweeteners, and waters of hydration. Exemplary excipients include, but are not limited to: butylated hydroxytoluene (BHT), calcium carbonate, calcium phosphate (dibasic), calcium stearate, croscarmellose, crosslinked polyvinyl pyrrolidone, citric acid, crospovidone, cysteine, ethylcellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methyl paraben, microcrystalline cellulose, polyethylene glycol, polyvinyl pyrrolidone, povidone, pregelatinized starch, propyl paraben, retinyl palmitate, shellac, silicon dioxide, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E, vitamin C, and xylitol.

[00530] Pharmaceuticallyacceptable salts: Pharmaceutically acceptable salts of the compounds described herein are forms of the disclosed compounds wherein the acid or base moiety is in its salt form (e.g., as generated by reacting a free base group with a suitable organic acid). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. Pharmaceutically acceptable salts include the conventional non-toxic salts, for example, from non-toxic inorganic or organic acids. In some embodiments, a pharmaceutically acceptable salt is prepared from a parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, Pharmaceutical Salts: Properties, Selection, and Use, P.H. Stahl and C.G. Wermuth (eds.), Wiley-VCH, 2008, and Berge et al., Journal of Pharmaceutical Science, 66, 1-19 (1977), each of which is incorporated herein by reference in its entirety. Pharmaceutically acceptable solvate: The term "pharmaceutically acceptable solvate," as used herein, refers to a crystalline form of a compound wherein molecules of a suitable solvent are incorporated in the crystal lattice. For example, solvates may be prepared by crystallization, recrystallization, or precipitation from a solution that includes organic solvents, water, or a mixture thereof. Examples of suitable solvents are ethanol, water (for example, mono-, di-, and tri-hydrates), N-methylpyrrolidinone (NMP), dimethyl sulfoxide (DMSO), N, N'-dimethylformamide (DMF), N, N'-dimethylacetamide (DMAC), 1,3-dimethyl 2-imidazolidinone (DMEU), 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPU), acetonitrile (ACN), propylene glycol, ethyl acetate, benzyl alcohol, 2-pyrrolidone, benzyl benzoate, and the like. When water is the solvent, the solvate is referred to as a "hydrate." In some embodiments, the solvent incorporated into a solvate is of a type or at a level that is physiologically tolerable to an organism to which the solvate is administered (e.g., in a unit dosage form of a pharmaceutical composition).

[00531] Stable: As used herein "stable" refers to a compound or entity that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and preferably capable of formulation into an efficacious therapeutic agent.

[00532] Stabilized: As used herein, the term "stabilize", "stabilized," "stabilized region" means to make or become stable. In some embodiments, stability is measured relative to an absolute value. In some embodiments, stability is measured relative to a secondary status or state or to a reference compound or entity.

[00533] StandardCAR: As used herein, the term "standard CAR" refers to the standard design of a chimeric antigen receptor. The components of a CAR fusion protein including the extracellular scFv fragment, transmembrane domain and one or more intracellular domains are linearly constructed as a single fusion protein.

[00534] Stimulus response element (SRE): the term "stimulus response element (SRE), as used herein, is a component of an effector module which is joined, attached, linked to or associated with one or more payloads of the effector module and in some instances, is responsible for the responsive nature of the effector module to one or more stimuli. As used herein, the "responsive" nature of an SRE to a stimulus may be characterized by a covalent or non-covalent interaction, a direct or indirect association or a structural or chemical reaction to the stimulus. Further, the response of any SRE to a stimulus may be a matter of degree or kind. The response may be a partial response. The response may be a reversible response. The response may ultimately lead to a regulated signal or output. Such output signal may be of a relative nature to the stimulus, e.g., producing a modulatory effect of between 1 and 100 or a factored increase or decrease such as 2 fold, 3-fold, 4-fold, 5-fold, 10-fold or more. One non-limiting example of an SRE is a destabilizing domain (DD).

[00535] Subject: As used herein, the term "subject" or "patient" refers to any organism to which a composition in accordance with the invention may be administered, e.g., for experimental, diagnostic, prophylactic, and/or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and humans) and/or plants.

[00536] T cell: A T cell is an immune cell that produces T cell receptors (TCRs). T cells can be naive (not exposed to antigen; increased expression of CD62L, CCR7, CD28, CD3, CD127, and CD45RA, and decreased expression of CD45RO as compared to TcM), memory T cells (TM) (antigen-experienced and long-lived), and effector cells (antigen-experienced, cytotoxic). TM can be further divided into subsets of central memory T cells (TcM, increased expression of CD62L, CCR7, CD28, CD127, CD45RO, and CD95, and decreased expression of CD54RA as compared to naive T cell and effector memory T cells (TEM, decreased expression of CD62L, CCR7, CD28, CD45RA, and increased expression of CD127 as compared to naive T cells or TcM). Effector T cells (TE) refers to antigen-experienced CD8+ cytotoxic T lymphocytes that have decreased expression of CD62L, CCR7, CD28, and are positive for granzyme and perforin as compared to TcM. Other exemplary T cells include regulatory T cells, such as CD4+ CD25+ (Foxp3+) regulatory T cells and Treg17 cells, as well as Trl, Th3, CD8+CD28-, and Qa-1 restricted T cells.

[00537] T cell receptor: T cell receptor (TCR) refers to an immunoglobulin superfamily member having a variable antigen binding domain, a constant domain, a transmembrane region, and a short cytoplasmic tail, which is capable of specifically binding to an antigen peptide bound to a MHC receptor. A TCR can be found on the surface of a cell or in soluble form and generally is comprised of a heterodimer having a and P chains (also known as TCRa and TCR, respectively), or y and 6 chains (also known as TCRy and TCR, respectively). The extracellular portion of TCR chains (e.g., a-chain, p-chain) contains two immunoglobulin domains, a variable domain (e.g., a-chain variable domain or Va, p-chain variable domain or Vp) at the N-terminus, and one constant domain (e.g., a-chain constant domain or Ca and p-chain constant domain or Cp,) adjacent to the cell membrane. Similar to immunoglobulin, the variable domains contain complementary determining regions (CDRs) separated by framework regions (FRs). A TCR is usually associated with the CD3 complex to form a TCR complex. As used herein, the term

"TCR complex" refers to a complex formed by the association of CD3 with TCR. For example, a TCR complex can be composed of a CD3y chain, a CD36 chain, two CD3 chains, a homodimer of CD3Q chains, a TCRa chain, and a TCRP chain. Alternatively, a TCR complex can be composed of a CD3y chain, a CD36 chain, two CD3c chains, a homodimer of CD3Q chains, a TCRy chain, and a TCR6 chain. A "component of a TCR complex," as used herein, refers to a TCR chain (i.e., TCRa, TCR, TCRy or TCR), a CD3 chain (i.e., CD37, CD36, CD3c or CD3(), or a complex formed by two or more TCR chains or CD3 chains (e.g., a complex of TCRa and TCR, a complex of TCRy and TCR, a complex of CD3c and CD36, a complex of CD3y and CD3, or a sub-TCR complex of TCRa, TCR3, CD3y, CD36, and two CD3 chains.

[00538] Therapeutically effective amount: As used herein, the term "therapeutically effective amount" means an amount of an agent to be delivered (e.g., nucleic acid, drug, therapeutic agent, diagnostic agent, prophylactic agent, etc.) that is sufficient, when administered to a subject suffering from or susceptible to an infection, disease, disorder, and/or condition, to treat, improve symptoms of, diagnose, prevent, and/or delay the onset of the infection, disease, disorder, and/or condition. In some embodiments, a therapeutically effective amount is provided in a single dose. In some embodiments, a therapeutically effective amount is administered in a dosage regimen comprising a plurality of doses. Those skilled in the art will appreciate that in some embodiments, a unit dosage form may be considered to comprise a therapeutically effective amount of a particular agent or entity if it comprises an amount that is effective when administered as part of such a dosage regimen.

[00539] Treatment or treating: As used herein, the terms "treatment" or "treating" denote an approach for obtaining a beneficial or desired result including and preferably a beneficial or desired clinical result. Such beneficial or desired clinical results include, but are not limited to, one or more of the following: reducing the proliferation of (or destroying) cancerous cells or other diseased, reducing metastasis of cancerous cells found in cancers, shrinking the size of the tumor, decreasing symptoms resulting from the disease, increasing the quality of life of those suffering from the disease, decreasing the dose of other medications required to treat the disease, delaying the progression of the disease, and/or prolonging survival of individuals.

[00540] Tune: As used herein, the term "tune" means to adjust, balance or adapt one thing in response to a stimulus or toward a particular outcome. In one non-limiting example, the SREs and/or DDs of the present invention adjust, balance or adapt the function or structure of compositions to which they are appended, attached or associated with in response to particular stimuli and/or environments. EQUIVALENTS AND SCOPE

[00541] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments in accordance with the invention described herein. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the appended claims.

[00542] In the claims, articles such as "a," "an," and "the" may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include "or" between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or the entire group members are present in, employed in or otherwise relevant to a given product or process.

[00543] It is also noted that the term "comprising" is intended to be open and permits but does not require the inclusion of additional elements or steps. When the term "comprising" is used herein, the term "consisting of' is thus also encompassed and disclosed.

[00544] Where ranges are given, endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[00545] In addition, it is to be understood that any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Since such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the compositions of the invention (e.g., any antibiotic, therapeutic or active ingredient; any method of production; any method of use; etc.) can be excluded from any one or more claims, for any reason, whether or not related to the existence of prior art.

[00546] It is to be understood that the words which have been used are words of description rather than limitation, and that changes may be made within the purview of the appended claims without departing from the true scope and spirit of the invention in its broader aspects. EXAMPLES Example 1. Generation of novel ligand responsive SREs or DDs by mutagenesis screening Study design

[00547] To engineer constructs that display ligand dependent stability, a candidate ligand binding domain (LBD) is selected and a cell-based screen using yellow fluorescent protein (YFP) as a reporter for protein stability is designed to identify mutants of the candidate LBD possessing the desired characteristics of a destabilizing domain: low protein levels in the absence of a ligand of the LBD, (i.e., low basal stability), large dynamic range, robust and predictable dose-response behavior, and rapid kinetics of degradation (Banaszynski, et al., (2006) Cell; 126(5): 995-1004). The candidate LBD binds to a desired ligand but not endogenous signaling molecules.

[00548] The candidate LBD sequence (as a template) is first mutated using a combination of nucleotide analog mutagenesis and error-prone PCR, to generate libraries of mutants based on the template candidate domain sequence. The libraries generated are cloned in-frame at either the 5'- or 3'-ends of the YFP gene, and a retroviral expression system is used to stably transduce the libraries of YFP fusions into NIH3T3 fibroblasts.

[00549] The transduced NIH3T3 cells are subjected to three to four rounds of sorting using fluorescence-activated cell sorting (FACS) to screen the libraries of candidate DDs. Transduced NIH3T3 cells are cultured in the absence of the high affinity ligand of the ligand binding domain (LBD), and cells that exhibit low levels of YFP expression are selected through FACS. Screening Strategy I

[00550] The selected cell population is cultured in the presence of the high affinity ligand of the ligand binding domain for a period of time (e.g., 24 hours), at which point cells are sorted again by FACS. Cells that exhibit high levels of YFP expression are selected through FACS and the selected cell population is split into two groups and treated again with the high affinity ligand of the ligand binding domain at different concentrations; one group is treated with the lower concentration of the ligand and the other is treated with a high concentration of the ligand, for a period of time (e.g., 24 hours), at which point cells are sorted again by FACS. Cells expressing mutants that are responsive to lower concentrations of the ligand are isolated.

[00551] The isolated cells responsive to the lower concentration of the ligand are treated with the ligand again and cells exhibiting low fluorescence levels are collected 4 hours following removal of the ligand from the media. This fourth sorting is designed to enrich cells that exhibit fast kinetics of degradation (Iwamoto et al., Chem Biol. 2010 Sep 24; 17(9): 981-988). Screening Strategy II

[00552] The selected cell population is subject to additional one or more sorts by FACS in the absence of high affinity ligand of LBD and cells that exhibit low levels of YFP expression are selected for further analysis. Cells are treated with high affinity ligand of the ligand binding domain, for a period of time (e.g. 24 hours), and sorted again by FACS. Cells expressing high levels of YFP are selected for through FACS. Cells with high expression of YFP are treated with ligand again and cells exhibiting low fluorescence levels are collected 4 hours following removal of the ligand from the media to enrich cells that exhibit fast kinetics of degradation. Any of the sorting steps may be repeated to identify DDs with ligand dependent stability.

[00553] The cells are recovered after sorting. The identified candidate cells are harvested and the genomic DNA is extracted. The candidate DDs are amplified by PCR and isolated. The candidate DDs are sequenced and compared to the LBD template to identify the mutations in candidate DDs. Example 2. DD regulated recombinant IL12 expression

[00554] FKBP (DD)-IL12 and DHFR (DD)-IL12 constructs were packaged into pLVX IRES Puro lentiviral vectors with CMV, EFla, or PGK promoters or without a promoter. The IL12 consists of two subunits, p40 and p35 which are separated by a linker. A p40 signal sequence was inserted next to the DD or IL12. In several constructs, a furin protease cleavage site or a modified furin site was included.

[00555] HEK293T cells were transiently transfected with 200ng or 1pg of FKBP-IL12 plasmids (OT-IL12-001 to OT-IL12-005), and subsequently treated with 10IpM Shield-i or vehicle control for 6 hours. Culture media was collected from transfected cells and diluted 1:50 to measure IL12 levels using p40 ELISA. The stabilization ratio was defined as fold change in IL12 expression with ligand treatment compared to treatment with DMSO (i.e. in the absence of ligand) with the same construct. Stabilization ratio greater than 1 is desired. The average IL12 ELISA readings and stabilization ratio are presented in Table 15. Table 15: Ligand dependent IL12 induction Construct Vehicle l1 M Stabilization ID Shield-1 ratio

OT-1L12-001 1289.61 1748.95 1.36 OT-1L12-002 18.01 50.73 2.82 OT-1L12-003 1762.55 2138.25 1.21 OT-1L12-004 385.95 1567.62 4.06 OT-1L12-005 1188.42 2670.80 2.25 HEK293T -12.921 -22.015 |

[00556] OT-IL12-002 and OT- IL12-004 showed low level of IL12 expression in the absence of ligand when compared to IL12 levels in HEK 293T parental cells. Treatment with Shield-I resulted in an increase in IL12 levels in OT-IL12-002, OT-IL12-004, and OT-IL12-005 constructs and a stabilization ratio between 2 and 4. These data show that OT-IL12-002 and OT IL12-004 are destabilized in the absence of these constructs are stabilized by Shield-1.

[00557] IL12 expression was measured in cells following stable transduction. 500,000 cells stably transduced with OT-IL12-004 were plated in a 12 well plate and incubated overnight in growth media consisting of Dulbecco's Modified Eagle medium (DMEM) and 10% fetal bovine serum (FBS). The next day, cells were treated with 1IpM Shield-i or vehicle control for 6 or 24 hours. Following treatment with Shield-1, growth media was collected from the cells and diluted 10, 40, 160 or 640 fold and IL12 levels were quantified using IL12-p4 ELISA. The stabilization ratio was defined as fold change in IL12 expression with ligand treatment compared to treatment with DMSO (i.e. in the absence of ligand) with the same construct. Stabilization ratio greater than 1 is desired. The average IL12 ELISA readings and stabilization ratio at 6 hours are presented in Table 16. Table 16: Ligand dependent IL12 induction (6 hours) Media 6 hours dilution Vehicle Shield-1 Stabilization (fold) ratio 10 0.17 0.58 3.35 40 0.10 0.26 2.62 160 0.08 0.12 1.41 640 0.09 0.08 0.93

[00558] ILI2 stabilization ratio greater than 1 was observed at 10, 40 and 160-fold dilutions of media, indicating that IL12 is stabilized by Shield-i treatment at these dilutions at 6 hours.

[00559] The average ILI2 ELISA readings and stabilization ratio at 24 hours are presented in Table 17. Table 17: Ligand dependent IL12 induction (24 hours) 24 hours

Media Stabilization dilution Vehicle Shield-1 ratio (fold) 10 0.28 1.33 4.69 40 0.12 0.79 6.39 160 0.09 0.30 3.44 640 0.08 0.12 1.46

[00560] IL12 stabilization ratio was greater than 1 at all media dilutions tested and the highest stabilization ratio was observed at 40-fold dilution of media at 24 hours, suggesting ligand dependent stabilization.

[00561] To evaluate Shield-i dependent FKBP-1L12 induction over time, 2 million cells were plated in growth medium and incubated overnight in the presence of1PM Shield-i or vehicle control. Cells were then incubated for with the ligand for 2, 4,6, 8, 24, 48, or 72 hours and growth media was collected for the cells at all time points. Growth media was diluted 400-fold and IL12 levels were measured using IL12 p40 ELISA. The stabilization ratio was defined as fold change in IL12 expression with ligand treatment compared to treatment with DMSO (i.e. in the absence of ligand) with the same construct. Stabilization ratio greater than 1 is desired. Average IL12 ELISA readings and stabilization ratio are presented in Table 18. Table 18: IL12 induction over time Time Vehicle Shield-1 Stabilization (hrs) ratio 2 0.13 0.18 1.41 4 0.14 0.26 1.89 6 0.13 0.29 2.30 8 0.14 0.28 1.99 24 0.18 0.99 5.47 48 0.23 1.79 7.71 72 0.26 1.63 6.28

[00562] Stabilization ratio increased overtime and peaked at 48 hours, suggesting that IL12 is stabilized by Shield-i with increasing duration of ligand treatment.

[00563] To evaluate the dependence of FKBP-IL12 production on Shield-i dose levels, OT IL12-004 transduced HEK293T cells were plated at different densities (40,000 cells, 20,000 cells, 10,000 cells or 5,000 cells per well) onto a 96-well plate. Following overnight incubation, cells were treated with growth medium containing 0 to 0IpM Shield-i for 24 hours. Media was then collected, diluted 400-fold and FKBP-IL12 levels were measured using IL12-p40 ELISA. Average ILI2 ELISA readings are presented in Table 19.

Table 19: Dose and cell number dependent IL12 induction Shield-1 40000 20000 10000 5000 (JIM) cells/well cells/well cells/well cells/well 10 623.77 656.70 214.11 193.62 3.333333 670.64 618.10 273.74 207.55 1.111111 677.27 872.24 322.56 203.71 0.37037 368.17 582.71 250.49 172.50 0.123457 197.29 343.34 156.98 95.92 0.041152 171.50 205.68 63.79 48.89 0.013717 117.25 103.56 13.30 -2.35 0.004572 66.34 60.58 2.11 -8.53 0.001524 100.43 39.55 -13.58 -21.76 0 83.49 7.92 -21.76 -26.97

[00564] A dose dependent IL12 induction was observed at all cell numbers tested. IL12 induction increased with Shield-i up to a dose of pM; following which IL12 induction plateaued. Notably, greater IL12 induction was observed at 2000 and 4000 cells/well. Example 3. DD regulated recombinant IL12 mediated functions in HEK293T cells

[00565] HEK-Blue sensor cells (InvivoGen, San Diego, CA) were utilized to evaluate whether DD regulated IL12 is capable of regulating signaling downstream of IL12. In these cells, the IL12 receptor, STAT4 and downstream transcriptional elements are linked to a reporter gene such that IL12 signaling can be monitored. One million HEK 293T were transfected with 200ng of OT-IL12-003 plasmid using Lipofectamine 2000 (Thermo Fisher Scientific, Waltham, MA). 48 hours after transfection, cells were treated with growth media containing 10pM Shield-1, incubated for another 24 hours, following which, media was collected. 50,000 HEK 293 Blue sensor cells were plated onto 96 well plates and incubated overnight with media (at different dilutions) from Shield-i treated OT-IL12-003 expressing HEK293T cells. After overnight incubation, 20 pl media was removed from each well and incubated with 180 Pl Quanti-Blue reagent (InvivoGen, San Diego, CA) for 30 minutes at 37°C. Absorption was measured at 620 nm using a spectrophotometer. To generate a standard curve, 180 Pl Quanti-Blue reagent was

mixed with 20 pl of recombinant IL12 at following concentrations 500, 250, 125, 62.5, 31.25, 15.62, 7.8 and 3.9 pg/ml. Functional IL12 concentrations were determined by comparing the optical density of each sample with IL12 standard curve. Measurable levels of functional IL12 were reached with 640-fold dilutions of IL12 containing growth media and further plateaued at higher concentrations of the media (Figure 19A).

[00566] The dependence of functional IL12 production on the dose of Shield-i used was measured. 10,000 HEK293T cells stably transduced with OT-IL12-004 were plated onto 96 well plates and treated with growth media containing 10, 3.33, 1.11, 0.37, 0.12, 0.04, 0.01, 0.005, 0.002 or 0 pM Shield-i for 24 hours. Following Shield-i treatment, media from cells was diluted 200-fold and 20pL of the diluted media was added to HEK Blue sensor cells. After overnight incubation, 20 pl of media was removed from each well and incubated with 180 Pl Quanti-Blue reagent (InvivoGen, San Diego, CA) for 30 minutes at 37°C. Absorption was measured at 620 nm using a spectrophotometer. To generate a standard curve, 180 Pl Quanti-Blue reagent was mixed with 20 pl of recombinant IL12 at following concentrations 500, 250, 125, 62.5, 31.25, 15.62, 7.8 and 3.9 pg/ml. Functional IL12 concentrations were determined by comparing the optical density of each sample with IL12 standard curve. A dose dependent increase in the levels of functional IL12 levels was observed (Figure 19B). Example 4. DD regulated recombinant IL12 expression in vivo

[00567] SKOV3 tumor cells expressing FBP regulated-IL12 (#OT-IL12-009) or parental cells were implanted into SCID Beige mice (Day 0). Mice implanted with FKBP IL12 were dosed intraperitoneally with Shield- (10mg/kg) or vehicle control on Day 2 and Day 7, while the parental cells were left untreated. Blood samples were collected at 0, 2, 4, 6, 8 and 24 hours after Shield-i dosing and plasma human IL12 levels were measured using ELISA. The average adjusted concentration of plasma IL12 is presented in Figure 19C. At Day 2, IL12 levels increased in Shield-i treatment and the levels were higher than vehicle control at 4, 6, 8, and 24 hours. Maximum ILI2 levels were detected in Shield-i treated mice at 8 hours following treatment. In contrast, at day 7, IL12 levels were very low and almost comparable to the IL12 levels in parental SKOV3 cells.

[00568] The experiment was repeated 28 days following implantation of SKOV3 tumor cells. Mice were split into three groups, with the groups receiving 1, 2 or 3 doses of ligand or vehicle control. Mice received multiple doses with a two-hour interval. Blood samples were collected right before the first dose (0 hours), and 6 hours and 24 hours after the first dosing. Plasma ILI2 levels were measured and average IL12 concentrations are shown in Figure 19D. The two dose and three dosing scheme resulted in higher plasma ILI2 levels when compared to vehicle treated samples. Peak plasma IL12 levels was detected at 6 hours following shield-i treatment with all dosing schemes, and the highest IL12 plasma levels were detected with the three-dose regimen. This demonstrates the ligand dependent stabilization of IL12 in vivo.

Example 5. DD regulated IL15

[00569] To test ligand dependent IL15 production, 1 million HEK-293T cells were plated in a 6-well plate in growth media containing DMEM and 10% FBS and incubated overnight at 37°C at 5% C02. Cells were then transfected with 100ng of OT-IL15-001(constitutive) or OT-IL15 002 (ecDHFR-IL15) using Lipofectamine 2000 and incubated for 48 hrs. Following the incubation, media was exchanged for growth medium with1OpM Trimethoprim or vehicle control and further incubated for 24 hrs. Media was collected and the undiluted samples or samples diluted 4, 16, 256, 1024, 4096 or 16384-fold were tested using human IL15 ELISA. The stabilization ratio was defined as fold change in IL15 expression with ligand treatment compared to treatment with DMSO (i.e. in the absence of ligand) with the same construct. Stabilization ratio greater than 1 is desired. Average IL15 ELISA readings and stabilization ratio are presented in Table 20. Table 20: DD-IL15 induction Media Vehicle 10 pM Stabilization dilution (fold) TMP ratio 1 0.396 0.820 2.073 4 0.154 0.287 1.867 16 0.074 0.116 1.567 64 0.056 0.073 1.301 256 0.053 0.057 1.075 1024 0.053 0.048 0.910 4096 0.049 0.049 0.995 16384 0.050 0.049 0.994

[00570] The 16-fold, 4-fold diluted, and undiluted media samples showed stabilization ratio greater than 1.5, suggesting a Trimethoprim dependent stabilization of IL15 at these dilutions. Example 6. DD regulated expression of IL15-IL15Ra fusion molecule

[00571] A fusion molecule is generated by fusing membrane bound IL15, IL15 Receptor alpha subunit (ILI5Ra) and DDs such as ecDHFR (DD), FKBP (DD), or human DHFR (DD). These fusion molecules were cloned into pLVX-EFla-IRES-Puro vector.

[00572] To test ligand dependent IL15-IL15Ra production, 1 million HEK-293T cells were plated in a 6-well plate in growth media containing DMEM and 10 FBS and incubated overnight at 37°C, 5% C02. Cells were then transfected with 100ng of constitutive IL15-IL15Ra (OT IL15-008) or DD linked IL15-IL15Ra (OT-IL15-006, OT-IL15-007, OT-IL15-009, OT-IL15 010, OT-IL15-011) using Lipofectamine 2000 and incubated for 24 hrs. Followingthe incubation, media is exchanged for growth medium with or without 1OpM Trimethoprim or 1PM Shield-i and further incubated for 24 hrs. Cells were harvested and IL15 levels are analyzed via western blotting using human IL15 antibody (Abcam, Cambridge, UK). OT-IL15-009 showed the strong ligand (Trimethoprim) dependent stabilization of IL15, while OT-IL15-006 and OT IL15-007 showed modest ligand dependent stabilization of IL15 (Figure 20A).

[00573] Surface expression of membrane bound IL15-IL15Ra constructs (OT-IL15-006, OT IL15-007, OT-IL15-008, OT-IL15-009, OT-IL15-010, OT-IL15-011) was determined by FACS using anti-IL15 and anti-IL15Ra antibodies. HEK293T cells were transfected with IL15-IL15Ra constructs and then treated with suitable ligand (Shield-i or Trimethoprim). 48 hours after transfection, cells were analyzed using FACS. As expected, constitutive IL15-IL15Ra construct OT-IL15-008 showed high surface expression of IL15 and IL15Ra both in the presence and absence of ligand. Consistent with the results from the western blot, OT-IL15-009 showed the strong ligand (Trimethoprim) dependent surface expression of IL15 and IL15Ra (Figure 20B, Figure 20C).

[00574] Membrane bound-IL15-IL15Ra constructs (OT-IL15-008 to OT IL15-011) were transduced into human colorectal carcinoma cell line, HCT-116 and stable integrants were selected with 2pg of puromycin. Stably integrated cells were then incubated for 24 hours in the

presence or absence of10IpM Trimethoprim or1IpM Methotrexate.

[00575] Surface expression of IL15 -IL15Ra fusion constructs was examined by staining with PE- conjugated IL15Ra antibody (Cat no. 330207, Biolegend, San Diego, CA). The median fluorescence intensity obtained with the different constructs in the presence or absence of the corresponding ligand is presented in Table 21. Table 21: Surface expression of IL15-IL15Ra fusion constructs Median Fluorescence Construct Intensity DMSO lOpM 1ptM TMP MTX HCT-116 cells (control) 273 OT-IL15-008 (Constitutive) 5315 7019 OT-1L15-006 (ecDHFR (R12Y, E129K) 764 2978 OT-1L15-010 (hDHFR (Y1221, A125F)) 2657 5775 15864 OT-IL15-011(hDHFR (Q36F, N65F, Y1221)) 1560 4010 14509

[00576] The stabilization ratio was calculated as the fold change in GFP intensity in ligand treated samples compared to treatment with DMSO (i.e. in the absence of ligand) with the same construct. The destabilization ratio was calculated as the fold change in GFP intensity in the DD regulated constructs compared to the constitutive construct (OT-IL15-008) in the absence of the ligand. Destabilization ratios less than 1 and stabilization ratios greater than 1 are desired in DDs. The ratios are presented in Table 22. Table 22: IL15-IL15Ra destabilization and stabilization ratios Construct Destabilization Stabilizationratio ratio TMP MTX OT-1L15-008 (Constitutive) 19.47 1.32 OT-1L15-006 (ecDHFR (R12Y, E129K) 0.14 3.90 OT-ILl5-010 (hDHFR (Y1221, A125F)) 3.48 2.17 5.97 OT-1L15-011(hDHFR (Q36F, N65F, Y1221)) 0.59 2.57 9.30

[00577] Destabilization ratios less than one was observed with OT-IL15-006 (ecDHFR (R12H, E129K)) and OT-IL15-011(hDHFR (Q36F, N65F, Y1221)) indicating a strong destabilization in the absence of ligand. Stabilization ratio greater than 1 was observed with all constructs with TMP treatment and with both OT-IL15-010 and 11 with MTX treatment. These data show that OT-IL15-006 and OT-IL15-011 are both strongly destabilized in the absence of ligand and strongly stabilized in the presence of ligand.

[00578] The expression and ligand-dependent stabilization of IL15-ILI5Ra constructs (OT IL15-008 to OT-IL15-011) was measured in HCT-116. Cells were incubated with 1OpM Trimethoprim or 1IpM Methotrexate or DMSO for 24 hours. Following incubation, cells were harvested and cell extracts were prepared. Cell extracts were run on SDS-PAGE and western blotted with anti-IL15 antibody (Catalog No. 7213, Abcam, Cambridge, UK). As shown in Figure 20D, the IL15/IL5Ra constitutive construct (OT-IL15-008) showed ligand independent IL15 expression while the DD regulated constructs (OT-IL15-009 to OT-IL15-011) showed ligand dependent IL15 expression. The identity of the IL15 bands was also confirmed by immunoblotting with the anti-human DHFR antibody (Catalog No. 117705, Genetex, Irvine, CA). As shown in Figure 20D, both IL15-IL5Ra fusion constructs (OT-IL15-010 and 011) showed ligand dependent expression of DHFR expression.

[00579] To evaluate the dose dependence of ligand induced stabilization, IL15-ILI5Ra fusion constructs namely, OT-IL15-009 (ecDHFR (R12Y, Y100I)), OT-IL15-010 (hDHFR (Y1221, A125F)), and OT-IL15-011 (hDHFR (Q36F, N65F, Y1221)) were stably transduced into HCT 116 cells and incubated with increasing concentrations of Trimethoprim for 24 hours. Surface expression of IL15-IL15Ra fusion construct was quantified by FACS using IL15Ra- PE antibody. The median fluorescence intensity with increasing doses of TMP is represented in Table 23. Table 23: Surface expression of IL15-IL15Ra Median Fluorescence Intensity Dose ecDHFR hDHFR hDHFR (Q36F, (pM) (R12Y, 1001) (Y1221, N65F, Y1221) A125F) DMSO 1260 3034 2357 0.01 1384 2791 2291 0.02 1492 2833 2216 0.05 1947 2924 2054 0.14 2741 2740 2150 0.41 3360 2817 2400 1.23 4014 2890 2251 3.7 4265 3117 2494 11.11 4267 3473 2841 33.33 4485 4019 3409 100 4633 5227 4592

[00580] As shown in Table 23, all three constructs showed a dose dependent increase in median fluorescence intensity indicating a dose dependent increase in surface expression of IL15 IL15Ra fusion upon addition of DD stabilizing ligand.

[00581] The time course of ligand dependent stabilization of IL15-IL15Ra fusion constructs was measured in HCT-116 cells. Cells were transduced with OT-IL15-009 (ecDHFR (R12Y, Y100I) construct and incubated with 1OpM Trimethoprim for 0, 12, 16, 24, 48 or 72 hours. Following incubations, surface expression of IL15-IL15Ra fusion construct was quantified by FACS using IL15Ra- PE antibody and compared to parental untransfected cells. The median fluorescence intensity (MFI) over time is represented in Table 24. Table 24: Time course of IL15-IL15Ra surface expression Time MFI (hours) Parental 3054 0 4004 12 7054 16 9390 24 14056 48 28644 72 35303

[00582] As shown in Table 24, OT-IL15-009 (ecDHFR (R12Y, Y100I) showed a time dependent increase in median fluorescence intensity indicating that the surface expression of IL15-IL15Ra fusion increased with increased duration of treatment with DD stabilizing ligand. Example 7. DD regulated CD19 CAR expression

[00583] A CD19 CAR fusion polypeptide was linked to either FKBP-DD, ecDHFR -DD or human DHFR- DD and the constructs were cloned into pLVX-IRES-Puro vector.

[00584] FKBP, ecDHFR and hDHFR DDs were positioned either between the CD19 scFv and the CD8ahinge (OT-CD19C-002, OT-CD19C-003), between the CD8ahinge and the transmembrane domain (OT-CD19C-004, OT-CD19C-005) or at the C terminus of the construct (OT-CD19C-007, OT-CD19C-008, OT-CD19C-009, OT-CD19C-010, OT-CD19C-011). In some instances, a furin cleavage site was added between the DD and the CD19 scFv. A constitutively expressed CAR construct, OT-CD19C-001 was used as a positive control.

[00585] To test ligand dependent expression of DD-CD19 CAR constructs, 1 million HEK 293T cells were cultured in growth medium containing DMEM and 10% FBS and transfected with CAR constructs using Lipofectamine 2000. 48 hours after transfection, cells were treated with 1IpM or10pM Shield-1, 10IpM Trimethoprim, 1IpM Methotrexate, or vehicle control and incubated for 24 hours. Cells were harvested, lysed and immunoblotted for CD3 Zeta, a component of the CAR, using anti-CD247 (BD Pharmingen, Franklin Lanes, NJ) and Alexa 555 conjugated-goat-anti mouse antibody (red) (Li-Cor, Lincoln, NE). Lysates were also immunoblotted for Actin with Alexa 488-conjugated secondary antibody (green) to confirm uniform protein loading in all the samples. Compared to the untreated control, OT-CD19C-002 and OT-CD19C-003 showed increased levels of CD3 Zeta in the presence of ligands Shield-I and TMP respectively indicating the stabilization of the CD19 CAR (Figure 21A). As shown in Figure 21B, OT-CD19C-008 and OT-CD19C-010 constructs showed strong increase in CD3 Zeta levels in the presence of Methotrexate and low levels in the absence of ligand, indicating a strong ligand-dependent stabilization of CD19 CAR. OT-CD19C-007 and OT-CD19C-009 showed modest increase in CD3 Zeta levels in the presence of Shield- and Methotrexate respectively, indicating a modest ligand-dependent stabilization of CD19 CAR. As expected, the constructively expressed, OT-CD19C-001 showed strong expression of CD19 CAR in the absence of ligand treatment.

[00586] Lysates from cells expressing CD19 CAR constructs were also immunoblotted for 4 1 BB, a component of the CAR. As shown in Figure 21C, OT-CD19C-008, OT-CD19C-009, OT

CD19C-010 and OT-CD19C-011 showed low levels of 4-1 BB in the absence of ligand and high levels of 4-1 BB in the presence of the ligand, Methotrexate, indicating a strong ligand dependent stabilization of CD19 CAR using these constructs. OT-CD19C-003, OT-CD19C-006 and OT-CD19C-007 showed modest increase in 4-1BB expression levels with treatment of corresponding ligands- TMP and Shield-1, indicating a modest ligand dependent stabilization of CD19 CAR. Constructs OT-CD19N-014 and OT-CD19N-015, which contain a furin cleavage site, showed an additional, smaller 4 1BB sized protein product upon treatment with MTX. This smaller sized 4-1BB protein band was only seen with the addition of the ligand and its molecular weight is consistent with the size of the CD19 CAR in OT-CD19-001. These data indicate that the furin cleavage occurs only with ligand treatment.

[00587] Surface expression of DD-CD19 CAR constructs in HEK 293T cells was measured using Fluorescence activated cell sorting (FACS) with Protein L-Biotin-Strepavidin Allophycocyanin which binds to the kappa light chain of the CAR (ThermoFisher Scientific, Waltham, MA). Cells were treated with1IpM Shield-1, 1pM Methotrexate,10IpM Trimethoprim or vehicle control for 24 hours and subject to FACS analysis. As shown in Figure 21D, surface expression of OT-CD19C-002 with FKBP-DD was detected only in the presence of Shield-1, while OT-CD19C-003 with ecDHFR-DD showed surface expression only in the presence of Trimethoprim. As expected, constitutively expressed construct OT-C19C-001 showed high expression both in ligand and control vehicle treated cells. Additional constructs were analyzed by FACS with Protein L-Biotin-Strepavidin-Allophycocyanin in a separate experiment. The percentage of GFP positive cells obtained with each construct in the presence or absence of ligand is presented in Table 25. In Table 25, N/A indicates not applicable.

Table 25: Percentage GFP positive cells

Construct Ligand Percentage GFP positive cells No Ligand Ligand OT-CD19C-001 N/A 46.8 45.4 OT-CD19C-006 TMP 46.6 43.6 OT-CD19C-007 Shield-1 28.9 34 OT-CD19C-008 MTX 15.8 31.3 OT-CD19C-009 MTX 16.5 34.2 OT-CD19C-010 MTX 14.8 33 OT-CD19C-011 MTX 14.5 32.9 OT-CD19C-012 TMP 19.1 18.7

OT-CD19C-013 Shield-1 0.91 0.4

OT-CD19C-014 MTX 4.68 16.2

OT-CD19C-015 MTX 3.04 18.2

[005881 An increase in the percentage GFP positive cells was observed with OT-CD19C-007, OT-CD19C-008, OT-CD19C-009, OT-CD19C-010, OT-CD19C-011, OT-CD19C-014, and OT CD19C-015. The highest increase in the percentage of GFP positive cells was observed with OT CD19C-014, and OT-CD19C-015 constructs.

[00589] The mean fluorescence intensities are presented in Table 26. In Table 26, MFI represents mean fluorescence intensity. The stabilization ratio was calculated as the fold change in GFP intensity in ligand treated samples compared to treatment with DMSO (i.e. in the absence of ligand) with the same construct. The destabilization ratio was calculated as the fold change in GFP intensity in the DD regulated constructs compared to the constitutive construct (OT CD19C-001) in the absence of the ligand. Destabilization ratios less than 1 and stabilization ratios greater than 1 are desired.

Table 26: CD19 CAR surface expression

Construct Ligand MFI Destabiliz Stabilization ation Ratio Ratio No Ligand Ligand OT-CD19C-001 N/A 453 407 0.90 OT-CD19C-006 TMP 425 325 0.94 0.76 OT-CD19C-007 Shield-1 132 123 0.29 0.93 OT-CD19C-008 MTX 89.4 148 0.20 1.66 OT-CD19C-009 MTX 93.3 200 0.21 2.14 OT-CD19C-010 MTX 85.6 160 0.19 1.87 OT-CD19C-011 MTX 83.3 172 0.18 2.06 OT-CD19C-012 TMP 112 105 0.25 0.94 OT-CD19C-013 Shield-1 61 49.5 0.13 0.81 OT-CD19C-014 MTX 78.6 124 0.17 1.58 OT-CD19C-015 MTX 73.3 143 0.16 1.95

[00590] A destabilization ration less than 1 was observed with all constructs indicating that all DD regulated constructs are destabilized in the absence of ligand. A stabilization ratio of greater than 1 was observed with OT-CD19C-008, OT-CD19C-009, OT-CD19C-010, OT-CD19C-011, OT-CD19C-014 and OT-CD19C-015. Notably, these constructs were also destabilized in the absence of ligand and therefore represent suitable CD19-DD constructs. Example 8. In vitro T cell assay development

[00591] The goal of the study was to determine the T cell stimulation regimen and dose of IL12 needed to maximize T cell persistence and T cell differentiation in vitro. The study recapitulates the design of the adoptive cell therapy regimen wherein the T cells were initially exposed to the antigen in vitro which results in activation followed by a resting phase and finally in vivo transfer where the T cells encounter the antigen again. T cells were stimulated CD3/CD28 beads or soluble CD3/CD28 on day 0 and the CD3/CD28 stimulus was washed off at the end of 48 hours. Cells were treated with a dose of IL12 ranging from 0.01- 1000 ng/mL. On day 9, the Th1 phenotype of the cells was evaluated by examining the frequency of IFNgamma positive CD4+ cells and CD8+ cells. On day 14, cells were divided into two groups- one group received a second CD3/CD28 stimulation and a second group that was not stimulated. On day 16, the Th1 phenotype was evaluated in both groups using FACS. The results for day 16 are presented in Figure 22. IFN gamma expression was higher in cells that received a CD3/CD28 restimulation on day 14 compared to cells that did not receive second stimulation. This indicates that both antigen restimulation and IL12 exposure were required for the Th1 phenotype. Further, as little as 0.1 ng/mL of IL12 was able to cause ThI- skewing and IFN gamma production from T cells in vitro, and higher doses of IL12 further improved this effect. Example 9. Measuring human T cell responses in vitro and in vivo

[00592] IL12 promotes the differentiation of naive T cells into Th1 cells which results in the secretion of IFN gamma from T cells. Human T cells were treated with IL12 or left untreated and analyzed by flow cytometry for the expression of IFN gamma and T cell marker CD3. Treatment with IL12 resulted in the differentiation of T cells as measured by an increase in the percentage of IFN gamma positive T cells from 0.21 to 22.3 (see inset of Figure 23A).

[00593] To test if membrane bound IL15/IL15Ra fusion protein (OT-IL15-008) can induce human T cell expansion, human T cells were transduced with the construct. T cell proliferation was measured by evaluating forward and side scatter of the T cell population using flow cytometry. Transduction with membrane bound IL15/IL15Ra fusion construct resulted in the expansion of human T cells (58.9) compared to control untransfected cells (37.8) (Figure 23B).

[00594] Tracking T cells following their adoptive transfer is critical to determine their distribution at different sites in the host, their identity and persistence over time. Human T cells were stimulated with CD3/CD28 beads and incubated with 50U/ml of IL2. Cells were expanded in vitro for 7 days with IL2 supplementation on day 3 and day 5. On day 5, the CD3/CD28 beads were removed and the cells were cultured for two days. On day 7, cells were washed to remove IL2 and 5 million human T cells were injected intravenously into immune compromised, NOD.Cg-Prkddcid 2rgtm1Wjl/SzJ mice. Blood samples were obtained 4, 24, 120 and 168 hours after cell transfer. Mice were euthanized 168 hours after cell transfer and the bone marrow and spleen were harvested. Immune cells were isolated from all samples and analyzed for the presence of human T cells using CD3 and CD45 cell surface markers. As shown in Figure 23C, the percentage of CD3 positive, CD45 positive human T cells in the blood was higher in animals injected with human T cells, especially at 120 and 168 hours. CD3 positive, CD45 positive human T cells were also detected in the spleen and bone marrow of animals injected with human T cells. As expected no CD3 positive, CD45 positive human T cells were detected in control animals that were not injected with human T cells.

[00595] To determine the identity of the T cells following adoptive transfer, blood samples were collected from mice 48 hours after injection. CD4 and CD8 T cells were analyzed for surface expression of CD45RA and CD62L. Both markers are highly expressed in naYve T cells but are lost as the T cells become antigen exposure. As shown in Figure 23D, human CD4 and CD8 T cells showed high surface expression of both markers prior to injecting into mice, but was lost 48 hours after in vivo cell transfer indicating that the human T cells are exposed to the antigen in vivo. Example 10. DD regulated IL12 mediated functions

[00596] DD-IL12 function is characterized in vivo by evaluating the ability of tumor cells expressing these constructs to establish tumors and proliferate under the treatment of corresponding synthetic ligands e.g. Shield-1, Trimethoprim or Methotrexate. 2-10 million HCT 116 cells stably transduced with the constructs are subcutaneously xenografted with 50 matrigel into mice capable of producing functional B and NK cells. Approximately, two weeks after injection, when the tumors reach a size of approximately 300 cubic mm, mice are dosed with corresponding stabilizing ligands e.g. Shield-1, Trimethoprim or Methotrexate at varying concentrations every two days. Shield-i is injected with a carrier consisting of 10 Dimethylacetamide, 10 Solutol HS15, and 80 saline. Tumor volume and body weight are monitored twice a week and the experiment is terminated once the tumors reach 1000 cubic mm in size. Plasma and tumor samples are collected 8 hours after the last dose of the ligand andIL12 as well as the ligand levels are measured.

[00597] To evaluate the ability of IL12 expressing cells to form tumors, HCT-116 cells stably transduced with DD-IL12 constructs are pretreated with corresponding stabilizing ligands, Shield-1, Trimethoprim or Methotrexate and subsequently xenografted into mice. Reduction in tumor growth and a concomitant increase in IL12 levels in ligand treated mice compared to untreated controls is indicative conditional regulation of IL12 in vivo. Example 11. DD regulated recombinant IL12 mediated functions in T cells

[00598] Functional responses to DD-IL12 is evaluated in primary human T cells and in human cell lines/transformed hematopoietic cell lines e.g. Raji cells. Human T cells are purified from peripheral blood mononuclear cells (PBMCs) by negative selection using CD4+ T- cell isolation kit (Miltenyi Biotec, Germany). T cells are treated with growth media from HEK 293T cells expressing DD-IL12 constructs for 5 days. Cells are then activated with beads conjugated with CD3/CD28 beads (Thermo Fisher Scientific, Waltham, MA) at the ratio of 3 beads per T cell and cultured for 3 days. Functional response to DD-IL12 is determined by measuring Interferon gamma in CD3 positive cells using flow cytometry following treatment with ligand or vehicle control. IL12 promotes the differentiation of naive T cells into Th1 cells which results in the secretion of IFN gamma from T cells.

[00599] To evaluate IL12 induced phosphorylation of STAT4 (Signal transducer and activator of transcription 4), human T-cells are isolated from PBMCs and activated with phytohemagglutinin (PHA, 2pg/ml) for 3 days followed by treatment with 50 IU/ml of Interleukin 2 (IL2) for 24hrs. Cells are then washed, resuspended in fresh media and rested for 4 hrs in the presence of ligand or vehicle control. Supernatant from DD-IL12 expressing HEK293T cells is added to the primary cells, followed by incubation for 30 minutes. Cells are then harvested and STAT4 phosphorylation is analyzed using STAT4 antibody (Cell Signaling Technology, Danvers, MA). Example 12. Functional analysis of DD regulated IL15-IL15Ra fusion molecule

[00600] Activation via IL15 can sustain T cell persistence by conferring a survival advantage. In addition, IL15/ILI5Ra fusion molecule has been shown to confer a memory phenotype on T cells and increase proliferation of NK cells (Hurton (2016), PNAS, 113: E7788-7797; the contents of which are incorporated herein by reference in their entirety).

[00601] To evaluate signaling by DD regulated IL15-ILI5Ra fusion constructs, NK-92 cells are incubated with HCT-116 cells expressing DD regulated IL15-ILI5Ra fusion constructs. Trans signaling by IL15/ILI5Ra is expected to increase STAT5 phosphorylation in NK92, which is measured by western blotting, and by FACS. Proliferation of NK92 cells is also measured.

[00602] To evaluate the effect of DD regulated IL15-ILI5Ra fusion constructs on primary T cells, cells are transduced with the fusion constructs. T cell proliferation in the absence of exogenous IL15 supplementation is measured. The T cell memory phenotype is measured by quantifying CD62L expression by FACS.

[00603] To assess if DD-IL15/IL15R expressing T cells maintain prolonged persistence in vivo, DD modified T cells are injected into mice. Constructs are tagged with luciferase reporter to allow in vivo tracking in mice. Mice are treated with vehicle control or corresponding ligand, Shield-1, Trimethoprim or Methotrexate depending on the construct utilized and monitored over a period of 40-50 days using bioluminescent imaging (PerkinElmer, Massachusetts). Mice treated with ligand are expected to retain T cells expressing DD-IL15/IL15Ra while T cells in vehicle control treated animals are not expected to persist. Example 13. DD regulated CD19 CAR expression and function in T cells

[00604] Ligand dependent expression of DD-CD19 CAR constructs is evaluated in primary human T cells and in immortalized/transformed hematopoietic cell lines e.g. Raji cells, Jurkat cells and K562 cells. Human T cells are purified from peripheral blood mononuclear cells (PBMCs) by negative selection using CD4+ T- cell isolation kit (Miltenyi Biotec, Germany). Primary T cells and hematopoietic cell lines are stably transduced with DD-CD19 CAR constructs. Cells are treated with 10pM Shield-1, 10pM Trimethoprim, 1pM Methotrexate or vehicle control and immunoblotted for CD3 Zeta using anti CD247 antibody.

[00605] The production of functional DD-CD19 CAR is analyzed in primary human T cells or human cell lines (NALM6, K562, Jurkat and Raji cells). Cells are incubated with CD19 expressing antigen presenting cells or CD19/Fc fusion protein in the presence of DD stabilizing ligands Shield-1, TMP or MTX. After incubation, cells are stained with fluorescently labelled anti-CD69 antibodies and analyzed by flow cytometry. Cells with high CD69 expression are considered to have a functional DD-CD19 CAR. Functional response to DD-CD19 CAR is also determined by measuring interferon gamma levels using ELISA. DD-CD19 CAR expressing cells are expected to demonstrate higher Interferon gamma levels in the presence of ligand than untreated cells.

[00606] Cytolytic potential of DD-CD19 CAR expressing cells is evaluated in primary human T cells or human cell lines (e.g. NALM6, K562 and Raji) using Chromium-51 Release Assay. Target cells are loaded with of Na2 51 CrO , washed twice and resuspended in phenol red-free 4

growth medium. Untreated or ligand treated DD-CD19 CAR and mock transduced cells are coincubated with CD 19 expressing target cells at various effector: target cell ratios, and chromium release into the supernatant is measured using a liquid scintillation counter. Cells with DD-CD19 CAR are expected to demonstrate specific cytolysis only in the presence of ligand. Cells with DD-CD19 CAR in the absence of ligand or mock transfected cells are expected to show minimal cytolytic activity.

[00607] The in vivo antitumor efficacy of DD-CD19 CAR is also evaluated. Immune compromised mice are injected with luciferase expressing human leukemic cell lines (NALM-6). Subsequently, mice are injected with DD-CD19 CAR T cells via tail vein injections. Mice are subdivided into treatment groups and are treated with a range of ligand doses. Two control groups are also included in the study: a control group that did not receive any ligand and another group that did not receive any T cells. Tumor burden as measured by luciferase activity is monitored over time using bioluminescent imaging. Mice treated with DD-CD19 CAR T cells and ligand are expected to have a reduced tumor burden when compared to control animals. Example 14. Evaluation of antitumor response of DD regulated payloads in syngeneic mouse models

[00608] The efficacy of cancer immunotherapy in organisms with intact immune cells is evaluated using syngeneic mouse models e.g. pMEL-1 and 4T1 mouse models. Immune cells such as T cells and NK cells are isolated from syngeneic mice and transduced with DD regulated payloads such as DD-IL12, DD-IL15, DD1L15-IL15Ra, and DD-CD19 CAR,. Cells are then injected into mice bearing subcutaneous syngeneic tumors and treated with varying concentrations of ligand, Shield-1, Trimethoprim or Methotrexate, depending on the DD used. Mice treated with immune cells transduced with DD regulated payload are expected to have a reduced tumor burden when compared to control animals. Example 15. Optimizing workflow for discovery of DD-regulated immunotherapeutic agents

[00609] To identify DD-CD19 CAR constructs suitable for immunotherapy, constructs are introduced into cell lines e.g. HEK293T cells and Jurkat cells. The expression of the construct in the presence or absence of the corresponding ligand is tested. Constructs which show low basal expression in the absence of ligand and robust, ligand-dose responsive expression are selected for further analysis. If no DD-CD19 CAR constructs show ligand-dependent expression, then constructs are redesigned and the experiment is repeated till a regulatable construct is identified. Next, the ligand dependent regulation of the DD-CD19 CAR constructs is tested in vitro in primary T cells. If the constructs show low basal expression in the absence of the ligand and ligand dose responsive expression, they are subject to in vivo PK/PD proof of concept experiments. Otherwise, the constructs are redesigned and the new constructs are subject to similar analysis. The constitutively expressing CD19 CAR constructs are transduced into T cells and CD19 CAR expression is measured in parallel to the regulated construct. If no expression is detected in vitro, efforts are refocused on testing DD- CD19 CAR constructs in vitro in T cells. In contrast, if the constitutive constructs show expression, then the expression of CD19 CAR is measured in vivo.

[00610] To test in vivo PK/PD, mice are injected with T cells expressing DD-CD19 CAR constructs and the test group is dosed with the ligand corresponding to the DD, while the control group is dosed with the appropriate vehicle control. Constructs that display ligand-dependent expression of CD19 CAR are selected for in vivo functional proof of concept experiments. Parallel experiments are also conducted using the constitutive CD19 CAR constructs. If constitutive CD19 CAR expression is detected in vivo, then the constructs are selected for functional experiments. If no expression is detected in vivo, then constructs are redesigned.

[00611] Functional analysis in vivo is performed by testing if the constitutive and DD regulated CD19 CAR expressing T cells display anti-tumor activity in a constitutive or ligand dependent manner respectively. If yes, then in vivo proof of concept is achieved and constructs suitable for immunotherapy are identified. If none of the DD regulated constructs show anti-tumor activity, then alternate dosing regimens are explored. If the constitutive CD19 CAR constructs do not show anti-tumor activity, then efforts are focused on identifying DD-CD19 CAR constructs that show in vivo expression in T cells. Example 16. Co-expression of DD regulated payloads

[00612] Toxicity related to systemic administration of interleukins can be circumvented by using CAR-T cells to deliver interleukins to the target tissue. This combinatorial approach also has greater anti-tumor activity than interleukin and CAR therapy alone. Cells are co-transfected with CD19 CAR (constitutive or DD regulated) and DD-Interleukin e.g. DD-IL12, DD-IL15 and DD-IL15/IL15Ra constructs. Transfected cells are treated with stabilizing ligands depending on the DD utilized. CD19 CAR expression is evaluated by immunoblotting for CD3 zeta. DD-IL12, DD-IL15 and DD-IL15/IL15Ra expression in the media is measured by ELISA.

Example 17. CAR expression and functionality in T cells

[00613] Primary T cells were transduced with CD19 CAR constructs. Surface expression of CD19 CAR construct was measured using Fluorescence activated cell sorting (FACS) with Protein L-Biotin-Strepavidin-Allophycocyanin which binds to the kappa light chain of the CAR (ThermoFisher Scientific, Waltham, MA). To determine the percentage of the CD4 and CD8 sub populations of CAR T cells, cells were analyzed by anti CD4, anti CD8 antibodies and Protein L. As shown in Figure 24A, 67.3 % of CAR positive cells obtained were CD4 positive, while only 14.2% cells were CD8 positive.

[00614] To test the ability of CD19 CAR cells to kill target cells, primary T cell populations transduced with OT-CD19N-001 or OT-CD19N-017 were cocultured with K562 cells expressing CD19 (target cells) at a ratio of 5:1. Additional control combinations of T cells and target cells were also set up. These included CAR expressing T cells co cultured with K562 cells, T cells co cultured with K562 cells expressing CD19 and K562 cells expressing CD19 without T cell co culture. K562 cells were fluorescently labelled with NucLight Red and co cultured with T cells for 30 hours. Cell death was monitored by labelling cells with Annexin V and K562 target cell death was measured by evaluating Annexin V staining in NucLight Red positive cells. The ratio of Annexin V staining per target cell area was calculated. As shown in Figure 24B, OT-CD19N 001 or OT-CD19N-017 expressing T cells were effective in killing target K562 cells expressing CD19. A low level of target cell killing was observed when untransduced T cells were cocultured with CD19 expressing target cells. As expected, cell death was minimal in the co culture of OT-CD19N-001 expressing T cells and K562 cells (without CD19 expression). These data show that CD19 CAR cells are effective in killing their corresponding target cells.

Example 18. Regulated expression of IL15-IL15Ra in T cells

[00615] DD regulated IL15-IL15Ra constructs such as OT-IL15-009 or constitutively expressed constructs such as OT-IL15-008 were transduced into T cells such as primary T cells or SupTI cells. The transduction was carried out at two different lentivirus concentrations, 5 PIl and 20 Pl for the DD regulated construct using Lentiboost TM (Sirion Biotech, Germany). 4 days after transduction, cells were treated with 10IpM TMP or DMSO control for 24 and 48 hours. Samples were analyzed with an anti IL15Ra antibody using FACS. Additional controls samples such as cells treated with Lentiboost only, untransduced cells treated with DMSO or TMP, and Isotype controls were included in the FACS analysis. The FACS results are depicted in Figure 25A for 24 hours of TMP treatment and in Figure 25B for 48 hours of TMP treatment. In both figures, DMSO-A and TMP-A indicate cells treated with 5 pl of lentivirus and DMSO- B and TMP-B indicate cells treated with 20 pl of lentivirus. Treatment of T cells expressing OT-IL15-009 with TMP for 24 hours resulted in an increase in the expression of ILI5Ra in T cells with both doses of lentivirus used. Additionally, very low levels of IL15Ra were detected in the DMSO treated samples under the same conditions as well as in untransduced T cells. As expected, the constitutively expressed construct, OT-IL15-008 showed high expression of IL15Ra. TMP dependent expression of OT-IL15-009 was not observed in SupT1 cells (Figure 25A). Similar results were observed for both T cells and SupT1 cells at 48 hours (Figure 25B). These results show that tight regulation of IL15-IL15Ra constructs can be achieved in primary T cells.

[00616] The surface expression of IL15 and ILI5Ra was measured for OT-IL15-008 and OT IL15-009. The percentage of cells expressing IL15, ILI5Ra or both on the cell surface is presented in Table 27.

Table 27: Surface expression of IL15 and IL15Ra

% Positive cells OT-1L15-008 OT-1L15-009 IL15 and IL15Ra positive 2.03 0.51 IL15Ra positive 13.0 15.8 IL15 positive 0.29 0.60

[00617] As shown in Table 27, the percentage of cells with detectable surface expression of IL15 and IL15Ra was less than 5% with both constructs. Further, the percentage of cells with surface expression of IL15Ra was much higher than the percentage of cells with detectable surface expression of IL15.

[00618] The effect of increasing doses of TMP on ILI5Ra expression in T cells was measured using the OT-IL15-009 construct. T cells were treated with a range of doses of TMP starting from 0.156 pM to 160 pM for 24 hours. IL15Ra expression was measured using FACS. As shown in Figure 25C, the percentage of IL15Ra expressing T cells with OT-IL15-009 cells was detected even at the lowest concentration of TMP and the percentage of ILI5Ra positive cells at the lowest concentration of TMP was higher than the untreated control. The percentage of ILI5Ra cells increased with increasing doses of TMP.

Example 19. TMP dose responsive expression of IL15-IL15Ra

[00619] IL15-IL15Ra fusion constructs, OT-IL15-008, OT-IL15-009, and OT-IL15-010 were stably expressed in HCT116 cells treated with increasing doses of TMP ranging from 10IPM, 33pM, and 100IpM TMP for 24 hours. Cell lysates were immunoblotted with anti IL15Ra antibody. As shown in Figure 26, IL15Ra expression of OT-IL15-009 was virtually undetectable in the absence of TMP, and addition of increasing doses of TMP resulted in an increase in IL15Ra levels. Modest increase in IL15Ra expression was observed with OT-IL15-010 construct with the addition of TMP. As expected, the constitutive construct, OT-IL15-008 showed strong expression of ILI5Ra both in the presence and absence of ligand.

Example 20. Effect of IL15-IL15Ra on T cell persistence and T cell memory phenotype

[00620] The effect of constitutively expressed IL15-IL15Ra fusion construct, OT-IL15-008 on T cell persistence was measured in NSG mice. T cells were transduced with OT-IL15-008 and 4 million cells T cells were injected intravenously into NSG mice (number of mice =3). As a control, additional mice were injected with untransduced T cells. Blood samples were obtained from mice at 2, 3, 4, 5 and 6 weeks after injection and analyzed by FACS for the presence of CD8 and/or CD4 positive human T cells expressing IL15 and IL15Ra. The percentage of human T cells in the blood was calculated as the percentage of total T cells i.e. human T cells (measured using anti-human CD45 antibody) and the mouse T cells and endothelial cells (measured using the anti-mouse CD45 antibody). As shown in Figure 27 A, the percentage of T cells in the blood at 2 weeks was greater in mice injected with T cells transduced with OT-IL15-008 compared to control mice that were injected with untransduced T cells. This observed increase in T cells decreased over 3,4, and 5 weeks, and the percentage of T cells was comparable between the two cohorts. At 6 weeks, one of the mice injected with OT-IL15-008 transduced T cells showed a higher percentage of human T cells in the blood. Thus, at 2 weeks, the frequency of human T cells in the blood is increased in the blood of mice injected with OT-IL15-008 transduced T cells.

[00621] The number of T cells in the blood was measured by comparing the number of human T cells in 50 uL of mouse blood using anti-human CD45 antibody as a marker for human T cells and anti-murine CD3 antibody as a marker for murine endothelial cells. As shown in Figure 27B, the number of human T cells in the blood increased at 2 weeks in mice injected with OT-IL15 008 transduced T cells, as compared to mice injected with untransduced T cells. The difference between the two cohorts was diminished at 3 weeks and 4 weeks. At 6 weeks, one of the mice injected with OT-IL15-008 transduced T cells showed a higher number of human T cells in the blood. Thus, at 2 weeks, the frequency and number of human T cells in the blood is increased in the blood of mice injected with OT-IL15-008 transduced T cells. These data support the role of IL15-ILI5Ra fusion proteins in T cell persistence. The increased T cell frequency and number observed at 6 weeks in one of the mice may be due to graft versus host disease.

[00622] The effect of OT-IL15-008 expression on the CD4 and CD8 subset of T cells was measured prior to injecting into mice (Week 0) and 2 weeks after injection. As shown in Figure 27C, the ratio of CD4 and CD8 cells was 1:1 prior to injecting into mice. However, at 2 weeks, the proportion of CD4 positive cells was much higher than the CD8 positive cells in the transduced cells, indicating that OT-IL15-008 causes a preferential expansion of CD4 positive cells. The expression of the OT-IL15-008 construct within the CD4 and CD8 subsets was measured using anti IL15Ra antibody. As shown in Figure 27D, prior to injections, 25 % of the OT-IL15-008 transduced CD4 T cells and CD8 T cells expressed IL15Ra. At week 2, the percentage of IL15Ra positive CD4 and CD8 T cells increased to 80% indicating a preferential expansion of T cells transduced with OT-IL15-008. As expected, untransduced control T cells were negative for IL15Ra expression.

Example 21. IL12 dependent, re-stimulation independent Th1 markers

[00623] T cells require T cell receptor restimulation in vivo or in vitro stimulation with CD3/CD28 to produce IFNgamma. To study the effect of IL12 activity on T cells in the absence of restimulation, several T cell markers were explored. T cells were expanded using one of the following 4 expansions strategies (i) Day 10 cytokine switch from IL2 to IL12, CD3/CD28 stimulation from day 0 to day10 with no restimulation (ii) Day 10 cytokine switch from IL2 to IL12, CD3/CD28 stimulation from day 0 to day 10 and restimulation at with CD3/CD28 from day 12 to day 14 (iii) Day 10 cytokine switch from IL2 to IL12, CD3/CD28 stimulation from day 0 to day3 with no restimulation (iv) Day 10 cytokine switch from IL2 to IL12, CD3/CD28 stimulation from day 0 to day 3 and restimulation at with CD3/CD28 from day 12 to day 14. Markers tested include CD69, IFNg, Perforin, CXCR3, Granzyme B, CCR5, CXCR6, Ki-67 and T-bet. IFNg appears to be the most robust and consistent marker for IL12 activity on human T cells, but requires re-stimulation of T cells to induce production. Th1 markers which increase in response to IL12 in the absence of re-stimulation and IL2 (likely in vivo conditions) include Ki 67, T-bet, Perforin, CXCR3, and CCR5.

Example 22. Effect of cytokines on NK cell proliferation and activation

[00624] Immune cells such as Natural Killer cells depend on cytokines such as IL15 for their proliferation and survival. This dependence on cytokines can be used to test the functionality of DD regulated or constitutively expressed cytokines and cytokine fusion proteins.

[00625] The dependency of the NK-92 cells on cytokines for activation was tested. Cells were initially cultured for 3 days with IL2, following which, cells were washed twice and cultured in media without IL2 for 7 hours. The cells were cultured for 18 hours in the presence of IL12 (10 ng/ml) or varying concentrations of IL15 (100 ng/ml, 20 ng/ml, 4 ng/ml, 0.8 ng/ml, 0.16 ng/ml, 0.032 ng/ml, 0.0064 ng/ml and 0.00128 ng/ml). NK-92 cell activation in response to IL15 and IL12 treatment was evaluated by FACS analysis using a panel of markers whose increased expression is associated with NK cell activation. These markers include NKG2D, CD71, CD69; chemokine receptors such as CCR5, CXCR4, and CXCR3, Perforin, Granzyme B and Interferon gamma (IFNg). Prior to FACS analysis for IFNg, cells were cultured for 4 hours with Brefeldin A. NK cells respond to external stimuli such as cytokines in their environment through the phosphorylation of proteins JAK/STAT, ERK, and p38/MAPK pathways which are important for cell activation, signaling and differentiation pathways. The phosphorylation of AKT, STAT3 and STAT5 in response to cytokine addition was measured by FACS. Since phosphorylation events are transient NK-92 cells were treated with the cytokines for 15 or 60 minutes, prior to the analysis. The fold change in mean fluorescence intensities compared to untreated for IL15 treatment are presented in Table 28.

Table 28: IL15 induced markers

IL15 dose CD69 CXCR4 Perforin Granzyme pSTAT5 pSTAT5 IFNgamma (ng/ml) B (15 (60 mins) mins) 100 1.91 3.87 1.67 1.48 1.98 2.34 9.00 20 2.10 3.62 1.57 1.40 1.96 2.35 5.55 4 1.59 3.03 1.28 1.16 1.81 2.35 2.76 0.8 1.18 2.10 1.16 1.09 1.76 2.17 1.92 0.16 0.99 1.41 1.04 1.03 1.44 2.08 2.41 0.032 1.05 1.14 0.92 0.92 1.23 1.67 0.95 0.0064 1.11 1.19 0.79 0.78 1.03 1.26 0.85 0.00128 1.07 1.15 0.85 0.88 0.99 1.04 1.19

[00626] Treatment with IL15 resulted in an increase in the expression of CD69, CXCR4, Perforin, Granzyme B, and IFNg. The effect of IL15 on these markers was dose dependent with a higher dose of IL15 resulting in a corresponding upregulation of markers. Phosphorylation of STAT5 was increased both at 15 and 60 minutes after the addition of IL2 or ILS5. Taken together, these results show that cytokines can activate NK cells.

[00627] The fold change in activation markers observed with IL12 treatment are shown in Table 29.

Table 29: IL12 induced markers

Marker Fold change CCR5 1.60 Perforin 1.67 Granzyme 1.87 IFNg 1.74 IFNg (supernatant) 666.15

[00628] Treatment with IL12 resulted in an increase in the expression of markers CD69, CCR5, Perforin, Granzyme B, and IFNgamma. Further, IFNg levels secreted by NK-92 cells into the media higher than untreated controls upon treatment with IL12. Treatment with IL2 resulted in an increase in the expression of CXCR4, Perforin, Granzyme B, and IFNg. Further, IFNg levels secreted by NK-92 cells into the supernatant was higher than untreated controls upon treatment with IL2.

Example 23. Effect of cytokines on T cell expansion and activation

[00629] To test the requirement of IL2 and IL12 for T cells expansion and activation, T cells were stimulated with soluble CD3/CD28, CD3/CD28 Dynabeads or left unstimulated for two days. Each of these groups was further split into two sub groups. One sub group was treated with IL2 and 100 ng/ml of IL12 while the second sub group was treated with IL2 only for the duration of the stimulation. For the soluble CD3/CD28 stimulated cells, a third subgroup that was only treated with 100 ng/ml was also included. T cell expansion over the course of 14 days was measured and the fold change in T cells expansion is shown in Figure 28A. CD3/CD28 dynabeads plus IL2 with or without IL12 had the most profound impact on T cell expansion followed by the T cells treated with soluble CD3/CD28 plus IL2 with or without IL12. Unstimulated cells and cell treated with soluble CD3/CD28 cells that did receive IL2 treatment were unable to expand over the course of the experiment. These results show that IL2 is required for T cell expansion, but IL12 may be dispensable.

[00630] The effect of IL12 on T cell activation was measured by determining the frequency of IFNgamma positive CD4+ and CD8 + T cells. IFNg is produced by activated T cells. Three different stimulation protocols were used. In the first protocol, cells were stimulated with CD3/CD28 dynabeads for 2 days, following which the beads were washed off and the cells were treated with varying concentrations of IL12 for 7 days (from day 2 to day 9). At day 9, cells were restimulated with soluble CD3/CD28 and the frequency of IFNgamma positive cells was determined by FACS. The results are presented in Figure 28B as the percentage of cells. In the second protocol, following 2 day CD3/CD28 dynabeads stimulation, T cells were maintained in culture for a longer duration of 14 days i.e. from day 2 to day 16. At day 16 cells, were restimulated with soluble CD3/CD28. At day 16, the frequency of IFNgamma positive cells was measured. The results are presented in Figure 28C as the percentage of cells. In the third protocol, T cells were initially stimulated for 2 days with CD3/CD28 dynabeads and IL2, followed by treatment with IL2 only for 9 days (i.e. from day 2 to day 11), followed by IL12 treatment for 2 to 5 days. In the last two days of the experiment, cells were also restimulated with soluble CD3/CD28. IFNgamma positive CD4 and CD8 cells were measured using FACS. The third protocol mimics the environment that is presented to T cells in adoptive cell therapy, both during in vitro transduction and T cells expansion as well as the in vivo. The results are presented in Figure 28D as the percentage of cells. In both 7-day treatment with IL12 as well as 14-day treatment with IL12, shown in Figure 28B and Figure 28C respectively, restimulation with CD3/CD28 cells at the end of the experiment increased the percentage of IFNgamma positive cells. A half maximum effective concentration (EC50) of IL12 observed with the first protocol for CD8 cells was 50 pg/ml. The EC50 of IL12 observed with the second protocol was 12 pg/ml for CD4 cells and 65 pg/ml for CD8 cells. Long-term culture with CD3/CD28 further increased the dependence on re-stimulation and IL12 for IFNg production.

[00631] The results obtained with the third stimulation protocol are presented in Figure 28D. Immune cells treated with IL12 for the final 5 days of the experiment combined with CD3/CD28 restimulation showed the highest percentage of IFN gamma positive cells (EC50 = 24 pg/ml for CD4 cells and 40 pg/ml for CD8 cells), followed by cells that received IL12 for 2 days. Thus, T cells expanded in vitro can later differentiate in response to IL12, but restimulation may be required for IFNg production.

[00632] Taken together these results indicate that IL12 can stimulate IFN production in T cells when restimulated with CD3/CD28.

Example 24. Promoter selection for expression of SREs in T cells

[00633] The expression of SREs in a vector can be driven by either the retroviral long terminal repeat (LTR) or by cellular or viral promoters located upstream of the SRE. The activity of the promoter may vary with the cell type and thus promoter selection must be optimized for each cell type. To identify optimal promoters, AcGFP (SEQ ID NO. 870) was cloned into pLVX. IRES Puro construct with a CMV or an EFla promoter. Patient derived T cells and Sup Ti cells were transduced with the constructs and GFP expression was measured at day 3 and day 5 after transduction using FACS. As shown in Figure 29, both the CMV promoter and the EFla can drive the expression of GFP in SupT1 cells and T cells. The percentage of GFP positive T cells was higher when GFP expression was driven by CMV promoter compared to an EFla promoter, both at 3 days and 6 days after transduction. In contrast, the percentage of GFP positive cells was much higher when GFP expression was driven by the EF la promoter when compared to the CMV promoter. Thus, the optimum promoter suitable for expression differs based on the cell type.

Example 25. Effect of ligand on T cell proliferation

[00634] The effect of ligands specific to the SREs of the invention on immune cell proliferation was measured to identify concentrations of the ligand that did not inhibit T cell growth or survival. T cells derived from two different donors were stimulated with CD3/CD28 and treated with ligand TMP at doses ranging from 0.04 pM to 160 pM or DMSO. The percentage of divided cells within the CD4 and the CD8 populations of T cells was measured using FACS. Concentrations of TMP ranging from 0.04 pM to 40 pM showed no effect on the percentage of

divided cells within the CD8 and CD4 populations, while 160 pM concentration of TMP resulted in an 70-90% reduction in the percentage of divided cells. Thus, the optimal concentration of TMP for T cell based experiments was determined to be less than 160 PM.

Example 26. Effect of DD regulated CD19 CAR on tonic signaling

[00635] Chronic antigen activation can result in T cell exhaustion. To test if DD regulated CD19 CAR constructs induce tonic signaling, irradiated K562 cells expressing CD19 are plated into culture plates 12 hours before the addition of T cells expressing DD regulated CD19 CAR constructs with Interleukin 2. Cells are counted every two days and media is replaced. For repeated stimulations, cells are transferred to a new plate with K562-CD19 cells after 24 hours (for two stimulations) or every 12 hours (for four stimulations). For each condition, T cells are counted and analyzed by FACS for CAR, phenotypic and exhaustion markers every 12 hours. DD regulated constructs were analyzed in the presence or absence of ligand. Markers analyzed include CD25 and CD69 for activation status; CD62 and CD45RA for memory status; and exhaustion markers PD1, TIM3 and LAG3. DD regulated CD19 CAR constructs are expected to induce a lower percentage of cells that are positive for all three exhaustion markers- i.e.PD1, TIM3 and LAG3 and a higher percentage of cells that are CD45A+/CD62L+ indicating less differentiated T cells. Constitutively expressed CD19CAR constructs may induce the expression of all three exhaustion markers and may have a more differentiated phenotype with a higher proportion of CD45-/CD62L- and CD45+/CD62L- cells.

Example 27. Functional analysis of DD regulated CD19 CAR

[00636] To test the ability of DD regulated CD19 CAR cells to kill target cells, primary T cell populations transduced with DD regulated CD19 CAR constructs are co cultured with K562 cells expressing CD19 (target cells) at a ratio of 5:1 in the presence or absence of the ligand specific to the DD e.g. Shield-1, TMP or MTX. Additional control combinations of T cells and target cells are also set up. These include DD regulated CAR expressing T cells co cultured with K562 cells (in the presence or absence of the ligand), T cells co cultured with K562 cells expressing CD19 and K562 cells expressing CD19 without T cell co culture. The K562 cells are fluorescently labelled with NucLight Red and co cultured with T cells for 30 hours. Cell death is monitored by labelling cells with Annexin V and the cell death in target K562 cells is monitored by evaluating cells that are positive for both Annexin V and NucLight Red. The ratio of Annexin V staining per target cell area is calculated. DD-CD19CAR expressing T cells are expected to be effective in killing target K562 cells expressing CD19 only in the presence of the ligand specific to the DD. Minimal target cell death is expected to occur when untransduced T cells are cocultured with CD19 expressing target cells; and with DD-CAR T cells (with or without ligand treatment) plus K562 cells (without CD19 expression).

Example 28. Generation of CD19 scFvs using the large phage antibody libraries

Construction of Primary Phagemid Library

[00637] Total RNA is prepared from 40 different samples of human peripheral blood lymphocytes and cDNA is synthesized using random primers. IgM variable regions are amplified using an IgM 3'primer and 5'VH primers. Pooled primers are also used to amplify the Vk and VL. An additional PCR step is added to include restriction sites as well as to introduce a region of overlap containing an scFv loxP linker. scFvs are obtained by mixing equimolar amounts of VH and VL genes and performing assembly. The scFvs are then cloned into pDAN5 vectors to obtain a primary library of approximately 10 8.

Recombination and secondary of the secondary library

[00638] To induce recombination, bacterial strain BS1365 (which express Cre-recombinases constitutively) are infected with primary phagemid library at an MOI of 20:1. This results in bacteria containing multiple phagemids, each of which encodes different VH and VL genes, which can be recombined by the Cre recombinase. Since the phagemid arise from bacteria containing many different scFv, the phenotype and genotype are not coupled. Phagemids derived from the bacteria are used to infect bacteria that do not express Cre (e.g. DH5a) at a low MOI of < 0.1 to couple genotype to phenotype.

CD9 expression constructs and cell lines

[00639] Human CD19 isoforms described in Table 14 are cloned into appropriate vectors and transfected into cell lines with low endogenous CD19 expression such as K562 and 3T3 cell lines. The CD19 expressing lines i.e. K562- CD19 or 3T3 -CD19 cells, are used for positive selection of scFvs in the phage display library. The parental K562 and 3T3 are used for the negative selection.

Selection of antibodies recognizing CD19 on cell surface

[00640] The secondary phage display library is pre-cleared by screening with parental cells to remove non-specific binding phages. The precleared phages are incubated with K562-CD19 or 3T3-CD19 cells, and bound phages are recovered and amplified for next round of selection. Three rounds of selection are performed to enrich for CD19 binders. FMC63-distinct scFvs i.e. scFvs that bind to epitopes distinct from FMC63, are selected in a parallel selection process by blocking the FMC63 epitope with an excess of FMC63 antibody.

[00641] The affinity of the scFv to CD19 is a critical aspect that determines the performance of the antibody in pharmacokinetic and immune response assays. Affinity measurements for 96 scFv clones are made using techniques such as ELISA and surface plasma resonance which provide on-rate (Ka), off-rate (Kd), and affinity constant (KD).

[00642] scFv clones with desired off rates are subjected to Sanger sequencing to identify unique clones that bind to CD19 expressing cells but not parental cells. Identified clones are then subject to epitope binning, using a competitive immunoassay that is used to characterize and then sort a library of scFvs against a target protein, e.g. CD19. scFvs against CD19 are tested against all other CD19 scFvs identified from the library, in a pairwise fashion to identify scFvs that prevent the binding of other scFvs to an epitope of CD19 antigen. After a profile is created for each CD19 scFv, a competitive blocking profile is created for each scFv relative to the others. Closely related binning profiles indicate that the antibodies have the same or a closely related epitope are binned together.

[00643] scFvs obtained at each of step of the selection process are subject to deep sequencing methods such as Ion Torrent/MiSeq. Heavy chain CDR3 sequences, including those that do not bind to FMC63 are identified using the Abmining ToolBox (D'Angelo S et al. (2014)MAbs. 6(1): 160-172) and top ranking HCDR3s are identified. HCDR3 specific primers designed from the DNA sequence of the top ranked sequences are then used to amplify scFv clones by inverse PCR and the PCR product is cloned into expression vectors.

Example 29. CD19 scFv affinity

[00644] The affinity of the scFv to the CD19 antigen is a critical aspect that determines the performance of the antibody in pharmacokinetic and immune response assays. Affinity measurements are made using techniques such as ELISA and surface plasma resonance which provide on-rate (Ka), off-rate (Kd), and affinity constant (KD).

[00645] Antibodies with varying affinities are identified using cells that have high or low ectopic expression of CD19. K562-CD19 cells and parental K562 cells with low CD19 expression are sorted by FACS using CD19 antibodies e.g. FMC63 to determine surface expression of CD19. Cells are sorted into bottom 5% (i.e. low CD19 expressing cells), top 5% (high CD19 expressing cells) and the rest of the population of cells is categorized as median CD19 expressing cells.

Example 30. Screening strategy for identifying FMC63-distinct CD19 scFvs

CD19/Fc fusion proteins

[00646] FMC63 binds to human CD19 in the region encoded by exon 2. To identify FMC63 distinct CD19 scFvs, human CD19 (Exon 1-4) or human CD19 (Exon 1,3,4) are fused with IgG to generate CD19-IgG fusion proteins, CD19slgG1-4 and CD19slgG1,3,4 respectively. CD19 IgG fusion proteins are used for antibody screening. 96-well plates are coated with capture antibodies and incubated with CD19slgG-4 or CD19slgG1,3,4 fusion protein. The plates are washed and incubated with candidate CD19 scFvs identified in Example 28. The plates are washed again and incubated again with reporter (e.g. Alkaline phosphatase) conjugated detection antibodies and detected using reporter compatible detection methods. Capture antibodies may be antihuman IgG Fc antibodies, or the FMC63 antibody (as a control). The detection antibody may be anti-human IgM antibody. FMC63-distinct CD19 scFvs are expected to bind to (CD19slgG1,3,4) and (CD19slgG1-4). In contrast, candidate CD19 scFvs that bind to epitopes that are identical or overlap with FMC63's epitope are expected to only bind to (CD19slgG-4).

Competition assay

[00647] CD19 expressing K562 cells are incubated with nano molar concentrations of tagged candidate CD19 scFvs e.g. identified in Example 28 and fixed concentration of tagged FMC63 scFv for competition binding assays. Cells are washed and stained with the secondary antibody corresponding to the tag used in the candidate CD19 scFv. Mean fluorescence intensity is measured using flow cytometry. Asa negative control, CD19 K562 expressing cells are incubated with varying concentrations of tagged candidate CD19 scFv alone or FMC63 alone. For FMC63-distinct CD19 scFvs, it is expected that there will be no competition for binding to CD19 between the candidate CD19 scFvs and FMC63. Thus, the mean fluorescence intensity of the tagged candidate CD19 scFv is expected to increase with increasing concentrations of the candidate CD19 scFv, while the mean fluorescence intensity of tagged FMC63 antibody is not expected to decrease with increasing concentrations of the candidate CD19 scFv. This would indicate that the FMC63 is not displaced from its epitope by the addition of the candidate CD19 scFv, suggesting distinct binding epitopes. For candidate CD19 scFv that bind to the same epitope as FMC63, a decrease in the fluorescence intensity of FMC63 with increasing concentrations of the candidate CD19 scFv is expected.

Example 31. Functional analysis of FMC63-distinct CD19 CAR constructs

[00648] FMC63-distinct CD19 scFvs engineered to generate FMC63-distinct CD19 CAR constructs with destabilizing domains, linkers, transmembrane and intracellular domains described in Table 1, and Tables 6, 7, 8A or 8B. The ability of FMC63-distinct CD19 CAR to induce cell activation, cytotoxicity and proliferation is compared to the FMC63-CD19 based CAR constructs in Jurkat cells. Constructs are also analyzed for their ability to induce the upregulation of exhaustion markers, PD1, TIM3 and LAG3, and constructs that are positive for multiple exhaustion markers are excluded from the analysis. Constructs that can induce Jurkat cell activation and cytotoxicity but not exhaustion markers are transduced into T cells and their efficacy is compared with the constitutively expressed FMC63-based CD19 CAR construct. It is expected that DD regulated FMC63-distinct CD19 CAR constructs will demonstrate superior cytotoxic capabilities with minimal tonic signaling as compared to FMC63 CD19 CAR constructs.

Example 32. Ligand dependent target cell death induced by DD regulated CD19 CAR

[00649] To test the antigen specificity of cell killing by T cells engineered to express constitutive or DD-containing CAR construct, CD19 was ectopically expressed in the antigen negative K562 cell line. CD19 expression was measured using anti-CD19 antibody conjugated to Phycoerythrin (PE). Figure 30A shows the expression of CD19 in parental K562 cells and K562 CD19 cells, wherein CD19 is ectopically expressed.

[00650] To test the ability of DD regulated CD19 CAR cells to kill target cells, primary T cell populations were transduced with DD regulated CD19 CAR constructs, OT-CD19-024 with human DHFR DD and an EFla promoter. Transduced T cells were co cultured with K562 cells expressing CD19 (target cells) at a ratio of 5:1 in the presence or absence of TMP (1OOpM). Additional control combinations of T cells and target cells were also set up. These included DD regulated CAR expressing T cells co cultured with antigen-negative K562 cells (in the presence or absence of the ligand), untransduced T cells co cultured with K562 cells expressing CD19 and K562 cells expressing CD19 without T cell co culture. The T cells utilized for this experiment were transduced with the OT-CD19-024 construct (or untransduced) and expanded for 11 days using protocols described in previous examples, frozen, thawed and co-cultured with target cells. Target cells were treated with Mitomycin C to prevent their proliferation. The K562 or K562 CD19 target cells stably expressing the fluorescent protein NucLight Red were co cultured with T cells for 300 hours. Cell death was monitored by labelling cells with Annexin V and the cell death in target K562 and K562-CD19 cells was monitored by evaluating cells that were positive for both Annexin V and NucLight Red using the IncuCyte@ Live Cell Analysis System (Essen Biosciences, Ann Arbor, MI). The results are presented in Figure 30B, where the killed target cells represented on the y axis are based on target cells that are positive for both NucLight Red and Annexin V. Figure 30C, shows the killed target size as measured in (pM/well) at day 5. Target cell killing was observed with the OT-CD19-024 construct only in TMP treated co cultures of T cells and K562 target cells ectopically expressing CD19. No cell killing was observed in untreated controls of the same co-culture set up and when T cells were co cultured with parental K562 cells that do not express CD19 in the presence or absence of ligand. These data show that regulated CARs display ligand- and target-dependent cell killing with minimal basal off-state.

Example 33. In vitro CAR-T cell functional analysis

[00651] The efficacy of T cells expressing DD regulated CD19 CAR constructs in functionally interacting with target cells is evaluated. To interact with the CD19CAR T cells, the chosen target cells express CD19 naturally or ectopically. In this context, target cells which have high endogenous expression of CD19 such as Nalm6, Raji, Reh, Sem, Kopn8, and Daudi cells. Alternatively, target cell lines may be engineered by ectopic expression of CD19 in cell lines that have low endogenous expression of CD19 such as K562. Multiple assays are used to measure functionality. Prior to co culture, the target cells are optionally cultured in the presence of presence of mitomycin C to prevent target cell proliferation. This ensures that target cell growth does not out compete T cell growth. Cytotoxicity assays are used to measure the ability of T cells induce target cell death. Target cells are engineered to express Renilla or Firefly luciferase and co cultured with T cells expressing DD regulated CD19 CAR constructs for 18 to 24 hours in the presence of the ligand related to the DD or vehicle control. At the end of co culture, cells are lysed and luciferase activity is measured using appropriate substrate. Luciferase activity is expected to increase when DD regulated CD19 CAR expressing T cells are co cultured with CD19 expressing target cells in the presence of ligand. Cytotoxicity is not expected in vehicle control cells or when the target cells do not express CD19 are utilized.

[00652] Engagement of the CD19 CAR with CD19 antigen results in the activation of T cells which is measured 24 hours after co culture of CAR expressing T cells and target cells. Activation of T cells is evaluated by measuring levels of IFNg, IL2, and CD69. T cell proliferation in response to antigen mediated T cell activation is measured by labelling T cells with Carboxyfluorescein succinimidyl ester, which is used to trace cells across multiple generations. Labelled T cells are cultured with Mitomycin treated target cells and cell proliferation is tracked over a period of 3 to 5 days. T cell proliferation and activation is expected to increase when DD regulated CD19 CAR expressing T cells are co cultured with CD19 expressing target cells in the presence of ligand. Both parameters are not expected in vehicle control cells or when the target cells do not express CD19 are utilized.

[00653] Activation of T cells results in degranulation, an exocytic process by which cytotoxic T cells release molecules like perforin and granzymes which enable target cell killing. Degranulation is measured by analysis of media for indications of exocytosis e.g. CD107 by FACS and by markers of degranulation such as perforin and granzyme using immunoassays.

Example 34. Ligand dependent target cell death induced by DD regulated CD19 CAR

[00654] To test the ability of DD regulated CD19 CAR cells to kill target cells, primary T cell populations are transduced with DD regulated CD19 CAR constructs are co cultured with K562 cells expressing CD19 (target cells) at a ratio of 5:1 in the presence or absence of the ligand specific to the DD e.g. Shield-i (1pM),TMP (100pM) or MTX. Constructs with FKBP, ecDHFR or human DHFR DDs may be utilized. Constructs with either CMV, EFla or PGK promoters may also be used. Multiple combinations of T cells and target cells are set up. These included DD regulated CAR expressing T cells co cultured with K562 cells (in the presence or absence of the ligand), T cells co cultured with K562 cells expressing CD19 and K562 cells expressing CD19 without T cell co culture. Additional controls include target cells only; untransduced T cells; T cells transduced with empty vector. The T cells utilized for this experiment are expanded for 11 days using protocols described in previous examples, frozen, thawed and transduced with the CD19 CAR constructs. Target cells are treated with Mitomycin C to prevent their proliferation. The K562 cells are fluorescently labelled with NucLight Red and co cultured with T cells for 300 hours. Cell death is monitored by labelling cells with Annexin V and the cell death in target K562 cells is monitored by evaluating cells that are positive for both Annexin V and NucLight Red using the IncuCyte@ Live Cell Analysis System (Essen Biosciences, Ann Arbor, MI). Target cell killing is expected with the DD regulated CAR constructs only in the presence of ligand and when K562 target cells ectopically expressing CD19 are utilized. No cell killing is expected in untreated controls of the same co-culture set up and when T cells are co cultured with parental K562 cells that do not express CD19 in the presence or absence of ligand. Constitutive constructs are predicted to show cell killing both in the presence of ligand. Cell killing is also not expected in cocultures with untransduced T cells, T cells transduced with empty vector; and cultures of target cells only.

Example 35. Effect of Ligand on Cytokine Expression

[00655] To study the effect of ligand on the expression of cytokines in regulated CD19 CAR constructs, T cell populations were transduced with empty vector, OT-CD19-017, OT-CD19 023, OT-CD19-024, or OT-CD19-025. 5x10 4 transduced T cells were co cultured for 48 hours at an E:T (effector to target cell) ratio of 5:1 in the presence or absence of TMP or Shield-1. Target cells were treated with 50 ug/ml of Mitomycin C to prevent their proliferation. The cytokine concentration of IFNy and IL2 in the media supernatant were determined for each construct using MSD V-PLEX Proinflammatory Panel 1 Human Kit. The readout was obtained using a MESO QuickPlex SQ120. As shown in Figure 31A, a 6 fold increase in IFNy concentration was seen with the addition of ligand for OT-CD19-024, and a 2 fold increase in IFN concentration was seen with the addition of ligand for OT-CD19-025. As shown inFigure 31B, a 6 fold increase in IL2 was seen for OT-CD19-024 with the addition of ligand and a 9 fold increase was seen for OT-CD19-025 with TMP.

Example 36. In vivo time course study of IL12 levels in mice

[00656] HCT116 parental cells or cells transduced with IL12 constructs (OT-IL12-020, OT IL12-026, or OT-IL12-029) were injected into immune compromised CD1 nude mice (n=4 per group) according to the study design in Table 30 below.

Table 30. Study Design HCT116 cells Day 15 Dose Concentration Route of Day 15 Dose Vehicle n/a Intraperitoneal OT-1L12-026 Shield-1 (1x) 10 mg/kg Intraperitoneal Shield-1 (3x, 2h apart) 10 mg/kg Intraperitoneal Vehicle n/a Intraperitoneal OT-1L12-029 Shield-1 (1x) 10 mg/kg Intraperitoneal Shield-1 (3x, 2h apart) 10 mg/kg Intraperitoneal Vehicle n/a Intraperitoneal OT-IL12-020 Shield-1 (1x) 10 mg/kg Intraperitoneal

n/a Intraperitoneal Parental Vehicle Shield-1 (1x) 10 mg/kg Intraperitoneal

[00657] The mice were bled (blood harvested for plasma PK and IL12 MSD) at day 14 after subcutaneous injection of 5x10 6 cells (day 0), and 6, 10, and 24 hours post the day 15 dosing. At the end of the study, tumor and kidneys were minced with the razor in 500 ul PBS, spun down, and supernatant isolated for IL12 Meso Scale Diagnostic(MSD) assay.

[00658] As shown in Figure 32A, the basal plasma IL12 levels of the DD constructs were high, but the OT-IL12-026 and OT-IL12-029 constructs were still 100-fold lower than the constitutive (OT-IL12-020) construct. When Figure 32A is shown as fold change from pre-dose plasma, OT IL12-026 shows regulation at 6 and 10 hours. Figures 32B and 32C show that IL12 is detectable in kidney (Figure 32B) and tumor (Figure 32C) and the levels coordinate with plasma levels.

Example 37. In vivo time course study of IL12 levels in mice

[00659] HCT116 parental cells or cells transduced with IL12 constructs (OT-IL12-020, OT IL12-026) were injected subcutaneously into Matrigel plus in female NSG mice (implant 200 ul matrigel plug with 1x107 cells) (n=4) according to the study design in Table 31 below. Table 31. Study Design HCT116 cells Dose Harvest Plug Coverage above EC50 Vehicle (1x) 8 hours after 1'dose Vehicle (1x) 24 hours after 1" dose AquaShield-100 mg/kg (1x) 8 hours after 1'dose 4 hours AquaShield-100 mg/kg (2x, 4 hours 8 hours after 1'dose 8 hours OT-IL12-026 between doses) AquaShield-100 mg/kg (1x) 24 hours after 1' dose 4 hours AquaShield-100 mg/kg (2x, 4 hours 24 hours after 1' dose 8 hours between doses) AquaShield-100 mg/kg (3x, 4 hours 24 hours after 1St dose 12 hours between doses) OT-IL12-020 Vehicle (1x) 24 hours after 1" dose Parental Vehicle (1x) 24 hours after 1" dose

[00660] Terminal collection of plasma (for IL12 MSD), plug supernatants and kidneys were collected. As shown in Figure 33A, regulation of IL12 was achieved in vivo with high dose Aquashield. There was less regulation observed in the plasma (Figure 33B) and there was some flexi-IL12 detected in the kidneys (Figure 33C).

Example 38. Shield-1 Can Induce -40-50x Increases in IL12 Production by Primary Human T Cells Transduced with the IL12-026 Construct

[00661] On Day 0, primary human T cells were stimulated with Dynabeads (T-expander CD3/CD28) at a 3:1 bead:cell ratio. The next day, lentiviruses (empty vector (pLVX-EFla IRES-Puro), OT-IL12-020 (constitutive), or OT-IL12-026 (regulated)) were added at a multiplicity of infection (MOI) of 10 in the presence of LentiBOOST and 5% FBS. On day 2, the cells were washed to remove the LentiBOOST and the bead:cell ratio was reduced to 1:3, and fresh 10% media and IL2 were added. On days 6, 9, and 13 the cells were counted for equal cell number plating, media replaced, ligand was added, and cells were either left unstimulated or restimulated with soluble ImmunoCult TM Human CD3/CD28 T Cell Activator (StemCell Technologies). After overnight incubation (on days 7, 10, and 14), the supernatants were collected for ILI2p4O and p70 MSD assay, and transduction efficiency was analyzed by FACS. OT-IL12-026 T cells were found to be 7% transduced, and OT-IL12-020 (constitutive) T cells were 13% transduced on day 7. Restimulation was shown to increase the expression of IL12 (Figure 34A). Ligand increased production of IL12 by 10-day expanded OT-IL12-026 expressing T cells by 40-50 fold (Figure 34B and Figure 34C).

Example 39. Dose Response of Shield-1 on Transduced T Cells

[00662] Human T cells were activated with CD3/CD28 Dynabeads (Life Technologies) for 1 day prior to transduction with lentiviruses (OT-IL12-026 or vector control), followed by 12-13 days of expansion in culture. T cells that had been transduced with different amounts of virus (4-40 MOI) were exposed to either a dose response of Shield-i for 24h (left panel). T cells that had been transduced at an MOI of 14 were treated with luM Shield-i or vehicle control for increasing amounts of time (right panel). The levels of IL12 that had accumulated in the supernatants (from 100,000 cells per 200uL media) were measured using human IL12p40 MSD V-plex assay kits (Meso Scale Discovery).

[00663] From the analysis, it was shown that the increase in IL12 production by T cells expressing OT-IL12-026 is dose responsive to the ligand, Shield-i Figure 35A, and accumulates over time Figure 35B.

Example 40. In Vivo Dose Response, and Repeat Dosing of AquaShield in NSG Mice with Transferred T Cells Expressing OT-IL12-026

[00664] Primary human T cells were stimulated with Dynabeads (T-expander CD3/CD28) at a 3:1 bead:cell ratio. The next day, lentiviruses (OT-IL12-020 (constitutive), OT-IL12-026 (regulated), or vector control) were added at a multiplicity of infection (MOI) of 10 in the presence of LentiBOOST and 5% FBS. The following day, T cells were washed to remove the LentiBOOST and the bead:cell ratio was reduced to 1:3, and fresh 10% media and IL2 were added. The T cells were expanded for a total of 10 days, and then 25x106 vector control or OT IL12-026 transduced T cells or 10x10 6 constitutive OT-IL12-020 transduced T cells were transferred into NSG mice (study day 0). Three days after cell transfer, the animals were dosed with either vehicle or AquaShield (10, 50 or 100mg/kg). Blood was sampled for plasma analysis of IL12p7Oby MSD assay at 0, 4, 8, and 24h post dosing (Figure 36A). Clear dose responsive increases in plasma IL12 was observed.

[00665] On day 5 post T cell transfer, animals were dosed a second time with AquaShield (Figure 36B). A second increase in plasma IL12 was observed upon repeat dosing with AquaShield. Example 41. In Vivo Regulation of DD-12 Expressed in T Cells

[00666] To determine whether ligand can stabilize DD-IL12 in vivo upon sequential dosing of AquaShield, T cells are transduced with DD-IL12-expressing constructs (OT-IL12-020 or OT IL12-026) and implanted into mice (n=4 per group) (day 0) as outlined in the study design below.

Table 32. Study Design

Group Description A Empty Vector, Day 3-6: oral vehicle daily for 4 days B OT-IL12-020, Day 3-6: oral vehicle daily for 4 days C OT-IL12-026: Day 3-6: oral vehicle daily for 4 days D OT-IL12-026, Day 3-6: Aquashield 50 mg/kg orally daily for 4 days E OT-IL12-026, Day 4 and 6: Aquashield 50 mg/kg orally F Empty Vector, Day 5 and 10: oral vehicle G OT-IL12-020, Day 5 and 10: oral vehicle H OT-IL12-026, Day 5 and 10: oral vehicle I OT-IL12-026, Day 5 and 10: Aquashield 50 mg/kg orally J OT-1L12-026, Day 10: Aquashield 50 mg/kg orally

[00667] For each group, a pre-bleed sample is collected as well as samples at 4 hours and 24 hours after each dose. At the end of the study, tissue and organ samples are collected. FACS analysis is conducted to determine cell numbers and Th1 markers.

[00668] On Day 0, primary human T cells were stimulated with Dynabeads (T-expander CD3/CD28) at a 3:1 bead:cell ratio. The next day, lentiviruses (empty vector (pLVX-EFla IRES-Puro), OT-IL12-020 (constitutive), or OT-IL12-026 (regulated)) were added at a multiplicity of infection (MOI) of 10 in the presence of LentiBOOST and 5% FBS. On day 2, the cells were washed to remove the LentiBOOST and the bead:cell ratio was reduced to 1:3, and fresh 10% media and IL2 were added.

[00669] In vitro evaluation of these cells is shown under Figure 37A-37C.

[00670] After 10 days of expansion, T cells were injected into NSG mice (12 x 106 cells injected, cells were 15% (constitutive) and 7.5% (regulated) IL12 positive by FACS). For each group, a pre-bleed sample was collected as well as plasma samples at 4 hours and 24 hours after each dose. At the end of the study, tissue and organ samples are collected. FACS analysis was conducted to determine T cell numbers in the blood and to assess Th1 phenotypic markers.

[00671] As shown in Figure 37A, IL12 expression in response to sequential pulsed doses of ligand (50 mg/kg Aquashield administered orally on day 4 and 6 (50 mpk Aquashield q48hr)) was elevated in the plasma of mice with T cells expressing OT-IL12-026 as compared to the vehicle treated controls. T cells expressing the empty vector control did not produce IL12. T cells transduced with OT-IL12-020 (IL12-020), the constitutive control, produced IL12 throughout the time course.

[00672] In Figure 37B, elevated plasma IL12 expression in response to sequential pulsed doses of ligand (50 mg/kg Aquashield administered orally for 4 days (day 3-6) (50 mpk Aquashield QDx4)) was seen in mice bearing OT-IL12-026 expressing T cells as compared to the vehicle treated controls. Cells transduced with OT-IL12-020 (IL12-020), the constitutive control, produced IL12 throughout the time course.

[00673] Figure 37C shows the IL12 expression over 11 days for the constitutive construct OT IL12-020 (IL12-020). Ligand-regulated expression of IL12 from T cells expressing DD-IL12 from the construct OT-IL12-026 was seen in mice treated with 50 mg/kg Aquashield administered orally on day 5 and 10 (50 mpk Aquashield d5/10). T cells expressing the empty vector control did not produce IL12.

[00674] Figure 37D shows ligand-induced regulation of plasma IL12 expression from T cells expressing DD-IL12 from the construct OT-IL12-026 when mice were treated orally with 50 mg/kg Aquashield on day 10 (50 mpk Aquashield d10). The single ligand pulse increased plasma IL12 levels over those detected in vehicle-treated control mice harboring OT-IL12-026 expressing T cells.

[00675] Regulation of IL12 for all constructs shown in Figures 37A-37D did not impact IFN levels, instead the levels of IFNy gradually rose over time. This is likely due to the exposure of the T cells to IL12 in culture during the in vitro expansion phase. However, ligand-induced regulation of IL12 increased granzyme B (GrB) (Figure 37E) and perforin expression (Figure 29F) by CD8+ T cells in vivo at day 7 post in vivo T cell transfer.

Example 42. Effect of PGK Promoter and N-terminal FKBP

[00676] HEK293T cells were transiently transfected with Lipofectamine 3000 and 2ug plasmid DNA each of: OT-IL12-019 (PGK promoter), OT-IL12-020 (EFalpha promoter), OT-IL12-025 (PGK promoter, C-terminal FKBP domain), OT-IL12-026 (EF alpha promoter, C-terminal

FKBP domain), OT-IL12-046 (N-terminal FKBP). Ligand (luM Shield-1) was added one day after transfection, and the cells were further cultured for 2 more days. IL12 secretion into the supernatants was quantitated by IL12p4O MSD assay. Genomic DNA (gDNA) and messenger RNA (mRNA) was purified from the cells. The levels of construct DNA integration into the cellular genome and levels of IL12 mRNA expression were quantitated by qPCR using primers specific to the WPRE element and IL12 within the respective constructs.

[00677] The gDNA qPCR analysis demonstrated that the FKBP DD-containing constructs had integrated to similar levels within the cellular genomes, and that the PGK promoter, as expected, generated less IL12 mRNA expression than the EF alpha promoter (Figure 38A).

[00678] Due to the lower levels of mRNA transcription induced by the PGK promoter, the IL12p4O MSD assay also demonstrated that the PGK promoter reduced both basal and peak IL12 levels of secretion as compared to the construct using the EFlalpha promoter. Thelowerbasal levels of IL12 production downstream of the PGK promoter resulted in -2 fold improved ligand induced IL12 regulation as compared with the construct with the EFlalpha promoter (Figure 38B). More specifically, the ligand-induced regulation of IL12 expression increased from 6-fold to 13-fold with the change from the EFlalpha to the PGK promoter, respectively.

[00679] Constructs containing FKBP either at the N-terminus or at the C-terminus of IL12 were integrated similarly into the cellular genome and generated similar levels of mRNA (Figure 38A). However, while C-terminal containing FKBP constructs regulate IL12 expression, the N terminal-containing FKBP construct failed to regulate IL12 expression (Figure 38B). Example 43. Kinetics of ligand-dependent stabilization of DD-IL15- IL15Ra

[00680] The on/off kinetics of ligand-dependent stabilization of DD-IL15-IL15Ra was measured in CD4 positive T cells. T cells were activated with CD3/CD28 beads at 3:1 bead to T cell ratio in 24-well plates for 24 hrs. Lentivirus was added to wells in the presence of LentiBoost reagent, and cells were incubated for another 24 hrs and washed. Cells were resuspended in fresh media, and media was added every 2-3 days to expand and maintain cells at 0.5-1x10 6/ml. After 7 days of expansion, T cells transduced with the ecDHFR DD-IL15-IL15Ra fusion construct (OT-IL15-009) were treated with100pM ecDHFR ligand Trimethoprim (TMP) or vehicle control, DMSO. At multiple time points (i.e., 1, 2, 4, 6, 8, 15, 22 and 24 hrs) after TMP treatment, the transduced T cells were collected and analyzed for ILI5Ra surface expression using anti-ILI5Ra antibodies by flow cytometry. Untransduced T cells were used as a negative control. The T cells were sorted into CD4 positive and CD8 positive populations and the percentage of IL15Ra positive CD4 positive T cells was analyzed. Figure 39 shows the kinetics of surface expression of IL15Ra on CD4 T cells after TMP treatment. Among the CD4 positive T cells transduced with the OT-IL15-009 construct, the proportion of cells with surface expression of IL15Ra remained similar for both TMP treated and DMSO treated cells until 2 hrs after TMP treatment, and was comparable to that of untransduced cells. However, from 4 hrs after TMP treatment, the cells transduced with the OT-IL15-009 construct and treated with TMP exhibited an increased proportion of cells with surface expression of IL15Ra. This trend was observed until 22 hours after treatment with TMP. The CD4 positive T cells with surface expressed IL15Ra cells constituted ~-% of untransduced cells, indicating that the proportion of cells that expressed endogenous IL15Ra is low. Example 44. Ligand-dependent stabilization of DD-IL15-IL15Ra fusion molecules in vivo

[00681] To examine whether ligand treatment induces stabilization of the DD-IL15-IL15Ra fusion molecules in vivo, HCT116 cells transduced with the OT-IL15-009 construct were implanted subcutaneously in BALB/c nude mice and treated with TMP. TMP was orally administered to mice at a dose of 100 mg/kg, twice a day for11 days after implantation, followed by administration of TMP at the dose of 300 mg/kg, twice a day for 6 days. As a negative control, separate mice implanted with HCT116 cells transduced with the OT-IL15-009 construct were treated with the vehicle twice a day for 17 days. At 4 hrs after the last dosing of TMP or the vehicle control, tumors were harvested from the mice and analyzed for the levels of IL15-IL15Ra fusion molecules by western blotting. As shown in Figure 40, HCT116 tumors harvested from mice treated with TMP exhibited elevated levels of IL15-IL15Ra expression, compared to tumors treated with the vehicle. The GAPDH level was analyzed as a loading control. These data show that administration of ligand enabled stabilization of the DD-IL15 IL15Ra fusion molecule in vivo.

[00682] Consistent with the efficacy of TMP-dependent IL15-IL15Ra stabilization in vivo, elevated levels of TMP (399.38 ng/g tumor) were observed in HCT116 tumors harvested from mice treated with TMP for 17 days. The levels of TMP associated with HCT116 tumors were considerably higher than those observed in mouse plasma at day 3 (15.67 ng/ml plasma) and at day 17 (99.5 ng/ml plasma), indicating that the orally administered TMP was successfully delivered to and accumulated in HCT116 tumors implanted in mice.

Example 45. Shedding resistant IL15-IL15Ra constructs

[00683] To maintain the efficiency of the trans-presentation of IL15 via the IL15-ILI5Ra fusion molecule, the IL15-IL15Ra shedding needs to be prevented. For this purpose, new DD-IL15 ILI5Ra and constitutive IL15-ILI5Ra constructs are designed through a variety of modifications on the IL15-IL15Ra fusion molecule. For example, the IL15 molecule or the IL15Ra molecule is truncated or mutated to remove presumable cleavage sites. ILI5Ra has a cleavage site (PQGHSDTT from the position 168 to 175 of SEQ ID NO. 803) in the extracellular domain immediately distal to the transmembrane domain of the receptor, as described by Bergamaschi C et al. (2008). J Biol Chem ;283(7):4189-99; Anthony SM et al. (2015). PLoS One. 10(3): e0120274), and International Patent Application Publication Nos. W02014066527 and W02009002562 (the contents of each of which are incorporated herein by reference in their entirety). Tumor necrosis factor-alpha-converting enzyme (TACE/ADAM17) has been implicated as a protease that cleaves between glycine (at the position 170 of SEQ ID NO. 803) and histidine (at the position 171 of SEQ ID NO. 803) and generates a naturally occurring soluble form of IL15Ra. The same mechanism can be responsible for the IL15-IL15Ra shedding. Hence, the cleavage site of ILI5Ra is mutated such that cleavage by an endogenous protease is prevented. The mutation of the cleavage site is introduced by substitution, insertion or deletion of amino acid residues. The IL15-IL15Ra fusion molecule is also modified such that the full length or truncated IL15-IL15Ra fusion molecule is fused to heterologous hinge domains and/or heterologous transmembrane domains. As non-limiting examples, variants of ILI5Ra can be utilized. Additionally, the length and sequence of the linkers that connect IL15 and IL15Ra are modified.

[00684] To confirm that the modifications on the IL15-ILI5Ra fusion molecule prevent shedding, the new DD-IL15-IL15Ra or constitutive IL15-IL15Ra constructs are introduced into HCT-116 cells. Surface expression of IL15 and ILI5Ra on the HCT-116 cells is examined by flow cytometry using anti-IL15 and IL15Ra antibodies to assess surface IL15-IL15Ra shedding. The presence or absence of IL15 in the cell culture supernatant is also analyzed by MSD assay. As a functional assay based on the sensitivity of NK cell activation by shed IL15 in tumor supernatant, the transwell assay is conducted using HCT-116 cells transduced with new DD IL15-IL15Ra or constitutive IL15-IL15Ra expressing constructs and NK cells. The new DD IL15-ILI5Ra-expressing constructs that do not induce activation of NK cells in the presence of ligand and the new constitutive IL15-IL15Ra-expressing constructs that do not induce activation of NK cells are chosen for use in future experiments. Example 46. Regulated expression of IL15-IL15Ra fusion molecule with C-terminal DD

[00685] A fusion molecule is generated by fusing membrane bound IL15, IL15 Receptor alpha subunit (IL15Ra) and a human DHFR (DD). These fusion molecules were cloned into pLVX EFla-IRES-Puro vector.

[00686] To test ligand dependent IL15-IL15Ra production, 1 million HEK-293T cells were plated in a 6-well plate in growth media containing DMEM and 10 FBS and incubated overnight at 37°C, 5% C02. Cells were then transfected with 100ng of constitutive IL15-IL15Ra (OT IL15-008) or DD linked IL15-IL15Ra (OT-IL15-037 or OT-IL15-040) using Lipofectamine 2000 and incubated for 24 hrs. Following the incubation, media is exchanged for growth medium with or without 50pM Trimethoprim (TMP) and further incubated for 48 hrs. Cells were harvested and IL15 levels are analyzed via western blotting using human IL15 antibody (Abcam, Cambridge, UK). The molecular weight of IL15Ra in OT-IL15-037 and OT-IL15-040 appeared to be the same as OT-IL15-008.

[00687] To test if IL15 is shed into the media, supernatant from HEK293 cells expressing IL15 IL15Ra fusion constructs was subject to immunoassays such as MSD (Rockville, Maryland). 48 hours after transfection, cells were analyzed and, as expected, constitutive IL15-IL15Ra construct OT-IL15-008 showed high surface expression of IL15 in the presence and absence of ligand. OT-IL15-037 and OT-IL15-040 showed the ligand (Trimethoprim) dependent surface expression of IL15 and IL15Ra (Figure 41). The detection of membrane bound IL15-IL15Ra fusion constructs in the supernatant suggests that IL15 constructs are likely shed from the cell surface.

Example 47. Effect TMP exposure to TMP in vitro on membrane bound IL15 expression

[00688] In order to determine if the dose and time of exposure to TMP in vitro influenced membrane bound IL15 expression, an in vitro dose response study was conducted with T cells expressing OT-IL15-073.For this purpose, T cells were activated with CD3/CD28 beads at 3:1 bead to T cell ratio in 24-well plates for 24 hrs. Lentivirus was added to wells. After 24 hrs, fresh media was added every 2-3 days to expand cells while maintaining cells at 0.5-1x10 6/ml. On day 11 of expansion. T cells treated with TMP starting at 100 uM, 1Ox dilutions and 9 points were analyzed after 2 hours in culture (washed 3x after TMP addition, fresh media added without TMP for 22 hours), 6 hours in culture, or 24 hours in culture and the results are shown in Figure

42A. As shown in Figure 42B and Table 33, this study showed that TMP ligand regulates membrane bound IL15 expression and the dose and time of exposure to TMP in vitro influences membrane bound IL15 expression. Table 33. Membrane Bound IL15 Expression TMP EC50, uM EC90, uM EC50, uM (total EC90, uM (total Treatment (%IL15+IL15Ra+) (%IL15+IL15Ra+) IL15 MFI) IL15 MFI) 24 hour 0.035 0.255 0.063 0.75 24 hour (wash 59.6 11.1 66.9 at 2 hours) 11.5 6 hours 0.021 0.81 0.030 0.88

Example 48. Regulated membrane bound IL15 expression in vivo

[00689] To evaluate regulation of membrane bound IL15 in vivo, 2 constructs were selected for evaluation in vivo. Four group of T cells were used for this study and are outlined in Table 34. In Table 31, "N" represents the number of mice in each group. Table 34. T Cell Groups Group N T Cells Treatment 1 4 Untransduced 24 OT-IL15-071 (pELNS vector, EFla promoter, membrane bound IL15 sequence from OT-IL15-008) 4 OT-IL15-073 (pELNS vector, EFla promoter, Vehicle 3 membrane bound IL15 sequence from OT-IL15-009) 4 OT-1L15-073 (pELNS vector, EFla promoter, TMP 4 membrane bound IL15 sequence from OT-IL15-009)

[00690] The T cells which were to be used as part of the in vivo study were evaluated 6 days post transduction, day of implant (day 9 post transduction) and 13 days post transduction and the cells in Groups 2-4 showed expression of the constructs.

[00691] T cells outlined in Table 31 were administered to mice by intravenous administration (3.9 x 106 cells per mouse implanted). On day 3 the mice were dosed with 500 mg/kg of TMP 3 times (4 hours between doses) and bled 2 hours after each dose. The mice were again bled on day 4, 24 hours after the first TMP dose.

[00692] Figures 43A-43C show the expression of membrane bound IL15, 2, 6, 10, and 24 hours after the first TMP dose, using IL15 staining (Figure 43A), IL15Ra staining (Figure 43B), and IL15/ILI5Ra double ++ staining (Figure 43C). Figure 43D are FACS plots for each mouse 10 hours after the first TMP dose. Figure 43E shows the expression of membrane bound IL15 in blood 2, 6, 10, and 24 hours after the first TMP dose and Figure 43F shows the plasma TMP levels 2, 6, 10, and 24 hours after the first TMP dose.

Example 49. Effect of long term intraperitoneal (IP) or oral (PO) TMP dosing on T cell function

[00693] In this study, T cells transduced with OT-IL15-071 or OT-IL15-073 (no lentiBoost) were administered intravenously to mice (15 x 106 per mouse). 6 study groups were evaluated for this study: (1) untransduced, (2) OT-IL15-071 T cells, (3) OT-IL15-073 PO vehicle, (4) OT IL15-073 PO TMP 500 mg/kg), (5) OT-IL15-073 IP vehicle, and (6) OT-IL15-073 IP TMP 300 mg/kg. The study design is shown in Table 35. PO dosing is 500 mg/kg TMP inO.1M citrate and IP dosing is 300 mg/kg TMP lactate in water. Table 35. Study Design Timepoin Dose Sample Collection t Day -3 Inject T cells in mice by IV administration Day0 PO1xorIP1x 4 hours PO 1x 6 hours Bleed (survival) 24 hours PO 2x or IP 1x Bleed (survival) Day2 PO1xorIP1x Day3 PO1xorIP1x Day4 PO2xorIP1x 120 hours PO 2x or IP 1x Bleed (survival) 126 hours Bleed (survival) Day6 PO2xorIP1x Day7 PO2xorIP1x Day 8 Bleed (survival) Day 19 Bleed (survival) Day 25 Bleed (terminal)

[00694] The regulated expression in blood was analyzed 6 hours and 24 hours after the first dose, and 6 hours after the 5thdose.

[00695] OT-IL15-071 showed expression of membrane bound IL15 and the untransduced control did not show any expression.

[00696] Regulation of membrane bound IL15 was seen with repeat PO and IP dosing. As seen in Figure 44, regulated expression of membrane bound IL15 was detected 6 hours after the first dose on day 0, and 6 hours after dosing on day 5 (126 hrs) with both PO and IP dosing. There was no increase in expression in mice treated with vehicle.

[00697] While the present invention has been described at some length and with some particularity with respect to the several described embodiments, it is not intended that it should be limited to any such particulars or embodiments or any particular embodiment, but it is to be construed with references to the appended claims so as to provide the broadest possible interpretation of such claims in view of the prior art and, therefore, to effectively encompass the intended scope of the invention.

[00698] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, section headings, the materials, methods, and examples are illustrative only and not intended to be limiting.

[00699] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

[00700] Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

Sequence Listing 1 Sequence Listing Information 11 Aug 2023

1-1 File Name 108407-1396217-014AU2 - SEQUENCE LISTING.xml 1-2 DTD Version V1_3 1-3 Software Name WIPO Sequence 1-4 Software Version 2.3.0 1-5 Production Date 2023-08-07 1-6 Original free text language code 1-7 Non English free text language code 2 General Information 2-1 Current application: IP Office 2023214349

2-2 Current application: Application number 2-3 Current application: Filing 2018-03-02 date 2-4 Current application: 108407-1396217-014AU2 Applicant file reference 2-5 Earliest priority application: US IP Office 2-6 Earliest priority application: 62/466,601 Application number 2-7 Earliest priority application: 2017-03-03 Filing date 2-8en Applicant name OBSIDIAN THERAPEUTICS, INC. 2-8 Applicant name: Name Latin 2-9en Inventor name 2-9 Inventor name: Name Latin 2-10en Invention title CD19 COMPOSITIONS AND METHODS FOR IMMUNOTHERAPY 2-11 Sequence Total Quantity 1235

3-1 Sequences 3-1-1 Sequence Number [ID] 1 3-1-2 Molecule Type AA 3-1-3 Length 159 11 Aug 2023

3-1-4 Features source 1..159 Location/Qualifiers mol_type=protein organism=Escherichia coli NonEnglishQualifier Value 3-1-5 Residues MISLIAALAV DRVIGMENAM PWNLPADLAW FKRNTLNKPV IMGRHTWESI GRPLPGRKNI 60 ILSSQPGTDD RVTWVKSVDE AIAACGDVPE IMVIGGGRVY EQFLPKAQKL YLTHIDAEVE 120 GDTHFPDYEP DDWESVFSEF HDADAQNSHS YCFEILERR 159 3-2 Sequences 3-2-1 Sequence Number [ID] 2 3-2-2 Molecule Type AA 3-2-3 Length 187 3-2-4 Features source 1..187 2023214349

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-2-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-3 Sequences 3-3-1 Sequence Number [ID] 3 3-3-2 Molecule Type AA 3-3-3 Length 107 3-3-4 Features source 1..107 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-3-5 Residues GVQVETISPG DGRTFPKRGQ TCVVHYTGML EDGKKFDSSR DRNKPFKFML GKQEVIRGWE 60 EGVAQMSVGQ RAKLTISPDY AYGATGHPGI IPPHATLVFD VELLKLE 107 3-4 Sequences 3-4-1 Sequence Number [ID] 4 3-4-2 Molecule Type AA 3-4-3 Length 327 3-4-4 Features source 1..327 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-4-5 Residues MEETRELQSL AAAVVPSAQT LKITDFSFSD FELSDLETAL CTIRMFTDLN LVQNFQMKHE 60 VLCRWILSVK KNYRKNVAYH NWRHAFNTAQ CMFAALKAGK IQNKLTDLEI LALLIAALSH 120 DLDHRGVNNS YIQRSEHPLA QLYCHSIMEH HHFDQCLMIL NSPGNQILSG LSIEEYKTTL 180 KIIKQAILAT DLALYIKRRG EFFELIRKNQ FNLEDPHQKE LFLAMLMTAC DLSAITKPWP 240 IQQRIAELVA TEFFDQGDRE RKELNIEPTD LMNREKKNKI PSMQVGFIDA ICLQLYEALT 300 HVSEDCFPLL DGCRKNRQKW QALAEQQ 327 3-5 Sequences 3-5-1 Sequence Number [ID] 5 3-5-2 Molecule Type AA 3-5-3 Length 189 3-5-4 Features source 1..189 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-5-5 Residues SVEAVQEITE YAKSIPGFVN LDLNDQVTLL KYGVHEIIYT MLASLMNKDG VLISEGQGFM 60 TREFLKSLRK PFGDFMEPKF EFAVKFNALE LDDSDLAIFI AVIILSGDRP GLLNVKPIED 120 IQDNLLQALE LQLKLNHPES SQLFAKLLQK MTDLRQIVTE HVQLLQVIKK TETDMSLHPL 180 LQEIYKDLY 189 3-6 Sequences 3-6-1 Sequence Number [ID] 6 3-6-2 Molecule Type AA 3-6-3 Length 260 3-6-4 Features source 1..260 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-6-5 Residues MSHHWGYGKH NGPEHWHKDF PIAKGERQSP VDIDTHTAKY DPSLKPLSVS YDQATSLRIL 60 NNGHAFNVEF DDSQDKAVLK GGPLDGTYRL IQFHFHWGSL DGQGSEHTVD KKKYAAELHL 120 VHWNTKYGDF GKAVQQPDGL AVLGIFLKVG SAKPGLQKVV DVLDSIKTKG KSADFTNFDP 180

RGLLPESLDY WTYPGSLTTP PLLECVTWIV LKEPISVSSE QVLKFRKLNF NGEGEPEELM 240 VDNWRPAQPL KNRQIKASFK 260 3-7 Sequences 3-7-1 Sequence Number [ID] 7 3-7-2 Molecule Type AA 11 Aug 2023

3-7-3 Length 231 3-7-4 Features source 1..231 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-7-5 Residues MAGKKVLIVY AHQEPKSFNG SLKNVAVDEL SRQGCTVTVS DLYAMNLEPR ATDKDITGTL 60 SNPEVFNYGV ETHEAYKQRS LASDITDEQK KVREADLVIF QFPLYWFSVP AILKGWMDRV 120 LCQGFAFDIP GFYDSGLLQG KLALLSVTTG GTAEMYTKTG VNGDSRYFLW PLQHGTLHFC 180 GFKVLAPQIS FAPEIASEEE RKGMVAAWSQ RLQTIWKEEP IPCTAHWHFG Q 231 3-8 Sequences 3-8-1 Sequence Number [ID] 8 2023214349

3-8-2 Molecule Type AA 3-8-3 Length 159 3-8-4 Features REGION 1..159 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..159 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-8-5 Residues MISLIAALAV DYVIGMENAM PWNLPADLAW FKRNTLNKPV IMGRHTWESI GRPLPGRKNI 60 ILSSQPGTDD RVTWVKSVDE AIAACGDVPE IMVIGGGRVI EQFLPKAQKL YLTHIDAEVE 120 GDTHFPDYEP DDWESVFSEF HDADAQNSHS YCFEILERR 159 3-9 Sequences 3-9-1 Sequence Number [ID] 9 3-9-2 Molecule Type AA 3-9-3 Length 158 3-9-4 Features REGION 1..158 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..158 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-9-5 Residues ISLIAALAVD YVIGMENAMP WNLPADLAWF KRNTLNKPVI MGRHTWESIG RPLPGRKNII 60 LSSQPGTDDR VTWVKSVDEA IAACGDVPEI MVIGGGRVIE QFLPKAQKLY LTHIDAEVEG 120 DTHFPDYEPD DWESVFSEFH DADAQNSHSY CFEILERR 158 3-10 Sequences 3-10-1 Sequence Number [ID] 10 3-10-2 Molecule Type AA 3-10-3 Length 158 3-10-4 Features REGION 1..158 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..158 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-10-5 Residues ISLIAALAVD HVIGMENAMP WNLPADLAWF KRNTLNKPVI MGRHTWESIG RPLPGRKNII 60 LSSQPGTDDR VTWVKSVDEA IAACGDVPEI MVIGGGRVYE QFLPKAQKLY LTHIDAEVEG 120 DTHFPDYKPD DWESVFSEFH DADAQNSHSY CFEILERR 158 3-11 Sequences 3-11-1 Sequence Number [ID] 11 3-11-2 Molecule Type AA 3-11-3 Length 107 3-11-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..107 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-11-5 Residues GVQVETISPG DGRTFPKRGQ TCVVHYTGML EDGKKVDSSR DRNKPFKFML GKQEVIRGWE 60 EGVAQMSVGQ RAKLTISPDY AYGATGHPGI IPPHATLVFD VELLKPE 107 3-12 Sequences 3-12-1 Sequence Number [ID] 12 3-12-2 Molecule Type AA 3-12-3 Length 107 3-12-4 Features REGION 1..107

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..107 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-12-5 Residues GVQVETISPG DGRTFPKRGQ TCVVHYTGML GDGKKVDSSR DRNKPFKFML GKQEVIRGWE 60 EGVAQMSVGQ GAKLTISPDY AYGATGHPGI IPPHATLVFD VELLELE 107 3-13 Sequences 3-13-1 Sequence Number [ID] 13 3-13-2 Molecule Type AA 3-13-3 Length 187 3-13-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-13-5 Residues MVGSLNCIVA VSQNMGVGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-14 Sequences 3-14-1 Sequence Number [ID] 14 3-14-2 Molecule Type AA 3-14-3 Length 187 3-14-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-14-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWSS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-15 Sequences 3-15-1 Sequence Number [ID] 15 3-15-2 Molecule Type AA 3-15-3 Length 187 3-15-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-15-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKDRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-16 Sequences 3-16-1 Sequence Number [ID] 16 3-16-2 Molecule Type AA 3-16-3 Length 187 3-16-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-16-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL REPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-17 Sequences 3-17-1 Sequence Number [ID] 17 3-17-2 Molecule Type AA 3-17-3 Length 187 3-17-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-17-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELVNKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-18 Sequences 3-18-1 Sequence Number [ID] 18 3-18-2 Molecule Type AA 3-18-3 Length 187 3-18-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-18-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-19 Sequences 3-19-1 Sequence Number [ID] 19 3-19-2 Molecule Type AA 3-19-3 Length 187 3-19-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-19-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMYHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-20 Sequences 3-20-1 Sequence Number [ID] 20 3-20-2 Molecule Type AA 3-20-3 Length 187 3-20-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-20-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRII QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-21 Sequences 3-21-1 Sequence Number [ID] 21 3-21-2 Molecule Type AA 3-21-3 Length 187 3-21-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-21-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEEND 187 3-22 Sequences 3-22-1 Sequence Number [ID] 22 3-22-2 Molecule Type AA 3-22-3 Length 187 3-22-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-22-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKDD 187 3-23 Sequences 3-23-1 Sequence Number [ID] 23 3-23-2 Molecule Type AA 3-23-3 Length 187 3-23-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-23-5 Residues MVGSLNRIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PECPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-24 Sequences 3-24-1 Sequence Number [ID] 24 3-24-2 Molecule Type AA 3-24-3 Length 187 3-24-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-24-5 Residues MVGSLNCIVV VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAYFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-25 Sequences 3-25-1 Sequence Number [ID] 25 3-25-2 Molecule Type AA 3-25-3 Length 187 3-25-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-25-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFKRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-26 Sequences 3-26-1 Sequence Number [ID] 26 3-26-2 Molecule Type AA 3-26-3 Length 187 3-26-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-26-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VITGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTIIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-27 Sequences 3-27-1 Sequence Number [ID] 27 3-27-2 Molecule Type AA 3-27-3 Length 187 3-27-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-27-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKAWFS 60 IPEKNRPLKG RANLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-28 Sequences 3-28-1 Sequence Number [ID] 28 3-28-2 Molecule Type AA 3-28-3 Length 187 3-28-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-28-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPGKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGFKYKF 180 EVYEKND 187 3-29 Sequences 3-29-1 Sequence Number [ID] 29 3-29-2 Molecule Type AA 3-29-3 Length 187 3-29-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-29-5 Residues MVGSLNCIVA VSQNMGIGKN TDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-30 Sequences 3-30-1 Sequence Number [ID] 30 3-30-2 Molecule Type AA 3-30-3 Length 187 3-30-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-30-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINNVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-31 Sequences 3-31-1 Sequence Number [ID] 31 3-31-2 Molecule Type AA 3-31-3 Length 187 3-31-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-31-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLFLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-32 Sequences 3-32-1 Sequence Number [ID] 32 3-32-2 Molecule Type AA 3-32-3 Length 187 3-32-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-32-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSADDALKL TEQPELANKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDAFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-33 Sequences 3-33-1 Sequence Number [ID] 33 3-33-2 Molecule Type AA 3-33-3 Length 187 3-33-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-33-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 AIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-34 Sequences 3-34-1 Sequence Number [ID] 34 3-34-2 Molecule Type AA 3-34-3 Length 187 3-34-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-34-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEFMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-35 Sequences 3-35-1 Sequence Number [ID] 35 3-35-2 Molecule Type AA 3-35-3 Length 187 3-35-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-35-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG RLKLFVTRIM QDFGSDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-36 Sequences 3-36-1 Sequence Number [ID] 36 3-36-2 Molecule Type AA 3-36-3 Length 187 3-36-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-36-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVRRIM QDLESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-37 Sequences 3-37-1 Sequence Number [ID] 37 3-37-2 Molecule Type AA 3-37-3 Length 187 3-37-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-37-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKHKF 180 GVYEKND 187 3-38 Sequences 3-38-1 Sequence Number [ID] 38 3-38-2 Molecule Type AA 3-38-3 Length 187 3-38-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-38-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVHEEND 187 3-39 Sequences 3-39-1 Sequence Number [ID] 39 3-39-2 Molecule Type AA 3-39-3 Length 187 3-39-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-39-5 Residues MVGSLNCIAA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRRLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFL EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-40 Sequences 3-40-1 Sequence Number [ID] 40 3-40-2 Molecule Type AA 3-40-3 Length 187 3-40-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-40-5 Residues MVGSLNCVVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLELFVTRIM QDFESDTFFP EIDLEKYKLL PECPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-41 Sequences 3-41-1 Sequence Number [ID] 41 3-41-2 Molecule Type AA 3-41-3 Length 187 3-41-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-41-5 Residues MVGSLNCIVA VSQNMGIGKN GDSPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 AYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKCKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-42 Sequences 3-42-1 Sequence Number [ID] 42 3-42-2 Molecule Type AA 3-42-3 Length 187 3-42-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-42-5 Residues MVGSLNCIVA VSQNMGIGEN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHLL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 GVYEKND 187 3-43 Sequences 3-43-1 Sequence Number [ID] 43 3-43-2 Molecule Type AA 3-43-3 Length 187 3-43-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-43-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFFRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKFRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-44 Sequences 3-44-1 Sequence Number [ID] 44 3-44-2 Molecule Type AA 3-44-3 Length 187 3-44-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-44-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMRKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIV QDFESDTFFP EIDLEKYKLL PEYPGVLCDV QEEKGIKYKF 180 EVYEKND 187 3-45 Sequences 3-45-1 Sequence Number [ID] 45 3-45-2 Molecule Type AA 3-45-3 Length 187 3-45-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-45-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKA DMVWIVGGSS 120 VYKEAMNHPG HLKLFMTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIRYKF 180 EVYEKND 187 3-46 Sequences 3-46-1 Sequence Number [ID] 46 3-46-2 Molecule Type AA 3-46-3 Length 186 3-46-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-46-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFFRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEFMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-47 Sequences 3-47-1 Sequence Number [ID] 47 3-47-2 Molecule Type AA 3-47-3 Length 187 3-47-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-47-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQDL VIMGKKTWSS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 11 Aug 2023

VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIGLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-48 Sequences 3-48-1 Sequence Number [ID] 48 3-48-2 Molecule Type AA 3-48-3 Length 187 3-48-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-48-5 Residues MVGSLNCIVA VSQNMGIGKN EDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RVNLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGTKYKF 180 EVYEKND 187 3-49 Sequences 3-49-1 Sequence Number [ID] 49 3-49-2 Molecule Type AA 3-49-3 Length 449 3-49-4 Features REGION 1..449 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..449 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-49-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPPVAGP 240 SVFLFPPKPK DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSRDEL 360 TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS KLTVDKSRWQ 420 QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449 3-50 Sequences 3-50-1 Sequence Number [ID] 50 3-50-2 Molecule Type AA 3-50-3 Length 223 3-50-4 Features REGION 1..223 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..223 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-50-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSC 223 3-51 Sequences 3-51-1 Sequence Number [ID] 51 3-51-2 Molecule Type AA 3-51-3 Length 234 3-51-4 Features REGION 1..234 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..234 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-51-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSNYHLE NEVARLKKLS GGTAALGCLV KDYFPEPVTV SWNSGALTSG 180 VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSC 234 3-52 Sequences 3-52-1 Sequence Number [ID] 52 3-52-2 Molecule Type AA

3-52-3 Length 460 3-52-4 Features REGION 1..460 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..460 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-52-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSNYHLE NEVARLKKLS GGTAALGCLV KDYFPEPVTV SWNSGALTSG 180 VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSCDKTHTC 240 PPCPAPPVAG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA 300 KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKG LPSSIEKTIS KAKGQPREPQ 360 VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY 420 SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 460 3-53 Sequences 2023214349

3-53-1 Sequence Number [ID] 53 3-53-2 Molecule Type AA 3-53-3 Length 241 3-53-4 Features REGION 1..241 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..241 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-53-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKRLTIIK DNSKSQVFLK MNSLQTDDTA IYYCAKHYYY GGSYAMDYWG QGTSVTVSSA 120 STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG 180 LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKKVEPK SCGGGGSNYH LENEVARLKK 240 L 241 3-54 Sequences 3-54-1 Sequence Number [ID] 54 3-54-2 Molecule Type AA 3-54-3 Length 471 3-54-4 Features REGION 1..471 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..471 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-54-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCGGGGSNY HLENEVARLK 240 KLGGSDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN 300 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK GLPSSIEKTI 360 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 420 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 471 3-55 Sequences 3-55-1 Sequence Number [ID] 55 3-55-2 Molecule Type AA 3-55-3 Length 120 3-55-4 Features REGION 1..120 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..120 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-55-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 3-56 Sequences 3-56-1 Sequence Number [ID] 56 3-56-2 Molecule Type AA 3-56-3 Length 111 3-56-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-56-5 Residues DIQLTQSPAS LAVSLGQRAT ISCKASQSVD YDGDSYLNWY QQIPGQPPKL LIYDASNLVS 60 GIPPRFSGSG SGTDFTLNIH PVEKVDAATY HCQQSTEDPW TFGGGTKLEI K 111 3-57 Sequences 3-57-1 Sequence Number [ID] 57 3-57-2 Molecule Type AA 11 Aug 2023

3-57-3 Length 464 3-57-4 Features REGION 1..464 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..464 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-57-5 Residues MEWSWIFLFL LSGTAGVHSE VQLQQSGPEL IKPGASVKMS CKASGYTFTS YVMHWVKQKP 60 GQGLEWIGYI NPYNDGTKYN EKFKGKATLT SDKSSSTAYM ELSSLTSEDS AVYYCARGTY 120 YYGSRVFDYW GQGTTLTVSS AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT 180 WNSGSLSSGV HTFPAVLQSD LYTLSSSVTV PSSTWPSETV TCNVAHPASS TKVDKKIVPR 240 2023214349

DCGCKPCICT VPEVSSVFIF PPKPKDVLTI TLTPKVTCVV VDISKDDPEV QFSWFVDDVE 300 VHTAQTQPRE EQFNSTFRSV SELPIMHQDW LNGKEFKCRV NSAAFPAPIE KTISKTKGRP 360 KAPQVYTIPP PKEQMAKDKV SLTCMITDFF PEDITVEWQW NGQPAENYKN TQPIMDTDGS 420 YFVYSKLNVQ KSNWEAGNTF TCSVLHEGLH NHHTEKSLSH SPGK 464 3-58 Sequences 3-58-1 Sequence Number [ID] 58 3-58-2 Molecule Type AA 3-58-3 Length 137 3-58-4 Features REGION 1..137 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..137 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-58-5 Residues DIVMTQAAPS IPVTPGESVS ISCRSSKSLL NSNGNTYLYW FLQRPGQSPQ LLIYRMSNLA 60 SGVPDRFSGS GSGTAFTLRI SRVEAEDVGV YYCMQHLEYP FTFGAGTKLE LKRSDPLINK 120 ERGGGGSGGG GSGGGGS 137 3-59 Sequences 3-59-1 Sequence Number [ID] 59 3-59-2 Molecule Type AA 3-59-3 Length 124 3-59-4 Features REGION 1..124 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..124 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-59-5 Residues QVQLQQSGAE VKKPGSSVKV SCKASGYAFS SYWMNWVRQR PGQGLEWIGQ IWPGDGDTNY 60 NGKFKGRATI TADESTNTAY MELSSLRSED TAFYSCARRE TTTVGRYYYA MDYWGQGTTV 120 TVSS 124 3-60 Sequences 3-60-1 Sequence Number [ID] 60 3-60-2 Molecule Type AA 3-60-3 Length 130 3-60-4 Features REGION 1..130 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..130 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-60-5 Residues QITLKESGPT LVKPTQTLTL TCTFSGFSLS TSGVGVGWIR QPPGKALEWL ALIYWDDDKR 60 YSPSLKSRLT ITKDTSKNQV VLTMTNMDPV DTATYYCAHI DYGSGSYSPR TSYYYYMSVW 120 GKGTTVTVSS 130 3-61 Sequences 3-61-1 Sequence Number [ID] 61 3-61-2 Molecule Type AA 3-61-3 Length 125 3-61-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-61-5 Residues QVQLVQSGGG VVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60

ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSS 125 3-62 Sequences 3-62-1 Sequence Number [ID] 62 3-62-2 Molecule Type AA 11 Aug 2023

3-62-3 Length 125 3-62-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-62-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSS 125 3-63 Sequences 2023214349

3-63-1 Sequence Number [ID] 63 3-63-2 Molecule Type AA 3-63-3 Length 228 3-63-4 Features REGION 1..228 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..228 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-63-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHT 228 3-64 Sequences 3-64-1 Sequence Number [ID] 64 3-64-2 Molecule Type AA 3-64-3 Length 98 3-64-4 Features REGION 1..98 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain MOD_RES 64..65 note=Any amino acid MOD_RES 68..69 note=Any amino acid MOD_RES 93 note=Any amino acid MOD_RES 98 note=Any amino acid source 1..98 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-64-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSXXGRXXI SRDNAKNSLF LQMNSLRAED TAXYYCAX 98 3-65 Sequences 3-65-1 Sequence Number [ID] 65 3-65-2 Molecule Type AA 3-65-3 Length 125 3-65-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain MOD_RES 76 note=Any amino acid source 1..125 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-65-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAXNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSS 125 3-66 Sequences 3-66-1 Sequence Number [ID] 66 3-66-2 Molecule Type AA 3-66-3 Length 125 3-66-4 Features REGION 1..125

Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-66-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSS 125 3-67 Sequences 3-67-1 Sequence Number [ID] 67 3-67-2 Molecule Type AA 3-67-3 Length 125 3-67-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-67-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSS 125 3-68 Sequences 3-68-1 Sequence Number [ID] 68 3-68-2 Molecule Type AA 3-68-3 Length 125 3-68-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-68-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSS 125 3-69 Sequences 3-69-1 Sequence Number [ID] 69 3-69-2 Molecule Type AA 3-69-3 Length 125 3-69-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-69-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSS 125 3-70 Sequences 3-70-1 Sequence Number [ID] 70 3-70-2 Molecule Type AA 3-70-3 Length 125 3-70-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-70-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRLA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAKD TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSS 125 3-71 Sequences 3-71-1 Sequence Number [ID] 71 3-71-2 Molecule Type AA 3-71-3 Length 125 3-71-4 Features REGION 1..125 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..125 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-71-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSS 125 3-72 Sequences 11 Aug 2023

3-72-1 Sequence Number [ID] 72 3-72-2 Molecule Type AA 3-72-3 Length 464 3-72-4 Features REGION 1..464 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..464 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-72-5 Residues MEWSWIFLFL LSGTAGVHSE VQLQQSGPEL IKPGASVKMS CKASGYTFTS YVMHWVKQKP 60 GQGLEWIGYI NPYNDGTKYN EKFKGKATLT SDKSSSTAYM ELSSLTSEDS AVYYCARGTY 120 2023214349

YYGSRVFDYW GQGTTLTVSS AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT 180 WNSGSLSSGV HTFPAVLQSD LYTLSSSVTV PSSTWPSETV TCNVAHPASS TKVDKKIVPR 240 DCGCKPCICT VPEVSSVFIF PPKPKDVLTI TLTPKVTCVV VDISKDDPEV QFSWFVDDVE 300 VHTAQTQPRE EQFNSTFRSV SELPIMHQDW LNGKEFKCRV NSAAFPAPIE KTISKTKGRP 360 KAPQVYTIPP PKEQMAKDKV SLTCMITDFF PEDITVEWQW NGQPAENYKN TQPIMDTDGS 420 YFVYSKLNVQ KSNWEAGNTF TCSVLHEGLH NHHTEKSLSH SPGK 464 3-73 Sequences 3-73-1 Sequence Number [ID] 73 3-73-2 Molecule Type AA 3-73-3 Length 120 3-73-4 Features REGION 1..120 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..120 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-73-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 3-74 Sequences 3-74-1 Sequence Number [ID] 74 3-74-2 Molecule Type AA 3-74-3 Length 218 3-74-4 Features REGION 1..218 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..218 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-74-5 Residues EVQLVESGGG LVQPGGSLRL SCAASGVSLP DYGVSWVRQS PGKGLEWVAV IWGSETTYYA 60 DSVKGRFTIS ADTSKNTYLQ MNSLRAEDTA WYCSRHYYYG GSYAMDYWGQ GTLVTVSSAS 120 TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL 180 YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEP 218 3-75 Sequences 3-75-1 Sequence Number [ID] 75 3-75-2 Molecule Type AA 3-75-3 Length 219 3-75-4 Features REGION 1..219 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..219 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-75-5 Residues EVQLVESGGG LVQPGGSLRL SCAASGVSLP DYGVSWVRQS PGKGLEWVAV IWGSETTYYA 60 DSVKGRFTIS ADTSKNTYLQ MNSLRAEDTA IYYCSRHYYY GGSYAMDYWG QGTLVTVSSA 120 STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG 180 LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKKVEP 219 3-76 Sequences 3-76-1 Sequence Number [ID] 76 3-76-2 Molecule Type AA 3-76-3 Length 460 3-76-4 Features REGION 1..460 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..460 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-76-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSNYHLE NEVARLKKLS GGTAALGCLV KDYFPEPVTV SWNSGALTSG 180 11 Aug 2023

VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSCDKTHTC 240 PPCPAPPVAG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA 300 KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKG LPSSIEKTIS KAKGQPREPQ 360 VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY 420 SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 460 3-77 Sequences 3-77-1 Sequence Number [ID] 77 3-77-2 Molecule Type AA 3-77-3 Length 242 3-77-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain 2023214349

source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-77-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCGGGGSNY HLENEVARLK 240 KL 242 3-78 Sequences 3-78-1 Sequence Number [ID] 78 3-78-2 Molecule Type AA 3-78-3 Length 471 3-78-4 Features REGION 1..471 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..471 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-78-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTVSS 120 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCGGGGSNY HLENEVARLK 240 KLGGSDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN 300 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK GLPSSIEKTI 360 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 420 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 471 3-79 Sequences 3-79-1 Sequence Number [ID] 79 3-79-2 Molecule Type AA 3-79-3 Length 118 3-79-4 Features REGION 1..118 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..118 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-79-5 Residues EVKLQESGPG LVAPSQSLSV TCTVSGVSLP DYGVSWIRQP PRKGLEWLGV IWGSETTYYN 60 SALKSRLTII KDNSKSQVFL KMNSLQTDDT AIYYCAKHYY YGGSYAMDYW GQGTSVTV 118 3-80 Sequences 3-80-1 Sequence Number [ID] 80 3-80-2 Molecule Type AA 3-80-3 Length 119 3-80-4 Features REGION 1..119 Location/Qualifiers note=Description of Artificial Sequence: Synthetic heavy chain variab le domain source 1..119 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-80-5 Residues EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK PGQGLEWIGY INPYNDGTKY 60 NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT YYYGSRVFDY WGQGTTLTV 119 3-81 Sequences 3-81-1 Sequence Number [ID] 81 3-81-2 Molecule Type AA

3-81-3 Length 112 3-81-4 Features REGION 1..112 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..112 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-81-5 Residues DIQLTQSPSS LSASVGDRVT ITCKASQSVD YDGDSYLNWY QQIPGKAPKL LIYDASNLVS 60 GIPPRFSGSG SGTDYTFTIS SLQPEDIATY HCQQSTEDPW TFGGGTKLQI KR 112 3-82 Sequences 3-82-1 Sequence Number [ID] 82 3-82-2 Molecule Type AA 3-82-3 Length 447 3-82-4 Features REGION 1..447 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..447 2023214349

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-82-5 Residues QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYWMYWVRQA TGQGLEWMGR IDPNSGSTKY 60 NEKFKNRFTI SRDDSKNTAY LQMNSLKTED TAVYYCARDY RKGLYAMDYW GQGTTVTVSS 120 ASTKGPSVFP LAPCSRSTSE STAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 GLYSLSSVVT VPSSSLGTKT YTCNVDHKPS NTKVDKRVES KYGPPCPPCP APEFLGGPSV 240 FLFPPKPKDT LMISRTPEVT CVVVDVSQED PEVQFNWYVD GVEVHNAKTK PREEQFNSTY 300 RVVSVLTVLH QDWLNGKEYK CKVSNKGLPS SIEKTISKAK GQPREPQVYT LPPSQEEMTK 360 NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSRL TVDKSRWQEG 420 NVFSCSVMHE ALHNHYTQKS LSLSLGK 447 3-83 Sequences 3-83-1 Sequence Number [ID] 83 3-83-2 Molecule Type AA 3-83-3 Length 111 3-83-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-83-5 Residues QAVLTQPSSV SGAPGQRVTI SCTGSSSNIG AGYDVHWYQQ LPGTAPKLLI YGNSNRPSGV 60 PDRFSGSKSG TSASLAVTGL QAEDEADYYC QSYDSSLSDV VFGGGTKLTV L 111 3-84 Sequences 3-84-1 Sequence Number [ID] 84 3-84-2 Molecule Type AA 3-84-3 Length 107 3-84-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..107 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-84-5 Residues EIVMTQSPSS LPASVGDRVT ITCRASQNIK TYLHWYQQKP GKAPNLLIYA ASNLQIGVPS 60 RFSGSGSGTD FTLTISSLQP EDFATYFCQQ SYITPPTFGQ GTRLEIK 107 3-85 Sequences 3-85-1 Sequence Number [ID] 85 3-85-2 Molecule Type AA 3-85-3 Length 214 3-85-4 Features REGION 1..214 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..214 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-85-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEIKRTV AAPSVFIFPP 120 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180 LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214 3-86 Sequences 3-86-1 Sequence Number [ID] 86 3-86-2 Molecule Type AA 3-86-3 Length 237 3-86-4 Features REGION 1..237

Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..237 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-86-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEIKRTV AAPSVFIFPP 120 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSGG GGSNYHLENE 180 VARLKKLGGG GSDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC 237 3-87 Sequences 3-87-1 Sequence Number [ID] 87 3-87-2 Molecule Type AA 3-87-3 Length 107 3-87-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..107 2023214349

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-87-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEIT 107 3-88 Sequences 3-88-1 Sequence Number [ID] 88 3-88-2 Molecule Type AA 3-88-3 Length 107 3-88-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..107 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-88-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEIT 107 3-89 Sequences 3-89-1 Sequence Number [ID] 89 3-89-2 Molecule Type AA 3-89-3 Length 115 3-89-4 Features REGION 1..115 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..115 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-89-5 Residues DIVMTQAAPS IPVTPGESVS ISCRSSKSLL NSNGNTYLYW FLQRPGQSPQ LLIYRMSNLA 60 SGVPDRFSGS GSGTAFTLRI SRVEAEDVGV YYCMQHLEYP FTFGAGTKLE LKRAD 115 3-90 Sequences 3-90-1 Sequence Number [ID] 90 3-90-2 Molecule Type AA 3-90-3 Length 107 3-90-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..107 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-90-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEIT 107 3-91 Sequences 3-91-1 Sequence Number [ID] 91 3-91-2 Molecule Type AA 3-91-3 Length 112 3-91-4 Features REGION 1..112 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..112 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-91-5 Residues DIVMTQAAPS IPVTPGESVS ISCRSSKSLL NSNGNTYLYW FLQRPGQSPQ LLIYRMSNLA 60 SGVPDRFSGS GSGTAFTLRI SRVEAEDVGV YYCMQHLEYP FTFGAGTKLE LK 112

3-92 Sequences 3-92-1 Sequence Number [ID] 92 3-92-2 Molecule Type AA 3-92-3 Length 106 11 Aug 2023

3-92-4 Features REGION 1..106 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..106 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-92-5 Residues QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA PQLMLYDVSK RPSGVPHRFS 60 GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVLFGGG TKLTVL 106 3-93 Sequences 3-93-1 Sequence Number [ID] 93 3-93-2 Molecule Type AA 3-93-3 Length 106 2023214349

3-93-4 Features REGION 1..106 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..106 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-93-5 Residues QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA PQLMLYDVSK RPSGVPHRFS 60 GSRSGRAASL IISGLQTEDE ADYFCSSYAG RYNSVLFGGG TKLTVL 106 3-94 Sequences 3-94-1 Sequence Number [ID] 94 3-94-2 Molecule Type AA 3-94-3 Length 110 3-94-4 Features REGION 1..110 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..110 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-94-5 Residues QSALTQPASV SGSPGQSITI FCTGTSSDVG GYNYVSWYQQ LPGTAPKLLI YSNNQRPSGV 60 PDRFSGSKSG TSASLAISGL RSEDEADYYC AAWDDSLSVV FGGGTKLTVL 110 3-95 Sequences 3-95-1 Sequence Number [ID] 95 3-95-2 Molecule Type AA 3-95-3 Length 109 3-95-4 Features REGION 1..109 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..109 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-95-5 Residues QSVLTQPPSV SAAPGQEVTI SCSGSSSNIG NNYVSWYQQL PGTAPKLLIY DNDKRPSGIP 60 DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDGNLSAVF GGGTKVTVL 109 3-96 Sequences 3-96-1 Sequence Number [ID] 96 3-96-2 Molecule Type AA 3-96-3 Length 108 3-96-4 Features REGION 1..108 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..108 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-96-5 Residues SYELTQDPAV SVALGQTVRI TCQGDSLRSY YASWYQQKPG QAPVLVIYDK NNRPSGIPDR 60 FSGSSSGNTA SLTITGAQAE DEADYYCNSR DSSGNNWVFG GGTKLTVL 108 3-97 Sequences 3-97-1 Sequence Number [ID] 97 3-97-2 Molecule Type AA 3-97-3 Length 107 3-97-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..107 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-97-5 Residues AIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLNWYQQRA GKAPELLIYA ASNLQSGVPS 60 RFSGSGSGTD FTLTITSVQP EDFATYFCQQ GDAFPLTFGP GTKVTIR 107 3-98 Sequences 3-98-1 Sequence Number [ID] 98 11 Aug 2023

3-98-2 Molecule Type AA 3-98-3 Length 109 3-98-4 Features REGION 1..109 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..109 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-98-5 Residues EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP GQAPRLLIYD ASNRATGIPA 60 RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF GQGTKLEIK 109 3-99 Sequences 2023214349

3-99-1 Sequence Number [ID] 99 3-99-2 Molecule Type AA 3-99-3 Length 109 3-99-4 Features REGION 1..109 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..109 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-99-5 Residues AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP GRAPKLLIYD ASNVKAGVPS 60 RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF GQGTKLDIK 109 3-100 Sequences 3-100-1 Sequence Number [ID] 100 3-100-2 Molecule Type AA 3-100-3 Length 111 3-100-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-100-5 Residues QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL PGTAPKLLIY DNNKRPSGIP 60 DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDSSLNRDW VFGGGTKLTV L 111 3-101 Sequences 3-101-1 Sequence Number [ID] 101 3-101-2 Molecule Type AA 3-101-3 Length 109 3-101-4 Features REGION 1..109 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain MOD_RES 5..6 note=Any amino acid MOD_RES 8..9 note=Any amino acid MOD_RES 93 note=Any amino acid MOD_RES 104 note=Any amino acid source 1..109 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-101-5 Residues QSVLXXPXXA SGSPGQSVTV SCTGTGRDIG AYDYVSWYQQ HPGKAPKLLI YGVNKRPSGV 60 PDRFSGSKSD NTASLTVSGL QVEDEADYYC SSXAGRKYVF GTGXKVTVL 109 3-102 Sequences 3-102-1 Sequence Number [ID] 102 3-102-2 Molecule Type AA 3-102-3 Length 112 3-102-4 Features REGION 1..112 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain MOD_RES 61 note=Any amino acid source 1..112 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-102-5 Residues QSALTQPASV SGSPGQSITI SCTETSSDLG GYNYVSWYQH RPGKAPKLII YDVTVRPSGV 60 XDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL WVFGGGTKLT VL 112 3-103 Sequences 11 Aug 2023

3-103-1 Sequence Number [ID] 103 3-103-2 Molecule Type AA 3-103-3 Length 112 3-103-4 Features REGION 1..112 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..112 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-103-5 Residues QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH RPGKAPKLII YDVTVRPSGV 60 SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL WVFGGGTKLT VL 112 2023214349

3-104 Sequences 3-104-1 Sequence Number [ID] 104 3-104-2 Molecule Type AA 3-104-3 Length 110 3-104-4 Features REGION 1..110 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..110 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-104-5 Residues QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH NPGKAPKLII YDVTKRPSGV 60 SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV FGTGTKLDIK 110 3-105 Sequences 3-105-1 Sequence Number [ID] 105 3-105-2 Molecule Type AA 3-105-3 Length 112 3-105-4 Features REGION 1..112 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..112 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-105-5 Residues QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH RPGKAPKLII YDVTVRPSGV 60 SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL WVFGGGTKLD IK 112 3-106 Sequences 3-106-1 Sequence Number [ID] 106 3-106-2 Molecule Type AA 3-106-3 Length 111 3-106-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-106-5 Residues QSVLTQPRSL SGSPGQSVTI ACTGASTDVG GYNYVSWYQQ HPGKAPKLMI YDVNKRPSGV 60 PDRFSGSKSG NTAFLTISGL QAEDEADYYC CSYAGSYTFE VFGGGTKLTV L 111 3-107 Sequences 3-107-1 Sequence Number [ID] 107 3-107-2 Molecule Type AA 3-107-3 Length 111 3-107-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-107-5 Residues QLVLTQPPSV SGSPGQSVTF SCTGASSDVG GYDHVSWYQH HPGKGPKLLI YDVSKRPSGV 60 PDRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGYYTYW LFGGGTKVTV L 111 3-108 Sequences 3-108-1 Sequence Number [ID] 108 3-108-2 Molecule Type AA 3-108-3 Length 106 3-108-4 Features REGION 1..106

Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..106 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-108-5 Residues QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA PQLMLYDVSK RPSGVPHRFS 60 GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVPFGGG TKLTVL 106 3-109 Sequences 3-109-1 Sequence Number [ID] 109 3-109-2 Molecule Type AA 3-109-3 Length 99 3-109-4 Features REGION 1..99 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..99 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-109-5 Residues SYVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQF PGTAPKLLIY SNNQRPSGVP 60 DRFSGSKSGT SASLAISGLQ SEDEAEYYCA AWDDSLNVV 99 3-110 Sequences 3-110-1 Sequence Number [ID] 110 3-110-2 Molecule Type AA 3-110-3 Length 110 3-110-4 Features REGION 1..110 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..110 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-110-5 Residues QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL PGTAPKLLIY DNNKRPSGIP 60 DRFSGSKSGT SATLGITGLQ TGDEGDYYCG TWDISLRFGV FGGGTKVTVL 110 3-111 Sequences 3-111-1 Sequence Number [ID] 111 3-111-2 Molecule Type AA 3-111-3 Length 111 3-111-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-111-5 Residues QSVLTQPRSV SGSPGQSVTI SCTGPISGVG DYTSVSWYQH YPGKTPKLII YDVTQRPSGV 60 PNRFSGSKSG NTASLTISGL QADDEADYYC CSYEAPTHTY VFGTGTKLTV L 111 3-112 Sequences 3-112-1 Sequence Number [ID] 112 3-112-2 Molecule Type AA 3-112-3 Length 124 3-112-4 Features REGION 1..124 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..124 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-112-5 Residues QVQLQQSGAE LVRPGSSVKI SCKASGYAFS SYWMNWVKQR PGQGLEWIGQ IWPGDGDTNY 60 NGKFKGKATL TADESSSTAY MQLSSLASED SAVYFCARRE TTTVGRYYYA MDYWGQGTTV 120 TVSS 124 3-113 Sequences 3-113-1 Sequence Number [ID] 113 3-113-2 Molecule Type AA 3-113-3 Length 239 3-113-4 Features REGION 1..239 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..239 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-113-5 Residues MRCLAEFLGL LVLWIPGAIG DIVMTQAAPS IPVTPGESVS ISCRSSKSLL NSNGNTYLYW 60 FLQRPGQSPQ LLIYRMSNLA SGVPDRFSGS GSGTAFTLRI SRVEAEDVGV YYCMQHLEYP 120 FTFGAGTKLE LKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER 180

QNGVLNSWTD QDSKDSTYSM SSTLTLTKDE YERHNSYTCE ATHKTSTSPI VKSFNRNEC 239 3-114 Sequences 3-114-1 Sequence Number [ID] 114 3-114-2 Molecule Type AA 11 Aug 2023

3-114-3 Length 111 3-114-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-114-5 Residues QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH HPGKAPKLMI YDFSKRPSGV 60 PDRFSGSKSG NTASLTISGL QAEDEADYYC SSYAAISPNY VFGTGTKLTV L 111 3-115 Sequences 3-115-1 Sequence Number [ID] 115 3-115-2 Molecule Type AA 2023214349

3-115-3 Length 110 3-115-4 Features REGION 1..110 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..110 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-115-5 Residues QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH NPGKAPKLII YDVTKRPSGV 60 SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV FGTGTKLTVL 110 3-116 Sequences 3-116-1 Sequence Number [ID] 116 3-116-2 Molecule Type AA 3-116-3 Length 111 3-116-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-116-5 Residues QSALTQPASV SGSPGQSITI SCTGTSSDVG AYNFVSWYQQ LPGTAPKFLI YDNNKRPPGI 60 PDRFSGSKSG TSATLGITGL QTGDEADYYC ATWDSGLSAV VFGGGTKLTV L 111 3-117 Sequences 3-117-1 Sequence Number [ID] 117 3-117-2 Molecule Type AA 3-117-3 Length 109 3-117-4 Features REGION 1..109 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..109 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-117-5 Residues AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP GRAPKLLIYD ASNVKAGVPS 60 RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF GQGTKLEIK 109 3-118 Sequences 3-118-1 Sequence Number [ID] 118 3-118-2 Molecule Type AA 3-118-3 Length 108 3-118-4 Features REGION 1..108 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..108 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-118-5 Residues AIRMTQSPST LSASVGDRVT ITCRASQSIS HYLAWYQQKP GKAPKLLIFD ASRLASGVPS 60 RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYGAPMFTFG PGTRVDLK 108 3-119 Sequences 3-119-1 Sequence Number [ID] 119 3-119-2 Molecule Type AA 3-119-3 Length 107 3-119-4 Features REGION 1..107 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..107 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-119-5 Residues DIQLTQSPST LSASVGDRVT ITCRASQSIS RWLAWYQQKP GKAPKLLIYD ASNLETGVPS 60 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPLTFGG GTKVEIK 107 3-120 Sequences 11 Aug 2023

3-120-1 Sequence Number [ID] 120 3-120-2 Molecule Type AA 3-120-3 Length 109 3-120-4 Features REGION 1..109 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..109 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-120-5 Residues EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP GQAPRLLIYD ASNRATGIPA 60 RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF GQGTKLDIK 109 2023214349

3-121 Sequences 3-121-1 Sequence Number [ID] 121 3-121-2 Molecule Type AA 3-121-3 Length 111 3-121-4 Features REGION 1..111 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..111 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-121-5 Residues QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH HPGKAPKLMI YDFSKRPSGV 60 PDRFSGSKSG NTASLTISGL QAEDEADYYC CSYAAISPNY VFGTGTKLTV L 111 3-122 Sequences 3-122-1 Sequence Number [ID] 122 3-122-2 Molecule Type AA 3-122-3 Length 121 3-122-4 Features REGION 1..121 Location/Qualifiers note=Description of Artificial Sequence: Synthetic light chain variab le domain source 1..121 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-122-5 Residues EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK PGQGLEWIGY INPYNDGTKY 60 NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT YYYGSRVFDY WGQGTTLTVS 120 S 121 3-123 Sequences 3-123-1 Sequence Number [ID] 123 3-123-2 Molecule Type AA 3-123-3 Length 263 3-123-4 Features REGION 1..263 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..263 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-123-5 Residues WSHPQFEKGG GGSGGGGSDI QMTQTTSSLS ASLGDRVTIS CRASQDISKY LNWYQQKPDG 60 TVKLLIYHTS RLHSGVPSRF SGSGSGTDYS LTISNLEQED IATYFCQQGN TLPYTFGGGT 120 KLEITGSTSG SGKPGSGEGS TKGEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSS 263 3-124 Sequences 3-124-1 Sequence Number [ID] 124 3-124-2 Molecule Type AA 3-124-3 Length 247 3-124-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-124-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGGS GSGNWSHPQF 120 EKGSGSGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG VSWIRQPPRK GLEWLGVIWG 180 SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY YCAKHYYYGG SYAMDYWGQG 240

TSVTVSS 247 3-125 Sequences 3-125-1 Sequence Number [ID] 125 3-125-2 Molecule Type AA 11 Aug 2023

3-125-3 Length 242 3-125-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-125-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSQVQLQESG PGLVKPSETL SLTCTVSGVS LPDYGVSWIR QPPGKGLEWI GVIWGSETTY 180 YSSSLKSRVT ISKDNSKNQV SLKLSSVTAA DTAVYYCAKH YYYGGSYAMD YWGQGTLVTV 240 SS 242 2023214349

3-126 Sequences 3-126-1 Sequence Number [ID] 126 3-126-2 Molecule Type AA 3-126-3 Length 247 3-126-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-126-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYN 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSGGGGS EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP 180 GQAPRLLIYH TSRLHSGIPA RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ 240 GTKLEIK 247 3-127 Sequences 3-127-1 Sequence Number [ID] 127 3-127-2 Molecule Type AA 3-127-3 Length 248 3-127-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..248 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-127-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS SYELTQDPAV SVALGQTVRI TCQGDSLRSY YASWYQQKPG 180 QAPVLVIYDK NNRPSGIPDR FSGSSSGNTA SLTITGAQAE DEADYYCNSR DSSGNNWVFG 240 GGTKLTVL 248 3-128 Sequences 3-128-1 Sequence Number [ID] 128 3-128-2 Molecule Type AA 3-128-3 Length 242 3-128-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-128-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSQVQLQESG PGLVKPSETL SLTCTVSGVS LPDYGVSWIR QPPGKGLEWI GVIWGSETTY 180 YNSSLKSRVT ISKDNSKNQV SLKLSSVTAA DTAVYYCAKH YYYGGSYAMD YWGQGTLVTV 240 SS 242 3-129 Sequences 3-129-1 Sequence Number [ID] 129 3-129-2 Molecule Type AA 3-129-3 Length 242 3-129-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-129-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYN 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSEIVMT QSPATLSLSP GERATLSCRA SQDISKYLNW YQQKPGQAPR 180 LLIYHTSRLH SGIPARFSGS GSGTDYTLTI SSLQPEDFAV YFCQQGNTLP YTFGQGTKLE 240 11 Aug 2023

IK 242 3-130 Sequences 3-130-1 Sequence Number [ID] 130 3-130-2 Molecule Type AA 3-130-3 Length 242 3-130-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-130-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSQVQLQESG PGLVKPSETL SLTCTVSGVS LPDYGVSWIR QPPGKGLEWI GVIWGSETTY 180 YQSSLKSRVT ISKDNSKNQV SLKLSSVTAA DTAVYYCAKH YYYGGSYAMD YWGQGTLVTV 240 SS 242 3-131 Sequences 3-131-1 Sequence Number [ID] 131 3-131-2 Molecule Type AA 3-131-3 Length 246 3-131-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-131-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVLFGGG 240 TKLTVL 246 3-132 Sequences 3-132-1 Sequence Number [ID] 132 3-132-2 Molecule Type AA 3-132-3 Length 252 3-132-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-132-5 Residues QITLKESGPT LVKPTQTLTL TCTFSGFSLS TSGVGVGWIR QPPGKALEWL ALIYWDDDKR 60 YSPSLKSRLT ITKDTSKNQV VLTMTNMDPV DTATYYCAHI DYGSGSYSPR TSYYYYMSVW 120 GKGTTVTVSS GGGGSGGGGS GGGGSAIQLT QSPSFLSASV GDRVTITCRA SQGISSYLNW 180 YQQRAGKAPE LLIYAASNLQ SGVPSRFSGS GSGTDFTLTI TSVQPEDFAT YFCQQGDAFP 240 LTFGPGTKVT IR 252 3-133 Sequences 3-133-1 Sequence Number [ID] 133 3-133-2 Molecule Type AA 3-133-3 Length 249 3-133-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-133-5 Residues QVQLVQSGGG VVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP 180 GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF 240 GQGTKLEIK 249 3-134 Sequences 3-134-1 Sequence Number [ID] 134 3-134-2 Molecule Type AA 3-134-3 Length 249

3-134-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-134-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 GQGTKLDIK 249 3-135 Sequences 3-135-1 Sequence Number [ID] 135 3-135-2 Molecule Type AA 3-135-3 Length 251 3-135-4 Features REGION 1..251 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-135-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDSSLNRDW 240 VFGGGTKLTV L 251 3-136 Sequences 3-136-1 Sequence Number [ID] 136 3-136-2 Molecule Type AA 3-136-3 Length 252 3-136-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-136-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-137 Sequences 3-137-1 Sequence Number [ID] 137 3-137-2 Molecule Type AA 3-137-3 Length 252 3-137-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-137-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-138 Sequences 3-138-1 Sequence Number [ID] 138 3-138-2 Molecule Type AA 3-138-3 Length 252 3-138-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-138-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240

WVFGGGTKLT VL 252 3-139 Sequences 3-139-1 Sequence Number [ID] 139 3-139-2 Molecule Type AA 11 Aug 2023

3-139-3 Length 252 3-139-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-139-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 2023214349

3-140 Sequences 3-140-1 Sequence Number [ID] 140 3-140-2 Molecule Type AA 3-140-3 Length 252 3-140-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-140-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-141 Sequences 3-141-1 Sequence Number [ID] 141 3-141-2 Molecule Type AA 3-141-3 Length 252 3-141-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment MOD_RES 76 note=Any amino acid MOD_RES 201 note=Any amino acid source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-141-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAXNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTETSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV XDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-142 Sequences 3-142-1 Sequence Number [ID] 142 3-142-2 Molecule Type AA 3-142-3 Length 252 3-142-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-142-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-143 Sequences 3-143-1 Sequence Number [ID] 143 3-143-2 Molecule Type AA 3-143-3 Length 250 3-143-4 Features REGION 1..250

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-143-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH 180 NPGKAPKLII YDVTKRPSGV SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV 240 FGTGTKLDIK 250 3-144 Sequences 3-144-1 Sequence Number [ID] 144 3-144-2 Molecule Type AA 3-144-3 Length 252 3-144-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment 2023214349

source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-144-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLD IK 252 3-145 Sequences 3-145-1 Sequence Number [ID] 145 3-145-2 Molecule Type AA 3-145-3 Length 236 3-145-4 Features REGION 1..236 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..236 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-145-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSQSVLT QPRSLSGSPG QSVTIACTGA STDVGGYNYV SWYQQHPGKA PKLMIYDVNK 180 RPSGVPDRFS GSKSGNTAFL TISGLQAEDE ADYYCCSYAG SYTFEVFGGG TKLTVL 236 3-146 Sequences 3-146-1 Sequence Number [ID] 146 3-146-2 Molecule Type AA 3-146-3 Length 251 3-146-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-146-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QLVLTQPPSV SGSPGQSVTF SCTGASSDVG GYDHVSWYQH 180 HPGKGPKLLI YDVSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGYYTYW 240 LFGGGTKVTV L 251 3-147 Sequences 3-147-1 Sequence Number [ID] 147 3-147-2 Molecule Type AA 3-147-3 Length 246 3-147-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-147-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVPFGGG 240 TKLTVL 246 3-148 Sequences

3-148-1 Sequence Number [ID] 148 3-148-2 Molecule Type AA 3-148-3 Length 239 3-148-4 Features REGION 1..239 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..239 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-148-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS SYVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQF 180 PGTAPKLLIY SNNQRPSGVP DRFSGSKSGT SASLAISGLQ SEDEAEYYCA AWDDSLNVV 239 3-149 Sequences 3-149-1 Sequence Number [ID] 149 3-149-2 Molecule Type AA 2023214349

3-149-3 Length 250 3-149-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-149-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEGDYYCG TWDISLRFGV 240 FGGGTKVTVL 250 3-150 Sequences 3-150-1 Sequence Number [ID] 150 3-150-2 Molecule Type AA 3-150-3 Length 251 3-150-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-150-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRLA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAKD TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPRSV SGSPGQSVTI SCTGPISGVG DYTSVSWYQH 180 YPGKTPKLII YDVTQRPSGV PNRFSGSKSG NTASLTISGL QADDEADYYC CSYEAPTHTY 240 VFGTGTKLTV L 251 3-151 Sequences 3-151-1 Sequence Number [ID] 151 3-151-2 Molecule Type AA 3-151-3 Length 242 3-151-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-151-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYS 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSEIVMT QSPATLSLSP GERATLSCRA SQDISKYLNW YQQKPGQAPR 180 LLIYHTSRLH SGIPARFSGS GSGTDYTLTI SSLQPEDFAV YFCQQGNTLP YTFGQGTKLE 240 IK 242 3-152 Sequences 3-152-1 Sequence Number [ID] 152 3-152-2 Molecule Type AA 3-152-3 Length 242 3-152-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-152-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYQ 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120

GGGGSGGGGS GGGGSEIVMT QSPATLSLSP GERATLSCRA SQDISKYLNW YQQKPGQAPR 180 LLIYHTSRLH SGIPARFSGS GSGTDYTLTI SSLQPEDFAV YFCQQGNTLP YTFGQGTKLE 240 IK 242 3-153 Sequences 3-153-1 Sequence Number [ID] 153 11 Aug 2023

3-153-2 Molecule Type AA 3-153-3 Length 246 3-153-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-153-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 2023214349

PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCSSYAG RYNSVLFGGG 240 TKLTVL 246 3-154 Sequences 3-154-1 Sequence Number [ID] 154 3-154-2 Molecule Type AA 3-154-3 Length 249 3-154-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-154-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP 180 GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF 240 GQGTKLDIK 249 3-155 Sequences 3-155-1 Sequence Number [ID] 155 3-155-2 Molecule Type AA 3-155-3 Length 249 3-155-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-155-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 GQGTKLEIK 249 3-156 Sequences 3-156-1 Sequence Number [ID] 156 3-156-2 Molecule Type AA 3-156-3 Length 252 3-156-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-156-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-157 Sequences 3-157-1 Sequence Number [ID] 157 3-157-2 Molecule Type AA 3-157-3 Length 495 3-157-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-157-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 11 Aug 2023

YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-158 Sequences 3-158-1 Sequence Number [ID] 158 3-158-2 Molecule Type AA 3-158-3 Length 247 2023214349

3-158-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-158-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSGGGGSQVQ LQESGPGLVK PSETLSLTCT VSGVSLPDYG VSWIRQPPGK GLEWIGVIWG 180 SETTYYSSSL KSRVTISKDN SKNQVSLKLS SVTAADTAVY YCAKHYYYGG SYAMDYWGQG 240 TLVTVSS 247 3-159 Sequences 3-159-1 Sequence Number [ID] 159 3-159-2 Molecule Type AA 3-159-3 Length 251 3-159-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-159-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH 180 HPGKAPKLMI YDFSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC SSYAAISPNY 240 VFGTGTKLTV L 251 3-160 Sequences 3-160-1 Sequence Number [ID] 160 3-160-2 Molecule Type AA 3-160-3 Length 250 3-160-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-160-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH 180 NPGKAPKLII YDVTKRPSGV SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV 240 FGTGTKLTVL 250 3-161 Sequences 3-161-1 Sequence Number [ID] 161 3-161-2 Molecule Type AA 3-161-3 Length 247 3-161-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-161-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS DIQLTQSPST LSASVGDRVT ITCRASQSIS RWLAWYQQKP 180 GKAPKLLIYD ASNLETGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPLTFGG 240

GTKVEIK 247 3-162 Sequences 3-162-1 Sequence Number [ID] 162 3-162-2 Molecule Type AA 11 Aug 2023

3-162-3 Length 248 3-162-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..248 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-162-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPST LSASVGDRVT ITCRASQSIS HYLAWYQQKP 180 GKAPKLLIFD ASRLASGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYGAPMFTFG 240 PGTRVDLK 248 2023214349

3-163 Sequences 3-163-1 Sequence Number [ID] 163 3-163-2 Molecule Type AA 3-163-3 Length 242 3-163-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-163-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGGG GSGGGGSGGG 120 GSEVKLQESG PGLVAPSQSL SVTCTVSGVS LPDYGVSWIR QPPRKGLEWL GVIWGSETTY 180 YNSALKSRLT IIKDNSKSQV FLKMNSLQTD DTAIYYCAKH YYYGGSYAMD YWGQGTSVTV 240 SS 242 3-164 Sequences 3-164-1 Sequence Number [ID] 164 3-164-2 Molecule Type AA 3-164-3 Length 251 3-164-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-164-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDVG AYNFVSWYQQ 180 LPGTAPKFLI YDNNKRPPGI PDRFSGSKSG TSATLGITGL QTGDEADYYC ATWDSGLSAV 240 VFGGGTKLTV L 251 3-165 Sequences 3-165-1 Sequence Number [ID] 165 3-165-2 Molecule Type AA 3-165-3 Length 247 3-165-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-165-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSGGGGSQVQ LQESGPGLVK PSETLSLTCT VSGVSLPDYG VSWIRQPPGK GLEWIGVIWG 180 SETTYYQSSL KSRVTISKDN SKNQVSLKLS SVTAADTAVY YCAKHYYYGG SYAMDYWGQG 240 TLVTVSS 247 3-166 Sequences 3-166-1 Sequence Number [ID] 166 3-166-2 Molecule Type AA 3-166-3 Length 250 3-166-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-166-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI FCTGTSSDVG GYNYVSWYQQ 180 LPGTAPKLLI YSNNQRPSGV PDRFSGSKSG TSASLAISGL RSEDEADYYC AAWDDSLSVV 240 11 Aug 2023

FGGGTKLTVL 250 3-167 Sequences 3-167-1 Sequence Number [ID] 167 3-167-2 Molecule Type AA 3-167-3 Length 252 3-167-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-167-5 Residues EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK PGQGLEWIGY INPYNDGTKY 60 NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT YYYGSRVFDY WGQGTTLTVS 120 SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR SSKSLLNSNG NTYLYWFLQR 180 PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE AEDVGVYYCM QHLEYPFTFG 240 AGTKLELKRS DP 252 3-168 Sequences 3-168-1 Sequence Number [ID] 168 3-168-2 Molecule Type AA 3-168-3 Length 247 3-168-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-168-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYS 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSGGGGS EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP 180 GQAPRLLIYH TSRLHSGIPA RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ 240 GTKLEIK 247 3-169 Sequences 3-169-1 Sequence Number [ID] 169 3-169-2 Molecule Type AA 3-169-3 Length 247 3-169-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-169-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYQ 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSGGGGS EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP 180 GQAPRLLIYH TSRLHSGIPA RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ 240 GTKLEIK 247 3-170 Sequences 3-170-1 Sequence Number [ID] 170 3-170-2 Molecule Type AA 3-170-3 Length 249 3-170-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-170-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQEVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNDKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDGNLSAVF 240 GGGTKVTVL 249 3-171 Sequences 3-171-1 Sequence Number [ID] 171 3-171-2 Molecule Type AA 3-171-3 Length 251

3-171-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-171-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH 180 HPGKAPKLMI YDFSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC CSYAAISPNY 240 VFGTGTKLTV L 251 3-172 Sequences 3-172-1 Sequence Number [ID] 172 3-172-2 Molecule Type AA 3-172-3 Length 247 3-172-4 Features REGION 1..247 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-172-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSGGGGSQVQ LQESGPGLVK PSETLSLTCT VSGVSLPDYG VSWIRQPPGK GLEWIGVIWG 180 SETTYYNSSL KSRVTISKDN SKNQVSLKLS SVTAADTAVY YCAKHYYYGG SYAMDYWGQG 240 TLVTVSS 247 3-173 Sequences 3-173-1 Sequence Number [ID] 173 3-173-2 Molecule Type AA 3-173-3 Length 241 3-173-4 Features REGION 1..241 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..241 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-173-5 Residues QVQLQQSGPE LVKPGASVKI SCKASGYAFS SSWMNWVKQR PGKGLEWIGR IYPGDEDTNY 60 SGKFKDKATL TADKSSTTAY MQLSSLTSED SAVYFCARSL LYGDYLDYWG QGTTLTVSSG 120 GGGSGGGGSG GGGSQIVLTQ SPAIMSASPG EKVTMTCSAS SSVSYMHWYQ QKSGTSPKRW 180 IYDTSKLASG VPDRFSGSGS GTSYFLTINN MEAEDAATYY CQQWNINPLT FGAGTKLELK 240 R 241 3-174 Sequences 3-174-1 Sequence Number [ID] 174 3-174-2 Molecule Type AA 3-174-3 Length 248 3-174-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..248 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-174-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS SYELTQDPAV SVALGQTVRI TCQGDSLRSY YASWYQQKPG 180 QAPVLVIYDK NNRPSGIPDR FSGSSSGNTA SLTITGAQAE DEADYYCNSR DSSGNNWVFG 240 GGTKLTVL 248 3-175 Sequences 3-175-1 Sequence Number [ID] 175 3-175-2 Molecule Type AA 3-175-3 Length 246 3-175-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-175-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVLFGGG 240

TKLTVL 246 3-176 Sequences 3-176-1 Sequence Number [ID] 176 3-176-2 Molecule Type AA 11 Aug 2023

3-176-3 Length 252 3-176-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-176-5 Residues QITLKESGPT LVKPTQTLTL TCTFSGFSLS TSGVGVGWIR QPPGKALEWL ALIYWDDDKR 60 YSPSLKSRLT ITKDTSKNQV VLTMTNMDPV DTATYYCAHI DYGSGSYSPR TSYYYYMSVW 120 GKGTTVTVSS GGGGSGGGGS GGGGSAIQLT QSPSFLSASV GDRVTITCRA SQGISSYLNW 180 YQQRAGKAPE LLIYAASNLQ SGVPSRFSGS GSGTDFTLTI TSVQPEDFAT YFCQQGDAFP 240 LTFGPGTKVT IR 252 2023214349

3-177 Sequences 3-177-1 Sequence Number [ID] 177 3-177-2 Molecule Type AA 3-177-3 Length 249 3-177-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-177-5 Residues QVQLVQSGGG VVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP 180 GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF 240 GQGTKLEIK 249 3-178 Sequences 3-178-1 Sequence Number [ID] 178 3-178-2 Molecule Type AA 3-178-3 Length 249 3-178-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-178-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 GQGTKLDIK 249 3-179 Sequences 3-179-1 Sequence Number [ID] 179 3-179-2 Molecule Type AA 3-179-3 Length 251 3-179-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-179-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDSSLNRDW 240 VFGGGTKLTV L 251 3-180 Sequences 3-180-1 Sequence Number [ID] 180 3-180-2 Molecule Type AA 3-180-3 Length 252 3-180-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-180-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 11 Aug 2023

WVFGGGTKLT VL 252 3-181 Sequences 3-181-1 Sequence Number [ID] 181 3-181-2 Molecule Type AA 3-181-3 Length 252 3-181-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-181-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-182 Sequences 3-182-1 Sequence Number [ID] 182 3-182-2 Molecule Type AA 3-182-3 Length 249 3-182-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment MOD_RES 64..65 note=Any amino acid MOD_RES 68..69 note=Any amino acid MOD_RES 93 note=Any amino acid MOD_RES 98 note=Any amino acid MOD_RES 102 note=Any amino acid MOD_RES 104 note=Any amino acid MOD_RES 113 note=Any amino acid MOD_RES 145..146 note=Any amino acid MOD_RES 148..149 note=Any amino acid MOD_RES 233 note=Any amino acid MOD_RES 244 note=Any amino acid source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-182-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSXXGRXXI SRDNAKNSLF LQMNSLRAED TAXYYCAXDQ GXHXYDSAEH AFXIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLXXPXXA SGSPGQSVTV SCTGTGRDIG AYDYVSWYQQ 180 HPGKAPKLLI YGVNKRPSGV PDRFSGSKSD NTASLTVSGL QVEDEADYYC SSXAGRKYVF 240 GTGXKVTVL 249 3-183 Sequences 3-183-1 Sequence Number [ID] 183 3-183-2 Molecule Type AA 3-183-3 Length 252 3-183-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-183-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120

VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-184 Sequences 3-184-1 Sequence Number [ID] 184 11 Aug 2023

3-184-2 Molecule Type AA 3-184-3 Length 252 3-184-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-184-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 2023214349

RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-185 Sequences 3-185-1 Sequence Number [ID] 185 3-185-2 Molecule Type AA 3-185-3 Length 252 3-185-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-185-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-186 Sequences 3-186-1 Sequence Number [ID] 186 3-186-2 Molecule Type AA 3-186-3 Length 252 3-186-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment MOD_RES 76 note=Any amino acid MOD_RES 201 note=Any amino acid source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-186-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAXNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTETSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV XDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-187 Sequences 3-187-1 Sequence Number [ID] 187 3-187-2 Molecule Type AA 3-187-3 Length 252 3-187-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-187-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-188 Sequences 3-188-1 Sequence Number [ID] 188 3-188-2 Molecule Type AA

3-188-3 Length 250 3-188-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-188-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH 180 NPGKAPKLII YDVTKRPSGV SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV 240 FGTGTKLDIK 250 3-189 Sequences 3-189-1 Sequence Number [ID] 189 3-189-2 Molecule Type AA 3-189-3 Length 252 2023214349

3-189-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-189-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLD IK 252 3-190 Sequences 3-190-1 Sequence Number [ID] 190 3-190-2 Molecule Type AA 3-190-3 Length 236 3-190-4 Features REGION 1..236 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..236 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-190-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSQSVLT QPRSLSGSPG QSVTIACTGA STDVGGYNYV SWYQQHPGKA PKLMIYDVNK 180 RPSGVPDRFS GSKSGNTAFL TISGLQAEDE ADYYCCSYAG SYTFEVFGGG TKLTVL 236 3-191 Sequences 3-191-1 Sequence Number [ID] 191 3-191-2 Molecule Type AA 3-191-3 Length 251 3-191-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-191-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QLVLTQPPSV SGSPGQSVTF SCTGASSDVG GYDHVSWYQH 180 HPGKGPKLLI YDVSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGYYTYW 240 LFGGGTKVTV L 251 3-192 Sequences 3-192-1 Sequence Number [ID] 192 3-192-2 Molecule Type AA 3-192-3 Length 246 3-192-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-192-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVPFGGG 240

TKLTVL 246 3-193 Sequences 3-193-1 Sequence Number [ID] 193 3-193-2 Molecule Type AA 11 Aug 2023

3-193-3 Length 239 3-193-4 Features REGION 1..239 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..239 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-193-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS SYVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQF 180 PGTAPKLLIY SNNQRPSGVP DRFSGSKSGT SASLAISGLQ SEDEAEYYCA AWDDSLNVV 239 3-194 Sequences 2023214349

3-194-1 Sequence Number [ID] 194 3-194-2 Molecule Type AA 3-194-3 Length 250 3-194-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-194-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEGDYYCG TWDISLRFGV 240 FGGGTKVTVL 250 3-195 Sequences 3-195-1 Sequence Number [ID] 195 3-195-2 Molecule Type AA 3-195-3 Length 251 3-195-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-195-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRLA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAKD TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPRSV SGSPGQSVTI SCTGPISGVG DYTSVSWYQH 180 YPGKTPKLII YDVTQRPSGV PNRFSGSKSG NTASLTISGL QADDEADYYC CSYEAPTHTY 240 VFGTGTKLTV L 251 3-196 Sequences 3-196-1 Sequence Number [ID] 196 3-196-2 Molecule Type AA 3-196-3 Length 273 3-196-4 Features REGION 1..273 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..273 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-196-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR SDP 273 3-197 Sequences 3-197-1 Sequence Number [ID] 197 3-197-2 Molecule Type AA 3-197-3 Length 270 3-197-4 Features REGION 1..270 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..270 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-197-5 Residues MALPVTALLL PLALLLHAAR PEVKLQESGP GLVAPSQSLS VTCTVSGVSL PDYGVSWIRQ 60 PPRKGLEWLG VIWGSETTYY NSALKSRLTI IKDNSKSQVF LKMNSLQTDD TAIYYCAKHY 120 YYGGSYAMDY WGQGTSVTVS SGGGGSGGGG SGGGGSDIQM TQTTSSLSAS LGDRVTISCR 180 ASQDISKYLN WYQQKPDGTV KLLIYHTSRL HSGVPSRFSG SGSGTDYSLT ISNLEQEDIA 240 TYFCQQGNTL PYTFGGGTKL EITRSDPTSS 270 11 Aug 2023

3-198 Sequences 3-198-1 Sequence Number [ID] 198 3-198-2 Molecule Type AA 3-198-3 Length 277 3-198-4 Features REGION 1..277 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..277 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-198-5 Residues MAPAMESPTL LCVALLFFAP DGVLAEVQLQ QSGPELIKPG ASVKMSCKAS GYTFTSYVMH 60 2023214349

WVKQKPGQGL EWIGYINPYN DGTKYNEKFK GKATLTSDKS SSTAYMELSS LTSEDSAVYY 120 CARGTYYYGS RVFDYWGQGT TLTVSSGGGG SGGGGSGGGG SDIVMTQAAP SIPVTPGESV 180 SISCRSSKSL LNSNGNTYLY WFLQRPGQSP QLLIYRMSNL ASGVPDRFSG SGSGTAFTLR 240 ISRVEAEDVG VYYCMQHLEY PFTFGAGTKL ELKRSDP 277 3-199 Sequences 3-199-1 Sequence Number [ID] 199 3-199-2 Molecule Type AA 3-199-3 Length 246 3-199-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-199-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCSSYAG RYNSVLFGGG 240 TKLTVL 246 3-200 Sequences 3-200-1 Sequence Number [ID] 200 3-200-2 Molecule Type AA 3-200-3 Length 249 3-200-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-200-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP 180 GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF 240 GQGTKLDIK 249 3-201 Sequences 3-201-1 Sequence Number [ID] 201 3-201-2 Molecule Type AA 3-201-3 Length 249 3-201-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-201-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 GQGTKLEIK 249 3-202 Sequences 3-202-1 Sequence Number [ID] 202 3-202-2 Molecule Type AA 3-202-3 Length 252 3-202-4 Features REGION 1..252

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-202-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-203 Sequences 3-203-1 Sequence Number [ID] 203 3-203-2 Molecule Type AA 3-203-3 Length 251 3-203-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment 2023214349

source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-203-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH 180 HPGKAPKLMI YDFSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC SSYAAISPNY 240 VFGTGTKLTV L 251 3-204 Sequences 3-204-1 Sequence Number [ID] 204 3-204-2 Molecule Type AA 3-204-3 Length 250 3-204-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-204-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH 180 NPGKAPKLII YDVTKRPSGV SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV 240 FGTGTKLTVL 250 3-205 Sequences 3-205-1 Sequence Number [ID] 205 3-205-2 Molecule Type AA 3-205-3 Length 247 3-205-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-205-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS DIQLTQSPST LSASVGDRVT ITCRASQSIS RWLAWYQQKP 180 GKAPKLLIYD ASNLETGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPLTFGG 240 GTKVEIK 247 3-206 Sequences 3-206-1 Sequence Number [ID] 206 3-206-2 Molecule Type AA 3-206-3 Length 248 3-206-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..248 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-206-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPST LSASVGDRVT ITCRASQSIS HYLAWYQQKP 180 GKAPKLLIFD ASRLASGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYGAPMFTFG 240 PGTRVDLK 248

3-207 Sequences 3-207-1 Sequence Number [ID] 207 3-207-2 Molecule Type AA 3-207-3 Length 251 11 Aug 2023

3-207-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-207-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDVG AYNFVSWYQQ 180 LPGTAPKFLI YDNNKRPPGI PDRFSGSKSG TSATLGITGL QTGDEADYYC ATWDSGLSAV 240 VFGGGTKLTV L 251 3-208 Sequences 2023214349

3-208-1 Sequence Number [ID] 208 3-208-2 Molecule Type AA 3-208-3 Length 250 3-208-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-208-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI FCTGTSSDVG GYNYVSWYQQ 180 LPGTAPKLLI YSNNQRPSGV PDRFSGSKSG TSASLAISGL RSEDEADYYC AAWDDSLSVV 240 FGGGTKLTVL 250 3-209 Sequences 3-209-1 Sequence Number [ID] 209 3-209-2 Molecule Type AA 3-209-3 Length 249 3-209-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-209-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQEVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNDKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDGNLSAVF 240 GGGTKVTVL 249 3-210 Sequences 3-210-1 Sequence Number [ID] 210 3-210-2 Molecule Type AA 3-210-3 Length 251 3-210-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-210-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH 180 HPGKAPKLMI YDFSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC CSYAAISPNY 240 VFGTGTKLTV L 251 3-211 Sequences 3-211-1 Sequence Number [ID] 211 3-211-2 Molecule Type AA 3-211-3 Length 249 3-211-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-211-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 GQGTKLDIK 249 11 Aug 2023

3-212 Sequences 3-212-1 Sequence Number [ID] 212 3-212-2 Molecule Type AA 3-212-3 Length 242 3-212-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-212-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 2023214349

RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSQVQLQESG PGLVKPSETL SLTCTVSGVS LPDYGVSWIR QPPGKGLEWI GVIWGSETTY 180 YSSSLKSRVT ISKDNSKNQV SLKLSSVTAA DTAVYYCAKH YYYGGSYAMD YWGQGTLVTV 240 SS 242 3-213 Sequences 3-213-1 Sequence Number [ID] 213 3-213-2 Molecule Type AA 3-213-3 Length 245 3-213-4 Features REGION 1..245 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..245 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-213-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGST SGSGKPGSGE 120 GSTKGEVKLQ ESGPGLVAPS QSLSVTCTVS GVSLPDYGVS WIRQPPRKGL EWLGVIWGSE 180 TTYYNSALKS RLTIIKDNSK SQVFLKMNSL QTDDTAIYYC AKHYYYGGSY AMDYWGQGTS 240 VTVSS 245 3-214 Sequences 3-214-1 Sequence Number [ID] 214 3-214-2 Molecule Type AA 3-214-3 Length 119 3-214-4 Features REGION 1..119 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..119 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-214-5 Residues QVQLLESGAE LVRPGSSVKI SCKASGYAFS SYWMNWVKQR PGQGLEWIGQ IYPGDGDTNY 60 NGKFKGQATL TADKSSSTAY MQLSGLTSED SAVYSCARKT ISSVVDFYFD YWGQGTTVT 119 3-215 Sequences 3-215-1 Sequence Number [ID] 215 3-215-2 Molecule Type AA 3-215-3 Length 438 3-215-4 Features REGION 1..438 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..438 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-215-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYVKLQ ESGPGLVAPS QSLSVTCTVS 120 GVSLPDYGVS WIRQPPRKGL EWLGVIWGSE TTYYNSALKS RLTIIKDNSK SQVFLKMNSL 180 QTDDTAIYYC AKHYYYGGSY AMDYWGQGTS VTVSSTTTPA PRPPTPAPTI ASQPLSLRPE 240 ACRPAAGGAV HTRGLDFACD IYIWAPLAGT CGVLLLSLVI TLYCKRGRKK LLYIFKQPFM 300 RPVQTTQEED GCSCRFPEEE EGGCELRVKF SRSADAPAYK QGQNQLYNEL NLGRREEYDV 360 LDKRRGRDPE MGGKPRRKNP QEGLYNELQK DKMAEAYSEI GMKGERRRGK GHDGLYQGLS 420 TATKDTYDAL HMQALPPR 438 3-216 Sequences 3-216-1 Sequence Number [ID] 216 3-216-2 Molecule Type AA 3-216-3 Length 272 3-216-4 Features REGION 1..272

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..272 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-216-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR SD 272 3-217 Sequences 3-217-1 Sequence Number [ID] 217 3-217-2 Molecule Type AA 3-217-3 Length 267 3-217-4 Features REGION 1..267 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment 2023214349

source 1..267 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-217-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP DLVKPGASVK ISCKASGYSF TGYYMHWVKQ 60 SHGKSLEWIG RINPNNGVTL YNQKFKDKAI LTVDKSSTTA YMELRSLTSE DSAVYYCARS 120 TMITNYVMDY WGQVTSVTVS SGGGGSGGGG SGGGGSSIVM TQTPTFLLVS AGDRVTITCK 180 ASQSVSNDVA WYQQKPGQSP TLLISYTSSR YAGVPDRFIG SGYGTDFTFT ISTLQAEDLA 240 VYFCQQDYNS PPTFGGGTKL EIKRSDP 267 3-218 Sequences 3-218-1 Sequence Number [ID] 218 3-218-2 Molecule Type AA 3-218-3 Length 270 3-218-4 Features REGION 1..270 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..270 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-218-5 Residues MALPVTALLL PLALLLHAAR PEVKLQESGP GLVAPSQSLS VTCTVSGVSL PDYGVSWIRQ 60 PPRKGLEWLG VIWGSETTYY NSALKSRLTI IKDNSKSQVF LKMNSLQTDD TAIYYCAKHY 120 YYGGSYAMDY WGQGTSVTVS SGGGGSGGGG SGGGGSDIQM TQTTSSLSAS LGDRVTISCR 180 ASQDISKYLN WYQQKPDGTV KLLIYHTSRL HSGVPSRFSG SGSGTDYSLT ISNLEQEDIA 240 TYFCQQGNTL PYTFGGGTKL EITRSDPTSS 270 3-219 Sequences 3-219-1 Sequence Number [ID] 219 3-219-2 Molecule Type AA 3-219-3 Length 277 3-219-4 Features REGION 1..277 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..277 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-219-5 Residues MAPAMESPTL LCVALLFFAP DGVLAEVQLQ QSGPELIKPG ASVKMSCKAS GYTFTSYVMH 60 WVKQKPGQGL EWIGYINPYN DGTKYNEKFK GKATLTSDKS SSTAYMELSS LTSEDSAVYY 120 CARGTYYYGS RVFDYWGQGT TLTVSSGGGG SGGGGSGGGG SDIVMTQAAP SIPVTPGESV 180 SISCRSSKSL LNSNGNTYLY WFLQRPGQSP QLLIYRMSNL ASGVPDRFSG SGSGTAFTLR 240 ISRVEAEDVG VYYCMQHLEY PFTFGAGTKL ELKRSDP 277 3-220 Sequences 3-220-1 Sequence Number [ID] 220 3-220-2 Molecule Type AA 3-220-3 Length 242 3-220-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-220-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSQVQLQESG PGLVKPSETL SLTCTVSGVS LPDYGVSWIR QPPGKGLEWI GVIWGSETTY 180 YQSSLKSRVT ISKDNSKNQV SLKLSSVTAA DTAVYYCAKH YYYGGSYAMD YWGQGTLVTV 240 SS 242

3-221 Sequences 3-221-1 Sequence Number [ID] 221 3-221-2 Molecule Type AA 3-221-3 Length 242 11 Aug 2023

3-221-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-221-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYS 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSEIVMT QSPATLSLSP GERATLSCRA SQDISKYLNW YQQKPGQAPR 180 LLIYHTSRLH SGIPARFSGS GSGTDYTLTI SSLQPEDFAV YFCQQGNTLP YTFGQGTKLE 240 IK 242 3-222 Sequences 2023214349

3-222-1 Sequence Number [ID] 222 3-222-2 Molecule Type AA 3-222-3 Length 242 3-222-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-222-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYQ 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSEIVMT QSPATLSLSP GERATLSCRA SQDISKYLNW YQQKPGQAPR 180 LLIYHTSRLH SGIPARFSGS GSGTDYTLTI SSLQPEDFAV YFCQQGNTLP YTFGQGTKLE 240 IK 242 3-223 Sequences 3-223-1 Sequence Number [ID] 223 3-223-2 Molecule Type AA 3-223-3 Length 247 3-223-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-223-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSGGGGSQVQ LQESGPGLVK PSETLSLTCT VSGVSLPDYG VSWIRQPPGK GLEWIGVIWG 180 SETTYYSSSL KSRVTISKDN SKNQVSLKLS SVTAADTAVY YCAKHYYYGG SYAMDYWGQG 240 TLVTVSS 247 3-224 Sequences 3-224-1 Sequence Number [ID] 224 3-224-2 Molecule Type AA 3-224-3 Length 247 3-224-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-224-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSGGGGSQVQ LQESGPGLVK PSETLSLTCT VSGVSLPDYG VSWIRQPPGK GLEWIGVIWG 180 SETTYYQSSL KSRVTISKDN SKNQVSLKLS SVTAADTAVY YCAKHYYYGG SYAMDYWGQG 240 TLVTVSS 247 3-225 Sequences 3-225-1 Sequence Number [ID] 225 3-225-2 Molecule Type AA 3-225-3 Length 247 3-225-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-225-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYS 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSGGGGS EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP 180 GQAPRLLIYH TSRLHSGIPA RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ 240 GTKLEIK 247 11 Aug 2023

3-226 Sequences 3-226-1 Sequence Number [ID] 226 3-226-2 Molecule Type AA 3-226-3 Length 247 3-226-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-226-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYQ 60 2023214349

SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSGGGGS EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP 180 GQAPRLLIYH TSRLHSGIPA RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ 240 GTKLEIK 247 3-227 Sequences 3-227-1 Sequence Number [ID] 227 3-227-2 Molecule Type AA 3-227-3 Length 247 3-227-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-227-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSGGGGSQVQ LQESGPGLVK PSETLSLTCT VSGVSLPDYG VSWIRQPPGK GLEWIGVIWG 180 SETTYYNSSL KSRVTISKDN SKNQVSLKLS SVTAADTAVY YCAKHYYYGG SYAMDYWGQG 240 TLVTVSS 247 3-228 Sequences 3-228-1 Sequence Number [ID] 228 3-228-2 Molecule Type AA 3-228-3 Length 247 3-228-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-228-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYN 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSGGGGS EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP 180 GQAPRLLIYH TSRLHSGIPA RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ 240 GTKLEIK 247 3-229 Sequences 3-229-1 Sequence Number [ID] 229 3-229-2 Molecule Type AA 3-229-3 Length 242 3-229-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-229-5 Residues EIVMTQSPAT LSLSPGERAT LSCRASQDIS KYLNWYQQKP GQAPRLLIYH TSRLHSGIPA 60 RFSGSGSGTD YTLTISSLQP EDFAVYFCQQ GNTLPYTFGQ GTKLEIKGGG GSGGGGSGGG 120 GSQVQLQESG PGLVKPSETL SLTCTVSGVS LPDYGVSWIR QPPGKGLEWI GVIWGSETTY 180 YNSSLKSRVT ISKDNSKNQV SLKLSSVTAA DTAVYYCAKH YYYGGSYAMD YWGQGTLVTV 240 SS 242 3-230 Sequences 3-230-1 Sequence Number [ID] 230 3-230-2 Molecule Type AA 3-230-3 Length 495 3-230-4 Features REGION 1..495

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..495 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-230-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-231 Sequences 3-231-1 Sequence Number [ID] 231 2023214349

3-231-2 Molecule Type AA 3-231-3 Length 242 3-231-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-231-5 Residues QVQLQESGPG LVKPSETLSL TCTVSGVSLP DYGVSWIRQP PGKGLEWIGV IWGSETTYYN 60 SSLKSRVTIS KDNSKNQVSL KLSSVTAADT AVYYCAKHYY YGGSYAMDYW GQGTLVTVSS 120 GGGGSGGGGS GGGGSEIVMT QSPATLSLSP GERATLSCRA SQDISKYLNW YQQKPGQAPR 180 LLIYHTSRLH SGIPARFSGS GSGTDYTLTI SSLQPEDFAV YFCQQGNTLP YTFGQGTKLE 240 IK 242 3-232 Sequences 3-232-1 Sequence Number [ID] 232 3-232-2 Molecule Type AA 3-232-3 Length 242 3-232-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-232-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGGG GSGGGGSGGG 120 GSEVKLQESG PGLVAPSQSL SVTCTVSGVS LPDYGVSWIR QPPRKGLEWL GVIWGSETTY 180 YNSALKSRLT IIKDNSKSQV FLKMNSLQTD DTAIYYCAKH YYYGGSYAMD YWGQGTSVTV 240 SS 242 3-233 Sequences 3-233-1 Sequence Number [ID] 233 3-233-2 Molecule Type AA 3-233-3 Length 252 3-233-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-233-5 Residues EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK PGQGLEWIGY INPYNDGTKY 60 NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT YYYGSRVFDY WGQGTTLTVS 120 SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR SSKSLLNSNG NTYLYWFLQR 180 PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE AEDVGVYYCM QHLEYPFTFG 240 AGTKLELKRS DP 252 3-234 Sequences 3-234-1 Sequence Number [ID] 234 3-234-2 Molecule Type AA 3-234-3 Length 250 3-234-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-234-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITKAG GGGSGGGGSG 120

GGGSGGGGSE VKLQESGPGL VAPSQSLSVT CTVSGVSLPD YGVSWIRQPP RKGLEWLGVI 180 WGSETTYYNS ALKSRLTIIK DNSKSQVFLK MNSLQTDDTA IYYCAKHYYY GGSYAMDYWG 240 QGTSVTVSSD 250 3-235 Sequences 3-235-1 Sequence Number [ID] 235 11 Aug 2023

3-235-2 Molecule Type AA 3-235-3 Length 242 3-235-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-235-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGGG GSGGGGSGGG 120 GSEVKLQESG PGLVAPSQSL SVTCTVSGVS LPDYGVSWIR QPPRKGLEWL GVIWGSETTY 180 2023214349

YNSALKSRLT IIKDNSKSQV FLKMNSLQTD DTAIYYCAKH YYYGGSYAMD YWGQGTSVTV 240 SS 242 3-236 Sequences 3-236-1 Sequence Number [ID] 236 3-236-2 Molecule Type AA 3-236-3 Length 251 3-236-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-236-5 Residues EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK PGQGLEWIGY INPYNDGTKY 60 NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT YYYGSRVFDY WGQGTTLTVS 120 SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR SSKSLLNSNG NTYLYWFLQR 180 PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE AEDVGVYYCM QHLEYPFTFG 240 AGTKLELKRA D 251 3-237 Sequences 3-237-1 Sequence Number [ID] 237 3-237-2 Molecule Type AA 3-237-3 Length 271 3-237-4 Features REGION 1..271 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..271 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-237-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSHHHHHHH H 271 3-238 Sequences 3-238-1 Sequence Number [ID] 238 3-238-2 Molecule Type AA 3-238-3 Length 248 3-238-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..248 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-238-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS SYELTQDPAV SVALGQTVRI TCQGDSLRSY YASWYQQKPG 180 QAPVLVIYDK NNRPSGIPDR FSGSSSGNTA SLTITGAQAE DEADYYCNSR DSSGNNWVFG 240 GGTKLTVL 248 3-239 Sequences 3-239-1 Sequence Number [ID] 239 3-239-2 Molecule Type AA 3-239-3 Length 246 3-239-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-239-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 11 Aug 2023

VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVLFGGG 240 TKLTVL 246 3-240 Sequences 3-240-1 Sequence Number [ID] 240 3-240-2 Molecule Type AA 3-240-3 Length 252 3-240-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-240-5 Residues QITLKESGPT LVKPTQTLTL TCTFSGFSLS TSGVGVGWIR QPPGKALEWL ALIYWDDDKR 60 YSPSLKSRLT ITKDTSKNQV VLTMTNMDPV DTATYYCAHI DYGSGSYSPR TSYYYYMSVW 120 GKGTTVTVSS GGGGSGGGGS GGGGSAIQLT QSPSFLSASV GDRVTITCRA SQGISSYLNW 180 YQQRAGKAPE LLIYAASNLQ SGVPSRFSGS GSGTDFTLTI TSVQPEDFAT YFCQQGDAFP 240 LTFGPGTKVT IR 252 3-241 Sequences 3-241-1 Sequence Number [ID] 241 3-241-2 Molecule Type AA 3-241-3 Length 249 3-241-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-241-5 Residues QVQLVQSGGG VVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP 180 GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF 240 GQGTKLEIK 249 3-242 Sequences 3-242-1 Sequence Number [ID] 242 3-242-2 Molecule Type AA 3-242-3 Length 251 3-242-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-242-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDSSLNRDW 240 VFGGGTKLTV L 251 3-243 Sequences 3-243-1 Sequence Number [ID] 243 3-243-2 Molecule Type AA 3-243-3 Length 252 3-243-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-243-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-244 Sequences 3-244-1 Sequence Number [ID] 244

3-244-2 Molecule Type AA 3-244-3 Length 249 3-244-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment 11 Aug 2023

MOD_RES 64..65 note=Any amino acid MOD_RES 68..69 note=Any amino acid MOD_RES 93 note=Any amino acid MOD_RES 98 note=Any amino acid MOD_RES 102 note=Any amino acid MOD_RES 104 note=Any amino acid 2023214349

MOD_RES 113 note=Any amino acid MOD_RES 145..146 note=Any amino acid MOD_RES 148..149 note=Any amino acid MOD_RES 233 note=Any amino acid MOD_RES 244 note=Any amino acid source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-244-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSXXGRXXI SRDNAKNSLF LQMNSLRAED TAXYYCAXDQ GXHXYDSAEH AFXIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLXXPXXA SGSPGQSVTV SCTGTGRDIG AYDYVSWYQQ 180 HPGKAPKLLI YGVNKRPSGV PDRFSGSKSD NTASLTVSGL QVEDEADYYC SSXAGRKYVF 240 GTGXKVTVL 249 3-245 Sequences 3-245-1 Sequence Number [ID] 245 3-245-2 Molecule Type AA 3-245-3 Length 252 3-245-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment MOD_RES 76 note=Any amino acid MOD_RES 201 note=Any amino acid source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-245-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAXNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTETSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV XDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-246 Sequences 3-246-1 Sequence Number [ID] 246 3-246-2 Molecule Type AA 3-246-3 Length 250 3-246-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-246-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH 180 NPGKAPKLII YDVTKRPSGV SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV 240 FGTGTKLDIK 250 3-247 Sequences

3-247-1 Sequence Number [ID] 247 3-247-2 Molecule Type AA 3-247-3 Length 252 3-247-4 Features REGION 1..252 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-247-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLD IK 252 3-248 Sequences 3-248-1 Sequence Number [ID] 248 2023214349

3-248-2 Molecule Type AA 3-248-3 Length 236 3-248-4 Features REGION 1..236 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..236 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-248-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSQSVLT QPRSLSGSPG QSVTIACTGA STDVGGYNYV SWYQQHPGKA PKLMIYDVNK 180 RPSGVPDRFS GSKSGNTAFL TISGLQAEDE ADYYCCSYAG SYTFEVFGGG TKLTVL 236 3-249 Sequences 3-249-1 Sequence Number [ID] 249 3-249-2 Molecule Type AA 3-249-3 Length 251 3-249-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-249-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QLVLTQPPSV SGSPGQSVTF SCTGASSDVG GYDHVSWYQH 180 HPGKGPKLLI YDVSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGYYTYW 240 LFGGGTKVTV L 251 3-250 Sequences 3-250-1 Sequence Number [ID] 250 3-250-2 Molecule Type AA 3-250-3 Length 246 3-250-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-250-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCCSYAG RYNSVPFGGG 240 TKLTVL 246 3-251 Sequences 3-251-1 Sequence Number [ID] 251 3-251-2 Molecule Type AA 3-251-3 Length 239 3-251-4 Features REGION 1..239 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..239 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-251-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120

VTVSSGGGGS GGGGSGGGGS SYVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQF 180 PGTAPKLLIY SNNQRPSGVP DRFSGSKSGT SASLAISGLQ SEDEAEYYCA AWDDSLNVV 239 3-252 Sequences 3-252-1 Sequence Number [ID] 252 3-252-2 Molecule Type AA 11 Aug 2023

3-252-3 Length 250 3-252-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-252-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNNKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEGDYYCG TWDISLRFGV 240 2023214349

FGGGTKVTVL 250 3-253 Sequences 3-253-1 Sequence Number [ID] 253 3-253-2 Molecule Type AA 3-253-3 Length 251 3-253-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-253-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRLA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAKD TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPRSV SGSPGQSVTI SCTGPISGVG DYTSVSWYQH 180 YPGKTPKLII YDVTQRPSGV PNRFSGSKSG NTASLTISGL QADDEADYYC CSYEAPTHTY 240 VFGTGTKLTV L 251 3-254 Sequences 3-254-1 Sequence Number [ID] 254 3-254-2 Molecule Type AA 3-254-3 Length 246 3-254-4 Features REGION 1..246 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..246 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-254-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPRSV SGFPGQSVTI SCTGTTSDDV SWYQQHPGKA 180 PQLMLYDVSK RPSGVPHRFS GSRSGRAASL IISGLQTEDE ADYFCSSYAG RYNSVLFGGG 240 TKLTVL 246 3-255 Sequences 3-255-1 Sequence Number [ID] 255 3-255-2 Molecule Type AA 3-255-3 Length 249 3-255-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-255-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS EIVLTQSPAT LSLSPGETAT LSCRASQSIN HYLAWYQQKP 180 GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFATYYCQQ SYSHPRMYTF 240 GQGTKLDIK 249 3-256 Sequences 3-256-1 Sequence Number [ID] 256 3-256-2 Molecule Type AA 3-256-3 Length 249 3-256-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-256-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 11 Aug 2023

GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 GQGTKLEIK 249 3-257 Sequences 3-257-1 Sequence Number [ID] 257 3-257-2 Molecule Type AA 3-257-3 Length 252 3-257-4 Features REGION 1..252 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..252 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-257-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDLG GYNYVSWYQH 180 RPGKAPKLII YDVTVRPSGV SDRFSGSKSG NTASLTISGL QAEDEADYYC GSYTSSSTLL 240 WVFGGGTKLT VL 252 3-258 Sequences 3-258-1 Sequence Number [ID] 258 3-258-2 Molecule Type AA 3-258-3 Length 251 3-258-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-258-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH 180 HPGKAPKLMI YDFSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC SSYAAISPNY 240 VFGTGTKLTV L 251 3-259 Sequences 3-259-1 Sequence Number [ID] 259 3-259-2 Molecule Type AA 3-259-3 Length 250 3-259-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-259-5 Residues QVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGHSITI SCTGTRSDVG GFDYVSWYQH 180 NPGKAPKLII YDVTKRPSGV SNRFSGAKSG ITASLTISGL QAEDEADYYC TSYRPGPTFV 240 FGTGTKLTVL 250 3-260 Sequences 3-260-1 Sequence Number [ID] 260 3-260-2 Molecule Type AA 3-260-3 Length 247 3-260-4 Features REGION 1..247 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..247 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-260-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS DIQLTQSPST LSASVGDRVT ITCRASQSIS RWLAWYQQKP 180 GKAPKLLIYD ASNLETGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPLTFGG 240 GTKVEIK 247 3-261 Sequences 3-261-1 Sequence Number [ID] 261 3-261-2 Molecule Type AA

3-261-3 Length 248 3-261-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..248 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-261-5 Residues QMQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPST LSASVGDRVT ITCRASQSIS HYLAWYQQKP 180 GKAPKLLIFD ASRLASGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYGAPMFTFG 240 PGTRVDLK 248 3-262 Sequences 3-262-1 Sequence Number [ID] 262 3-262-2 Molecule Type AA 3-262-3 Length 251 2023214349

3-262-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-262-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI SCTGTSSDVG AYNFVSWYQQ 180 LPGTAPKFLI YDNNKRPPGI PDRFSGSKSG TSATLGITGL QTGDEADYYC ATWDSGLSAV 240 VFGGGTKLTV L 251 3-263 Sequences 3-263-1 Sequence Number [ID] 263 3-263-2 Molecule Type AA 3-263-3 Length 250 3-263-4 Features REGION 1..250 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..250 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-263-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QSALTQPASV SGSPGQSITI FCTGTSSDVG GYNYVSWYQQ 180 LPGTAPKLLI YSNNQRPSGV PDRFSGSKSG TSASLAISGL RSEDEADYYC AAWDDSLSVV 240 FGGGTKLTVL 250 3-264 Sequences 3-264-1 Sequence Number [ID] 264 3-264-2 Molecule Type AA 3-264-3 Length 249 3-264-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-264-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS QSVLTQPPSV SAAPGQEVTI SCSGSSSNIG NNYVSWYQQL 180 PGTAPKLLIY DNDKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYCG TWDGNLSAVF 240 GGGTKVTVL 249 3-265 Sequences 3-265-1 Sequence Number [ID] 265 3-265-2 Molecule Type AA 3-265-3 Length 251 3-265-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-265-5 Residues EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGRIGY 60 ADSVKGRFTI SRDNAKNSLF LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTM 120 VTVSSGGGGS GGGGSGGGGS QAVLTQPRSV SGSPGQSVTI SCTGISSGVD SHRYVSWYQH 180

HPGKAPKLMI YDFSKRPSGV PDRFSGSKSG NTASLTISGL QAEDEADYYC CSYAAISPNY 240 VFGTGTKLTV L 251 3-266 Sequences 3-266-1 Sequence Number [ID] 266 3-266-2 Molecule Type AA 11 Aug 2023

3-266-3 Length 249 3-266-4 Features REGION 1..249 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..249 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-266-5 Residues EVQLVQSGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG ISWNSGSIGY 60 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARDQ GYHYYDSAEH AFDIWGQGTV 120 VTVSSGGGGS GGGGSGGGGS AIRMTQSPSS LSASVGDRVT VTCQASQDIS NYLNWYQQKP 180 GRAPKLLIYD ASNVKAGVPS RFSGGGSGTD FTLTISSLQP EDFATYYCQQ SYSTPQAYTF 240 2023214349

GQGTKLDIK 249 3-267 Sequences 3-267-1 Sequence Number [ID] 267 3-267-2 Molecule Type AA 3-267-3 Length 277 3-267-4 Features REGION 1..277 Location/Qualifiers note=Description of Artificial Sequence: Synthetic single chain varia ble fragment source 1..277 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-267-5 Residues MAPAMESPTL LCVALLFFAP DGVLAEVQLQ QSGPELIKPG ASVKMSCKAS GYTFTSYVMH 60 WVKQKPGQGL EWIGYINPYN DGTKYNEKFK GKATLTSDKS SSTAYMELSS LTSEDSAVYY 120 CARGTYYVGS RVFDYWGQGT TLTVSSGGGG SGGGGSGGGG SDIVMTQAAP SIPVTPGESV 180 SISCRSSKSL LNSNGNTYLY WFLQRPGQSP QLLIYRMSNL ASGVPDRFSG SGSGTAFTLR 240 ISRVEAEDVG VYVCMQHLEY PFTFGAGTKL ELKRSDP 277 3-268 Sequences 3-268-1 Sequence Number [ID] 268 3-268-2 Molecule Type AA 3-268-3 Length 120 3-268-4 Features source 1..120 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-268-5 Residues WRRKRKEKQS ETSPKEFLTI YEDVKDLKTR RNHEQEQTFP GGGSTIYSMI QSQSSAPTSQ 60 EPAYTLYSLI QPSRKSGSRK RNHSPSFNST IYEVIGKSQP KAQNPARLSR KELENFDVYS 120 3-269 Sequences 3-269-1 Sequence Number [ID] 269 3-269-2 Molecule Type AA 3-269-3 Length 49 3-269-4 Features source 1..49 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-269-5 Residues HQRRKYRSNK GESPVEPAEP CRYSCPREEE GSTIPIQEDY RKPEPACSP 49 3-270 Sequences 3-270-1 Sequence Number [ID] 270 3-270-2 Molecule Type AA 3-270-3 Length 110 3-270-4 Features source 1..110 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-270-5 Residues RRHQGKQNEL SDTAGREINL VDAKLKSEQT EASTRQNSQV LLSETGIYDN DPDLCFRMQE 60 GSEVYSNPCL EENKPGVYAS LNHSVIGPNS RLARNVKEAP TEYASICVRS 110 3-271 Sequences 3-271-1 Sequence Number [ID] 271 3-271-2 Molecule Type AA 3-271-3 Length 114 3-271-4 Features source 1..114 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-271-5 Residues CCLRRHQGKQ NELSDTAGRE INLVDAHLKS EQTEASTRQN SQVLLSETGI YDNDPDLCFR 60

MQEGSEVYSN PCLEENKPGI VYASLNHSVI GPNSRLARNV KEAPTEYASI CVRS 114 3-272 Sequences 3-272-1 Sequence Number [ID] 272 3-272-2 Molecule Type AA 11 Aug 2023

3-272-3 Length 27 3-272-4 Features source 1..27 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-272-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWV 27 3-273 Sequences 3-273-1 Sequence Number [ID] 273 3-273-2 Molecule Type AA 3-273-3 Length 42 3-273-4 Features source 1..42 Location/Qualifiers mol_type=protein 2023214349

organism=Homo sapiens NonEnglishQualifier Value 3-273-5 Residues KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGC EL 42 3-274 Sequences 3-274-1 Sequence Number [ID] 274 3-274-2 Molecule Type AA 3-274-3 Length 44 3-274-4 Features source 1..44 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-274-5 Residues FWVRSKRSRL LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRS 44 3-275 Sequences 3-275-1 Sequence Number [ID] 275 3-275-2 Molecule Type AA 3-275-3 Length 41 3-275-4 Features source 1..41 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-275-5 Residues RSKRSRGGHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR S 41 3-276 Sequences 3-276-1 Sequence Number [ID] 276 3-276-2 Molecule Type AA 3-276-3 Length 43 3-276-4 Features source 1..43 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-276-5 Residues RSKRSRGGHS DYIVINMTPR RPGPTRKHYQ PYAPPRDFAA YRS 43 3-277 Sequences 3-277-1 Sequence Number [ID] 277 3-277-2 Molecule Type AA 3-277-3 Length 220 3-277-4 Features source 1..220 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-277-5 Residues MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE FRASLHKGLD 60 SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ NLYVNQTDIY FCKIEVMYPP 120 PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV TVAFIIFWVR 180 SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS 220 3-278 Sequences 3-278-1 Sequence Number [ID] 278 3-278-2 Molecule Type AA 3-278-3 Length 187 3-278-4 Features source 1..187 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-278-5 Residues RRACRKRIRQ KLHLCYPVQT SQPKLELVDS RPRRSSTQLR SGASVTEPVA EERGLMSQPL 60 METCHSVGAA YLESLPLQDA SPAGGPSSPR DLPEPRVSTE HTNNKIEKIY IMKADTVIVG 120 TVKAELPEGR GLAGPAEPEL EEELEADHTP HYPEQETEPP LGSCSDVMLS VEEEGKEDPL 180

PTAASGK 187 3-279 Sequences 3-279-1 Sequence Number [ID] 279 3-279-2 Molecule Type AA 11 Aug 2023

3-279-3 Length 187 3-279-4 Features source 1..187 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-279-5 Residues RRACRKRIRQ KLHLCYPVQT SQPKLELVDS RPRRSSTQLR SGASVTEPVA EERGLMSQPL 60 METCHSVGAA YLESLPLQDA SPAGGPSSPR DLPEPRVSTE HTNNKIEKIY IMKADTVIVG 120 TVKAELPEGR GLAGPAEPEL EEELEADHTP HYPEQETEPP LGSCSDVMLS VEEEGKEDPL 180 PTAASGK 187 3-280 Sequences 3-280-1 Sequence Number [ID] 280 3-280-2 Molecule Type AA 2023214349

3-280-3 Length 54 3-280-4 Features source 1..54 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-280-5 Residues HIWQLRSQCM WPRETQLLLE VPPSTEDARS CQFPEEERGE RSAEEKGRLG DLWV 54 3-281 Sequences 3-281-1 Sequence Number [ID] 281 3-281-2 Molecule Type AA 3-281-3 Length 60 3-281-4 Features source 1..60 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-281-5 Residues CVKRRKPRGD VVKVIVSVQR KRQEAEGEAT VIEALQAPPD VTTVAVEETI PSFTGRSPNH 60 3-282 Sequences 3-282-1 Sequence Number [ID] 282 3-282-2 Molecule Type AA 3-282-3 Length 35 3-282-4 Features source 1..35 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-282-5 Residues TKKKYSSSVH DPNGEYMFMR AVNTAKKSRL TDVTL 35 3-283 Sequences 3-283-1 Sequence Number [ID] 283 3-283-2 Molecule Type AA 3-283-3 Length 38 3-283-4 Features source 1..38 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-283-5 Residues CWLTKKKYSS SVHDPNGEYM FMRAVNTAKK SRLTDVTL 38 3-284 Sequences 3-284-1 Sequence Number [ID] 284 3-284-2 Molecule Type AA 3-284-3 Length 54 3-284-4 Features source 1..54 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-284-5 Residues HLWRRQWRPR RFSALEQGIH PPQAQSKIEE LEQEPEPEPE PEPEPEPEPE PEQL 54 3-285 Sequences 3-285-1 Sequence Number [ID] 285 3-285-2 Molecule Type AA 3-285-3 Length 42 3-285-4 Features source 1..42 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-285-5 Residues ALYLLRRDQR LPPDAHKPPG GGSFRTPIQE EQADAHSTLA KI 42 3-286 Sequences

3-286-1 Sequence Number [ID] 286 3-286-2 Molecule Type AA 3-286-3 Length 37 3-286-4 Features source 1..37 11 Aug 2023

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-286-5 Residues RRDQRLPPDA HKPPGGGSFR TPIQEEQADA HSTLAKI 37 3-287 Sequences 3-287-1 Sequence Number [ID] 287 3-287-2 Molecule Type AA 3-287-3 Length 42 3-287-4 Features source 1..42 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 2023214349

3-287-5 Residues KRGRKKLLYI FKQPFMRPVQ TIQEEDGCSC RFPEEEEGGC EL 42 3-288 Sequences 3-288-1 Sequence Number [ID] 288 3-288-2 Molecule Type AA 3-288-3 Length 42 3-288-4 Features source 1..42 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-288-5 Residues KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGY EL 42 3-289 Sequences 3-289-1 Sequence Number [ID] 289 3-289-2 Molecule Type AA 3-289-3 Length 225 3-289-4 Features source 1..225 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-289-5 Residues TGTTTPAPRP PTPAPTIASQ PLSLRPEACR PAAGGAVHTR GLDFACDIYI WAPLAGTCGV 60 LLLSLVITLY CKRGRKKLLY IFKQPFMRPV QTTQEEDGCS CRFPEEEEGG CELRVKFSRS 120 ADAPAYQQGQ NQLYNELNLG RREEYDVLDK RRGRDPEMGG KPRRKNPQEG LYNELQKDKM 180 AEAYSEIGMK GERRRGKGHD GLYQGLSTAT KDTYDALHMQ ALPPR 225 3-290 Sequences 3-290-1 Sequence Number [ID] 290 3-290-2 Molecule Type AA 3-290-3 Length 154 3-290-4 Features source 1..154 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-290-5 Residues KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA DAPAYQQGQN 60 QLYNELNLGR REEYDVLDKR RGRDPEMGGK PRRKNPQEGL YNELQKDKMA EAYSEIGMKG 120 ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 154 3-291 Sequences 3-291-1 Sequence Number [ID] 291 3-291-2 Molecule Type AA 3-291-3 Length 194 3-291-4 Features source 1..194 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-291-5 Residues KRIKPIVWPS LPDHKKTLEH LCKKPRKNLN VSFNPESFLD CQIHRVDDIQ ARDEVEGFLQ 60 DTFPQQLEES EKQRLGGDVQ SPNCPSEDVV ITPESFGRDS SLTCLAGNVS ACDAPILSSS 120 RSLDCRESGK NGPHVYQDLL LSLGTTNSTL PPPFSLQSGI LTLNPVAQGQ PILTSLGSNQ 180 EEAYVTMSSF YQNQ 194 3-292 Sequences 3-292-1 Sequence Number [ID] 292 3-292-2 Molecule Type AA 3-292-3 Length 47 3-292-4 Features source 1..47 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value

3-292-5 Residues RFSVVKRGRK KLLYIFKQPF MRPVQTTQEE DGCSCRFPEE EEGGCEL 47 3-293 Sequences 3-293-1 Sequence Number [ID] 293 3-293-2 Molecule Type AA 11 Aug 2023

3-293-3 Length 341 3-293-4 Features source 1..341 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-293-5 Residues RKKRKDAKNN EVSFSQIKPK KSKLIRVENF EAYFKKQQAD SNCGFAEEYE DLKLVGISQP 60 KYAAELAENR GKNRYNNVLP YDISRVKLSV QTHSTDDYIN ANYMPGYHSK KDFIATQGPL 120 PNTLKDFWRM VWEKNVYAII MLTKCVEQGR TKCEEYWPSK QAQDYGDITV AMTSEIVLPE 180 WTIRDFTVKN IQTSESHPLR QFHFTSWPDH GVPDTTDLLI NFRYLVRDYM KQSPPESPIL 240 VHCSAGVGRT GTFIAIDRLI YQIENENTVD VYGIVYDLRM HRPLMVQTED QYVFLNQCVL 300 DIVRSQKDSK VDLIYQNTTA MTIYENLAPV TTFGKTNGYI A 341 3-294 Sequences 2023214349

3-294-1 Sequence Number [ID] 294 3-294-2 Molecule Type AA 3-294-3 Length 48 3-294-4 Features source 1..48 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-294-5 Residues QRRKYRSNKG ESPVEPAEPC HYSCPREEEG STIPIQEDYR KPEPACSP 48 3-295 Sequences 3-295-1 Sequence Number [ID] 295 3-295-2 Molecule Type AA 3-295-3 Length 6 3-295-4 Features source 1..6 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-295-5 Residues FAAYRS 6 3-296 Sequences 3-296-1 Sequence Number [ID] 296 3-296-2 Molecule Type AA 3-296-3 Length 68 3-296-4 Features source 1..68 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-296-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVRSK RSRLLHSDYM NMTPRRPGPT RKHYQPYAPP 60 RDFAAYRS 68 3-297 Sequences 3-297-1 Sequence Number [ID] 297 3-297-2 Molecule Type AA 3-297-3 Length 41 3-297-4 Features source 1..41 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-297-5 Residues RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR S 41 3-298 Sequences 3-298-1 Sequence Number [ID] 298 3-298-2 Molecule Type AA 3-298-3 Length 40 3-298-4 Features source 1..40 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-298-5 Residues SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS 40 3-299 Sequences 3-299-1 Sequence Number [ID] 299 3-299-2 Molecule Type AA 3-299-3 Length 106 3-299-4 Features source 1..106 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value

3-299-5 Residues IEVMYPPPYL DNEKSNGTII HVKGKHLCPS PLFPGPSKPF WVLVVVGGVL ACYSLLVTVA 60 FIIFWRSKRS RLLHSDYMNM TPRRPGPTRK HYQPYAPPRD FAAYRS 106 3-300 Sequences 3-300-1 Sequence Number [ID] 300 3-300-2 Molecule Type AA 11 Aug 2023

3-300-3 Length 200 3-300-4 Features source 1..200 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-300-5 Residues RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR SRFSVVKRGR KKLLYIFKQP 60 FMRPVQTTQE EDGCSCRFPE EEEGGCELRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY 120 DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG 180 LSTATKDTYD ALHMQALPPR 200 3-301 Sequences 3-301-1 Sequence Number [ID] 301 2023214349

3-301-2 Molecule Type AA 3-301-3 Length 222 3-301-4 Features source 1..222 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-301-5 Residues AAAIEVMYPP PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV 60 TVAFIIFWVR SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS RVKFSRSADA 120 PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN ELQKDKMAEA 180 YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 222 3-302 Sequences 3-302-1 Sequence Number [ID] 302 3-302-2 Molecule Type AA 3-302-3 Length 188 3-302-4 Features source 1..188 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-302-5 Residues RSKRSRLLHS DYNMTPRRPG PTRKHYQPYA PPRDFAAYRS RDQRLPPDAH KPPGGGSFRT 60 PIQEEQADAH STLAKIRVKF SRSADAPAYQ QGQNQLYNEL NLGRREEYDV LDKRRGRDPE 120 MGGKPRRKNP QEGLYNELQK DKMAEAYSEI GMKGERRRGK GHDGLYQGLS TATKDTYDAL 180 HMQALPPR 188 3-303 Sequences 3-303-1 Sequence Number [ID] 303 3-303-2 Molecule Type AA 3-303-3 Length 70 3-303-4 Features source 1..70 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-303-5 Residues MFWVLVVVGG VLACYSLLVT VAFIIFWVKR GRKKLLYIFK QPFMRPVQTT QEEDGCSCRF 60 PEEEEGGCEL 70 3-304 Sequences 3-304-1 Sequence Number [ID] 304 3-304-2 Molecule Type AA 3-304-3 Length 108 3-304-4 Features source 1..108 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-304-5 Residues IEVMYPPPYL DNEKSNGTII HVKGKHLCPS PLFPGPSKPF WVLVVVGGVL ACYSLLVTVA 60 FIIFWVKRGR KKLLYIFKQP FMRPVQTTQE EDGCSCRFPE EEEGGCEL 108 3-305 Sequences 3-305-1 Sequence Number [ID] 305 3-305-2 Molecule Type AA 3-305-3 Length 153 3-305-4 Features source 1..153 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-305-5 Residues RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR SRVKFSRSAD APAYQQGQNQ 60 LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY NELQKDKMAE AYSEIGMKGE 120 RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 153 3-306 Sequences

3-306-1 Sequence Number [ID] 306 3-306-2 Molecule Type AA 3-306-3 Length 151 3-306-4 Features source 1..151 11 Aug 2023

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-306-5 Residues KRSRLLHSDY MNMTPRRPGP TRKHYQPYAP PRDFAAYRSR VKFSRSADAP AYQQGQNQLY 60 NELNLGRREE YDVLDKRRGR DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR 120 RGKGHDGLYQ GLSTATKDTY DALHMQALPP R 151 3-307 Sequences 3-307-1 Sequence Number [ID] 307 3-307-2 Molecule Type AA 3-307-3 Length 171 3-307-4 Features source 1..171 Location/Qualifiers mol_type=protein 2023214349

organism=Homo sapiens NonEnglishQualifier Value 3-307-5 Residues MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL 60 GKRILDPRGI YRCNGTDIYK DKESTVQVHY RMCQSCVELD PATVAGIIVT DVIATLLLAL 120 GVFCFAGHET GRLSGAADTQ ALLRNDQVYQ PLRDRDDAQY SHLGGNWARN K 171 3-308 Sequences 3-308-1 Sequence Number [ID] 308 3-308-2 Molecule Type AA 3-308-3 Length 127 3-308-4 Features source 1..127 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-308-5 Residues MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL 60 GKRILDPRGI YRCNGTDIYK DKESTVQVHY RTADTQALLR NDQVYQPLRD RDDAQYSHLG 120 GNWARNK 127 3-309 Sequences 3-309-1 Sequence Number [ID] 309 3-309-2 Molecule Type AA 3-309-3 Length 21 3-309-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-309-5 Residues DQVYQPLRDR DDAQYSHLGG N 21 3-310 Sequences 3-310-1 Sequence Number [ID] 310 3-310-2 Molecule Type AA 3-310-3 Length 171 3-310-4 Features source 1..171 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-310-5 Residues MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL 60 GKRILDPRGI YRCNGTDIYK DKESTVQVHY RMCQSCVELD PATVAGIIVT DVIATLLLAL 120 GVFCFAGHET GRLSGAADTQ ALLRNDQVYQ PLRDRDDAQY SHLGGNWARN K 171 3-311 Sequences 3-311-1 Sequence Number [ID] 311 3-311-2 Molecule Type AA 3-311-3 Length 127 3-311-4 Features source 1..127 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-311-5 Residues MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL 60 GKRILDPRGI YRCNGTDIYK DKESTVQVHY RTADTQALLR NDQVYQPLRD RDDAQYSHLG 120 GNWARNK 127 3-312 Sequences 3-312-1 Sequence Number [ID] 312 3-312-2 Molecule Type AA 3-312-3 Length 21 3-312-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-312-5 Residues DQVYQPLRDR DDAQYSHLGG N 21 3-313 Sequences 11 Aug 2023

3-313-1 Sequence Number [ID] 313 3-313-2 Molecule Type AA 3-313-3 Length 207 3-313-4 Features source 1..207 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-313-5 Residues MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ 60 HNDKNIGGDE DDKNIGSDED HLSLKEFSEL EQSGYYVCYP RGSKPEDANF YLYLRARVCE 120 NCMEMDVMSV ATIVIVDICI TGGLLLLVYY WSKNRKAKAK PVTRGAGAGG RQRGQNKERP 180 PPVPNPDYEP IRKGQRDLYS GLNQRRI 207 3-314 Sequences 2023214349

3-314-1 Sequence Number [ID] 314 3-314-2 Molecule Type AA 3-314-3 Length 21 3-314-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-314-5 Residues NPDYEPIRKG QRDLYSGLNQ R 21 3-315 Sequences 3-315-1 Sequence Number [ID] 315 3-315-2 Molecule Type AA 3-315-3 Length 182 3-315-4 Features source 1..182 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-315-5 Residues MEQGKGLAVL ILAIILLQGT LAQSIKGNHL VKVYDYQEDG SVLLTCDAEA KNITWFKDGK 60 MIGFLTEDKK KWNLGSNAKD PRGMYQCKGS QNKSKPLQVY YRMCQNCIEL NAATISGFLF 120 AEIVSIFVLA VGVYFIAGQD GVRQSRASDK QTLLPNDQLY QPLKDREDDQ YSHLQGNQLR 180 RN 182 3-316 Sequences 3-316-1 Sequence Number [ID] 316 3-316-2 Molecule Type AA 3-316-3 Length 21 3-316-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-316-5 Residues DQLYQPLKDR EDDQYSHLQG N 21 3-317 Sequences 3-317-1 Sequence Number [ID] 317 3-317-2 Molecule Type AA 3-317-3 Length 21 3-317-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-317-5 Residues DQLYQPLKDR EDDQYSHLQG N 21 3-318 Sequences 3-318-1 Sequence Number [ID] 318 3-318-2 Molecule Type AA 3-318-3 Length 182 3-318-4 Features source 1..182 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-318-5 Residues MEQGKGLAVL ILAIILLQGT LAQSIKGNHL VKVYDYQEDG SVLLTCDAEA KNITWFKDGK 60 MIGFLTEDKK KWNLGSNAKD PRGMYQCKGS QNKSKPLQVY YRMCQNCIEL NAATISGFLF 120 AEIVSIFVLA VGVYFIAGQD GVRQSRASDK QTLLPNDQLY QPLKDREDDQ YSHLQGNQLR 180 RN 182 3-319 Sequences 3-319-1 Sequence Number [ID] 319 3-319-2 Molecule Type AA

3-319-3 Length 163 3-319-4 Features source 1..163 Location/Qualifiers mol_type=protein organism=Homo sapiens 11 Aug 2023

NonEnglishQualifier Value 3-319-5 Residues MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD 60 APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY NELQKDKMAE 120 AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 163 3-320 Sequences 3-320-1 Sequence Number [ID] 320 3-320-2 Molecule Type AA 3-320-3 Length 164 3-320-4 Features source 1..164 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 2023214349

3-320-5 Residues MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD 60 APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP QRRKNPQEGL YNELQKDKMA 120 EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 164 3-321 Sequences 3-321-1 Sequence Number [ID] 321 3-321-2 Molecule Type AA 3-321-3 Length 164 3-321-4 Features source 1..164 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-321-5 Residues MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD 60 APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP QRRKNPQEGL YNELQKDKMA 120 EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 164 3-322 Sequences 3-322-1 Sequence Number [ID] 322 3-322-2 Molecule Type AA 3-322-3 Length 21 3-322-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-322-5 Residues NQLYNELNLG RREEYDVLDK R 21 3-323 Sequences 3-323-1 Sequence Number [ID] 323 3-323-2 Molecule Type AA 3-323-3 Length 112 3-323-4 Features source 1..112 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-323-5 Residues RVKFSRSADA PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN 60 ELQKDKMAEA YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 112 3-324 Sequences 3-324-1 Sequence Number [ID] 324 3-324-2 Molecule Type AA 3-324-3 Length 21 3-324-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-324-5 Residues DGLYQGLSTA TKDTYDALHM Q 21 3-325 Sequences 3-325-1 Sequence Number [ID] 325 3-325-2 Molecule Type AA 3-325-3 Length 112 3-325-4 Features source 1..112 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-325-5 Residues RVKFSRSAEP PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN 60 ELQKDKMAEA YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 112 3-326 Sequences

3-326-1 Sequence Number [ID] 326 3-326-2 Molecule Type AA 3-326-3 Length 113 3-326-4 Features source 1..113 11 Aug 2023

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-326-5 Residues RVKFSRSADA PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPQ RRKNPQEGLY 60 NELQKDKMAE AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 113 3-327 Sequences 3-327-1 Sequence Number [ID] 327 3-327-2 Molecule Type AA 3-327-3 Length 114 3-327-4 Features source 1..114 Location/Qualifiers mol_type=protein organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-327-5 Residues RSRVKFSRSA DAPAYQQGQN QLYNELNLGR REEYDVLDKR RGRDPEMGGK PRRKNPQEGL 60 YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 114 3-328 Sequences 3-328-1 Sequence Number [ID] 328 3-328-2 Molecule Type AA 3-328-3 Length 98 3-328-4 Features source 1..98 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-328-5 Residues RVKFSRSADA PAYQQGEYDV LDKRRGRDPE MGGKPRRKNP QEGLYNELQK DKMAEAYSEI 60 GMKGERRRGK GHDGLYQGLS TATKDTYDAL HMQALPPR 98 3-329 Sequences 3-329-1 Sequence Number [ID] 329 3-329-2 Molecule Type AA 3-329-3 Length 112 3-329-4 Features source 1..112 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-329-5 Residues RVKFSRSADA PAYQQGQNQL YNELNLGRRE EVDVLDKRRG RDPEMGGKPR RKNPQEGLYN 60 ELQKDKMAEA YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 112 3-330 Sequences 3-330-1 Sequence Number [ID] 330 3-330-2 Molecule Type AA 3-330-3 Length 173 3-330-4 Features source 1..173 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-330-5 Residues MIPAVVLLLL LLVEQAAALG EPQLCYILDA ILFLVGIVLT LLVCRLKIQV RKAAITSYEK 60 SRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY 120 NELQKDKMAE AVSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 173 3-331 Sequences 3-331-1 Sequence Number [ID] 331 3-331-2 Molecule Type AA 3-331-3 Length 113 3-331-4 Features source 1..113 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-331-5 Residues LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY 60 NELQKDKMAE AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 113 3-332 Sequences 3-332-1 Sequence Number [ID] 332 3-332-2 Molecule Type AA 3-332-3 Length 60 3-332-4 Features source 1..60 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-332-5 Residues RVKFSRSADA PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPQ RRKNPQEGLY 60

3-333 Sequences 3-333-1 Sequence Number [ID] 333 3-333-2 Molecule Type AA 3-333-3 Length 114 11 Aug 2023

3-333-4 Features source 1..114 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-333-5 Residues LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP QRRKNPQEGL 60 YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 114 3-334 Sequences 3-334-1 Sequence Number [ID] 334 3-334-2 Molecule Type AA 3-334-3 Length 113 3-334-4 Features source 1..113 Location/Qualifiers mol_type=protein 2023214349

organism=Homo sapiens NonEnglishQualifier Value 3-334-5 Residues RRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY 60 NELQKDKMAE AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 113 3-335 Sequences 3-335-1 Sequence Number [ID] 335 3-335-2 Molecule Type AA 3-335-3 Length 21 3-335-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-335-5 Residues NQLYNELNLG RREEYDVLDK R 21 3-336 Sequences 3-336-1 Sequence Number [ID] 336 3-336-2 Molecule Type AA 3-336-3 Length 22 3-336-4 Features source 1..22 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-336-5 Residues EGLYNELQKD KMAEAYSEIG MK 22 3-337 Sequences 3-337-1 Sequence Number [ID] 337 3-337-2 Molecule Type AA 3-337-3 Length 21 3-337-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-337-5 Residues DGLYQGLSTA TKDTYDALHM Q 21 3-338 Sequences 3-338-1 Sequence Number [ID] 338 3-338-2 Molecule Type AA 3-338-3 Length 112 3-338-4 Features source 1..112 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-338-5 Residues RVKFSRSADA PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN 60 ELQKDKMAEA YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 112 3-339 Sequences 3-339-1 Sequence Number [ID] 339 3-339-2 Molecule Type AA 3-339-3 Length 112 3-339-4 Features source 1..112 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-339-5 Residues RVKFSRSADA PAYKQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN 60 ELQKDKMAEA YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 112 3-340 Sequences 3-340-1 Sequence Number [ID] 340

3-340-2 Molecule Type AA 3-340-3 Length 110 3-340-4 Features source 1..110 Location/Qualifiers mol_type=protein 11 Aug 2023

organism=Homo sapiens NonEnglishQualifier Value 3-340-5 Residues RVKFSRSADA PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN 60 ELQKDKMAEA YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP 110 3-341 Sequences 3-341-1 Sequence Number [ID] 341 3-341-2 Molecule Type AA 3-341-3 Length 137 3-341-4 Features source 1..137 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 2023214349

3-341-5 Residues DPKLCYLLDG ILFIYGVILT ALFLRVKFSR SADAPAYQQG QNQLYNELNL GRREEYDVLD 60 KRRGRDPEMG GKPQRRKNPQ EGLYNELQKD KMAEAYSEIG MKGERRRGKG HDGLYQGLST 120 ATKDTYDALH MQALPPR 137 3-342 Sequences 3-342-1 Sequence Number [ID] 342 3-342-2 Molecule Type AA 3-342-3 Length 163 3-342-4 Features source 1..163 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-342-5 Residues MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD 60 APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY NELQKDKMAE 120 AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 163 3-343 Sequences 3-343-1 Sequence Number [ID] 343 3-343-2 Molecule Type AA 3-343-3 Length 38 3-343-4 Features source 1..38 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-343-5 Residues RSRDQRLPPD AHKPPGGGSF RTPIQEEQAD AHSTLAKI 38 3-344 Sequences 3-344-1 Sequence Number [ID] 344 3-344-2 Molecule Type AA 3-344-3 Length 226 3-344-4 Features source 1..226 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-344-5 Residues MPGGPGVLQA LPATIFLLFL LSAVYLGPGC QALWMHKVPA SLMVSLGEDA HFQCPHNSSN 60 NANVTWWRVL HGNYTWPPEF LGPGEDPNGT LIIQNVNKSH GGIYVCRVQE GNESYQQSCG 120 TYLRVRQPPP RPFLDMGEGT KNRIITAEGI ILLFCAVVPG TLLLFRKRWQ NEKLGLDAGD 180 EYEDENLYEG LNLDDCSMYE DISRGLQGTY QDVGSLNIGD VQLEKP 226 3-345 Sequences 3-345-1 Sequence Number [ID] 345 3-345-2 Molecule Type AA 3-345-3 Length 188 3-345-4 Features source 1..188 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-345-5 Residues MPGGPGVLQA LPATIFLLFL LSAVYLGPGC QALWMHKVPA SLMVSLGEDA HFQCPHNSSN 60 NANVTWWRVL HGNYTWPPEF LGPGEDPNEP PPRPFLDMGE GTKNRIITAE GIILLFCAVV 120 PGTLLLFRKR WQNEKLGLDA GDEYEDENLY EGLNLDDCSM YEDISRGLQG TYQDVGSLNI 180 GDVQLEKP 188 3-346 Sequences 3-346-1 Sequence Number [ID] 346 3-346-2 Molecule Type AA 3-346-3 Length 226 3-346-4 Features source 1..226 Location/Qualifiers mol_type=protein organism=Homo sapiens

NonEnglishQualifier Value 3-346-5 Residues MPGGPGVLQA LPATIFLLFL LSAVYLGPGC QALWMHKVPA SLMVSLGEDA HFQCPHNSSN 60 NANVTWWRVL HGNYTWPPEF LGPGEDPNGT LIIQNVNKSH GGIYVCRVQE GNESYQQSCG 120 TYLRVRQPPP RPFLDMGEGT KNRIITAEGI ILLFCAVVPG TLLLFRKRWQ NEKLGLDAGD 180 EYEDENLYEG LNLDDCSMYE DISRGLQGTY QDVGSLNIGD VQLEKP 226 11 Aug 2023

3-347 Sequences 3-347-1 Sequence Number [ID] 347 3-347-2 Molecule Type AA 3-347-3 Length 21 3-347-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-347-5 Residues ENLYEGLNLD DCSMYEDISR G 21 3-348 Sequences 3-348-1 Sequence Number [ID] 348 2023214349

3-348-2 Molecule Type AA 3-348-3 Length 84 3-348-4 Features source 1..84 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-348-5 Residues FVPVFLPAKP TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA 60 PLAGTCGVLL LSLVITLYCN HRNR 84 3-349 Sequences 3-349-1 Sequence Number [ID] 349 3-349-2 Molecule Type AA 3-349-3 Length 84 3-349-4 Features source 1..84 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-349-5 Residues FVPVFLPAKP ITTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA 60 PLAGTCGVLL LSLVITLYCN HRNR 84 3-350 Sequences 3-350-1 Sequence Number [ID] 350 3-350-2 Molecule Type AA 3-350-3 Length 47 3-350-4 Features source 1..47 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-350-5 Residues PTTTPAPRPP TPAPTIASQP LSLRPEACRP AAGGAVHTRG LDFACDI 47 3-351 Sequences 3-351-1 Sequence Number [ID] 351 3-351-2 Molecule Type AA 3-351-3 Length 41 3-351-4 Features source 1..41 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-351-5 Residues AVSLSKMLKK RSPLTTGVFV KMAPTEAECE KQFQPYFIPI N 41 3-352 Sequences 3-352-1 Sequence Number [ID] 352 3-352-2 Molecule Type AA 3-352-3 Length 47 3-352-4 Features source 1..47 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-352-5 Residues AVSLSKMLKK RSPLTTGVYM NMTPRRPECE KQFQPYAPPR DFAAYRS 47 3-353 Sequences 3-353-1 Sequence Number [ID] 353 3-353-2 Molecule Type AA 3-353-3 Length 20 3-353-4 Features source 1..20 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value

3-353-5 Residues RPRRSPAQDG KVYINMPGRG 20 3-354 Sequences 3-354-1 Sequence Number [ID] 354 3-354-2 Molecule Type AA 11 Aug 2023

3-354-3 Length 113 3-354-4 Features source 1..113 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-354-5 Residues MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 60 VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD VYSDLNTQRP YYK 113 3-355 Sequences 3-355-1 Sequence Number [ID] 355 3-355-2 Molecule Type AA 3-355-3 Length 112 3-355-4 Features source 1..112 2023214349

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-355-5 Residues MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 60 VYFLGRLVPR GRGAAEATRK QRITETESPY QELQGQRSDV YSDLNTQRPY YK 112 3-356 Sequences 3-356-1 Sequence Number [ID] 356 3-356-2 Molecule Type AA 3-356-3 Length 102 3-356-4 Features source 1..102 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-356-5 Residues MGGLEPCSRL LLLPLLLAVS DCSCSTVSPG VLAGIVMGDL VLTVLIALAV YFLGRLVPRG 60 RGAAEAATRK QRITETESPY QELQGQRSDV YSDLNTQRPY YK 102 3-357 Sequences 3-357-1 Sequence Number [ID] 357 3-357-2 Molecule Type AA 3-357-3 Length 101 3-357-4 Features source 1..101 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-357-5 Residues MGGLEPCSRL LLLPLLLAVS DCSCSTVSPG VLAGIVMGDL VLTVLIALAV YFLGRLVPRG 60 RGAAEATRKQ RITETESPYQ ELQGQRSDVY SDLNTQRPYY K 101 3-358 Sequences 3-358-1 Sequence Number [ID] 358 3-358-2 Molecule Type AA 3-358-3 Length 113 3-358-4 Features source 1..113 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-358-5 Residues MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 60 VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD VYSDLNTQRP YYK 113 3-359 Sequences 3-359-1 Sequence Number [ID] 359 3-359-2 Molecule Type AA 3-359-3 Length 112 3-359-4 Features source 1..112 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-359-5 Residues MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 60 VYFLGRLVPR GRGAAEATRK QRITETESPY QELQGQRSDV YSDLNTQRPY YK 112 3-360 Sequences 3-360-1 Sequence Number [ID] 360 3-360-2 Molecule Type AA 3-360-3 Length 102 3-360-4 Features source 1..102 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value

3-360-5 Residues MGGLEPCSRL LLLPLLLAVS DCSCSTVSPG VLAGIVMGDL VLTVLIALAV YFLGRLVPRG 60 RGAAEAATRK QRITETESPY QELQGQRSDV YSDLNTQRPY YK 102 3-361 Sequences 3-361-1 Sequence Number [ID] 361 3-361-2 Molecule Type AA 11 Aug 2023

3-361-3 Length 101 3-361-4 Features source 1..101 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-361-5 Residues MGGLEPCSRL LLLPLLLAVS DCSCSTVSPG VLAGIVMGDL VLTVLIALAV YFLGRLVPRG 60 RGAAEATRKQ RITETESPYQ ELQGQRSDVY SDLNTQRPYY K 101 3-362 Sequences 3-362-1 Sequence Number [ID] 362 3-362-2 Molecule Type AA 3-362-3 Length 21 2023214349

3-362-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-362-5 Residues ESPYQELQGQ RSDVYSDLNT Q 21 3-363 Sequences 3-363-1 Sequence Number [ID] 363 3-363-2 Molecule Type AA 3-363-3 Length 21 3-363-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-363-5 Residues ESPYQELQGQ RSDVYSDLNT Q 21 3-364 Sequences 3-364-1 Sequence Number [ID] 364 3-364-2 Molecule Type AA 3-364-3 Length 49 3-364-4 Features source 1..49 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-364-5 Residues RSQCMWPRET QLLLEVPPST EDARSCQFPE EERGERSAEE KGRLGDLWV 49 3-365 Sequences 3-365-1 Sequence Number [ID] 365 3-365-2 Molecule Type AA 3-365-3 Length 35 3-365-4 Features source 1..35 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-365-5 Residues TKKKYSSSVH DPNGEFMFMR AVNTAKKSRL TDVTL 35 3-366 Sequences 3-366-1 Sequence Number [ID] 366 3-366-2 Molecule Type AA 3-366-3 Length 39 3-366-4 Features source 1..39 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-366-5 Residues KSRQTPPLAS VEMEAMEALP VTWGTSSRDE DLENCSHHL 39 3-367 Sequences 3-367-1 Sequence Number [ID] 367 3-367-2 Molecule Type AA 3-367-3 Length 149 3-367-4 Features source 1..149 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-367-5 Residues RRDQRLPPDA HKPPGGGSFR TPIQEEQADA HSTLAKIRVK FSRSADAPAY QQGQNQLYNE 60 LNLGRREEYD VLDKRRGRDP EMGGKPRRKN PQEGLYNELQ KDKMAEAYSE IGMKGERRRG 120 KGHDGLYQGL STATKDTYDA LHMQALPPR 149 3-368 Sequences

3-368-1 Sequence Number [ID] 368 3-368-2 Molecule Type AA 3-368-3 Length 619 3-368-4 Features source 1..619 11 Aug 2023

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-368-5 Residues MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL VHDVRFHHFP 60 IERQLNGTYA IAGGKAHCGP AELCEFYSRD PDGLPCNLRK PCNRPSGLEP QPGVFDCLRD 120 AMVRDYVRQT WKLEGEALEQ AIISQAPQVE KLIATTAHER MPWYHSSLTR EEAERKLYSG 180 AQTDGKFLLR PRKEQGTYAL SLIYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK 240 LKADGLIYCL KEACPNSSAS NASGAAAPTL PAHPSTLTHP QRRIDTLNSD GYTPEPARIT 300 SPDKPRPMPM DTSVYESPYS DPEELKDKKL FLKRDNLLIA DIELGCGNFG SVRQGVYRMR 360 KKQIDVAIKV LKQGTEKADT EEMMREAQIM HQLDNPYIVR LIGVCQAEAL MLVMEMAGGG 420 PLHKFLVGKR EEIPVSNVAE LLHQVSMGMK YLEEKNFVHR DLAARNVLLV NRHYAKISDF 480 GLSKALGADD SYYTARSAGK WPLKWYAPEC INFRKFSSRS DVWSYGVTMW EALSYGQKPY 540 KKMKGPEVMA FIEQGKRMEC PPECPPELYA LMSDCWIYKW EDRPDFLTVE QRMRACYYSL 600 2023214349

ASKVEGPPGS TQKAEAACA 619 3-369 Sequences 3-369-1 Sequence Number [ID] 369 3-369-2 Molecule Type AA 3-369-3 Length 180 3-369-4 Features source 1..180 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-369-5 Residues MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE FRASLHKGLD 60 SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ NLYVNQTDIY FCKIEVMYPP 120 PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV TVAFIIFWVR 180 3-370 Sequences 3-370-1 Sequence Number [ID] 370 3-370-2 Molecule Type AA 3-370-3 Length 240 3-370-4 Features source 1..240 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-370-5 Residues MGNSCYNIVA TLLLVLNFER TRSLQDPCSN CPAGTFCDNN RNQICSPCPP NSFSSAGGQR 60 TCDICRQCKG VFRTRKECSS TSNAECDCTP GFHCLGAGCS MCEQDCKQGQ ELTKKGCKDC 120 CFGTFNDQKR GICRPWTNCS LDGKSVLVNG TKERDVVCGP SPADLSPGAS SVTPPAPARE 180 PGHSPQIISF FLALTSTALL FLLFFLTLRF SVVKRGRKKL LYIFKQPFMR PVQTTQEEDG 240 3-371 Sequences 3-371-1 Sequence Number [ID] 371 3-371-2 Molecule Type AA 3-371-3 Length 86 3-371-4 Features source 1..86 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-371-5 Residues MIPAVVLLLL LLVEQAAALG EPQLCYILDA ILFLYGIVLT LLYCRLKIQV RKAAITSYEK 60 SDGVYTGLST RNQETYETLK HEKPPQ 86 3-372 Sequences 3-372-1 Sequence Number [ID] 372 3-372-2 Molecule Type AA 3-372-3 Length 21 3-372-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-372-5 Residues DGVYTGLSTR NQETYETLKH E 21 3-373 Sequences 3-373-1 Sequence Number [ID] 373 3-373-2 Molecule Type AA 3-373-3 Length 66 3-373-4 Features source 1..66 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-373-5 Residues DPKLCYILDA ILFLYGIVLT LLYCRLKIQV RKAAITSYEK SDGVYTGLST RNQETYETLK 60 HEKPPQ 66

3-374 Sequences 3-374-1 Sequence Number [ID] 374 3-374-2 Molecule Type AA 3-374-3 Length 21 11 Aug 2023

3-374-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-374-5 Residues DGVYTGLSTR NQETYETLKH E 21 3-375 Sequences 3-375-1 Sequence Number [ID] 375 3-375-2 Molecule Type AA 3-375-3 Length 46 3-375-4 Features source 1..46 Location/Qualifiers mol_type=protein organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-375-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDI 46 3-376 Sequences 3-376-1 Sequence Number [ID] 376 3-376-2 Molecule Type AA 3-376-3 Length 31 3-376-4 Features source 1..31 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-376-5 Residues IISFFLALTS TALLFLLFFL TLRFSVVKRG R 31 3-377 Sequences 3-377-1 Sequence Number [ID] 377 3-377-2 Molecule Type AA 3-377-3 Length 27 3-377-4 Features source 1..27 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-377-5 Residues IISFFLALTS TALLFLLFFL TLRFSVV 27 3-378 Sequences 3-378-1 Sequence Number [ID] 378 3-378-2 Molecule Type AA 3-378-3 Length 26 3-378-4 Features source 1..26 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-378-5 Residues VAAILGLGLV LGLLGPLAIL LALYLL 26 3-379 Sequences 3-379-1 Sequence Number [ID] 379 3-379-2 Molecule Type AA 3-379-3 Length 363 3-379-4 Features source 1..363 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-379-5 Residues AVFGCIFGAL VIVTVGGFIF WRKKRKDAKN NEVSFSQIKP KKSKLIRVEN FEAYFKKQQA 60 DSNCGFAEEY EDLKLVGISQ PKYAAELAEN RGKNRYNNVL PYDISRVKLS VQTHSTDDYI 120 NANYMPGYHS KKDFIATQGP LPNTLKDFWR MVWEKNVYAI IMLTKCVEQG RTKCEEYWPS 180 KQAQDYGDIT VAMTSEIVLP EVVTIRDFTV KNIQTSESHP LRQFHFTSWP DHGVPDTTDL 240 LINFRYLVRD YMKQSPPESP ILVHCSAGVG RTGTFIAIDR LIYQIENENT VDVYGIVYDL 300 RMHRPLMVQT EDQYVFLNQC VLDIVRSQKD SKVDLIYQNT TAMTIYENLA PVTTFGKTNG 360 YIA 363 3-380 Sequences 3-380-1 Sequence Number [ID] 380 3-380-2 Molecule Type AA 3-380-3 Length 21 3-380-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-380-5 Residues AVFGCIFGAL VIVTVGGFIF W 21

3-381 Sequences 3-381-1 Sequence Number [ID] 381 3-381-2 Molecule Type AA 3-381-3 Length 185 11 Aug 2023

3-381-4 Features source 1..185 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-381-5 Residues KEITNALETW GALGQDINLD IPSFQMSDDI DDIKWEKTSD KKKIAQFRKE KETFKEKDTY 60 KLFKNGTLKI KHLKTDDQDI YKVSIYDTKG KNVLEKIFDL KIQERVSKPK ISWTCINTTL 120 TCEVMNGTDP ELNLYQDGKH LKLSQRVITH KWTTSLSAKF KCTAGNKVSK ESSVEPVSCP 180 EKGLD 185 3-382 Sequences 3-382-1 Sequence Number [ID] 382 3-382-2 Molecule Type AA 3-382-3 Length 106 2023214349

3-382-4 Features source 1..106 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-382-5 Residues IEVMYPPPYL DNEKSNGTIT HVKGKHLCPS PLFPGPSKPF WVLVVVGGVL ACYSLLVTVA 60 HIFWVRSKRS RLLHSDYMNM TPRRPGPTRK HYQPYAPPRD FAAYRS 106 3-383 Sequences 3-383-1 Sequence Number [ID] 383 3-383-2 Molecule Type AA 3-383-3 Length 27 3-383-4 Features source 1..27 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-383-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWV 27 3-384 Sequences 3-384-1 Sequence Number [ID] 384 3-384-2 Molecule Type AA 3-384-3 Length 66 3-384-4 Features source 1..66 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-384-5 Residues IEVMYPPPYL DNEKSNGTII HVKGKHLCPS PLFPGPSKPF WVLVVVGGVL ACYSLLVTVA 60 FIIFWV 66 3-385 Sequences 3-385-1 Sequence Number [ID] 385 3-385-2 Molecule Type AA 3-385-3 Length 33 3-385-4 Features source 1..33 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-385-5 Residues IFWVLVVVGG VLACYSLLVT VAFIIFWVRS KRR 33 3-386 Sequences 3-386-1 Sequence Number [ID] 386 3-386-2 Molecule Type AA 3-386-3 Length 68 3-386-4 Features source 1..68 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-386-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVRSK RSRLLHSDYM NMTPRRPGPT RKHYQPYAPP 60 RDFAAYRS 68 3-387 Sequences 3-387-1 Sequence Number [ID] 387 3-387-2 Molecule Type AA 3-387-3 Length 28 3-387-4 Features source 1..28 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-387-5 Residues MFWVLVVVGG VLACYSLLVT VAFIIFWV 28

3-388 Sequences 3-388-1 Sequence Number [ID] 388 3-388-2 Molecule Type AA 3-388-3 Length 26 11 Aug 2023

3-388-4 Features source 1..26 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-388-5 Residues FWVLVVVGGV LACYSLLVTV AFHFWV 26 3-389 Sequences 3-389-1 Sequence Number [ID] 389 3-389-2 Molecule Type AA 3-389-3 Length 28 3-389-4 Features source 1..28 Location/Qualifiers mol_type=protein organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-389-5 Residues MFWVLVVVGG VLACYSGGVT VAFIIFWV 28 3-390 Sequences 3-390-1 Sequence Number [ID] 390 3-390-2 Molecule Type AA 3-390-3 Length 26 3-390-4 Features source 1..26 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-390-5 Residues WVLVVVGGVL ACYSLLVTVA FIIFWV 26 3-391 Sequences 3-391-1 Sequence Number [ID] 391 3-391-2 Molecule Type AA 3-391-3 Length 69 3-391-4 Features source 1..69 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-391-5 Residues PFWVLVVVGG VLACYSLLVT VAFIIFWVRS KRSRLLHSDY MNMTPRRPGP TRKHYQPYAP 60 PRDFAAYRS 69 3-392 Sequences 3-392-1 Sequence Number [ID] 392 3-392-2 Molecule Type AA 3-392-3 Length 180 3-392-4 Features source 1..180 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-392-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVRSK RSRLLHSDYM NMTPRRPGPT RKHYQPYAPP 60 RDFAAYRSRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY DVLDKRRGRD PEMGGKPRRK 120 NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG LSTATKDTYD ALHMQALPPR 180 3-393 Sequences 3-393-1 Sequence Number [ID] 393 3-393-2 Molecule Type AA 3-393-3 Length 216 3-393-4 Features source 1..216 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-393-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVRSK RSRLLHSDYM NMTPRRPGPT RKHYQPYAPP 60 RDFAAYRSRD QRLPPDAHKP PGGGSFRTPI QEEQADAHST LAKIRVKFSR SADAPAYQQG 120 QNQLYNELNL GRREEYDVLD KRRGRDPEMG GKPRRKNPQE GLYNELQKDK MAEAYSEIGM 180 KGERRRGKGH DGLYQGLSTA TKDTYDALHM QALPPR 216 3-394 Sequences 3-394-1 Sequence Number [ID] 394 3-394-2 Molecule Type AA 3-394-3 Length 140 3-394-4 Features source 1..140 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-394-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVRRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY 60

DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG 120 LSTATKDTYD ALHMQALPPR 140 3-395 Sequences 3-395-1 Sequence Number [ID] 395 3-395-2 Molecule Type AA 11 Aug 2023

3-395-3 Length 222 3-395-4 Features source 1..222 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-395-5 Residues AAAIEVMYPP PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV 60 TVAFIIFWVR SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS RVKFSRSADA 120 PAYQQGQNQL YNELNLGRRE EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN ELQKDKMAEA 180 YSEIGMKGER RRGKGHDGLY QGLSTATKDT YDALHMQALP PR 222 3-396 Sequences 3-396-1 Sequence Number [ID] 396 2023214349

3-396-2 Molecule Type AA 3-396-3 Length 23 3-396-4 Features source 1..23 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-396-5 Residues LCYLLDGILF IYGVILTALF LRV 23 3-397 Sequences 3-397-1 Sequence Number [ID] 397 3-397-2 Molecule Type AA 3-397-3 Length 51 3-397-4 Features source 1..51 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-397-5 Residues MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF L 51 3-398 Sequences 3-398-1 Sequence Number [ID] 398 3-398-2 Molecule Type AA 3-398-3 Length 21 3-398-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-398-5 Residues LCYLLDGILF IYGVILTALF L 21 3-399 Sequences 3-399-1 Sequence Number [ID] 399 3-399-2 Molecule Type AA 3-399-3 Length 25 3-399-4 Features source 1..25 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-399-5 Residues ALIVLGGVAG LLLFIGLGIF FCVRC 25 3-400 Sequences 3-400-1 Sequence Number [ID] 400 3-400-2 Molecule Type AA 3-400-3 Length 22 3-400-4 Features source 1..22 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-400-5 Residues MALIVLGGVA GLLLFIGLGI FF 22 3-401 Sequences 3-401-1 Sequence Number [ID] 401 3-401-2 Molecule Type AA 3-401-3 Length 725 3-401-4 Features source 1..725 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-401-5 Residues ALIAFLAFLI IVTSIALLVV LYKIYDLHKK RSCNLDEQQE LVERDDEKQL MNVEPIHADI 60 LLETYKRKIA DEGRLFLAEF QSIPRVFSKF PIKEARKPFN QNKNRYVDIL PYDYNRVELS 120

EINGDAGSNY INASYIDGFK EPRKYIAAQG PRDETVDDFW RMIWEQKATV IVMVTRCEEG 180 NRNKCAEYWP SMEEGTRAFG DVVVKINQHK RCPDYIIQKL NIVNKKEKAT GREVTHIQFT 240 SWPDHGVPED PHLLLKLRRR VNAFSNFFSG PIWHCSAGVG RTGTYIGIDA MLEGLEAENK 300 VDVYGYVVKL RRQRCLMVQV EAQYILIHQA LVEYNQFGET EVNLSELHPY LHNMKKRDPP 360 SEPSPLEAEF QRLPSYRSWR TQHIGNQEEN KSKNRNSNVI PYDYNRVPLK HELEMSKESE 420 11 Aug 2023

HDSDESSDDD SDSEEPSKYI NASFIMSYWK PEVMIAAQGP LKETIGDFWQ MIFQRKVKVI 480 VMLTELKHGD QEICAQYWGE GKQTYGDIEV DLKDTDKSST YTLRVFELRH SKRKDSRTVY 540 QYQYTNWSVE QLPAEPKELI SMIQWKQKLP QKNSSEGNKH HKSTPLLIHC RDGSQQTGIF 600 CALLNLLESA ETEEWDIFQW KALRKARPGM VSTFEQYQFL YDVIASTYPA QNGQVKKNNH 660 QEDKIEFDNE VDKVKQDANC VNPLGAPEKL PEAKEQAEGS EPTSGTEGPE HSVNGPASPA 720 LNQGS 725 3-402 Sequences 3-402-1 Sequence Number [ID] 402 3-402-2 Molecule Type AA 3-402-3 Length 23 3-402-4 Features source 1..23 Location/Qualifiers mol_type=protein 2023214349

organism=Homo sapiens NonEnglishQualifier Value 3-402-5 Residues PLFIPVAVMV TAFSGLAFII WLA 23 3-403 Sequences 3-403-1 Sequence Number [ID] 403 3-403-2 Molecule Type AA 3-403-3 Length 24 3-403-4 Features source 1..24 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-403-5 Residues ALPAALAVIS FLLGLGLGVA CVLA 24 3-404 Sequences 3-404-1 Sequence Number [ID] 404 3-404-2 Molecule Type AA 3-404-3 Length 21 3-404-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-404-5 Residues MALPVTALLL PLALLLHAAR P 21 3-405 Sequences 3-405-1 Sequence Number [ID] 405 3-405-2 Molecule Type AA 3-405-3 Length 286 3-405-4 Features source 1..286 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-405-5 Residues AAAFVPVFLP AKPTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT RGLDFACDIY 60 IWAPLAGTCG VLLLSLVITL YCNHRNRSKR SRLLHSDYMN MTPRRPGPTR KHYQPYAPPR 120 DFAAYRSRFS VVKRGRKKLL YIFKQPFMRP VQTTQEEDGC SCRFPEEEEG GCELRVKFSR 180 SADAPAYQQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG GKPRRKNPQE GLYNELQKDK 240 MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM QALPPR 286 3-406 Sequences 3-406-1 Sequence Number [ID] 406 3-406-2 Molecule Type AA 3-406-3 Length 226 3-406-4 Features source 1..226 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-406-5 Residues AAATTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT RGLDFACDIY IWAPLAGTCG 60 VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC SCRFPEEEEG GCELRVKFSR 120 SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG GKPRRKNPQE GLYNELQKDK 180 MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM QALPPR 226 3-407 Sequences 3-407-1 Sequence Number [ID] 407 3-407-2 Molecule Type AA 3-407-3 Length 83 3-407-4 Features source 1..83 Location/Qualifiers mol_type=protein organism=Homo sapiens

NonEnglishQualifier Value 3-407-5 Residues FVPVFLPAKP TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA 60 PLAGTCGVLL LSLVITLYCN HRN 83 3-408 Sequences 3-408-1 Sequence Number [ID] 408 11 Aug 2023

3-408-2 Molecule Type AA 3-408-3 Length 22 3-408-4 Features source 1..22 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-408-5 Residues IWAPLAGTCG VLLLSLVITL YC 22 3-409 Sequences 3-409-1 Sequence Number [ID] 409 3-409-2 Molecule Type AA 3-409-3 Length 24 2023214349

3-409-4 Features source 1..24 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-409-5 Residues IYIWAPLAGT CGVLLLSLVI TLYC 24 3-410 Sequences 3-410-1 Sequence Number [ID] 410 3-410-2 Molecule Type AA 3-410-3 Length 25 3-410-4 Features source 1..25 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-410-5 Residues IYIWAPLAGT CGVLLLSLVI TLYCR 25 3-411 Sequences 3-411-1 Sequence Number [ID] 411 3-411-2 Molecule Type AA 3-411-3 Length 71 3-411-4 Features source 1..71 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-411-5 Residues PTTTPAPRPP TPAPTIASQP LSLRPEACRP AAGGAVHTRG LDFACDIYIW APLAGTCGVL 60 LLSLVITLYC N 71 3-412 Sequences 3-412-1 Sequence Number [ID] 412 3-412-2 Molecule Type AA 3-412-3 Length 25 3-412-4 Features source 1..25 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-412-5 Residues IYIWAPLAGT CGVLLLSLVI TLVCR 25 3-413 Sequences 3-413-1 Sequence Number [ID] 413 3-413-2 Molecule Type AA 3-413-3 Length 21 3-413-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-413-5 Residues IYIWAPLAGT CGVLLLSLVI T 21 3-414 Sequences 3-414-1 Sequence Number [ID] 414 3-414-2 Molecule Type AA 3-414-3 Length 23 3-414-4 Features source 1..23 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-414-5 Residues IYIWAPLAGT CGVLLLSLVI TLY 23 3-415 Sequences

3-415-1 Sequence Number [ID] 415 3-415-2 Molecule Type AA 3-415-3 Length 101 3-415-4 Features source 1..101 11 Aug 2023

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-415-5 Residues APVGLVARLA DESGHVVLRW LPPPETPMTS HIRYEVDVSA GNGAGSVQRV EILEGRTECV 60 LSNLRGRTRY TFAVRARMAE PSFGGFWSAW SEPVSLLTPS D 101 3-416 Sequences 3-416-1 Sequence Number [ID] 416 3-416-2 Molecule Type AA 3-416-3 Length 52 3-416-4 Features source 1..52 Location/Qualifiers mol_type=protein organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-416-5 Residues FFIPLLVVIL FAVDTGLFIS TQQQVTFLLK IKRTRKGFRL LNPHPKPNPK NN 52 3-417 Sequences 3-417-1 Sequence Number [ID] 417 3-417-2 Molecule Type AA 3-417-3 Length 257 3-417-4 Features source 1..257 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-417-5 Residues MAPAMESPTL LCVALLFFAP DGVLAVPQKP KVSLNPPWNR IFKGENVTLT CNGNNFFEVS 60 STKWFHNGSL SEETNSSLNI VNAKFEDSGE YKCQHQQVNE SEPVYLEVFS DWLLLQASAE 120 VVMEGQPLFL RCHGWRNWDV YKVIYYKDGE ALKYWYENHN ISITNATVED SGTYYCTGKV 180 WQLDYESEPL NITVIKAPRE KYWLQFFIPL LVVILFAVDT GLFISTQQQV TFLLKIKRTR 240 KGFRLLNPHP KPNPKNN 257 3-418 Sequences 3-418-1 Sequence Number [ID] 418 3-418-2 Molecule Type AA 3-418-3 Length 244 3-418-4 Features source 1..244 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-418-5 Residues MDTESNRRAN LALPQEPSSV PAFEVLEISP QEVSSGRLLK SASSPPLHTW LTVLKKEQEF 60 LGVTQILTAM ICLCFGTVVC SVLDISHIEG DIFSSFKAGY PFWGAIFFSI SGMLSIISER 120 RNATYLVRGS LGANTASSIA GGTGITILII NLKKSLAYIH IHSCQKFFET KCFMASFSTE 180 IVVMMLFLTI LGLGSAVSLT ICGAGEELKG NKVPEDRVYE ELNIYSATYS ELEDPGEMSP 240 PIDL 244 3-419 Sequences 3-419-1 Sequence Number [ID] 419 3-419-2 Molecule Type AA 3-419-3 Length 86 3-419-4 Features source 1..86 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-419-5 Residues MIPAVVLLLL LLVEQAAALG EPQLCYILDA ILFLYGIVLT LLYCRLKIQV RKAAITSYEK 60 SDGVYTGLST RNQETYETLK HEKPPQ 86 3-420 Sequences 3-420-1 Sequence Number [ID] 420 3-420-2 Molecule Type AA 3-420-3 Length 54 3-420-4 Features source 1..54 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-420-5 Residues DIFIPLLVVI LFAVDTGLFI STQQQVTFLL KIKRTRKGFR LLNPHPKPNP KNNR 54 3-421 Sequences 3-421-1 Sequence Number [ID] 421 3-421-2 Molecule Type AA 3-421-3 Length 31 3-421-4 Features source 1..31 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-421-5 Residues PLGWLTVVLL AVAACVLLLT SAQLGLHIWQ L 31 3-422 Sequences 11 Aug 2023

3-422-1 Sequence Number [ID] 422 3-422-2 Molecule Type AA 3-422-3 Length 24 3-422-4 Features source 1..24 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-422-5 Residues SIISAVVGIL LVVVLGVVFG ILII 24 3-423 Sequences 3-423-1 Sequence Number [ID] 423 3-423-2 Molecule Type AA 3-423-3 Length 113 2023214349

3-423-4 Features source 1..113 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-423-5 Residues CHPECQPQNG SVTCFGPEAD QCVACAHYKD PPFCVARCPS GVKPDLSYMP IWKFPDEEGA 60 CQPCPINCTH SCVDLDDKGC PAEQRASPLT SIISAVVGIL LVVVLGVVFG ILI 113 3-424 Sequences 3-424-1 Sequence Number [ID] 424 3-424-2 Molecule Type AA 3-424-3 Length 21 3-424-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-424-5 Residues FLVIIVILSA LFLGTLACFC V 21 3-425 Sequences 3-425-1 Sequence Number [ID] 425 3-425-2 Molecule Type AA 3-425-3 Length 68 3-425-4 Features source 1..68 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-425-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVRSK RSRLLHSDYM NMTPRRPGPT RKHYQAYAAA 60 RDFAAYRS 68 3-426 Sequences 3-426-1 Sequence Number [ID] 426 3-426-2 Molecule Type AA 3-426-3 Length 5 3-426-4 Features source 1..5 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-426-5 Residues DKTHT 5 3-427 Sequences 3-427-1 Sequence Number [ID] 427 3-427-2 Molecule Type AA 3-427-3 Length 4 3-427-4 Features source 1..4 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-427-5 Residues CPPC 4 3-428 Sequences 3-428-1 Sequence Number [ID] 428 3-428-2 Molecule Type AA 3-428-3 Length 15 3-428-4 Features source 1..15 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-428-5 Residues CPEPKSCDTP PPCPR 15

3-429 Sequences 3-429-1 Sequence Number [ID] 429 3-429-2 Molecule Type AA 3-429-3 Length 12 11 Aug 2023

3-429-4 Features source 1..12 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-429-5 Residues ELKTPLGDTT HT 12 3-430 Sequences 3-430-1 Sequence Number [ID] 430 3-430-2 Molecule Type AA 3-430-3 Length 10 3-430-4 Features source 1..10 Location/Qualifiers mol_type=protein organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-430-5 Residues KSCDKTHTCP 10 3-431 Sequences 3-431-1 Sequence Number [ID] 431 3-431-2 Molecule Type AA 3-431-3 Length 7 3-431-4 Features source 1..7 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-431-5 Residues KCCVDCP 7 3-432 Sequences 3-432-1 Sequence Number [ID] 432 3-432-2 Molecule Type AA 3-432-3 Length 7 3-432-4 Features source 1..7 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-432-5 Residues KYGPPCP 7 3-433 Sequences 3-433-1 Sequence Number [ID] 433 3-433-2 Molecule Type AA 3-433-3 Length 16 3-433-4 Features source 1..16 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-433-5 Residues VEPKSPDKTH TCPPCP 16 3-434 Sequences 3-434-1 Sequence Number [ID] 434 3-434-2 Molecule Type AA 3-434-3 Length 16 3-434-4 Features source 1..16 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-434-5 Residues LDPKSSDKTH TCPPCP 16 3-435 Sequences 3-435-1 Sequence Number [ID] 435 3-435-2 Molecule Type AA 3-435-3 Length 39 3-435-4 Features source 1..39 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-435-5 Residues IEVMYPPPYL DNEKSNGTII HVKGKHLCPS PLFPGPSKP 39 3-436 Sequences 3-436-1 Sequence Number [ID] 436 3-436-2 Molecule Type AA 3-436-3 Length 12 3-436-4 Features source 1..12

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-436-5 Residues GGAVHTRGLD FA 12 11 Aug 2023

3-437 Sequences 3-437-1 Sequence Number [ID] 437 3-437-2 Molecule Type AA 3-437-3 Length 45 3-437-4 Features source 1..45 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-437-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACD 45 3-438 Sequences 3-438-1 Sequence Number [ID] 438 3-438-2 Molecule Type AA 2023214349

3-438-3 Length 48 3-438-4 Features source 1..48 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-438-5 Residues AKPTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT RGLDFACD 48 3-439 Sequences 3-439-1 Sequence Number [ID] 439 3-439-2 Molecule Type AA 3-439-3 Length 45 3-439-4 Features source 1..45 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-439-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACD 45 3-440 Sequences 3-440-1 Sequence Number [ID] 440 3-440-2 Molecule Type AA 3-440-3 Length 45 3-440-4 Features source 1..45 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-440-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACD 45 3-441 Sequences 3-441-1 Sequence Number [ID] 441 3-441-2 Molecule Type AA 3-441-3 Length 79 3-441-4 Features source 1..79 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-441-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDEPKSP DKTHTCPPCP 60 APPVAGPSVF LFPPKPKDT 79 3-442 Sequences 3-442-1 Sequence Number [ID] 442 3-442-2 Molecule Type AA 3-442-3 Length 51 3-442-4 Features source 1..51 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-442-5 Residues PAKPTTTPAP RPPTPAPTIA SQPLSLRPEA CRPAAGGAVH TRGLDFACDI Y 51 3-443 Sequences 3-443-1 Sequence Number [ID] 443 3-443-2 Molecule Type AA 3-443-3 Length 69 3-443-4 Features source 1..69 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-443-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL 60

LSLVITLYC 69 3-444 Sequences 3-444-1 Sequence Number [ID] 444 3-444-2 Molecule Type AA 11 Aug 2023

3-444-3 Length 44 3-444-4 Features source 1..44 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-444-5 Residues TTPAPRPPTP APTIASQPLS LRPEACRPAA GGAVHTRGLD FACD 44 3-445 Sequences 3-445-1 Sequence Number [ID] 445 3-445-2 Molecule Type AA 3-445-3 Length 47 3-445-4 Features source 1..47 Location/Qualifiers mol_type=protein 2023214349

organism=Homo sapiens NonEnglishQualifier Value 3-445-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIY 47 3-446 Sequences 3-446-1 Sequence Number [ID] 446 3-446-2 Molecule Type AA 3-446-3 Length 11 3-446-4 Features source 1..11 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-446-5 Residues LDKTHTCPPC P 11 3-447 Sequences 3-447-1 Sequence Number [ID] 447 3-447-2 Molecule Type AA 3-447-3 Length 101 3-447-4 Features source 1..101 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-447-5 Residues APVGLVARLA DESGHVVLRW LPPPETPMTS HIRYEVDVSA GNGAGSVQRV EILEGRTECV 60 LSNLRGRTRY TFAVRARMAE PSFGGFWSAW SEPVSLLTPS D 101 3-448 Sequences 3-448-1 Sequence Number [ID] 448 3-448-2 Molecule Type AA 3-448-3 Length 16 3-448-4 Features source 1..16 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-448-5 Residues GLAVSTISSF FPPGYQ 16 3-449 Sequences 3-449-1 Sequence Number [ID] 449 3-449-2 Molecule Type AA 3-449-3 Length 16 3-449-4 Features source 1..16 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-449-5 Residues GLAVSTISSF FPPGYQ 16 3-450 Sequences 3-450-1 Sequence Number [ID] 450 3-450-2 Molecule Type AA 3-450-3 Length 282 3-450-4 Features source 1..282 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-450-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMW LEDQREVNTS GFAPARPPPQ PGSTTFWAWS 240 VLRVPAPPSP QPATYTCVVS HEDSRTLLNA SRSLEVSYVT DH 282

3-451 Sequences 3-451-1 Sequence Number [ID] 451 3-451-2 Molecule Type AA 3-451-3 Length 246 11 Aug 2023

3-451-4 Features source 1..246 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-451-5 Residues YVTVSSQDPA EPKSPDKTHT CPPCPAPELL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD 60 VSHEDPEVKF NWYVDGVEVH NAKTKPREEQ YNSTYRVVSV LTVLHQDWLN GKEYKCKVSN 120 KALPAPIEKT ISKAKGQPRE PQVYTLPPSR DELTKNQVSL TCLVKGFYPS DIAVEWESNG 180 QPENNYKTTP PVLDSDGSFF LYSKLTVDKS RWQQGNVFSC SVMHEALHNH YTQKSLSLSP 240 GKKDPK 246 3-452 Sequences 3-452-1 Sequence Number [ID] 452 3-452-2 Molecule Type AA 2023214349

3-452-3 Length 45 3-452-4 Features source 1..45 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-452-5 Residues KPTTTPAPRP PTPAPTIASQ PLSLRPEACR PAAGGAVHTR GLDFA 45 3-453 Sequences 3-453-1 Sequence Number [ID] 453 3-453-2 Molecule Type AA 3-453-3 Length 16 3-453-4 Features source 1..16 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-453-5 Residues LEPKSCDKTH TCPPCP 16 3-454 Sequences 3-454-1 Sequence Number [ID] 454 3-454-2 Molecule Type AA 3-454-3 Length 43 3-454-4 Features source 1..43 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-454-5 Residues KPTTTPAPRP PTPAPTIASQ PLSLRPEACR PAAGGAVHTR GLD 43 3-455 Sequences 3-455-1 Sequence Number [ID] 455 3-455-2 Molecule Type AA 3-455-3 Length 15 3-455-4 Features source 1..15 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-455-5 Residues EPKSCDKTHT CPPCP 15 3-456 Sequences 3-456-1 Sequence Number [ID] 456 3-456-2 Molecule Type AA 3-456-3 Length 16 3-456-4 Features source 1..16 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-456-5 Residues ELKTPLGDTH TCPRCP 16 3-457 Sequences 3-457-1 Sequence Number [ID] 457 3-457-2 Molecule Type AA 3-457-3 Length 15 3-457-4 Features source 1..15 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-457-5 Residues EPKSCDTPPP CPRCP 15 3-458 Sequences

3-458-1 Sequence Number [ID] 458 3-458-2 Molecule Type AA 3-458-3 Length 12 3-458-4 Features source 1..12 11 Aug 2023

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-458-5 Residues ESKYGPPCPS CP 12 3-459 Sequences 3-459-1 Sequence Number [ID] 459 3-459-2 Molecule Type AA 3-459-3 Length 12 3-459-4 Features source 1..12 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 2023214349

3-459-5 Residues ERKCCVECPP CP 12 3-460 Sequences 3-460-1 Sequence Number [ID] 460 3-460-2 Molecule Type AA 3-460-3 Length 229 3-460-4 Features source 1..229 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-460-5 Residues ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229 3-461 Sequences 3-461-1 Sequence Number [ID] 461 3-461-2 Molecule Type AA 3-461-3 Length 119 3-461-4 Features source 1..119 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-461-5 Residues ESKYGPPCPP CPGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE 60 NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 119 3-462 Sequences 3-462-1 Sequence Number [ID] 462 3-462-2 Molecule Type AA 3-462-3 Length 282 3-462-4 Features source 1..282 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-462-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMW LEDQREVNTS GFAPARPPPQ PGSTTFWAWS 240 VLRVPAPPSP QPATYTCVVS HEDSRTLLNA SRSLEVSYVT DH 282 3-463 Sequences 3-463-1 Sequence Number [ID] 463 3-463-2 Molecule Type AA 3-463-3 Length 281 3-463-4 Features source 1..281 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-463-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLHPSLPPQ RLMALREPAA QAPVKLSLNL 180 LASSDPPEAA SWLLCEVSGF SPPNILLMWL EDQREVNTSG FAPARPPPQP GSTTFWAWSV 240 LRVPAPPSPQ PATYTCVVSH EDSRTLLNAS RSLEVSYVTD H 281 3-464 Sequences 3-464-1 Sequence Number [ID] 464 3-464-2 Molecule Type AA 3-464-3 Length 283 3-464-4 Features source 1..283

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-464-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 11 Aug 2023

LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMV VLEDQREVNT SGFAPARPPP QPGSTTFWAW 240 SVLRVPAPPS PQPATYTCVV SHEDSRTLLN ASRSLEVSYV TDH 283 3-465 Sequences 3-465-1 Sequence Number [ID] 465 3-465-2 Molecule Type AA 3-465-3 Length 58 3-465-4 Features source 1..58 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 2023214349

3-465-5 Residues ESPKAQASSV PTAQPQAEGS LAKATTAPAT TRNTGRGGEE KKKEKEKEEQ EERETKTP 58 3-466 Sequences 3-466-1 Sequence Number [ID] 466 3-466-2 Molecule Type AA 3-466-3 Length 282 3-466-4 Features source 1..282 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-466-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMW LEDQREVNTS GFAPARPPPQ PGSTTFWAWS 240 VLRVPAPPSP QPATYTCVVS HEDSRTLLNA SRSLEVSYVT DH 282 3-467 Sequences 3-467-1 Sequence Number [ID] 467 3-467-2 Molecule Type AA 3-467-3 Length 282 3-467-4 Features source 1..282 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-467-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMW LEDQREVNTS GFAPARPPPQ PGSTTFWAWS 240 VLRVPAPPSP QPATYTCVVS HEDSRTLLNA SRSLEVSYVT DH 282 3-468 Sequences 3-468-1 Sequence Number [ID] 468 3-468-2 Molecule Type AA 3-468-3 Length 282 3-468-4 Features source 1..282 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-468-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMW LEDQREVNTS GFAPARPPPQ PGSTTFWAWS 240 VLRVPAPPSP QPATYTCVVS HEDSRTLLNA SRSLEVSYVT DH 282 3-469 Sequences 3-469-1 Sequence Number [ID] 469 3-469-2 Molecule Type AA 3-469-3 Length 282 3-469-4 Features source 1..282 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-469-5 Residues RWPESPKAQA SSVPTAQPQA EGSLAKATTA PATTRNTGRG GEEKKKEKEK EEQEERETKT 60 PECPSHTQPL GVYLLTPAVQ DLWLRDKATF TCFVVGSDLK DAHLTWEVAG KVPTGGVEEG 120 LLERHSNGSQ SQHSRLTLPR SLWNAGTSVT CTLNHPSLPP QRLMALREPA AQAPVKLSLN 180 LLASSDPPEA ASWLLCEVSG FSPPNILLMW LEDQREVNTS GFAPARPPPQ PGSTTFWAWS 240 VLRVPAPPSP QPATYTCVVS HEDSRTLLNA SRSLEVSYVT DH 282 3-470 Sequences

3-470-1 Sequence Number [ID] 470 3-470-2 Molecule Type AA 3-470-3 Length 234 3-470-4 Features MOD_RES 91 11 Aug 2023

Location/Qualifiers note=Selenocysteine source 1..234 mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-470-5 Residues AEPKSPDKTH TCPPCPAPPV AGPSVFLFPP KPKDTLMIAR TPEVTCVVVD VSHEDPEVKF 60 NWYVDGVEVH NAKTKPREEQ YNSTYRVVSV XTVLHQDWLN GKEYKCKVSN KALPAPIEKT 120 ISKAKGQPRE PQVYTLPPSR DELTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP 180 PVLDSDGSFF LYSKLTVDKS RWQQGNVFSC SVMHEALHNH YTQKSLSLSP GKKD 234 3-471 Sequences 3-471-1 Sequence Number [ID] 471 3-471-2 Molecule Type AA 2023214349

3-471-3 Length 234 3-471-4 Features source 1..234 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-471-5 Residues AEPKSPDKTH TCPPCPAPPV AGPSVFLFPP KPKDTLMIAR TPEVTCVVVD VSHEDPEVKF 60 NWYVDGVEVH NAKTKPREEQ YNSTYRVVSV LTVLHQDWLN GKEYKCKVSN KALPAPIEKT 120 ISKAKGQPRE PQVYTLPPSR DELTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP 180 PVLDSDGSFF LYSKLTVDKS RWQQGNVFSC SVMHEALHNH YTQKSLSLSP GKKD 234 3-472 Sequences 3-472-1 Sequence Number [ID] 472 3-472-2 Molecule Type AA 3-472-3 Length 20 3-472-4 Features source 1..20 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-472-5 Residues AEPKSPDKTH TCPPCPKDPK 20 3-473 Sequences 3-473-1 Sequence Number [ID] 473 3-473-2 Molecule Type AA 3-473-3 Length 15 3-473-4 Features source 1..15 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-473-5 Residues EPKSCDKTHT CPPCP 15 3-474 Sequences 3-474-1 Sequence Number [ID] 474 3-474-2 Molecule Type AA 3-474-3 Length 233 3-474-4 Features source 1..233 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-474-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEVKCKVSNK ALPAPIEKTI 120 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 180 VLDSDGSFFL VSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG KKD 233 3-475 Sequences 3-475-1 Sequence Number [ID] 475 3-475-2 Molecule Type AA 3-475-3 Length 13 3-475-4 Features source 1..13 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-475-5 Residues SVFLFPPKPK DTL 13 3-476 Sequences 3-476-1 Sequence Number [ID] 476 3-476-2 Molecule Type AA 3-476-3 Length 231 3-476-4 Features source 1..231

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-476-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI 120 11 Aug 2023

SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 180 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 231 3-477 Sequences 3-477-1 Sequence Number [ID] 477 3-477-2 Molecule Type AA 3-477-3 Length 235 3-477-4 Features source 1..235 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-477-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 2023214349

WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI 120 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 180 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG KKDPK 235 3-478 Sequences 3-478-1 Sequence Number [ID] 478 3-478-2 Molecule Type AA 3-478-3 Length 223 3-478-4 Features source 1..223 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-478-5 Residues VECPPCPAPP VAGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV 60 HNAKTKPREE QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKGLPSSIEK TISKAKGQPR 120 EPQVYTLPPS REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF 180 FLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 223 3-479 Sequences 3-479-1 Sequence Number [ID] 479 3-479-2 Molecule Type AA 3-479-3 Length 235 3-479-4 Features source 1..235 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-479-5 Residues DPAEPKSPDK THTCPPCPAP PVAGPSVFLF PPKPKDTLMI ARTPEVTCVV VDVSHEDPEV 60 KFNWYVDGVE VHNAKTKPRE EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE 120 KTISKAKGQP REPQVYTLPP SRDELTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT 180 TPPVLDSDGS FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGKK 235 3-480 Sequences 3-480-1 Sequence Number [ID] 480 3-480-2 Molecule Type AA 3-480-3 Length 12 3-480-4 Features source 1..12 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-480-5 Residues ERKCCVECPP CP 12 3-481 Sequences 3-481-1 Sequence Number [ID] 481 3-481-2 Molecule Type AA 3-481-3 Length 17 3-481-4 Features source 1..17 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-481-5 Residues ELKTPLGDTT HTCPRCP 17 3-482 Sequences 3-482-1 Sequence Number [ID] 482 3-482-2 Molecule Type AA 3-482-3 Length 61 3-482-4 Features source 1..61 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-482-5 Residues ELKTPLGDTH TCPRCPEPKS CDTPPPCPRC PEPKSCDTPP PCPRCPEPKS CDTPPPCPRC 60

P 61 3-483 Sequences 3-483-1 Sequence Number [ID] 483 3-483-2 Molecule Type AA 11 Aug 2023

3-483-3 Length 230 3-483-4 Features source 1..230 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-483-5 Residues ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGKM 230 3-484 Sequences 3-484-1 Sequence Number [ID] 484 3-484-2 Molecule Type AA 2023214349

3-484-3 Length 230 3-484-4 Features source 1..230 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-484-5 Residues ESKYGPPCPP CPAPEFEGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFQS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGKM 230 3-485 Sequences 3-485-1 Sequence Number [ID] 485 3-485-2 Molecule Type AA 3-485-3 Length 12 3-485-4 Features source 1..12 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-485-5 Residues SPNMVPHAHH AQ 12 3-486 Sequences 3-486-1 Sequence Number [ID] 486 3-486-2 Molecule Type AA 3-486-3 Length 107 3-486-4 Features source 1..107 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-486-5 Residues GQPREPQVYT LPPSQEEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS 60 DGSFFLYSRL TVDKSRWQEG NVFSCSVMHE ALHNHYTQKS LSLSLGK 107 3-487 Sequences 3-487-1 Sequence Number [ID] 487 3-487-2 Molecule Type AA 3-487-3 Length 129 3-487-4 Features source 1..129 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-487-5 Residues ESKYGPPCPP CPGGGSSGGG SGGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA 60 VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ 120 KSLSLSLGK 129 3-488 Sequences 3-488-1 Sequence Number [ID] 488 3-488-2 Molecule Type AA 3-488-3 Length 229 3-488-4 Features source 1..229 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-488-5 Residues ESKYGPPCPS CPAPEFEGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHQAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFVPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229 3-489 Sequences 3-489-1 Sequence Number [ID] 489 3-489-2 Molecule Type AA

3-489-3 Length 229 3-489-4 Features source 1..229 Location/Qualifiers mol_type=protein organism=Homo sapiens 11 Aug 2023

NonEnglishQualifier Value 3-489-5 Residues ESKYGPPCPP CPAPEFEGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHQAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFVPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229 3-490 Sequences 3-490-1 Sequence Number [ID] 490 3-490-2 Molecule Type AA 3-490-3 Length 230 3-490-4 Features source 1..230 Location/Qualifiers mol_type=protein organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-490-5 Residues ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGKM 230 3-491 Sequences 3-491-1 Sequence Number [ID] 491 3-491-2 Molecule Type DNA 3-491-3 Length 36 3-491-4 Features source 1..36 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-491-5 Residues gaatctaagt acggaccgcc ctgcccccct tgccct 36 3-492 Sequences 3-492-1 Sequence Number [ID] 492 3-492-2 Molecule Type AA 3-492-3 Length 12 3-492-4 Features source 1..12 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-492-5 Residues ESKYGPPCPP CP 12 3-493 Sequences 3-493-1 Sequence Number [ID] 493 3-493-2 Molecule Type AA 3-493-3 Length 119 3-493-4 Features source 1..119 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-493-5 Residues ESKYGPPCPP CPGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE 60 NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 119 3-494 Sequences 3-494-1 Sequence Number [ID] 494 3-494-2 Molecule Type AA 3-494-3 Length 229 3-494-4 Features source 1..229 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-494-5 Residues ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229 3-495 Sequences 3-495-1 Sequence Number [ID] 495 3-495-2 Molecule Type AA 3-495-3 Length 229 3-495-4 Features source 1..229 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value

3-495-5 Residues ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229 3-496 Sequences 11 Aug 2023

3-496-1 Sequence Number [ID] 496 3-496-2 Molecule Type AA 3-496-3 Length 12 3-496-4 Features source 1..12 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-496-5 Residues ESKYGPPCPP CP 12 3-497 Sequences 3-497-1 Sequence Number [ID] 497 3-497-2 Molecule Type AA 2023214349

3-497-3 Length 9 3-497-4 Features source 1..9 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-497-5 Residues YGPPCPPCP 9 3-498 Sequences 3-498-1 Sequence Number [ID] 498 3-498-2 Molecule Type AA 3-498-3 Length 10 3-498-4 Features source 1..10 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-498-5 Residues KYGPPCPPCP 10 3-499 Sequences 3-499-1 Sequence Number [ID] 499 3-499-2 Molecule Type AA 3-499-3 Length 13 3-499-4 Features source 1..13 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-499-5 Residues EVVKYGPPCP PCP 13 3-500 Sequences 3-500-1 Sequence Number [ID] 500 3-500-2 Molecule Type AA 3-500-3 Length 229 3-500-4 Features source 1..229 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-500-5 Residues ESKYGPPCPS CPAPEFLGGP SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY 60 VDGVEVHNAK TKPREEQFNS TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK 120 AKGQPREPQV YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 180 DSDGSFFLYS RLTVDLSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 229 3-501 Sequences 3-501-1 Sequence Number [ID] 501 3-501-2 Molecule Type AA 3-501-3 Length 22 3-501-4 Features source 1..22 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-501-5 Residues ESKYGPPCPP CPGGGSSGGG SG 22 3-502 Sequences 3-502-1 Sequence Number [ID] 502 3-502-2 Molecule Type AA 3-502-3 Length 231 3-502-4 Features source 1..231 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value

3-502-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI 120 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTIPP 180 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 231 3-503 Sequences 11 Aug 2023

3-503-1 Sequence Number [ID] 503 3-503-2 Molecule Type AA 3-503-3 Length 231 3-503-4 Features source 1..231 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-503-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPLEKTI 120 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTIPP 180 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 231 2023214349

3-504 Sequences 3-504-1 Sequence Number [ID] 504 3-504-2 Molecule Type AA 3-504-3 Length 231 3-504-4 Features source 1..231 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-504-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI 120 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 180 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 231 3-505 Sequences 3-505-1 Sequence Number [ID] 505 3-505-2 Molecule Type AA 3-505-3 Length 68 3-505-4 Features source 1..68 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-505-5 Residues TTPAPRPPTP APTIASQPLS LRPEACRPAA GGAVHTRGLD FACDIYIWAP LAGTCGVLLL 60 SLVITLYC 68 3-506 Sequences 3-506-1 Sequence Number [ID] 506 3-506-2 Molecule Type AA 3-506-3 Length 243 3-506-4 Features source 1..243 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-506-5 Residues DIQMTQSSSY LSVSLGGRVT ITCKASDHIN NWLAWYQQKP GNAPRLLISG ATSLETGVPS 60 RFSGSGSGKD YTLSITSLQT EDVATYYCQQ YWSTPFTFGS GTKLEIKGGG GSGGGGSGGG 120 GSQVQLKESG PGLVAPSQSL SITSTVSGFS LSRYSVHWVR QPPGKGLEWL GMIWGGGSTD 180 YNSALKSRLS ISKDNSKSQV FLKMNSLQTD DTAMYYCARN EGDTTAGTWF AYWGQGTLVT 240 VSS 243 3-507 Sequences 3-507-1 Sequence Number [ID] 507 3-507-2 Molecule Type AA 3-507-3 Length 62 3-507-4 Features source 1..62 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-507-5 Residues ALSNSIMYFS HFVPVFLPAK PTTTPAPRPP TPAPTIASQP LSLRPEACRP AAGGAVHTRG 60 LD 62 3-508 Sequences 3-508-1 Sequence Number [ID] 508 3-508-2 Molecule Type AA 3-508-3 Length 68 3-508-4 Features source 1..68 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-508-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL 60

LSLVITLY 68 3-509 Sequences 3-509-1 Sequence Number [ID] 509 3-509-2 Molecule Type AA 11 Aug 2023

3-509-3 Length 70 3-509-4 Features source 1..70 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-509-5 Residues KPTTTPAPRP PTPAPTIASQ PLSLRPEACR PAAGGAVHTR GLDFACDIYI WAPLAGTCGV 60 LLLSLVITLY 70 3-510 Sequences 3-510-1 Sequence Number [ID] 510 3-510-2 Molecule Type AA 3-510-3 Length 680 3-510-4 Features REGION 1..680 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..680 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-510-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSESK YGPPCPPCPA PEFEGGPSVF LFPPKPKDTL 300 MISRTPEVTC VVVDVSQEDP EVQFNWYVDG VEVHNAKTKP REEQFNSTYR VVSVLTVLHQ 360 DWLNGKEYKC KVSNKGLPSS IEKTISKAKG QPREPQVYTL PPSQEEMTKN QVSLTCLVKG 420 FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT VDKSRWQEGN VFSCSVMHEA 480 LHNHYTQKSL SLSLGKMFWV LVVVGGVLAC YSLLVTVAFI IFWVRSKRSR GGHSDYMNMT 540 PRRPGPTRKH YQPYAPPRDF AAYRSGGGRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY 600 DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG 660 LSTATKDTYD ALHMQALPPR 680 3-511 Sequences 3-511-1 Sequence Number [ID] 511 3-511-2 Molecule Type AA 3-511-3 Length 680 3-511-4 Features REGION 1..680 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..680 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-511-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSESK YGPPCPPCPA PEFLGGPSVF LFPPKPKDTL 300 MISRTPEVTC VVVDVSQEDP EVQFNWYVDG VEVHNAKTKP REEQFQSTYR VVSVLTVLHQ 360 DWLNGKEYKC KVSNKGLPSS IEKTISKAKG QPREPQVYTL PPSQEEMTKN QVSLTCLVKG 420 FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT VDKSRWQEGN VFSCSVMHEA 480 LHNHYTQKSL SLSLGKMFWV LVVVGGVLAC YSLLVTVAFI IFWVRSKRSR GGHSDYMNMT 540 PRRPGPTRKH YQPYAPPRDF AAYRSGGGRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY 600 DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG 660 LSTATKDTYD ALHMQALPPR 680 3-512 Sequences 3-512-1 Sequence Number [ID] 512 3-512-2 Molecule Type AA 3-512-3 Length 680 3-512-4 Features REGION 1..680 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..680 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-512-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSESK YGPPCPPCPA PEFEGGPSVF LFPPKPKDTL 300 MISRTPEVTC VVVDVSQEDP EVQFNWYVDG VEVHNAKTKP REEQFQSTYR VVSVLTVLHQ 360

DWLNGKEYKC KVSNKGLPSS IEKTISKAKG QPREPQVYTL PPSQEEMTKN QVSLTCLVKG 420 FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT VDKSRWQEGN VFSCSVMHEA 480 LHNHYTQKSL SLSLGKMFWV LVVVGGVLAC YSLLVTVAFI IFWVRSKRSR GGHSDYMNMT 540 PRRPGPTRKH YQPYAPPRDF AAYRSGGGRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY 600 DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG 660 11 Aug 2023

LSTATKDTYD ALHMQALPPR 680 3-513 Sequences 3-513-1 Sequence Number [ID] 513 3-513-2 Molecule Type AA 3-513-3 Length 580 3-513-4 Features REGION 1..580 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..580 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-513-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSESK YGPPCPPCPG GGSSGGGSGG QPREPQVYTL 300 PPSQEEMTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT 360 VDKSRWQEGN VFSCSVMHEA LHNHYTQKSL SLSLGKMFWV LVVVGGVLAC YSLLVTVAFI 420 IFWVRSKRSR GGHSDYMNMT PRRPGPTRKH YQPYAPPRDF AAYRSGGGRV KFSRSADAPA 480 YQQGQNQLYN ELNLGRREEY DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS 540 EIGMKGERRR GKGHDGLYQG LSTATKDTYD ALHMQALPPR 580 3-514 Sequences 3-514-1 Sequence Number [ID] 514 3-514-2 Molecule Type AA 3-514-3 Length 711 3-514-4 Features REGION 1..711 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..711 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-514-5 Residues MLLLVTSLLL LCELPHPAFL LIPDIQMTQQ TTSSLSASLG DRVTISCRAS SQDISKYLNW 60 YQQKPDGTVK LLLIYHTSRL HSGVPSRFSG SGGSGTDYSL TISNLEQEDI ATYYFCQQGN 120 TLPYTFGGGT KLEIITGSTS GSGKPGSGEG STKGEEVKLQ ESGPGLVAPS QSLSVTTCTV 180 SGVSLPDYGV SWIRQPPPRK GLEWLGVIWG SETTYYNSSA LKSRLTIIKD NSKSQVFLKK 240 MNSLQTDDTA IYYCAKHYYY YGGSYAMDYW GQGTSVTVSS EESKYGPPCP PCPAPEFLGG 300 PSSVFLFPPK PKDTLMISRT PEVVTCVVVD VSQEDPEVQF NWYVVDGVEV HNAKTKPREE 360 QFNSTTYRVV SVLTVLHQDW LNGKEYYKCK VSNKGLPSSI EKTISKAAKG QPREPQVYTL 420 PPSQEEMTTK NQVSLTCLVK GFYPSDIAVV EWESNGQPEN NYKTTPPVLD DSDGSFFLYS 480 RLTVDKSRWQ EEGNVFSCSV MHEALHNHYT QKKSLSLSLG KMFWVLVVVG GVLLACYSLL 540 VTVAFIIFWV RSKRRSRGGH SDYMNMTPRR PGPTRRKHYQ PYAPPRDFAA YRSRVKKFSR 600 SADAPAYQQG QNQLYNEELN LGRREEYDVL DKRRGRDPPE MGGKPRRKNP QEGLYNELQQ 660 KDKMAEAYSE IGMKGERRRG GKGHDGLYQG LSTATKDTYD AALHMQALPP R 711 3-515 Sequences 3-515-1 Sequence Number [ID] 515 3-515-2 Molecule Type AA 3-515-3 Length 495 3-515-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-515-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR ADTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-516 Sequences 3-516-1 Sequence Number [ID] 516 3-516-2 Molecule Type AA 3-516-3 Length 495 3-516-4 Features REGION 1..495

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-516-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-517 Sequences 3-517-1 Sequence Number [ID] 517 2023214349

3-517-2 Molecule Type AA 3-517-3 Length 484 3-517-4 Features REGION 1..484 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..484 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-517-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDMW APLAGTCGVL LLSLVITLYC KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC 360 RFPEEEEGGC ELRVKFSRSA DAPAYKQGQN QLYNELNLGR REEYDVLDKR RGRDPEMGGK 420 PRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA 480 LPPR 484 3-518 Sequences 3-518-1 Sequence Number [ID] 518 3-518-2 Molecule Type AA 3-518-3 Length 476 3-518-4 Features REGION 1..476 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..476 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-518-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSESK YGPPCPPCPM FWVLVVVGGV LACYSLLVTV 300 AFIIFWVKRG RKKLLYIFKQ PFMRPVQTTQ EEDGCSCRFP EEEEGGCELR VKFSRSADAP 360 AYQQGQNQLY NELNLGRREE YDVLDKRRGR DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY 420 SEIGMKGERR RGKGHDGLYQ GLSTATKDTY DALHMQALPP RLEGGGEGRG SLLTCG 476 3-519 Sequences 3-519-1 Sequence Number [ID] 519 3-519-2 Molecule Type AA 3-519-3 Length 248 3-519-4 Features REGION 1..248 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..248 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-519-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITKAG GGGSGGGGSG 120 GGGSGGGGSE VKLQESGPGL VAPSQSLSVT CTVSGVSLPD YGVSWIRQPP RKGLEWLGVI 180 WGSETTYYNS ALKSRLTIIK DNSKSQVFLK MNSLQTDDTA IYYCAKHYYY GGSYAMDYWG 240 QGTSVTVS 248 3-520 Sequences 3-520-1 Sequence Number [ID] 520 3-520-2 Molecule Type AA 3-520-3 Length 254 3-520-4 Features REGION 1..254

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..254 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-520-5 Residues RCDIQMTQSP SSLSASVGDR VTITCRASED IYFNLVWYQQ KPGKAPKLLI YDTNRLADGV 60 PSRFSGSGSG TQYTLTISSL QPEDFATYYC QHYKNYPLTF GQGTKLEIKR SGGGGSGGGG 120 SGGGGSGGGG SRSEVQLVES GGGLVQPGGS LRLSCAASGF TLSNYGMHWI RQAPGKGLEW 180 VSSISLNGGS TYYRDSVKGR FTISRDNAKS TLYLQMNSLR AEDTAVYYCA AQDAYTGGYF 240 DYWGQGTLVT VSSM 254 3-521 Sequences 3-521-1 Sequence Number [ID] 521 3-521-2 Molecule Type AA 3-521-3 Length 489 3-521-4 Features REGION 1..489 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor 2023214349

source 1..489 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-521-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTRTTTPA PRPPTPAPTI ASQPLSLRPE ACRPAAGGAV 300 HTRGLDFACD IYIWAPLAGT CGVLLLSLVI TLYCAVSLSK MLKKRSPLTT GVYVKMPPTE 360 PECEKQFQPY FIPINSARVK FSRSADAPAY KQGQNQLYNE LNLGRREEYD VLDKRRGRDP 420 EMGGKPRRKN PQEGLYNELQ KDKMAEAYSE IGMKGERRRG KGHDGLYQGL STATKDTYDA 480 LHMQALPPR 489 3-522 Sequences 3-522-1 Sequence Number [ID] 522 3-522-2 Molecule Type AA 3-522-3 Length 522 3-522-4 Features REGION 1..522 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..522 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-522-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCALYLLRRD QRLPPDAHKP PGGGSFRTPI 360 QEEQADAHST LAKIRSKRSR LLHSDYMNMT PRRPGPTRKH YQPYAPPRDF AAYRSGVQVE 420 TISPGDGRTF PKRGQTCVVH YTGMLEDGKK FDSSRDRNKP FKFMLGKQEV IRGWEEGVAQ 480 MSVGQRAKLT ISPDYAYGAT GHPGIIPPHA TLVFDVELLK LE 522 3-523 Sequences 3-523-1 Sequence Number [ID] 523 3-523-2 Molecule Type AA 3-523-3 Length 508 3-523-4 Features REGION 1..508 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..508 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-523-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCALYLLRRD QRLPPDAHKP PGGGSFRTPI 360 QEEQADAHST LAKIRSKRSR LLHSDYMNMT PRRPGPTRKH YQPYAPPRDF AAYRSILWHE 420 MWHEGLIEAS RLYFGERNVK GMFEVLEPLH AMMERGPQTL KETSFNQAYG RDLMEAQEWC 480 RKYMKSGNVK DLLQAWDLYY HVFRRISK 508 3-524 Sequences 3-524-1 Sequence Number [ID] 524 3-524-2 Molecule Type AA 3-524-3 Length 528

3-524-4 Features REGION 1..528 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..528 mol_type=protein 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-524-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCQRRKYRSN KGESPVEPAE PCHYSCPREE 360 EGSTIPIQED YRKPEPACSP RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR 420 SGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFM LGKQEVIRGW 480 EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF DVELLKLE 528 3-525 Sequences 2023214349

3-525-1 Sequence Number [ID] 525 3-525-2 Molecule Type AA 3-525-3 Length 514 3-525-4 Features REGION 1..514 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..514 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-525-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCQRRKYRSN KGESPVEPAE PCHYSCPREE 360 EGSTIPIQED YRKPEPACSP RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR 420 SILWHEMWHE GLIEASRLYF GERNVKGMFE VLEPLHAMME RGPQTLKETS FNQAYGRDLM 480 EAQEWCRKYM KSGNVKDLLQ AWDLYYHVFR RISK 514 3-526 Sequences 3-526-1 Sequence Number [ID] 526 3-526-2 Molecule Type AA 3-526-3 Length 522 3-526-4 Features REGION 1..522 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..522 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-526-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRSKRSR LLHSDYMNMT PRRPGPTRKH YQPYAPPRDF AAYRSGVQVE 420 TISPGDGRTF PKRGQTCVVH YTGMLEDGKK FDSSRDRNKP FKFMLGKQEV IRGWEEGVAQ 480 MSVGQRAKLT ISPDYAYGAT GHPGIIPPHA TLVFDVELLK LE 522 3-527 Sequences 3-527-1 Sequence Number [ID] 527 3-527-2 Molecule Type AA 3-527-3 Length 508 3-527-4 Features REGION 1..508 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..508 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-527-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRSKRSR LLHSDYMNMT PRRPGPTRKH YQPYAPPRDF AAYRSILWHE 420 MWHEGLIEAS RLYFGERNVK GMFEVLEPLH AMMERGPQTL KETSFNQAYG RDLMEAQEWC 480 RKYMKSGNVK DLLQAWDLYY HVFRRISK 508

3-528 Sequences 3-528-1 Sequence Number [ID] 528 3-528-2 Molecule Type AA 3-528-3 Length 495 11 Aug 2023

3-528-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-528-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 2023214349

QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-529 Sequences 3-529-1 Sequence Number [ID] 529 3-529-2 Molecule Type AA 3-529-3 Length 495 3-529-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-529-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-530 Sequences 3-530-1 Sequence Number [ID] 530 3-530-2 Molecule Type AA 3-530-3 Length 495 3-530-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-530-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-531 Sequences 3-531-1 Sequence Number [ID] 531 3-531-2 Molecule Type AA 3-531-3 Length 495 3-531-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-531-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240

AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 11 Aug 2023

3-532 Sequences 3-532-1 Sequence Number [ID] 532 3-532-2 Molecule Type AA 3-532-3 Length 495 3-532-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-532-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 2023214349

PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-533 Sequences 3-533-1 Sequence Number [ID] 533 3-533-2 Molecule Type AA 3-533-3 Length 495 3-533-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-533-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-534 Sequences 3-534-1 Sequence Number [ID] 534 3-534-2 Molecule Type AA 3-534-3 Length 495 3-534-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-534-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-535 Sequences 3-535-1 Sequence Number [ID] 535 3-535-2 Molecule Type AA 3-535-3 Length 495 3-535-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-535-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 11 Aug 2023

AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-536 Sequences 3-536-1 Sequence Number [ID] 536 3-536-2 Molecule Type AA 3-536-3 Length 251 3-536-4 Features REGION 1..251 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor 2023214349

source 1..251 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-536-5 Residues EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK PGQGLEWIGY INPYNDGTKY 60 NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT YYYGSRVFDY WGQGTTLTVS 120 SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR SSKSLLNSNG NTYLYWFLQR 180 PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE AEDVGVYYCM QHLEYPFTFG 240 AGTKLELKRA D 251 3-537 Sequences 3-537-1 Sequence Number [ID] 537 3-537-2 Molecule Type AA 3-537-3 Length 495 3-537-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-537-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-538 Sequences 3-538-1 Sequence Number [ID] 538 3-538-2 Molecule Type AA 3-538-3 Length 495 3-538-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-538-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-539 Sequences 3-539-1 Sequence Number [ID] 539 3-539-2 Molecule Type AA 3-539-3 Length 495 3-539-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-539-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 11 Aug 2023

SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-540 Sequences 3-540-1 Sequence Number [ID] 540 3-540-2 Molecule Type AA 3-540-3 Length 495 3-540-4 Features REGION 1..495 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-540-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR ADTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-541 Sequences 3-541-1 Sequence Number [ID] 541 3-541-2 Molecule Type AA 3-541-3 Length 495 3-541-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-541-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-542 Sequences 3-542-1 Sequence Number [ID] 542 3-542-2 Molecule Type AA 3-542-3 Length 495 3-542-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-542-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR ADTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-543 Sequences 3-543-1 Sequence Number [ID] 543 3-543-2 Molecule Type AA 3-543-3 Length 495

3-543-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-543-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-544 Sequences 2023214349

3-544-1 Sequence Number [ID] 544 3-544-2 Molecule Type AA 3-544-3 Length 495 3-544-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-544-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR ADTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-545 Sequences 3-545-1 Sequence Number [ID] 545 3-545-2 Molecule Type AA 3-545-3 Length 495 3-545-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-545-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-546 Sequences 3-546-1 Sequence Number [ID] 546 3-546-2 Molecule Type AA 3-546-3 Length 494 3-546-4 Features REGION 1..494 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..494 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-546-5 Residues METDTLLLWV LLLWVPGSTG DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP 60 DGTVKLLIYH TSRLHSGVPS RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG 120 GTKLEITKAG GGGSGGGGSG GGGSGGGGSE VKLQESGPGL VAPSQSLSVT CTVSGVSLPD 180 YGVSWIRQPP RKGLEWLGVI WGSETTYYNS ALKSRLTIIK DNSKSQVFLK MNSLQTDDTA 240 IYYCAKHYYY GGSYAMDYWG QGTSVTVSSD PTTTPAPRPP TPAPTIASQP LSLRPEACRP 300 AAGGAVHTRG LDFACDIYIW APLAGTCGVL LLSLVITLYC KRGRKKLLYI FKQPFMRPVQ 360 TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA DAPAYQQGQN QLYNELNLGR REEYDVLDKR 420 RGRDPEMGGK PRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK 480 DTYDALHMQA LPPR 494

3-547 Sequences 3-547-1 Sequence Number [ID] 547 3-547-2 Molecule Type AA 3-547-3 Length 494 11 Aug 2023

3-547-4 Features REGION 1..494 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..494 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-547-5 Residues METDTLLLWV LLLWVPGSTG DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP 60 DGTVKLLIYH TSRLHSGVPS RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG 120 GTKLEITKAG GGGSGGGGSG GGGSGGGGSE VKLQESGPGL VAPSQSLSVT CTVSGVSLPD 180 YGVSWIRQPP RKGLEWLGVI WGSETTYYNS ALKSRLTIIK DNSKSQVFLK MNSLQTDDTA 240 IYYCAKHYYY GGSYAMDYWG QGTSVTVSSD PTTTPAPRPP TPAPTIASQP LSLRPEACRP 300 AAGGAVHTRG LDFACDIYIW APLAGTCGVL LLSLVITLYC KRGRKKLLYI FKQPFMRPVQ 360 2023214349

TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA DAPAYQQGQN QLYNELNLGR REEYDVLDKR 420 RGRDPEMGGK PRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK 480 DTYDALHMQA LPPR 494 3-548 Sequences 3-548-1 Sequence Number [ID] 548 3-548-2 Molecule Type AA 3-548-3 Length 144 3-548-4 Features REGION 1..144 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..144 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-548-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSE 144 3-549 Sequences 3-549-1 Sequence Number [ID] 549 3-549-2 Molecule Type AA 3-549-3 Length 486 3-549-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-549-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-550 Sequences 3-550-1 Sequence Number [ID] 550 3-550-2 Molecule Type AA 3-550-3 Length 486 3-550-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-550-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYQSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-551 Sequences

3-551-1 Sequence Number [ID] 551 3-551-2 Molecule Type AA 3-551-3 Length 486 3-551-4 Features REGION 1..486 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-551-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 2023214349

GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-552 Sequences 3-552-1 Sequence Number [ID] 552 3-552-2 Molecule Type AA 3-552-3 Length 486 3-552-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-552-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-553 Sequences 3-553-1 Sequence Number [ID] 553 3-553-2 Molecule Type AA 3-553-3 Length 491 3-553-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-553-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYSSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-554 Sequences 3-554-1 Sequence Number [ID] 554 3-554-2 Molecule Type AA 3-554-3 Length 491 3-554-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-554-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYQSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300

GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-555 Sequences 11 Aug 2023

3-555-1 Sequence Number [ID] 555 3-555-2 Molecule Type AA 3-555-3 Length 491 3-555-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-555-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 2023214349

YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-556 Sequences 3-556-1 Sequence Number [ID] 556 3-556-2 Molecule Type AA 3-556-3 Length 491 3-556-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-556-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-557 Sequences 3-557-1 Sequence Number [ID] 557 3-557-2 Molecule Type AA 3-557-3 Length 491 3-557-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-557-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-558 Sequences 3-558-1 Sequence Number [ID] 558 3-558-2 Molecule Type AA 3-558-3 Length 491 3-558-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-558-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 11 Aug 2023

GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-559 Sequences 3-559-1 Sequence Number [ID] 559 3-559-2 Molecule Type AA 3-559-3 Length 491 3-559-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 2023214349

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-559-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY NSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-560 Sequences 3-560-1 Sequence Number [ID] 560 3-560-2 Molecule Type AA 3-560-3 Length 486 3-560-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-560-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYNSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-561 Sequences 3-561-1 Sequence Number [ID] 561 3-561-2 Molecule Type AA 3-561-3 Length 486 3-561-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-561-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-562 Sequences 3-562-1 Sequence Number [ID] 562 3-562-2 Molecule Type AA 3-562-3 Length 495 3-562-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-562-5 Residues MALPVTALLL PLALLLHAAR PEVQLQQSGP ELIKPGASVK MSCKASGYTF TSYVMHWVKQ 60 KPGQGLEWIG YINPYNDGTK YNEKFKGKAT LTSDKSSSTA YMELSSLTSE DSAVYYCARG 120 TYYYGSRVFD YWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQAAPSIPV TPGESVSISC 180 RSSKSLLNSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLRISRV 240 EAEDVGVYYC MQHLEYPFTF GAGTKLELKR ADTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-563 Sequences 3-563-1 Sequence Number [ID] 563 3-563-2 Molecule Type AA 2023214349

3-563-3 Length 495 3-563-4 Features REGION 1..495 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..495 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-563-5 Residues METDTLLLWV LLLWVPGSTG EVQLQQSGPE LIKPGASVKM SCKASGYTFT SYVMHWVKQK 60 PGQGLEWIGY INPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSED SAVYYCARGT 120 YYYGSRVFDY WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQAAPSIPVT PGESVSISCR 180 SSKSLLNSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DRFSGSGSGT AFTLRISRVE 240 AEDVGVYYCM QHLEYPFTFG AGTKLELKRS DPTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYQQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPR 495 3-564 Sequences 3-564-1 Sequence Number [ID] 564 3-564-2 Molecule Type AA 3-564-3 Length 530 3-564-4 Features REGION 1..530 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..530 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-564-5 Residues MALPVTALLL PLALLLHAAR PDIMMTQSPS SLAVSAGEKV TMTCKSSQSV LYSSNQKNYL 60 AWYQQKPGQS PKLLIYWAST RESGVPDRFT GSGSGTDFTL TISSVQPEDL AVYYCHQYLS 120 SHTFGGGTKL EIKRGGGGSG GGGSGGGGSQ LQQPGAELVR PGSSVKLSCK ASGYTFTRYW 180 IHWVKQRPIQ GLEWIGNIDP SDSETHYNQK FKDKATLTVD KSSGTAYMQL SSLTSEDSAV 240 YYCATEDLYY AMEYWGQGTS VTVSSTTTPA PRPPTPAPTI ASQPLSLRPE ACRPAAGGAV 300 HTRGLDFACD IYIWAPLAGT CGVLLLSLVI TLYCRSKRSR LLHSDYMNMT PRRPGPTRKH 360 YQPYAPPRDF AAYRSKRGRK KLLYIFKQPF MRPVQTTQEE DGCSCRFPEE EEGGCELRVK 420 FSRSADAPAY QQGQNQLYNE LNLGRREEYD VLDKRRGRDP EMGGKPQRRK NPQEGLYNEL 480 QKDKMAEAYS EIGMKGERRR GKGHDGLYQG LSTATKDTYD ALHMQALPPR 530 3-565 Sequences 3-565-1 Sequence Number [ID] 565 3-565-2 Molecule Type AA 3-565-3 Length 486 3-565-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-565-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYQSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-566 Sequences 3-566-1 Sequence Number [ID] 566

3-566-2 Molecule Type AA 3-566-3 Length 486 3-566-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor 11 Aug 2023

source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-566-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 2023214349

QALPPR 486 3-567 Sequences 3-567-1 Sequence Number [ID] 567 3-567-2 Molecule Type AA 3-567-3 Length 486 3-567-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-567-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-568 Sequences 3-568-1 Sequence Number [ID] 568 3-568-2 Molecule Type AA 3-568-3 Length 491 3-568-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-568-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYSSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-569 Sequences 3-569-1 Sequence Number [ID] 569 3-569-2 Molecule Type AA 3-569-3 Length 491 3-569-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-569-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYQSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360

EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-570 Sequences 3-570-1 Sequence Number [ID] 570 11 Aug 2023

3-570-2 Molecule Type AA 3-570-3 Length 491 3-570-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-570-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 2023214349

TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-571 Sequences 3-571-1 Sequence Number [ID] 571 3-571-2 Molecule Type AA 3-571-3 Length 491 3-571-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-571-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-572 Sequences 3-572-1 Sequence Number [ID] 572 3-572-2 Molecule Type AA 3-572-3 Length 491 3-572-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-572-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-573 Sequences 3-573-1 Sequence Number [ID] 573 3-573-2 Molecule Type AA 3-573-3 Length 491 3-573-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-573-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60

PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 11 Aug 2023

EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-574 Sequences 3-574-1 Sequence Number [ID] 574 3-574-2 Molecule Type AA 3-574-3 Length 491 3-574-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-574-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY NSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-575 Sequences 3-575-1 Sequence Number [ID] 575 3-575-2 Molecule Type AA 3-575-3 Length 486 3-575-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-575-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYNSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-576 Sequences 3-576-1 Sequence Number [ID] 576 3-576-2 Molecule Type AA 3-576-3 Length 465 3-576-4 Features REGION 1..465 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..465 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-576-5 Residues MGTSLLCWMA LCLLGADHAD AQVQLQQSGP ELVKPGASVK ISCKASGYAF SSSWMNWVKQ 60 RPGKGLEWIG RIYPGDEDTN YSGKFKDKAT LTADKSSTTA YMQLSSLTSE DSAVYFCARS 120 LLYGDYLDYW GQGTTLTVSS GGGGSGGGGS GGGGSQIVLT QSPAIMSASP GEKVTMTCSA 180 SSSVSYMHWY QQKSGTSPKR WIYDTSKLAS GVPDRFSGSG SGTSYFLTIN NMEAEDAATY 240 YCQQWNINPL TFGAGTKLEL KRSDPAEPKS PDKTHTCPPC PKDPKFWVLV VVGGVLACYS 300 LLVTVAFIIF WVRSKRSRLL HSDYMNMTPR RPGPTRKHYQ PYAPPRDFAA YRSRVKFSRS 360 ADAPAYQQGQ NQLYNELNLG RREEYDVLDK RRGRDPEMGG KPRRKNPQEG LYNELQKDKM 420 AEAYSEIGMK GERRRGKGHD GLYQGLSTAT KDTYDALHMQ ALPPR 465 3-577 Sequences 3-577-1 Sequence Number [ID] 577 3-577-2 Molecule Type AA 3-577-3 Length 681 3-577-4 Features REGION 1..681 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..681 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-577-5 Residues MGTSLLCWMA LCLLGADHAD AQVQLQQSGP ELVKPGASVK ISCKASGYAF SSSWMNWVKQ 60 RPGKGLEWIG RIYPGDEDTN YSGKFKDKAT LTADKSSTTA YMQLSSLTSE DSAVYFCARS 120 11 Aug 2023

LLYGDYLDYW GQGTTLTVSS GGGGSGGGGS GGGGSQIVLT QSPAIMSASP GEKVTMTCSA 180 SSSVSYMHWY QQKSGTSPKR WIYDTSKLAS GVPDRFSGSG SGTSYFLTIN NMEAEDAATY 240 YCQQWNINPL TFGAGTKLEL KRSDPAEPKS PDKTHTCPPC PAPPVAGPSV FLFPPKPKDT 300 LMIARTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH 360 QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK 420 GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE 480 ALHNHYTQKS LSLSPGKKDP KFWVLVVVGG VLACYSLLVT VAFIIFWVRS KRSRLLHSDY 540 MNMTPRRPGP TRKHYQPYAP PRDFAAYRSR VKFSRSADAP AYQQGQNQLY NELNLGRREE 600 YDVLDKRRGR DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ 660 GLSTATKDTY DALHMQALPP R 681 3-578 Sequences 3-578-1 Sequence Number [ID] 578 2023214349

3-578-2 Molecule Type AA 3-578-3 Length 838 3-578-4 Features REGION 1..838 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..838 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-578-5 Residues MLLLVTSLLL CELPHPAFLL IPQSVKESEG DLVTPAGNLT LTCTASGSDI NDYPISWVRQ 60 APGKGLEWIG FINSGGSTWY ASWVKGRFTI SRTSTTVDLK MTSLTTDDTA TYFCARGYST 120 YYGDFNIWGP GTLVTISSGG GGSGGGGSGG GGSELVMTQT PSSTSGAVGG TVTINCQASQ 180 SIDSNLAWFQ QKPGQPPTLL IYRASNLASG VPSRFSGSRS GTEYTLTISG VQREDAATYY 240 CLGGVGNVSY RTSFGGGTEV VVKESKYGPP CPPCPMFWVL VVVGGVLACY SLLVTVAFII 300 FWVKRGRKKL LYIFKQPFMR PVQTTQEEDG CSCRFPEEEE GGCELRVKFS RSADAPAYQQ 360 GQNQLYNELN LGRREEYDVL DKRRGRDPEM GGKPRRKNPQ EGLYNELQKD KMAEAYSEIG 420 MKGERRRGKG HDGLYQGLST ATKDTYDALH MQALPPRLEG GGEGRGSLLT CGDVEENPGP 480 RMLLLVTSLL LCELPHPAFL LIPRKVCNGI GIGEFKDSLS INATNIKHFK NCTSISGDLH 540 ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF ENLEIIRGRT 600 KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL FGTSGQKTKI 660 ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN LLEGEPREFV 720 ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM GENNTLVWKY 780 ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV ALGIGLFM 838 3-579 Sequences 3-579-1 Sequence Number [ID] 579 3-579-2 Molecule Type AA 3-579-3 Length 1055 3-579-4 Features REGION 1..1055 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..1055 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-579-5 Residues MLLLVTSLLL CELPHPAFLL IPQSVKESEG DLVTPAGNLT LTCTASGSDI NDYPISWVRQ 60 APGKGLEWIG FINSGGSTWY ASWVKGRFTI SRTSTTVDLK MTSLTTDDTA TYFCARGYST 120 YYGDFNIWGP GTLVTISSGG GGSGGGGSGG GGSELVMTQT PSSTSGAVGG TVTINCQASQ 180 SIDSNLAWFQ QKPGQPPTLL IYRASNLASG VPSRFSGSRS GTEYTLTISG VQREDAATYY 240 CLGGVGNVSY RTSFGGGTEV VVKESKYGPP CPPCPAPEFL GGPSVFLFPP KPKDTLMISR 300 TPEVTCVVVD VSQEDPEVQF NWYVDGVEVH NAKTKPREEQ FNSTYRVVSV LTVLHQDWLN 360 GKEYKCKVSN KGLPSSIEKT ISKAKGQPRE PQVYTLPPSQ EEMTKNQVSL TCLVKGFYPS 420 DIAVEWESNG QPENNYKTTP PVLDSDGSFF LYSRLTVDKS RWQEGNVFSC SVMHEALHNH 480 YTQKSLSLSL GKMFWVLVVV GGVLACYSLL VTVAFIIFWV KRGRKKLLYI FKQPFMRPVQ 540 TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA DAPAYQQGQN QLYNELNLGR REEYDVLDKR 600 RGRDPEMGGK PRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK 660 DTYDALHMQA LPPRLEGGGE GRGSLLTCGD VEENPGPRML LLVTSLLLCE LPHPAFLLIP 720 RKVCNGIGIG EFKDSLSINA TNIKHFKNCT SISGDLHILP VAFRGDSFTH TPPLDPQELD 780 ILKTVKEITG FLLIQAWPEN RTDLHAFENL EIIRGRTKQH GQFSLAVVSL NITSLGLRSL 840 KEISDGDVII SGNKNLCYAN TINWKKLFGT SGQKTKIISN RGENSCKATG QVCHALCSPE 900 GCWGPEPRDC VSCRNVSRGR ECVDKCNLLE GEPREFVENS ECIQCHPECL PQAMNITCTG 960 RGPDNCIQCA HYIDGPHCVK TCPAGVMGEN NTLVWKYADA GHVCHLCHPN CTYGCTGPGL 1020 EGCPTNGPKI PSIATGMVGA LLLLLVVALG IGLFM 1055 3-580 Sequences 3-580-1 Sequence Number [ID] 580 3-580-2 Molecule Type AA 3-580-3 Length 945 3-580-4 Features REGION 1..945

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..945 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-580-5 Residues MLLLVTSLLL CELPHPAFLL IPQSVKESEG DLVTPAGNLT LTCTASGSDI NDYPISWVRQ 60 APGKGLEWIG FINSGGSTWY ASWVKGRFTI SRTSTTVDLK MTSLTTDDTA TYFCARGYST 120 YYGDFNIWGP GTLVTISSGG GGSGGGGSGG GGSELVMTQT PSSTSGAVGG TVTINCQASQ 180 SIDSNLAWFQ QKPGQPPTLL IYRASNLASG VPSRFSGSRS GTEYTLTISG VQREDAATYY 240 CLGGVGNVSY RTSFGGGTEV VVKESKYGPP CPPCPGQPRE PQVYTLPPSQ EEMTKNQVSL 300 TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF LYSRLTVDKS RWQEGNVFSC 360 SVMHEALHNH YTQKSLSLSL GKMFWVLVVV GGVLACYSLL VTVAFIIFWV KRGRKKLLYI 420 FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA DAPAYQQGQN QLYNELNLGR 480 REEYDVLDKR RGRDPEMGGK PRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG 540 LYQGLSTATK DTYDALHMQA LPPRLEGGGE GRGSLLTCGD VEENPGPRML LLVTSLLLCE 600 LPHPAFLLIP RKVCNGIGIG EFKDSLSINA TNIKHFKNCT SISGDLHILP VAFRGDSFTH 660 TPPLDPQELD ILKTVKEITG FLLIQAWPEN RTDLHAFENL EIIRGRTKQH GQFSLAVVSL 720 2023214349

NITSLGLRSL KEISDGDVII SGNKNLCYAN TINWKKLFGT SGQKTKIISN RGENSCKATG 780 QVCHALCSPE GCWGPEPRDC VSCRNVSRGR ECVDKCNLLE GEPREFVENS ECIQCHPECL 840 PQAMNITCTG RGPDNCIQCA HYIDGPHCVK TCPAGVMGEN NTLVWKYADA GHVCHLCHPN 900 CTYGCTGPGL EGCPTNGPKI PSIATGMVGA LLLLLVVALG IGLFM 945 3-581 Sequences 3-581-1 Sequence Number [ID] 581 3-581-2 Molecule Type AA 3-581-3 Length 845 3-581-4 Features REGION 1..845 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..845 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-581-5 Residues MLLLVTSLLL CELPHPAFLL IPQEQLVESG GRLVTPGGSL TLSCKASGFD FSAYYMSWVR 60 QAPGKGLEWI ATIYPSSGKT YYATWVNGRF TISSDNAQNT VDLQMNSLTA ADRATYFCAR 120 DSYADDGALF NIWGPGTLVT ISSGGGGSGG GGSGGGGSEL VLTQSPSVSA ALGSPAKITC 180 TLSSAHKTDT IDWYQQLQGE APRYLMQVQS DGSYTKRPGV PDRFSGSSSG ADRYLIIPSV 240 QADDEADYYC GADYIGGYVF GGGTQLTVTG ESKYGPPCPP CPMFWVLVVV GGVLACYSLL 300 VTVAFIIFWV KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA 360 DAPAYQQGQN QLYNELNLGR REEYDVLDKR RGRDPEMGGK PRRKNPQEGL YNELQKDKMA 420 EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPRLEGGGE GRGSLLTCGD 480 VEENPGPRML LLVTSLLLCE LPHPAFLLIP RKVCNGIGIG EFKDSLSINA TNIKHFKNCT 540 SISGDLHILP VAFRGDSFTH TPPLDPQELD ILKTVKEITG FLLIQAWPEN RTDLHAFENL 600 EIIRGRTKQH GQFSLAVVSL NITSLGLRSL KEISDGDVII SGNKNLCYAN TINWKKLFGT 660 SGQKTKIISN RGENSCKATG QVCHALCSPE GCWGPEPRDC VSCRNVSRGR ECVDKCNLLE 720 GEPREFVENS ECIQCHPECL PQAMNITCTG RGPDNCIQCA HYIDGPHCVK TCPAGVMGEN 780 NTLVWKYADA GHVCHLCHPN CTYGCTGPGL EGCPTNGPKI PSIATGMVGA LLLLLVVALG 840 IGLFM 845 3-582 Sequences 3-582-1 Sequence Number [ID] 582 3-582-2 Molecule Type AA 3-582-3 Length 952 3-582-4 Features REGION 1..952 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..952 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-582-5 Residues MLLLVTSLLL CELPHPAFLL IPQEQLVESG GRLVTPGGSL TLSCKASGFD FSAYYMSWVR 60 QAPGKGLEWI ATIYPSSGKT YYATWVNGRF TISSDNAQNT VDLQMNSLTA ADRATYFCAR 120 DSYADDGALF NIWGPGTLVT ISSGGGGSGG GGSGGGGSEL VLTQSPSVSA ALGSPAKITC 180 TLSSAHKTDT IDWYQQLQGE APRYLMQVQS DGSYTKRPGV PDRFSGSSSG ADRYLIIPSV 240 QADDEADYYC GADYIGGYVF GGGTQLTVTG ESKYGPPCPP CPGQPREPQV YTLPPSQEEM 300 TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ 360 EGNVFSCSVM HEALHNHYTQ KSLSLSLGKM FWVLVVVGGV LACYSLLVTV AFIIFWVKRG 420 RKKLLYIFKQ PFMRPVQTTQ EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYQQGQNQLY 480 NELNLGRREE YDVLDKRRGR DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR 540 RGKGHDGLYQ GLSTATKDTY DALHMQALPP RLEGGGEGRG SLLTCGDVEE NPGPRMLLLV 600 TSLLLCELPH PAFLLIPRKV CNGIGIGEFK DSLSINATNI KHFKNCTSIS GDLHILPVAF 660 RGDSFTHTPP LDPQELDILK TVKEITGFLL IQAWPENRTD LHAFENLEII RGRTKQHGQF 720 SLAVVSLNIT SLGLRSLKEI SDGDVIISGN KNLCYANTIN WKKLFGTSGQ KTKIISNRGE 780 NSCKATGQVC HALCSPEGCW GPEPRDCVSC RNVSRGRECV DKCNLLEGEP REFVENSECI 840 QCHPECLPQA MNITCTGRGP DNCIQCAHYI DGPHCVKTCP AGVMGENNTL VWKYADAGHV 900 CHLCHPNCTY GCTGPGLEGC PTNGPKIPSI ATGMVGALLL LLVVALGIGL FM 952 3-583 Sequences

3-583-1 Sequence Number [ID] 583 3-583-2 Molecule Type AA 3-583-3 Length 1062 3-583-4 Features REGION 1..1062 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..1062 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-583-5 Residues MLLLVTSLLL CELPHPAFLL IPQEQLVESG GRLVTPGGSL TLSCKASGFD FSAYYMSWVR 60 QAPGKGLEWI ATIYPSSGKT YYATWVNGRF TISSDNAQNT VDLQMNSLTA ADRATYFCAR 120 DSYADDGALF NIWGPGTLVT ISSGGGGSGG GGSGGGGSEL VLTQSPSVSA ALGSPAKITC 180 TLSSAHKTDT IDWYQQLQGE APRYLMQVQS DGSYTKRPGV PDRFSGSSSG ADRYLIIPSV 240 QADDEADYYC GADYIGGYVF GGGTQLTVTG ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK 300 DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY VDGVEVHNAK TKPREEQFNS TYRVVSVLTV 360 LHQDWLNGKE YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSQEEM TKNQVSLTCL 420 2023214349

VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM 480 HEALHNHYTQ KSLSLSLGKM FWVLVVVGGV LACYSLLVTV AFIIFWVKRG RKKLLYIFKQ 540 PFMRPVQTTQ EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYQQGQNQLY NELNLGRREE 600 YDVLDKRRGR DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ 660 GLSTATKDTY DALHMQALPP RLEGGGEGRG SLLTCGDVEE NPGPRMLLLV TSLLLCELPH 720 PAFLLIPRKV CNGIGIGEFK DSLSINATNI KHFKNCTSIS GDLHILPVAF RGDSFTHTPP 780 LDPQELDILK TVKEITGFLL IQAWPENRTD LHAFENLEII RGRTKQHGQF SLAVVSLNIT 840 SLGLRSLKEI SDGDVIISGN KNLCYANTIN WKKLFGTSGQ KTKIISNRGE NSCKATGQVC 900 HALCSPEGCW GPEPRDCVSC RNVSRGRECV DKCNLLEGEP REFVENSECI QCHPECLPQA 960 MNITCTGRGP DNCIQCAHYI DGPHCVKTCP AGVMGENNTL VWKYADAGHV CHLCHPNCTY 1020 GCTGPGLEGC PTNGPKIPSI ATGMVGALLL LLVVALGIGL FM 1062 3-584 Sequences 3-584-1 Sequence Number [ID] 584 3-584-2 Molecule Type AA 3-584-3 Length 502 3-584-4 Features REGION 1..502 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..502 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-584-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180 ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNR SKRSRLLHSD 360 YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS RVKFSRSADA PAYQQGQNQL YNELNLGRRE 420 EYDVLDKRRG RDPEMGGKPR RKNPQEGLYN ELQKDKMAEA YSEIGMKGER RRGKGHDGLY 480 QGLSTATKDT YDALHMQALP PR 502 3-585 Sequences 3-585-1 Sequence Number [ID] 585 3-585-2 Molecule Type AA 3-585-3 Length 508 3-585-4 Features REGION 1..508 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..508 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-585-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180 ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNR FSVVKRGRKK 360 LLYIFKQPFM RPVQTTQEED GCSCRFPEEE EGGCELRVKF SRSADAPAYQ QGQNQLYNEL 420 NLGRREEYDV LDKRRGRDPE MGGKPRRKNP QEGLYNELQK DKMAEAYSEI GMKGERRRGK 480 GHDGLYQGLS TATKDTYDAL HMQALPPR 508 3-586 Sequences 3-586-1 Sequence Number [ID] 586 3-586-2 Molecule Type AA 3-586-3 Length 509 3-586-4 Features REGION 1..509 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..509 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-586-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 11 Aug 2023

GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180 ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNQ RRKYRSNKGE 360 SPVEPAEPCR YSCPREEEGS TIPIQEDYRK PEPACSPRVK FSRSADAPAY QQGQNQLYNE 420 LNLGRREEYD VLDKRRGRDP EMGGKPRRKN PQEGLYNELQ KDKMAEAYSE IGMKGERRRG 480 KGHDGLYQGL STATKDTYDA LHMQALPPR 509 3-587 Sequences 3-587-1 Sequence Number [ID] 587 3-587-2 Molecule Type AA 3-587-3 Length 550 2023214349

3-587-4 Features REGION 1..550 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..550 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-587-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180 ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNR SKRSRLLHSD 360 YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS QRRKYRSNKG ESPVEPAEPC RYSCPREEEG 420 STIPIQEDYR KPEPACSPRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY DVLDKRRGRD 480 PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG LSTATKDTYD 540 ALHMQALPPR 550 3-588 Sequences 3-588-1 Sequence Number [ID] 588 3-588-2 Molecule Type AA 3-588-3 Length 556 3-588-4 Features REGION 1..556 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..556 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-588-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180 ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNQ RRKYRSNKGE 360 SPVEPAEPCR YSCPREEEGS TIPIQEDYRK PEPACSPRFS VVKRGRKKLL YIFKQPFMRP 420 VQTTQEEDGC SCRFPEEEEG GCELRVKFSR SADAPAYQQG QNQLYNELNL GRREEYDVLD 480 KRRGRDPEMG GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA 540 TKDTYDALHM QALPPR 556 3-589 Sequences 3-589-1 Sequence Number [ID] 589 3-589-2 Molecule Type AA 3-589-3 Length 506 3-589-4 Features REGION 1..506 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..506 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-589-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSAAA FVPVFLPAKP TTTPAPRPPT PAPTIASQPL 300 SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL LSLVITLYCN HRNRSKRSRL 360 LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRSRVKFSR SADAPAYQQG QNQLYNELNL 420 GRREEYDVLD KRRGRDPEMG GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH 480 DGLYQGLSTA TKDTYDALHM QALPPR 506 3-590 Sequences

3-590-1 Sequence Number [ID] 590 3-590-2 Molecule Type AA 3-590-3 Length 560 3-590-4 Features REGION 1..560 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..560 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-590-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSAAA FVPVFLPAKP TTTPAPRPPT PAPTIASQPL 300 SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL LSLVITLYCN HRNQRRKYRS 360 NKGESPVEPA EPCRYSCPRE EEGSTIPIQE DYRKPEPACS PRFSVVKRGR KKLLYIFKQP 420 2023214349

FMRPVQTTQE EDGCSCRFPE EEEGGCELRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY 480 DVLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG 540 LSTATKDTYD ALHMQALPPR 560 3-591 Sequences 3-591-1 Sequence Number [ID] 591 3-591-2 Molecule Type AA 3-591-3 Length 513 3-591-4 Features REGION 1..513 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..513 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-591-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSAAA FVPVFLPAKP TTTPAPRPPT PAPTIASQPL 300 SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL LSLVITLYCN HRNQRRKYRS 360 NKGESPVEPA EPCRYSCPRE EEGSTIPIQE DYRKPEPACS PRVKFSRSAD APAYQQGQNQ 420 LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY NELQKDKMAE AYSEIGMKGE 480 RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 513 3-592 Sequences 3-592-1 Sequence Number [ID] 592 3-592-2 Molecule Type AA 3-592-3 Length 554 3-592-4 Features REGION 1..554 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..554 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-592-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSAAA FVPVFLPAKP TTTPAPRPPT PAPTIASQPL 300 SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL LSLVITLYCN HRNRSKRSRL 360 LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRSQRRKYR SNKGESPVEP AEPCRYSCPR 420 EEEGSTIPIQ EDYRKPEPAC SPRVKFSRSA DAPAYQQGQN QLYNELNLGR REEYDVLDKR 480 RGRDPEMGGK PRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK 540 DTYDALHMQA LPPR 554 3-593 Sequences 3-593-1 Sequence Number [ID] 593 3-593-2 Molecule Type AA 3-593-3 Length 476 3-593-4 Features REGION 1..476 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..476 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-593-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180

ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNR SKRSRLLHSD 360 YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS QRRKYRSNKG ESPVEPAEPC RYSCPREEEG 420 STIPIQEDYR KPEPACSPQV RKAAITSYEK SDGVYTGLST RNQETYETLK HEKPPQ 476 11 Aug 2023

3-594 Sequences 3-594-1 Sequence Number [ID] 594 3-594-2 Molecule Type AA 3-594-3 Length 480 3-594-4 Features REGION 1..480 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..480 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-594-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 2023214349

KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSAAA FVPVFLPAKP TTTPAPRPPT PAPTIASQPL 300 SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL LSLVITLYCN HRNRSKRSRL 360 LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRSQRRKYR SNKGESPVEP AEPCRYSCPR 420 EEEGSTIPIQ EDYRKPEPAC SPQVRKAAIT SYEKSDGVYT GLSTRNQETY ETLKHEKPPQ 480 3-595 Sequences 3-595-1 Sequence Number [ID] 595 3-595-2 Molecule Type AA 3-595-3 Length 428 3-595-4 Features REGION 1..428 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..428 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-595-5 Residues MALPVTALLL PLALLLHAAR PEIVLTQSPG TLSLSPGERA TLSCRASQSV SSSYLAWYQQ 60 KPGQAPRLLI YGASSRATGI PDRFSGSGSG TDFTLTISRL EPEDFAVYYC QQYGSSRFTF 120 GPGTKVDIKG STSGSGKPGS GEGSTKGQVQ LVQSGAEVKK PGSSVKVSCK DSGGTFSSYA 180 ISWVRQAPGQ GLEWMGGIIP IFGTTNYAQQ FQGRVTITAD ESTSTAYMEL SSLRSEDTAV 240 YYCAREAVAA DWLDPWGQGT LVTVSSFVPV FLPAKPTTTP APRPPTPAPT IASQPLSLRP 300 EACRPAAGGA VHTRGLDFAC DIYIWAPLAG TCGVLLLSLV ITLYCNHRNR SKRSRLLHSD 360 YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS QVRKAAITSY EKSDGVYTGL STRNQETYET 420 LKHEKPPQ 428 3-596 Sequences 3-596-1 Sequence Number [ID] 596 3-596-2 Molecule Type AA 3-596-3 Length 432 3-596-4 Features REGION 1..432 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..432 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-596-5 Residues MLLLVTSLLL CELPHPAFLL IPDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 60 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 120 GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG 180 VSWIRQPPRK GLEWLGVIWG SETTYYNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY 240 YCAKHYYYGG SYAMDYWGQG TSVTVSSAAA FVPVFLPAKP TTTPAPRPPT PAPTIASQPL 300 SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL LSLVITLYCN HRNRSKRSRL 360 LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRSQVRKAA ITSYEKSDGV YTGLSTRNQE 420 TYETLKHEKP PQ 432 3-597 Sequences 3-597-1 Sequence Number [ID] 597 3-597-2 Molecule Type AA 3-597-3 Length 486 3-597-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-597-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120

QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 11 Aug 2023

GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-598 Sequences 3-598-1 Sequence Number [ID] 598 3-598-2 Molecule Type AA 3-598-3 Length 486 3-598-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-598-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYQSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-599 Sequences 3-599-1 Sequence Number [ID] 599 3-599-2 Molecule Type AA 3-599-3 Length 486 3-599-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-599-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-600 Sequences 3-600-1 Sequence Number [ID] 600 3-600-2 Molecule Type AA 3-600-3 Length 486 3-600-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-600-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-601 Sequences 3-601-1 Sequence Number [ID] 601 3-601-2 Molecule Type AA 3-601-3 Length 491 3-601-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-601-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 11 Aug 2023

QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYSSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-602 Sequences 3-602-1 Sequence Number [ID] 602 3-602-2 Molecule Type AA 3-602-3 Length 491 2023214349

3-602-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-602-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYQSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-603 Sequences 3-603-1 Sequence Number [ID] 603 3-603-2 Molecule Type AA 3-603-3 Length 491 3-603-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-603-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-604 Sequences 3-604-1 Sequence Number [ID] 604 3-604-2 Molecule Type AA 3-604-3 Length 491 3-604-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-604-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-605 Sequences 3-605-1 Sequence Number [ID] 605 3-605-2 Molecule Type AA

3-605-3 Length 491 3-605-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-605-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 2023214349

3-606 Sequences 3-606-1 Sequence Number [ID] 606 3-606-2 Molecule Type AA 3-606-3 Length 491 3-606-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-606-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-607 Sequences 3-607-1 Sequence Number [ID] 607 3-607-2 Molecule Type AA 3-607-3 Length 491 3-607-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-607-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY NSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-608 Sequences 3-608-1 Sequence Number [ID] 608 3-608-2 Molecule Type AA 3-608-3 Length 486 3-608-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-608-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYNSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420

GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-609 Sequences 3-609-1 Sequence Number [ID] 609 3-609-2 Molecule Type AA 11 Aug 2023

3-609-3 Length 486 3-609-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-609-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 2023214349

HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-610 Sequences 3-610-1 Sequence Number [ID] 610 3-610-2 Molecule Type AA 3-610-3 Length 486 3-610-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-610-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYSSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-611 Sequences 3-611-1 Sequence Number [ID] 611 3-611-2 Molecule Type AA 3-611-3 Length 486 3-611-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-611-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYQSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-612 Sequences 3-612-1 Sequence Number [ID] 612 3-612-2 Molecule Type AA 3-612-3 Length 486 3-612-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-612-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120

YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 11 Aug 2023

GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-613 Sequences 3-613-1 Sequence Number [ID] 613 3-613-2 Molecule Type AA 3-613-3 Length 486 3-613-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-613-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSEIVM TQSPATLSLS PGERATLSCR 180 ASQDISKYLN WYQQKPGQAP RLLIYHTSRL HSGIPARFSG SGSGTDYTLT ISSLQPEDFA 240 VYFCQQGNTL PYTFGQGTKL EIKTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-614 Sequences 3-614-1 Sequence Number [ID] 614 3-614-2 Molecule Type AA 3-614-3 Length 491 3-614-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-614-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYSSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-615 Sequences 3-615-1 Sequence Number [ID] 615 3-615-2 Molecule Type AA 3-615-3 Length 491 3-615-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-615-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYQSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-616 Sequences 3-616-1 Sequence Number [ID] 616 3-616-2 Molecule Type AA 3-616-3 Length 491 3-616-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-616-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY SSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 11 Aug 2023

YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-617 Sequences 3-617-1 Sequence Number [ID] 617 3-617-2 Molecule Type AA 3-617-3 Length 491 2023214349

3-617-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-617-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY QSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-618 Sequences 3-618-1 Sequence Number [ID] 618 3-618-2 Molecule Type AA 3-618-3 Length 491 3-618-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-618-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-619 Sequences 3-619-1 Sequence Number [ID] 619 3-619-2 Molecule Type AA 3-619-3 Length 491 3-619-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-619-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSGGGGSQV QLQESGPGLV KPSETLSLTC TVSGVSLPDY 180 GVSWIRQPPG KGLEWIGVIW GSETTYYNSS LKSRVTISKD NSKNQVSLKL SSVTAADTAV 240 YYCAKHYYYG GSYAMDYWGQ GTLVTVSSTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 3-620 Sequences 3-620-1 Sequence Number [ID] 620 3-620-2 Molecule Type AA

3-620-3 Length 491 3-620-4 Features REGION 1..491 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..491 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-620-5 Residues MALPVTALLL PLALLLHAAR PQVQLQESGP GLVKPSETLS LTCTVSGVSL PDYGVSWIRQ 60 PPGKGLEWIG VIWGSETTYY NSSLKSRVTI SKDNSKNQVS LKLSSVTAAD TAVYYCAKHY 120 YYGGSYAMDY WGQGTLVTVS SGGGGSGGGG SGGGGSGGGG SEIVMTQSPA TLSLSPGERA 180 TLSCRASQDI SKYLNWYQQK PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ 240 PEDFAVYFCQ QGNTLPYTFG QGTKLEIKTT TPAPRPPTPA PTIASQPLSL RPEACRPAAG 300 GAVHTRGLDF ACDIYIWAPL AGTCGVLLLS LVITLYCKRG RKKLLYIFKQ PFMRPVQTTQ 360 EEDGCSCRFP EEEEGGCELR VKFSRSADAP AYKQGQNQLY NELNLGRREE YDVLDKRRGR 420 DPEMGGKPRR KNPQEGLYNE LQKDKMAEAY SEIGMKGERR RGKGHDGLYQ GLSTATKDTY 480 DALHMQALPP R 491 2023214349

3-621 Sequences 3-621-1 Sequence Number [ID] 621 3-621-2 Molecule Type AA 3-621-3 Length 486 3-621-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-621-5 Residues MALPVTALLL PLALLLHAAR PEIVMTQSPA TLSLSPGERA TLSCRASQDI SKYLNWYQQK 60 PGQAPRLLIY HTSRLHSGIP ARFSGSGSGT DYTLTISSLQ PEDFAVYFCQ QGNTLPYTFG 120 QGTKLEIKGG GGSGGGGSGG GGSQVQLQES GPGLVKPSET LSLTCTVSGV SLPDYGVSWI 180 RQPPGKGLEW IGVIWGSETT YYNSSLKSRV TISKDNSKNQ VSLKLSSVTA ADTAVYYCAK 240 HYYYGGSYAM DYWGQGTLVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-622 Sequences 3-622-1 Sequence Number [ID] 622 3-622-2 Molecule Type AA 3-622-3 Length 527 3-622-4 Features REGION 1..527 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..527 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-622-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGST SGSGKPGSGE 120 GSTKGEVKLQ ESGPGLVAPS QSLSVTCTVS GVSLPDYGVS WIRQPPRKGL EWLGVRWGSE 180 TTYYNSALKS RLTIIKDNSK SQVFLKMNSL QTDDTAIYYC AKHYYYGGSY AMDYWGQGTS 240 VTVSSAAIEV MYPPPYLDNE KSNGTIIHVK GKHLCPSPLF PGPSKPFWVL VVVGGVLACY 300 SLLVTVAFII FWVRSKRSRL LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRSASGGGG 360 SGGGGSKSRQ TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLGGGGS GGGGSRVKFS 420 RSADAPAYQQ GQNQLYNELN LGRREEYDVL DKRRGRDPEM GGKPRRKNPQ EGLYNELQKD 480 KMAEAYSEIG MKGERRRGKG HDGLYQGLST ATKDTYDALH MQALPPR 527 3-623 Sequences 3-623-1 Sequence Number [ID] 623 3-623-2 Molecule Type AA 3-623-3 Length 527 3-623-4 Features REGION 1..527 Location/Qualifiers note=Description of Artificial Sequence: Synthetic chimeric antigen r eceptor source 1..527 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-623-5 Residues MGTSLLCWMA LCLLGADHAD AQVQLQQSGP ELVKPGASVK ISCKASGYAF SSSWMNWVKQ 60 RPGKGLEWIG RIYPGDEDTN YSGKFKDKAT LTADKSSTTA YMQLSSLTSE DSAVYFCARS 120 LLYGDYLDYW GQGTTLTVSS GGGGSGGGGS GGGGSQIVLT QSPAIMSASP GEKVTMTCSA 180 SSSVSYMHWY QQKSGTSPKR WIYDTSKLAS GVPDRFSGSG SGTSYFLTIN NMEAEDAATY 240 YCQQWNINPL TFGAGTKLEL KRSDPTTTPA PRPPTPAPTI ASQPLSLRPE ACRPAAGGAV 300 HTRGLDFACD IFWVLVVVGG VLACYSLLVT VAFIIFWVRS KRSRLLHSDY MNMTPRRPGP 360 TRKHYQPYAP PRDFAAYRSR DQRLPPDAHK PPGGGSFRTP IQEEQADAHS TLAKIRVKFS 420

RSADAPAYQQ GQNQLYNELN LGRREEYDVL DKRRGRDPEM GGKPRRKNPQ EGLYNELQKD 480 KMAEAYSEIG MKGERRRGKG HDGLYQGLST ATKDTYDALH MQALPPR 527 3-624 Sequences 3-624-1 Sequence Number [ID] 624 3-624-2 Molecule Type AA 11 Aug 2023

3-624-3 Length 242 3-624-4 Features REGION 1..242 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..242 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-624-5 Residues DIQMTQTTSS LSASLGDRVT ISCRASQDIS KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS 60 RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ GNTLPYTFGG GTKLEITGGG GSGGGGSGGG 120 GSEVKLQESG PGLVAPSQSL SVTCTVSGVS LPDYGVSWIR QPPRKGLEWL GVIWGSETTY 180 YNSALKSRLT IIKDNSKSQV FLKMNSLQTD DTAIYYCAKH YYYGGSYAMD YWGQGTSVTV 240 2023214349

SS 242 3-625 Sequences 3-625-1 Sequence Number [ID] 625 3-625-2 Molecule Type AA 3-625-3 Length 69 3-625-4 Features source 1..69 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-625-5 Residues TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA PLAGTCGVLL 60 LSLVITLYC 69 3-626 Sequences 3-626-1 Sequence Number [ID] 626 3-626-2 Molecule Type DNA 3-626-3 Length 726 3-626-4 Features misc_feature 1..726 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..726 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-626-5 Residues gacatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 60 atcagttgca gggcaagtca ggacattagt aaatatttaa attggtatca gcagaaacca 120 gatggaactg ttaaactcct gatctaccat acatcaagat tacactcagg agtcccatca 180 aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa 240 gaagatattg ccacttactt ttgccaacag ggtaatacgc ttccgtacac gttcggaggg 300 gggaccaagc tggagatcac aggtggcggt ggctcgggcg gtggtgggtc gggtggcggc 360 ggatctgagg tgaaactgca ggagtcagga cctggcctgg tggcgccctc acagagcctg 420 tccgtcacat gcactgtctc aggggtctca ttacccgact atggtgtaag ctggattcgc 480 cagcctccac gaaagggtct ggagtggctg ggagtaatat ggggtagtga aaccacatac 540 tataattcag ctctcaaatc cagactgacc atcatcaagg acaactccaa gagccaagtt 600 ttcttaaaaa tgaacagtct gcaaactgat gacacagcca tttactactg tgccaaacat 660 tattactacg gtggtagcta tgctatggac tactggggcc aaggaacctc agtcaccgtc 720 tcctca 726 3-627 Sequences 3-627-1 Sequence Number [ID] 627 3-627-2 Molecule Type DNA 3-627-3 Length 207 3-627-4 Features misc_feature 1..207 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..207 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-627-5 Residues accacaaccc cagcacctcg cccaccaaca ccagcaccaa ccatcgcatc ccagccactg 60 tctctgaggc ccgaggcatg taggcctgca gcaggaggcg ccgtgcacac caggggcctg 120 gactttgcct gcgatatcta tatctgggca ccactggcag gaacatgtgg cgtgctgctg 180 ctgtccctgg tcatcaccct gtattgc 207 3-628 Sequences 3-628-1 Sequence Number [ID] 628 3-628-2 Molecule Type AA 3-628-3 Length 21 3-628-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens

NonEnglishQualifier Value 3-628-5 Residues MALPVTALLL PLALLLHAAR P 21 3-629 Sequences 3-629-1 Sequence Number [ID] 629 11 Aug 2023

3-629-2 Molecule Type AA 3-629-3 Length 5 3-629-4 Features REGION 1..5 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..5 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-629-5 Residues GGSGG 5 3-630 Sequences 3-630-1 Sequence Number [ID] 630 3-630-2 Molecule Type AA 2023214349

3-630-3 Length 12 3-630-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic cleavage site source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-630-5 Residues ESRRVRRNKR SK 12 3-631 Sequences 3-631-1 Sequence Number [ID] 631 3-631-2 Molecule Type AA 3-631-3 Length 143 3-631-4 Features REGION 1..143 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..143 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-631-5 Residues MDWTWILFLV AAATRVHSYP YDVPDYANWV NVISDLKKIE DLIQSMHIDA TLYTESDVHP 60 SCKVTAMKCF LLELQVISLE SGDASIHDTV ENLIILANNS LSSNGNVTES GCKECEELEE 120 KNIKEFLQSF VHIVQMFINT SGS 143 3-632 Sequences 3-632-1 Sequence Number [ID] 632 3-632-2 Molecule Type DNA 3-632-3 Length 918 3-632-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-632-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca cctgaggagg atggcatcac ctggacactg 120 gatcagagct ccgaggtgct gggaagcggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatttgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gcggtgcgag gccaagaatt atagcggccg gttcacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtctag ccggggctcc 420 tctgacccac agggagtgac atgcggagca gccaccctgt ccgccgagcg ggtgagaggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tcctgcagca 540 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacaagct ccttctttat cagggacatc atcaagcctg atccccctaa gaacctgcag 660 ctgaagccac tgaagaattc tcgccaggtg gaggtgagct gggagtaccc agacacctgg 720 tccacacccc actcttattt cagcctgacc ttttgcgtgc aggtgcaggg caagtccaag 780 cgggagaaga aggacagagt gttcaccgat aagacatctg ccaccgtgat ctgtcggaag 840 aacgcctcca tctctgtgag ggcccaggat cgctactatt ctagctcctg gagcgagtgg 900 gcatccgtgc catgttct 918 3-633 Sequences 3-633-1 Sequence Number [ID] 633 3-633-2 Molecule Type DNA 3-633-3 Length 918 3-633-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-633-5 Residues atctgggagc tcaagaaaga cgtgtacgtg gtggaactgg actggtaccc cgacgcccct 60 ggcgaaatgg tggtgctgac atgcgacacc cctgaggagg atggcattac ctggaccctc 120 11 Aug 2023 gatcagagct ccgaggtgct gggcagcggc aaaaccctga ccatccaggt gaaggagttt 180 ggcgatgccg gccagtacac atgtcacaag ggcggcgagg tgctgagcca ctccctgctg 240 ctgctccaca agaaggaaga tggcatctgg agcaccgaca ttctgaagga tcagaaggag 300 cccaagaaca agacattcct gaggtgtgag gccaagaact acagcggcag gtttacctgc 360 tggtggctga caacaatcag caccgacctc acattctccg tcaagtcctc caggggttct 420 tccgaccctc aaggcgtgac atgcggcgct gccaccctga gcgctgagag agtcaggggc 480 gacaacaagg agtacgagta cagcgtcgaa tgtcaggagg acagcgcctg tcccgccgct 540 gaagagagcc tgcctatcga ggtgatggtg gacgccgtgc acaaactgaa gtatgagaat 600 tacacctcca gcttcttcat cagggacatc atcaaacccg atccccccaa gaacctgcag 660 ctgaagcctc tgaagaacag cagacaggtc gaagtgtcct gggagtaccc tgatacctgg 720 tccacacccc acagctactt cagcctgacc ttttgcgtgc aggtgcaggg caagagcaaa 780 agggagaaga aggacagggt gtttaccgac aagacctccg ccacagtgat ttgcagaaag 840 2023214349 aacgcctcca tcagcgtgag ggcccaggac aggtattaca gcagctcctg gagcgaatgg 900 gctagcgtgc cctgtagc 918 3-634 Sequences 3-634-1 Sequence Number [ID] 634 3-634-2 Molecule Type DNA 3-634-3 Length 918 3-634-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-634-5 Residues atctgggagc tcaagaaaga cgtgtacgtg gtggaactgg actggtaccc cgacgcccct 60 ggcgaaatgg tggtgctgac atgcgacacc cctgaggagg atggcattac ctggaccctc 120 gatcagagct ccgaggtgct gggcagcggc aaaaccctga ccatccaggt gaaggagttt 180 ggcgatgccg gccagtacac atgtcacaag ggcggcgagg tgctgagcca ctccctgctg 240 ctgctccaca agaaggaaga tggcatctgg agcaccgaca ttctgaagga tcagaaggag 300 cccaagaaca agacattcct gaggtgtgag gccaagaact acagcggcag gtttacctgc 360 tggtggctga caacaatcag caccgacctc acattctccg tcaagtcctc caggggttct 420 tccgaccctc aaggcgtgac atgcggcgct gccaccctga gcgctgagag agtcaggggc 480 gacaacaagg agtacgagta cagcgtcgaa tgtcaggagg acagcgcctg tcccgccgct 540 gaagagagcc tgcctatcga ggtgatggtg gacgccgtgc acaaactgaa gtatgagaat 600 tacacctcca gcttcttcat cagggacatc atcaaacccg atccccccaa gaacctgcag 660 ctgaagcctc tgaagaacag cagacaggtc gaagtgtcct gggagtaccc tgatacctgg 720 tccacacccc acagctactt cagcctgacc ttttgcgtgc aggtgcaggg caagagcaaa 780 agggagaaga aggacagggt gtttaccgac aagacctccg ccacagtgat ttgcagaaag 840 aacgcctcca tcagcgtgag ggcccaggac aggtattaca gcagctcctg gagcgaatgg 900 gctagcgtgc cctgtagc 918 3-635 Sequences 3-635-1 Sequence Number [ID] 635 3-635-2 Molecule Type AA 3-635-3 Length 486 3-635-4 Features REGION 1..486 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..486 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-635-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPR 486 3-636 Sequences 3-636-1 Sequence Number [ID] 636 3-636-2 Molecule Type AA 3-636-3 Length 593 3-636-4 Features REGION 1..593 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..593 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-636-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 11 Aug 2023

RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSGVQVETI SPGDGRTFPK RGQTCVVHYT GMLEDGKKVD 300 SSRDRNKPFK FMLGKQEVIR GWEEGVAQMS VGQRAKLTIS PDYAYGATGH PGIIPPHATL 360 VFDVELLKPE TTTPAPRPPT PAPTIASQPL SLRPEACRPA AGGAVHTRGL DFACDIYIWA 420 PLAGTCGVLL LSLVITLYCK RGRKKLLYIF KQPFMRPVQT TQEEDGCSCR FPEEEEGGCE 480 LRVKFSRSAD APAYKQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY 540 NELQKDKMAE AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 593 3-637 Sequences 3-637-1 Sequence Number [ID] 637 3-637-2 Molecule Type AA 3-637-3 Length 644 3-637-4 Features REGION 1..644 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..644 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-637-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSISLIAAL AVDYVIGMEN AMPWNLPADL AWFKRNTLNK 300 PVIMGRHTWE SIGRPLPGRK NIILSSQPGT DDRVTWVKSV DEAIAACGDV PEIMVIGGGR 360 VIEQFLPKAQ KLYLTHIDAE VEGDTHFPDY EPDDWESVFS EFHDADAQNS HSYCFEILER 420 RTTTPAPRPP TPAPTIASQP LSLRPEACRP AAGGAVHTRG LDFACDIYIW APLAGTCGVL 480 LLSLVITLYC KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA 540 DAPAYKQGQN QLYNELNLGR REEYDVLDKR RGRDPEMGGK PRRKNPQEGL YNELQKDKMA 600 EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 644 3-638 Sequences 3-638-1 Sequence Number [ID] 638 3-638-2 Molecule Type AA 3-638-3 Length 593 3-638-4 Features REGION 1..593 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..593 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-638-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDGV QVETISPGDG RTFPKRGQTC VVHYTGMLED GKKVDSSRDR NKPFKFMLGK 360 QEVIRGWEEG VAQMSVGQRA KLTISPDYAY GATGHPGIIP PHATLVFDVE LLKPEIYIWA 420 PLAGTCGVLL LSLVITLYCK RGRKKLLYIF KQPFMRPVQT TQEEDGCSCR FPEEEEGGCE 480 LRVKFSRSAD APAYKQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP RRKNPQEGLY 540 NELQKDKMAE AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQAL PPR 593 3-639 Sequences 3-639-1 Sequence Number [ID] 639 3-639-2 Molecule Type AA 3-639-3 Length 644 3-639-4 Features REGION 1..644 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..644 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-639-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIS LIAALAVDYV IGMENAMPWN LPADLAWFKR NTLNKPVIMG RHTWESIGRP 360 LPGRKNIILS SQPGTDDRVT WVKSVDEAIA ACGDVPEIMV IGGGRVIEQF LPKAQKLYLT 420 HIDAEVEGDT HFPDYEPDDW ESVFSEFHDA DAQNSHSYCF EILERRIYIW APLAGTCGVL 480 LLSLVITLYC KRGRKKLLYI FKQPFMRPVQ TTQEEDGCSC RFPEEEEGGC ELRVKFSRSA 540

DAPAYKQGQN QLYNELNLGR REEYDVLDKR RGRDPEMGGK PRRKNPQEGL YNELQKDKMA 600 EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR 644 3-640 Sequences 3-640-1 Sequence Number [ID] 640 3-640-2 Molecule Type AA 11 Aug 2023

3-640-3 Length 649 3-640-4 Features REGION 1..649 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..649 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-640-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 2023214349

HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GISLIAALAV DHVIGMENAM PWNLPADLAW FKRNTLNKPV IMGRHTWESI 540 GRPLPGRKNI ILSSQPGTDD RVTWVKSVDE AIAACGDVPE IMVIGGGRVY EQFLPKAQKL 600 YLTHIDAEVE GDTHFPDYKP DDWESVFSEF HDADAQNSHS YCFEILERR 649 3-641 Sequences 3-641-1 Sequence Number [ID] 641 3-641-2 Molecule Type AA 3-641-3 Length 598 3-641-4 Features REGION 1..598 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..598 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-641-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GGVQVETISP GDGRTFPKRG QTCVVHYTGM LGDGKKVDSS RDRNKPFKFM 540 LGKQEVIRGW EEGVAQMSVG QGAKLTISPD YAYGATGHPG IIPPHATLVF DVELLELE 598 3-642 Sequences 3-642-1 Sequence Number [ID] 642 3-642-2 Molecule Type AA 3-642-3 Length 677 3-642-4 Features REGION 1..677 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..677 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-642-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL 540 VIMGKKTWFS IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV 600 DMVWIVGGSS VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV 660 QEEKGIKYKF EVYEKND 677 3-643 Sequences 3-643-1 Sequence Number [ID] 643 3-643-2 Molecule Type AA 3-643-3 Length 677 3-643-4 Features REGION 1..677 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..677 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-643-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL 540 VIMGKKTWFS IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV 600 DMVWIVGGSS VIKEFMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV 660 QEEKGIKYKF EVYEKND 677 3-644 Sequences 2023214349

3-644-1 Sequence Number [ID] 644 3-644-2 Molecule Type AA 3-644-3 Length 677 3-644-4 Features REGION 1..677 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..677 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-644-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFKRMTT TSSVEGKQNL 540 VIMGKKTWFS IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV 600 DMVWIVGGSS VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV 660 QEEKGIKYKF EVYEKND 677 3-645 Sequences 3-645-1 Sequence Number [ID] 645 3-645-2 Molecule Type AA 3-645-3 Length 677 3-645-4 Features REGION 1..677 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..677 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-645-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFFRMTT TSSVEGKQNL 540 VIMGKKTWFS IPEKFRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV 600 DMVWIVGGSS VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV 660 QEEKGIKYKF EVYEKND 677 3-646 Sequences 3-646-1 Sequence Number [ID] 646 3-646-2 Molecule Type AA 3-646-3 Length 607 3-646-4 Features REGION 1..607 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..607 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-646-5 Residues MALPVTALLL PLALLLHAAR PSGGVQVETI SPGDGRTFPK RGQTCVVHYT GMLEDGKKVD 60 SSRDRNKPFK FMLGKQEVIR GWEEGVAQMS VGQRAKLTIS PDYAYGATGH PGIIPPHATL 120

VFDVELLKPE ESRRVRRNKR SKDIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ 180 KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF 240 GGGTKLEITG GGGSGGGGSG GGGSEVKLQE SGPGLVAPSQ SLSVTCTVSG VSLPDYGVSW 300 IRQPPRKGLE WLGVIWGSET TYYNSALKSR LTIIKDNSKS QVFLKMNSLQ TDDTAIYYCA 360 KHYYYGGSYA MDYWGQGTSV TVSSTTTPAP RPPTPAPTIA SQPLSLRPEA CRPAAGGAVH 420 11 Aug 2023

TRGLDFACDI YIWAPLAGTC GVLLLSLVIT LYCKRGRKKL LYIFKQPFMR PVQTTQEEDG 480 CSCRFPEEEE GGCELRVKFS RSADAPAYKQ GQNQLYNELN LGRREEYDVL DKRRGRDPEM 540 GGKPRRKNPQ EGLYNELQKD KMAEAYSEIG MKGERRRGKG HDGLYQGLST ATKDTYDALH 600 MQALPPR 607 3-647 Sequences 3-647-1 Sequence Number [ID] 647 3-647-2 Molecule Type AA 3-647-3 Length 658 3-647-4 Features REGION 1..658 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..658 2023214349

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-647-5 Residues MALPVTALLL PLALLLHAAR PSGISLIAAL AVDYVIGMEN AMPWNLPADL AWFKRNTLNK 60 PVIMGRHTWE SIGRPLPGRK NIILSSQPGT DDRVTWVKSV DEAIAACGDV PEIMVIGGGR 120 VIEQFLPKAQ KLYLTHIDAE VEGDTHFPDY EPDDWESVFS EFHDADAQNS HSYCFEILER 180 RESRRVRRNK RSKDIQMTQT TSSLSASLGD RVTISCRASQ DISKYLNWYQ QKPDGTVKLL 240 IYHTSRLHSG VPSRFSGSGS GTDYSLTISN LEQEDIATYF CQQGNTLPYT FGGGTKLEIT 300 GGGGSGGGGS GGGGSEVKLQ ESGPGLVAPS QSLSVTCTVS GVSLPDYGVS WIRQPPRKGL 360 EWLGVIWGSE TTYYNSALKS RLTIIKDNSK SQVFLKMNSL QTDDTAIYYC AKHYYYGGSY 420 AMDYWGQGTS VTVSSTTTPA PRPPTPAPTI ASQPLSLRPE ACRPAAGGAV HTRGLDFACD 480 IYIWAPLAGT CGVLLLSLVI TLYCKRGRKK LLYIFKQPFM RPVQTTQEED GCSCRFPEEE 540 EGGCELRVKF SRSADAPAYK QGQNQLYNEL NLGRREEYDV LDKRRGRDPE MGGKPRRKNP 600 QEGLYNELQK DKMAEAYSEI GMKGERRRGK GHDGLYQGLS TATKDTYDAL HMQALPPR 658 3-648 Sequences 3-648-1 Sequence Number [ID] 648 3-648-2 Molecule Type AA 3-648-3 Length 686 3-648-4 Features REGION 1..686 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..686 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-648-5 Residues MALPVTALLL PLALLLHAAR PSGVGSLNCI VAVSQNMGIG KNGDLPWPPL RNEFRYFQRM 60 TTTSSVEGKQ NLVIMGKKTW FSIPEKNRPL KGRINLVLSR ELKEPPQGAH FLSRSLDDAL 120 KLTEQPELAN KVDMVWIVGG SSVIKEFMNH PGHLKLFVTR IMQDFESDTF FPEIDLEKYK 180 LLPEYPGVLS DVQEEKGIKY KFEVYEKNDE SRRVRRNKRS KDIQMTQTTS SLSASLGDRV 240 TISCRASQDI SKYLNWYQQK PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE 300 QEDIATYFCQ QGNTLPYTFG GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS 360 LSVTCTVSGV SLPDYGVSWI RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ 420 VFLKMNSLQT DDTAIYYCAK HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS 480 QPLSLRPEAC RPAAGGAVHT RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL 540 YIFKQPFMRP VQTTQEEDGC SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL 600 GRREEYDVLD KRRGRDPEMG GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH 660 DGLYQGLSTA TKDTYDALHM QALPPR 686 3-649 Sequences 3-649-1 Sequence Number [ID] 649 3-649-2 Molecule Type AA 3-649-3 Length 686 3-649-4 Features REGION 1..686 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..686 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-649-5 Residues MALPVTALLL PLALLLHAAR PSGVGSLNCI VAVSQNMGIG KNGDLPWPPL RNEFRYFKRM 60 TTTSSVEGKQ NLVIMGKKTW FSIPEKNRPL KGRINLVLSR ELKEPPQGAH FLSRSLDDAL 120 KLTEQPELAN KVDMVWIVGG SSVIKEAMNH PGHLKLFVTR IMQDFESDTF FPEIDLEKYK 180 LLPEYPGVLS DVQEEKGIKY KFEVYEKNDE SRRVRRNKRS KDIQMTQTTS SLSASLGDRV 240 TISCRASQDI SKYLNWYQQK PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE 300 QEDIATYFCQ QGNTLPYTFG GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS 360 LSVTCTVSGV SLPDYGVSWI RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ 420 VFLKMNSLQT DDTAIYYCAK HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS 480 QPLSLRPEAC RPAAGGAVHT RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL 540 YIFKQPFMRP VQTTQEEDGC SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL 600

GRREEYDVLD KRRGRDPEMG GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH 660 DGLYQGLSTA TKDTYDALHM QALPPR 686 3-650 Sequences 3-650-1 Sequence Number [ID] 650 3-650-2 Molecule Type DNA 11 Aug 2023

3-650-3 Length 726 3-650-4 Features misc_feature 1..726 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..726 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-650-5 Residues gacatccaga tgacacagac cacaagctcc ctgtccgcct ctctgggcga cagagtgacc 60 atcagctgcc gggcctccca ggatatctct aagtatctga actggtacca gcagaagccc 120 gatggcacag tgaagctgct gatctatcac accagccgcc tgcactccgg agtgccttct 180 aggttcagcg gctccggctc tggcacagac tacagcctga ccatctccaa cctggagcag 240 2023214349

gaggatatcg ccacctattt ctgccagcag ggcaatacac tgccttacac ctttggcggc 300 ggcacaaagc tggagatcac cggaggagga ggcagcggag gaggaggctc cggcggcggc 360 ggctctgagg tgaagctgca ggagtccgga ccaggcctgg tggcacctag ccagtccctg 420 tctgtgacat gtaccgtgtc cggcgtgtct ctgccagact acggcgtgtc ttggatcagg 480 cagccaccta ggaagggcct ggagtggctg ggcgtgatct ggggcagcga gacaacatac 540 tataattctg ccctgaagag cagactgaca atcatcaagg acaacagcaa gtcccaggtg 600 ttcctgaaga tgaatagcct gcagacagac gataccgcca tctactattg cgccaagcac 660 tactattacg gcggcagcta tgccatggat tactggggcc agggcacatc cgtgaccgtg 720 tctagc 726 3-651 Sequences 3-651-1 Sequence Number [ID] 651 3-651-2 Molecule Type DNA 3-651-3 Length 726 3-651-4 Features misc_feature 1..726 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..726 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-651-5 Residues gacatccaga tgacacagac cacaagctcc ctgagcgcct ccctgggcga cagagtgacc 60 atctcttgcc gggccagcca ggatatctcc aagtatctga actggtacca gcagaagccc 120 gatggcacag tgaagctgct gatctatcac acctctcgcc tgcacagcgg cgtgccttcc 180 aggttctctg gcagcggctc cggcacagac tactctctga ccatcagcaa cctggagcag 240 gaggatatcg ccacctattt ctgccagcag ggcaatacac tgccctacac ctttggcggc 300 ggcacaaagc tggagatcac cggcggcggc ggctctggag gaggaggcag cggcggagga 360 ggctccgagg tgaagctgca ggagtccgga ccaggcctgg tggcaccatc tcagagcctg 420 tccgtgacat gtaccgtgag cggcgtgtcc ctgcctgact acggcgtgag ctggatcaga 480 cagccaccta ggaagggcct ggagtggctg ggcgtgatct ggggctccga gacaacatac 540 tataactccg ccctgaagtc tcggctgacc atcatcaagg acaactctaa gagccaggtg 600 ttcctgaaga tgaattccct gcagacagac gataccgcca tctactattg cgccaagcac 660 tactattacg gcggctccta tgccatggat tactggggcc agggcacatc tgtgaccgtg 720 tctagc 726 3-652 Sequences 3-652-1 Sequence Number [ID] 652 3-652-2 Molecule Type DNA 3-652-3 Length 726 3-652-4 Features misc_feature 1..726 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..726 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-652-5 Residues gacatccaga tgacacagac cacaagctcc ctgagcgcct ccctgggcga cagagtgacc 60 atcagctgcc gggcctccca ggatatctct aagtatctga actggtacca gcagaagcca 120 gatggcacag tgaagctgct gatctatcac accagccgcc tgcactccgg agtgccctct 180 aggttctctg gcagcggctc cggcacagac tacagcctga ccatctccaa cctggagcag 240 gaggatatcg ccacctattt ctgccagcag ggcaatacac tgccatacac ctttggcggc 300 ggcacaaagc tggagatcac cggaggagga ggcagcggag gaggaggctc cggcggcggc 360 ggctctgagg tgaagctgca ggagtccgga ccaggcctgg tggcaccttc tcagagcctg 420 tccgtgacat gtaccgtgtc tggcgtgagc ctgcccgact acggcgtgtc ttggatcaga 480 cagccaccta ggaagggcct ggagtggctg ggcgtgatct ggggcagcga gacaacatac 540 tataattctg ccctgaagag caggctgacc atcatcaagg acaactctaa gagccaggtg 600 ttcctgaaga tgaattccct gcagacagac gataccgcca tctactattg cgccaagcac 660 tactattacg gcggctctta tgccatggat tactggggcc agggcacaag cgtgaccgtg 720 tctagc 726 3-653 Sequences

3-653-1 Sequence Number [ID] 653 3-653-2 Molecule Type DNA 3-653-3 Length 726 3-653-4 Features misc_feature 1..726 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..726 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-653-5 Residues gacatccaga tgacacagac cacaagctcc ctgagcgcct ccctgggcga cagagtgacc 60 atctcttgcc gggccagcca ggatatctcc aagtatctga actggtacca gcagaagcca 120 gatggcacag tgaagctgct gatctatcac acctctcgcc tgcacagcgg agtgccctcc 180 aggttctctg gcagcggctc cggcacagac tactctctga ccatcagcaa cctggagcag 240 gaggatatcg ccacctattt ctgccagcag ggcaatacac tgccctacac ctttggcggc 300 ggcacaaagc tggagatcac cggcggcggc ggctctggag gaggaggcag cggcggagga 360 ggctccgagg tgaagctgca ggagtccgga ccaggcctgg tggcaccatc tcagagcctg 420 2023214349

tccgtgacat gtaccgtgag cggcgtgtcc ctgcctgact acggcgtgag ctggatcaga 480 cagccaccta ggaagggcct ggagtggctg ggcgtgatct ggggctccga gacaacatac 540 tataattccg ccctgaagtc tcggctgaca atcatcaagg acaactctaa gagccaggtg 600 tttctgaaga tgaatagcct gcagacagac gataccgcca tctactattg cgccaagcac 660 tactattacg gcggctccta tgccatggat tactggggcc agggcacatc tgtgaccgtg 720 tctagc 726 3-654 Sequences 3-654-1 Sequence Number [ID] 654 3-654-2 Molecule Type DNA 3-654-3 Length 726 3-654-4 Features misc_feature 1..726 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 scFv sequence source 1..726 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-654-5 Residues gacatccaga tgacacagac cacaagctcc ctgagcgcct ccctgggcga cagagtgacc 60 atcagctgcc gggcctccca ggatatctct aagtatctga actggtacca gcagaagcca 120 gatggcacag tgaagctgct gatctatcac accagccgcc tgcactccgg agtgccctct 180 aggttctctg gcagcggctc cggcacagac tacagcctga ccatctccaa cctggagcag 240 gaggatatcg ccacctattt ctgccagcag ggcaatacac tgccatacac ctttggcggc 300 ggcacaaagc tggagatcac cggaggagga ggcagcggag gaggaggctc cggcggcggc 360 ggctctgagg tgaagctgca ggagtccgga ccaggcctgg tggcaccttc tcagagcctg 420 tccgtgacat gtaccgtgtc tggcgtgagc ctgcccgact acggcgtgtc ttggatcaga 480 cagccaccta ggaagggcct ggagtggctg ggcgtgatct ggggcagcga gacaacatac 540 tataattctg ccctgaagag caggctgaca atcatcaagg acaactctaa gagccaggtg 600 tttctgaaga tgaatagcct gcagacagac gataccgcca tctactattg tgccaagcac 660 tactattacg gcggcagcta tgccatggat tactggggcc agggcacatc cgtgaccgtg 720 tctagc 726 3-655 Sequences 3-655-1 Sequence Number [ID] 655 3-655-2 Molecule Type DNA 3-655-3 Length 207 3-655-4 Features source 1..207 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-655-5 Residues accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg 60 tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg 120 gacttcgcct gtgatatcta catctgggcg cccttggccg ggacttgtgg ggtccttctc 180 ctgtcactgg ttatcacttt actgccc 207 3-656 Sequences 3-656-1 Sequence Number [ID] 656 3-656-2 Molecule Type DNA 3-656-3 Length 135 3-656-4 Features misc_feature 1..135 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..135 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-656-5 Residues accacaaccc cagcacctcg cccaccaaca ccagcaccaa ccatcgcatc ccagccactg 60 tctctgaggc ccgaggcatg taggcctgca gcaggaggcg ccgtgcacac caggggcctg 120 gactttgcct gcgat 135 3-657 Sequences

3-657-1 Sequence Number [ID] 657 3-657-2 Molecule Type DNA 3-657-3 Length 135 3-657-4 Features misc_feature 1..135 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..135 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-657-5 Residues acaacaaccc cagcacccag acctccaaca cctgcaccaa ccatcgcaag ccagcctctg 60 tccctgaggc ccgaggcatg taggccagca gcaggaggcg ccgtgcacac ccggggcctg 120 gactttgcct gcgat 135 3-658 Sequences 3-658-1 Sequence Number [ID] 658 3-658-2 Molecule Type DNA 3-658-3 Length 135 2023214349

3-658-4 Features misc_feature 1..135 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..135 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-658-5 Residues accacaaccc cagcaccccg cccaccaaca cctgcaccaa ccatcgcctc ccagccactg 60 tctctgaggc ccgaggcatg taggcctgca gcaggaggcg ccgtgcacac caggggcctg 120 gactttgcct gcgat 135 3-659 Sequences 3-659-1 Sequence Number [ID] 659 3-659-2 Molecule Type DNA 3-659-3 Length 135 3-659-4 Features misc_feature 1..135 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..135 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-659-5 Residues accacaaccc cagcacccag accaccaaca cctgcaccaa ccatcgcaag ccagcctctg 60 tccctgcgcc cagaggcatg caggccagca gcaggaggag cagtgcacac ccggggcctg 120 gacttcgcat gtgat 135 3-660 Sequences 3-660-1 Sequence Number [ID] 660 3-660-2 Molecule Type DNA 3-660-3 Length 135 3-660-4 Features misc_feature 1..135 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..135 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-660-5 Residues accacaaccc cagcacctcg cccaccaaca ccagcaccaa ccatcgcatc ccagccactg 60 tctctgcgcc ccgaggcatg caggcctgca gcaggcggcg ccgtgcacac caggggcctg 120 gacttcgcct gtgat 135 3-661 Sequences 3-661-1 Sequence Number [ID] 661 3-661-2 Molecule Type DNA 3-661-3 Length 336 3-661-4 Features misc_feature 1..336 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..336 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-661-5 Residues agggtgaagt tttctaggag cgccgatgca ccagcatata agcagggaca gaaccagctg 60 tacaacgagc tgaatctggg caggagagag gagtacgacg tgctggataa gaggagggga 120 agggaccccg agatgggagg caagccaagg agaaagaacc cccaggaggg cctgtataat 180 gagctgcaga aggacaagat ggccgaggcc tactccgaga tcggcatgaa gggagagcgg 240 cgcaggggca agggacacga tggcctgtat cagggcctgt ctacagccac caaggacacc 300 tacgatgcac tgcacatgca ggccctgcct ccaagg 336 3-662 Sequences 3-662-1 Sequence Number [ID] 662 3-662-2 Molecule Type DNA

3-662-3 Length 336 3-662-4 Features misc_feature 1..336 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..336 11 Aug 2023

mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-662-5 Residues agggtgaagt tttccaggtc tgccgatgcc cccgcctata agcagggcca gaatcagctg 60 tacaacgagc tgaatctggg caggagagag gagtacgacg tgctggataa gaggagggga 120 cgcgaccccg agatgggagg caagcctagg agaaagaacc cacaggaggg cctgtataat 180 gagctgcaga aggacaagat ggccgaggcc tactctgaga tcggcatgaa gggagagcgg 240 cgcaggggca agggacacga tggcctgtat cagggcctga gcacagccac caaggacacc 300 tacgatgcac tgcacatgca ggccctgcca cctagg 336 3-663 Sequences 3-663-1 Sequence Number [ID] 663 3-663-2 Molecule Type DNA 2023214349

3-663-3 Length 336 3-663-4 Features misc_feature 1..336 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..336 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-663-5 Residues agggtgaagt ttagcaggtc cgccgatgcc ccagcctata agcagggcca gaaccagctg 60 tacaacgagc tgaatctggg caggagggaa gagtacgacg tgctggataa gaggagagga 120 agggaccccg agatgggagg caagccaagg aggaagaacc cacaggaggg cctgtataat 180 gagctgcaga aggacaagat ggccgaggcc tacagcgaga tcggcatgaa gggagagagg 240 agacggggca agggacacga tggcctgtat cagggcctgt ccacagccac caaggacacc 300 tacgatgcac tgcacatgca ggccctgcct ccaagg 336 3-664 Sequences 3-664-1 Sequence Number [ID] 664 3-664-2 Molecule Type DNA 3-664-3 Length 336 3-664-4 Features misc_feature 1..336 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..336 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-664-5 Residues agggtgaagt tttccaggtc tgccgatgcc ccagcctata agcagggcca gaatcagctg 60 tacaacgagc tgaatctggg caggagagag gagtacgacg tgctggataa gaggagggga 120 cgcgaccccg agatgggagg caagcctagg agaaagaacc cacaggaggg cctgtataat 180 gagctgcaga aggacaagat ggccgaggcc tactctgaga tcggcatgaa gggagagcgg 240 cgcaggggca agggacacga tggcctgtat cagggcctga gcacagccac caaggacacc 300 tacgatgcac tgcacatgca ggccctgcca cctagg 336 3-665 Sequences 3-665-1 Sequence Number [ID] 665 3-665-2 Molecule Type DNA 3-665-3 Length 336 3-665-4 Features misc_feature 1..336 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..336 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-665-5 Residues agggtgaagt ttagcaggtc cgccgatgcc ccagcctata agcagggcca gaaccagctg 60 tacaacgagc tgaatctggg caggagggaa gagtacgacg tgctggataa gaggagagga 120 agggaccccg agatgggagg caagccaagg aggaagaacc cacaggaggg cctgtataat 180 gagctgcaga aggacaagat ggccgaggcc tactccgaga tcggcatgaa gggagagagg 240 agacggggca agggacacga tggcctgtat cagggcctgt ctacagccac caaggacacc 300 tacgatgcac tgcacatgca ggccctgcct ccaagg 336 3-666 Sequences 3-666-1 Sequence Number [ID] 666 3-666-2 Molecule Type DNA 3-666-3 Length 126 3-666-4 Features misc_feature 1..126 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..126 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-666-5 Residues aagagaggcc ggaagaagct gctgtacatc ttcaagcagc ccttcatgag gcccgtgcag 60 acaacccagg aggaggacgg ctgcagctgt cggttcccag aggaggagga gggaggatgt 120 gagctg 126 3-667 Sequences 11 Aug 2023

3-667-1 Sequence Number [ID] 667 3-667-2 Molecule Type DNA 3-667-3 Length 126 3-667-4 Features misc_feature 1..126 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..126 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-667-5 Residues aagcgcggca ggaagaagct gctgtacatc ttcaagcagc cctttatgcg ccctgtgcag 60 acaacccagg aggaggacgg ctgcagctgt aggttcccag aggaggagga gggaggatgt 120 2023214349

gagctg 126 3-668 Sequences 3-668-1 Sequence Number [ID] 668 3-668-2 Molecule Type DNA 3-668-3 Length 126 3-668-4 Features misc_feature 1..126 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..126 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-668-5 Residues aagcgcggca ggaagaagct gctgtacatc ttcaagcagc cttttatgcg cccagtgcag 60 acaacccagg aggaggacgg ctgcagctgt aggttccctg aggaggagga gggaggatgt 120 gagctg 126 3-669 Sequences 3-669-1 Sequence Number [ID] 669 3-669-2 Molecule Type DNA 3-669-3 Length 126 3-669-4 Features misc_feature 1..126 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..126 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-669-5 Residues aagcgcggca ggaagaagct gctgtacatc ttcaagcagc cctttatgcg ccctgtgcag 60 acaacccagg aggaggacgg ctgcagctgt aggttccctg aggaggagga gggaggatgt 120 gagctg 126 3-670 Sequences 3-670-1 Sequence Number [ID] 670 3-670-2 Molecule Type DNA 3-670-3 Length 126 3-670-4 Features misc_feature 1..126 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..126 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-670-5 Residues aagcgcggca ggaagaagct gctgtacatc ttcaagcagc cttttatgcg cccagtgcag 60 acaacccagg aggaggacgg ctgcagctgt aggttccctg aggaggagga gggaggatgc 120 gagctg 126 3-671 Sequences 3-671-1 Sequence Number [ID] 671 3-671-2 Molecule Type DNA 3-671-3 Length 63 3-671-4 Features source 1..63 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-671-5 Residues atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg 60 ccg 63 3-672 Sequences 3-672-1 Sequence Number [ID] 672 3-672-2 Molecule Type DNA 3-672-3 Length 63

3-672-4 Features misc_feature 1..63 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..63 mol_type=other DNA 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-672-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 ccc 63 3-673 Sequences 3-673-1 Sequence Number [ID] 673 3-673-2 Molecule Type DNA 3-673-3 Length 63 3-673-4 Features misc_feature 1..63 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..63 mol_type=other DNA 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-673-5 Residues atggcactgc cagtgacagc cctgctgctg cctctggccc tgctgctgca cgcagccaga 60 cct 63 3-674 Sequences 3-674-1 Sequence Number [ID] 674 3-674-2 Molecule Type DNA 3-674-3 Length 63 3-674-4 Features misc_feature 1..63 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..63 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-674-5 Residues atggcactgc ctgtgacagc cctgctgctg ccactggccc tgctgctgca cgcagcccgc 60 cct 63 3-675 Sequences 3-675-1 Sequence Number [ID] 675 3-675-2 Molecule Type DNA 3-675-3 Length 63 3-675-4 Features misc_feature 1..63 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..63 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-675-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagcccgc 60 cct 63 3-676 Sequences 3-676-1 Sequence Number [ID] 676 3-676-2 Molecule Type DNA 3-676-3 Length 15 3-676-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-676-5 Residues ggaggcagcg gagga 15 3-677 Sequences 3-677-1 Sequence Number [ID] 677 3-677-2 Molecule Type DNA 3-677-3 Length 15 3-677-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-677-5 Residues ggaggctctg gagga 15 3-678 Sequences 3-678-1 Sequence Number [ID] 678 3-678-2 Molecule Type DNA

3-678-3 Length 15 3-678-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 11 Aug 2023

mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-678-5 Residues ggaggctccg gcgga 15 3-679 Sequences 3-679-1 Sequence Number [ID] 679 3-679-2 Molecule Type DNA 3-679-3 Length 15 3-679-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-679-5 Residues ggaggatccg gaggc 15 3-680 Sequences 3-680-1 Sequence Number [ID] 680 3-680-2 Molecule Type DNA 3-680-3 Length 15 3-680-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-680-5 Residues ggaggatctg gagga 15 3-681 Sequences 3-681-1 Sequence Number [ID] 681 3-681-2 Molecule Type DNA 3-681-3 Length 36 3-681-4 Features misc_feature 1..36 Location/Qualifiers note=Description of Artificial Sequence: Synthetic cleavage site source 1..36 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-681-5 Residues gagtctaggc gcgtgcggag aaataagcgg agcaag 36 3-682 Sequences 3-682-1 Sequence Number [ID] 682 3-682-2 Molecule Type DNA 3-682-3 Length 36 3-682-4 Features misc_feature 1..36 Location/Qualifiers note=Description of Artificial Sequence: Synthetic cleavage site source 1..36 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-682-5 Residues gagtctcgga gagtgaggcg caataagagg agcaag 36 3-683 Sequences 3-683-1 Sequence Number [ID] 683 3-683-2 Molecule Type DNA 3-683-3 Length 36 3-683-4 Features misc_feature 1..36 Location/Qualifiers note=Description of Artificial Sequence: Synthetic cleavage site source 1..36 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-683-5 Residues gagtccagga gagtgcggcg caacaagagg agcaag 36 3-684 Sequences 3-684-1 Sequence Number [ID] 684 3-684-2 Molecule Type DNA 3-684-3 Length 321 3-684-4 Features misc_feature 1..321

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-684-5 Residues ggagtgcagg tggagacaat ctctcctggc gatggccgga ccttcccaaa gagaggccag 60 acatgcgtgg tgcactacac cggcatgctg gaggacggca agaaggtgga cagctcccgg 120 gatagaaaca agccattcaa gtttatgctg ggcaagcagg aagtgatcag gggatgggag 180 gagggagtgg cacagatgtc tgtgggccag agagccaagc tgacaatcag ccctgattac 240 gcatatggag caaccggaca cccaggaatc atcccacctc acgccaccct ggtgtttgat 300 gtggagctgc tgaagccaga g 321 3-685 Sequences 3-685-1 Sequence Number [ID] 685 3-685-2 Molecule Type DNA 3-685-3 Length 321 3-685-4 Features misc_feature 1..321 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-685-5 Residues ggcgtgcagg tggagacaat ctcccctggc gatggccgga ccttcccaaa gagaggccag 60 acatgcgtgg tgcactacac cggcatgctg gaggacggca agaaggtgga cagctcccgg 120 gatagaaaca agcctttcaa gtttatgctg ggcaagcagg aagtgatcag gggatgggag 180 gagggagtgg cacagatgtc tgtgggccag agagccaagc tgacaatcag ccctgattac 240 gcatatggag caaccggaca cccaggaatc atcccacctc acgccaccct ggtgtttgac 300 gtggagctgc tgaagccaga g 321 3-686 Sequences 3-686-1 Sequence Number [ID] 686 3-686-2 Molecule Type DNA 3-686-3 Length 321 3-686-4 Features misc_feature 1..321 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-686-5 Residues ggagtgcagg tggagacaat ctcccctggc gatggcagga ccttcccaaa gcgcggccag 60 acatgcgtgg tgcactacac cggcatgctg gaggacggca agaaggtgga cagctcccgg 120 gatagaaaca agccattcaa gtttatgctg ggcaagcagg aagtgatcag gggatgggag 180 gagggagtgg cacagatgtc cgtgggacag cgcgccaagc tgacaatctc tcctgattac 240 gcatatggag caaccggaca cccaggaatc atcccacctc acgccaccct ggtgtttgac 300 gtggagctgc tgaagcccga g 321 3-687 Sequences 3-687-1 Sequence Number [ID] 687 3-687-2 Molecule Type DNA 3-687-3 Length 474 3-687-4 Features misc_feature 1..474 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-687-5 Residues atctctctga tcgccgccct ggccgtggat tacgtgatcg gcatggagaa cgccatgcca 60 tggaatctgc cagcagacct ggcatggttc aagaggaaca cactgaataa gccagtgatc 120 atgggcagac acacctggga gtccatcggc cggccactgc caggcagaaa gaacatcatc 180 ctgagctccc agcccggcac agacgatagg gtgacctggg tgaagagcgt ggacgaggca 240 atcgcagcat gcggcgatgt gcctgagatc atggtcatcg gaggaggacg cgtgatcgag 300 cagttcctgc caaaggccca gaagctgtac ctgacacaca tcgatgccga ggtggagggc 360 gacacccact ttcctgatta tgagccagac gattgggagt ccgtgttctc tgagtttcac 420 gacgccgatg cccagaactc tcacagctat tgttttgaga tcctggagcg gaga 474 3-688 Sequences 3-688-1 Sequence Number [ID] 688 3-688-2 Molecule Type DNA 3-688-3 Length 324 3-688-4 Features misc_feature 1..324 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..324 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value

3-688-5 Residues ggcgtgcagg tggagacaat cagccccggc gatggccgga cctttcctaa gagaggccag 60 acatgcgtgg tgcactacac cggcatgctg ggcgacggca agaaggtgga cagctccagg 120 gatcgcaata agcccttcaa gtttatgctg ggcaagcagg aagtgatcag gggatgggag 180 gagggagtgg cacagatgtc cgtgggacag ggcgccaagc tgacaatctc tccagattac 240 gcatatggag caaccggaca cccaggaatc atcccacccc acgccaccct ggtgttcgac 300 11 Aug 2023

gtggagctgc tggagctgga gtga 324 3-689 Sequences 3-689-1 Sequence Number [ID] 689 3-689-2 Molecule Type DNA 3-689-3 Length 324 3-689-4 Features misc_feature 1..324 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..324 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 2023214349

3-689-5 Residues ggagtgcagg tggagacaat cagccccggc gatggcagga cctttcctaa gcgcggccag 60 acatgcgtgg tgcactacac cggcatgctg ggcgacggca agaaggtgga cagctcccgg 120 gatagaaata agcccttcaa gtttatgctg ggcaagcagg aagtgatcag aggctgggag 180 gagggagtgg cacagatgtc tgtgggacag ggcgccaagc tgacaatcag cccagattac 240 gcatatggag caaccggaca cccaggaatc atcccacccc acgccaccct ggtgttcgac 300 gtggagctgc tggagctgga gtga 324 3-690 Sequences 3-690-1 Sequence Number [ID] 690 3-690-2 Molecule Type DNA 3-690-3 Length 324 3-690-4 Features misc_feature 1..324 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..324 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-690-5 Residues ggcgtgcagg tggagacaat cagccccggc gatggccgga cctttcctaa gcgcggccag 60 acatgcgtgg tgcactacac cggcatgctg ggcgacggca agaaggtgga cagctccagg 120 gatagaaaca agccattcaa gtttatgctg ggcaagcagg aagtgatcag aggatgggag 180 gagggagtgg cacagatgtc cgtgggacag ggcgccaagc tgacaatctc tccagattac 240 gcatatggag caaccggaca cccaggaatc atcccacccc acgccaccct ggtgttcgac 300 gtggagctgc tggagctgga gtga 324 3-691 Sequences 3-691-1 Sequence Number [ID] 691 3-691-2 Molecule Type DNA 3-691-3 Length 324 3-691-4 Features misc_feature 1..324 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..324 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-691-5 Residues ggagtgcagg tggagacaat cagcccaggc gacggaagga cattcccaaa gaggggacag 60 acctgcgtgg tgcactacac aggcatgctg ggcgatggca agaaggtgga cagctcccgg 120 gatagaaaca agcccttcaa gtttatgctg ggcaagcagg aagtgatcag gggatgggag 180 gagggagtgg cacagatgtc cgtgggacag ggcgccaagc tgaccatctc tcctgactac 240 gcctatggag caacaggaca cccaggaatc atcccacctc acgccaccct ggtgtttgat 300 gtggagctgc tggagctgga gtga 324 3-692 Sequences 3-692-1 Sequence Number [ID] 692 3-692-2 Molecule Type DNA 3-692-3 Length 474 3-692-4 Features misc_feature 1..474 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-692-5 Residues atctccctga tcgccgccct ggccgtggat tatgtgatcg gcatggagaa cgccatgccc 60 tggaatctgc ccgccgacct ggcctggttc aagaggaata ccctgaacaa gcccgtcatc 120 atgggcaggc acacctggga aagcatcggc agacccctgc ccggcaggaa gaacatcatc 180 ctgtccagcc agcccggcac cgacgacaga gtgacctggg tgaagagcgt ggacgaagct 240 atcgccgctt gcggcgacgt gcccgagatc atggtgatcg gcggcggcag ggtgatcgaa 300 cagttcctgc ccaaggccca gaagctgtac ctgacccaca tcgatgccga ggtggaaggc 360 gatacacact tccccgatta cgaacctgac gactgggaaa gcgtgttttc cgaattccac 420 gacgccgacg cccagaacag ccacagctac tgcttcgaga tcctggaaag aagg 474 3-693 Sequences 3-693-1 Sequence Number [ID] 693 3-693-2 Molecule Type DNA 11 Aug 2023

3-693-3 Length 561 3-693-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-693-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 2023214349

actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-694 Sequences 3-694-1 Sequence Number [ID] 694 3-694-2 Molecule Type DNA 3-694-3 Length 558 3-694-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-694-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 attaaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-695 Sequences 3-695-1 Sequence Number [ID] 695 3-695-2 Molecule Type DNA 3-695-3 Length 561 3-695-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-695-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aattcatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-696 Sequences 3-696-1 Sequence Number [ID] 696 3-696-2 Molecule Type DNA 3-696-3 Length 561 3-696-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value

3-696-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttcagaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaaga accgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 11 Aug 2023

gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagt tcatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgattg a 561 3-697 Sequences 3-697-1 Sequence Number [ID] 697 3-697-2 Molecule Type DNA 3-697-3 Length 561 3-697-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 2023214349

mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-697-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttcaagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-698 Sequences 3-698-1 Sequence Number [ID] 698 3-698-2 Molecule Type DNA 3-698-3 Length 561 3-698-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-698-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttaagaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaaga accgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagg ccatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgattg a 561 3-699 Sequences 3-699-1 Sequence Number [ID] 699 3-699-2 Molecule Type DNA 3-699-3 Length 561 3-699-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-699-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttcaagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agttccgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-700 Sequences 3-700-1 Sequence Number [ID] 700

3-700-2 Molecule Type DNA 3-700-3 Length 561 3-700-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) 11 Aug 2023

source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-700-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttttcaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaagt tccgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagg ccatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 2023214349

gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgattg a 561 3-701 Sequences 3-701-1 Sequence Number [ID] 701 3-701-2 Molecule Type DNA 3-701-3 Length 1461 3-701-4 Features misc_feature 1..1461 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1461 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-701-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaaggtg a 1461 3-702 Sequences 3-702-1 Sequence Number [ID] 702 3-702-2 Molecule Type DNA 3-702-3 Length 1782 3-702-4 Features misc_feature 1..1782 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1782 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-702-5 Residues atggcactgc cagtgacagc cctgctgctg cctctggccc tgctgctgca cgcagccaga 60 cctgacatcc agatgacaca gaccacaagc tccctgagcg cctccctggg cgacagagtg 120 accatctctt gccgggccag ccaggatatc tccaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacacctctc gcctgcacag cggcgtgcct 240 tccaggttct ctggcagcgg ctccggcaca gactactctc tgaccatcag caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcccta cacctttggc 360 ggcggcacaa agctggagat caccggcggc ggcggctctg gaggaggagg cagcggcgga 420 ggaggctccg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc atctcagagc 480 ctgtccgtga catgtaccgt gagcggcgtg tccctgcctg actacggcgt gagctggatc 540 agacagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggctc cgagacaaca 600 tactataact ccgccctgaa gtctcggctg accatcatca aggacaactc taagagccag 660 gtgttcctga agatgaattc cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggctc ctatgccatg gattactggg gccagggcac atctgtgacc 780 gtgtctagcg gcgtgcaggt ggagacaatc agcccaggcg acggacgcac ctttccaaag 840 11 Aug 2023 aggggacaga catgcgtggt gcactacacc ggcatgctgg aggatggcaa gaaggtggac 900 tcctctagag atcggaataa gccattcaag tttatgctgg gcaagcagga agtgatcaga 960 ggctgggagg agggagtggc acagatgtct gtgggacagc gggccaagct gacaatcagc 1020 cctgactatg catacggagc aaccggacac ccaggaatca tcccaccaca cgccacactg 1080 gtgttcgatg tggagctgct gaagcctgag acaacaaccc cagcacccag acctccaaca 1140 cctgcaccaa ccatcgcaag ccagcctctg tccctgaggc ccgaggcatg taggccagca 1200 gcaggaggcg ccgtgcacac ccggggcctg gactttgcct gcgatatcta tatctgggca 1260 ccactggcag gaacatgtgg cgtgctgctg ctgtccctgg tcatcaccct gtattgcaag 1320 cgcggcagga agaagctgct gtacatcttc aagcagccct ttatgcgccc tgtgcagaca 1380 acccaggagg aggacggctg cagctgtagg ttcccagagg aggaggaggg aggatgtgag 1440 ctgagggtga agttttccag gtctgccgat gcccccgcct ataagcaggg ccagaatcag 1500 ctgtacaacg agctgaatct gggcaggaga gaggagtacg acgtgctgga taagaggagg 1560 2023214349 ggacgcgacc ccgagatggg aggcaagcct aggagaaaga acccacagga gggcctgtat 1620 aatgagctgc agaaggacaa gatggccgag gcctactctg agatcggcat gaagggagag 1680 cggcgcaggg gcaagggaca cgatggcctg tatcagggcc tgagcacagc caccaaggac 1740 acctacgatg cactgcacat gcaggccctg ccacctaggt ga 1782 3-703 Sequences 3-703-1 Sequence Number [ID] 703 3-703-2 Molecule Type DNA 3-703-3 Length 1935 3-703-4 Features misc_feature 1..1935 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1935 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-703-5 Residues atggcactgc ctgtgacagc cctgctgctg ccactggccc tgctgctgca cgcagcccgc 60 cctgacatcc agatgacaca gaccacaagc tccctgagcg cctccctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 ccagatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgccc 240 tctaggttct ctggcagcgg ctccggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgccata cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc ttctcagagc 480 ctgtccgtga catgtaccgt gtctggcgtg agcctgcccg actacggcgt gtcttggatc 540 agacagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcaggctg accatcatca aggacaactc taagagccag 660 gtgttcctga agatgaattc cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggctc ttatgccatg gattactggg gccagggcac aagcgtgacc 780 gtgtctagca tctccctgat cgccgccctg gcagtggact acgtgatcgg catggagaac 840 gccatgccct ggaatctgcc tgccgatctg gcctggttta agagaaacac actgaataag 900 cccgtgatca tgggccggca cacctgggag tctatcggca ggcccctgcc tggcaggaag 960 aacatcatcc tgtcctctca gcctggcaca gacgatagag tgacctgggt gaagagcgtg 1020 gacgaggcaa tcgcagcatg tggcgatgtg cccgagatca tggtcatcgg cggcggcaga 1080 gtgatcgagc agttcctgcc taaggcccag aagctgtatc tgacacacat cgacgccgag 1140 gtggagggcg acacccactt tccagattac gagcccgacg attgggagtc cgtgttctct 1200 gagtttcacg acgccgatgc ccagaattcc cactcttatt gcttcgagat cctggagagg 1260 agaaccacaa ccccagcacc ccgcccacca acacctgcac caaccatcgc ctcccagcca 1320 ctgtctctga ggcccgaggc atgtaggcct gcagcaggag gcgccgtgca caccaggggc 1380 ctggactttg cctgcgatat ctacatctgg gcacctctgg caggaacatg tggcgtgctg 1440 ctgctgtccc tggtcatcac cctgtattgc aagcgcggca ggaagaagct gctgtacatc 1500 ttcaagcagc cttttatgcg cccagtgcag acaacccagg aggaggacgg ctgcagctgt 1560 aggttccctg aggaggagga gggaggatgt gagctgaggg tgaagtttag caggtccgcc 1620 gatgccccag cctataagca gggccagaac cagctgtaca acgagctgaa tctgggcagg 1680 agggaagagt acgacgtgct ggataagagg agaggaaggg accccgagat gggaggcaag 1740 ccaaggagga agaacccaca ggagggcctg tataatgagc tgcagaagga caagatggcc 1800 gaggcctaca gcgagatcgg catgaaggga gagaggagac ggggcaaggg acacgatggc 1860 ctgtatcagg gcctgtccac agccaccaag gacacctacg atgcactgca catgcaggcc 1920 ctgcctccaa ggtga 1935 3-704 Sequences 3-704-1 Sequence Number [ID] 704 3-704-2 Molecule Type DNA 3-704-3 Length 1782 3-704-4 Features misc_feature 1..1782 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1782 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-704-5 Residues atggcactgc cagtgacagc cctgctgctg cctctggccc tgctgctgca cgcagccaga 60 cctgacatcc agatgacaca gaccacaagc tccctgagcg cctccctggg cgacagagtg 120 accatctctt gccgggccag ccaggatatc tccaagtatc tgaactggta ccagcagaag 180 ccagatggca cagtgaagct gctgatctat cacacctctc gcctgcacag cggagtgccc 240 11 Aug 2023

tccaggttct ctggcagcgg ctccggcaca gactactctc tgaccatcag caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcccta cacctttggc 360 ggcggcacaa agctggagat caccggcggc ggcggctctg gaggaggagg cagcggcgga 420 ggaggctccg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc atctcagagc 480 ctgtccgtga catgtaccgt gagcggcgtg tccctgcctg actacggcgt gagctggatc 540 agacagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggctc cgagacaaca 600 tactataatt ccgccctgaa gtctcggctg acaatcatca aggacaactc taagagccag 660 gtgtttctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggctc ctatgccatg gattactggg gccagggcac atctgtgacc 780 gtgtctagca ccacaacccc agcacccaga ccaccaacac ctgcaccaac catcgcaagc 840 cagcctctgt ccctgcgccc agaggcatgc aggccagcag caggaggagc agtgcacacc 900 cggggcctgg acttcgcatg tgatggagtg caggtggaga caatctcccc aggcgacggc 960 2023214349

agaacctttc ccaagcgggg ccagacatgc gtggtgcact ataccggcat gctggaggat 1020 ggcaagaagg tggactcctc tagagatcgg aacaagccat tcaagtttat gctgggcaag 1080 caggaagtga tcagaggctg ggaggaggga gtggcacaga tgtctgtggg acagcgggcc 1140 aagctgacaa tcagcccaga ctatgcatac ggagcaaccg gacaccctgg aatcatccct 1200 ccacacgcca ccctggtgtt cgatgtggag ctgctgaagc ctgagatcta catctgggca 1260 ccactggcag gaacatgcgg cgtgctgctg ctgtccctgg tcatcaccct gtattgtaag 1320 cgcggcagga agaagctgct gtacatcttc aagcagccct ttatgcgccc tgtgcagaca 1380 acccaggagg aggacggctg cagctgtagg ttccctgagg aggaggaggg aggatgtgag 1440 ctgagggtga agttttccag gtctgccgat gccccagcct ataagcaggg ccagaatcag 1500 ctgtacaacg agctgaatct gggcaggaga gaggagtacg acgtgctgga taagaggagg 1560 ggacgcgacc ccgagatggg aggcaagcct aggagaaaga acccacagga gggcctgtat 1620 aatgagctgc agaaggacaa gatggccgag gcctactctg agatcggcat gaagggagag 1680 cggcgcaggg gcaagggaca cgatggcctg tatcagggcc tgagcacagc caccaaggac 1740 acctacgatg cactgcacat gcaggccctg ccacctaggt ga 1782 3-705 Sequences 3-705-1 Sequence Number [ID] 705 3-705-2 Molecule Type DNA 3-705-3 Length 1935 3-705-4 Features misc_feature 1..1935 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1935 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-705-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagcccgc 60 cctgacatcc agatgacaca gaccacaagc tccctgagcg cctccctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 ccagatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgccc 240 tctaggttct ctggcagcgg ctccggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgccata cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc ttctcagagc 480 ctgtccgtga catgtaccgt gtctggcgtg agcctgcccg actacggcgt gtcttggatc 540 agacagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcaggctg acaatcatca aggacaactc taagagccag 660 gtgtttctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgtgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgcgccc cgaggcatgc aggcctgcag caggcggcgc cgtgcacacc 900 aggggcctgg acttcgcctg tgatatctcc ctgatcgccg ccctggcagt ggactacgtg 960 atcggcatgg agaacgccat gccctggaat ctgcctgccg atctggcctg gtttaagaga 1020 aacacactga ataagcccgt gatcatgggc cggcacacct gggagagcat cggcagacct 1080 ctgccaggcc ggaagaacat catcctgtcc tctcagcctg gcacagacga tagagtgacc 1140 tgggtgaagt ccgtggacga ggcaatcgca gcatgcggcg atgtgcccga gatcatggtc 1200 atcggcggcg gcagagtgat cgagcagttc ctgcctaagg cccagaagct gtatctgaca 1260 cacatcgacg ccgaggtgga gggcgacacc cactttccag attacgagcc cgacgattgg 1320 gagtccgtgt tctctgagtt tcacgacgcc gatgcccaga attcccactc ttattgtttc 1380 gagatcctgg agagaagaat ctacatctgg gcacctctgg caggaacatg cggcgtgctg 1440 ctgctgtctc tggtcatcac cctgtattgt aagcgcggca ggaagaagct gctgtacatc 1500 ttcaagcagc cttttatgcg cccagtgcag acaacccagg aggaggacgg ctgcagctgt 1560 aggttccctg aggaggagga gggaggatgc gagctgaggg tgaagtttag caggtccgcc 1620 gatgccccag cctataagca gggccagaac cagctgtaca acgagctgaa tctgggcagg 1680 agggaagagt acgacgtgct ggataagagg agaggaaggg accccgagat gggaggcaag 1740 ccaaggagga agaacccaca ggagggcctg tataatgagc tgcagaagga caagatggcc 1800 gaggcctact ccgagatcgg catgaaggga gagaggagac ggggcaaggg acacgatggc 1860 ctgtatcagg gcctgtctac agccaccaag gacacctacg atgcactgca catgcaggcc 1920 ctgcctccaa ggtga 1935

3-706 Sequences 3-706-1 Sequence Number [ID] 706 3-706-2 Molecule Type DNA 3-706-3 Length 1950 11 Aug 2023

3-706-4 Features misc_feature 1..1950 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1950 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-706-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 2023214349

ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggcagcgga ggaatctccc tgatcgccgc cctggcagtg 1500 gaccacgtga tcggcatgga gaacgccatg ccatggaatc tgcccgccga tctggcctgg 1560 ttcaagcgga acaccctgaa taagccagtg atcatgggca gacacacatg ggagtctatc 1620 ggcaggcccc tgcctggacg caagaacatc atcctgagct cccagcccgg caccgacgat 1680 agggtgacat gggtgaagtc cgtggacgag gcaatcgcag catgcggcga tgtgcccgag 1740 atcatggtca tcggcggcgg cagagtgtac gagcagttcc tgcctaaggc ccagaagctg 1800 tatctgaccc acatcgacgc cgaggtggag ggcgacacac actttcctga ttacaagcca 1860 gacgattggg agtccgtgtt ctctgagttt cacgacgccg atgcccagaa ttctcacagc 1920 tattgttttg agatcctgga gcggagatga 1950 3-707 Sequences 3-707-1 Sequence Number [ID] 707 3-707-2 Molecule Type DNA 3-707-3 Length 1797 3-707-4 Features misc_feature 1..1797 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1797 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-707-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggctctgga ggaggagtgc aggtggagac aatcagccca 1500 11 Aug 2023 ggcgacggaa ggacattccc aaagagggga cagacctgcg tggtgcacta cacaggcatg 1560 ctgggcgatg gcaagaaggt ggacagctcc cgggatagaa acaagccctt caagtttatg 1620 ctgggcaagc aggaagtgat caggggatgg gaggagggag tggcacagat gtccgtggga 1680 cagggcgcca agctgaccat ctctcctgac tacgcctatg gagcaacagg acacccagga 1740 atcatcccac ctcacgccac cctggtgttt gatgtggagc tgctggagct ggagtga 1797 3-708 Sequences 3-708-1 Sequence Number [ID] 708 3-708-2 Molecule Type DNA 3-708-3 Length 2034 3-708-4 Features misc_feature 1..2034 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2034 2023214349 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-708-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggcagcgga ggagtgggct ccctgaactg catcgtggcc 1500 gtgagccaga acatgggcat cggcaagaat ggcgacctgc cttggccacc tctgaggaac 1560 gagttcagat actttcagag gatgaccaca accagctccg tggagggcaa gcagaacctg 1620 gtcatcatgg gcaagaagac atggttctct atccccgaga agaaccgccc tctgaagggc 1680 cggatcaatc tggtgctgag cagagagctg aaggagccac cacagggagc acacttcctg 1740 agccggagcc tggacgatgc cctgaagctg accgagcagc ccgagctggc caacaaggtg 1800 gacatggtgt ggatcgtggg cggctctagc gtgatcaagg aggccatgaa tcacccaggc 1860 cacctgaagc tgttcgtgac aagaatcatg caggactttg agtccgatac cttctttccc 1920 gagatcgacc tggagaagta caagctgctg cctgagtatc caggcgtgct gtctgatgtg 1980 caggaggaga agggcatcaa gtacaagttc gaggtgtatg agaagaatga ttga 2034 3-709 Sequences 3-709-1 Sequence Number [ID] 709 3-709-2 Molecule Type DNA 3-709-3 Length 2034 3-709-4 Features misc_feature 1..2034 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2034 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-709-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 11 Aug 2023 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggcagcgga ggagtgggct ccctgaactg catcgtggcc 1500 gtgagccaga acatgggcat cggcaagaat ggcgacctgc cttggccacc tctgaggaac 1560 2023214349 gagttcagat actttcagag gatgaccaca accagctccg tggagggcaa gcagaacctg 1620 gtcatcatgg gcaagaagac atggttctct atccccgaga agaaccgccc tctgaagggc 1680 cggatcaatc tggtgctgag cagagagctg aaggagccac cacagggagc acacttcctg 1740 agccggagcc tggacgatgc cctgaagctg accgagcagc ccgagctggc caacaaggtg 1800 gacatggtgt ggatcgtggg cggctctagc gtgatcaagg agttcatgaa tcacccaggc 1860 cacctgaagc tgttcgtgac aagaatcatg caggactttg agtccgatac cttctttccc 1920 gagatcgacc tggagaagta caagctgctg cctgagtatc caggcgtgct gtctgatgtg 1980 caggaggaga agggcatcaa gtacaagttc gaggtgtatg agaagaatga ttga 2034 3-710 Sequences 3-710-1 Sequence Number [ID] 710 3-710-2 Molecule Type DNA 3-710-3 Length 2034 3-710-4 Features misc_feature 1..2034 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2034 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-710-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggcagcgga ggagtgggct ccctgaactg catcgtggcc 1500 gtgagccaga acatgggcat cggcaagaat ggcgacctgc cttggccacc tctgaggaac 1560 gagttcagat actttaagag gatgaccaca accagctccg tggagggcaa gcagaacctg 1620 gtcatcatgg gcaagaagac atggttctct atccccgaga agaaccgccc tctgaagggc 1680 cggatcaatc tggtgctgag cagagagctg aaggagccac cacagggagc acacttcctg 1740 agccggagcc tggacgatgc cctgaagctg accgagcagc ccgagctggc caacaaggtg 1800 gacatggtgt ggatcgtggg cggctctagc gtgatcaagg aggccatgaa tcacccaggc 1860 cacctgaagc tgttcgtgac aagaatcatg caggactttg agtccgatac cttctttccc 1920 gagatcgacc tggagaagta caagctgctg cctgagtatc caggcgtgct gtctgatgtg 1980 caggaggaga agggcatcaa gtacaagttc gaggtgtatg agaagaatga ttga 2034 3-711 Sequences 3-711-1 Sequence Number [ID] 711 3-711-2 Molecule Type DNA 3-711-3 Length 2034 3-711-4 Features misc_feature 1..2034

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2034 mol_type=other DNA organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-711-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 2023214349

cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggcagcgga ggagtgggct ccctgaactg catcgtggcc 1500 gtgagccaga acatgggcat cggcaagaat ggcgacctgc cttggccacc tctgaggaac 1560 gagttcagat actttttcag gatgaccaca accagctccg tggagggcaa gcagaacctg 1620 gtcatcatgg gcaagaagac atggttctct atccccgaga agttccgccc tctgaagggc 1680 cggatcaatc tggtgctgag cagagagctg aaggagccac cacagggagc acacttcctg 1740 agccggagcc tggacgatgc cctgaagctg accgagcagc ccgagctggc caacaaggtg 1800 gacatggtgt ggatcgtggg cggctctagc gtgatcaagg aggccatgaa tcacccaggc 1860 cacctgaagc tgttcgtgac aagaatcatg caggactttg agtccgatac cttctttccc 1920 gagatcgacc tggagaagta caagctgctg cctgagtatc caggcgtgct gtctgatgtg 1980 caggaggaga agggcatcaa gtacaagttc gaggtgtatg agaagaatga ttga 2034 3-712 Sequences 3-712-1 Sequence Number [ID] 712 3-712-2 Molecule Type DNA 3-712-3 Length 1824 3-712-4 Features misc_feature 1..1824 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1824 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-712-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 ccttctggag gcgtgcaggt ggagacaatc agcccaggcg acggacgcac cttcccaaag 120 aggggacaga catgcgtggt gcactacacc ggcatgctgg aggatggcaa gaaggtggac 180 agctccagag atcggaacaa gccattcaag tttatgctgg gcaagcagga agtgatcaga 240 ggatgggagg agggagtggc acagatgagc gtgggacagc gggccaagct gacaatctcc 300 cctgactatg catacggagc aaccggacac ccaggaatca tcccacctca cgccacactg 360 gtgttcgacg tggagctgct gaagcctgag gagtccagga gagtgcggcg caacaagcgg 420 tctaaggata tccagatgac acagaccaca agctccctgt ccgcctctct gggcgacaga 480 gtgaccatca gctgccgggc ctcccaggat atctctaagt atctgaactg gtaccagcag 540 aagcccgatg gcacagtgaa gctgctgatc tatcacacca gccgcctgca ctccggagtg 600 ccttctaggt tcagcggctc cggctctggc acagactaca gcctgaccat ctccaacctg 660 gagcaggagg atatcgccac ctatttctgc cagcagggca atacactgcc ttacaccttt 720 ggcggcggca caaagctgga gatcaccgga ggaggaggca gcggaggagg aggctccggc 780 ggcggcggct ctgaggtgaa gctgcaggag tccggaccag gcctggtggc acctagccag 840 tccctgtctg tgacatgtac cgtgtccggc gtgtctctgc cagactacgg cgtgtcttgg 900 atcaggcagc cacctaggaa gggcctggag tggctgggcg tgatctgggg cagcgagaca 960 acatactata attctgccct gaagagcaga ctgacaatca tcaaggacaa cagcaagtcc 1020 caggtgttcc tgaagatgaa tagcctgcag acagacgata ccgccatcta ctattgcgcc 1080 aagcactact attacggcgg cagctatgcc atggattact ggggccaggg cacatccgtg 1140 accgtgtcta gcaccacaac cccagcacct cgcccaccaa caccagcacc aaccatcgca 1200 tcccagccac tgtctctgag gcccgaggca tgtaggcctg cagcaggagg cgccgtgcac 1260 accaggggcc tggactttgc ctgcgatatc tatatctggg caccactggc aggaacatgt 1320 ggcgtgctgc tgctgtccct ggtcatcacc ctgtattgca agagaggccg gaagaagctg 1380 ctgtacatct tcaagcagcc cttcatgagg cccgtgcaga caacccagga ggaggacggc 1440 tgcagctgtc ggttcccaga ggaggaggag ggaggatgtg agctgagggt gaagttttct 1500 aggagcgccg atgcaccagc atataagcag ggacagaacc agctgtacaa cgagctgaat 1560 ctgggcagga gagaggagta cgacgtgctg gataagagga ggggaaggga ccccgagatg 1620 ggaggcaagc caaggagaaa gaacccccag gagggcctgt ataatgagct gcagaaggac 1680 aagatggccg aggcctactc cgagatcggc atgaagggag agcggcgcag gggcaaggga 1740 cacgatggcc tgtatcaggg cctgtctaca gccaccaagg acacctacga tgcactgcac 1800 11 Aug 2023 atgcaggccc tgcctccaag gtga 1824 3-713 Sequences 3-713-1 Sequence Number [ID] 713 3-713-2 Molecule Type DNA 3-713-3 Length 1977 3-713-4 Features misc_feature 1..1977 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1977 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 2023214349

3-713-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 ccttctggaa tcagcctgat cgccgccctg gcagtggact acgtgatcgg catggagaac 120 gccatgccct ggaatctgcc tgccgatctg gcctggttca agagaaacac actgaataag 180 cccgtgatca tgggccggca cacctgggag tccatcggca ggcccctgcc tggcaggaag 240 aacatcatcc tgagctccca gcctggcaca gacgatagag tgacctgggt gaagagcgtg 300 gacgaggcaa tcgcagcatg cggcgatgtg cccgagatca tggtcatcgg cggcggcaga 360 gtgatcgagc agttcctgcc taaggcccag aagctgtatc tgacacacat cgacgccgag 420 gtggagggcg acacccactt tccagattac gagcccgacg attgggagtc cgtgttctct 480 gagtttcacg acgccgatgc ccagaacagc cactcctact gcttcgagat cctggagagg 540 agagagtctc ggcgcgtgag gagaaataag agaagcaagg acatccagat gacacagacc 600 acaagctccc tgtccgcctc tctgggcgac agagtgacca tcagctgccg ggcctcccag 660 gatatctcta agtatctgaa ctggtaccag cagaagcccg atggcacagt gaagctgctg 720 atctatcaca ccagccgcct gcactccgga gtgccttcta ggttcagcgg ctccggctct 780 ggcacagact acagcctgac catctccaac ctggagcagg aggatatcgc cacctatttc 840 tgccagcagg gcaatacact gccttacacc tttggcggcg gcacaaagct ggagatcacc 900 ggaggaggag gcagcggagg aggaggctcc ggcggcggcg gctctgaggt gaagctgcag 960 gagtccggac caggcctggt ggcacctagc cagtccctgt ctgtgacatg taccgtgtcc 1020 ggcgtgtctc tgccagacta cggcgtgtct tggatcaggc agccacctag gaagggcctg 1080 gagtggctgg gcgtgatctg gggcagcgag acaacatact ataattctgc cctgaagagc 1140 agactgacaa tcatcaagga caacagcaag tcccaggtgt tcctgaagat gaatagcctg 1200 cagacagacg ataccgccat ctactattgc gccaagcact actattacgg cggcagctat 1260 gccatggatt actggggcca gggcacatcc gtgaccgtgt ctagcaccac aaccccagca 1320 cctcgcccac caacaccagc accaaccatc gcatcccagc cactgtctct gaggcccgag 1380 gcatgtaggc ctgcagcagg aggcgccgtg cacaccaggg gcctggactt tgcctgcgat 1440 atctatatct gggcaccact ggcaggaaca tgtggcgtgc tgctgctgtc cctggtcatc 1500 accctgtatt gcaagagagg ccggaagaag ctgctgtaca tcttcaagca gcccttcatg 1560 aggcccgtgc agacaaccca ggaggaggac ggctgcagct gtcggttccc agaggaggag 1620 gagggaggat gtgagctgag ggtgaagttt tctaggagcg ccgatgcacc agcatataag 1680 cagggacaga accagctgta caacgagctg aatctgggca ggagagagga gtacgacgtg 1740 ctggataaga ggaggggaag ggaccccgag atgggaggca agccaaggag aaagaacccc 1800 caggagggcc tgtataatga gctgcagaag gacaagatgg ccgaggccta ctccgagatc 1860 ggcatgaagg gagagcggcg caggggcaag ggacacgatg gcctgtatca gggcctgtct 1920 acagccacca aggacaccta cgatgcactg cacatgcagg ccctgcctcc aaggtga 1977 3-714 Sequences 3-714-1 Sequence Number [ID] 714 3-714-2 Molecule Type DNA 3-714-3 Length 2061 3-714-4 Features misc_feature 1..2061 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2061 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-714-5 Residues atggcactgc cagtgaccgc cctgctgctg cctctggccc tgctgctgca cgcagccaga 60 ccaagcggag tgggctccct gaactgcatc gtggccgtga gccagaacat gggcatcggc 120 aagaatggcg acctgccatg gccacctctg aggaacgagt tcaggtactt tcagagaatg 180 accacaacca gctccgtgga gggcaagcag aacctggtca tcatgggcaa gaagacctgg 240 ttcagcatcc ccgagaagaa caggcctctg aagggcagaa tcaatctggt gctgtccagg 300 gagctgaagg agccaccaca gggagcccac tttctgtctc gcagcctgga cgatgccctg 360 aagctgacag agcagcccga gctggccaac aaggtggata tggtgtggat cgtgggcggc 420 tctagcgtga tcaaggagtt catgaatcac cccggccacc tgaagctgtt cgtgaccagg 480 atcatgcagg actttgagtc cgatacattc tttcctgaga tcgacctgga gaagtataag 540 ctgctgccag agtaccccgg cgtgctgagc gatgtgcagg aggagaaggg catcaagtat 600 aagtttgagg tgtacgagaa gaacgacgag tctaggagag tgcggcgcaa taagagaagc 660 aaggacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 720 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 780 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 840 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 900 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 960 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 1020 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 1080 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 1140 11 Aug 2023 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 1200 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 1260 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 1320 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 1380 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 1440 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 1500 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 1560 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1620 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1680 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1740 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1800 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1860 2023214349 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1920 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1980 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 2040 caggccctgc ctccaaggtg a 2061 3-715 Sequences 3-715-1 Sequence Number [ID] 715 3-715-2 Molecule Type DNA 3-715-3 Length 2061 3-715-4 Features misc_feature 1..2061 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2061 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-715-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 ccaagcggag tgggctccct gaactgcatc gtggccgtga gccagaacat gggcatcggc 120 aagaatggcg acctgccatg gccacctctg aggaacgagt tcaggtactt taagagaatg 180 accacaacca gctccgtgga gggcaagcag aacctggtca tcatgggcaa gaagacctgg 240 ttcagcatcc ccgagaagaa caggcctctg aagggcagaa tcaatctggt gctgtccagg 300 gagctgaagg agccaccaca gggagcccac tttctgtctc gcagcctgga cgatgccctg 360 aagctgacag agcagcccga gctggccaac aaggtggata tggtgtggat cgtgggcggc 420 tctagcgtga tcaaggaggc catgaatcac cccggccacc tgaagctgtt cgtgaccagg 480 atcatgcagg actttgagtc cgatacattc tttcctgaga tcgacctgga gaagtataag 540 ctgctgccag agtaccccgg cgtgctgagc gatgtgcagg aggagaaggg catcaagtat 600 aagttcgagg tgtacgagaa gaacgacgag tctaggagag tgcggcgcaa taagagaagc 660 aaggacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 720 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 780 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 840 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 900 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 960 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 1020 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 1080 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 1140 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 1200 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 1260 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 1320 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 1380 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 1440 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 1500 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 1560 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1620 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1680 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1740 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1800 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1860 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1920 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1980 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 2040 caggccctgc ctccaaggtg a 2061 3-716 Sequences 3-716-1 Sequence Number [ID] 716 3-716-2 Molecule Type DNA 3-716-3 Length 603 3-716-4 Features misc_feature 1..603 Location/Qualifiers note=Description of Artificial Sequence: Synthetic promoter source 1..603 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-716-5 Residues aagcttggga gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca 60 acgacccccg cccattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga 120 ctttccattg acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc 180 11 Aug 2023 aagtgtatca tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct 240 ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat 300 tagtcatcgc tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc 360 ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt 420 ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa 480 tgggcggtag gcgtgtacgg tgggaggtct atataagcag agctcgttta gtgaaccgtc 540 agatcgcctg gagacgccat ccacgctgtt ttgacctcca tagaagacac cgactctact 600 aga 603 3-717 Sequences 3-717-1 Sequence Number [ID] 717 3-717-2 Molecule Type DNA 3-717-3 Length 1339 2023214349

3-717-4 Features misc_feature 1..1339 Location/Qualifiers note=Description of Artificial Sequence: Synthetic promoter source 1..1339 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-717-5 Residues cgatagtaat tcatacaaaa ggactcgccc ctgccttggg gaatcccagg gaccgtcgtt 60 aaactcccac taacgtagaa cccagagatc gctgcgttcc cgccccctca cccgcccgct 120 ctcgtcatca ctgaggtgga gaagagcatg cgtgaggctc cggtgcccgt cagtgggcag 180 agcgcacatc gcccacagtc cccgagaagt tggggggagg ggtcggcaat tgaaccggtg 240 cctagagaag gtggcgcggg gtaaactggg aaagtgatgt cgtgtactgg ctccgccttt 300 ttcccgaggg tgggggagaa ccgtatataa gtgcagtagt cgccgtgaac gttctttttc 360 gcaacgggtt tgccgccaga acacaggtaa gtgccgtgtg tggttcccgc gggcctggcc 420 tctttacggg ttatggccct tgcgtgcctt gaattacttc cacgcccctg gctgcagtac 480 gtgattcttg atcccgagct tcgggttgga agtgggtggg agagttcgag gccttgcgct 540 taaggagccc cttcgcctcg tgcttgagtt gaggcctggc ttgggcgctg gggccgccgc 600 gtgcgaatct ggtggcacct tcgcgcctgt ctcgctgctt tcgataagtc tctagccatt 660 taaaattttt gatgacctgc tgcgacgctt tttttctggc aagatagtct tgtaaatgcg 720 ggccaagatc tgcacactgg tatttcggtt tttggggccg cgggcggcga cggggcccgt 780 gcgtcccagc gcacatgttc ggcgaggcgg ggcctgcgag cgcggccacc gagaatcgga 840 cgggggtagt ctcaagctgg ccggcctgct ctggtgcctg gcctcgcgcc gccgtgtatc 900 gccccgccct gggcggcaag gctggcccgg tcggcaccag ttgcgtgagc ggaaagatgg 960 ccgcttcccg gccctgctgc agggagctca aaatggagga cgcggcgctc gggagagcgg 1020 gcgggtgagt cacccacaca aaggaaaagg gcctttccgt cctcagccgt cgcttcatgt 1080 gactccacgg agtaccgggc gccgtccagg cacctcgatt agttctcgag cttttggagt 1140 acgtcgtctt taggttgggg ggaggggttt tatgcgatgg agtttcccca cactgagtgg 1200 gtggagactg aagttaggcc agcttggcac ttgatgtaat tctccttgga atttgccctt 1260 tttgagtttg gatcttggtt cattctcaag cctcagacag tggttcaaag tttttttctt 1320 ccatttcagg tgtcgtgag 1339 3-718 Sequences 3-718-1 Sequence Number [ID] 718 3-718-2 Molecule Type DNA 3-718-3 Length 399 3-718-4 Features misc_feature 1..399 Location/Qualifiers note=Description of Artificial Sequence: Synthetic promoter source 1..399 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-718-5 Residues ccggtaggcg ccaaccggct ccgttctttg gtggcccctt cgcgccacct tctactcctc 60 ccctagtcag gaagttcccc cccgccccgc agctcgcgtc gtgcaggacg tgacaaatgg 120 aagtagcacg tctcactagt ctcgtgcaga tggacagcac cgctgagcaa tggaagcggg 180 taggcctttg gggcagcggc caatagcagc tttgctcctt cgctttctgg gctcagaggc 240 tgggaagggg tgggtccggg ggcgggctca ggggcgggct caggggcggg gcgggcgccc 300 gaaggtcctc cggaggcccg gcattctgca cgcttcaaaa gcgcacgtct gccgcgctgt 360 tctcctcttc ctcatctccg ggcctttcga cctgcagcc 399 3-719 Sequences 3-719-1 Sequence Number [ID] 719 3-719-2 Molecule Type AA 3-719-3 Length 22 3-719-4 Features source 1..22 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-719-5 Residues MCHQQLVISW FSLVFLASPL VA 22

3-720 Sequences 3-720-1 Sequence Number [ID] 720 3-720-2 Molecule Type AA 3-720-3 Length 15 11 Aug 2023

3-720-4 Features REGION 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-720-5 Residues GGGGSGGGGS GGGGS 15 3-721 Sequences 3-721-1 Sequence Number [ID] 721 3-721-2 Molecule Type AA 3-721-3 Length 9 3-721-4 Features source 1..9 2023214349

Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-721-5 Residues SARNRQKRS 9 3-722 Sequences 3-722-1 Sequence Number [ID] 722 3-722-2 Molecule Type AA 3-722-3 Length 8 3-722-4 Features source 1..8 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-722-5 Residues ARNRQKRS 8 3-723 Sequences 3-723-1 Sequence Number [ID] 723 3-723-2 Molecule Type AA 3-723-3 Length 306 3-723-4 Features REGION 1..306 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..306 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-723-5 Residues IWELKKDVYV VELDWYPDAP GEMVVLTCDT PEEDGITWTL DQSSEVLGSG KTLTIQVKEF 60 GDAGQYTCHK GGEVLSHSLL LLHKKEDGIW STDILKDQKE PKNKTFLRCE AKNYSGRFTC 120 WWLTTISTDL TFSVKSSRGS SDPQGVTCGA ATLSAERVRG DNKEYEYSVE CQEDSACPAA 180 EESLPIEVMV DAVHKLKYEN YTSSFFIRDI IKPDPPKNLQ LKPLKNSRQV EVSWEYPDTW 240 STPHSYFSLT FCVQVQGKSK REKKDRVFTD KTSATVICRK NASISVRAQD RYYSSSWSEW 300 ASVPCS 306 3-724 Sequences 3-724-1 Sequence Number [ID] 724 3-724-2 Molecule Type AA 3-724-3 Length 197 3-724-4 Features REGION 1..197 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..197 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-724-5 Residues RNLPVATPDP GMFPCLHHSQ NLLRAVSNML QKARQTLEFY PCTSEEIDHE DITKDKTSTV 60 EACLPLELTK NESCLNSRET SFITNGSCLA SRKTSFMMAL CLSSIYEDLK MYQVEFKTMN 120 AKLLMDPKRQ IFLDQNMLAV IDELMQALNF NSETVPQKSS LEEPDFYKTK IKLCILLHAF 180 RIRAVTIDRV MSYLNAS 197 3-725 Sequences 3-725-1 Sequence Number [ID] 725 3-725-2 Molecule Type AA 3-725-3 Length 389 3-725-4 Features REGION 1..389 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..389 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-725-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSGSGATNFS LLKQAGDVEE NPGPLSKGEE DNMAIIKEFM RFKVHMEGSV 180 NGHEFEIEGE GEGRPYEGTQ TAKLKVTKGG PLPFAWDILS PQFMYGSKAY VKHPADIPDY 240 LKLSFPEGFK WERVMNFEDG GVVTVTQDSS LQDGEFIYKV KLRGTNFPSD GPVMQKKTMG 300 11 Aug 2023

WEASSERMYP EDGALKGEIK QRLKLKDGGH YDAEVKTTYK AKKPVQLPGA YNVNIKLDIT 360 SHNEDYTIVE QYERAEGRHS TGGMDELYK 389 3-726 Sequences 3-726-1 Sequence Number [ID] 726 3-726-2 Molecule Type AA 3-726-3 Length 577 3-726-4 Features REGION 1..577 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..577 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-726-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSGSVGSLNC IVAVSQNMGI GKNGDLPWPP LRNEFRYFQR MTTTSSVEGK 180 QNLVIMGKKT WFSIPEKNRP LKGRINLVLS RELKEPPQGA HFLSRSLDDA LKLTEQPELA 240 NKVDMVWIVG GSSVIKEAMN HPGHLKLFVT RIMQDFESDT FFPEIDLEKY KLLPEYPGVL 300 SDVQEEKGIK YKFEVYEKND GSGATNFSLL KQAGDVEENP GPLSKGEEDN MAIIKEFMRF 360 KVHMEGSVNG HEFEIEGEGE GRPYEGTQTA KLKVTKGGPL PFAWDILSPQ FMYGSKAYVK 420 HPADIPDYLK LSFPEGFKWE RVMNFEDGGV VTVTQDSSLQ DGEFIYKVKL RGTNFPSDGP 480 VMQKKTMGWE ASSERMYPED GALKGEIKQR LKLKDGGHYD AEVKTTYKAK KPVQLPGAYN 540 VNIKLDITSH NEDYTIVEQY ERAEGRHSTG GMDELYK 577 3-727 Sequences 3-727-1 Sequence Number [ID] 727 3-727-2 Molecule Type AA 3-727-3 Length 652 3-727-4 Features REGION 1..652 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..652 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-727-5 Residues MCHQQLVISW FSLVFLASPL VAGVQVETIS PGDGRTFPKR GQTCVVHYTG MLEDGKKVDS 60 SRDRNKPFKF MLGKQEVIRG WEEGVAQMSV GQRAKLTISP DYAYGATGHP GIIPPHATLV 120 FDVELLKPEG GSGGIWELKK DVYVVELDWY PDAPGEMVVL TCDTPEEDGI TWTLDQSSEV 180 LGSGKTLTIQ VKEFGDAGQY TCHKGGEVLS HSLLLLHKKE DGIWSTDILK DQKEPKNKTF 240 LRCEAKNYSG RFTCWWLTTI STDLTFSVKS SRGSSDPQGV TCGAATLSAE RVRGDNKEYE 300 YSVECQEDSA CPAAEESLPI EVMVDAVHKL KYENYTSSFF IRDIIKPDPP KNLQLKPLKN 360 SRQVEVSWEY PDTWSTPHSY FSLTFCVQVQ GKSKREKKDR VFTDKTSATV ICRKNASISV 420 RAQDRYYSSS WSEWASVPCS GGGGSGGGGS GGGGSRNLPV ATPDPGMFPC LHHSQNLLRA 480 VSNMLQKARQ TLEFYPCTSE EIDHEDITKD KTSTVEACLP LELTKNESCL NSRETSFITN 540 GSCLASRKTS FMMALCLSSI YEDLKMYQVE FKTMNAKLLM DPKRQIFLDQ NMLAVIDELM 600 QALNFNSETV PQKSSLEEPD FYKTKIKLCI LLHAFRIRAV TIDRVMSYLN AS 652 3-728 Sequences 3-728-1 Sequence Number [ID] 728 3-728-2 Molecule Type AA 3-728-3 Length 653 3-728-4 Features REGION 1..653 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..653 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-728-5 Residues MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKVDSS RDRNKPFKFM LGKQEVIRGW 60 EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPHATLVF DVELLKPEGG SGGMCHQQLV 120 ISWFSLVFLA SPLVAIWELK KDVYVVELDW YPDAPGEMVV LTCDTPEEDG ITWTLDQSSE 180 VLGSGKTLTI QVKEFGDAGQ YTCHKGGEVL SHSLLLLHKK EDGIWSTDIL KDQKEPKNKT 240 FLRCEAKNYS GRFTCWWLTT ISTDLTFSVK SSRGSSDPQG VTCGAATLSA ERVRGDNKEY 300 EYSVECQEDS ACPAAEESLP IEVMVDAVHK LKYENYTSSF FIRDIIKPDP PKNLQLKPLK 360 NSRQVEVSWE YPDTWSTPHS YFSLTFCVQV QGKSKREKKD RVFTDKTSAT VICRKNASIS 420 VRAQDRYYSS SWSEWASVPC SGGGGSGGGG SGGGGSRNLP VATPDPGMFP CLHHSQNLLR 480 AVSNMLQKAR QTLEFYPCTS EEIDHEDITK DKTSTVEACL PLELTKNESC LNSRETSFIT 540 NGSCLASRKT SFMMALCLSS IYEDLKMYQV EFKTMNAKLL MDPKRQIFLD QNMLAVIDEL 600 MQALNFNSET VPQKSSLEEP DFYKTKIKLC ILLHAFRIRA VTIDRVMSYL NAS 653 3-729 Sequences 3-729-1 Sequence Number [ID] 729 3-729-2 Molecule Type AA

3-729-3 Length 656 3-729-4 Features REGION 1..656 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..656 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-729-5 Residues MCHQQLVISW FSLVFLASPL VAGVQVETIS PGDGRTFPKR GQTCVVHYTG MLEDGKKVDS 60 SRDRNKPFKF MLGKQEVIRG WEEGVAQMSV GQRAKLTISP DYAYGATGHP GIIPPHATLV 120 FDVELLKPES ARNRQKRSIW ELKKDVYVVE LDWYPDAPGE MVVLTCDTPE EDGITWTLDQ 180 SSEVLGSGKT LTIQVKEFGD AGQYTCHKGG EVLSHSLLLL HKKEDGIWST DILKDQKEPK 240 NKTFLRCEAK NYSGRFTCWW LTTISTDLTF SVKSSRGSSD PQGVTCGAAT LSAERVRGDN 300 KEYEYSVECQ EDSACPAAEE SLPIEVMVDA VHKLKYENYT SSFFIRDIIK PDPPKNLQLK 360 PLKNSRQVEV SWEYPDTWST PHSYFSLTFC VQVQGKSKRE KKDRVFTDKT SATVICRKNA 420 SISVRAQDRY YSSSWSEWAS VPCSGGGGSG GGGSGGGGSR NLPVATPDPG MFPCLHHSQN 480 LLRAVSNMLQ KARQTLEFYP CTSEEIDHED ITKDKTSTVE ACLPLELTKN ESCLNSRETS 540 FITNGSCLAS RKTSFMMALC LSSIYEDLKM YQVEFKTMNA KLLMDPKRQI FLDQNMLAVI 600 2023214349

DELMQALNFN SETVPQKSSL EEPDFYKTKI KLCILLHAFR IRAVTIDRVM SYLNAS 656 3-730 Sequences 3-730-1 Sequence Number [ID] 730 3-730-2 Molecule Type AA 3-730-3 Length 655 3-730-4 Features REGION 1..655 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..655 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-730-5 Residues MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW 60 TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ 120 KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV 180 RGDNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN 240 LQLKPLKNSR QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC 300 RKNASISVRA QDRYYSSSWS EWASVPCSGG GGSGGGGSGG GGSRNLPVAT PDPGMFPCLH 360 HSQNLLRAVS NMLQKARQTL EFYPCTSEEI DHEDITKDKT STVEACLPLE LTKNESCLNS 420 RETSFITNGS CLASRKTSFM MALCLSSIYE DLKMYQVEFK TMNAKLLMDP KRQIFLDQNM 480 LAVIDELMQA LNFNSETVPQ KSSLEEPDFY KTKIKLCILL HAFRIRAVTI DRVMSYLNAS 540 ARNRQKRSGV QVETISPGDG RTFPKRGQTC VVHYTGMLGD GKKVDSSRDR NKPFKFMLGK 600 QEVIRGWEEG VAQMSVGQGA KLTISPDYAY GATGHPGIIP PHATLVFDVE LLELE 655 3-731 Sequences 3-731-1 Sequence Number [ID] 731 3-731-2 Molecule Type AA 3-731-3 Length 651 3-731-4 Features REGION 1..651 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..651 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-731-5 Residues MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW 60 TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ 120 KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV 180 RGDNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN 240 LQLKPLKNSR QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC 300 RKNASISVRA QDRYYSSSWS EWASVPCSGG GGSGGGGSGG GGSRNLPVAT PDPGMFPCLH 360 HSQNLLRAVS NMLQKARQTL EFYPCTSEEI DHEDITKDKT STVEACLPLE LTKNESCLNS 420 RETSFITNGS CLASRKTSFM MALCLSSIYE DLKMYQVEFK TMNAKLLMDP KRQIFLDQNM 480 LAVIDELMQA LNFNSETVPQ KSSLEEPDFY KTKIKLCILL HAFRIRAVTI DRVMSYLNAS 540 GGSGGVQVET ISPGDGRTFP KRGQTCVVHY TGMLGDGKKV DSSRDRNKPF KFMLGKQEVI 600 RGWEEGVAQM SVGQGAKLTI SPDYAYGATG HPGIIPPHAT LVFDVELLEL E 651 3-732 Sequences 3-732-1 Sequence Number [ID] 732 3-732-2 Molecule Type AA 3-732-3 Length 540 3-732-4 Features REGION 1..540 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..540 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-732-5 Residues MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW 60

TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ 120 KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV 180 RGDNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN 240 LQLKPLKNSR QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC 300 RKNASISVRA QDRYYSSSWS EWASVPCSGG GGSGGGGSGG GGSRNLPVAT PDPGMFPCLH 360 11 Aug 2023

HSQNLLRAVS NMLQKARQTL EFYPCTSEEI DHEDITKDKT STVEACLPLE LTKNESCLNS 420 RETSFITNGS CLASRKTSFM MALCLSSIYE DLKMYQVEFK TMNAKLLMDP KRQIFLDQNM 480 LAVIDELMQA LNFNSETVPQ KSSLEEPDFY KTKIKLCILL HAFRIRAVTI DRVMSYLNAS 540 3-733 Sequences 3-733-1 Sequence Number [ID] 733 3-733-2 Molecule Type AA 3-733-3 Length 710 3-733-4 Features REGION 1..710 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..710 mol_type=protein 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-733-5 Residues MCHQQLVISW FSLVFLASPL VAISLIAALA VDYVIGMENA MPWNLPADLA WFKRNTLNKP 60 VIMGRHTWES IGRPLPGRKN IILSSQPGTD DRVTWVKSVD EAIAACGDVP EIMVIGGGRV 120 IEQFLPKAQK LYLTHIDAEV EGDTHFPDYE PDDWESVFSE FHDADAQNSH SYCFEILERR 180 ESRRVRRNKR SKIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW TLDQSSEVLG 240 SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ KEPKNKTFLR 300 CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV RGDNKEYEYS 360 VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN LQLKPLKNSR 420 QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC RKNASISVRA 480 QDRYYSSSWS EWASVPCSGG GGSGGGGSGG GGSRNLPVAT PDPGMFPCLH HSQNLLRAVS 540 NMLQKARQTL EFYPCTSEEI DHEDITKDKT STVEACLPLE LTKNESCLNS RETSFITNGS 600 CLASRKTSFM MALCLSSIYE DLKMYQVEFK TMNAKLLMDP KRQIFLDQNM LAVIDELMQA 660 LNFNSETVPQ KSSLEEPDFY KTKIKLCILL HAFRIRAVTI DRVMSYLNAS 710 3-734 Sequences 3-734-1 Sequence Number [ID] 734 3-734-2 Molecule Type AA 3-734-3 Length 738 3-734-4 Features REGION 1..738 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..738 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-734-5 Residues MCHQQLVISW FSLVFLASPL VAVGSLNCIV AVSQNMGIGK NGDLPWPPLR NEFRYFFRMT 60 TTSSVEGKQN LVIMGKKTWF SIPEKNRPLK GRINLVLSRE LKEPPQGAHF LSRSLDDALK 120 LTEQPELANK VDMVWIVGGS SVIKEFMNHP GHLKLFVTRI MQDFESDTFF PEIDLEKYKL 180 LPEYPGVLSD VQEEKGIKYK FEVYEKNDES RRVRRNKRSK IWELKKDVYV VELDWYPDAP 240 GEMVVLTCDT PEEDGITWTL DQSSEVLGSG KTLTIQVKEF GDAGQYTCHK GGEVLSHSLL 300 LLHKKEDGIW STDILKDQKE PKNKTFLRCE AKNYSGRFTC WWLTTISTDL TFSVKSSRGS 360 SDPQGVTCGA ATLSAERVRG DNKEYEYSVE CQEDSACPAA EESLPIEVMV DAVHKLKYEN 420 YTSSFFIRDI IKPDPPKNLQ LKPLKNSRQV EVSWEYPDTW STPHSYFSLT FCVQVQGKSK 480 REKKDRVFTD KTSATVICRK NASISVRAQD RYYSSSWSEW ASVPCSGGGG SGGGGSGGGG 540 SRNLPVATPD PGMFPCLHHS QNLLRAVSNM LQKARQTLEF YPCTSEEIDH EDITKDKTST 600 VEACLPLELT KNESCLNSRE TSFITNGSCL ASRKTSFMMA LCLSSIYEDL KMYQVEFKTM 660 NAKLLMDPKR QIFLDQNMLA VIDELMQALN FNSETVPQKS SLEEPDFYKT KIKLCILLHA 720 FRIRAVTIDR VMSYLNAS 738 3-735 Sequences 3-735-1 Sequence Number [ID] 735 3-735-2 Molecule Type AA 3-735-3 Length 659 3-735-4 Features REGION 1..659 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..659 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-735-5 Residues MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW 60 TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ 120 KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV 180 RGDNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN 240 LQLKPLKNSR QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC 300 RKNASISVRA QDRYYSSSWS EWASVPCSGG GGSGGGGSGG GGSRNLPVAT PDPGMFPCLH 360 HSQNLLRAVS NMLQKARQTL EFYPCTSEEI DHEDITKDKT STVEACLPLE LTKNESCLNS 420 RETSFITNGS CLASRKTSFM MALCLSSIYE DLKMYQVEFK TMNAKLLMDP KRQIFLDQNM 480 LAVIDELMQA LNFNSETVPQ KSSLEEPDFY KTKIKLCILL HAFRIRAVTI DRVMSYLNAS 540

ESRRVRRNKR SKGVQVETIS PGDGRTFPKR GQTCVVHYTG MLGDGKKVDS SRDRNKPFKF 600 MLGKQEVIRG WEEGVAQMSV GQGAKLTISP DYAYGATGHP GIIPPHATLV FDVELLELE 659 3-736 Sequences 3-736-1 Sequence Number [ID] 736 3-736-2 Molecule Type DNA 11 Aug 2023

3-736-3 Length 66 3-736-4 Features source 1..66 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-736-5 Residues atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 60 gtggcc 66 3-737 Sequences 3-737-1 Sequence Number [ID] 737 3-737-2 Molecule Type DNA 3-737-3 Length 66 2023214349

3-737-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-737-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc atcccctctg 60 gtggca 66 3-738 Sequences 3-738-1 Sequence Number [ID] 738 3-738-2 Molecule Type DNA 3-738-3 Length 66 3-738-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-738-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc cagccctctg 60 gtggcc 66 3-739 Sequences 3-739-1 Sequence Number [ID] 739 3-739-2 Molecule Type DNA 3-739-3 Length 66 3-739-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-739-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc aagccctctg 60 gtggca 66 3-740 Sequences 3-740-1 Sequence Number [ID] 740 3-740-2 Molecule Type DNA 3-740-3 Length 66 3-740-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-740-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc atccccactg 60 gtggca 66 3-741 Sequences 3-741-1 Sequence Number [ID] 741 3-741-2 Molecule Type DNA 3-741-3 Length 66 3-741-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-741-5 Residues atgtgccacc aacagctcgt gatcagctgg ttctccctgg tgttcctggc tagccccctg 60 gtggcc 66 3-742 Sequences 3-742-1 Sequence Number [ID] 742 11 Aug 2023

3-742-2 Molecule Type DNA 3-742-3 Length 66 3-742-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-742-5 Residues atgtgccacc agcagctggt catctcttgg ttcagcctgg tgtttctggc ctcccccctg 60 gtggcc 66 3-743 Sequences 2023214349

3-743-1 Sequence Number [ID] 743 3-743-2 Molecule Type DNA 3-743-3 Length 66 3-743-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-743-5 Residues atgtgccacc agcagctggt catctcctgg ttctctctgg tgtttctggc atctcctctg 60 gtggca 66 3-744 Sequences 3-744-1 Sequence Number [ID] 744 3-744-2 Molecule Type DNA 3-744-3 Length 66 3-744-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-744-5 Residues atgtgccacc agcagctggt catctcttgg ttcagcctgg tgtttctggc atccccactg 60 gtggca 66 3-745 Sequences 3-745-1 Sequence Number [ID] 745 3-745-2 Molecule Type AA 3-745-3 Length 19 3-745-4 Features REGION 1..19 Location/Qualifiers note=Description of Artificial Sequence: Synthetic spacer source 1..19 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-745-5 Residues ATNFSLLKQA GDVEENPGP 19 3-746 Sequences 3-746-1 Sequence Number [ID] 746 3-746-2 Molecule Type DNA 3-746-3 Length 57 3-746-4 Features misc_feature 1..57 Location/Qualifiers note=Description of Artificial Sequence: Synthetic spacer source 1..57 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-746-5 Residues gcaaccaatt ttagtctact taaacaagca ggtgatgtag aagaaaatcc aggtcca 57 3-747 Sequences 3-747-1 Sequence Number [ID] 747 3-747-2 Molecule Type AA 3-747-3 Length 306 3-747-4 Features REGION 1..306 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..306 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-747-5 Residues IWELKKDVYV VELDWYPDAP GEMVVLTCDT PEEDGITWTL DQSSEVLGSG KTLTIQVKEF 60 GDAGQYTCHK GGEVLSHSLL LLHKKEDGIW STDILKDQKE PKNKTFLRCE AKNYSGRFTC 120 WWLTTISTDL TFSVKSSRGS SDPQGVTCGA ATLSAERVRG DNKEYEYSVE CQEDSACPAA 180 11 Aug 2023

EESLPIEVMV DAVHKLKYEN YTSSFFIRDI IKPDPPNNLQ LKPLKNSRQV EVSWEYPDTW 240 STPHSYFSLT FCVQVQGKSK REKKDRVFTD KTSATVICRK NASISVRAQD RYYSSSWSEW 300 ASVPCS 306 3-748 Sequences 3-748-1 Sequence Number [ID] 748 3-748-2 Molecule Type DNA 3-748-3 Length 918 3-748-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-748-5 Residues atatgggaac tgaagaaaga tgtttatgtc gtagaattgg attggtatcc ggatgcccct 60 ggagaaatgg tggtcctcac ctgtgacacc cctgaagaag atggtatcac ctggaccttg 120 gaccagagca gtgaggtctt aggctctggc aaaaccctga ccatccaagt caaagagttt 180 ggagatgctg gccagtacac ctgtcacaaa ggaggcgagg ttctaagcca ttcgctcctg 240 ctgcttcaca aaaaggaaga tggaatttgg tccactgata ttttaaagga ccagaaagaa 300 cccaaaaata agacctttct aagatgcgag gccaagaatt attctggacg tttcacctgc 360 tggtggctga cgacaatcag tactgatttg acattcagtg tcaaaagcag cagaggctct 420 tctgaccccc aaggggtgac gtgcggagct gctacactct ctgcagagag agtcagaggg 480 gacaacaagg agtatgagta ctcagtggag tgccaggagg acagtgcctg cccagctgct 540 gaggagagtc tgcccattga ggtcatggtg gatgccgttc acaagctcaa gtatgaaaac 600 tacaccagca gcttcttcat cagggacatc atcaaacctg acccacccaa caacttgcag 660 ctgaagccat taaagaattc tcggcaggtg gaggtcagct gggagtaccc tgacacctgg 720 agtactccac attcctactt ctccctgaca ttctgcgttc aggtccaggg caagagcaag 780 agagaaaaga aagatagagt cttcaccgac aagacctcag ccacggtcat ctgccgcaaa 840 aatgccagca ttagcgtgcg ggcccaggac cgctactata gctcatcttg gagcgaatgg 900 gcatctgtgc cctgcagt 918 3-749 Sequences 3-749-1 Sequence Number [ID] 749 3-749-2 Molecule Type DNA 3-749-3 Length 432 3-749-4 Features misc_feature 1..432 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..432 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-749-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagctaccca 60 tacgatgttc cagattacgc taactgggtg aacgtgatct ccgacctgaa aaagatcgag 120 gatttgatcc agagcatgca cattgacgcc accctgtata ccgagtccga cgtgcacccg 180 agttgcaagg tgactgccat gaagtgcttc ctgctggagc tgcaagtgat cagcctggag 240 agcggcgacg ccagcatcca cgacaccgtg gaaaacctta tcattctggc caacaatagc 300 ctgagcagca acggcaacgt gaccgaaagc ggatgtaagg aatgcgagga actggaagag 360 aagaatatca aagaattcct gcaaagcttc gtgcacatcg tgcagatgtt catcaacact 420 tctggatcct ga 432 3-750 Sequences 3-750-1 Sequence Number [ID] 750 3-750-2 Molecule Type DNA 3-750-3 Length 27 3-750-4 Features source 1..27 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-750-5 Residues agcgccagga atcgccagaa gcggtcc 27 3-751 Sequences 3-751-1 Sequence Number [ID] 751 3-751-2 Molecule Type DNA 3-751-3 Length 24 3-751-4 Features source 1..24 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-751-5 Residues gcccggaata gacagaagag atct 24 3-752 Sequences

3-752-1 Sequence Number [ID] 752 3-752-2 Molecule Type DNA 3-752-3 Length 921 3-752-4 Features misc_feature 1..921 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..921 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-752-5 Residues atatgggaac tgaagaaaga tgtttatgtc gtagaattgg attggtatcc ggatgcccct 60 ggagaaatgg tggtcctcac ctgtgacacc cctgaagaag atggtatcac ctggaccttg 120 gaccagagca gtgaggtctt aggctctggc aaaaccctga ccatccaagt caaagagttt 180 ggagatgctg gccagtacac ctgtcacaaa ggaggcgagg ttctaagcca ttcgctcctg 240 ctgcttcaca aaaaggaaga tggaatttgg tccactgata ttttaaagga ccagaaagaa 300 cccaaaaata agacctttct aagatgcgag gccaagaatt attctggacg tttcacctgc 360 tggtggctga cgacaatcag tactgatttg acattcagtg tcaaaagcag cagaggctct 420 2023214349

tctgaccccc aaggggtgac gtgcggagct gctacactct ctgcagagag agtcagaggg 480 gacaacaagg agtatgagta ctcagtggag tgccaggagg acagtgcctg cccagctgct 540 gaggagagtc tgcccattga ggtcatggtg gatgccgttc acaagctcaa gtatgaaaac 600 tacaccagca gcttcttcat cagggacatc atcaaacctg acccacccaa gaacttgcag 660 ctgaagccat taaagaattc tcggcaggtg gaggtcagct gggagtaccc tgacacctgg 720 agtactccac attcctactt ctccctgaca ttctgcgttc aggtccaggg caagagcaag 780 agagaaaaga aagatagagt cttcacggac aagacctcag ccacggtcat ctgccgcaaa 840 aatgccagca ttagcgtgcg ggcccaggac cgctactata gctcatcttg gagcgaatgg 900 gcatctgtgc cctgcagtta g 921 3-753 Sequences 3-753-1 Sequence Number [ID] 753 3-753-2 Molecule Type DNA 3-753-3 Length 918 3-753-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-753-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca cctgaggagg atggcatcac ctggacactg 120 gatcagtcta gcgaggtgct gggcagcggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatttgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gcggtgcgag gccaagaatt atagcggccg gttcacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtcctc taggggcagc 420 tccgaccccc agggcgtgac atgcggagca gccaccctgt ccgccgagag ggtgcgcggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tccagcagca 540 gaggagagcc tgcctatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacatcta gcttctttat ccgggacatc atcaagcccg atccacccaa gaacctgcag 660 ctgaagcctc tgaagaattc tagacaggtg gaggtgagct gggagtaccc agacacctgg 720 tccacacccc actcttattt cagcctgacc ttttgcgtgc aggtgcaggg caagagcaag 780 agggagaaga aggaccgcgt gttcaccgat aagacatccg ccaccgtgat ctgtaggaag 840 aacgcctcca tctctgtgag ggcccaggat cgctactatt cctctagctg gtccgagtgg 900 gcctctgtgc cctgtagc 918 3-754 Sequences 3-754-1 Sequence Number [ID] 754 3-754-2 Molecule Type DNA 3-754-3 Length 918 3-754-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-754-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca ccagaggagg atggcatcac ctggacactg 120 gatcagtcta gcgaggtgct gggcagcggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatttgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gcggtgcgag gccaagaatt atagcggccg gttcacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtcctc taggggcagc 420 tccgaccccc agggcgtgac atgcggagca gccaccctgt ccgccgagag ggtgcgcggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tccagcagca 540 gaggagagcc tgcctatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacatcta gcttctttat ccgggacatc atcaagcccg atccacccaa gaacctgcag 660 ctgaagcctc tgaagaattc tagacaggtg gaggtgagct gggagtaccc agacacctgg 720 tccacacccc actcttattt cagcctgacc ttttgcgtgc aggtgcaggg caagtccaag 780 agggagaaga aggaccgcgt gttcaccgat aagacatctg ccaccgtgat ctgtaggaag 840 aacgcctcca tctctgtgag ggcccaggat cgctactatt cctctagctg gtccgagtgg 900 gcctctgtgc cctgtagc 918 11 Aug 2023

3-755 Sequences 3-755-1 Sequence Number [ID] 755 3-755-2 Molecule Type DNA 3-755-3 Length 918 3-755-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-755-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 2023214349

ggcgagatgg tggtgctgac ctgcgacaca cctgaggagg atggcatcac ctggacactg 120 gatcagtcta gcgaggtgct gggctccggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatctgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gaggtgcgag gccaagaatt atagcggccg ctttacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtcctc taggggcagc 420 tccgaccccc agggcgtgac atgcggagca gccaccctgt ccgccgagcg ggtgagaggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tccagcagca 540 gaggagagcc tgcctatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacatcta gcttctttat cagggacatc atcaagcccg atccacccaa gaacctgcag 660 ctgaagcctc tgaagaattc tcgccaggtg gaggtgagct gggagtaccc agacacctgg 720 agcacacccc actcttattt cagcctgacc ttttgcgtgc aggtgcaggg caagtctaag 780 cgggagaaga aggacagagt gttcaccgat aagacaagcg ccaccgtgat ctgtcggaag 840 aacgcctcca tctctgtgcg ggcccaggat agatactatt cctctagctg gtccgagtgg 900 gcctctgtgc cctgtagc 918 3-756 Sequences 3-756-1 Sequence Number [ID] 756 3-756-2 Molecule Type DNA 3-756-3 Length 918 3-756-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-756-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca cctgaggagg atggcatcac ctggacactg 120 gatcagagct ccgaggtgct gggaagcggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatttgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gaggtgcgag gccaagaatt atagcggccg ctttacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtctag cagaggctcc 420 tctgaccccc agggcgtgac atgcggagca gccaccctgt ccgccgagcg ggtgagaggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tcctgcagca 540 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacaagct ccttctttat cagggacatc atcaagcctg atccccctaa gaacctgcag 660 ctgaagccac tgaagaattc tcgccaggtg gaggtgagct gggagtaccc agacacctgg 720 tccacacccc actcttattt cagcctgacc ttttgcgtgc aggtgcaggg caagagcaag 780 agggagaaga aggaccgcgt gttcaccgat aagacatccg ccaccgtgat ctgtcggaag 840 aacgcctcca tctctgtgcg ggcccaggat agatactatt ctagctcctg gtccgagtgg 900 gcctctgtgc cctgtagc 918 3-757 Sequences 3-757-1 Sequence Number [ID] 757 3-757-2 Molecule Type DNA 3-757-3 Length 918 3-757-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-757-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca cctgaggagg atggcatcac ctggacactg 120 gatcagagct ccgaggtgct gggaagcggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatttgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gcggtgcgag gccaagaatt atagcggccg gttcacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtctag ccggggctcc 420 tctgacccac agggagtgac atgcggagca gccaccctgt ccgccgagcg ggtgagaggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tcctgcagca 540 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 11 Aug 2023 tatacaagct ccttctttat cagggacatc atcaagcctg atccccctaa gaacctgcag 660 ctgaagccac tgaagaattc tcgccaggtg gaggtgagct gggagtaccc agacacctgg 720 tccacacccc actcttattt cagcctgacc ttttgcgtgc aggtgcaggg caagtccaag 780 cgggagaaga aggacagagt gttcaccgat aagacatctg ccaccgtgat ctgtcggaag 840 aacgcctcca tctctgtgag ggcccaggat cgctactatt ctagctcctg gagcgagtgg 900 gcatccgtgc catgttct 918 3-758 Sequences 3-758-1 Sequence Number [ID] 758 3-758-2 Molecule Type DNA 3-758-3 Length 918 3-758-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload 2023214349 source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-758-5 Residues atctgggagc tcaagaaaga cgtgtacgtg gtggaactgg actggtaccc cgacgcccct 60 ggcgaaatgg tggtgctgac atgcgacacc cctgaggagg atggcattac ctggaccctc 120 gatcagagct ccgaggtgct gggcagcggc aaaaccctga ccatccaggt gaaggagttt 180 ggcgatgccg gccagtacac atgtcacaag ggcggcgagg tgctgagcca ctccctgctg 240 ctgctccaca agaaggaaga tggcatctgg agcaccgaca ttctgaagga tcagaaggag 300 cccaagaaca agacattcct gaggtgtgag gccaagaact acagcggcag gtttacctgc 360 tggtggctga caacaatcag caccgacctc acattctccg tcaagtcctc caggggttct 420 tccgaccctc aaggcgtgac atgcggcgct gccaccctga gcgctgagag agtcaggggc 480 gacaacaagg agtacgagta cagcgtcgaa tgtcaggagg acagcgcctg tcccgccgct 540 gaagagagcc tgcctatcga ggtgatggtg gacgccgtgc acaaactgaa gtatgagaat 600 tacacctcca gcttcttcat cagggacatc atcaaacccg atccccccaa gaacctgcag 660 ctgaagcctc tgaagaacag cagacaggtc gaagtgtcct gggagtaccc tgatacctgg 720 tccacacccc acagctactt cagcctgacc ttttgcgtgc aggtgcaggg caagagcaaa 780 agggagaaga aggacagggt gtttaccgac aagacctccg ccacagtgat ttgcagaaag 840 aacgcctcca tcagcgtgag ggcccaggac aggtattaca gcagctcctg gagcgaatgg 900 gctagcgtgc cctgtagc 918 3-759 Sequences 3-759-1 Sequence Number [ID] 759 3-759-2 Molecule Type DNA 3-759-3 Length 918 3-759-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-759-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca cccgaggagg atggcatcac ctggacactg 120 gatcagtcta gcgaggtgct gggctccggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac ctgtcacaag ggcggcgagg tgctgtccca ctctctgctg 240 ctgctgcaca agaaggagga cggcatctgg tctacagaca tcctgaagga tcagaaggag 300 cctaagaaca agaccttcct gcggtgcgag gccaagaatt atagcggccg gttcacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtcctc tcggggcagc 420 tccgacccac agggagtgac atgcggagca gccaccctgt ccgccgagag ggtgcgcggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tccagcagca 540 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacatcta gcttctttat ccgggacatc atcaagcccg atccccctaa gaacctgcag 660 ctgaagcctc tgaagaattc tagacaggtg gaggtgagct gggagtaccc cgacacctgg 720 agcacacctc acagctattt ctccctgacc ttttgcgtgc aggtgcaggg caagtccaag 780 agggagaaga aggaccgcgt gttcaccgat aagacatctg ccaccgtgat ctgtcggaag 840 aacgccagca tctccgtgag ggcccaggat cgctactatt cctctagctg gtctgagtgg 900 gccagcgtgc cctgttcc 918 3-760 Sequences 3-760-1 Sequence Number [ID] 760 3-760-2 Molecule Type DNA 3-760-3 Length 918 3-760-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-760-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc tgatgcccca 60 ggcgagatgg tggtgctgac atgcgacacc cccgaggagg atggcatcac atggaccctg 120 gatcagtcct ctgaggtgct gggctccggc aagacactga ccatccaggt gaaggagttc 180 ggcgacgccg gccagtacac ctgtcacaag ggaggagagg tgctgagcca ctccctgctg 240 11 Aug 2023

ctgctgcaca agaaggagga cggcatctgg tccaccgaca tcctgaagga tcagaaggag 300 cccaagaaca agacattcct gagatgcgag gccaagaatt atagcggcag gtttacctgt 360 tggtggctga caaccatctc cacagatctg accttttctg tgaagagctc ccggggctct 420 agcgaccctc agggagtgac ctgcggagca gccacactgt ccgccgagcg ggtgagaggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tcctgcagca 540 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacctcct ctttctttat cagagacatc atcaagccag atcctccaaa gaacctgcag 660 ctgaagcccc tgaagaatag caggcaggtg gaggtgtcct gggagtaccc agacacatgg 720 agcacccccc acagctattt ctccctgaca ttttgcgtgc aggtgcaggg caagtccaag 780 cgcgagaaga aggaccgggt gttcacagat aagacctctg ccacagtgat ctgtcgcaag 840 aacgcctcta tcagcgtgcg cgcccaggat cggtactata gctcctcttg gtctgagtgg 900 gccagcgtgc cttgttcc 918 2023214349

3-761 Sequences 3-761-1 Sequence Number [ID] 761 3-761-2 Molecule Type DNA 3-761-3 Length 918 3-761-4 Features misc_feature 1..918 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..918 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-761-5 Residues atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc cgatgcccct 60 ggcgagatgg tggtgctgac ctgcgacaca cctgaggagg atggcatcac ctggacactg 120 gatcagagct ccgaggtgct gggcagcggc aagaccctga caatccaggt gaaggagttc 180 ggcgacgccg gccagtacac atgtcacaag ggcggcgagg tgctgtctca cagcctgctg 240 ctgctgcaca agaaggagga cggcatctgg tccacagaca tcctgaagga tcagaaggag 300 ccaaagaaca agaccttcct gaggtgcgag gccaagaatt attctggcag gttcacctgt 360 tggtggctga ccacaatcag caccgatctg acattttccg tgaagtctag ccggggctcc 420 tctgaccccc agggagtgac atgcggagca gccaccctgt ccgccgagag ggtgagaggc 480 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tcctgcagca 540 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 600 tatacaagct ccttctttat cagggacatc atcaagcctg atccccctaa gaacctgcag 660 ctgaagccac tgaagaattc tagacaggtg gaggtgagct gggagtaccc agacacctgg 720 agcacacccc actcctattt ctctctgacc ttttgcgtgc aggtgcaggg caagagcaag 780 agggagaaga aggacagagt gttcaccgat aagacatccg ccaccgtgat ctgtcggaag 840 aacgcctcca tctctgtgcg ggcccaggat cgctactatt ctagctcctg gagcgagtgg 900 gcatccgtgc catgttct 918 3-762 Sequences 3-762-1 Sequence Number [ID] 762 3-762-2 Molecule Type DNA 3-762-3 Length 594 3-762-4 Features misc_feature 1..594 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..594 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-762-5 Residues agaaacctcc ccgtggccac tccagaccca ggaatgttcc catgccttca ccactcccaa 60 aacctgctga gggccgtcag caacatgctc cagaaggcca gacaaactct agaattttac 120 ccttgcactt ctgaagagat tgatcatgaa gatatcacaa aagataaaac cagcacagtg 180 gaggcctgtt taccattgga attaaccaag aatgagagtt gcctaaattc cagagagacc 240 tctttcataa ctaatgggag ttgcctggcc tccagaaaga cctcttttat gatggccctg 300 tgccttagta gtatttatga agacttgaag atgtaccagg tggagttcaa gaccatgaat 360 gcaaagcttc tgatggatcc taagaggcag atctttctag atcaaaacat gctggcagtt 420 attgatgagc tgatgcaggc cctgaatttc aacagtgaga ctgtgccaca aaaatcctcc 480 cttgaagaac cggattttta taaaactaaa atcaagctct gcatacttct tcatgctttc 540 agaattcggg cagtgactat tgatagagtg atgagctatc tgaatgcttc ctaa 594 3-763 Sequences 3-763-1 Sequence Number [ID] 763 3-763-2 Molecule Type DNA 3-763-3 Length 594 3-763-4 Features misc_feature 1..594 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..594 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-763-5 Residues cgcaatctgc cagtggccac ccctgaccca ggcatgttcc cctgcctgca ccacagccag 60 aacctgctga gggccgtgtc caatatgctg cagaaggccc gccagacact ggagttttac 120 ccttgtacct ctgaggagat cgaccacgag gatatcacaa aggataagac cagcacagtg 180 gaggcctgcc tgccactgga gctgaccaag aacgagtcct gtctgaacag ccgggaaacc 240 11 Aug 2023

agcttcatca ccaacggctc ctgcctggcc tctcgcaaga ccagcttcat gatggccctg 300 tgcctgtcct ctatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagcggcag atctttctgg atcagaatat gctggccgtg 420 atcgacgagc tgatgcaggc cctgaacttc aatagcgaga cagtgccaca gaagagctcc 480 ctggaggagc ccgatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttt 540 cggatcagag ccgtgaccat cgacagagtg atgtcctatc tgaatgcctc ttga 594 3-764 Sequences 3-764-1 Sequence Number [ID] 764 3-764-2 Molecule Type DNA 3-764-3 Length 594 3-764-4 Features misc_feature 1..594 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload 2023214349

source 1..594 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-764-5 Residues cgcaatctgc cagtggccac ccctgaccca ggcatgttcc cctgcctgca ccacagccag 60 aacctgctga gggccgtgtc caatatgctg cagaaggccc gccagacact ggagttttac 120 ccttgtacca gcgaggagat cgaccacgag gatatcacaa aggataagac ctccacagtg 180 gaggcctgcc tgccactgga gctgaccaag aacgagtcct gtctgaacag ccgggaaacc 240 agcttcatca ccaacggctc ctgcctggcc tctcgcaaga ccagcttcat gatggccctg 300 tgcctgtcct ctatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagcggcag atctttctgg atcagaatat gctggccgtg 420 atcgacgagc tgatgcaggc cctgaacttc aatagcgaga cagtgccaca gaagagctcc 480 ctggaggagc ccgatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttt 540 cggatcagag ccgtgaccat cgacagagtg atgtcctatc tgaatgcctc ttga 594 3-765 Sequences 3-765-1 Sequence Number [ID] 765 3-765-2 Molecule Type DNA 3-765-3 Length 594 3-765-4 Features misc_feature 1..594 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..594 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-765-5 Residues agaaatctgc cagtggccac ccctgaccca ggcatgttcc cctgcctgca ccactctcag 60 aacctgctgc gggccgtgag caatatgctg cagaaggcca gacagacact ggagttttac 120 ccttgtacct ccgaggagat cgaccacgag gatatcacaa aggataagac ctctacagtg 180 gaggcctgcc tgccactgga gctgaccaag aacgagtcct gtctgaacag ccgggaaacc 240 agcttcatca ccaacggctc ctgcctggcc tctagaaaga ccagcttcat gatggccctg 300 tgcctgtcct ctatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagaggcag atctttctgg atcagaatat gctggccgtg 420 atcgacgagc tgatgcaggc cctgaacttc aatagcgaga cagtgccaca gaagagctcc 480 ctggaggagc ccgatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttt 540 aggatccgcg ccgtgaccat cgaccgcgtg atgtcctatc tgaatgcctc ttga 594 3-766 Sequences 3-766-1 Sequence Number [ID] 766 3-766-2 Molecule Type DNA 3-766-3 Length 591 3-766-4 Features misc_feature 1..591 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..591 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-766-5 Residues agaaatctgc cagtggcaac ccctgaccca ggaatgttcc cttgcctgca ccacagccag 60 aacctgctgc gggccgtgtc caatatgctg cagaaggcca gacagacact ggagttttac 120 ccttgtacct ctgaggagat cgaccacgag gatatcacaa aggataagac cagcacagtg 180 gaggcctgcc tgccactgga gctgaccaag aacgagtcct gtctgaacag ccgggaaacc 240 agcttcatca ccaacggctc ctgcctggcc tctcgcaaga ccagcttcat gatggccctg 300 tgcctgtcta gcatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagaggcag atctttctgg atcagaatat gctggccgtg 420 atcgacgagc tgatgcaggc cctgaacttc aatagcgaga cagtgccaca gaagtcctct 480 ctggaggagc ccgatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttt 540 aggatccgcg ccgtgaccat cgacagagtg atgtcctatc tgaacgcctc t 591 3-767 Sequences

3-767-1 Sequence Number [ID] 767 3-767-2 Molecule Type DNA 3-767-3 Length 591 3-767-4 Features misc_feature 1..591 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..591 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-767-5 Residues agaaatctgc cagtggcaac ccctgaccca ggaatgttcc cttgcctgca ccacagccag 60 aacctgctga gggccgtgtc caatatgctg cagaaggccc gccagacact ggagttttac 120 ccttgtacca gcgaggagat cgaccacgag gatatcacaa aggataagac ctccacagtg 180 gaggcctgcc tgccactgga gctgaccaag aacgagagct gtctgaattc ccgggagaca 240 tctttcatca ccaacggcag ctgcctggcc tccagaaaga catcttttat gatggccctg 300 tgcctgtcta gcatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagaggcag atctttctgg atcagaatat gctggccgtg 420 2023214349

atcgacgagc tgatgcaggc cctgaacttc aatagcgaga cagtgccaca gaagtcctct 480 ctggaggagc ccgatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttt 540 aggatccgcg ccgtgaccat cgaccgcgtg atgtcttatc tgaacgcatc c 591 3-768 Sequences 3-768-1 Sequence Number [ID] 768 3-768-2 Molecule Type DNA 3-768-3 Length 594 3-768-4 Features misc_feature 1..594 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..594 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-768-5 Residues agaaacctgc ctgtcgctac ccccgacccc ggaatgttcc cctgcctgca ccactcccag 60 aacctcctga gggccgtgtc caacatgctg cagaaggcta gacagaccct cgaattctac 120 ccctgtacca gcgaggagat cgaccatgag gacatcacca aggataagac cagcaccgtg 180 gaggcttgcc tgcctctgga gctgaccaaa aacgagagct gcctgaacag cagggaaacc 240 agcttcatta ccaacggctc ctgcctggcc tccaggaaga catccttcat gatggccctg 300 tgcctcagca gcatctacga ggacctgaag atgtatcagg tggagtttaa gaccatgaat 360 gccaagctgc tgatggaccc taagaggcag atcttcctgg accagaatat gctggccgtg 420 attgacgagc tgatgcaggc cctcaacttt aacagcgaga ccgtgcccca gaaaagcagc 480 ctcgaagagc ctgacttcta caaaaccaag attaagctgt gtatcctgct gcacgccttc 540 aggatcaggg ccgtgaccat cgacagggtg atgagctacc tgaacgccag ctaa 594 3-769 Sequences 3-769-1 Sequence Number [ID] 769 3-769-2 Molecule Type DNA 3-769-3 Length 597 3-769-4 Features misc_feature 1..597 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..597 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-769-5 Residues agaaatctgc cagtggccac ccctgaccca ggcatgttcc cctgcctgca ccacagccag 60 aacctgctga gggccgtgtc caatatgctg cagaaggccc gccagacact ggagttttac 120 ccctgtacca gcgaggagat cgaccacgag gatatcacaa aggataagac ctccacagtg 180 gaggcctgcc tgcctctgga gctgaccaag aacgagtctt gtctgaatag cagggagaca 240 tccttcatca ccaacggctc ttgcctggcc agccgcaaga catcctttat gatggccctg 300 tgcctgtcct ctatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagaggcag atctttctgg atcagaatat gctggccgtg 420 atcgacgagc tgatgcaggc cctgaacttc aattccgaga cagtgcctca gaagagctcc 480 ctggaggagc cagatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttt 540 cggatcagag ccgtgaccat cgaccgcgtg atgtcttatc tgaatgccag cggatcc 597 3-770 Sequences 3-770-1 Sequence Number [ID] 770 3-770-2 Molecule Type DNA 3-770-3 Length 597 3-770-4 Features misc_feature 1..597 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..597 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-770-5 Residues cggaatctgc ctgtggcaac ccccgaccct ggaatgttcc catgcctgca ccacagccag 60 aacctgctgc gcgccgtgtc caatatgctg cagaaggccc ggcagaccct ggagttttac 120 ccatgtacaa gcgaggagat cgaccacgag gatatcacca aggataagac atccaccgtg 180 gaggcatgcc tgccactgga gctgacaaag aacgagtctt gtctgaacag ccgggagaca 240 agcttcatca caaacggctc ttgcctggcc agccggaaga cctcctttat gatggccctg 300 tgcctgagct ccatctacga ggacctgaag atgtatcagg tggagttcaa gacaatgaac 360 gccaagctgc tgatggaccc caagcgccag atctttctgg atcagaatat gctggccgtg 420 11 Aug 2023 atcgacgagc tgatgcaggc cctgaacttt aatagcgaga cagtgcccca gaagtctagc 480 ctggaggagc ctgatttcta caagacaaag atcaagctgt gcatcctgct gcacgccttc 540 cggatcagag ccgtgaccat cgacagagtg atgtcttatc tgaatgccag cggatcc 597 3-771 Sequences 3-771-1 Sequence Number [ID] 771 3-771-2 Molecule Type DNA 3-771-3 Length 591 3-771-4 Features misc_feature 1..591 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..591 mol_type=other DNA 2023214349 organism=synthetic construct NonEnglishQualifier Value 3-771-5 Residues cgcaatctgc cagtggcaac ccctgaccca ggaatgttcc cttgcctgca ccacagccag 60 aacctgctgc gggccgtgtc caatatgctg cagaaggccc gccagacact ggagttttac 120 ccttgtacct ctgaggagat cgaccacgag gatatcacaa aggataagac cagcacagtg 180 gaggcctgcc tgccactgga gctgaccaag aacgagagct gtctgaattc cagggagaca 240 tctttcatca ccaacggcag ctgcctggcc tccagaaaga catcttttat gatggccctg 300 tgcctgtcta gcatctacga ggacctgaag atgtatcagg tggagttcaa gaccatgaac 360 gccaagctgc tgatggaccc taagaggcag atctttctgg atcagaatat gctggccgtg 420 atcgacgagc tgatgcaggc cctgaacttc aattccgaga cagtgccaca gaagtcctct 480 ctggaggagc ccgatttcta caagaccaag atcaagctgt gcatcctgct gcacgccttc 540 aggatcaggg ccgtgaccat cgacagagtg atgagctatc tgaacgccag c 591 3-772 Sequences 3-772-1 Sequence Number [ID] 772 3-772-2 Molecule Type DNA 3-772-3 Length 477 3-772-4 Features misc_feature 1..477 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..477 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-772-5 Residues atctctctga ttgcggcgct ggcagttgac tacgttattg gcatggaaaa cgcgatgcca 60 tggaacctcc cggctgacct ggcgtggttc aaacgtaaca ccctgaacaa acctgtgatc 120 atgggtcgtc acacctggga atctattggc cgtcctctcc cgggtcgtaa aaacatcatt 180 ctgtcttctc agccaggcac cgacgaccgt gttacctggg ttaaaagcgt tgacgaagcg 240 attgctgcgt gcggtgatgt tcctgaaatt atggtgatcg gcggtggccg tgttatcgaa 300 cagttcctgc cgaaagcgca gaaactgtac ctgacccaca tcgacgcgga agttgaaggt 360 gacacccact tcccggacta cgaaccggat gattgggaga gcgtattctc cgaattccat 420 gatgcggatg cgcaaaactc tcattcttac tgttttgaaa tcctggaacg tcgttga 477 3-773 Sequences 3-773-1 Sequence Number [ID] 773 3-773-2 Molecule Type DNA 3-773-3 Length 558 3-773-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-773-5 Residues gtgggcagcc tgaactgtat cgtggccgtg tcccagaaca tgggcatcgg caagaatggc 60 gatctgccat ggccccctct gcggaacgag ttcagatact tctttaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacctg gttttctatc 180 cccgagaaga acagacctct gaagggcagg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgaca 300 gagcagccag agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagt ttatgaatca ccccggccac ctgaagctgt tcgtgaccag aatcatgcag 420 gactttgagt ccgatacatt ctttcctgag atcgatctgg agaagtacaa gctgctgcca 480 gagtatcccg gcgtgctgtc tgacgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaacgat 558 3-774 Sequences 3-774-1 Sequence Number [ID] 774 3-774-2 Molecule Type DNA 3-774-3 Length 1959 3-774-4 Features misc_feature 1..1959 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1959 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-774-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc atcccctctg 60 gtggcaggag tgcaggtgga gacaatctct cctggcgatg gccggacctt cccaaagaga 120 ggccagacat gcgtggtgca ctacaccggc atgctggagg acggcaagaa ggtggacagc 180 tcccgggata gaaacaagcc attcaagttt atgctgggca agcaggaagt gatcagggga 240 tgggaggagg gagtggcaca gatgtctgtg ggccagagag ccaagctgac aatcagccct 300 gattacgcat atggagcaac cggacaccca ggaatcatcc cacctcacgc caccctggtg 360 tttgatgtgg agctgctgaa gccagaggga ggatccggag gcatctggga gctgaagaag 420 gacgtgtacg tggtggagct ggactggtat cccgatgccc ctggcgagat ggtggtgctg 480 acctgcgaca cacctgagga ggatggcatc acctggacac tggatcagtc tagcgaggtg 540 ctgggcagcg gcaagaccct gacaatccag gtgaaggagt tcggcgacgc cggccagtac 600 acatgtcaca agggcggcga ggtgctgtct cacagcctgc tgctgctgca caagaaggag 660 gacggcattt ggtccacaga catcctgaag gatcagaagg agccaaagaa caagaccttc 720 ctgcggtgcg aggccaagaa ttatagcggc cggttcacct gttggtggct gaccacaatc 780 2023214349

agcaccgatc tgacattttc cgtgaagtcc tctaggggca gctccgaccc ccagggcgtg 840 acatgcggag cagccaccct gtccgccgag agggtgcgcg gcgataacaa ggagtacgag 900 tattccgtgg agtgccagga ggactctgcc tgtccagcag cagaggagag cctgcctatc 960 gaagtgatgg tggatgccgt gcacaagctg aagtacgaga attatacatc tagcttcttt 1020 atccgggaca tcatcaagcc cgatccaccc aagaacctgc agctgaagcc tctgaagaat 1080 tctagacagg tggaggtgag ctgggagtac ccagacacct ggtccacacc ccactcttat 1140 ttcagcctga ccttttgcgt gcaggtgcag ggcaagagca agagggagaa gaaggaccgc 1200 gtgttcaccg ataagacatc cgccaccgtg atctgtagga agaacgcctc catctctgtg 1260 agggcccagg atcgctacta ttcctctagc tggtccgagt gggcctctgt gccctgtagc 1320 ggaggaggag gatccggagg aggaggatct ggcggcggcg gcagccgcaa tctgccagtg 1380 gccacccctg acccaggcat gttcccctgc ctgcaccaca gccagaacct gctgagggcc 1440 gtgtccaata tgctgcagaa ggcccgccag acactggagt tttacccttg tacctctgag 1500 gagatcgacc acgaggatat cacaaaggat aagaccagca cagtggaggc ctgcctgcca 1560 ctggagctga ccaagaacga gtcctgtctg aacagccggg aaaccagctt catcaccaac 1620 ggctcctgcc tggcctctcg caagaccagc ttcatgatgg ccctgtgcct gtcctctatc 1680 tacgaggacc tgaagatgta tcaggtggag ttcaagacca tgaacgccaa gctgctgatg 1740 gaccctaagc ggcagatctt tctggatcag aatatgctgg ccgtgatcga cgagctgatg 1800 caggccctga acttcaatag cgagacagtg ccacagaaga gctccctgga ggagcccgat 1860 ttctacaaga ccaagatcaa gctgtgcatc ctgctgcacg cctttcggat cagagccgtg 1920 accatcgaca gagtgatgtc ctatctgaat gcctcttga 1959 3-775 Sequences 3-775-1 Sequence Number [ID] 775 3-775-2 Molecule Type DNA 3-775-3 Length 1962 3-775-4 Features misc_feature 1..1962 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1962 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-775-5 Residues atgggcgtgc aggtggagac aatctcccct ggcgatggcc ggaccttccc aaagagaggc 60 cagacatgcg tggtgcacta caccggcatg ctggaggacg gcaagaaggt ggacagctcc 120 cgggatagaa acaagccttt caagtttatg ctgggcaagc aggaagtgat caggggatgg 180 gaggagggag tggcacagat gtctgtgggc cagagagcca agctgacaat cagccctgat 240 tacgcatatg gagcaaccgg acacccagga atcatcccac ctcacgccac cctggtgttt 300 gacgtggagc tgctgaagcc agagggagga tctggaggaa tgtgccacca gcagctggtc 360 atcagctggt tctccctggt gtttctggcc agccctctgg tggccatctg ggagctgaag 420 aaggacgtgt acgtggtgga gctggactgg tatcccgatg cccctggcga gatggtggtg 480 ctgacctgcg acacaccaga ggaggatggc atcacctgga cactggatca gtctagcgag 540 gtgctgggca gcggcaagac cctgacaatc caggtgaagg agttcggcga cgccggccag 600 tacacatgtc acaagggcgg cgaggtgctg tctcacagcc tgctgctgct gcacaagaag 660 gaggacggca tttggtccac agacatcctg aaggatcaga aggagccaaa gaacaagacc 720 ttcctgcggt gcgaggccaa gaattatagc ggccggttca cctgttggtg gctgaccaca 780 atcagcaccg atctgacatt ttccgtgaag tcctctaggg gcagctccga cccccagggc 840 gtgacatgcg gagcagccac cctgtccgcc gagagggtgc gcggcgataa caaggagtac 900 gagtattccg tggagtgcca ggaggactct gcctgtccag cagcagagga gagcctgcct 960 atcgaagtga tggtggatgc cgtgcacaag ctgaagtacg agaattatac atctagcttc 1020 tttatccggg acatcatcaa gcccgatcca cccaagaacc tgcagctgaa gcctctgaag 1080 aattctagac aggtggaggt gagctgggag tacccagaca cctggtccac accccactct 1140 tatttcagcc tgaccttttg cgtgcaggtg cagggcaagt ccaagaggga gaagaaggac 1200 cgcgtgttca ccgataagac atctgccacc gtgatctgta ggaagaacgc ctccatctct 1260 gtgagggccc aggatcgcta ctattcctct agctggtccg agtgggcctc tgtgccctgt 1320 agcggaggag gaggatccgg aggaggagga tctggcggcg gcggcagccg caatctgcca 1380 gtggccaccc ctgacccagg catgttcccc tgcctgcacc acagccagaa cctgctgagg 1440 gccgtgtcca atatgctgca gaaggcccgc cagacactgg agttttaccc ttgtaccagc 1500 gaggagatcg accacgagga tatcacaaag gataagacct ccacagtgga ggcctgcctg 1560 ccactggagc tgaccaagaa cgagtcctgt ctgaacagcc gggaaaccag cttcatcacc 1620 aacggctcct gcctggcctc tcgcaagacc agcttcatga tggccctgtg cctgtcctct 1680 atctacgagg acctgaagat gtatcaggtg gagttcaaga ccatgaacgc caagctgctg 1740 atggacccta agcggcagat ctttctggat cagaatatgc tggccgtgat cgacgagctg 1800 atgcaggccc tgaacttcaa tagcgagaca gtgccacaga agagctccct ggaggagccc 1860 gatttctaca agaccaagat caagctgtgc atcctgctgc acgcctttcg gatcagagcc 1920 11 Aug 2023 gtgaccatcg acagagtgat gtcctatctg aatgcctctt ga 1962 3-776 Sequences 3-776-1 Sequence Number [ID] 776 3-776-2 Molecule Type DNA 3-776-3 Length 1971 3-776-4 Features misc_feature 1..1971 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1971 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 2023214349

3-776-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc aagccctctg 60 gtggcaggag tgcaggtgga gacaatctcc cctggcgatg gcaggacctt cccaaagcgc 120 ggccagacat gcgtggtgca ctacaccggc atgctggagg acggcaagaa ggtggacagc 180 tcccgggata gaaacaagcc attcaagttt atgctgggca agcaggaagt gatcagggga 240 tgggaggagg gagtggcaca gatgtccgtg ggacagcgcg ccaagctgac aatctctcct 300 gattacgcat atggagcaac cggacaccca ggaatcatcc cacctcacgc caccctggtg 360 tttgacgtgg agctgctgaa gcccgagagc gccaggaatc gccagaagcg gtccatctgg 420 gagctgaaga aggacgtgta cgtggtggag ctggactggt atcccgatgc ccctggcgag 480 atggtggtgc tgacctgcga cacacctgag gaggatggca tcacctggac actggatcag 540 tctagcgagg tgctgggctc cggcaagacc ctgacaatcc aggtgaagga gttcggcgac 600 gccggccagt acacatgtca caagggcggc gaggtgctgt ctcacagcct gctgctgctg 660 cacaagaagg aggacggcat ctggtccaca gacatcctga aggatcagaa ggagccaaag 720 aacaagacct tcctgaggtg cgaggccaag aattatagcg gccgctttac ctgttggtgg 780 ctgaccacaa tcagcaccga tctgacattt tccgtgaagt cctctagggg cagctccgac 840 ccccagggcg tgacatgcgg agcagccacc ctgtccgccg agcgggtgag aggcgataac 900 aaggagtacg agtattccgt ggagtgccag gaggactctg cctgtccagc agcagaggag 960 agcctgccta tcgaagtgat ggtggatgcc gtgcacaagc tgaagtacga gaattataca 1020 tctagcttct ttatcaggga catcatcaag cccgatccac ccaagaacct gcagctgaag 1080 cctctgaaga attctcgcca ggtggaggtg agctgggagt acccagacac ctggagcaca 1140 ccccactctt atttcagcct gaccttttgc gtgcaggtgc agggcaagtc taagcgggag 1200 aagaaggaca gagtgttcac cgataagaca agcgccaccg tgatctgtcg gaagaacgcc 1260 tccatctctg tgcgggccca ggatagatac tattcctcta gctggtccga gtgggcctct 1320 gtgccctgta gcggaggagg aggatccgga ggaggaggat ctggcggcgg cggcagcaga 1380 aatctgccag tggccacccc tgacccaggc atgttcccct gcctgcacca ctctcagaac 1440 ctgctgcggg ccgtgagcaa tatgctgcag aaggccagac agacactgga gttttaccct 1500 tgtacctccg aggagatcga ccacgaggat atcacaaagg ataagacctc tacagtggag 1560 gcctgcctgc cactggagct gaccaagaac gagtcctgtc tgaacagccg ggaaaccagc 1620 ttcatcacca acggctcctg cctggcctct agaaagacca gcttcatgat ggccctgtgc 1680 ctgtcctcta tctacgagga cctgaagatg tatcaggtgg agttcaagac catgaacgcc 1740 aagctgctga tggaccctaa gaggcagatc tttctggatc agaatatgct ggccgtgatc 1800 gacgagctga tgcaggccct gaacttcaat agcgagacag tgccacagaa gagctccctg 1860 gaggagcccg atttctacaa gaccaagatc aagctgtgca tcctgctgca cgcctttagg 1920 atccgcgccg tgaccatcga ccgcgtgatg tcctatctga atgcctcttg a 1971 3-777 Sequences 3-777-1 Sequence Number [ID] 777 3-777-2 Molecule Type DNA 3-777-3 Length 1968 3-777-4 Features misc_feature 1..1968 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1968 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-777-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc atccccactg 60 gtggcaatct gggagctgaa gaaggacgtg tacgtggtgg agctggactg gtatcccgat 120 gcccctggcg agatggtggt gctgacctgc gacacacctg aggaggatgg catcacctgg 180 acactggatc agagctccga ggtgctggga agcggcaaga ccctgacaat ccaggtgaag 240 gagttcggcg acgccggcca gtacacatgt cacaagggcg gcgaggtgct gtctcacagc 300 ctgctgctgc tgcacaagaa ggaggacggc atttggtcca cagacatcct gaaggatcag 360 aaggagccaa agaacaagac cttcctgagg tgcgaggcca agaattatag cggccgcttt 420 acctgttggt ggctgaccac aatcagcacc gatctgacat tttccgtgaa gtctagcaga 480 ggctcctctg acccccaggg cgtgacatgc ggagcagcca ccctgtccgc cgagcgggtg 540 agaggcgata acaaggagta cgagtattcc gtggagtgcc aggaggactc tgcctgtcct 600 gcagcagagg agagcctgcc aatcgaagtg atggtggatg ccgtgcacaa gctgaagtac 660 gagaattata caagctcctt ctttatcagg gacatcatca agcctgatcc ccctaagaac 720 ctgcagctga agccactgaa gaattctcgc caggtggagg tgagctggga gtacccagac 780 acctggtcca caccccactc ttatttcagc ctgacctttt gcgtgcaggt gcagggcaag 840 agcaagaggg agaagaagga ccgcgtgttc accgataaga catccgccac cgtgatctgt 900 cggaagaacg cctccatctc tgtgcgggcc caggatagat actattctag ctcctggtcc 960 gagtgggcct ctgtgccctg tagcggagga ggaggatccg gaggaggagg atctggcgga 1020 ggaggcagca gaaatctgcc agtggcaacc cctgacccag gaatgttccc ttgcctgcac 1080 cacagccaga acctgctgcg ggccgtgtcc aatatgctgc agaaggccag acagacactg 1140 11 Aug 2023 gagttttacc cttgtacctc tgaggagatc gaccacgagg atatcacaaa ggataagacc 1200 agcacagtgg aggcctgcct gccactggag ctgaccaaga acgagtcctg tctgaacagc 1260 cgggaaacca gcttcatcac caacggctcc tgcctggcct ctcgcaagac cagcttcatg 1320 atggccctgt gcctgtctag catctacgag gacctgaaga tgtatcaggt ggagttcaag 1380 accatgaacg ccaagctgct gatggaccct aagaggcaga tctttctgga tcagaatatg 1440 ctggccgtga tcgacgagct gatgcaggcc ctgaacttca atagcgagac agtgccacag 1500 aagtcctctc tggaggagcc cgatttctac aagaccaaga tcaagctgtg catcctgctg 1560 cacgccttta ggatccgcgc cgtgaccatc gacagagtga tgtcctatct gaacgcctct 1620 gcccggaata gacagaagag atctggcgtg caggtggaga caatcagccc cggcgatggc 1680 cggacctttc ctaagagagg ccagacatgc gtggtgcact acaccggcat gctgggcgac 1740 ggcaagaagg tggacagctc cagggatcgc aataagccct tcaagtttat gctgggcaag 1800 caggaagtga tcaggggatg ggaggaggga gtggcacaga tgtccgtggg acagggcgcc 1860 2023214349 aagctgacaa tctctccaga ttacgcatat ggagcaaccg gacacccagg aatcatccca 1920 ccccacgcca ccctggtgtt cgacgtggag ctgctggagc tggagtga 1968 3-778 Sequences 3-778-1 Sequence Number [ID] 778 3-778-2 Molecule Type DNA 3-778-3 Length 1956 3-778-4 Features misc_feature 1..1956 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1956 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-778-5 Residues atgtgccacc agcagctggt catcagctgg ttctccctgg tgtttctggc atccccactg 60 gtggcaatct gggagctgaa gaaggacgtg tacgtggtgg agctggactg gtatcccgat 120 gcccctggcg agatggtggt gctgacctgc gacacacctg aggaggatgg catcacctgg 180 acactggatc agagctccga ggtgctggga agcggcaaga ccctgacaat ccaggtgaag 240 gagttcggcg acgccggcca gtacacatgt cacaagggcg gcgaggtgct gtctcacagc 300 ctgctgctgc tgcacaagaa ggaggacggc atttggtcca cagacatcct gaaggatcag 360 aaggagccaa agaacaagac cttcctgcgg tgcgaggcca agaattatag cggccggttc 420 acctgttggt ggctgaccac aatcagcacc gatctgacat tttccgtgaa gtctagccgg 480 ggctcctctg acccacaggg agtgacatgc ggagcagcca ccctgtccgc cgagcgggtg 540 agaggcgata acaaggagta cgagtattcc gtggagtgcc aggaggactc tgcctgtcct 600 gcagcagagg agagcctgcc aatcgaagtg atggtggatg ccgtgcacaa gctgaagtac 660 gagaattata caagctcctt ctttatcagg gacatcatca agcctgatcc ccctaagaac 720 ctgcagctga agccactgaa gaattctcgc caggtggagg tgagctggga gtacccagac 780 acctggtcca caccccactc ttatttcagc ctgacctttt gcgtgcaggt gcagggcaag 840 tccaagcggg agaagaagga cagagtgttc accgataaga catctgccac cgtgatctgt 900 cggaagaacg cctccatctc tgtgagggcc caggatcgct actattctag ctcctggagc 960 gagtgggcat ccgtgccatg ttctggagga ggaggaagcg gaggaggagg atccggcgga 1020 ggaggctcta gaaatctgcc agtggcaacc cctgacccag gaatgttccc ttgcctgcac 1080 cacagccaga acctgctgag ggccgtgtcc aatatgctgc agaaggcccg ccagacactg 1140 gagttttacc cttgtaccag cgaggagatc gaccacgagg atatcacaaa ggataagacc 1200 tccacagtgg aggcctgcct gccactggag ctgaccaaga acgagagctg tctgaattcc 1260 cgggagacat ctttcatcac caacggcagc tgcctggcct ccagaaagac atcttttatg 1320 atggccctgt gcctgtctag catctacgag gacctgaaga tgtatcaggt ggagttcaag 1380 accatgaacg ccaagctgct gatggaccct aagaggcaga tctttctgga tcagaatatg 1440 ctggccgtga tcgacgagct gatgcaggcc ctgaacttca atagcgagac agtgccacag 1500 aagtcctctc tggaggagcc cgatttctac aagaccaaga tcaagctgtg catcctgctg 1560 cacgccttta ggatccgcgc cgtgaccatc gaccgcgtga tgtcttatct gaacgcatcc 1620 ggaggatctg gaggagtgca ggtggagaca atcagccccg gcgatggcag gacctttcct 1680 aagcgcggcc agacatgcgt ggtgcactac accggcatgc tgggcgacgg caagaaggtg 1740 gacagctccc gggatagaaa taagcccttc aagtttatgc tgggcaagca ggaagtgatc 1800 agaggctggg aggagggagt ggcacagatg tctgtgggac agggcgccaa gctgacaatc 1860 agcccagatt acgcatatgg agcaaccgga cacccaggaa tcatcccacc ccacgccacc 1920 ctggtgttcg acgtggagct gctggagctg gagtga 1956 3-779 Sequences 3-779-1 Sequence Number [ID] 779 3-779-2 Molecule Type DNA 3-779-3 Length 1623 3-779-4 Features misc_feature 1..1623 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1623 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-779-5 Residues atgtgccacc aacagctcgt gatcagctgg ttctccctgg tgttcctggc tagccccctg 60 gtggccatct gggagctcaa gaaagacgtg tacgtggtgg aactggactg gtaccccgac 120 gcccctggcg aaatggtggt gctgacatgc gacacccctg aggaggatgg cattacctgg 180 accctcgatc agagctccga ggtgctgggc agcggcaaaa ccctgaccat ccaggtgaag 240 gagtttggcg atgccggcca gtacacatgt cacaagggcg gcgaggtgct gagccactcc 300 ctgctgctgc tccacaagaa ggaagatggc atctggagca ccgacattct gaaggatcag 360 11 Aug 2023 aaggagccca agaacaagac attcctgagg tgtgaggcca agaactacag cggcaggttt 420 acctgctggt ggctgacaac aatcagcacc gacctcacat tctccgtcaa gtcctccagg 480 ggttcttccg accctcaagg cgtgacatgc ggcgctgcca ccctgagcgc tgagagagtc 540 aggggcgaca acaaggagta cgagtacagc gtcgaatgtc aggaggacag cgcctgtccc 600 gccgctgaag agagcctgcc tatcgaggtg atggtggacg ccgtgcacaa actgaagtat 660 gagaattaca cctccagctt cttcatcagg gacatcatca aacccgatcc ccccaagaac 720 ctgcagctga agcctctgaa gaacagcaga caggtcgaag tgtcctggga gtaccctgat 780 acctggtcca caccccacag ctacttcagc ctgacctttt gcgtgcaggt gcagggcaag 840 agcaaaaggg agaagaagga cagggtgttt accgacaaga cctccgccac agtgatttgc 900 agaaagaacg cctccatcag cgtgagggcc caggacaggt attacagcag ctcctggagc 960 gaatgggcta gcgtgccctg tagcggagga ggaggcagcg gaggaggagg ttctggagga 1020 ggcggcagca gaaacctgcc tgtcgctacc cccgaccccg gaatgttccc ctgcctgcac 1080 2023214349 cactcccaga acctcctgag ggccgtgtcc aacatgctgc agaaggctag acagaccctc 1140 gaattctacc cctgtaccag cgaggagatc gaccatgagg acatcaccaa ggataagacc 1200 agcaccgtgg aggcttgcct gcctctggag ctgaccaaaa acgagagctg cctgaacagc 1260 agggaaacca gcttcattac caacggctcc tgcctggcct ccaggaagac atccttcatg 1320 atggccctgt gcctcagcag catctacgag gacctgaaga tgtatcaggt ggagtttaag 1380 accatgaatg ccaagctgct gatggaccct aagaggcaga tcttcctgga ccagaatatg 1440 ctggccgtga ttgacgagct gatgcaggcc ctcaacttta acagcgagac cgtgccccag 1500 aaaagcagcc tcgaagagcc tgacttctac aaaaccaaga ttaagctgtg tatcctgctg 1560 cacgccttca ggatcagggc cgtgaccatc gacagggtga tgagctacct gaacgccagc 1620 taa 1623 3-780 Sequences 3-780-1 Sequence Number [ID] 780 3-780-2 Molecule Type DNA 3-780-3 Length 2130 3-780-4 Features misc_feature 1..2130 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2130 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-780-5 Residues atgtgccacc agcagctggt catctcttgg ttcagcctgg tgtttctggc ctcccccctg 60 gtggccatct ctctgatcgc cgccctggcc gtggattacg tgatcggcat ggagaacgcc 120 atgccatgga atctgccagc agacctggca tggttcaaga ggaacacact gaataagcca 180 gtgatcatgg gcagacacac ctgggagtcc atcggccggc cactgccagg cagaaagaac 240 atcatcctga gctcccagcc cggcacagac gatagggtga cctgggtgaa gagcgtggac 300 gaggcaatcg cagcatgcgg cgatgtgcct gagatcatgg tcatcggagg aggacgcgtg 360 atcgagcagt tcctgccaaa ggcccagaag ctgtacctga cacacatcga tgccgaggtg 420 gagggcgaca cccactttcc tgattatgag ccagacgatt gggagtccgt gttctctgag 480 tttcacgacg ccgatgccca gaactctcac agctattgtt ttgagatcct ggagcggaga 540 gagtctaggc gcgtgcggag aaataagcgg agcaagatct gggagctgaa gaaggacgtg 600 tacgtggtgg agctggactg gtatcccgat gcccctggcg agatggtggt gctgacctgc 660 gacacacccg aggaggatgg catcacctgg acactggatc agtctagcga ggtgctgggc 720 tccggcaaga ccctgacaat ccaggtgaag gagttcggcg acgccggcca gtacacctgt 780 cacaagggcg gcgaggtgct gtcccactct ctgctgctgc tgcacaagaa ggaggacggc 840 atctggtcta cagacatcct gaaggatcag aaggagccta agaacaagac cttcctgcgg 900 tgcgaggcca agaattatag cggccggttc acctgttggt ggctgaccac aatcagcacc 960 gatctgacat tttccgtgaa gtcctctcgg ggcagctccg acccacaggg agtgacatgc 1020 ggagcagcca ccctgtccgc cgagagggtg cgcggcgata acaaggagta cgagtattcc 1080 gtggagtgcc aggaggactc tgcctgtcca gcagcagagg agagcctgcc aatcgaagtg 1140 atggtggatg ccgtgcacaa gctgaagtac gagaattata catctagctt ctttatccgg 1200 gacatcatca agcccgatcc ccctaagaac ctgcagctga agcctctgaa gaattctaga 1260 caggtggagg tgagctggga gtaccccgac acctggagca cacctcacag ctatttctcc 1320 ctgacctttt gcgtgcaggt gcagggcaag tccaagaggg agaagaagga ccgcgtgttc 1380 accgataaga catctgccac cgtgatctgt cggaagaacg ccagcatctc cgtgagggcc 1440 caggatcgct actattcctc tagctggtct gagtgggcca gcgtgccctg ttccggcggc 1500 ggcggctctg gaggaggagg cagcggcgga ggaggctcca gaaatctgcc agtggccacc 1560 cctgacccag gcatgttccc ctgcctgcac cacagccaga acctgctgag ggccgtgtcc 1620 aatatgctgc agaaggcccg ccagacactg gagttttacc cctgtaccag cgaggagatc 1680 gaccacgagg atatcacaaa ggataagacc tccacagtgg aggcctgcct gcctctggag 1740 ctgaccaaga acgagtcttg tctgaatagc agggagacat ccttcatcac caacggctct 1800 tgcctggcca gccgcaagac atcctttatg atggccctgt gcctgtcctc tatctacgag 1860 gacctgaaga tgtatcaggt ggagttcaag accatgaacg ccaagctgct gatggaccct 1920 aagaggcaga tctttctgga tcagaatatg ctggccgtga tcgacgagct gatgcaggcc 1980 ctgaacttca attccgagac agtgcctcag aagagctccc tggaggagcc agatttctac 2040 aagaccaaga tcaagctgtg catcctgctg cacgcctttc ggatcagagc cgtgaccatc 2100 gaccgcgtga tgtcttatct gaatgccagc 2130 3-781 Sequences

3-781-1 Sequence Number [ID] 781 3-781-2 Molecule Type DNA 3-781-3 Length 2214 3-781-4 Features misc_feature 1..2214 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2214 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-781-5 Residues atgtgccacc agcagctggt catctcctgg ttctctctgg tgtttctggc atctcctctg 60 gtggcagtgg gcagcctgaa ctgtatcgtg gccgtgtccc agaacatggg catcggcaag 120 aatggcgatc tgccatggcc ccctctgcgg aacgagttca gatacttctt taggatgacc 180 acaaccagct ccgtggaggg caagcagaac ctggtcatca tgggcaagaa gacctggttt 240 tctatccccg agaagaacag acctctgaag ggcaggatca atctggtgct gagcagagag 300 ctgaaggagc caccacaggg agcacacttc ctgagccgga gcctggacga tgccctgaag 360 ctgacagagc agccagagct ggccaacaag gtggacatgg tgtggatcgt gggcggctct 420 2023214349

agcgtgatca aggagtttat gaatcacccc ggccacctga agctgttcgt gaccagaatc 480 atgcaggact ttgagtccga tacattcttt cctgagatcg atctggagaa gtacaagctg 540 ctgccagagt atcccggcgt gctgtctgac gtgcaggagg agaagggcat caagtacaag 600 ttcgaggtgt atgagaagaa cgatgagtct cggagagtga ggcgcaataa gaggagcaag 660 atctgggagc tgaagaagga cgtgtacgtg gtggagctgg actggtatcc tgatgcccca 720 ggcgagatgg tggtgctgac atgcgacacc cccgaggagg atggcatcac atggaccctg 780 gatcagtcct ctgaggtgct gggctccggc aagacactga ccatccaggt gaaggagttc 840 ggcgacgccg gccagtacac ctgtcacaag ggaggagagg tgctgagcca ctccctgctg 900 ctgctgcaca agaaggagga cggcatctgg tccaccgaca tcctgaagga tcagaaggag 960 cccaagaaca agacattcct gagatgcgag gccaagaatt atagcggcag gtttacctgt 1020 tggtggctga caaccatctc cacagatctg accttttctg tgaagagctc ccggggctct 1080 agcgaccctc agggagtgac ctgcggagca gccacactgt ccgccgagcg ggtgagaggc 1140 gataacaagg agtacgagta ttccgtggag tgccaggagg actctgcctg tcctgcagca 1200 gaggagagcc tgccaatcga agtgatggtg gatgccgtgc acaagctgaa gtacgagaat 1260 tatacctcct ctttctttat cagagacatc atcaagccag atcctccaaa gaacctgcag 1320 ctgaagcccc tgaagaatag caggcaggtg gaggtgtcct gggagtaccc agacacatgg 1380 agcacccccc acagctattt ctccctgaca ttttgcgtgc aggtgcaggg caagtccaag 1440 cgcgagaaga aggaccgggt gttcacagat aagacctctg ccacagtgat ctgtcgcaag 1500 aacgcctcta tcagcgtgcg cgcccaggat cggtactata gctcctcttg gtctgagtgg 1560 gccagcgtgc cttgttccgg cggcggcggc tctggaggag gaggcagcgg cggaggaggc 1620 tcccggaatc tgcctgtggc aacccccgac cctggaatgt tcccatgcct gcaccacagc 1680 cagaacctgc tgcgcgccgt gtccaatatg ctgcagaagg cccggcagac cctggagttt 1740 tacccatgta caagcgagga gatcgaccac gaggatatca ccaaggataa gacatccacc 1800 gtggaggcat gcctgccact ggagctgaca aagaacgagt cttgtctgaa cagccgggag 1860 acaagcttca tcacaaacgg ctcttgcctg gccagccgga agacctcctt tatgatggcc 1920 ctgtgcctga gctccatcta cgaggacctg aagatgtatc aggtggagtt caagacaatg 1980 aacgccaagc tgctgatgga ccccaagcgc cagatctttc tggatcagaa tatgctggcc 2040 gtgatcgacg agctgatgca ggccctgaac tttaatagcg agacagtgcc ccagaagtct 2100 agcctggagg agcctgattt ctacaagaca aagatcaagc tgtgcatcct gctgcacgcc 2160 ttccggatca gagccgtgac catcgacaga gtgatgtctt atctgaatgc cagc 2214 3-782 Sequences 3-782-1 Sequence Number [ID] 782 3-782-2 Molecule Type DNA 3-782-3 Length 1980 3-782-4 Features misc_feature 1..1980 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1980 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-782-5 Residues atgtgccacc agcagctggt catctcttgg ttcagcctgg tgtttctggc atccccactg 60 gtggcaatct gggagctgaa gaaggacgtg tacgtggtgg agctggactg gtatcccgat 120 gcccctggcg agatggtggt gctgacctgc gacacacctg aggaggatgg catcacctgg 180 acactggatc agagctccga ggtgctgggc agcggcaaga ccctgacaat ccaggtgaag 240 gagttcggcg acgccggcca gtacacatgt cacaagggcg gcgaggtgct gtctcacagc 300 ctgctgctgc tgcacaagaa ggaggacggc atctggtcca cagacatcct gaaggatcag 360 aaggagccaa agaacaagac cttcctgagg tgcgaggcca agaattattc tggcaggttc 420 acctgttggt ggctgaccac aatcagcacc gatctgacat tttccgtgaa gtctagccgg 480 ggctcctctg acccccaggg agtgacatgc ggagcagcca ccctgtccgc cgagagggtg 540 agaggcgata acaaggagta cgagtattcc gtggagtgcc aggaggactc tgcctgtcct 600 gcagcagagg agagcctgcc aatcgaagtg atggtggatg ccgtgcacaa gctgaagtac 660 gagaattata caagctcctt ctttatcagg gacatcatca agcctgatcc ccctaagaac 720 ctgcagctga agccactgaa gaattctaga caggtggagg tgagctggga gtacccagac 780 acctggagca caccccactc ctatttctct ctgacctttt gcgtgcaggt gcagggcaag 840 agcaagaggg agaagaagga cagagtgttc accgataaga catccgccac cgtgatctgt 900 cggaagaacg cctccatctc tgtgcgggcc caggatcgct actattctag ctcctggagc 960 gagtgggcat ccgtgccatg ttctggagga ggaggcagcg gcggaggagg ctccggcggc 1020 ggcggctctc gcaatctgcc agtggcaacc cctgacccag gaatgttccc ttgcctgcac 1080 cacagccaga acctgctgcg ggccgtgtcc aatatgctgc agaaggcccg ccagacactg 1140 gagttttacc cttgtacctc tgaggagatc gaccacgagg atatcacaaa ggataagacc 1200 agcacagtgg aggcctgcct gccactggag ctgaccaaga acgagagctg tctgaattcc 1260 agggagacat ctttcatcac caacggcagc tgcctggcct ccagaaagac atcttttatg 1320 atggccctgt gcctgtctag catctacgag gacctgaaga tgtatcaggt ggagttcaag 1380 11 Aug 2023 accatgaacg ccaagctgct gatggaccct aagaggcaga tctttctgga tcagaatatg 1440 ctggccgtga tcgacgagct gatgcaggcc ctgaacttca attccgagac agtgccacag 1500 aagtcctctc tggaggagcc cgatttctac aagaccaaga tcaagctgtg catcctgctg 1560 cacgccttca ggatcagggc cgtgaccatc gacagagtga tgagctatct gaacgccagc 1620 gagtccagga gagtgcggcg caacaagagg agcaagggcg tgcaggtgga gacaatcagc 1680 cccggcgatg gccggacctt tcctaagcgc ggccagacat gcgtggtgca ctacaccggc 1740 atgctgggcg acggcaagaa ggtggacagc tccagggata gaaacaagcc attcaagttt 1800 atgctgggca agcaggaagt gatcagagga tgggaggagg gagtggcaca gatgtccgtg 1860 ggacagggcg ccaagctgac aatctctcca gattacgcat atggagcaac cggacaccca 1920 ggaatcatcc caccccacgc caccctggtg ttcgacgtgg agctgctgga gctggagtga 1980 3-783 Sequences 3-783-1 Sequence Number [ID] 783 2023214349

3-783-2 Molecule Type AA 3-783-3 Length 20 3-783-4 Features source 1..20 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-783-5 Residues MYRMQLLSCI ALSLALVTNS 20 3-784 Sequences 3-784-1 Sequence Number [ID] 784 3-784-2 Molecule Type AA 3-784-3 Length 6 3-784-4 Features REGION 1..6 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..6 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-784-5 Residues EFSTEF 6 3-785 Sequences 3-785-1 Sequence Number [ID] 785 3-785-2 Molecule Type AA 3-785-3 Length 114 3-785-4 Features source 1..114 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-785-5 Residues NWVNVISDLK KIEDLIQSMH IDATLYTESD VHPSCKVTAM KCFLLELQVI SLESGDASIH 60 DTVENLIILA NNSLSSNGNV TESGCKECEE LEEKNIKEFL QSFVHIVQMF INTS 114 3-786 Sequences 3-786-1 Sequence Number [ID] 786 3-786-2 Molecule Type AA 3-786-3 Length 134 3-786-4 Features REGION 1..134 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..134 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-786-5 Residues MYRMQLLSCI ALSLALVTNS NWVNVISDLK KIEDLIQSMH IDATLYTESD VHPSCKVTAM 60 KCFLLELQVI SLESGDASIH DTVENLIILA NNSLSSNGNV TESGCKECEE LEEKNIKEFL 120 QSFVHIVQMF INTS 134 3-787 Sequences 3-787-1 Sequence Number [ID] 787 3-787-2 Molecule Type AA 3-787-3 Length 303 3-787-4 Features REGION 1..303 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..303 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-787-5 Residues MYRMQLLSCI ALSLALVTNS EFSTEFISLI AALAVDYVIG MENAMPWNLP ADLAWFKRNT 60 LNKPVIMGRH TWESIGRPLP GRKNIILSSQ PGTDDRVTWV KSVDEAIAAC GDVPEIMVIG 120

GGRVIEQFLP KAQKLYLTHI DAEVEGDTHF PDYEPDDWES VFSEFHDADA QNSHSYCFEI 180 LERRGGSGGN WVNVISDLKK IEDLIQSMHI DATLYTESDV HPSCKVTAMK CFLLELQVIS 240 LESGDASIHD TVENLIILAN NSLSSNGNVT ESGCKECEEL EEKNIKEFLQ SFVHIVQMFI 300 NTS 303 3-788 Sequences 11 Aug 2023

3-788-1 Sequence Number [ID] 788 3-788-2 Molecule Type DNA 3-788-3 Length 60 3-788-4 Features source 1..60 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-788-5 Residues atgtaccgaa tgcaactgct gagctgcatc gccctgagcc tggcactcgt gaccaacagc 60 3-789 Sequences 3-789-1 Sequence Number [ID] 789 3-789-2 Molecule Type DNA 2023214349

3-789-3 Length 60 3-789-4 Features misc_feature 1..60 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..60 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-789-5 Residues atgtacagga tgcaactcct gtcttgcatt gcactaagtc ttgcacttgt cacaaacagt 60 3-790 Sequences 3-790-1 Sequence Number [ID] 790 3-790-2 Molecule Type DNA 3-790-3 Length 60 3-790-4 Features misc_feature 1..60 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..60 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-790-5 Residues atgtacagga tgcagctgct gagctgcatc gccctgagcc tggccctggt gaccaacagc 60 3-791 Sequences 3-791-1 Sequence Number [ID] 791 3-791-2 Molecule Type DNA 3-791-3 Length 60 3-791-4 Features misc_feature 1..60 Location/Qualifiers note=Description of Artificial Sequence: Synthetic signal sequence source 1..60 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-791-5 Residues atgtacagaa tgcagctgct gagctgcatc gccctgtccc tcgccctggt gaccaactcc 60 3-792 Sequences 3-792-1 Sequence Number [ID] 792 3-792-2 Molecule Type DNA 3-792-3 Length 18 3-792-4 Features misc_feature 1..18 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..18 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-792-5 Residues gagttcagca ccgagttt 18 3-793 Sequences 3-793-1 Sequence Number [ID] 793 3-793-2 Molecule Type DNA 3-793-3 Length 18 3-793-4 Features misc_feature 1..18 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..18 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-793-5 Residues gagttctcca ccgagttc 18

3-794 Sequences 3-794-1 Sequence Number [ID] 794 3-794-2 Molecule Type DNA 3-794-3 Length 345 11 Aug 2023

3-794-4 Features source 1..345 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-794-5 Residues aactgggtga atgtaataag tgatttgaaa aaaattgaag atcttattca atctatgcat 60 attgatgcta ctttatatac ggaaagtgat gttcacccca gttgcaaagt aacagcaatg 120 aagtgctttc tcttggagtt acaagttatt tcacttgagt ccggagatgc aagtattcat 180 gatacagtag aaaatctgat catcctagca aacaacagtt tgtcttctaa tgggaatgta 240 acagaatctg gatgcaaaga atgtgaggaa ctggaggaaa aaaatattaa agaatttttg 300 cagagttttg tacatattgt ccaaatgttc atcaacactt cttga 345 3-795 Sequences 3-795-1 Sequence Number [ID] 795 2023214349

3-795-2 Molecule Type DNA 3-795-3 Length 345 3-795-4 Features misc_feature 1..345 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..345 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-795-5 Residues aactgggtga acgtgatctc cgacctgaag aagatcgagg acctgatcca gtccatgcac 60 atcgacgcca ccctgtacac cgagagcgac gtgcacccta gctgcaaggt gaccgccatg 120 aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgatgc cagcatccac 180 gacacagtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaatgtg 240 accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300 cagtccttcg tgcacatcgt gcagatgttc atcaacacca gctaa 345 3-796 Sequences 3-796-1 Sequence Number [ID] 796 3-796-2 Molecule Type DNA 3-796-3 Length 345 3-796-4 Features misc_feature 1..345 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..345 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-796-5 Residues aactgggtca acgtgatcag cgacctgaag aagatcgagg acctcatcca gtccatgcac 60 attgacgcca ccctgtacac cgagtccgat gtgcacccta gctgcaaggt gaccgccatg 120 aaatgcttcc tgctggagct gcaggtcatc tccttagaaa gcggcgatgc ctccatccac 180 gacaccgtgg agaacctgat catcctggcc aataactccc tgagcagcaa cggcaacgtg 240 accgagagcg gctgcaaaga gtgtgaagag ctggaggaga agaacattaa ggagttcctg 300 cagagcttcg tgcacatcgt gcaaatgttc atcaacacca gctaa 345 3-797 Sequences 3-797-1 Sequence Number [ID] 797 3-797-2 Molecule Type DNA 3-797-3 Length 342 3-797-4 Features misc_feature 1..342 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..342 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-797-5 Residues aactgggtga acgtgatctc cgacctgaaa aagatcgagg atttgatcca gagcatgcac 60 attgacgcca ccctgtatac cgagtccgac gtgcacccga gttgcaaggt gactgccatg 120 aagtgcttcc tgctggagct gcaagtgatc agcctggaga gcggcgacgc cagcatccac 180 gacaccgtgg aaaaccttat cattctggcc aacaatagcc tgagcagcaa cggcaacgtg 240 accgaaagcg gatgtaagga atgcgaggaa ctggaagaga agaatatcaa agaattcctg 300 caaagcttcg tgcacatcgt gcagatgttc atcaacactt ct 342 3-798 Sequences 3-798-1 Sequence Number [ID] 798 3-798-2 Molecule Type DNA 3-798-3 Length 477 3-798-4 Features misc_feature 1..477 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..477 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-798-5 Residues atctctctga ttgcggcgct ggcagttgac cacgttattg gcatggaaaa cgcgatgcca 60 tggaacctcc cggctgacct ggcgtggttc aaacgtaaca ccctgaacaa acctgtgatc 120 atgggtcgtc acacctggga atctattggc cgtcctctcc cgggtcgtaa aaacatcatt 180 11 Aug 2023 ctgtcttctc agccaggcac cgacgaccgt gttacctggg ttaaaagcgt tgacgaagcg 240 attgctgcgt gcggtgatgt tcctgaaatt atggtgatcg gcggtggccg tgtttacgaa 300 cagttcctgc cgaaagcgca gaaactgtac ctgacccaca tcgacgcgga agttgaaggt 360 gacacccact tcccggacta caaaccggat gattgggaga gcgtattctc cgaattccat 420 gatgcggatg cgcaaaactc tcattcttac tgttttgaaa tcctggaacg tcgttga 477 3-799 Sequences 3-799-1 Sequence Number [ID] 799 3-799-2 Molecule Type DNA 3-799-3 Length 405 3-799-4 Features misc_feature 1..405 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide 2023214349 source 1..405 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-799-5 Residues atgtacagga tgcagctgct gagctgcatc gccctgagcc tggccctggt gaccaacagc 60 aactgggtga acgtgatctc cgacctgaag aagatcgagg acctgatcca gtccatgcac 120 atcgacgcca ccctgtacac cgagagcgac gtgcacccta gctgcaaggt gaccgccatg 180 aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgatgc cagcatccac 240 gacacagtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaatgtg 300 accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 360 cagtccttcg tgcacatcgt gcagatgttc atcaacacca gctaa 405 3-800 Sequences 3-800-1 Sequence Number [ID] 800 3-800-2 Molecule Type DNA 3-800-3 Length 912 3-800-4 Features misc_feature 1..912 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..912 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-800-5 Residues atgtacagaa tgcagctgct gagctgcatc gccctgtccc tcgccctggt gaccaactcc 60 gagttctcca ccgagttcat ctccctgatc gccgccctgg ccgtggatta tgtgatcggc 120 atggagaacg ccatgccctg gaatctgccc gccgacctgg cctggttcaa gaggaatacc 180 ctgaacaagc ccgtcatcat gggcaggcac acctgggaaa gcatcggcag acccctgccc 240 ggcaggaaga acatcatcct gtccagccag cccggcaccg acgacagagt gacctgggtg 300 aagagcgtgg acgaagctat cgccgcttgc ggcgacgtgc ccgagatcat ggtgatcggc 360 ggcggcaggg tgatcgaaca gttcctgccc aaggcccaga agctgtacct gacccacatc 420 gatgccgagg tggaaggcga tacacacttc cccgattacg aacctgacga ctgggaaagc 480 gtgttttccg aattccacga cgccgacgcc cagaacagcc acagctactg cttcgagatc 540 ctggaaagaa ggggaggctc cggcggaaac tgggtcaacg tgatcagcga cctgaagaag 600 atcgaggacc tcatccagtc catgcacatt gacgccaccc tgtacaccga gtccgatgtg 660 caccctagct gcaaggtgac cgccatgaaa tgcttcctgc tggagctgca ggtcatctcc 720 ttagaaagcg gcgatgcctc catccacgac accgtggaga acctgatcat cctggccaat 780 aactccctga gcagcaacgg caacgtgacc gagagcggct gcaaagagtg tgaagagctg 840 gaggagaaga acattaagga gttcctgcag agcttcgtgc acatcgtgca aatgttcatc 900 aacaccagct aa 912 3-801 Sequences 3-801-1 Sequence Number [ID] 801 3-801-2 Molecule Type AA 3-801-3 Length 18 3-801-4 Features source 1..18 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-801-5 Residues MDWTWILFLV AAATRVHS 18 3-802 Sequences 3-802-1 Sequence Number [ID] 802 3-802-2 Molecule Type AA 3-802-3 Length 26 3-802-4 Features REGION 1..26 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..26 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-802-5 Residues SGGGSGGGGS GGGGSGGGGS GGGSLQ 26 3-803 Sequences 3-803-1 Sequence Number [ID] 803 11 Aug 2023

3-803-2 Molecule Type AA 3-803-3 Length 237 3-803-4 Features source 1..237 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-803-5 Residues ITCPPPMSVE HADIWVKSYS LYSRERYICN SGFKRKAGTS SLTECVLNKA TNVAHWTTPS 60 LKCIRDPALV HQRPAPPSTV TTAGVTPQPE SLSPSGKEPA ASSPSSNNTA ATTAAIVPGS 120 QLMPSKSPST GTTEISSHES SHGTPSQTTA KNWELTASAS HQPPGVYPQG HSDTTVAIST 180 STVLLCGLSA VSLLACYLKS RQTPPLASVE MEAMEALPVT WGTSSRDEDL ENCSHHL 237 3-804 Sequences 3-804-1 Sequence Number [ID] 804 2023214349

3-804-2 Molecule Type AA 3-804-3 Length 555 3-804-4 Features REGION 1..555 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..555 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-804-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGISL IAALAVDHVI GMENAMPWNL 420 PADLAWFKRN TLNKPVIMGR HTWESIGRPL PGRKNIILSS QPGTDDRVTW VKSVDEAIAA 480 CGDVPEIMVI GGGRVYEQFL PKAQKLYLTH IDAEVEGDTH FPDYKPDDWE SVFSEFHDAD 540 AQNSHSYCFE ILERR 555 3-805 Sequences 3-805-1 Sequence Number [ID] 805 3-805-2 Molecule Type AA 3-805-3 Length 504 3-805-4 Features REGION 1..504 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..504 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-805-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGGVQ VETISPGDGR TFPKRGQTCV 420 VHYTGMLGDG KKVDSSRDRN KPFKFMLGKQ EVIRGWEEGV AQMSVGQGAK LTISPDYAYG 480 ATGHPGIIPP HATLVFDVEL LELE 504 3-806 Sequences 3-806-1 Sequence Number [ID] 806 3-806-2 Molecule Type AA 3-806-3 Length 395 3-806-4 Features REGION 1..395 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..395 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-806-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHL 395 3-807 Sequences

3-807-1 Sequence Number [ID] 807 3-807-2 Molecule Type AA 3-807-3 Length 555 3-807-4 Features REGION 1..555 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..555 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-807-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGISL IAALAVDYVI GMENAMPWNL 420 2023214349

PADLAWFKRN TLNKPVIMGR HTWESIGRPL PGRKNIILSS QPGTDDRVTW VKSVDEAIAA 480 CGDVPEIMVI GGGRVIEQFL PKAQKLYLTH IDAEVEGDTH FPDYEPDDWE SVFSEFHDAD 540 AQNSHSYCFE ILERR 555 3-808 Sequences 3-808-1 Sequence Number [ID] 808 3-808-2 Molecule Type AA 3-808-3 Length 583 3-808-4 Features REGION 1..583 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..583 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-808-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGVGS LNCIVAVSQN MGIGKNGDLP 420 WPPLRNEFRY FQRMTTTSSV EGKQNLVIMG KKTWFSIPEK NRPLKGRINL VLSRELKEPP 480 QGAHFLSRSL DDALKLTEQP ELANKVDMVW IVGGSSVIKE FMNHPGHLKL FVTRIMQDFE 540 SDTFFPEIDL EKYKLLPEYP GVLSDVQEEK GIKYKFEVYE KND 583 3-809 Sequences 3-809-1 Sequence Number [ID] 809 3-809-2 Molecule Type AA 3-809-3 Length 583 3-809-4 Features REGION 1..583 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..583 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-809-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGVGS LNCIVAVSQN MGIGKNGDLP 420 WPPLRNEFRY FFRMTTTSSV EGKQNLVIMG KKTWFSIPEK FRPLKGRINL VLSRELKEPP 480 QGAHFLSRSL DDALKLTEQP ELANKVDMVW IVGGSSVIKE AMNHPGHLKL FVTRIMQDFE 540 SDTFFPEIDL EKYKLLPEYP GVLSDVQEEK GIKYKFEVYE KND 583 3-810 Sequences 3-810-1 Sequence Number [ID] 810 3-810-2 Molecule Type DNA 3-810-3 Length 54 3-810-4 Features source 1..54 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-810-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagc 54 3-811 Sequences 3-811-1 Sequence Number [ID] 811 3-811-2 Molecule Type DNA

3-811-3 Length 78 3-811-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 11 Aug 2023

mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-811-5 Residues tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 60 ggaggaggga gcttgcaa 78 3-812 Sequences 3-812-1 Sequence Number [ID] 812 3-812-2 Molecule Type DNA 3-812-3 Length 714 3-812-4 Features source 1..714 Location/Qualifiers mol_type=other DNA organism=Homo sapiens 2023214349

NonEnglishQualifier Value 3-812-5 Residues atcacgtgcc ctccccccat gtccgtggaa cacgcagaca tctgggtcaa gagctacagc 60 ttgtactcca gggagcggta catttgtaac tctggtttca agcgtaaagc cggcacgtcc 120 agcctgacgg agtgcgtgtt gaacaaggcc acgaatgtcg cccactggac aacccccagt 180 ctcaaatgca ttagagaccc tgccctggtt caccaaaggc cagcgccacc ctccacagta 240 acgacggcag gggtgacccc acagccagag agcctctccc cttctggaaa agagcccgca 300 gcttcatctc ccagctcaaa caacacagcg gccacaacag cagctattgt cccgggctcc 360 cagctgatgc cttcaaaatc accttccaca ggaaccacag agataagcag tcatgagtcc 420 tcccacggca ccccctctca gacaacagcc aagaactggg aactcacagc atccgcctcc 480 caccagccgc caggtgtgta tccacagggc cacagcgaca ccactgtggc tatctccacg 540 tccactgtcc tgctgtgtgg gctgagcgct gtgtctctcc tggcatgcta cctcaagtca 600 aggcaaactc ccccgctggc cagcgttgaa atggaagcca tggaggctct gccggtgact 660 tgggggacca gcagcagaga tgaagacttg gaaaactgct ctcaccacct atga 714 3-813 Sequences 3-813-1 Sequence Number [ID] 813 3-813-2 Molecule Type DNA 3-813-3 Length 711 3-813-4 Features misc_feature 1..711 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..711 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-813-5 Residues attacctgcc cccctccgat gagcgtggag cacgccgaca tctgggtcaa gagctacagc 60 ttgtatagta gggagcggta catctgtaac agcgggttca agaggaaggc cgggaccagc 120 tcactgaccg agtgcgtgtt gaacaaggcc accaacgtgg cccactggac cacccctagc 180 cttaagtgca tcagggaccc agcgctcgta caccagagac ccgcgcctcc ctctacggta 240 accacggcag gcgtaacccc ccagcccgag agcctgtccc cgagcggcaa ggagcctgca 300 gcgagcagcc cctcaagcaa caacacagcc gctaccaccg cggcaatcgt gcccggcagc 360 cagctgatgc cctcaaagag ccccagcacc ggcaccactg agataagcag ccacgagagc 420 tcacacggca ctccctcaca gaccactgcc aagaattggg agctgaccgc ctctgccagc 480 caccagcccc caggcgtgta tccccagggc cacagcgaca ccacggtcgc catcagcaca 540 tctacagtgc ttttgtgcgg ccttagcgcc gtgtcactgc tggcatgcta cttgaaaagt 600 aggcaaactc cccctcttgc cagtgtggaa atggaggcca tggaagccct gcccgtgacc 660 tggggcacca gttctaggga cgaggacctt gagaactgct cacatcattt g 711 3-814 Sequences 3-814-1 Sequence Number [ID] 814 3-814-2 Molecule Type DNA 3-814-3 Length 474 3-814-4 Features misc_feature 1..474 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-814-5 Residues atctctctga ttgcggcgct ggcagttgac tacgttattg gcatggaaaa cgcgatgcca 60 tggaacctcc cggctgacct ggcgtggttc aaacgtaaca ccctgaacaa acctgtgatc 120 atgggtcgtc acacctggga atctattggc cgtcctctcc cgggtcgtaa aaacatcatt 180 ctgtcttctc agccaggcac cgacgaccgt gttacctggg ttaaaagcgt tgacgaagcg 240 attgctgcgt gcggtgatgt tcctgaaatt atggtgatcg gcggtggccg tgttatcgaa 300 cagttcctgc cgaaagcgca gaaactgtac ctgacccaca tcgacgcgga agttgaaggt 360 gacacccact tcccggacta cgaaccggat gattgggaga gcgtattctc cgaattccat 420 gatgcggatg cgcaaaactc tcattcttac tgttttgaaa tcctggaacg tcgt 474 3-815 Sequences 3-815-1 Sequence Number [ID] 815

3-815-2 Molecule Type DNA 3-815-3 Length 474 3-815-4 Features misc_feature 1..474 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) 11 Aug 2023

source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-815-5 Residues atctctctga ttgcggcgct ggcagttgac cacgttattg gcatggaaaa cgcgatgcca 60 tggaacctcc cggctgacct ggcgtggttc aaacgtaaca ccctgaacaa acctgtgatc 120 atgggtcgtc acacctggga atctattggc cgtcctctcc cgggtcgtaa aaacatcatt 180 ctgtcttctc agccaggcac cgacgaccgt gttacctggg ttaaaagcgt tgacgaagcg 240 attgctgcgt gcggtgatgt tcctgaaatt atggtgatcg gcggtggccg tgtttacgaa 300 cagttcctgc cgaaagcgca gaaactgtac ctgacccaca tcgacgcgga agttgaaggt 360 gacacccact tcccggacta caaaccggat gattgggaga gcgtattctc cgaattccat 420 gatgcggatg cgcaaaactc tcattcttac tgttttgaaa tcctggaacg tcgt 474 2023214349

3-816 Sequences 3-816-1 Sequence Number [ID] 816 3-816-2 Molecule Type DNA 3-816-3 Length 1668 3-816-4 Features misc_feature 1..1668 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1668 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-816-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagcgg catctctctg 1200 attgcggcgc tggcagttga ccacgttatt ggcatggaaa acgcgatgcc atggaacctc 1260 ccggctgacc tggcgtggtt caaacgtaac accctgaaca aacctgtgat catgggtcgt 1320 cacacctggg aatctattgg ccgtcctctc ccgggtcgta aaaacatcat tctgtcttct 1380 cagccaggca ccgacgaccg tgttacctgg gttaaaagcg ttgacgaagc gattgctgcg 1440 tgcggtgatg ttcctgaaat tatggtgatc ggcggtggcc gtgtttacga acagttcctg 1500 ccgaaagcgc agaaactgta cctgacccac atcgacgcgg aagttgaagg tgacacccac 1560 ttcccggact acaaaccgga tgattgggag agcgtattct ccgaattcca tgatgcggat 1620 gcgcaaaact ctcattctta ctgttttgaa atcctggaac gtcgttga 1668 3-817 Sequences 3-817-1 Sequence Number [ID] 817 3-817-2 Molecule Type DNA 3-817-3 Length 1515 3-817-4 Features misc_feature 1..1515 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1515 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-817-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 11 Aug 2023 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagcgg cggcgtgcag 1200 gttgagacta taagcccagg cgacggcagg accttcccca agaggggcca gacatgcgtg 1260 gtgcactaca ccggcatgct tggcgacggc aaaaaggtgg actcaagcag ggacaggaac 1320 aagcccttca agttcatgtt gggcaaacag gaggtgatca gaggctggga ggagggtgtt 1380 gcccagatga gcgtggggca gggcgccaag ctcacgataa gtcccgatta cgcctacggc 1440 gccaccggtc accccggcat catcccccca cacgccaccc tggtgttcga cgtggaattg 1500 2023214349 ctggagctgg agtga 1515 3-818 Sequences 3-818-1 Sequence Number [ID] 818 3-818-2 Molecule Type DNA 3-818-3 Length 1188 3-818-4 Features misc_feature 1..1188 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1188 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-818-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgtga 1188 3-819 Sequences 3-819-1 Sequence Number [ID] 819 3-819-2 Molecule Type DNA 3-819-3 Length 1668 3-819-4 Features misc_feature 1..1668 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1668 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-819-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagcgg catctctctg 1200 11 Aug 2023 attgcggcgc tggcagttga ctacgttatt ggcatggaaa acgcgatgcc atggaacctc 1260 ccggctgacc tggcgtggtt caaacgtaac accctgaaca aacctgtgat catgggtcgt 1320 cacacctggg aatctattgg ccgtcctctc ccgggtcgta aaaacatcat tctgtcttct 1380 cagccaggca ccgacgaccg tgttacctgg gttaaaagcg ttgacgaagc gattgctgcg 1440 tgcggtgatg ttcctgaaat tatggtgatc ggcggtggcc gtgttatcga acagttcctg 1500 ccgaaagcgc agaaactgta cctgacccac atcgacgcgg aagttgaagg tgacacccac 1560 ttcccggact acgaaccgga tgattgggag agcgtattct ccgaattcca tgatgcggat 1620 gcgcaaaact ctcattctta ctgttttgaa atcctggaac gtcgttga 1668 3-820 Sequences 3-820-1 Sequence Number [ID] 820 3-820-2 Molecule Type DNA 3-820-3 Length 1752 2023214349

3-820-4 Features misc_feature 1..1752 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1752 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-820-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagcgg cgttggttcg 1200 ctaaactgca tcgtcgctgt gtcccagaac atgggcatcg gcaagaacgg ggacctgccc 1260 tggccaccgc tcaggaatga attcagatat ttccagagaa tgaccacaac ctcttcagta 1320 gaaggtaaac agaatctggt gattatgggt aagaagacct ggttctccat tcctgagaag 1380 aatcgacctt taaagggtag aattaattta gttctcagca gagaactcaa ggaacctcca 1440 caaggagctc attttctttc cagaagtcta gatgatgcct taaaacttac tgaacaacca 1500 gaattagcaa ataaagtaga catggtctgg atagttggtg gcagttctgt tattaaggaa 1560 ttcatgaatc acccaggcca tcttaaacta tttgtgacaa ggatcatgca agactttgaa 1620 agtgacacgt tttttccaga aattgatttg gagaaatata aacttctgcc agaataccca 1680 ggtgttctct ctgatgtcca ggaggagaaa ggcattaagt acaaatttga agtatatgag 1740 aagaatgatt ga 1752 3-821 Sequences 3-821-1 Sequence Number [ID] 821 3-821-2 Molecule Type DNA 3-821-3 Length 1752 3-821-4 Features misc_feature 1..1752 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1752 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-821-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 11 Aug 2023 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagcgg cgttggttcg 1200 ctaaactgca tcgtcgctgt gtcccagaac atgggcatcg gcaagaacgg ggacctgccc 1260 tggccaccgc tcaggaatga attcagatat ttcttcagaa tgaccacaac ctcttcagta 1320 gaaggtaaac agaatctggt gattatgggt aagaagacct ggttctccat tcctgagaag 1380 ttccgacctt taaagggtag aattaattta gttctcagca gagaactcaa ggaacctcca 1440 caaggagctc attttctttc cagaagtcta gatgatgcct taaaacttac tgaacaacca 1500 gaattagcaa ataaagtaga catggtctgg atagttggtg gcagttctgt tattaaggaa 1560 gccatgaatc acccaggcca tcttaaacta tttgtgacaa ggatcatgca agactttgaa 1620 2023214349 agtgacacgt tttttccaga aattgatttg gagaaatata aacttctgcc agaataccca 1680 ggtgttctct ctgatgtcca ggaggagaaa ggcattaagt acaaatttga agtatatgag 1740 aagaatgatt ga 1752 3-822 Sequences 3-822-1 Sequence Number [ID] 822 3-822-2 Molecule Type AA 3-822-3 Length 4 3-822-4 Features REGION 1..4 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..4 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-822-5 Residues GGSG 4 3-823 Sequences 3-823-1 Sequence Number [ID] 823 3-823-2 Molecule Type DNA 3-823-3 Length 12 3-823-4 Features misc_feature 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..12 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-823-5 Residues ggaggatctg ga 12 3-824 Sequences 3-824-1 Sequence Number [ID] 824 3-824-2 Molecule Type AA 3-824-3 Length 6 3-824-4 Features REGION 1..6 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..6 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-824-5 Residues GGSGGG 6 3-825 Sequences 3-825-1 Sequence Number [ID] 825 3-825-2 Molecule Type DNA 3-825-3 Length 18 3-825-4 Features misc_feature 1..18 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..18 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-825-5 Residues ggtggctctg gtggtggt 18 3-826 Sequences 3-826-1 Sequence Number [ID] 826 3-826-2 Molecule Type DNA 3-826-3 Length 18 3-826-4 Features misc_feature 1..18 Location/Qualifiers note=Description of Artificial Sequence: Synthetic Linker sequence source 1..18 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-826-5 Residues ggaggtagtg gtggaggc 18 3-827 Sequences 3-827-1 Sequence Number [ID] 827 3-827-2 Molecule Type AA 3-827-3 Length 5 3-827-4 Features REGION 1..5 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..5 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-827-5 Residues SGGGS 5 2023214349

3-828 Sequences 3-828-1 Sequence Number [ID] 828 3-828-2 Molecule Type DNA 3-828-3 Length 15 3-828-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-828-5 Residues tcaggtggcg gtagt 15 3-829 Sequences 3-829-1 Sequence Number [ID] 829 3-829-2 Molecule Type AA 3-829-3 Length 9 3-829-4 Features REGION 1..9 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..9 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-829-5 Residues GGSGGGSGG 9 3-830 Sequences 3-830-1 Sequence Number [ID] 830 3-830-2 Molecule Type DNA 3-830-3 Length 27 3-830-4 Features misc_feature 1..27 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..27 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-830-5 Residues ggaggtagtg gtggaggcag tggtgga 27 3-831 Sequences 3-831-1 Sequence Number [ID] 831 3-831-2 Molecule Type AA 3-831-3 Length 5 3-831-4 Features REGION 1..5 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..5 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-831-5 Residues GGGGG 5 3-832 Sequences 3-832-1 Sequence Number [ID] 832 3-832-2 Molecule Type AA 3-832-3 Length 5 3-832-4 Features REGION 1..5 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..5 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-832-5 Residues GGGGS 5 3-833 Sequences 11 Aug 2023

3-833-1 Sequence Number [ID] 833 3-833-2 Molecule Type AA 3-833-3 Length 10 3-833-4 Features REGION 1..10 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..10 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-833-5 Residues GGGGSGGGGS 10 3-834 Sequences 3-834-1 Sequence Number [ID] 834 2023214349

3-834-2 Molecule Type AA 3-834-3 Length 20 3-834-4 Features REGION 1..20 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..20 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-834-5 Residues GGGGSGGGGS GGGGSGGGGS 20 3-835 Sequences 3-835-1 Sequence Number [ID] 835 3-835-2 Molecule Type AA 3-835-3 Length 25 3-835-4 Features REGION 1..25 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..25 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-835-5 Residues GGGGSGGGGS GGGGSGGGGS GGGGS 25 3-836 Sequences 3-836-1 Sequence Number [ID] 836 3-836-2 Molecule Type AA 3-836-3 Length 30 3-836-4 Features REGION 1..30 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..30 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-836-5 Residues GGGGSGGGGS GGGGSGGGGS GGGGSGGGGS 30 3-837 Sequences 3-837-1 Sequence Number [ID] 837 3-837-2 Molecule Type AA 3-837-3 Length 5 3-837-4 Features REGION 1..5 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..5 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-837-5 Residues SSSSG 5 3-838 Sequences 3-838-1 Sequence Number [ID] 838 3-838-2 Molecule Type AA 3-838-3 Length 10 3-838-4 Features REGION 1..10 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..10 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-838-5 Residues SSSSGSSSSG 10 3-839 Sequences 3-839-1 Sequence Number [ID] 839 3-839-2 Molecule Type AA 11 Aug 2023

3-839-3 Length 15 3-839-4 Features REGION 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-839-5 Residues SSSSGSSSSG SSSSG 15 3-840 Sequences 3-840-1 Sequence Number [ID] 840 3-840-2 Molecule Type AA 3-840-3 Length 20 2023214349

3-840-4 Features REGION 1..20 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..20 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-840-5 Residues SSSSGSSSSG SSSSGSSSSG 20 3-841 Sequences 3-841-1 Sequence Number [ID] 841 3-841-2 Molecule Type AA 3-841-3 Length 25 3-841-4 Features REGION 1..25 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..25 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-841-5 Residues SSSSGSSSSG SSSSGSSSSG SSSSG 25 3-842 Sequences 3-842-1 Sequence Number [ID] 842 3-842-2 Molecule Type AA 3-842-3 Length 30 3-842-4 Features REGION 1..30 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..30 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-842-5 Residues SSSSGSSSSG SSSSGSSSSG SSSSGSSSSG 30 3-843 Sequences 3-843-1 Sequence Number [ID] 843 3-843-2 Molecule Type 3-843-3 Length 3-843-4 Features Location/Qualifiers NonEnglishQualifier Value 3-843-5 Residues 000 3 3-844 Sequences 3-844-1 Sequence Number [ID] 844 3-844-2 Molecule Type DNA 3-844-3 Length 15 3-844-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-844-5 Residues agcggcggtg gcagc 15 3-845 Sequences 3-845-1 Sequence Number [ID] 845 3-845-2 Molecule Type AA 3-845-3 Length 12

3-845-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..12 mol_type=protein 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-845-5 Residues GKSSGSGSES KS 12 3-846 Sequences 3-846-1 Sequence Number [ID] 846 3-846-2 Molecule Type AA 3-846-3 Length 15 3-846-4 Features REGION 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=protein organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-846-5 Residues GGSTSGSGKS SEGKG 15 3-847 Sequences 3-847-1 Sequence Number [ID] 847 3-847-2 Molecule Type AA 3-847-3 Length 19 3-847-4 Features REGION 1..19 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..19 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-847-5 Residues GSTSGSGKSS SEGSGSTKG 19 3-848 Sequences 3-848-1 Sequence Number [ID] 848 3-848-2 Molecule Type AA 3-848-3 Length 18 3-848-4 Features REGION 1..18 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..18 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-848-5 Residues GSTSGSGKPG SGEGSTKG 18 3-849 Sequences 3-849-1 Sequence Number [ID] 849 3-849-2 Molecule Type AA 3-849-3 Length 13 3-849-4 Features REGION 1..13 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..13 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-849-5 Residues VDYPYDVPDY ALD 13 3-850 Sequences 3-850-1 Sequence Number [ID] 850 3-850-2 Molecule Type DNA 3-850-3 Length 39 3-850-4 Features misc_feature 1..39 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..39 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-850-5 Residues gtcgactatc cctacgatgt tccggactac gcactggac 39 3-851 Sequences 3-851-1 Sequence Number [ID] 851 3-851-2 Molecule Type AA 3-851-3 Length 14 3-851-4 Features REGION 1..14 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..14 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-851-5 Residues EGKSSGSGSE SKEF 14 3-852 Sequences 3-852-1 Sequence Number [ID] 852 3-852-2 Molecule Type DNA 3-852-3 Length 561 3-852-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-852-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 2023214349

ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattacgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aatcatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-853 Sequences 3-853-1 Sequence Number [ID] 853 3-853-2 Molecule Type DNA 3-853-3 Length 561 3-853-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-853-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 acggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-854 Sequences 3-854-1 Sequence Number [ID] 854 3-854-2 Molecule Type DNA 3-854-3 Length 561 3-854-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-854-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaata acgttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-855 Sequences 3-855-1 Sequence Number [ID] 855 3-855-2 Molecule Type DNA 3-855-3 Length 561 3-855-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-855-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tatttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gttattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-856 Sequences 3-856-1 Sequence Number [ID] 856 3-856-2 Molecule Type DNA 2023214349

3-856-3 Length 561 3-856-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-856-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtg cagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacgc gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-857 Sequences 3-857-1 Sequence Number [ID] 857 3-857-2 Molecule Type DNA 3-857-3 Length 561 3-857-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-857-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gctattaagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-858 Sequences 3-858-1 Sequence Number [ID] 858 3-858-2 Molecule Type AA 3-858-3 Length 557 3-858-4 Features source 1..557 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-858-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP 60 FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE 120 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL 180 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVHPK GPKSLLSLEL KDDRPARDMW 240 VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL 300 IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG 360 LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF 420 YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS 480 PHGSAWDPSR EATSLAGSQS YEDMRGILYA APQLRSIRGQ PGPNHEEDAD SYENMDNPDG 540 PDPAWGGGGR MGTWSTR 557

3-859 Sequences 3-859-1 Sequence Number [ID] 859 3-859-2 Molecule Type AA 3-859-3 Length 556 11 Aug 2023

3-859-4 Features source 1..556 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-859-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP 60 FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE 120 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL 180 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVHPK GPKSLLSLEL KDDRPARDMW 240 VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL 300 IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG 360 LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF 420 YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS 480 2023214349

PHGSAWDPSR EATSLGSQSY EDMRGILYAA PQLRSIRGQP GPNHEEDADS YENMDNPDGP 540 DPAWGGGGRM GTWSTR 556 3-860 Sequences 3-860-1 Sequence Number [ID] 860 3-860-2 Molecule Type AA 3-860-3 Length 557 3-860-4 Features source 1..557 Location/Qualifiers mol_type=protein organism=Macaca mulatta NonEnglishQualifier Value 3-860-5 Residues MPPPCLLFFL LFLTPMEVRP QEPLVVKVEE GDNAVLQCLE GTSDGPTQQL VWCRDSPFEP 60 FLNLSLGLPG MGIRMGPLGI WLLIFNVSNQ TGGFYLCQPG LPSEKAWQPG WTVSVEGSGE 120 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LNSSQLYVWA KDRPEMWEGE PVCGPPRDSL 180 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVRPK GPKSSLLSLE LKDDRPDRDM 240 WVVDTGLLLT RATAQDAGKY YCHRGNWTKS FYLEITARPA LWHWLLRIGG WKVPAVTLTY 300 LIFCLCSLVG ILQLQRALVL RRKRKRMTDP TRRFFKVTPP PGSGPQNQYG NVLSLPTPTS 360 GLGRAQRWAA GLGGTAPSYG NPSSDVQVDG AVGSRSPPGA GPEEEEGEGY EEPDSEEGSE 420 FYENDSNFGQ DQLSQDGSGY ENPEDEPLGP EDEDSFSNAE SYENEDEELT QPVARTMDFL 480 SPHGSAWDPS REATSLGSQS YEDMRGLLYA APQLRTIRGQ PGPNHEEDAD SYENMDNPDG 540 PDPAWGGGGR MGTWSAR 557 3-861 Sequences 3-861-1 Sequence Number [ID] 861 3-861-2 Molecule Type AA 3-861-3 Length 557 3-861-4 Features REGION 1..557 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 mutant source 1..557 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-861-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP 60 FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE 120 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL 180 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVRPK GPKSLLSLEL KDDRPDRDMW 240 VVDTGLLLTR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL 300 IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG 360 LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF 420 YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS 480 PHGSAWDPSR EATSLAGSQS YEDMRGILYA APQLRSIRGQ PGPNHEEDAD SYENMDNPDG 540 PDPAWGGGGR MGTWSTR 557 3-862 Sequences 3-862-1 Sequence Number [ID] 862 3-862-2 Molecule Type AA 3-862-3 Length 557 3-862-4 Features REGION 1..557 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 mutant source 1..557 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-862-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP 60 FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE 120 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL 180 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVRPK GPKSLLSLEL KDDRPDRDMW 240 VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL 300 IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG 360

LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF 420 YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS 480 PHGSAWDPSR EATSLAGSQS YEDMRGILYA APQLRSIRGQ PGPNHEEDAD SYENMDNPDG 540 PDPAWGGGGR MGTWSTR 557 3-863 Sequences 11 Aug 2023

3-863-1 Sequence Number [ID] 863 3-863-2 Molecule Type AA 3-863-3 Length 467 3-863-4 Features REGION 1..467 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 mutant source 1..467 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-863-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEG ELFRWNVSDL GGLGCGLKNR SSEGPSSPSG 60 KLMSPKLYVW AKDRPEIWEG EPPCLPPRDS LNQSLSQDLT MAPGSTLWLS CGVPPDSVSR 120 2023214349

GPLSWTHVHP KGPKSLLSLE LKDDRPARDM WVMETGLLLP RATAQDAGKY YCHRGNLTMS 180 FHLEITARPV LWHWLLRTGG WKVSAVTLAY LIFCLCSLVG ILHLQRALVL RRKRKRMTDP 240 TRRFFKVTPP PGSGPQNQYG NVLSLPTPTS GLGRAQRWAA GLGGTAPSYG NPSSDVQADG 300 ALGSRSPPGV GPEEEEGEGY EEPDSEEDSE FYENDSNLGQ DQLSQDGSGY ENPEDEPLGP 360 EDEDSFSNAE SYENEDEELT QPVARTMDFL SPHGSAWDPS REATSLGSQS YEDMRGILYA 420 APQLRSIRGQ PGPNHEEDAD SYENMDNPDG PDPAWGGGGR MGTWSTR 467 3-864 Sequences 3-864-1 Sequence Number [ID] 864 3-864-2 Molecule Type AA 3-864-3 Length 278 3-864-4 Features REGION 1..278 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 mutant source 1..278 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-864-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP 60 FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE 120 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL 180 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVHPK GPKSLLSLEL KDDRPARDMW 240 VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARP 278 3-865 Sequences 3-865-1 Sequence Number [ID] 865 3-865-2 Molecule Type AA 3-865-3 Length 189 3-865-4 Features REGION 1..189 Location/Qualifiers note=Description of Artificial Sequence: Synthetic CD19 mutant source 1..189 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-865-5 Residues MPPPRLLFFL LFLTPMEVRP EEPLVVKVEG ELFRWNVSDL GGLGCGLKNR SSEGPSSPSG 60 KLMSPKLYVW AKDRPEIWEG EPPCLPPRDS LNQSLSQDLT MAPGSTLWLS CGVPPDSVSR 120 GPLSWTHVHP KGPKSLLSLE LKDDRPARDM WVMETGLLLP RATAQDAGKY YCHRGNLTMS 180 FHLEITARP 189 3-866 Sequences 3-866-1 Sequence Number [ID] 866 3-866-2 Molecule Type AA 3-866-3 Length 311 3-866-4 Features source 1..311 Location/Qualifiers mol_type=protein organism=Renilla reniformis NonEnglishQualifier Value 3-866-5 Residues MTSKVYDPEQ RKRMITGPQW WARCKQMNVL DSFINYYDSE KHAENAVIFL HGNAASSYLW 60 RHVVPHIEPV ARCIIPDLIG MGKSGKSGNG SYRLLDHYKY LTAWFELLNL PKKIIFVGHD 120 WGACLAFHYS YEHQDKIKAI VHAESVVDVI ESWDEWPDIE EDIALIKSEE GEKMVLENNF 180 FVETMLPSKI MRKLEPEEFA AYLEPFKEKG EVRRPTLSWP REIPLVKGGK PDVVQIVRNY 240 NAYLRASDDL PKMFIESDPG FFSNAIVEGA KKFPNTEFVK VKGLHFSQED APDEMGKYIK 300 SFVERVLKNE Q 311 3-867 Sequences 3-867-1 Sequence Number [ID] 867 3-867-2 Molecule Type DNA 3-867-3 Length 936 3-867-4 Features source 1..936 Location/Qualifiers mol_type=other DNA organism=Renilla reniformis NonEnglishQualifier Value 3-867-5 Residues atgacttcca aggtgtacga ccccgagcaa cgcaaacgca tgatcactgg gcctcagtgg 60 tgggctcgct gcaagcaaat gaacgtgctg gactccttca tcaactacta tgattccgag 120 aagcacgccg agaacgccgt gatttttctg catggtaacg ctgcctccag ctacctgtgg 180 11 Aug 2023 aggcacgtcg tgcctcacat cgagcccgtg gctagatgca tcatccctga tctgatcgga 240 atgggtaagt ccggcaagag cgggaatggc tcatatcgcc tcctggatca ctacaagtac 300 ctcaccgctt ggttcgagct gctgaacctt ccaaagaaaa tcatctttgt gggccacgac 360 tggggggctt gtctggcctt tcactactcc tacgagcacc aagacaagat caaggccatc 420 gtccatgctg agagtgtcgt ggacgtgatc gagtcctggg acgagtggcc tgacatcgag 480 gaggatatcg ccctgatcaa gagcgaagag ggcgagaaaa tggtgcttga gaataacttc 540 ttcgtcgaga ccatgctccc aagcaagatc atgcggaaac tggagcctga ggagttcgct 600 gcctacctgg agccattcaa ggagaagggc gaggttagac ggcctaccct ctcctggcct 660 cgcgagatcc ctctcgttaa gggaggcaag cccgacgtcg tccagattgt ccgcaactac 720 aacgcctacc ttcgggccag cgacgatctg cctaagatgt tcatcgagtc cgaccctggg 780 ttcttttcca acgctattgt cgagggagct aagaagttcc ctaacaccga gttcgtgaag 840 gtgaagggcc tccacttcag ccaggaggac gctccagatg aaatgggtaa gtacatcaag 900 2023214349 agcttcgtgg agcgcgtgct gaagaacgag cagtaa 936 3-868 Sequences 3-868-1 Sequence Number [ID] 868 3-868-2 Molecule Type AA 3-868-3 Length 550 3-868-4 Features source 1..550 Location/Qualifiers mol_type=protein organism=Photinus pyralis NonEnglishQualifier Value 3-868-5 Residues MEDAKNIKKG PAPFYPLEDG TAGEQLHKAM KRYALVPGTI AFTDAHIEVD ITYAEYFEMS 60 VRLAEAMKRY GLNTNHRIVV CSENSLQFFM PVLGALFIGV AVAPANDIYN ERELLNSMGI 120 SQPTVVFVSK KGLQKILNVQ KKLPIIQKII IMDSKTDYQG FQSMYTFVTS HLPPGFNEYD 180 FVPESFDRDK TIALIMNSSG STGLPKGVAL PHRTACVRFS HARDPIFGNQ IIPDTAILSV 240 VPFHHGFGMF TTLGYLICGF RVVLMYRFEE ELFLRSLQDY KIQSALLVPT LFSFFAKSTL 300 IDKYDLSNLH EIASGGAPLS KEVGEAVAKR FHLPGIRQGY GLTETTSAIL ITPEGDDKPG 360 AVGKVVPFFE AKVVDLDTGK TLGVNQRGEL CVRGPMIMSG YVNNPEATNA LIDKDGWLHS 420 GDIAYWDEDE HFFIVDRLKS LIKYKGYQVA PAELESILLQ HPNIFDAGVA GLPDDDAGEL 480 PAAVVVLEHG KTMTEKEIVD YVASQVTTAK KLRGGVVFVD EVPKGLTGKL DARKIREILI 540 KAKKGGKSKL 550 3-869 Sequences 3-869-1 Sequence Number [ID] 869 3-869-2 Molecule Type DNA 3-869-3 Length 1653 3-869-4 Features source 1..1653 Location/Qualifiers mol_type=other DNA organism=Photinus pyralis NonEnglishQualifier Value 3-869-5 Residues atggaagatg ccaaaaacat taagaagggc ccagcgccat tctacccact cgaagacggg 60 accgccggcg agcagctgca caaagccatg aagcgctacg ccctggtgcc cggcaccatc 120 gcctttaccg acgcacatat cgaggtggac attacctacg ccgagtactt cgagatgagc 180 gttcggctgg cagaagctat gaagcgctat gggctgaata caaaccatcg gatcgtggtg 240 tgcagcgaga atagcttgca gttcttcatg cccgtgttgg gtgccctgtt catcggtgtg 300 gctgtggccc cagctaacga catctacaac gagcgcgagc tgctgaacag catgggcatc 360 agccagccca ccgtcgtatt cgtgagcaag aaagggctgc aaaagatcct caacgtgcaa 420 aagaagctac cgatcataca aaagatcatc atcatggata gcaagaccga ctaccagggc 480 ttccaaagca tgtacacctt cgtgacttcc catttgccac ccggcttcaa cgagtacgac 540 ttcgtgcccg agagcttcga ccgggacaaa accatcgccc tgatcatgaa cagtagtggc 600 agtaccggat tgcccaaggg cgtagcccta ccgcaccgca ccgcttgtgt ccgattcagt 660 catgcccgcg accccatctt cggcaaccag atcatccccg acaccgctat cctcagcgtg 720 gtgccatttc accacggctt cggcatgttc accacgctgg gctacttgat ctgcggcttt 780 cgggtcgtgc tcatgtaccg cttcgaggag gagctattct tgcgcagctt gcaagactat 840 aagattcaat ctgccctgct ggtgcccaca ctatttagct tcttcgctaa gagcactctc 900 atcgacaagt acgacctaag caacttgcac gagatcgcca gcggcggggc gccgctcagc 960 aaggaggtag gtgaggccgt ggccaaacgc ttccacctac caggcatccg ccagggctac 1020 ggcctgacag aaacaaccag cgccattctg atcacccccg aaggggacga caagcctggc 1080 gcagtaggca aggtggtgcc cttcttcgag gctaaggtgg tggacttgga caccggtaag 1140 acactgggtg tgaaccagcg cggcgagctg tgcgtccgtg gccccatgat catgagcggc 1200 tacgttaaca accccgaggc tacaaacgct ctcatcgaca aggacggctg gctgcacagc 1260 ggcgacatcg cctactggga cgaggacgag cacttcttca tcgtggaccg gctgaagagc 1320 ctgatcaaat acaagggcta ccaggtagcc ccagccgaac tggagagcat cctgctgcaa 1380 caccccaaca tcttcgacgc cggggtcgcc ggcctgcccg acgacgatgc cggcgagctg 1440 cccgccgcag tcgtcgtgct ggaacacggt aaaaccatga ccgagaagga gatcgtggac 1500 tatgtggcca gccaggttac aaccgccaag aagctgcgcg gtggtgttgt gttcgtggac 1560 gaggtgccta aaggactgac cggcaagttg gacgcccgca agatccgcga gattctcatt 1620 aaggccaaga agggcggcaa gagcaagctg tga 1653 3-870 Sequences

3-870-1 Sequence Number [ID] 870 3-870-2 Molecule Type AA 3-870-3 Length 239 3-870-4 Features REGION 1..239 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..239 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-870-5 Residues MVSKGAELFT GIVPILIELN GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWPT 60 LVTTLSYGVQ CFSRYPDHMK QHDFFKSAMP EGYIQERTIF FEDDGNYKSR AEVKFEGDTL 120 VNRIELTGTD FKEDGNILGN KMEYNYNAHN VYIMTDKAKN GIKVNFKIRH NIEDGSVQLA 180 DHYQQNTPIG DGPVLLPDNH YLSTQSALSK DPNEKRDHMI YFGFVTAAAI THGMDELYK 239 3-871 Sequences 3-871-1 Sequence Number [ID] 871 3-871-2 Molecule Type AA 2023214349

3-871-3 Length 187 3-871-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-871-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKP TGRSGLADKV DMARIVGGSS 120 VCKEAIRYPG HPKLPVTRTM QDFESDTSLP EVALEKYKLL PEYPGVLSGA QEEKGARYKF 180 EAYERSD 187 3-872 Sequences 3-872-1 Sequence Number [ID] 872 3-872-2 Molecule Type AA 3-872-3 Length 187 3-872-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-872-5 Residues MAGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFGYFRRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKP TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYERND 187 3-873 Sequences 3-873-1 Sequence Number [ID] 873 3-873-2 Molecule Type AA 3-873-3 Length 187 3-873-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-873-5 Residues MVGSLNCIVA VSQNMSVGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHLL SRSLDGALKL TEQPELANKV DMVWIVGGSS 120 VYEEAMNHPG HLKLFVTRIV QDFESGTFFP EIDLERYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187 3-874 Sequences 3-874-1 Sequence Number [ID] 874 3-874-2 Molecule Type AA 3-874-3 Length 187 3-874-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-874-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYLQGMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKARPSEG GINLVLSREP KEPPQGAHFL SRSLDDALGL TEQPELANKV DMVWIVDGSS 120 VYKEAMNHPG HPKLFVTRVI QGFESGTFFP EIDLEKYKLL PEYPGVLSDV QEGKGIKYKF 180 EVYEKNG 187 3-875 Sequences

3-875-1 Sequence Number [ID] 875 3-875-2 Molecule Type AA 3-875-3 Length 187 3-875-4 Features REGION 1..187 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-875-5 Residues MVGSLNCIVA VSQNMGNGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDASRL TEQPELANKV DTVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP GIDLEKYKLL PGYPGVLSDV QGEKGIKYKF 180 EVYEKND 187 3-876 Sequences 3-876-1 Sequence Number [ID] 876 3-876-2 Molecule Type AA 2023214349

3-876-3 Length 187 3-876-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-876-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTGIM QGSESDTFFP EIDLERYELL PGYPGALSDV QEEKGIECKF 180 EVYEESD 187 3-877 Sequences 3-877-1 Sequence Number [ID] 877 3-877-2 Molecule Type AA 3-877-3 Length 187 3-877-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-877-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL REPPQGAHFL SRSLDDALRP TGQPELADKV DMVWIVGGSS 120 VYREAMNRPG HLKLFVTRIM QGFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKL 180 EVYEEND 187 3-878 Sequences 3-878-1 Sequence Number [ID] 878 3-878-2 Molecule Type AA 3-878-3 Length 187 3-878-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-878-5 Residues MVGSLNCIVA VSQSMGIGKN GDLSWPPLRN EFRYLQRMTT TSSVEGKQNL VITGKETWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SGGLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMSYPG HLKLLVTRIM QDSESDTFFP EIDLEKYKPP PEYPGVLSDV QEAKGIKYKL 180 EVYEKND 187 3-879 Sequences 3-879-1 Sequence Number [ID] 879 3-879-2 Molecule Type AA 3-879-3 Length 187 3-879-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-879-5 Residues MAGSLNCIVA VSQNMGVGKN GDLPWPPLRD GFRYFRRMTT TSSVEGKQNL VIMGKKTWSS 60 IPEKNRPLEG RTNLVLSREL KEPPQGAYLL SRSLDDALKL TEQPELADEA GMVWVVGGSS 120 VDKEAMNHPG HPKLSVTRIV QDFGSDAFFP EIDLEKCKLL PEYPGVLSDA QEERGIKYKF 180 EVYEKSD 187 3-880 Sequences

3-880-1 Sequence Number [ID] 880 3-880-2 Molecule Type AA 3-880-3 Length 187 3-880-4 Features REGION 1..187 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-880-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPPRH EFRYFQRVTT TSSAEGKQNL VIMGKKTWFS 60 IPEKNRPSKG RIGLVLSGEL KEPPQGAHFL SRSLDDTLRL TEQPELTNRV NMVWIVGGSS 120 VYKEAMNHPG HLRPVVTRIM QDFESDAFFP EVDLEKYRLL PEYPGVLSDV QGEKGIKYKF 180 EAYRKND 187 3-881 Sequences 3-881-1 Sequence Number [ID] 881 3-881-2 Molecule Type AA 2023214349

3-881-3 Length 186 3-881-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-881-5 Residues MVGSLNCIVT VSRSMGIGKD GDLSWPPLRS EFRYFQRTTA TSSVEGRQSL VIMGKRTWFS 60 TPERNRPLRG RANLVLSGEL KGPPQGAHLL SRSLDGALKL TEQPELADKV DVVRIVGGSS 120 VDEEAMNHPG HLKLFVTRVM RGFESDTLFP GIDLGKRKLL PEYPGVLSDV REEKGIKYKL 180 EVCGNN 186 3-882 Sequences 3-882-1 Sequence Number [ID] 882 3-882-2 Molecule Type AA 3-882-3 Length 186 3-882-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-882-5 Residues VGSLNCIVAV SQNMGVGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-883 Sequences 3-883-1 Sequence Number [ID] 883 3-883-2 Molecule Type AA 3-883-3 Length 186 3-883-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-883-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMNHPGH LKLFVTRIIQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-884 Sequences 3-884-1 Sequence Number [ID] 884 3-884-2 Molecule Type AA 3-884-3 Length 186 3-884-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-884-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMYHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-885 Sequences

3-885-1 Sequence Number [ID] 885 3-885-2 Molecule Type AA 3-885-3 Length 186 3-885-4 Features REGION 1..186 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-885-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMNHPGR LKLFVTRIMQ DFGSDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-886 Sequences 3-886-1 Sequence Number [ID] 886 3-886-2 Molecule Type AA 2023214349

3-886-3 Length 186 3-886-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-886-5 Residues VGSLNCIVAV SQNMGIGKNG SLPWPPLRNE MSYFSRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKSRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 YKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-887 Sequences 3-887-1 Sequence Number [ID] 887 3-887-2 Molecule Type AA 3-887-3 Length 186 3-887-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-887-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRND MRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIIGGSSV 120 YKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-888 Sequences 3-888-1 Sequence Number [ID] 888 3-888-2 Molecule Type AA 3-888-3 Length 186 3-888-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-888-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 YKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP GYPGVLSDVQ EEKGFKYKFE 180 VYEKND 186 3-889 Sequences 3-889-1 Sequence Number [ID] 889 3-889-2 Molecule Type AA 3-889-3 Length 186 3-889-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-889-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 YKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEEND 186 3-890 Sequences

3-890-1 Sequence Number [ID] 890 3-890-2 Molecule Type AA 3-890-3 Length 186 3-890-4 Features REGION 1..186 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-890-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEFMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-891 Sequences 3-891-1 Sequence Number [ID] 891 3-891-2 Molecule Type AA 2023214349

3-891-3 Length 186 3-891-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-891-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFFRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKFRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-892 Sequences 3-892-1 Sequence Number [ID] 892 3-892-2 Molecule Type AA 3-892-3 Length 186 3-892-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-892-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 YKEAMYHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-893 Sequences 3-893-1 Sequence Number [ID] 893 3-893-2 Molecule Type AA 3-893-3 Length 186 3-893-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-893-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 YKEAMNHPGR LKLFVTRIMQ DFGSDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-894 Sequences 3-894-1 Sequence Number [ID] 894 3-894-2 Molecule Type AA 3-894-3 Length 186 3-894-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-894-5 Residues VGSLNCIVAV SQNMGVGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 YKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-895 Sequences

3-895-1 Sequence Number [ID] 895 3-895-2 Molecule Type AA 3-895-3 Length 186 3-895-4 Features REGION 1..186 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-895-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFQRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-896 Sequences 3-896-1 Sequence Number [ID] 896 3-896-2 Molecule Type AA 2023214349

3-896-3 Length 187 3-896-4 Features REGION 1..187 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..187 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-896-5 Residues MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PGYPGVLSDV QEEKGFKYKF 180 EVYEKND 187 3-897 Sequences 3-897-1 Sequence Number [ID] 897 3-897-2 Molecule Type AA 3-897-3 Length 106 3-897-4 Features source 1..106 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-897-5 Residues IEVMYPPPYL DNEKSNGTII HVKGKHLCPS PLFPGPSKPF WVLWVGGVLA CYSLLVTVAF 60 IIFWVRSKRS RLLHSDYMNM TPRRPGPTRK HYQPYAPPRD FAAYRS 106 3-898 Sequences 3-898-1 Sequence Number [ID] 898 3-898-2 Molecule Type AA 3-898-3 Length 28 3-898-4 Features source 1..28 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-898-5 Residues FWVLVVVGGV LACYSLLVTV AFIIFWVR 28 3-899 Sequences 3-899-1 Sequence Number [ID] 899 3-899-2 Molecule Type AA 3-899-3 Length 73 3-899-4 Features source 1..73 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-899-5 Residues TPAPRPPTPA PTIASQPLSL RPEACRPAAG GAWTRGLDFA CDIYIWAPLA GTCGVLLLSL 60 VITLYCNHRN RRR 73 3-900 Sequences 3-900-1 Sequence Number [ID] 900 3-900-2 Molecule Type AA 3-900-3 Length 23 3-900-4 Features source 1..23 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-900-5 Residues LGLLVAGVLV LLVSLGVAIH LCC 23 3-901 Sequences 3-901-1 Sequence Number [ID] 901 3-901-2 Molecule Type AA 3-901-3 Length 27

3-901-4 Features source 1..27 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 11 Aug 2023

3-901-5 Residues ILLAGLVAAD AVASLLIVGA VFLCARR 27 3-902 Sequences 3-902-1 Sequence Number [ID] 902 3-902-2 Molecule Type AA 3-902-3 Length 21 3-902-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-902-5 Residues FWLPIGCAAF VVVCILGCIL I 21 3-903 Sequences 3-903-1 Sequence Number [ID] 903 2023214349

3-903-2 Molecule Type AA 3-903-3 Length 233 3-903-4 Features source 1..233 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-903-5 Residues EPKSPDKTHT CPPCPAPPVA GPSVFLFPPK PKDTLMIART PEVTCVVVDV SHEDPEVKFN 60 WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI 120 SKAKGQPREP QVYTLPPSRD ELTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 180 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG KKD 233 3-904 Sequences 3-904-1 Sequence Number [ID] 904 3-904-2 Molecule Type AA 3-904-3 Length 21 3-904-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-904-5 Residues LLFLILGVLS LLLLVTGAFG F 21 3-905 Sequences 3-905-1 Sequence Number [ID] 905 3-905-2 Molecule Type AA 3-905-3 Length 21 3-905-4 Features source 1..21 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-905-5 Residues VAAILGLGLV LGLLGPLAIL L 21 3-906 Sequences 3-906-1 Sequence Number [ID] 906 3-906-2 Molecule Type AA 3-906-3 Length 20 3-906-4 Features source 1..20 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-906-5 Residues VGWGGLLGSL VLLVWVLAVI 20 3-907 Sequences 3-907-1 Sequence Number [ID] 907 3-907-2 Molecule Type AA 3-907-3 Length 27 3-907-4 Features source 1..27 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-907-5 Residues FWALVVVAGV LFCYGLLVTV ALCVIWT 27 3-908 Sequences 3-908-1 Sequence Number [ID] 908 3-908-2 Molecule Type DNA 3-908-3 Length 1335 3-908-4 Features misc_feature 1..1335 Location/Qualifiers note=Description of Artificial Sequence: Synthetic promoter source 1..1335 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-908-5 Residues gagtaattca tacaaaagga ctcgcccctg ccttggggaa tcccagggac cgtcgttaaa 60 ctcccactaa cgtagaaccc agagatcgct gcgttcccgc cccctcaccc gcccgctctc 120 gtcatcactg aggtggagaa gagcatgcgt gaggctccgg tgcccgtcag tgggcagagc 180 gcacatcgcc cacagtcccc gagaagttgg ggggaggggt cggcaattga accggtgcct 240 agagaaggtg gcgcggggta aactgggaaa gtgatgtcgt gtactggctc cgcctttttc 300 ccgagggtgg gggagaaccg tatataagtg cagtagtcgc cgtgaacgtt ctttttcgca 360 acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg cctggcctct 420 ttacgggtta tggcccttgc gtgccttgaa ttacttccac gcccctggct gcagtacgtg 480 attcttgatc ccgagcttcg ggttggaagt gggtgggaga gttcgaggcc ttgcgcttaa 540 ggagcccctt cgcctcgtgc ttgagttgag gcctggcttg ggcgctgggg ccgccgcgtg 600 cgaatctggt ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa 660 aatttttgat gacctgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc 720 caagatctgc acactggtat ttcggttttt ggggccgcgg gcggcgacgg ggcccgtgcg 780 2023214349

tcccagcgca catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg 840 gggtagtctc aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc 900 ccgccctggg cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg 960 cttcccggcc ctgctgcagg gagctcaaaa tggaggacgc ggcgctcggg agagcgggcg 1020 ggtgagtcac ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac 1080 tccacggagt accgggcgcc gtccaggcac ctcgattagt tctcgagctt ttggagtacg 1140 tcgtctttag gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg 1200 gagactgaag ttaggccagc ttggcacttg atgtaattct ccttggaatt tgcccttttt 1260 gagtttggat cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca 1320 tttcaggtgt cgtga 1335 3-909 Sequences 3-909-1 Sequence Number [ID] 909 3-909-2 Molecule Type DNA 3-909-3 Length 15 3-909-4 Features misc_feature 1..15 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..15 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-909-5 Residues tcaggcgggg ggagt 15 3-910 Sequences 3-910-1 Sequence Number [ID] 910 3-910-2 Molecule Type DNA 3-910-3 Length 45 3-910-4 Features misc_feature 1..45 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..45 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-910-5 Residues ggaggaggag gatccggagg aggaggatct ggcggcggcg gcagc 45 3-911 Sequences 3-911-1 Sequence Number [ID] 911 3-911-2 Molecule Type DNA 3-911-3 Length 45 3-911-4 Features misc_feature 1..45 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..45 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-911-5 Residues ggaggaggag gatccggagg aggaggatct ggcggaggag gcagc 45 3-912 Sequences 3-912-1 Sequence Number [ID] 912 3-912-2 Molecule Type DNA 3-912-3 Length 45 3-912-4 Features misc_feature 1..45 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..45 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value

3-912-5 Residues ggaggaggag gaagcggagg aggaggatcc ggcggaggag gctct 45 3-913 Sequences 3-913-1 Sequence Number [ID] 913 3-913-2 Molecule Type DNA 11 Aug 2023

3-913-3 Length 45 3-913-4 Features misc_feature 1..45 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..45 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-913-5 Residues ggaggaggag gcagcggagg aggaggttct ggaggaggcg gcagc 45 3-914 Sequences 3-914-1 Sequence Number [ID] 914 3-914-2 Molecule Type DNA 3-914-3 Length 45 2023214349

3-914-4 Features misc_feature 1..45 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..45 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-914-5 Residues ggcggcggcg gctctggagg aggaggcagc ggcggaggag gctcc 45 3-915 Sequences 3-915-1 Sequence Number [ID] 915 3-915-2 Molecule Type DNA 3-915-3 Length 45 3-915-4 Features misc_feature 1..45 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..45 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-915-5 Residues ggaggaggag gcagcggcgg aggaggctcc ggcggcggcg gctct 45 3-916 Sequences 3-916-1 Sequence Number [ID] 916 3-916-2 Molecule Type DNA 3-916-3 Length 78 3-916-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-916-5 Residues tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 60 ggtggaggca gcttgcaa 78 3-917 Sequences 3-917-1 Sequence Number [ID] 917 3-917-2 Molecule Type DNA 3-917-3 Length 78 3-917-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-917-5 Residues tccggtggag gtagcggtgg agggggttct ggtggaggag gttctggagg tggaggttct 60 ggcggtgggt ccttgcaa 78 3-918 Sequences 3-918-1 Sequence Number [ID] 918 3-918-2 Molecule Type DNA 3-918-3 Length 78 3-918-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value

3-918-5 Residues tctggcggag gaagcggagg cggaggatct ggtggtggtg gatctggcgg cggtggtagt 60 ggcggaggtt ctctgcaa 78 3-919 Sequences 3-919-1 Sequence Number [ID] 919 3-919-2 Molecule Type DNA 11 Aug 2023

3-919-3 Length 78 3-919-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-919-5 Residues tccggggggg gtagcggggg agggggttcc ggcgggggag ggtctggagg gggaggttcc 60 ggcggggggt ccttgcaa 78 3-920 Sequences 3-920-1 Sequence Number [ID] 920 2023214349

3-920-2 Molecule Type DNA 3-920-3 Length 78 3-920-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-920-5 Residues tctggcggag gatctggagg aggcggatct ggaggaggag gcagtggagg cggaggatct 60 ggcggaggat ctctgcag 78 3-921 Sequences 3-921-1 Sequence Number [ID] 921 3-921-2 Molecule Type AA 3-921-3 Length 34 3-921-4 Features REGION 1..34 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..34 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-921-5 Residues SGGGSGGGGS GGGGSGGGGS GGGGSGGGGS GGGS 34 3-922 Sequences 3-922-1 Sequence Number [ID] 922 3-922-2 Molecule Type AA 3-922-3 Length 20 3-922-4 Features REGION 1..20 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..20 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-922-5 Residues SGGGSGGGGS GGGGSGGGGS 20 3-923 Sequences 3-923-1 Sequence Number [ID] 923 3-923-2 Molecule Type DNA 3-923-3 Length 102 3-923-4 Features misc_feature 1..102 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..102 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-923-5 Residues tctggtggcg ggagtggagg aggtgggtcc ggagggggag ggagcggtgg tggaggttcc 60 ggcggggggg gtagtggagg cggagggtca ggtgggggca gc 102 3-924 Sequences 3-924-1 Sequence Number [ID] 924 3-924-2 Molecule Type DNA 3-924-3 Length 60 3-924-4 Features misc_feature 1..60 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..60 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-924-5 Residues agtggtggcg ggtccggcgg tggtggtagc gggggtggag gctcaggtgg cggtggcagt 60 3-925 Sequences 3-925-1 Sequence Number [ID] 925 11 Aug 2023

3-925-2 Molecule Type AA 3-925-3 Length 20 3-925-4 Features REGION 1..20 Location/Qualifiers note=Description of Artificial Sequence: Synthetic cleavable peptide source 1..20 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-925-5 Residues GATNFSLLKQ AGDVEENPGP 20 3-926 Sequences 3-926-1 Sequence Number [ID] 926 3-926-2 Molecule Type DNA 2023214349

3-926-3 Length 60 3-926-4 Features misc_feature 1..60 Location/Qualifiers note=Description of Artificial Sequence: Synthetic cleavable peptide source 1..60 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-926-5 Residues ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa ccctggacct 60 3-927 Sequences 3-927-1 Sequence Number [ID] 927 3-927-2 Molecule Type DNA 3-927-3 Length 28 3-927-4 Features misc_feature 1..28 Location/Qualifiers note=Description of Artificial Sequence: Synthetic spacer source 1..28 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-927-5 Residues tctagataat acgactcact agagatcc 28 3-928 Sequences 3-928-1 Sequence Number [ID] 928 3-928-2 Molecule Type DNA 3-928-3 Length 16 3-928-4 Features misc_feature 1..16 Location/Qualifiers note=Description of Artificial Sequence: Synthetic spacer source 1..16 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-928-5 Residues tatggccaca accatg 16 3-929 Sequences 3-929-1 Sequence Number [ID] 929 3-929-2 Molecule Type DNA 3-929-3 Length 30 3-929-4 Features misc_feature 1..30 Location/Qualifiers note=Description of Artificial Sequence: Synthetic spacer source 1..30 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-929-5 Residues aatctagata atacgactca ctagagatcc 30 3-930 Sequences 3-930-1 Sequence Number [ID] 930 3-930-2 Molecule Type DNA 3-930-3 Length 54 3-930-4 Features source 1..54 Location/Qualifiers mol_type=other DNA organism=Homo sapiens NonEnglishQualifier Value 3-930-5 Residues atggactgga cctggattct gtttctggtg gccgctgcca caagagtgca cagc 54 3-931 Sequences 3-931-1 Sequence Number [ID] 931

3-931-2 Molecule Type DNA 3-931-3 Length 54 3-931-4 Features source 1..54 Location/Qualifiers mol_type=other DNA 11 Aug 2023

organism=Homo sapiens NonEnglishQualifier Value 3-931-5 Residues atggattgga cctggattct gtttctggtg gccgctgcca caagagtgca cagc 54 3-932 Sequences 3-932-1 Sequence Number [ID] 932 3-932-2 Molecule Type AA 3-932-3 Length 30 3-932-4 Features source 1..30 Location/Qualifiers mol_type=protein organism=Homo sapiens NonEnglishQualifier Value 3-932-5 Residues MAPRRARGCR TLGLPALLLL LLLRPPATRG 30 2023214349

3-933 Sequences 3-933-1 Sequence Number [ID] 933 3-933-2 Molecule Type DNA 3-933-3 Length 90 3-933-4 Features misc_feature 1..90 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..90 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-933-5 Residues atggccccgc ggcgggcgcg cggctgccgg accctcggtc tcccggcgct gctactgctg 60 ctgctgctcc ggccgccggc gacgcggggc 90 3-934 Sequences 3-934-1 Sequence Number [ID] 934 3-934-2 Molecule Type DNA 3-934-3 Length 561 3-934-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-934-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcgt cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-935 Sequences 3-935-1 Sequence Number [ID] 935 3-935-2 Molecule Type DNA 3-935-3 Length 561 3-935-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-935-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggtcctcc 180 attcctgaga agaaccgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-936 Sequences 3-936-1 Sequence Number [ID] 936

3-936-2 Molecule Type DNA 3-936-3 Length 561 3-936-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) 11 Aug 2023

source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-936-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga aggatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 2023214349

ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-937 Sequences 3-937-1 Sequence Number [ID] 937 3-937-2 Molecule Type DNA 3-937-3 Length 561 3-937-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-937-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 agggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-938 Sequences 3-938-1 Sequence Number [ID] 938 3-938-2 Molecule Type DNA 3-938-3 Length 561 3-938-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-938-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccaggagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagt aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-939 Sequences 3-939-1 Sequence Number [ID] 939 3-939-2 Molecule Type DNA 3-939-3 Length 561 3-939-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-939-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgta tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tagagaaata taaacttctg 480 11 Aug 2023 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-940 Sequences 3-940-1 Sequence Number [ID] 940 3-940-2 Molecule Type DNA 3-940-3 Length 561 3-940-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct 2023214349

NonEnglishQualifier Value 3-940-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcata 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-941 Sequences 3-941-1 Sequence Number [ID] 941 3-941-2 Molecule Type DNA 3-941-3 Length 561 3-941-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-941-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg aggagaatga t 561 3-942 Sequences 3-942-1 Sequence Number [ID] 942 3-942-2 Molecule Type DNA 3-942-3 Length 561 3-942-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-942-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtaattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaggtatatg agaaggatga t 561 3-943 Sequences 3-943-1 Sequence Number [ID] 943 3-943-2 Molecule Type DNA 3-943-3 Length 561 3-943-4 Features misc_feature 1..561

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-943-5 Residues atggttggtt cgctaaaccg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatgcc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-944 Sequences 3-944-1 Sequence Number [ID] 944 2023214349

3-944-2 Molecule Type DNA 3-944-3 Length 561 3-944-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-944-5 Residues atggttggtt cgctaaactg catcgttgtt gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc ttattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-945 Sequences 3-945-1 Sequence Number [ID] 945 3-945-2 Molecule Type DNA 3-945-3 Length 561 3-945-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-945-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcgg tagaaggtaa acagaatctg gtgattatgg gtaagaaggc ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agagctaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-946 Sequences 3-946-1 Sequence Number [ID] 946 3-946-2 Molecule Type DNA 3-946-3 Length 561 3-946-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-946-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag gatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttcttag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtt tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc cgtcttaaac tatttgtgac aaggatcatg 420 caagactttg gaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-947 Sequences 3-947-1 Sequence Number [ID] 947 11 Aug 2023

3-947-2 Molecule Type DNA 3-947-3 Length 561 3-947-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-947-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat acttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 2023214349

attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgag aaggatcatg 420 caagaccttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-948 Sequences 3-948-1 Sequence Number [ID] 948 3-948-2 Molecule Type DNA 3-948-3 Length 561 3-948-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-948-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gcacaaattt 540 ggagtatatg agaagaatga t 561 3-949 Sequences 3-949-1 Sequence Number [ID] 949 3-949-2 Molecule Type DNA 3-949-3 Length 561 3-949-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-949-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggagcctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagacttcg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtacatg aggagaatga t 561 3-950 Sequences 3-950-1 Sequence Number [ID] 950 3-950-2 Molecule Type DNA 3-950-3 Length 561 3-950-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-950-5 Residues atggttggtt cgctaaactg catcgccgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 11 Aug 2023 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaaggc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcta gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-951 Sequences 3-951-1 Sequence Number [ID] 951 3-951-2 Molecule Type DNA 3-951-3 Length 561 3-951-4 Features misc_feature 1..561 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-951-5 Residues atggttggtt cgctaaactg cgtcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttgaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatgcc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-952 Sequences 3-952-1 Sequence Number [ID] 952 3-952-2 Molecule Type DNA 3-952-3 Length 561 3-952-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-952-5 Residues atggttggct cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggactcgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gcttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaatg taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-953 Sequences 3-953-1 Sequence Number [ID] 953 3-953-2 Molecule Type DNA 3-953-3 Length 561 3-953-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-953-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcgagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcatcttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtctataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 ggagtatatg agaagaatga t 561

3-954 Sequences 3-954-1 Sequence Number [ID] 954 3-954-2 Molecule Type DNA 3-954-3 Length 561 11 Aug 2023

3-954-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-954-5 Residues atggttggtt cgctgaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcctcag tagaaggtaa gcagaatctg gtgattatgc gtaagaagac ctggttctcc 180 attcctgaga agaatagacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc ccattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggttagttgg tggcagttct 360 2023214349

gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcgtg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctgtgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaggtatatg agaagaatga t 561 3-955 Sequences 3-955-1 Sequence Number [ID] 955 3-955-2 Molecule Type DNA 3-955-3 Length 561 3-955-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-955-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat acttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagtcctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagca gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttatgac gaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgacc tggagaaata taaactcctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattag gtacaaattt 540 gaagtatatg agaagaatga t 561 3-956 Sequences 3-956-1 Sequence Number [ID] 956 3-956-2 Molecule Type DNA 3-956-3 Length 561 3-956-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-956-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acaggatctg gtgattatgg gtaagaagac ctggtcctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tgtttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattggtt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-957 Sequences 3-957-1 Sequence Number [ID] 957 3-957-2 Molecule Type DNA 3-957-3 Length 561 3-957-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-957-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 gaggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agagttaatt tagttcttag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttcc 360 11 Aug 2023 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggcgttct ctctgatgtc caggaggaga aaggcactaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-958 Sequences 3-958-1 Sequence Number [ID] 958 3-958-2 Molecule Type DNA 3-958-3 Length 561 3-958-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 2023214349 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-958-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc ccattttctc tccagaagtc tggatgatgc cctaaaacct 300 actggacgat caggattagc agataaagta gacatggccc ggatagttgg cggcagctct 360 gtttgtaagg aagccataag gtacccaggc caccctaagc tacctgtgac aaggaccatg 420 caagactttg aaagtgacac gtctcttcca gaagttgcct tggagaagta taagcttctg 480 ccagaatacc caggtgtgct ctctggtgcc caggaggaga agggcgctag gtacaagttt 540 gaagcatacg aaaggagtga t 561 3-959 Sequences 3-959-1 Sequence Number [ID] 959 3-959-2 Molecule Type DNA 3-959-3 Length 561 3-959-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-959-5 Residues atggctggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcggat atttccggag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaacct 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga agggcattaa gtacaaattt 540 gaagtatatg agaggaatga t 561 3-960 Sequences 3-960-1 Sequence Number [ID] 960 3-960-2 Molecule Type DNA 3-960-3 Length 561 3-960-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-960-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgagcgt cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat attttcagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcatcttctt tccagaagtc tagatggtgc cttaaaactt 300 actgagcaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttatgagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcgtg 420 caagactttg agagtggcac gtttttccca gaaattgatt tggagagata taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-961 Sequences 3-961-1 Sequence Number [ID] 961 3-961-2 Molecule Type DNA

3-961-3 Length 561 3-961-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 11 Aug 2023

mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-961-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atctccaggg aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga aggctcgacc ttcagagggt ggaattaatt tagttctcag tagagaaccc 240 aaggaacctc cacaaggagc tcatttcctt tccagaagtc tagatgatgc cttaggactt 300 actgaacaac cggaattagc aaataaagta gacatggtct ggatagttga tggcagctct 360 gtttataagg aagccatgaa tcacccaggc caccctaaac tatttgtgac aagggtcata 420 caaggctttg aaagtggcac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccagaatacc caggtgttct ctctgacgtc caggagggga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatgg t 561 2023214349

3-962 Sequences 3-962-1 Sequence Number [ID] 962 3-962-2 Molecule Type DNA 3-962-3 Length 561 3-962-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-962-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcaa cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tggatgatgc ctcaagactt 300 actgaacaac cagaattagc caataaagta gacacagtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca ggaattgatt tggagaaata taaacttctg 480 ccaggatacc caggtgttct ctctgatgtc cagggggaga aaggcattaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-963 Sequences 3-963-1 Sequence Number [ID] 963 3-963-2 Molecule Type DNA 3-963-3 Length 561 3-963-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-963-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac agggatcatg 420 caaggctctg aaagtgacac gttttttcca gaaattgatt tggagagata tgaacttctg 480 ccaggatacc caggtgctct ctctgatgtt caggaggaga aaggcattga gtgcaaattt 540 gaagtatatg aggagagtga c 561 3-964 Sequences 3-964-1 Sequence Number [ID] 964 3-964-2 Molecule Type DNA 3-964-3 Length 561 3-964-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-964-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagagctc 240 agggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaagacct 300 actggacaac cagaattagc agataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataggg aagccatgaa tcgcccaggc catcttaaac tgtttgtaac aaggatcatg 420 caaggctttg aaagtgacac gttttttcca gaaattgatt tggagaaata taagcttctg 480 ccagaatacc caggtgttct ctctgatgtc caggaggaga aaggcattaa gtacaaactt 540 11 Aug 2023 gaagtgtatg aggagaatga t 561 3-965 Sequences 3-965-1 Sequence Number [ID] 965 3-965-2 Molecule Type DNA 3-965-3 Length 561 3-965-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 2023214349

3-965-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga gcatgggcat cggcaagaac 60 ggggacctgt cctggccacc gctcaggaat gaattcagat atctccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattacgg gtaaggagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaatcaatt tagtcctcag cagagagctc 240 aaggaacctc cacaaggagc tcattttctt tccgggggtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgag ttacccaggc catcttaaac tacttgtgac aaggatcatg 420 caagactctg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacctccg 480 ccagaatacc caggtgttct ctctgatgtc caggaggcga aaggcattaa gtacaaactt 540 gaagtatatg agaagaatga t 561 3-966 Sequences 3-966-1 Sequence Number [ID] 966 3-966-2 Molecule Type DNA 3-966-3 Length 561 3-966-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-966-5 Residues atggctggtt cgctaaactg catcgtcgct gtgtcccaga atatgggcgt cggcaagaac 60 ggggacctgc cctggccacc gctcagggat ggattcagat atttccggag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggtcctcc 180 attcctgaga agaatcgacc tttagagggt agaactaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc ttatcttctt tccagaagtc tagatgatgc cttaaaactt 300 actgagcagc cagaattagc agatgaagca ggcatggtct gggtagttgg tggcagttct 360 gttgataagg aagccatgaa tcacccaggc catcccaaac tatctgtgac aaggatcgtg 420 caagactttg gaagtgacgc gttttttcca gaaattgatt tggagaaatg caaacttctg 480 ccagaatacc caggtgttct ctctgatgcc caggaggaga gaggcattaa gtacaaattt 540 gaagtatacg agaagagtga c 561 3-967 Sequences 3-967-1 Sequence Number [ID] 967 3-967-2 Molecule Type DNA 3-967-3 Length 561 3-967-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-967-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gcccaggcat gaattcagat atttccagag agtgaccaca 120 acctcttcag cagaaggtaa acagaatctg gtgattatgg gcaagaagac ctggttctcc 180 atccctgaga agaatcgacc ttcaaagggt agaattggtt tagttctcag cggagaactc 240 aaggaacctc cacagggagc ccactttctc tccaggagtc tagatgatac cttaagactt 300 actgaacaac cagaattaac gaatagagta aacatggtct ggatagttgg tggcagttct 360 gtttataagg aggccatgaa tcacccaggc caccttagac cagttgtgac aaggatcatg 420 caggactttg aaagcgacgc gttttttcca gaagttgact tggagaaata tagacttcta 480 ccagaatacc caggtgttct ctctgatgtc cagggggaga aaggcattaa gtacaaattt 540 gaagcatata ggaagaatga t 561 3-968 Sequences 3-968-1 Sequence Number [ID] 968 3-968-2 Molecule Type DNA 3-968-3 Length 558 3-968-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-968-5 Residues atggttggct cgctaaactg catcgtcact gtgtcccgga gcatgggcat cggcaaggac 60 ggggacctgt cctggccacc gctcaggagt gaattcaggt actttcagag aacgaccgca 120 acctcttcag tagaaggtag acagagtctg gtgatcatgg gcaagaggac ctggttctcc 180 actcctgaga ggaatcgacc cttaaggggt agagctaact tagttctcag cggagagctc 240 aagggacctc cacaaggagc tcatcttctt tccagaagtc tagatggtgc cttaaaactt 300 actgaacagc cagagttagc agataaagta gacgtggtcc ggatagttgg tggcagttct 360 gttgatgagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aagagtcatg 420 cggggctttg aaagtgatac gctttttcca ggaatcgact tggggaaacg taaacttctg 480 ccagaatacc caggtgttct ctctgatgtc cgggaggaga aaggcattaa gtacaaactt 540 gaagtatgtg ggaataat 558 3-969 Sequences 3-969-1 Sequence Number [ID] 969 3-969-2 Molecule Type DNA 2023214349

3-969-3 Length 558 3-969-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-969-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcgtcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 attaaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-970 Sequences 3-970-1 Sequence Number [ID] 970 3-970-2 Molecule Type DNA 3-970-3 Length 561 3-970-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-970-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 tataaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 ggatacccag gtgttctctc tgatgtccag gaggagaaag gctttaagta caaatttgaa 540 gtatatgaga agaatgattg a 561 3-971 Sequences 3-971-1 Sequence Number [ID] 971 3-971-2 Molecule Type DNA 3-971-3 Length 561 3-971-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-971-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 tataaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 ggatacccag gtgttctctc tgatgtccag gaggagaaag gctttaagta caaatttgaa 540 gtatatgaga agaatgattg a 561 3-972 Sequences 3-972-1 Sequence Number [ID] 972 3-972-2 Molecule Type DNA 11 Aug 2023

3-972-3 Length 558 3-972-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-972-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 2023214349

gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 tataaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgagg agaatgat 558 3-973 Sequences 3-973-1 Sequence Number [ID] 973 3-973-2 Molecule Type DNA 3-973-3 Length 561 3-973-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-973-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 attaaggaat tcatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgattg a 561 3-974 Sequences 3-974-1 Sequence Number [ID] 974 3-974-2 Molecule Type DNA 3-974-3 Length 558 3-974-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-974-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 attaaggaat tcatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-975 Sequences 3-975-1 Sequence Number [ID] 975 3-975-2 Molecule Type DNA 3-975-3 Length 561 3-975-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct

NonEnglishQualifier Value 3-975-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tcttcagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaagt tccgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 11 Aug 2023

gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 attaaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgattg a 561 3-976 Sequences 3-976-1 Sequence Number [ID] 976 3-976-2 Molecule Type DNA 3-976-3 Length 558 3-976-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) 2023214349

source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-976-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tcttcagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaagt tccgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 attaaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-977 Sequences 3-977-1 Sequence Number [ID] 977 3-977-2 Molecule Type DNA 3-977-3 Length 558 3-977-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-977-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 tataaggaag ccatgtatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-978 Sequences 3-978-1 Sequence Number [ID] 978 3-978-2 Molecule Type DNA 3-978-3 Length 558 3-978-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-978-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcatcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 tataaggaag ccatgaatca cccaggcaga cttaaactat ttgtgacaag gatcatgcaa 420 gactttggaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-979 Sequences

3-979-1 Sequence Number [ID] 979 3-979-2 Molecule Type DNA 3-979-3 Length 558 3-979-4 Features misc_feature 1..558 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-979-5 Residues gttggttcgc taaactgcat cgtcgctgtg tcccagaaca tgggcgtcgg caagaacggg 60 gacctgccct ggccaccgct caggaatgaa ttcagatatt tccagagaat gaccacaacc 120 tcttcagtag aaggtaaaca gaatctggtg attatgggta agaagacctg gttctccatt 180 cctgagaaga atcgaccttt aaagggtaga attaatttag ttctcagcag agaactcaag 240 gaacctccac aaggagctca ttttctttcc agaagtctag atgatgcctt aaaacttact 300 gaacaaccag aattagcaaa taaagtagac atggtctgga tagttggtgg cagttctgtt 360 tataaggaag ccatgaatca cccaggccat cttaaactat ttgtgacaag gatcatgcaa 420 2023214349

gactttgaaa gtgacacgtt ttttccagaa attgatttgg agaaatataa acttctgcca 480 gaatacccag gtgttctctc tgatgtccag gaggagaaag gcattaagta caaatttgaa 540 gtatatgaga agaatgat 558 3-980 Sequences 3-980-1 Sequence Number [ID] 980 3-980-2 Molecule Type DNA 3-980-3 Length 561 3-980-4 Features misc_feature 1..561 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..561 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-980-5 Residues atggttggtt cgctaaactg catcgtcgct gtgtcccaga acatgggcat cggcaagaac 60 ggggacctgc cctggccacc gctcaggaat gaattcagat atttccagag aatgaccaca 120 acctcttcag tagaaggtaa acagaatctg gtgattatgg gtaagaagac ctggttctcc 180 attcctgaga agaatcgacc tttaaagggt agaattaatt tagttctcag cagagaactc 240 aaggaacctc cacaaggagc tcattttctt tccagaagtc tagatgatgc cttaaaactt 300 actgaacaac cagaattagc aaataaagta gacatggtct ggatagttgg tggcagttct 360 gtttataagg aagccatgaa tcacccaggc catcttaaac tatttgtgac aaggatcatg 420 caagactttg aaagtgacac gttttttcca gaaattgatt tggagaaata taaacttctg 480 ccaggatacc caggtgttct ctctgatgtc caggaggaga aaggctttaa gtacaaattt 540 gaagtatatg agaagaatga t 561 3-981 Sequences 3-981-1 Sequence Number [ID] 981 3-981-2 Molecule Type AA 3-981-3 Length 186 3-981-4 Features REGION 1..186 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..186 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-981-5 Residues VGSLNCIVAV SQNMGIGKNG DLPWPPLRNE FRYFKRMTTT SSVEGKQNLV IMGKKTWFSI 60 PEKNRPLKGR INLVLSRELK EPPQGAHFLS RSLDDALKLT EQPELANKVD MVWIVGGSSV 120 IKEAMNHPGH LKLFVTRIMQ DFESDTFFPE IDLEKYKLLP EYPGVLSDVQ EEKGIKYKFE 180 VYEKND 186 3-982 Sequences 3-982-1 Sequence Number [ID] 982 3-982-2 Molecule Type DNA 3-982-3 Length 207 3-982-4 Features misc_feature 1..207 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..207 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-982-5 Residues acaacaaccc cagcacccag acctccaaca cctgcaccaa ccatcgcaag ccagcctctg 60 tccctgaggc ccgaggcatg taggccagca gcaggaggcg ccgtgcacac ccggggcctg 120 gactttgcct gcgatatcta tatctgggca ccactggcag gaacatgtgg cgtgctgctg 180 ctgtccctgg tcatcaccct gtattgc 207 3-983 Sequences 3-983-1 Sequence Number [ID] 983 3-983-2 Molecule Type DNA 3-983-3 Length 207

3-983-4 Features misc_feature 1..207 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..207 mol_type=other DNA 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-983-5 Residues accacaaccc cagcaccccg cccaccaaca cctgcaccaa ccatcgcctc ccagccactg 60 tctctgaggc ccgaggcatg taggcctgca gcaggaggcg ccgtgcacac caggggcctg 120 gactttgcct gcgatatcta catctgggca cctctggcag gaacatgtgg cgtgctgctg 180 ctgtccctgg tcatcaccct gtattgc 207 3-984 Sequences 3-984-1 Sequence Number [ID] 984 3-984-2 Molecule Type DNA 3-984-3 Length 207 3-984-4 Features misc_feature 1..207 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct 2023214349

source 1..207 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-984-5 Residues accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg 60 tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg 120 gacttcgcct gtgatatcta catctgggcg cccttggccg ggacttgtgg ggtccttctc 180 ctgtcactgg ttatcaccct ttactgc 207 3-985 Sequences 3-985-1 Sequence Number [ID] 985 3-985-2 Molecule Type DNA 3-985-3 Length 126 3-985-4 Features misc_feature 1..126 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..126 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-985-5 Residues aaacggggca gaaagaaact cctgtatata ttcaaacaac catttatgag accagtacaa 60 actactcaag aggaagatgg ctgtagctgc cgatttccag aagaagaaga aggaggatgt 120 gaactg 126 3-986 Sequences 3-986-1 Sequence Number [ID] 986 3-986-2 Molecule Type DNA 3-986-3 Length 336 3-986-4 Features misc_feature 1..336 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..336 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-986-5 Residues agagtgaagt tcagcaggag cgcagacgcc cccgcgtaca agcagggcca gaaccagctc 60 tataacgagc tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc 120 cgggaccctg agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat 180 gaactgcaga aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc 240 cggaggggca aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc 300 tacgacgccc ttcacatgca ggccctgccc cctcgc 336 3-987 Sequences 3-987-1 Sequence Number [ID] 987 3-987-2 Molecule Type DNA 3-987-3 Length 321 3-987-4 Features misc_feature 1..321 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-987-5 Residues ggcgtgcagg tggagacaat cagcccaggc gacggacgca cctttccaaa gaggggacag 60 acatgcgtgg tgcactacac cggcatgctg gaggatggca agaaggtgga ctcctctaga 120 gatcggaata agccattcaa gtttatgctg ggcaagcagg aagtgatcag aggctgggag 180 gagggagtgg cacagatgtc tgtgggacag cgggccaagc tgacaatcag ccctgactat 240 gcatacggag caaccggaca cccaggaatc atcccaccac acgccacact ggtgttcgat 300 gtggagctgc tgaagcctga g 321 3-988 Sequences

3-988-1 Sequence Number [ID] 988 3-988-2 Molecule Type DNA 3-988-3 Length 474 3-988-4 Features misc_feature 1..474 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-988-5 Residues atctccctga tcgccgccct ggcagtggac tacgtgatcg gcatggagaa cgccatgccc 60 tggaatctgc ctgccgatct ggcctggttt aagagaaaca cactgaataa gcccgtgatc 120 atgggccggc acacctggga gtctatcggc aggcccctgc ctggcaggaa gaacatcatc 180 ctgtcctctc agcctggcac agacgataga gtgacctggg tgaagagcgt ggacgaggca 240 atcgcagcat gtggcgatgt gcccgagatc atggtcatcg gcggcggcag agtgatcgag 300 cagttcctgc ctaaggccca gaagctgtat ctgacacaca tcgacgccga ggtggagggc 360 gacacccact ttccagatta cgagcccgac gattgggagt ccgtgttctc tgagtttcac 420 2023214349

gacgccgatg cccagaattc ccactcttat tgcttcgaga tcctggagag gaga 474 3-989 Sequences 3-989-1 Sequence Number [ID] 989 3-989-2 Molecule Type DNA 3-989-3 Length 321 3-989-4 Features misc_feature 1..321 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-989-5 Residues ggagtgcagg tggagacaat ctccccaggc gacggcagaa cctttcccaa gcggggccag 60 acatgcgtgg tgcactatac cggcatgctg gaggatggca agaaggtgga ctcctctaga 120 gatcggaaca agccattcaa gtttatgctg ggcaagcagg aagtgatcag aggctgggag 180 gagggagtgg cacagatgtc tgtgggacag cgggccaagc tgacaatcag cccagactat 240 gcatacggag caaccggaca ccctggaatc atccctccac acgccaccct ggtgttcgat 300 gtggagctgc tgaagcctga g 321 3-990 Sequences 3-990-1 Sequence Number [ID] 990 3-990-2 Molecule Type DNA 3-990-3 Length 72 3-990-4 Features misc_feature 1..72 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..72 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-990-5 Residues atctacatct gggcaccact ggcaggaaca tgcggcgtgc tgctgctgtc cctggtcatc 60 accctgtatt gt 72 3-991 Sequences 3-991-1 Sequence Number [ID] 991 3-991-2 Molecule Type DNA 3-991-3 Length 474 3-991-4 Features misc_feature 1..474 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-991-5 Residues atctccctga tcgccgccct ggcagtggac tacgtgatcg gcatggagaa cgccatgccc 60 tggaatctgc ctgccgatct ggcctggttt aagagaaaca cactgaataa gcccgtgatc 120 atgggccggc acacctggga gagcatcggc agacctctgc caggccggaa gaacatcatc 180 ctgtcctctc agcctggcac agacgataga gtgacctggg tgaagtccgt ggacgaggca 240 atcgcagcat gcggcgatgt gcccgagatc atggtcatcg gcggcggcag agtgatcgag 300 cagttcctgc ctaaggccca gaagctgtat ctgacacaca tcgacgccga ggtggagggc 360 gacacccact ttccagatta cgagcccgac gattgggagt ccgtgttctc tgagtttcac 420 gacgccgatg cccagaattc ccactcttat tgtttcgaga tcctggagag aaga 474 3-992 Sequences 3-992-1 Sequence Number [ID] 992 3-992-2 Molecule Type DNA 3-992-3 Length 72 3-992-4 Features misc_feature 1..72 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..72 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-992-5 Residues atctacatct gggcacctct ggcaggaaca tgcggcgtgc tgctgctgtc tctggtcatc 60 accctgtatt gt 72 11 Aug 2023

3-993 Sequences 3-993-1 Sequence Number [ID] 993 3-993-2 Molecule Type DNA 3-993-3 Length 474 3-993-4 Features misc_feature 1..474 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..474 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-993-5 Residues atctccctga tcgccgccct ggcagtggac cacgtgatcg gcatggagaa cgccatgcca 60 2023214349

tggaatctgc ccgccgatct ggcctggttc aagcggaaca ccctgaataa gccagtgatc 120 atgggcagac acacatggga gtctatcggc aggcccctgc ctggacgcaa gaacatcatc 180 ctgagctccc agcccggcac cgacgatagg gtgacatggg tgaagtccgt ggacgaggca 240 atcgcagcat gcggcgatgt gcccgagatc atggtcatcg gcggcggcag agtgtacgag 300 cagttcctgc ctaaggccca gaagctgtat ctgacccaca tcgacgccga ggtggagggc 360 gacacacact ttcctgatta caagccagac gattgggagt ccgtgttctc tgagtttcac 420 gacgccgatg cccagaattc tcacagctat tgttttgaga tcctggagcg gaga 474 3-994 Sequences 3-994-1 Sequence Number [ID] 994 3-994-2 Molecule Type DNA 3-994-3 Length 321 3-994-4 Features misc_feature 1..321 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-994-5 Residues ggagtgcagg tggagacaat cagcccaggc gacggaagga cattcccaaa gaggggacag 60 acctgcgtgg tgcactacac aggcatgctg ggcgatggca agaaggtgga cagctcccgg 120 gatagaaaca agcccttcaa gtttatgctg ggcaagcagg aagtgatcag gggatgggag 180 gagggagtgg cacagatgtc cgtgggacag ggcgccaagc tgaccatctc tcctgactac 240 gcctatggag caacaggaca cccaggaatc atcccacctc acgccaccct ggtgtttgat 300 gtggagctgc tggagctgga g 321 3-995 Sequences 3-995-1 Sequence Number [ID] 995 3-995-2 Molecule Type DNA 3-995-3 Length 558 3-995-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-995-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttcagaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaaga accgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagg ccatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgat 558 3-996 Sequences 3-996-1 Sequence Number [ID] 996 3-996-2 Molecule Type DNA 3-996-3 Length 558 3-996-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-996-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttcagaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaaga accgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagt tcatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 11 Aug 2023 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgat 558 3-997 Sequences 3-997-1 Sequence Number [ID] 997 3-997-2 Molecule Type DNA 3-997-3 Length 558 3-997-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA 2023214349 organism=synthetic construct NonEnglishQualifier Value 3-997-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttaagaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaaga accgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagg ccatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgat 558 3-998 Sequences 3-998-1 Sequence Number [ID] 998 3-998-2 Molecule Type DNA 3-998-3 Length 558 3-998-4 Features misc_feature 1..558 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..558 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-998-5 Residues gtgggctccc tgaactgcat cgtggccgtg agccagaaca tgggcatcgg caagaatggc 60 gacctgcctt ggccacctct gaggaacgag ttcagatact ttttcaggat gaccacaacc 120 agctccgtgg agggcaagca gaacctggtc atcatgggca agaagacatg gttctctatc 180 cccgagaagt tccgccctct gaagggccgg atcaatctgg tgctgagcag agagctgaag 240 gagccaccac agggagcaca cttcctgagc cggagcctgg acgatgccct gaagctgacc 300 gagcagcccg agctggccaa caaggtggac atggtgtgga tcgtgggcgg ctctagcgtg 360 atcaaggagg ccatgaatca cccaggccac ctgaagctgt tcgtgacaag aatcatgcag 420 gactttgagt ccgatacctt ctttcccgag atcgacctgg agaagtacaa gctgctgcct 480 gagtatccag gcgtgctgtc tgatgtgcag gaggagaagg gcatcaagta caagttcgag 540 gtgtatgaga agaatgat 558 3-999 Sequences 3-999-1 Sequence Number [ID] 999 3-999-2 Molecule Type DNA 3-999-3 Length 576 3-999-4 Features misc_feature 1..576 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..576 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-999-5 Residues cgcccctctc cctccccccc ccctaacgtt actggccgaa gccgcttgga ataaggccgg 60 tgtgcgtttg tctatatgtt attttccacc atattgccgt cttttggcaa tgtgagggcc 120 cggaaacctg gccctgtctt cttgacgagc attcctaggg gtctttcccc tctcgccaaa 180 ggaatgcaag gtctgttgaa tgtcgtgaag gaagcagttc ctctggaagc ttcttgaaga 240 caaacaacgt ctgtagcgac cctttgcagg cagcggaacc ccccacctgg cgacaggtgc 300 ctctgcggcc aaaagccacg tgtataagat acacctgcaa aggcggcaca accccagtgc 360 cacgttgtga gttggatagt tgtggaaaga gtcaaatggc tctcctcaag cgtattcaac 420 aaggggctga aggatgccca gaaggtaccc cattgtatgg gatctgatct ggggcctcgg 480 tgcacatgct ttacatgtgt ttagtcgagg ttaaaaaaac gtctaggccc cccgaaccac 540 ggggacgtgg ttttcctttg aaaaacacga tgataa 576 3-1000 Sequences 3-1000-1 Sequence Number [ID] 1000 3-1000-2 Molecule Type DNA 3-1000-3 Length 32

3-1000-4 Features misc_feature 1..32 Location/Qualifiers note=Description of Artificial Sequence: Synthetic oligonucleotide source 1..32 mol_type=other DNA 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-1000-5 Residues gcttgccaca acccacaagg agacgacctt cc 32

3-1001 Sequences 3-1001-1 Sequence Number [ID] 1001 3-1001-2 Molecule Type DNA 3-1001-3 Length 342 11 Aug 2023

3-1001-4 Features misc_feature 1..342 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..342 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1001-5 Residues aattgggtca acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60 atcgacgcca cactgtacac cgagtccgat gtgcacccta gctgcaaagt gaccgccatg 120 aagtgctttc tgctggaact gcaagtgatc agcctggaaa gcggcgacgc cagcatccac 180 gataccgtgg aaaatctgat catcctggcc aacaacagcc tgagcagcaa cggcaatgtg 240 accgagagcg gctgcaaaga gtgcgaggaa ctggaagaga agaacatcaa agagttcctc 300 cagagcttcg tccacatcgt gcagatgttc atcaacacca gc 342 2023214349

3-1002 Sequences 3-1002-1 Sequence Number [ID] 1002 3-1002-2 Molecule Type DNA 3-1002-3 Length 78 3-1002-4 Features misc_feature 1..78 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..78 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1002-5 Residues tctggcggag gaagcggagg cggaggatct ggtggtggtg gatctggcgg cggtggtagt 60 ggcggaggtt ctctgcaa 78 3-1003 Sequences 3-1003-1 Sequence Number [ID] 1003 3-1003-2 Molecule Type DNA 3-1003-3 Length 711 3-1003-4 Features misc_feature 1..711 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..711 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1003-5 Residues atcacctgtc ctccacctat gagcgtggaa cacgccgaca tctgggtcaa gagctacagc 60 ctgtacagca gagagcggta catctgcaac agcggcttca agagaaaggc cggcacaagc 120 agcctgaccg agtgtgtgct gaacaaggcc acaaacgtgg cccactggac cacacctagc 180 ctgaagtgca tcagagatcc cgctctggtt caccagaggc ctgctcctcc atctacagtg 240 acaacagctg gcgtgacccc tcagcctgag tctctgtctc catctggaaa agagcctgcc 300 gccagctctc ccagctctaa caatactgct gccaccacag ccgccatcgt gcctggatct 360 cagctgatgc ctagcaagag ccctagcacc ggcacaacag agatcagctc tcacgagtct 420 agccacggca ccccatctca gaccacagcc aagaattggg agctgaccgc ctctgcctct 480 catcagccac ctggtgttta ccctcaaggc cactctgata ccaccgtggc catcagcaca 540 agcacagtgc tgctgtgtgg actgtctgcc gtgtctctgc tggcctgcta cctgaagtct 600 agacagacac ctcctctggc cagcgtggaa atggaagcca tggaagctct gcctgtgaca 660 tggggcacca gcagcagaga tgaggacctc gagaattgca gccaccacct g 711 3-1004 Sequences 3-1004-1 Sequence Number [ID] 1004 3-1004-2 Molecule Type 3-1004-3 Length 3-1004-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1004-5 Residues 000 3 3-1005 Sequences 3-1005-1 Sequence Number [ID] 1005 3-1005-2 Molecule Type AA 3-1005-3 Length 677 3-1005-4 Features REGION 1..677 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..677 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1005-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120

GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 11 Aug 2023

GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGGSG GVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL 540 VIMGKKTWFS IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV 600 DMVWIVGGSS VIKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV 660 QEEKGIKYKF EVYEKND 677 3-1006 Sequences 3-1006-1 Sequence Number [ID] 1006 3-1006-2 Molecule Type AA 3-1006-3 Length 488 3-1006-4 Features REGION 1..488 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..488 2023214349

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1006-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGS 488 3-1007 Sequences 3-1007-1 Sequence Number [ID] 1007 3-1007-2 Molecule Type AA 3-1007-3 Length 508 3-1007-4 Features REGION 1..508 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..508 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1007-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGATN FSLLKQAGDV EENPGPGS 508 3-1008 Sequences 3-1008-1 Sequence Number [ID] 1008 3-1008-2 Molecule Type AA 3-1008-3 Length 497 3-1008-4 Features REGION 1..497 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..497 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1008-5 Residues MALPVTALLL PLALLLHAAR PYPYDVPDYA DIQMTQTTSS LSASLGDRVT ISCRASQDIS 60 KYLNWYQQKP DGTVKLLIYH TSRLHSGVPS RFSGSGSGTD YSLTISNLEQ EDIATYFCQQ 120 GNTLPYTFGG GTKLEITGGG GSGGGGSGGG GSEVKLQESG PGLVAPSQSL SVTCTVSGVS 180 LPDYGVSWIR QPPRKGLEWL GVIWGSETTY YNSALKSRLT IIKDNSKSQV FLKMNSLQTD 240 DTAIYYCAKH YYYGGSYAMD YWGQGTSVTV SSTTTPAPRP PTPAPTIASQ PLSLRPEACR 300 PAAGGAVHTR GLDFACDIYI WAPLAGTCGV LLLSLVITLY CKRGRKKLLY IFKQPFMRPV 360 QTTQEEDGCS CRFPEEEEGG CELRVKFSRS ADAPAYKQGQ NQLYNELNLG RREEYDVLDK 420 RRGRDPEMGG KPRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT 480 KDTYDALHMQ ALPPRGS 497 3-1009 Sequences 3-1009-1 Sequence Number [ID] 1009 3-1009-2 Molecule Type AA 3-1009-3 Length 502 3-1009-4 Features REGION 1..502

Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..502 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-1009-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRSGES RRVRRNKRSK GS 502 3-1010 Sequences 3-1010-1 Sequence Number [ID] 1010 2023214349

3-1010-2 Molecule Type 3-1010-3 Length 3-1010-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1010-5 Residues 000 3 3-1011 Sequences 3-1011-1 Sequence Number [ID] 1011 3-1011-2 Molecule Type 3-1011-3 Length 3-1011-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1011-5 Residues 000 3 3-1012 Sequences 3-1012-1 Sequence Number [ID] 1012 3-1012-2 Molecule Type DNA 3-1012-3 Length 591 3-1012-4 Features misc_feature 1..591 Location/Qualifiers note=Description of Artificial Sequence: Synthetic payload source 1..591 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1012-5 Residues agaaacctgc ctgtcgctac ccccgacccc ggaatgttcc cctgcctgca ccactcccag 60 aacctcctga gggccgtgtc caacatgctg cagaaggcta gacagaccct cgaattctac 120 ccctgtacca gcgaggagat cgaccatgag gacatcacca aggataagac cagcaccgtg 180 gaggcttgcc tgcctctgga gctgaccaaa aacgagagct gcctgaacag cagggaaacc 240 agcttcatta ccaacggctc ctgcctggcc tccaggaaga catccttcat gatggccctg 300 tgcctcagca gcatctacga ggacctgaag atgtatcagg tggagtttaa gaccatgaat 360 gccaagctgc tgatggaccc taagaggcag atcttcctgg accagaatat gctggccgtg 420 attgacgagc tgatgcaggc cctcaacttt aacagcgaga ccgtgcccca gaaaagcagc 480 ctcgaagagc ctgacttcta caaaaccaag attaagctgt gtatcctgct gcacgccttc 540 aggatcaggg ccgtgaccat cgacagggtg atgagctacc tgaacgccag t 591 3-1013 Sequences 3-1013-1 Sequence Number [ID] 1013 3-1013-2 Molecule Type DNA 3-1013-3 Length 321 3-1013-4 Features misc_feature 1..321 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1013-5 Residues ggagtgcagg tggagacaat cagccccggc gatggcagga cctttcctaa gcgcggccag 60 acatgcgtgg tgcactacac cggcatgctg ggcgacggca agaaggtgga cagctcccgg 120 gatagaaata agcccttcaa gtttatgctg ggcaagcagg aagtgatcag aggctgggag 180 gagggagtgg cacagatgtc tgtgggacag ggcgccaagc tgacaatcag cccagattac 240 gcatatggag caaccggaca cccaggaatc atcccacccc acgccaccct ggtgttcgac 300 gtggagctgc tggagctgga g 321 3-1014 Sequences 3-1014-1 Sequence Number [ID] 1014 3-1014-2 Molecule Type 3-1014-3 Length

3-1014-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1014-5 Residues 000 3 11 Aug 2023

3-1015 Sequences 3-1015-1 Sequence Number [ID] 1015 3-1015-2 Molecule Type AA 3-1015-3 Length 743 3-1015-4 Features REGION 1..743 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..743 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1015-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 2023214349

GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGSGA TNFSLLKQAG DVEENPGPLS KGEEDNMAII KEFMRFKVHM EGSVNGHEFE 540 IEGEGEGRPY EGTQTAKLKV TKGGPLPFAW DILSPQFMYG SKAYVKHPAD IPDYLKLSFP 600 EGFKWERVMN FEDGGVVTVT QDSSLQDGEF IYKVKLRGTN FPSDGPVMQK KTMGWEASSE 660 RMYPEDGALK GEIKQRLKLK DGGHYDAEVK TTYKAKKPVQ LPGAYNVNIK LDITSHNEDY 720 TIVEQYERAE GRHSTGGMDE LYK 743 3-1016 Sequences 3-1016-1 Sequence Number [ID] 1016 3-1016-2 Molecule Type AA 3-1016-3 Length 885 3-1016-4 Features REGION 1..885 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..885 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1016-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGSGA TNFSLLKQAG DVEENPGPNW VNVISDLKKI EDLIQSMHID ATLYTESDVH 540 PSCKVTAMKC FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE 600 EKNIKEFLQS FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA 660 DIWVKSYSLY SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ 720 RPAPPSTVTT AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT 780 TEISSHESSH GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS 840 LLACYLKSRQ TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHL 885 3-1017 Sequences 3-1017-1 Sequence Number [ID] 1017 3-1017-2 Molecule Type AA 3-1017-3 Length 907 3-1017-4 Features REGION 1..907 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..907 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1017-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGSGA TNFSLLKQAG DVEENPGPML LLVTSLLLCE LPHPAFLLIP NWVNVISDLK 540 KIEDLIQSMH IDATLYTESD VHPSCKVTAM KCFLLELQVI SLESGDASIH DTVENLIILA 600

NNSLSSNGNV TESGCKECEE LEEKNIKEFL QSFVHIVQMF INTSSGGGSG GGGSGGGGSG 660 GGGSGGGSLQ ITCPPPMSVE HADIWVKSYS LYSRERYICN SGFKRKAGTS SLTECVLNKA 720 TNVAHWTTPS LKCIRDPALV HQRPAPPSTV TTAGVTPQPE SLSPSGKEPA ASSPSSNNTA 780 ATTAAIVPGS QLMPSKSPST GTTEISSHES SHGTPSQTTA KNWELTASAS HQPPGVYPQG 840 HSDTTVAIST STVLLCGLSA VSLLACYLKS RQTPPLASVE MEAMEALPVT WGTSSRDEDL 900 11 Aug 2023

ENCSHHL 907 3-1018 Sequences 3-1018-1 Sequence Number [ID] 1018 3-1018-2 Molecule Type AA 3-1018-3 Length 903 3-1018-4 Features REGION 1..903 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..903 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-1018-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRGSGA TNFSLLKQAG DVEENPGPMD WTWILFLVAA ATRVHSNWVN VISDLKKIED 540 LIQSMHIDAT LYTESDVHPS CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL 600 SSNGNVTESG CKECEELEEK NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS 660 GGGSLQITCP PPMSVEHADI WVKSYSLYSR ERYICNSGFK RKAGTSSLTE CVLNKATNVA 720 HWTTPSLKCI RDPALVHQRP APPSTVTTAG VTPQPESLSP SGKEPAASSP SSNNTAATTA 780 AIVPGSQLMP SKSPSTGTTE ISSHESSHGT PSQTTAKNWE LTASASHQPP GVYPQGHSDT 840 TVAISTSTVL LCGLSAVSLL ACYLKSRQTP PLASVEMEAM EALPVTWGTS SRDEDLENCS 900 HHL 903 3-1019 Sequences 3-1019-1 Sequence Number [ID] 1019 3-1019-2 Molecule Type 3-1019-3 Length 3-1019-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1019-5 Residues 000 3 3-1020 Sequences 3-1020-1 Sequence Number [ID] 1020 3-1020-2 Molecule Type 3-1020-3 Length 3-1020-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1020-5 Residues 000 3 3-1021 Sequences 3-1021-1 Sequence Number [ID] 1021 3-1021-2 Molecule Type 3-1021-3 Length 3-1021-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1021-5 Residues 000 3 3-1022 Sequences 3-1022-1 Sequence Number [ID] 1022 3-1022-2 Molecule Type DNA 3-1022-3 Length 2034 3-1022-4 Features misc_feature 1..2034 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..2034 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1022-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 11 Aug 2023 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 2023214349 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg aggcagcgga ggagtgggct ccctgaactg catcgtggcc 1500 gtgagccaga acatgggcat cggcaagaat ggcgacctgc cttggccacc tctgaggaac 1560 gagttcagat actttcagag gatgaccaca accagctccg tggagggcaa gcagaacctg 1620 gtcatcatgg gcaagaagac atggttctct atccccgaga agaaccgccc tctgaagggc 1680 cggatcaatc tggtgctgag cagagagctg aaggagccac cacagggagc acacttcctg 1740 agccggagcc tggacgatgc cctgaagctg accgagcagc ccgagctggc caacaaggtg 1800 gacatggtgt ggatcgtggg cggctctagc gtgatcaagg aggccatgaa tcacccaggc 1860 cacctgaagc tgttcgtgac aagaatcatg caggactttg agtccgatac cttctttccc 1920 gagatcgacc tggagaagta caagctgctg cctgagtatc caggcgtgct gtctgatgtg 1980 caggaggaga agggcatcaa gtacaagttc gaggtgtatg agaagaatga ttga 2034 3-1023 Sequences 3-1023-1 Sequence Number [ID] 1023 3-1023-2 Molecule Type DNA 3-1023-3 Length 1467 3-1023-4 Features misc_feature 1..1467 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1467 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1023-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg atcctga 1467 3-1024 Sequences 3-1024-1 Sequence Number [ID] 1024 3-1024-2 Molecule Type AA 3-1024-3 Length 9 3-1024-4 Features REGION 1..9 Location/Qualifiers note=Description of Artificial Sequence: Synthetic HA Tag source 1..9 mol_type=protein organism=synthetic construct

NonEnglishQualifier Value 3-1024-5 Residues YPYDVPDYA 9 3-1025 Sequences 3-1025-1 Sequence Number [ID] 1025 11 Aug 2023

3-1025-2 Molecule Type DNA 3-1025-3 Length 27 3-1025-4 Features misc_feature 1..27 Location/Qualifiers note=Description of Artificial Sequence: Synthetic HA Tag source 1..27 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1025-5 Residues tacccatacg atgttccaga ttacgct 27 3-1026 Sequences 3-1026-1 Sequence Number [ID] 1026 3-1026-2 Molecule Type DNA 2023214349

3-1026-3 Length 27 3-1026-4 Features misc_feature 1..27 Location/Qualifiers note=Description of Artificial Sequence: Synthetic HA Tag source 1..27 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1026-5 Residues tatccttacg atgtgcccga ctatgct 27 3-1027 Sequences 3-1027-1 Sequence Number [ID] 1027 3-1027-2 Molecule Type DNA 3-1027-3 Length 27 3-1027-4 Features misc_feature 1..27 Location/Qualifiers note=Description of Artificial Sequence: Synthetic HA Tag source 1..27 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1027-5 Residues tatccgtacg acgtaccaga ctacgca 27 3-1028 Sequences 3-1028-1 Sequence Number [ID] 1028 3-1028-2 Molecule Type DNA 3-1028-3 Length 321 3-1028-4 Features misc_feature 1..321 Location/Qualifiers note=Description of Artificial Sequence: Synthetic destabilizing doma in (DD) source 1..321 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1028-5 Residues ggagtgcagg tggaaaccat ctccccagga gacgggcgca ccttccccaa gcgcggccag 60 acctgcgtgg tgcactacac cgggatgctt ggagatggaa agaaagttga ctcctcccgg 120 gacagaaaca agccctttaa gtttatgcta ggcaagcagg aggtgatccg aggctgggaa 180 gaaggggttg cccagatgag tgtgggtcag ggagccaaac tgactatatc tccagattat 240 gcctatggtg ccactgggca cccaggcatc atcccaccac atgccactct cgtcttcgat 300 gtggagcttc tagaactgga a 321 3-1029 Sequences 3-1029-1 Sequence Number [ID] 1029 3-1029-2 Molecule Type AA 3-1029-3 Length 235 3-1029-4 Features REGION 1..235 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polypeptide source 1..235 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1029-5 Residues LSKGEEDNMA IIKEFMRFKV HMEGSVNGHE FEIEGEGEGR PYEGTQTAKL KVTKGGPLPF 60 AWDILSPQFM YGSKAYVKHP ADIPDYLKLS FPEGFKWERV MNFEDGGVVT VTQDSSLQDG 120 EFIYKVKLRG TNFPSDGPVM QKKTMGWEAS SERMYPEDGA LKGEIKQRLK LKDGGHYDAE 180 VKTTYKAKKP VQLPGAYNVN IKLDITSHNE DYTIVEQYER AEGRHSTGGM DELYK 235 3-1030 Sequences 3-1030-1 Sequence Number [ID] 1030 3-1030-2 Molecule Type DNA 3-1030-3 Length 705

3-1030-4 Features misc_feature 1..705 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..705 mol_type=other DNA 11 Aug 2023

organism=synthetic construct NonEnglishQualifier Value 3-1030-5 Residues ttgagcaagg gcgaggagga caacatggcc atcatcaagg agttcatgcg cttcaaggtg 60 cacatggagg gctccgtgaa cggccacgag ttcgagatcg agggcgaggg cgagggccgc 120 ccctacgagg gcacccagac cgccaagctg aaggtgacca agggcggccc cctgcccttc 180 gcctgggaca tcctgtcccc tcagttcatg tacggctcca aggcctacgt gaagcacccc 240 gccgacatcc ccgactactt gaagctgtcc ttccccgagg gcttcaagtg ggagcgcgtg 300 atgaacttcg aggacggcgg cgtggtgacc gtgacccagg actcctccct gcaggacggc 360 gagttcatct acaaggtgaa gctgcgcggc accaacttcc cctccgacgg ccccgtaatg 420 cagaagaaga ccatgggctg ggaggcctcc tccgagcgga tgtaccccga ggacggcgcc 480 ctgaagggcg agatcaagca gaggctgaag ctgaaggacg gcggccacta cgacgccgag 540 gtcaagacca cctacaaggc caagaagccc gtgcagctgc ccggcgccta caacgtcaac 600 atcaagctgg acatcacctc ccacaacgag gactacacca tcgtggaaca gtacgagcgc 660 2023214349

gccgagggcc gccactccac cggcggcatg gacgagctgt acaag 705 3-1031 Sequences 3-1031-1 Sequence Number [ID] 1031 3-1031-2 Molecule Type AA 3-1031-3 Length 22 3-1031-4 Features REGION 1..22 Location/Qualifiers note=Description of Artificial Sequence: Synthetic peptide source 1..22 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1031-5 Residues MLLLVTSLLL CELPHPAFLL IP 22 3-1032 Sequences 3-1032-1 Sequence Number [ID] 1032 3-1032-2 Molecule Type DNA 3-1032-3 Length 66 3-1032-4 Features misc_feature 1..66 Location/Qualifiers note=Description of Artificial Sequence: Synthetic oligonucleotide source 1..66 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1032-5 Residues atgcttctcc tggtgacaag ccttctgctc tgtgagttac cacacccagc attcctcctg 60 atccca 66 3-1033 Sequences 3-1033-1 Sequence Number [ID] 1033 3-1033-2 Molecule Type DNA 3-1033-3 Length 1527 3-1033-4 Features misc_feature 1..1527 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1527 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1033-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg agctactaac ttcagcctgc tgaagcaggc tggagacgtg 1500 11 Aug 2023 gaggagaacc ctggacctgg atcctga 1527 3-1034 Sequences 3-1034-1 Sequence Number [ID] 1034 3-1034-2 Molecule Type DNA 3-1034-3 Length 1494 3-1034-4 Features misc_feature 1..1494 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1494 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 2023214349

3-1034-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 ccctatcctt acgatgtgcc cgactatgct gacatccaga tgacacagac cacaagctcc 120 ctgtccgcct ctctgggcga cagagtgacc atcagctgcc gggcctccca ggatatctct 180 aagtatctga actggtacca gcagaagccc gatggcacag tgaagctgct gatctatcac 240 accagccgcc tgcactccgg agtgccttct aggttcagcg gctccggctc tggcacagac 300 tacagcctga ccatctccaa cctggagcag gaggatatcg ccacctattt ctgccagcag 360 ggcaatacac tgccttacac ctttggcggc ggcacaaagc tggagatcac cggaggagga 420 ggcagcggag gaggaggctc cggcggcggc ggctctgagg tgaagctgca ggagtccgga 480 ccaggcctgg tggcacctag ccagtccctg tctgtgacat gtaccgtgtc cggcgtgtct 540 ctgccagact acggcgtgtc ttggatcagg cagccaccta ggaagggcct ggagtggctg 600 ggcgtgatct ggggcagcga gacaacatac tataattctg ccctgaagag cagactgaca 660 atcatcaagg acaacagcaa gtcccaggtg ttcctgaaga tgaatagcct gcagacagac 720 gataccgcca tctactattg cgccaagcac tactattacg gcggcagcta tgccatggat 780 tactggggcc agggcacatc cgtgaccgtg tctagcacca caaccccagc acctcgccca 840 ccaacaccag caccaaccat cgcatcccag ccactgtctc tgaggcccga ggcatgtagg 900 cctgcagcag gaggcgccgt gcacaccagg ggcctggact ttgcctgcga tatctatatc 960 tgggcaccac tggcaggaac atgtggcgtg ctgctgctgt ccctggtcat caccctgtat 1020 tgcaagagag gccggaagaa gctgctgtac atcttcaagc agcccttcat gaggcccgtg 1080 cagacaaccc aggaggagga cggctgcagc tgtcggttcc cagaggagga ggagggagga 1140 tgtgagctga gggtgaagtt ttctaggagc gccgatgcac cagcatataa gcagggacag 1200 aaccagctgt acaacgagct gaatctgggc aggagagagg agtacgacgt gctggataag 1260 aggaggggaa gggaccccga gatgggaggc aagccaagga gaaagaaccc ccaggagggc 1320 ctgtataatg agctgcagaa ggacaagatg gccgaggcct actccgagat cggcatgaag 1380 ggagagcggc gcaggggcaa gggacacgat ggcctgtatc agggcctgtc tacagccacc 1440 aaggacacct acgatgcact gcacatgcag gccctgcctc caaggggatc ctga 1494 3-1035 Sequences 3-1035-1 Sequence Number [ID] 1035 3-1035-2 Molecule Type DNA 3-1035-3 Length 1509 3-1035-4 Features misc_feature 1..1509 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1509 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1035-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaaggag tggtgagtcc aggagagtgc ggcgcaacaa gaggagcaag 1500 ggatcctga 1509 3-1036 Sequences 11 Aug 2023

3-1036-1 Sequence Number [ID] 1036 3-1036-2 Molecule Type 3-1036-3 Length 3-1036-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1036-5 Residues 000 3 3-1037 Sequences 3-1037-1 Sequence Number [ID] 1037 3-1037-2 Molecule Type DNA 3-1037-3 Length 3158 2023214349

3-1037-4 Features misc_feature 1..3158 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..3158 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1037-5 Residues atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg 60 ccggacatcc agatgacaca gactacatcc tccctgtctg cctctctggg agacagagtc 120 accatcagtt gcagggcaag tcaggacatt agtaaatatt taaattggta tcagcagaaa 180 ccagatggaa ctgttaaact cctgatctac catacatcaa gattacactc aggagtccca 240 tcaaggttca gtggcagtgg gtctggaaca gattattctc tcaccattag caacctggag 300 caagaagata ttgccactta cttttgccaa cagggtaata cgcttccgta cacgttcgga 360 ggggggacca agctggagat cacaggtggc ggtggctcgg gcggtggtgg gtcgggtggc 420 ggcggatctg aggtgaaact gcaggagtca ggacctggcc tggtggcgcc ctcacagagc 480 ctgtccgtca catgcactgt ctcaggggtc tcattacccg actatggtgt aagctggatt 540 cgccagcctc cacgaaaggg tctggagtgg ctgggagtaa tatggggtag tgaaaccaca 600 tactataatt cagctctcaa atccagactg accatcatca aggacaactc caagagccaa 660 gttttcttaa aaatgaacag tctgcaaact gatgacacag ccatttacta ctgtgccaaa 720 cattattact acggtggtag ctatgctatg gactactggg gccaaggaac ctcagtcacc 780 gtctcctcaa ccacgacgcc agcgccgcga ccaccaacac cggcgcccac catcgcgtcg 840 cagcccctgt ccctgcgccc agaggcgtgc cggccagcgg cggggggcgc agtgcacacg 900 agggggctgg acttcgcctg tgatatctac atctgggcgc ccttggccgg gacttgtggg 960 gtccttctcc tgtcactggt tatcaccctt tactgcaaac ggggcagaaa gaaactcctg 1020 tatatattca aacaaccatt tatgagacca gtacaaacta ctcaagagga agatggctgt 1080 agctgccgat ttccagaaga agaagaagga ggatgtgaac tgagagtgaa gttcagcagg 1140 agcgcagacg cccccgcgta caagcagggc cagaaccagc tctataacga gctcaatcta 1200 ggacgaagag aggagtacga tgttttggac aagagacgtg gccgggaccc tgagatgggg 1260 ggaaagccga gaaggaagaa ccctcaggaa ggcctgtaca atgaactgca gaaagataag 1320 atggcggagg cctacagtga gattgggatg aaaggcgagc gccggagggg caaggggcac 1380 gatggccttt accagggtct cagtacagcc accaaggaca cctacgacgc ccttcacatg 1440 caggccctgc cccctcgcac gcgttatccg tacgacgtac cagactacgc aggagtgcag 1500 gtggaaacca tctccccagg agacgggcgc accttcccca agcgcggcca gacctgcgtg 1560 gtgcactaca ccgggatgct tggagatgga aagaaagttg actcctcccg ggacagaaac 1620 aagcccttta agtttatgct aggcaagcag gaggtgatcc gaggctggga agaaggggtt 1680 gcccagatga gtgtgggtca gggagccaaa ctgactatat ctccagatta tgcctatggt 1740 gccactgggc acccaggcat catcccacca catgccactc tcgtcttcga tgtggagctt 1800 ctagaactgg aatgaatgca tcgatccgcg gcggccgcta cgtaaattcc gccccccccc 1860 cccctctccc tccccccccc ctaacgttac tggccgaagc cgcttggaat aaggccggtg 1920 tgcgtttgtc tatatgttat tttccaccat attgccgtct tttggcaatg tgagggcccg 1980 gaaacctggc cctgtcttct tgacgagcat tcctaggggt ctttcccctc tcgccaaagg 2040 aatgcaaggt ctgttgaatg tcgtgaagga agcagttcct ctggaagctt cttgaagaca 2100 aacaacgtct gtagcgaccc tttgcaggca gcggaacccc ccacctggcg acaggtgcct 2160 ctgcggccaa aagccacgtg tataagatac acctgcaaag gcggcacaac cccagtgcca 2220 cgttgtgagt tggatagttg tggaaagagt caaatggctc tcctcaagcg tattcaacaa 2280 ggggctgaag gatgcccaga aggtacccca ttgtatggga tctgatctgg ggcctcggtg 2340 cacatgcttt acatgtgttt agtcgaggtt aaaaaaacgt ctaggccccc cgaaccacgg 2400 ggacgtggtt ttcctttgaa aaacacgatg ataatatggc cacaaccatg atgagcaagg 2460 gcgaggagga taacatggcc atcatcaagg agttcatgcg cttcaaggtg cacatggagg 2520 gctccgtgaa cggccacgag ttcgagatcg agggcgaggg cgagggccgc ccctacgagg 2580 gcacccagac cgccaagctg aaggtgacca agggtggccc cctgcccttc gcctgggaca 2640 tcctgtcccc tcagttcatg tacggctcca aggcctacgt gaagcacccc gccgacatcc 2700 ccgactactt gaagctgtcc ttccccgagg gcttcaagtg ggagcgcgtg atgaacttcg 2760 aggacggcgg cgtggtgacc gtgacccagg actcctccct gcaggacggc gagttcatct 2820 acaaggtgaa gctgcgcggc accaacttcc cctccgacgg ccccgtaatg cagaagaaga 2880 ccatgggctg ggaggcctcc tccgagcgga tgtaccccga ggacggcgcc ctgaagggcg 2940 agatcaagca gaggctgaag ctgaaggacg gcggccacta cgacgctgag gtcaagacca 3000 cctacaaggc caagaagccc gtgcagctgc ccggcgccta caacgtcaac atcaagttgg 3060 acatcacctc ccacaacgag gactacacca tcgtggaaca gtacgaacgc gccgagggcc 3120 gccactccac cggcggcatg gacgagctgt acaagtaa 3158 3-1038 Sequences 3-1038-1 Sequence Number [ID] 1038 3-1038-2 Molecule Type 11 Aug 2023

3-1038-3 Length 3-1038-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1038-5 Residues 000 3 3-1039 Sequences 3-1039-1 Sequence Number [ID] 1039 3-1039-2 Molecule Type DNA 3-1039-3 Length 2232 3-1039-4 Features misc_feature 1..2232 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..2232 2023214349

mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1039-5 Residues atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg 60 ccggacatcc agatgacaca gactacatcc tccctgtctg cctctctggg agacagagtc 120 accatcagtt gcagggcaag tcaggacatt agtaaatatt taaattggta tcagcagaaa 180 ccagatggaa ctgttaaact cctgatctac catacatcaa gattacactc aggagtccca 240 tcaaggttca gtggcagtgg gtctggaaca gattattctc tcaccattag caacctggag 300 caagaagata ttgccactta cttttgccaa cagggtaata cgcttccgta cacgttcgga 360 ggggggacca agctggagat cacaggtggc ggtggctcgg gcggtggtgg gtcgggtggc 420 ggcggatctg aggtgaaact gcaggagtca ggacctggcc tggtggcgcc ctcacagagc 480 ctgtccgtca catgcactgt ctcaggggtc tcattacccg actatggtgt aagctggatt 540 cgccagcctc cacgaaaggg tctggagtgg ctgggagtaa tatggggtag tgaaaccaca 600 tactataatt cagctctcaa atccagactg accatcatca aggacaactc caagagccaa 660 gttttcttaa aaatgaacag tctgcaaact gatgacacag ccatttacta ctgtgccaaa 720 cattattact acggtggtag ctatgctatg gactactggg gccaaggaac ctcagtcacc 780 gtctcctcaa ccacgacgcc agcgccgcga ccaccaacac cggcgcccac catcgcgtcg 840 cagcccctgt ccctgcgccc agaggcgtgc cggccagcgg cggggggcgc agtgcacacg 900 agggggctgg acttcgcctg tgatatctac atctgggcgc ccttggccgg gacttgtggg 960 gtccttctcc tgtcactggt tatcaccctt tactgcaaac ggggcagaaa gaaactcctg 1020 tatatattca aacaaccatt tatgagacca gtacaaacta ctcaagagga agatggctgt 1080 agctgccgat ttccagaaga agaagaagga ggatgtgaac tgagagtgaa gttcagcagg 1140 agcgcagacg cccccgcgta caagcagggc cagaaccagc tctataacga gctcaatcta 1200 ggacgaagag aggagtacga tgttttggac aagagacgtg gccgggaccc tgagatgggg 1260 ggaaagccga gaaggaagaa ccctcaggaa ggcctgtaca atgaactgca gaaagataag 1320 atggcggagg cctacagtga gattgggatg aaaggcgagc gccggagggg caaggggcac 1380 gatggccttt accagggtct cagtacagcc accaaggaca cctacgacgc ccttcacatg 1440 caggccctgc cccctcgcgg atccggagct actaacttca gcctgctgaa gcaggctgga 1500 gacgtggagg agaaccctgg acctttgagc aagggcgagg aggacaacat ggccatcatc 1560 aaggagttca tgcgcttcaa ggtgcacatg gagggctccg tgaacggcca cgagttcgag 1620 atcgagggcg agggcgaggg ccgcccctac gagggcaccc agaccgccaa gctgaaggtg 1680 accaagggcg gccccctgcc cttcgcctgg gacatcctgt cccctcagtt catgtacggc 1740 tccaaggcct acgtgaagca ccccgccgac atccccgact acttgaagct gtccttcccc 1800 gagggcttca agtgggagcg cgtgatgaac ttcgaggacg gcggcgtggt gaccgtgacc 1860 caggactcct ccctgcagga cggcgagttc atctacaagg tgaagctgcg cggcaccaac 1920 ttcccctccg acggccccgt aatgcagaag aagaccatgg gctgggaggc ctcctccgag 1980 cggatgtacc ccgaggacgg cgccctgaag ggcgagatca agcagaggct gaagctgaag 2040 gacggcggcc actacgacgc cgaggtcaag accacctaca aggccaagaa gcccgtgcag 2100 ctgcccggcg cctacaacgt caacatcaag ctggacatca cctcccacaa cgaggactac 2160 accatcgtgg aacagtacga gcgcgccgag ggccgccact ccaccggcgg catggacgag 2220 ctgtacaagt aa 2232 3-1040 Sequences 3-1040-1 Sequence Number [ID] 1040 3-1040-2 Molecule Type DNA 3-1040-3 Length 2658 3-1040-4 Features misc_feature 1..2658 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..2658 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1040-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 11 Aug 2023 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 2023214349 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg ttcaggagct actaacttca gcctgctgaa gcaggctgga 1500 gacgtggagg agaaccctgg acctaactgg gtgaacgtga tctccgacct gaaaaagatc 1560 gaggatttga tccagagcat gcacattgac gccaccctgt ataccgagtc cgacgtgcac 1620 ccgagttgca aggtgactgc catgaagtgc ttcctgctgg agctgcaagt gatcagcctg 1680 gagagcggcg acgccagcat ccacgacacc gtggaaaacc ttatcattct ggccaacaat 1740 agcctgagca gcaacggcaa cgtgaccgaa agcggatgta aggaatgcga ggaactggaa 1800 gagaagaata tcaaagaatt cctgcaaagc ttcgtgcaca tcgtgcagat gttcatcaac 1860 acttcttcag gtggcggtag tggtggggga ggatctggag gcggaggaag cgggggtgga 1920 ggttcaggag gagggagctt gcaaattacc tgcccccctc cgatgagcgt ggagcacgcc 1980 gacatctggg tcaagagcta cagcttgtat agtagggagc ggtacatctg taacagcggg 2040 ttcaagagga aggccgggac cagctcactg accgagtgcg tgttgaacaa ggccaccaac 2100 gtggcccact ggaccacccc tagccttaag tgcatcaggg acccagcgct cgtacaccag 2160 agacccgcgc ctccctctac ggtaaccacg gcaggcgtaa ccccccagcc cgagagcctg 2220 tccccgagcg gcaaggagcc tgcagcgagc agcccctcaa gcaacaacac agccgctacc 2280 accgcggcaa tcgtgcccgg cagccagctg atgccctcaa agagccccag caccggcacc 2340 actgagataa gcagccacga gagctcacac ggcactccct cacagaccac tgccaagaat 2400 tgggagctga ccgcctctgc cagccaccag cccccaggcg tgtatcccca gggccacagc 2460 gacaccacgg tcgccatcag cacatctaca gtgcttttgt gcggccttag cgccgtgtca 2520 ctgctggcat gctacttgaa aagtaggcaa actccccctc ttgccagtgt ggaaatggag 2580 gccatggaag ccctgcccgt gacctggggc accagttcta gggacgagga ccttgagaac 2640 tgctcacatc atttgtga 2658 3-1041 Sequences 3-1041-1 Sequence Number [ID] 1041 3-1041-2 Molecule Type DNA 3-1041-3 Length 2724 3-1041-4 Features misc_feature 1..2724 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..2724 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1041-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg ttcaggagct actaacttca gcctgctgaa gcaggctgga 1500 gacgtggagg agaaccctgg acctatgctt ctcctggtga caagccttct gctctgtgag 1560 ttaccacacc cagcattcct cctgatccca aactgggtga acgtgatctc cgacctgaaa 1620 aagatcgagg atttgatcca gagcatgcac attgacgcca ccctgtatac cgagtccgac 1680 gtgcacccga gttgcaaggt gactgccatg aagtgcttcc tgctggagct gcaagtgatc 1740 agcctggaga gcggcgacgc cagcatccac gacaccgtgg aaaaccttat cattctggcc 1800 11 Aug 2023 aacaatagcc tgagcagcaa cggcaacgtg accgaaagcg gatgtaagga atgcgaggaa 1860 ctggaagaga agaatatcaa agaattcctg caaagcttcg tgcacatcgt gcagatgttc 1920 atcaacactt cttcaggtgg cggtagtggt gggggaggat ctggaggcgg aggaagcggg 1980 ggtggaggtt caggaggagg gagcttgcaa attacctgcc cccctccgat gagcgtggag 2040 cacgccgaca tctgggtcaa gagctacagc ttgtatagta gggagcggta catctgtaac 2100 agcgggttca agaggaaggc cgggaccagc tcactgaccg agtgcgtgtt gaacaaggcc 2160 accaacgtgg cccactggac cacccctagc cttaagtgca tcagggaccc agcgctcgta 2220 caccagagac ccgcgcctcc ctctacggta accacggcag gcgtaacccc ccagcccgag 2280 agcctgtccc cgagcggcaa ggagcctgca gcgagcagcc cctcaagcaa caacacagcc 2340 gctaccaccg cggcaatcgt gcccggcagc cagctgatgc cctcaaagag ccccagcacc 2400 ggcaccactg agataagcag ccacgagagc tcacacggca ctccctcaca gaccactgcc 2460 aagaattggg agctgaccgc ctctgccagc caccagcccc caggcgtgta tccccagggc 2520 2023214349 cacagcgaca ccacggtcgc catcagcaca tctacagtgc ttttgtgcgg ccttagcgcc 2580 gtgtcactgc tggcatgcta cttgaaaagt aggcaaactc cccctcttgc cagtgtggaa 2640 atggaggcca tggaagccct gcccgtgacc tggggcacca gttctaggga cgaggacctt 2700 gagaactgct cacatcattt gtga 2724 3-1042 Sequences 3-1042-1 Sequence Number [ID] 1042 3-1042-2 Molecule Type DNA 3-1042-3 Length 2712 3-1042-4 Features misc_feature 1..2712 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..2712 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1042-5 Residues atggcactgc ctgtgaccgc cctgctgctg ccactggccc tgctgctgca cgcagccagg 60 cccgacatcc agatgacaca gaccacaagc tccctgtccg cctctctggg cgacagagtg 120 accatcagct gccgggcctc ccaggatatc tctaagtatc tgaactggta ccagcagaag 180 cccgatggca cagtgaagct gctgatctat cacaccagcc gcctgcactc cggagtgcct 240 tctaggttca gcggctccgg ctctggcaca gactacagcc tgaccatctc caacctggag 300 caggaggata tcgccaccta tttctgccag cagggcaata cactgcctta cacctttggc 360 ggcggcacaa agctggagat caccggagga ggaggcagcg gaggaggagg ctccggcggc 420 ggcggctctg aggtgaagct gcaggagtcc ggaccaggcc tggtggcacc tagccagtcc 480 ctgtctgtga catgtaccgt gtccggcgtg tctctgccag actacggcgt gtcttggatc 540 aggcagccac ctaggaaggg cctggagtgg ctgggcgtga tctggggcag cgagacaaca 600 tactataatt ctgccctgaa gagcagactg acaatcatca aggacaacag caagtcccag 660 gtgttcctga agatgaatag cctgcagaca gacgataccg ccatctacta ttgcgccaag 720 cactactatt acggcggcag ctatgccatg gattactggg gccagggcac atccgtgacc 780 gtgtctagca ccacaacccc agcacctcgc ccaccaacac cagcaccaac catcgcatcc 840 cagccactgt ctctgaggcc cgaggcatgt aggcctgcag caggaggcgc cgtgcacacc 900 aggggcctgg actttgcctg cgatatctat atctgggcac cactggcagg aacatgtggc 960 gtgctgctgc tgtccctggt catcaccctg tattgcaaga gaggccggaa gaagctgctg 1020 tacatcttca agcagccctt catgaggccc gtgcagacaa cccaggagga ggacggctgc 1080 agctgtcggt tcccagagga ggaggaggga ggatgtgagc tgagggtgaa gttttctagg 1140 agcgccgatg caccagcata taagcaggga cagaaccagc tgtacaacga gctgaatctg 1200 ggcaggagag aggagtacga cgtgctggat aagaggaggg gaagggaccc cgagatggga 1260 ggcaagccaa ggagaaagaa cccccaggag ggcctgtata atgagctgca gaaggacaag 1320 atggccgagg cctactccga gatcggcatg aagggagagc ggcgcagggg caagggacac 1380 gatggcctgt atcagggcct gtctacagcc accaaggaca cctacgatgc actgcacatg 1440 caggccctgc ctccaagggg atccggagct actaacttca gcctgctgaa gcaggctgga 1500 gacgtggagg agaaccctgg acctatggac tggacctgga ttctgtttct ggtggccgct 1560 gccacaagag tgcacagcaa ttgggtcaac gtgatcagcg acctgaagaa gatcgaggac 1620 ctgatccaga gcatgcacat cgacgccaca ctgtacaccg agtccgatgt gcaccctagc 1680 tgcaaagtga ccgccatgaa gtgctttctg ctggaactgc aagtgatcag cctggaaagc 1740 ggcgacgcca gcatccacga taccgtggaa aatctgatca tcctggccaa caacagcctg 1800 agcagcaacg gcaatgtgac cgagagcggc tgcaaagagt gcgaggaact ggaagagaag 1860 aacatcaaag agttcctcca gagcttcgtc cacatcgtgc agatgttcat caacaccagc 1920 tctggcggag gaagcggagg cggaggatct ggtggtggtg gatctggcgg cggtggtagt 1980 ggcggaggtt ctctgcaaat cacctgtcct ccacctatga gcgtggaaca cgccgacatc 2040 tgggtcaaga gctacagcct gtacagcaga gagcggtaca tctgcaacag cggcttcaag 2100 agaaaggccg gcacaagcag cctgaccgag tgtgtgctga acaaggccac aaacgtggcc 2160 cactggacca cacctagcct gaagtgcatc agagatcccg ctctggttca ccagaggcct 2220 gctcctccat ctacagtgac aacagctggc gtgacccctc agcctgagtc tctgtctcca 2280 tctggaaaag agcctgccgc cagctctccc agctctaaca atactgctgc caccacagcc 2340 gccatcgtgc ctggatctca gctgatgcct agcaagagcc ctagcaccgg cacaacagag 2400 atcagctctc acgagtctag ccacggcacc ccatctcaga ccacagccaa gaattgggag 2460 ctgaccgcct ctgcctctca tcagccacct ggtgtttacc ctcaaggcca ctctgatacc 2520 accgtggcca tcagcacaag cacagtgctg ctgtgtggac tgtctgccgt gtctctgctg 2580 gcctgctacc tgaagtctag acagacacct cctctggcca gcgtggaaat ggaagccatg 2640 gaagctctgc ctgtgacatg gggcaccagc agcagagatg aggacctcga gaattgcagc 2700 caccacctgt ag 2712 3-1043 Sequences 3-1043-1 Sequence Number [ID] 1043 3-1043-2 Molecule Type 11 Aug 2023

3-1043-3 Length 3-1043-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1043-5 Residues 000 3 3-1044 Sequences 3-1044-1 Sequence Number [ID] 1044 3-1044-2 Molecule Type 3-1044-3 Length 3-1044-4 Features Location/Qualifiers 2023214349

NonEnglishQualifier Value 3-1044-5 Residues 000 3 3-1045 Sequences 3-1045-1 Sequence Number [ID] 1045 3-1045-2 Molecule Type 3-1045-3 Length 3-1045-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1045-5 Residues 000 3 3-1046 Sequences 3-1046-1 Sequence Number [ID] 1046 3-1046-2 Molecule Type 3-1046-3 Length 3-1046-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1046-5 Residues 000 3 3-1047 Sequences 3-1047-1 Sequence Number [ID] 1047 3-1047-2 Molecule Type 3-1047-3 Length 3-1047-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1047-5 Residues 000 3 3-1048 Sequences 3-1048-1 Sequence Number [ID] 1048 3-1048-2 Molecule Type 3-1048-3 Length 3-1048-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1048-5 Residues 000 3 3-1049 Sequences 3-1049-1 Sequence Number [ID] 1049 3-1049-2 Molecule Type 3-1049-3 Length 3-1049-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1049-5 Residues 000 3 3-1050 Sequences 3-1050-1 Sequence Number [ID] 1050 3-1050-2 Molecule Type 3-1050-3 Length 3-1050-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1050-5 Residues 000 3 3-1051 Sequences 3-1051-1 Sequence Number [ID] 1051

3-1051-2 Molecule Type 3-1051-3 Length 3-1051-4 Features Location/Qualifiers 11 Aug 2023

NonEnglishQualifier Value 3-1051-5 Residues 000 3 3-1052 Sequences 3-1052-1 Sequence Number [ID] 1052 3-1052-2 Molecule Type 3-1052-3 Length 3-1052-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1052-5 Residues 000 3 3-1053 Sequences 3-1053-1 Sequence Number [ID] 1053 2023214349

3-1053-2 Molecule Type 3-1053-3 Length 3-1053-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1053-5 Residues 000 3 3-1054 Sequences 3-1054-1 Sequence Number [ID] 1054 3-1054-2 Molecule Type 3-1054-3 Length 3-1054-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1054-5 Residues 000 3 3-1055 Sequences 3-1055-1 Sequence Number [ID] 1055 3-1055-2 Molecule Type DNA 3-1055-3 Length 1170 3-1055-4 Features misc_feature 1..1170 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1170 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1055-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaatgtaa taagtgattt gaaaaaaatt gaagatctta ttcaatctat gcatattgat 120 gctactttat atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 180 tttctcttgg agttacaagt tatttcactt gagtccggag atgcaagtat tcatgataca 240 gtagaaaatc tgatcatcct agcaaacaac agtttgtctt ctaatgggaa tgtaacagaa 300 tctggatgca aagaatgtga ggaactggag gaaaaaaata ttaaagaatt tttgcagagt 360 tttgtacata ttgtccaaat gttcatcaac acttctggat ccggagctac taacttcagc 420 ctgctgaagc aggctggaga cgtggaggag aaccctggac ctttgagcaa gggcgaggag 480 gacaacatgg ccatcatcaa ggagttcatg cgcttcaagg tgcacatgga gggctccgtg 540 aacggccacg agttcgagat cgagggcgag ggcgagggcc gcccctacga gggcacccag 600 accgccaagc tgaaggtgac caagggcggc cccctgccct tcgcctggga catcctgtcc 660 cctcagttca tgtacggctc caaggcctac gtgaagcacc ccgccgacat ccccgactac 720 ttgaagctgt ccttccccga gggcttcaag tgggagcgcg tgatgaactt cgaggacggc 780 ggcgtggtga ccgtgaccca ggactcctcc ctgcaggacg gcgagttcat ctacaaggtg 840 aagctgcgcg gcaccaactt cccctccgac ggccccgtaa tgcagaagaa gaccatgggc 900 tgggaggcct cctccgagcg gatgtacccc gaggacggcg ccctgaaggg cgagatcaag 960 cagaggctga agctgaagga cggcggccac tacgacgccg aggtcaagac cacctacaag 1020 gccaagaagc ccgtgcagct gcccggcgcc tacaacgtca acatcaagct ggacatcacc 1080 tcccacaacg aggactacac catcgtggaa cagtacgagc gcgccgaggg ccgccactcc 1140 accggcggca tggacgagct gtacaagtaa 1170 3-1056 Sequences 3-1056-1 Sequence Number [ID] 1056 3-1056-2 Molecule Type DNA 3-1056-3 Length 1734 3-1056-4 Features misc_feature 1..1734 Location/Qualifiers note=Description of Artificial Sequence: Synthetic polynucleotide source 1..1734 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value

3-1056-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaatgtaa taagtgattt gaaaaaaatt gaagatctta ttcaatctat gcatattgat 120 gctactttat atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 180 tttctcttgg agttacaagt tatttcactt gagtccggag atgcaagtat tcatgataca 240 gtagaaaatc tgatcatcct agcaaacaac agtttgtctt ctaatgggaa tgtaacagaa 300 11 Aug 2023

tctggatgca aagaatgtga ggaactggag gaaaaaaata ttaaagaatt tttgcagagt 360 tttgtacata ttgtccaaat gttcatcaac acttctggtt ccgttggttc gctaaactgc 420 atcgtcgctg tgtcccagaa catgggcatc ggcaagaacg gggacctgcc ctggccaccg 480 ctcaggaatg aattcagata tttccagaga atgaccacaa cctcttcagt agaaggtaaa 540 cagaatctgg tgattatggg taagaagacc tggttctcca ttcctgagaa gaatcgacct 600 ttaaagggta gaattaattt agttctcagc agagaactca aggaacctcc acaaggagct 660 cattttcttt ccagaagtct agatgatgcc ttaaaactta ctgaacaacc agaattagca 720 aataaagtag acatggtctg gatagttggt ggcagttctg ttattaagga agccatgaat 780 cacccaggcc atcttaaact atttgtgaca aggatcatgc aagactttga aagtgacacg 840 ttttttccag aaattgattt ggagaaatat aaacttctgc cagaataccc aggtgttctc 900 tctgatgtcc aggaggagaa aggcattaag tacaaatttg aagtatatga gaagaatgat 960 ggatccggag ctactaactt cagcctgctg aagcaggctg gagacgtgga ggagaaccct 1020 2023214349

ggacctttga gcaagggcga ggaggacaac atggccatca tcaaggagtt catgcgcttc 1080 aaggtgcaca tggagggctc cgtgaacggc cacgagttcg agatcgaggg cgagggcgag 1140 ggccgcccct acgagggcac ccagaccgcc aagctgaagg tgaccaaggg cggccccctg 1200 cccttcgcct gggacatcct gtcccctcag ttcatgtacg gctccaaggc ctacgtgaag 1260 caccccgccg acatccccga ctacttgaag ctgtccttcc ccgagggctt caagtgggag 1320 cgcgtgatga acttcgagga cggcggcgtg gtgaccgtga cccaggactc ctccctgcag 1380 gacggcgagt tcatctacaa ggtgaagctg cgcggcacca acttcccctc cgacggcccc 1440 gtaatgcaga agaagaccat gggctgggag gcctcctccg agcggatgta ccccgaggac 1500 ggcgccctga agggcgagat caagcagagg ctgaagctga aggacggcgg ccactacgac 1560 gccgaggtca agaccaccta caaggccaag aagcccgtgc agctgcccgg cgcctacaac 1620 gtcaacatca agctggacat cacctcccac aacgaggact acaccatcgt ggaacagtac 1680 gagcgcgccg agggccgcca ctccaccggc ggcatggacg agctgtacaa gtaa 1734 3-1057 Sequences 3-1057-1 Sequence Number [ID] 1057 3-1057-2 Molecule Type AA 3-1057-3 Length 175 3-1057-4 Features REGION 1..175 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..175 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1057-5 Residues ITCPPPMSVE HADIWVKSYS LYSRERYICN SGFKRKAGTS SLTECVLNKA TNVAHWTTPS 60 LKCIRDPALV HQRPAPPSTV TTAGVTPQPE SLSPSGKEPA ASSPSSNNTA ATTAAIVPGS 120 QLMPSKSPST GTTEISSHES SHGTPSQTTA KNWELTASAS HQPPGVYPQG HSDTT 175 3-1058 Sequences 3-1058-1 Sequence Number [ID] 1058 3-1058-2 Molecule Type DNA 3-1058-3 Length 525 3-1058-4 Features misc_feature 1..525 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..525 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1058-5 Residues attacctgcc cccctccgat gagcgtggag cacgccgaca tctgggtcaa gagctacagc 60 ttgtatagta gggagcggta catctgtaac agcgggttca agaggaaggc cgggaccagc 120 tcactgaccg agtgcgtgtt gaacaaggcc accaacgtgg cccactggac cacccctagc 180 cttaagtgca tcagggaccc agcgctcgta caccagagac ccgcgcctcc ctctacggta 240 accacggcag gcgtaacccc ccagcccgag agcctgtccc cgagcggcaa ggagcctgca 300 gcgagcagcc cctcaagcaa caacacagcc gctaccaccg cggcaatcgt gcccggcagc 360 cagctgatgc cctcaaagag ccccagcacc ggcaccactg agataagcag ccacgagagc 420 tcacacggca ctccctcaca gaccactgcc aagaattggg agctgaccgc ctctgccagc 480 caccagcccc caggcgtgta tccccagggc cacagcgaca ccacg 525 3-1059 Sequences 3-1059-1 Sequence Number [ID] 1059 3-1059-2 Molecule Type AA 3-1059-3 Length 235 3-1059-4 Features REGION 1..235 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..235 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1059-5 Residues MSKGEEDNMA IIKEFMRFKV HMEGSVNGHE FEIEGEGEGR PYEGTQTAKL KVTKGGPLPF 60

AWDILSPQFM YGSKAYVKHP ADIPDYLKLS FPEGFKWERV MNFEDGGVVT VTQDSSLQDG 120 EFIYKVKLRG TNFPSDGPVM QKKTMGWEAS SERMYPEDGA LKGEIKQRLK LKDGGHYDAE 180 VKTTYKAKKP VQLPGAYNVN IKLDITSHNE DYTIVEQYER AEGRHSTGGM DELYK 235 3-1060 Sequences 3-1060-1 Sequence Number [ID] 1060 11 Aug 2023

3-1060-2 Molecule Type DNA 3-1060-3 Length 708 3-1060-4 Features misc_feature 1..708 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..708 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1060-5 Residues atgagcaagg gcgaggagga taacatggcc atcatcaagg agttcatgcg cttcaaggtg 60 cacatggagg gctccgtgaa cggccacgag ttcgagatcg agggcgaggg cgagggccgc 120 ccctacgagg gcacccagac cgccaagctg aaggtgacca agggtggccc cctgcccttc 180 2023214349

gcctgggaca tcctgtcccc tcagttcatg tacggctcca aggcctacgt gaagcacccc 240 gccgacatcc ccgactactt gaagctgtcc ttccccgagg gcttcaagtg ggagcgcgtg 300 atgaacttcg aggacggcgg cgtggtgacc gtgacccagg actcctccct gcaggacggc 360 gagttcatct acaaggtgaa gctgcgcggc accaacttcc cctccgacgg ccccgtaatg 420 cagaagaaga ccatgggctg ggaggcctcc tccgagcgga tgtaccccga ggacggcgcc 480 ctgaagggcg agatcaagca gaggctgaag ctgaaggacg gcggccacta cgacgctgag 540 gtcaagacca cctacaaggc caagaagccc gtgcagctgc ccggcgccta caacgtcaac 600 atcaagttgg acatcacctc ccacaacgag gactacacca tcgtggaaca gtacgaacgc 660 gccgagggcc gccactccac cggcggcatg gacgagctgt acaagtaa 708 3-1061 Sequences 3-1061-1 Sequence Number [ID] 1061 3-1061-2 Molecule Type AA 3-1061-3 Length 583 3-1061-4 Features REGION 1..583 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..583 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1061-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGVGS LNCIVAVSQN MGIGKNGDLP 420 WPPLRNEFRY FQRMTTTSSV EGKQNLVIMG KKTWFSIPEK NRPLKGRINL VLSRELKEPP 480 QGAHFLSRSL DDALKLTEQP ELANKVDMVW IVGGSSVYKE AMNHPGHLKL FVTRIMQDFE 540 SDTFFPEIDL EKYKLLPEYP GVLSDVQEEK GIKYKFEVYE END 583 3-1062 Sequences 3-1062-1 Sequence Number [ID] 1062 3-1062-2 Molecule Type AA 3-1062-3 Length 583 3-1062-4 Features REGION 1..583 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..583 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1062-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGVGS LNCIVAVSQN MGIGKNGDLP 420 WPPLRNEFRY FQRMTTTSSV EGKQNLVIMG KKTWFSIPEK NRPLKGRINL VLSRELKEPP 480 QGAHFLSRSL DDALKLTEQP ELANKVDMVW IVGGSSVYKE AMNHPGHLKL FVTRIMQDFE 540 SDTFFPEIDL EKYKLLPGYP GVLSDVQEEK GFKYKFEVYE KND 583 3-1063 Sequences 3-1063-1 Sequence Number [ID] 1063 3-1063-2 Molecule Type AA 3-1063-3 Length 583 3-1063-4 Features REGION 1..583 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..583 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-1063-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGVGS LNCIVAVSQN MGIGKNGDLP 420 WPPLRNEFRY FQRMTTTSSV EGKQNLVIMG KKTWFSIPEK NRPLKGRINL VLSRELKEPP 480 QGAHFLSRSL DDALKLTEQP ELANKVDMVW IVGGSSVYKE AMYHPGHLKL FVTRIMQDFE 540 SDTFFPEIDL EKYKLLPEYP GVLSDVQEEK GIKYKFEVYE KND 583 3-1064 Sequences 3-1064-1 Sequence Number [ID] 1064 3-1064-2 Molecule Type AA 2023214349

3-1064-3 Length 404 3-1064-4 Features REGION 1..404 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..404 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1064-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQYP YDVPDYAITC PPPMSVEHAD 180 IWVKSYSLYS RERYICNSGF KRKAGTSSLT ECVLNKATNV AHWTTPSLKC IRDPALVHQR 240 PAPPSTVTTA GVTPQPESLS PSGKEPAASS PSSNNTAATT AAIVPGSQLM PSKSPSTGTT 300 EISSHESSHG TPSQTTAKNW ELTASASHQP PGVYPQGHSD TTVAISTSTV LLCGLSAVSL 360 LACYLKSRQT PPLASVEMEA MEALPVTWGT SSRDEDLENC SHHL 404 3-1065 Sequences 3-1065-1 Sequence Number [ID] 1065 3-1065-2 Molecule Type 3-1065-3 Length 3-1065-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1065-5 Residues 000 3 3-1066 Sequences 3-1066-1 Sequence Number [ID] 1066 3-1066-2 Molecule Type AA 3-1066-3 Length 403 3-1066-4 Features REGION 1..403 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..403 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1066-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGGSGGG GSGGGSITCP PPMSVEHADI 180 WVKSYSLYSR ERYICNSGFK RKAGTSSLTE CVLNKATNVA HWTTPSLKCI RDPALVHQRP 240 APPSTVTTAG VTPQPESLSP SGKEPAASSP SSNNTAATTA AIVPGSQLMP SKSPSTGTTE 300 ISSHESSHGT PSQTTAKNWE LTASASHQPP GVYPQGHSDT TVAISTSTVL LCGLSAVSLL 360 ACYLKSRQTP PLASVEMEAM EALPVTWGTS SRDEDLENCS HHL 403 3-1067 Sequences 3-1067-1 Sequence Number [ID] 1067 3-1067-2 Molecule Type AA 3-1067-3 Length 403 3-1067-4 Features REGION 1..403 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..403 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1067-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSYPYDVPDY ASGGGSITCP PPMSVEHADI 180 WVKSYSLYSR ERYICNSGFK RKAGTSSLTE CVLNKATNVA HWTTPSLKCI RDPALVHQRP 240 APPSTVTTAG VTPQPESLSP SGKEPAASSP SSNNTAATTA AIVPGSQLMP SKSPSTGTTE 300

ISSHESSHGT PSQTTAKNWE LTASASHQPP GVYPQGHSDT TVAISTSTVL LCGLSAVSLL 360 ACYLKSRQTP PLASVEMEAM EALPVTWGTS SRDEDLENCS HHL 403 3-1068 Sequences 3-1068-1 Sequence Number [ID] 1068 3-1068-2 Molecule Type AA 11 Aug 2023

3-1068-3 Length 371 3-1068-4 Features REGION 1..371 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..371 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1068-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGITCPPP MSVEHADIWV KSYSLYSRER YICNSGFKRK AGTSSLTECV 180 LNKATNVAHW TTPSLKCIRD PALVHQRPAP PSTVTTAGVT PQPESLSPSG KEPAASSPSS 240 2023214349

NNTAATTAAI VPGSQLMPSK SPSTGTTEIS SHESSHGTPS QTTAKNWELT ASASHQPPGV 300 YPQGHSDTTV AISTSTVLLC GLSAVSLLAC YLKSRQTPPL ASVEMEAMEA LPVTWGTSSR 360 DEDLENCSHH L 371 3-1069 Sequences 3-1069-1 Sequence Number [ID] 1069 3-1069-2 Molecule Type AA 3-1069-3 Length 407 3-1069-4 Features REGION 1..407 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..407 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1069-5 Residues MAPRRARGCR TLGLPALLLL LLLRPPATRG NWVNVISDLK KIEDLIQSMH IDATLYTESD 60 VHPSCKVTAM KCFLLELQVI SLESGDASIH DTVENLIILA NNSLSSNGNV TESGCKECEE 120 LEEKNIKEFL QSFVHIVQMF INTSSGGGSG GGGSGGGGSG GGGSGGGSLQ ITCPPPMSVE 180 HADIWVKSYS LYSRERYICN SGFKRKAGTS SLTECVLNKA TNVAHWTTPS LKCIRDPALV 240 HQRPAPPSTV TTAGVTPQPE SLSPSGKEPA ASSPSSNNTA ATTAAIVPGS QLMPSKSPST 300 GTTEISSHES SHGTPSQTTA KNWELTASAS HQPPGVYPQG HSDTTVAIST STVLLCGLSA 360 VSLLACYLKS RQTPPLASVE MEAMEALPVT WGTSSRDEDL ENCSHHL 407 3-1070 Sequences 3-1070-1 Sequence Number [ID] 1070 3-1070-2 Molecule Type AA 3-1070-3 Length 397 3-1070-4 Features REGION 1..397 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..397 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1070-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLGS 397 3-1071 Sequences 3-1071-1 Sequence Number [ID] 1071 3-1071-2 Molecule Type AA 3-1071-3 Length 555 3-1071-4 Features REGION 1..555 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..555 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1071-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSGISL IAALAVDYVI GMENAMPWNL 420 PADLAWFKRN TLNKPVIMGR HTWESIGRPL PGRKNIILSS QPGTDDRVTW VKSVDEAIAA 480

CGDVPEIMVI GGGRVIEQFL PKAQKLYLTH IDAEVEGDTH FPDYEPDDWE SVFSEFHDAD 540 AQNSHSYCFE ILERR 555 3-1072 Sequences 3-1072-1 Sequence Number [ID] 1072 3-1072-2 Molecule Type 11 Aug 2023

3-1072-3 Length 3-1072-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1072-5 Residues 000 3 3-1073 Sequences 3-1073-1 Sequence Number [ID] 1073 3-1073-2 Molecule Type 3-1073-3 Length 3-1073-4 Features Location/Qualifiers 2023214349

NonEnglishQualifier Value 3-1073-5 Residues 000 3 3-1074 Sequences 3-1074-1 Sequence Number [ID] 1074 3-1074-2 Molecule Type AA 3-1074-3 Length 573 3-1074-4 Features REGION 1..573 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..573 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1074-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGISLIA 420 ALAVDYVIGM ENAMPWNLPA DLAWFKRNTL NKPVIMGRHT WESIGRPLPG RKNIILSSQP 480 GTDDRVTWVK SVDEAIAACG DVPEIMVIGG GRVIEQFLPK AQKLYLTHID AEVEGDTHFP 540 DYEPDDWESV FSEFHDADAQ NSHSYCFEIL ERR 573 3-1075 Sequences 3-1075-1 Sequence Number [ID] 1075 3-1075-2 Molecule Type AA 3-1075-3 Length 414 3-1075-4 Features REGION 1..414 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..414 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1075-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGS 414 3-1076 Sequences 3-1076-1 Sequence Number [ID] 1076 3-1076-2 Molecule Type AA 3-1076-3 Length 601 3-1076-4 Features REGION 1..601 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..601 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1076-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300

KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGVGSLN 420 CIVAVSQNMG IGKNGDLPWP PLRNEFRYFQ RMTTTSSVEG KQNLVIMGKK TWFSIPEKNR 480 PLKGRINLVL SRELKEPPQG AHFLSRSLDD ALKLTEQPEL ANKVDMVWIV GGSSVYKEAM 540 NHPGHLKLFV TRIMQDFESD TFFPEIDLEK YKLLPEYPGV LSDVQEEKGI KYKFEVYEEN 600 11 Aug 2023

D 601 3-1077 Sequences 3-1077-1 Sequence Number [ID] 1077 3-1077-2 Molecule Type AA 3-1077-3 Length 601 3-1077-4 Features REGION 1..601 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..601 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-1077-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGVGSLN 420 CIVAVSQNMG IGKNGDLPWP PLRNEFRYFQ RMTTTSSVEG KQNLVIMGKK TWFSIPEKNR 480 PLKGRINLVL SRELKEPPQG AHFLSRSLDD ALKLTEQPEL ANKVDMVWIV GGSSVYKEAM 540 NHPGHLKLFV TRIMQDFESD TFFPEIDLEK YKLLPGYPGV LSDVQEEKGF KYKFEVYEKN 600 D 601 3-1078 Sequences 3-1078-1 Sequence Number [ID] 1078 3-1078-2 Molecule Type AA 3-1078-3 Length 601 3-1078-4 Features REGION 1..601 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..601 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1078-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGVGSLN 420 CIVAVSQNMG IGKNGDLPWP PLRNEFRYFQ RMTTTSSVEG KQNLVIMGKK TWFSIPEKNR 480 PLKGRINLVL SRELKEPPQG AHFLSRSLDD ALKLTEQPEL ANKVDMVWIV GGSSVYKEAM 540 NHPGRLKLFV TRIMQDFGSD TFFPEIDLEK YKLLPEYPGV LSDVQEEKGI KYKFEVYEKN 600 D 601 3-1079 Sequences 3-1079-1 Sequence Number [ID] 1079 3-1079-2 Molecule Type AA 3-1079-3 Length 601 3-1079-4 Features REGION 1..601 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..601 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1079-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGVGSLN 420 CIVAVSQNMG VGKNGDLPWP PLRNEFRYFQ RMTTTSSVEG KQNLVIMGKK TWFSIPEKNR 480 PLKGRINLVL SRELKEPPQG AHFLSRSLDD ALKLTEQPEL ANKVDMVWIV GGSSVYKEAM 540 NHPGHLKLFV TRIMQDFESD TFFPEIDLEK YKLLPEYPGV LSDVQEEKGI KYKFEVYEKN 600 D 601 3-1080 Sequences 3-1080-1 Sequence Number [ID] 1080 3-1080-2 Molecule Type AA

3-1080-3 Length 601 3-1080-4 Features REGION 1..601 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..601 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1080-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGVGSLN 420 CIVAVSQNMG IGKNGDLPWP PLRNEFRYFQ RMTTTSSVEG KQNLVIMGKK TWFSIPEKNR 480 PLKGRINLVL SRELKEPPQG AHFLSRSLDD ALKLTEQPEL ANKVDMVWIV GGSSVYKEAM 540 YHPGHLKLFV TRIMQDFESD TFFPEIDLEK YKLLPEYPGV LSDVQEEKGI KYKFEVYEKN 600 2023214349

D 601 3-1081 Sequences 3-1081-1 Sequence Number [ID] 1081 3-1081-2 Molecule Type AA 3-1081-3 Length 601 3-1081-4 Features REGION 1..601 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..601 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1081-5 Residues MDWTWILFLV AAATRVHSDY KDDDDKNWVN VISDLKKIED LIQSMHIDAT LYTESDVHPS 60 CKVTAMKCFL LELQVISLES GDASIHDTVE NLIILANNSL SSNGNVTESG CKECEELEEK 120 NIKEFLQSFV HIVQMFINTS SGGGSGGGGS GGGGSGGGGS GGGSLQYPYD VPDYAITCPP 180 PMSVEHADIW VKSYSLYSRE RYICNSGFKR KAGTSSLTEC VLNKATNVAH WTTPSLKCIR 240 DPALVHQRPA PPSTVTTAGV TPQPESLSPS GKEPAASSPS SNNTAATTAA IVPGSQLMPS 300 KSPSTGTTEI SSHESSHGTP SQTTAKNWEL TASASHQPPG VYPQGHSDTT VAISTSTVLL 360 CGLSAVSLLA CYLKSRQTPP LASVEMEAME ALPVTWGTSS RDEDLENCSH HLGSGVGSLN 420 CIVAVSQNMG VGKNGDLPWP PLRNEFRYFQ RMTTTSSVEG KQNLVIMGKK TWFSIPEKNR 480 PLKGRINLVL SRELKEPPQG AHFLSRSLDD ALKLTEQPEL ANKVDMVWIV GGSSVIKEAM 540 NHPGHLKLFV TRIMQDFESD TFFPEIDLEK YKLLPEYPGV LSDVQEEKGI KYKFEVYEKN 600 D 601 3-1082 Sequences 3-1082-1 Sequence Number [ID] 1082 3-1082-2 Molecule Type AA 3-1082-3 Length 681 3-1082-4 Features REGION 1..681 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..681 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1082-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLSRMDY KDDDDKDYKD DDDKDYKDDD 420 DKSRGSGATN FSLLKQAGDV EENPGPLSKG EEDNMAIIKE FMRFKVHMEG SVNGHEFEIE 480 GEGEGRPYEG TQTAKLKVTK GGPLPFAWDI LSPQFMYGSK AYVKHPADIP DYLKLSFPEG 540 FKWERVMNFE DGGVVTVTQD SSLQDGEFIY KVKLRGTNFP SDGPVMQKKT MGWEASSERM 600 YPEDGALKGE IKQRLKLKDG GHYDAEVKTT YKAKKPVQLP GAYNVNIKLD ITSHNEDYTI 660 VEQYERAEGR HSTGGMDELY K 681 3-1083 Sequences 3-1083-1 Sequence Number [ID] 1083 3-1083-2 Molecule Type AA 3-1083-3 Length 652 3-1083-4 Features REGION 1..652 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..652 mol_type=protein organism=synthetic construct NonEnglishQualifier Value

3-1083-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSSGGGSGGG GSGGGGSGGG GSGGGSLQIT CPPPMSVEHA DIWVKSYSLY 180 SRERYICNSG FKRKAGTSSL TECVLNKATN VAHWTTPSLK CIRDPALVHQ RPAPPSTVTT 240 AGVTPQPESL SPSGKEPAAS SPSSNNTAAT TAAIVPGSQL MPSKSPSTGT TEISSHESSH 300 11 Aug 2023

GTPSQTTAKN WELTASASHQ PPGVYPQGHS DTTVAISTST VLLCGLSAVS LLACYLKSRQ 360 TPPLASVEME AMEALPVTWG TSSRDEDLEN CSHHLGSGAT NFSLLKQAGD VEENPGPLSK 420 GEEDNMAIIK EFMRFKVHME GSVNGHEFEI EGEGEGRPYE GTQTAKLKVT KGGPLPFAWD 480 ILSPQFMYGS KAYVKHPADI PDYLKLSFPE GFKWERVMNF EDGGVVTVTQ DSSLQDGEFI 540 YKVKLRGTNF PSDGPVMQKK TMGWEASSER MYPEDGALKG EIKQRLKLKD GGHYDAEVKT 600 TYKAKKPVQL PGAYNVNIKL DITSHNEDYT IVEQYERAEG RHSTGGMDEL YK 652 3-1084 Sequences 3-1084-1 Sequence Number [ID] 1084 3-1084-2 Molecule Type 3-1084-3 Length 3-1084-4 Features Location/Qualifiers 2023214349

NonEnglishQualifier Value 3-1084-5 Residues 000 3 3-1085 Sequences 3-1085-1 Sequence Number [ID] 1085 3-1085-2 Molecule Type 3-1085-3 Length 3-1085-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1085-5 Residues 000 3 3-1086 Sequences 3-1086-1 Sequence Number [ID] 1086 3-1086-2 Molecule Type DNA 3-1086-3 Length 1752 3-1086-4 Features misc_feature 1..1752 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1752 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1086-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagtgg tgttggttcg 1200 ctaaactgca tcgtcgctgt gtcccagaac atgggcatcg gcaagaacgg ggacctgccc 1260 tggccaccgc tcaggaatga attcagatat ttccagagaa tgaccacaac ctcttcagta 1320 gaaggtaaac agaatctggt gattatgggt aagaagacct ggttctccat tcctgagaag 1380 aatcgacctt taaagggtag aattaattta gttctcagca gagaactcaa ggaacctcca 1440 caaggagctc attttctttc cagaagtcta gatgatgcct taaaacttac tgaacaacca 1500 gaattagcaa ataaagtaga catggtctgg atagttggtg gcagttctgt ttataaggaa 1560 gccatgaatc acccaggcca tcttaaacta tttgtgacaa ggatcatgca agactttgaa 1620 agtgacacgt tttttccaga aattgatttg gagaaatata aacttctgcc agaataccca 1680 ggtgttctct ctgatgtcca ggaggagaaa ggcattaagt acaaatttga agtatatgag 1740 gagaatgatt ga 1752 3-1087 Sequences 3-1087-1 Sequence Number [ID] 1087 3-1087-2 Molecule Type DNA 3-1087-3 Length 1752 3-1087-4 Features misc_feature 1..1752

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1752 mol_type=other DNA organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-1087-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 2023214349

gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagtgg tgttggttcg 1200 ctaaactgca tcgtcgctgt gtcccagaac atgggcatcg gcaagaacgg ggacctgccc 1260 tggccaccgc tcaggaatga attcagatat ttccagagaa tgaccacaac ctcttcagta 1320 gaaggtaaac agaatctggt gattatgggt aagaagacct ggttctccat tcctgagaag 1380 aatcgacctt taaagggtag aattaattta gttctcagca gagaactcaa ggaacctcca 1440 caaggagctc attttctttc cagaagtcta gatgatgcct taaaacttac tgaacaacca 1500 gaattagcaa ataaagtaga catggtctgg atagttggtg gcagttctgt ttataaggaa 1560 gccatgaatc acccaggcca tcttaaacta tttgtgacaa ggatcatgca agactttgaa 1620 agtgacacgt tttttccaga aattgatttg gagaaatata aacttctgcc aggataccca 1680 ggtgttctct ctgatgtcca ggaggagaaa ggctttaagt acaaatttga agtatatgag 1740 aagaatgatt ga 1752 3-1088 Sequences 3-1088-1 Sequence Number [ID] 1088 3-1088-2 Molecule Type DNA 3-1088-3 Length 1752 3-1088-4 Features misc_feature 1..1752 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1752 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1088-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgagtgg tgttggttcg 1200 ctaaactgca tcgtcgctgt gtcccagaac atgggcatcg gcaagaacgg ggacctgccc 1260 tggccaccgc tcaggaatga attcagatat ttccagagaa tgaccacaac ctcttcagta 1320 gaaggtaaac agaatctggt gattatgggt aagaagacct ggttctccat tcctgagaag 1380 aatcgacctt taaagggtag aattaattta gttctcagca gagaactcaa ggaacctcca 1440 caaggagctc attttctttc cagaagtcta gatgatgcct taaaacttac tgaacaacca 1500 gaattagcaa ataaagtaga catggtctgg atagttggtg gcagttctgt ttataaggaa 1560 gccatgtatc acccaggcca tcttaaacta tttgtgacaa ggatcatgca agactttgaa 1620 agtgacacgt tttttccaga aattgatttg gagaaatata aacttctgcc agaataccca 1680 ggtgttctct ctgatgtcca ggaggagaaa ggcattaagt acaaatttga agtatatgag 1740 aagaatgatt ga 1752 3-1089 Sequences 3-1089-1 Sequence Number [ID] 1089 3-1089-2 Molecule Type DNA 11 Aug 2023

3-1089-3 Length 1215 3-1089-4 Features misc_feature 1..1215 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1215 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1089-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 2023214349

agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggtg gaggcagctt gcaataccca 480 tacgatgttc cagattacgc tattacctgc ccccctccga tgagcgtgga gcacgccgac 540 atctgggtca agagctacag cttgtatagt agggagcggt acatctgtaa cagcgggttc 600 aagaggaagg ccgggaccag ctcactgacc gagtgcgtgt tgaacaaggc caccaacgtg 660 gcccactgga ccacccctag ccttaagtgc atcagggacc cagcgctcgt acaccagaga 720 cccgcgcctc cctctacggt aaccacggca ggcgtaaccc cccagcccga gagcctgtcc 780 ccgagcggca aggagcctgc agcgagcagc ccctcaagca acaacacagc cgctaccacc 840 gcggcaatcg tgcccggcag ccagctgatg ccctcaaaga gccccagcac cggcaccact 900 gagataagca gccacgagag ctcacacggc actccctcac agaccactgc caagaattgg 960 gagctgaccg cctctgccag ccaccagccc ccaggcgtgt atccccaggg ccacagcgac 1020 accacggtcg ccatcagcac atctacagtg cttttgtgcg gccttagcgc cgtgtcactg 1080 ctggcatgct acttgaaaag taggcaaact ccccctcttg ccagtgtgga aatggaggcc 1140 atggaagccc tgcccgtgac ctggggcacc agttctaggg acgaggacct tgagaactgc 1200 tcacatcatt tgtga 1215 3-1090 Sequences 3-1090-1 Sequence Number [ID] 1090 3-1090-2 Molecule Type 3-1090-3 Length 3-1090-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1090-5 Residues 000 3 3-1091 Sequences 3-1091-1 Sequence Number [ID] 1091 3-1091-2 Molecule Type DNA 3-1091-3 Length 1212 3-1091-4 Features misc_feature 1..1212 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1212 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1091-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttctg gtggcgggag tggaggaggt 420 gggtccggag ggggagggag cggtggtgga ggttccggcg gggggggtag tggaggcgga 480 gggtcaggtg ggggcagcat tacctgcccc cctccgatga gcgtggagca cgccgacatc 540 tgggtcaaga gctacagctt gtatagtagg gagcggtaca tctgtaacag cgggttcaag 600 aggaaggccg ggaccagctc actgaccgag tgcgtgttga acaaggccac caacgtggcc 660 cactggacca cccctagcct taagtgcatc agggacccag cgctcgtaca ccagagaccc 720 gcgcctccct ctacggtaac cacggcaggc gtaacccccc agcccgagag cctgtccccg 780 agcggcaagg agcctgcagc gagcagcccc tcaagcaaca acacagccgc taccaccgcg 840 gcaatcgtgc ccggcagcca gctgatgccc tcaaagagcc ccagcaccgg caccactgag 900 ataagcagcc acgagagctc acacggcact ccctcacaga ccactgccaa gaattgggag 960 ctgaccgcct ctgccagcca ccagccccca ggcgtgtatc cccagggcca cagcgacacc 1020 acggtcgcca tcagcacatc tacagtgctt ttgtgcggcc ttagcgccgt gtcactgctg 1080 gcatgctact tgaaaagtag gcaaactccc cctcttgcca gtgtggaaat ggaggccatg 1140 gaagccctgc ccgtgacctg gggcaccagt tctagggacg aggaccttga gaactgctca 1200 catcatttgt ga 1212 3-1092 Sequences

3-1092-1 Sequence Number [ID] 1092 3-1092-2 Molecule Type DNA 3-1092-3 Length 1212 3-1092-4 Features misc_feature 1..1212 11 Aug 2023

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1212 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1092-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttctagtg gtggcgggtc cggcggtggt 420 2023214349

ggtagcgggg gtggaggctc aggtggcggt ggcagttatc cttacgatgt gcccgactat 480 gcttcaggcg gggggagtat tacctgcccc cctccgatga gcgtggagca cgccgacatc 540 tgggtcaaga gctacagctt gtatagtagg gagcggtaca tctgtaacag cgggttcaag 600 aggaaggccg ggaccagctc actgaccgag tgcgtgttga acaaggccac caacgtggcc 660 cactggacca cccctagcct taagtgcatc agggacccag cgctcgtaca ccagagaccc 720 gcgcctccct ctacggtaac cacggcaggc gtaacccccc agcccgagag cctgtccccg 780 agcggcaagg agcctgcagc gagcagcccc tcaagcaaca acacagccgc taccaccgcg 840 gcaatcgtgc ccggcagcca gctgatgccc tcaaagagcc ccagcaccgg caccactgag 900 ataagcagcc acgagagctc acacggcact ccctcacaga ccactgccaa gaattgggag 960 ctgaccgcct ctgccagcca ccagccccca ggcgtgtatc cccagggcca cagcgacacc 1020 acggtcgcca tcagcacatc tacagtgctt ttgtgcggcc ttagcgccgt gtcactgctg 1080 gcatgctact tgaaaagtag gcaaactccc cctcttgcca gtgtggaaat ggaggccatg 1140 gaagccctgc ccgtgacctg gggcaccagt tctagggacg aggaccttga gaactgctca 1200 catcatttgt ga 1212 3-1093 Sequences 3-1093-1 Sequence Number [ID] 1093 3-1093-2 Molecule Type DNA 3-1093-3 Length 1116 3-1093-4 Features misc_feature 1..1116 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1116 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1093-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttctagtg gtattacctg cccccctccg 420 atgagcgtgg agcacgccga catctgggtc aagagctaca gcttgtatag tagggagcgg 480 tacatctgta acagcgggtt caagaggaag gccgggacca gctcactgac cgagtgcgtg 540 ttgaacaagg ccaccaacgt ggcccactgg accaccccta gccttaagtg catcagggac 600 ccagcgctcg tacaccagag acccgcgcct ccctctacgg taaccacggc aggcgtaacc 660 ccccagcccg agagcctgtc cccgagcggc aaggagcctg cagcgagcag cccctcaagc 720 aacaacacag ccgctaccac cgcggcaatc gtgcccggca gccagctgat gccctcaaag 780 agccccagca ccggcaccac tgagataagc agccacgaga gctcacacgg cactccctca 840 cagaccactg ccaagaattg ggagctgacc gcctctgcca gccaccagcc cccaggcgtg 900 tatccccagg gccacagcga caccacggtc gccatcagca catctacagt gcttttgtgc 960 ggccttagcg ccgtgtcact gctggcatgc tacttgaaaa gtaggcaaac tccccctctt 1020 gccagtgtgg aaatggaggc catggaagcc ctgcccgtga cctggggcac cagttctagg 1080 gacgaggacc ttgagaactg ctcacatcat ttgtga 1116 3-1094 Sequences 3-1094-1 Sequence Number [ID] 1094 3-1094-2 Molecule Type DNA 3-1094-3 Length 1224 3-1094-4 Features misc_feature 1..1224 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1224 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1094-5 Residues atggccccgc ggcgggcgcg cggctgccgg accctcggtc tcccggcgct gctactgctg 60 ctgctgctcc ggccgccggc gacgcggggc aactgggtga atgtaataag tgatttgaaa 120 aaaattgaag atcttattca atctatgcat attgatgcta ctttatatac ggaaagtgat 180 gttcacccca gttgcaaagt aacagcaatg aagtgctttc tcttggagtt acaagttatt 240 tcacttgagt ccggagatgc aagtattcat gatacagtag aaaatctgat catcctagca 300 aacaacagtt tgtcttctaa tgggaatgta acagaatctg gatgcaaaga atgtgaggaa 360 ctggaggaaa aaaatattaa agaatttttg cagagttttg tacatattgt ccaaatgttc 420 atcaacactt cttccggtgg aggtagcggt ggagggggtt ctggtggagg aggttctgga 480 11 Aug 2023 ggtggaggtt ctggcggtgg gtccttgcaa atcacgtgcc ctccccccat gtccgtggaa 540 cacgcagaca tctgggtcaa gagctacagc ttgtactcca gggagcggta catttgtaac 600 tctggtttca agcgtaaagc cggcacgtcc agcctgacgg agtgcgtgtt gaacaaggcc 660 acgaatgtcg cccactggac aacccccagt ctcaaatgca ttagagaccc tgccctggtt 720 caccaaaggc cagcgccacc ctccacagta acgacggcag gggtgacccc acagccagag 780 agcctctccc cttctggaaa agagcccgca gcttcatctc ccagctcaaa caacacagcg 840 gccacaacag cagctattgt cccgggctcc cagctgatgc cttcaaaatc accttccaca 900 ggaaccacag agataagcag tcatgagtcc tcccacggca ccccctctca gacaacagcc 960 aagaactggg aactcacagc atccgcctcc caccagccgc caggtgtgta tccacagggc 1020 cacagcgaca ccactgtggc tatctccacg tccactgtcc tgctgtgtgg gctgagcgct 1080 gtgtctctcc tggcatgcta cctcaagtca aggcaaactc ccccgctggc cagcgttgaa 1140 atggaagcca tggaggctct gccggtgact tgggggacca gcagcagaga tgaagacttg 1200 2023214349 gaaaactgct ctcaccacct atga 1224 3-1095 Sequences 3-1095-1 Sequence Number [ID] 1095 3-1095-2 Molecule Type DNA 3-1095-3 Length 1194 3-1095-4 Features misc_feature 1..1194 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1194 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1095-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaacgtga tctccgacct gaaaaagatc gaggatttga tccagagcat gcacattgac 120 gccaccctgt ataccgagtc cgacgtgcac ccgagttgca aggtgactgc catgaagtgc 180 ttcctgctgg agctgcaagt gatcagcctg gagagcggcg acgccagcat ccacgacacc 240 gtggaaaacc ttatcattct ggccaacaat agcctgagca gcaacggcaa cgtgaccgaa 300 agcggatgta aggaatgcga ggaactggaa gagaagaata tcaaagaatt cctgcaaagc 360 ttcgtgcaca tcgtgcagat gttcatcaac acttcttcag gtggcggtag tggtggggga 420 ggatctggag gcggaggaag cgggggtgga ggttcaggag gagggagctt gcaaattacc 480 tgcccccctc cgatgagcgt ggagcacgcc gacatctggg tcaagagcta cagcttgtat 540 agtagggagc ggtacatctg taacagcggg ttcaagagga aggccgggac cagctcactg 600 accgagtgcg tgttgaacaa ggccaccaac gtggcccact ggaccacccc tagccttaag 660 tgcatcaggg acccagcgct cgtacaccag agacccgcgc ctccctctac ggtaaccacg 720 gcaggcgtaa ccccccagcc cgagagcctg tccccgagcg gcaaggagcc tgcagcgagc 780 agcccctcaa gcaacaacac agccgctacc accgcggcaa tcgtgcccgg cagccagctg 840 atgccctcaa agagccccag caccggcacc actgagataa gcagccacga gagctcacac 900 ggcactccct cacagaccac tgccaagaat tgggagctga ccgcctctgc cagccaccag 960 cccccaggcg tgtatcccca gggccacagc gacaccacgg tcgccatcag cacatctaca 1020 gtgcttttgt gcggccttag cgccgtgtca ctgctggcat gctacttgaa aagtaggcaa 1080 actccccctc ttgccagtgt ggaaatggag gccatggaag ccctgcccgt gacctggggc 1140 accagttcta gggacgagga ccttgagaac tgctcacatc atttgggatc ctga 1194 3-1096 Sequences 3-1096-1 Sequence Number [ID] 1096 3-1096-2 Molecule Type 3-1096-3 Length 3-1096-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1096-5 Residues 000 3 3-1097 Sequences 3-1097-1 Sequence Number [ID] 1097 3-1097-2 Molecule Type 3-1097-3 Length 3-1097-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1097-5 Residues 000 3 3-1098 Sequences 3-1098-1 Sequence Number [ID] 1098 3-1098-2 Molecule Type DNA 3-1098-3 Length 1668 3-1098-4 Features misc_feature 1..1668 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1668 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1098-5 Residues atggactgga cctggattct gtttctggtg gccgctgcca caagagtgca cagcaattgg 60 gtcaacgtga tcagcgacct gaagaagatc gaggacctga tccagagcat gcacatcgac 120 gccacactgt acaccgagtc cgatgtgcac cctagctgca aagtgaccgc catgaagtgc 180 11 Aug 2023 tttctgctgg aactgcaagt gatcagcctg gaaagcggcg acgccagcat ccacgatacc 240 gtggaaaatc tgatcatcct ggccaacaac agcctgagca gcaacggcaa tgtgaccgag 300 agcggctgca aagagtgcga ggaactggaa gagaagaaca tcaaagagtt cctccagagc 360 ttcgtccaca tcgtgcagat gttcatcaac accagctctg gcggaggaag cggaggcgga 420 ggatctggtg gtggtggatc tggcggcggt ggtagtggcg gaggttctct gcaaatcacc 480 tgtcctccac ctatgagcgt ggaacacgcc gacatctggg tcaagagcta cagcctgtac 540 agcagagagc ggtacatctg caacagcggc ttcaagagaa aggccggcac aagcagcctg 600 accgagtgtg tgctgaacaa ggccacaaac gtggcccact ggaccacacc tagcctgaag 660 tgcatcagag atcccgctct ggttcaccag aggcctgctc ctccatctac agtgacaaca 720 gctggcgtga cccctcagcc tgagtctctg tctccatctg gaaaagagcc tgccgccagc 780 tctcccagct ctaacaatac tgctgccacc acagccgcca tcgtgcctgg atctcagctg 840 atgcctagca agagccctag caccggcaca acagagatca gctctcacga gtctagccac 900 2023214349 ggcaccccat ctcagaccac agccaagaat tgggagctga ccgcctctgc ctctcatcag 960 ccacctggtg tttaccctca aggccactct gataccaccg tggccatcag cacaagcaca 1020 gtgctgctgt gtggactgtc tgccgtgtct ctgctggcct gctacctgaa gtctagacag 1080 acacctcctc tggccagcgt ggaaatggaa gccatggaag ctctgcctgt gacatggggc 1140 accagcagca gagatgagga cctcgagaat tgcagccacc acctgagcgg catctctctg 1200 attgcggcgc tggcagttga ctacgttatt ggcatggaaa acgcgatgcc atggaacctc 1260 ccggctgacc tggcgtggtt caaacgtaac accctgaaca aacctgtgat catgggtcgt 1320 cacacctggg aatctattgg ccgtcctctc ccgggtcgta aaaacatcat tctgtcttct 1380 cagccaggca ccgacgaccg tgttacctgg gttaaaagcg ttgacgaagc gattgctgcg 1440 tgcggtgatg ttcctgaaat tatggtgatc ggcggtggcc gtgttatcga acagttcctg 1500 ccgaaagcgc agaaactgta cctgacccac atcgacgcgg aagttgaagg tgacacccac 1560 ttcccggact acgaaccgga tgattgggag agcgtattct ccgaattcca tgatgcggat 1620 gcgcaaaact ctcattctta ctgttttgaa atcctggaac gtcgttag 1668 3-1099 Sequences 3-1099-1 Sequence Number [ID] 1099 3-1099-2 Molecule Type 3-1099-3 Length 3-1099-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1099-5 Residues 000 3 3-1100 Sequences 3-1100-1 Sequence Number [ID] 1100 3-1100-2 Molecule Type 3-1100-3 Length 3-1100-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1100-5 Residues 000 3 3-1101 Sequences 3-1101-1 Sequence Number [ID] 1101 3-1101-2 Molecule Type DNA 3-1101-3 Length 1224 3-1101-4 Features misc_feature 1..1224 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1224 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1101-5 Residues atggccccgc ggcgggcgcg cggctgccgg accctcggtc tcccggcgct gctactgctg 60 ctgctgctcc ggccgccggc gacgcggggc aactgggtga atgtaataag tgatttgaaa 120 aaaattgaag atcttattca atctatgcat attgatgcta ctttatatac ggaaagtgat 180 gttcacccca gttgcaaagt aacagcaatg aagtgctttc tcttggagtt acaagttatt 240 tcacttgagt ccggagatgc aagtattcat gatacagtag aaaatctgat catcctagca 300 aacaacagtt tgtcttctaa tgggaatgta acagaatctg gatgcaaaga atgtgaggaa 360 ctggaggaaa aaaatattaa agaatttttg cagagttttg tacatattgt ccaaatgttc 420 atcaacactt cttccggggg gggtagcggg ggagggggtt ccggcggggg agggtctgga 480 gggggaggtt ccggcggggg gtccttgcaa atcacgtgcc ctccccccat gtccgtggaa 540 cacgcagaca tctgggtcaa gagctacagc ttgtactcca gggagcggta catttgtaac 600 tctggtttca agcgtaaagc cggcacgtcc agcctgacgg agtgcgtgtt gaacaaggcc 660 acgaatgtcg cccactggac aacccccagt ctcaaatgca ttagagaccc tgccctggtt 720 caccaaaggc cagcgccacc ctccacagta acgacggcag gggtgacccc acagccagag 780 agcctctccc cttctggaaa agagcccgca gcttcatctc ccagctcaaa caacacagcg 840 gccacaacag cagctattgt cccgggctcc cagctgatgc cttcaaaatc accttccaca 900 ggaaccacag agataagcag tcatgagtcc tcccacggca ccccctctca gacaacagcc 960 aagaactggg aactcacagc atccgcctcc caccagccgc caggtgtgta tccacagggc 1020 cacagcgaca ccactgtggc tatctccacg tccactgtcc tgctgtgtgg gctgagcgct 1080 gtgtctctcc tggcatgcta cctcaagtca aggcaaactc ccccgctggc cagcgttgaa 1140 atggaagcca tggaggctct gccggtgact tgggggacca gcagcagaga tgaagacttg 1200 gaaaactgct ctcaccacct atga 1224 11 Aug 2023

3-1102 Sequences 3-1102-1 Sequence Number [ID] 1102 3-1102-2 Molecule Type DNA 3-1102-3 Length 1722 3-1102-4 Features misc_feature 1..1722 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1722 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1102-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 2023214349

aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggaatctc tctgattgcg 1260 gcgctggcag ttgactacgt tattggcatg gaaaacgcga tgccatggaa cctcccggct 1320 gacctggcgt ggttcaaacg taacaccctg aacaaacctg tgatcatggg tcgtcacacc 1380 tgggaatcta ttggccgtcc tctcccgggt cgtaaaaaca tcattctgtc ttctcagcca 1440 ggcaccgacg accgtgttac ctgggttaaa agcgttgacg aagcgattgc tgcgtgcggt 1500 gatgttcctg aaattatggt gatcggcggt ggccgtgtta tcgaacagtt cctgccgaaa 1560 gcgcagaaac tgtacctgac ccacatcgac gcggaagttg aaggtgacac ccacttcccg 1620 gactacgaac cggatgattg ggagagcgta ttctccgaat tccatgatgc ggatgcgcaa 1680 aactctcatt cttactgttt tgaaatcctg gaacgtcgtt ga 1722 3-1103 Sequences 3-1103-1 Sequence Number [ID] 1103 3-1103-2 Molecule Type DNA 3-1103-3 Length 1245 3-1103-4 Features misc_feature 1..1245 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1245 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1103-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat cctga 1245 3-1104 Sequences 3-1104-1 Sequence Number [ID] 1104 3-1104-2 Molecule Type DNA 11 Aug 2023

3-1104-3 Length 1806 3-1104-4 Features misc_feature 1..1806 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1806 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1104-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 2023214349

ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggtgttgg ttcgctaaac 1260 tgcatcgtcg ctgtgtccca gaacatgggc atcggcaaga acggggacct gccctggcca 1320 ccgctcagga atgaattcag atatttccag agaatgacca caacctcttc agtagaaggt 1380 aaacagaatc tggtgattat gggtaagaag acctggttct ccattcctga gaagaatcga 1440 cctttaaagg gtagaattaa tttagttctc agcagagaac tcaaggaacc tccacaagga 1500 gctcattttc tttccagaag tctagatgat gccttaaaac ttactgaaca accagaatta 1560 gcaaataaag tagacatggt ctggatagtt ggtggcagtt ctgtttataa ggaagccatg 1620 aatcacccag gccatcttaa actatttgtg acaaggatca tgcaagactt tgaaagtgac 1680 acgttttttc cagaaattga tttggagaaa tataaacttc tgccagaata cccaggtgtt 1740 ctctctgatg tccaggagga gaaaggcatt aagtacaaat ttgaagtata tgaggagaat 1800 gattga 1806 3-1105 Sequences 3-1105-1 Sequence Number [ID] 1105 3-1105-2 Molecule Type DNA 3-1105-3 Length 1806 3-1105-4 Features misc_feature 1..1806 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1806 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1105-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggtgttgg ttcgctaaac 1260 tgcatcgtcg ctgtgtccca gaacatgggc atcggcaaga acggggacct gccctggcca 1320 ccgctcagga atgaattcag atatttccag agaatgacca caacctcttc agtagaaggt 1380 aaacagaatc tggtgattat gggtaagaag acctggttct ccattcctga gaagaatcga 1440 cctttaaagg gtagaattaa tttagttctc agcagagaac tcaaggaacc tccacaagga 1500 11 Aug 2023 gctcattttc tttccagaag tctagatgat gccttaaaac ttactgaaca accagaatta 1560 gcaaataaag tagacatggt ctggatagtt ggtggcagtt ctgtttataa ggaagccatg 1620 aatcacccag gccatcttaa actatttgtg acaaggatca tgcaagactt tgaaagtgac 1680 acgttttttc cagaaattga tttggagaaa tataaacttc tgccaggata cccaggtgtt 1740 ctctctgatg tccaggagga gaaaggcttt aagtacaaat ttgaagtata tgagaagaat 1800 gattga 1806 3-1106 Sequences 3-1106-1 Sequence Number [ID] 1106 3-1106-2 Molecule Type DNA 3-1106-3 Length 1806 3-1106-4 Features misc_feature 1..1806 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct 2023214349 source 1..1806 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1106-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggtgttgg ttcgctaaac 1260 tgcatcgtcg ctgtgtccca gaacatgggc atcggcaaga acggggacct gccctggcca 1320 ccgctcagga atgaattcag atatttccag agaatgacca caacctcttc agtagaaggt 1380 aaacagaatc tggtgattat gggtaagaag acctggttct ccattcctga gaagaatcga 1440 cctttaaagg gtagaattaa tttagttctc agcagagaac tcaaggaacc tccacaagga 1500 gctcattttc tttccagaag tctagatgat gccttaaaac ttactgaaca accagaatta 1560 gcaaataaag tagacatggt ctggatagtt ggtggcagtt ctgtttataa ggaagccatg 1620 aatcacccag gcagacttaa actatttgtg acaaggatca tgcaagactt tggaagtgac 1680 acgttttttc cagaaattga tttggagaaa tataaacttc tgccagaata cccaggtgtt 1740 ctctctgatg tccaggagga gaaaggcatt aagtacaaat ttgaagtata tgagaagaat 1800 gattga 1806 3-1107 Sequences 3-1107-1 Sequence Number [ID] 1107 3-1107-2 Molecule Type DNA 3-1107-3 Length 1806 3-1107-4 Features misc_feature 1..1806 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1806 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1107-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 11 Aug 2023 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggtgttgg ttcgctaaac 1260 tgcatcgtcg ctgtgtccca gaacatgggc gtcggcaaga acggggacct gccctggcca 1320 ccgctcagga atgaattcag atatttccag agaatgacca caacctcttc agtagaaggt 1380 aaacagaatc tggtgattat gggtaagaag acctggttct ccattcctga gaagaatcga 1440 cctttaaagg gtagaattaa tttagttctc agcagagaac tcaaggaacc tccacaagga 1500 gctcattttc tttccagaag tctagatgat gccttaaaac ttactgaaca accagaatta 1560 gcaaataaag tagacatggt ctggatagtt ggtggcagtt ctgtttataa ggaagccatg 1620 aatcacccag gccatcttaa actatttgtg acaaggatca tgcaagactt tgaaagtgac 1680 2023214349 acgttttttc cagaaattga tttggagaaa tataaacttc tgccagaata cccaggtgtt 1740 ctctctgatg tccaggagga gaaaggcatt aagtacaaat ttgaagtata tgagaagaat 1800 gattga 1806 3-1108 Sequences 3-1108-1 Sequence Number [ID] 1108 3-1108-2 Molecule Type DNA 3-1108-3 Length 1806 3-1108-4 Features misc_feature 1..1806 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1806 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1108-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggtgttgg ttcgctaaac 1260 tgcatcgtcg ctgtgtccca gaacatgggc atcggcaaga acggggacct gccctggcca 1320 ccgctcagga atgaattcag atatttccag agaatgacca caacctcttc agtagaaggt 1380 aaacagaatc tggtgattat gggtaagaag acctggttct ccattcctga gaagaatcga 1440 cctttaaagg gtagaattaa tttagttctc agcagagaac tcaaggaacc tccacaagga 1500 gctcattttc tttccagaag tctagatgat gccttaaaac ttactgaaca accagaatta 1560 gcaaataaag tagacatggt ctggatagtt ggtggcagtt ctgtttataa ggaagccatg 1620 tatcacccag gccatcttaa actatttgtg acaaggatca tgcaagactt tgaaagtgac 1680 acgttttttc cagaaattga tttggagaaa tataaacttc tgccagaata cccaggtgtt 1740 ctctctgatg tccaggagga gaaaggcatt aagtacaaat ttgaagtata tgagaagaat 1800 gattga 1806 3-1109 Sequences 3-1109-1 Sequence Number [ID] 1109 3-1109-2 Molecule Type DNA 3-1109-3 Length 1806 3-1109-4 Features misc_feature 1..1806 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1806 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1109-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcgactac 60 aaagacgatg acgacaagaa ctgggtgaac gtgatctccg acctgaaaaa gatcgaggat 120 ttgatccaga gcatgcacat tgacgccacc ctgtataccg agtccgacgt gcacccgagt 180 tgcaaggtga ctgccatgaa gtgcttcctg ctggagctgc aagtgatcag cctggagagc 240 ggcgacgcca gcatccacga caccgtggaa aaccttatca ttctggccaa caatagcctg 300 agcagcaacg gcaacgtgac cgaaagcgga tgtaaggaat gcgaggaact ggaagagaag 360 aatatcaaag aattcctgca aagcttcgtg cacatcgtgc agatgttcat caacacttct 420 11 Aug 2023 tcaggtggcg gtagtggtgg gggaggatct ggaggcggag gaagcggggg tggaggttca 480 ggtggaggca gcttgcaata cccatacgat gttccagatt acgctattac ctgcccccct 540 ccgatgagcg tggagcacgc cgacatctgg gtcaagagct acagcttgta tagtagggag 600 cggtacatct gtaacagcgg gttcaagagg aaggccggga ccagctcact gaccgagtgc 660 gtgttgaaca aggccaccaa cgtggcccac tggaccaccc ctagccttaa gtgcatcagg 720 gacccagcgc tcgtacacca gagacccgcg cctccctcta cggtaaccac ggcaggcgta 780 accccccagc ccgagagcct gtccccgagc ggcaaggagc ctgcagcgag cagcccctca 840 agcaacaaca cagccgctac caccgcggca atcgtgcccg gcagccagct gatgccctca 900 aagagcccca gcaccggcac cactgagata agcagccacg agagctcaca cggcactccc 960 tcacagacca ctgccaagaa ttgggagctg accgcctctg ccagccacca gcccccaggc 1020 gtgtatcccc agggccacag cgacaccacg gtcgccatca gcacatctac agtgcttttg 1080 tgcggcctta gcgccgtgtc actgctggca tgctacttga aaagtaggca aactccccct 1140 2023214349 cttgccagtg tggaaatgga ggccatggaa gccctgcccg tgacctgggg caccagttct 1200 agggacgagg accttgagaa ctgctcacat catttgggat ccggtgttgg ttcgctaaac 1260 tgcatcgtcg ctgtgtccca gaacatgggc gtcggcaaga acggggacct gccctggcca 1320 ccgctcagga atgaattcag atatttccag agaatgacca caacctcttc agtagaaggt 1380 aaacagaatc tggtgattat gggtaagaag acctggttct ccattcctga gaagaatcga 1440 cctttaaagg gtagaattaa tttagttctc agcagagaac tcaaggaacc tccacaagga 1500 gctcattttc tttccagaag tctagatgat gccttaaaac ttactgaaca accagaatta 1560 gcaaataaag tagacatggt ctggatagtt ggtggcagtt ctgttattaa ggaagccatg 1620 aatcacccag gccatcttaa actatttgtg acaaggatca tgcaagactt tgaaagtgac 1680 acgttttttc cagaaattga tttggagaaa tataaacttc tgccagaata cccaggtgtt 1740 ctctctgatg tccaggagga gaaaggcatt aagtacaaat ttgaagtata tgagaagaat 1800 gattga 1806 3-1110 Sequences 3-1110-1 Sequence Number [ID] 1110 3-1110-2 Molecule Type DNA 3-1110-3 Length 2046 3-1110-4 Features misc_feature 1..2046 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2046 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1110-5 Residues atggattgga cctggattct gtttctggtg gccgctgcca caagagtgca cagcaactgg 60 gtgaatgtga tcagcgacct gaagaagatc gaggatctga tccagagcat gcacattgat 120 gccaccctgt acacagaatc tgatgtgcac cctagctgta aagtgaccgc catgaagtgt 180 tttctgctgg agctgcaggt gatttctctg gaaagcggag atgcctctat ccacgacaca 240 gtggagaatc tgatcatcct ggccaacaat agcctgagca gcaatggcaa tgtgacagag 300 tctggctgta aggagtgtga ggagctggag gagaagaaca tcaaggagtt tctgcagagc 360 tttgtgcaca tcgtgcagat gttcatcaat acaagctctg gcggaggatc tggaggaggc 420 ggatctggag gaggaggcag tggaggcgga ggatctggcg gaggatctct gcagattaca 480 tgccctcctc caatgtctgt ggagcacgcc gatatttggg tgaagtccta cagcctgtac 540 agcagagaga gatacatctg caacagcggc tttaagagaa aggccggcac ctcttctctg 600 acagagtgcg tgctgaataa ggccacaaat gtggcccact ggacaacacc tagcctgaag 660 tgcattagag atcctgccct ggtccaccag aggcctgccc ctccatctac agtgacaaca 720 gccggagtga cacctcagcc tgaatctctg agcccttctg gaaaagaacc tgccgccagc 780 tctcctagct ctaataatac cgccgccaca acagccgcca ttgtgcctgg atctcagctg 840 atgcctagca agtctcctag cacaggcaca acagagatca gcagccacga atcttctcac 900 ggaacacctt ctcagaccac cgccaagaat tgggagctga cagcctctgc ctctcaccag 960 cctccaggag tgtatcctca gggccactct gatacaacag tggccatcag cacatctaca 1020 gtgctgctgt gtggactgtc tgccgtgtct ctgctggcct gttacctgaa gtctagacag 1080 acacctcctc tggcctctgt ggagatggag gccatggaag ccctgcctgt gacatgggga 1140 acaagcagca gagatgagga cctggagaat tgttctcacc acctgtcgcg aatggactac 1200 aaggacgatg acgacaagga ttataaagat gatgatgata aagattataa agacgacgat 1260 gataagtcgc gaggatccgg agctactaac ttcagcctgc tgaagcaggc tggagacgtg 1320 gaggagaacc ctggaccttt gagcaagggc gaggaggaca acatggccat catcaaggag 1380 ttcatgcgct tcaaggtgca catggagggc tccgtgaacg gccacgagtt cgagatcgag 1440 ggcgagggcg agggccgccc ctacgagggc acccagaccg ccaagctgaa ggtgaccaag 1500 ggcggccccc tgcccttcgc ctgggacatc ctgtcccctc agttcatgta cggctccaag 1560 gcctacgtga agcaccccgc cgacatcccc gactacttga agctgtcctt ccccgagggc 1620 ttcaagtggg agcgcgtgat gaacttcgag gacggcggcg tggtgaccgt gacccaggac 1680 tcctccctgc aggacggcga gttcatctac aaggtgaagc tgcgcggcac caacttcccc 1740 tccgacggcc ccgtaatgca gaagaagacc atgggctggg aggcctcctc cgagcggatg 1800 taccccgagg acggcgccct gaagggcgag atcaagcaga ggctgaagct gaaggacggc 1860 ggccactacg acgccgaggt caagaccacc tacaaggcca agaagcccgt gcagctgccc 1920 ggcgcctaca acgtcaacat caagctggac atcacctccc acaacgagga ctacaccatc 1980 gtggaacagt acgagcgcgc cgagggccgc cactccaccg gcggcatgga cgagctgtac 2040 aagtaa 2046

3-1111 Sequences 3-1111-1 Sequence Number [ID] 1111 3-1111-2 Molecule Type DNA 3-1111-3 Length 1959 11 Aug 2023

3-1111-4 Features misc_feature 1..1959 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1959 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1111-5 Residues atggattgga cctggattct gtttctggtg gccgctgcca caagagtgca cagcaactgg 60 gtgaatgtga tcagcgacct gaagaagatc gaggatctga tccagagcat gcacattgat 120 gccaccctgt acacagaatc tgatgtgcac cctagctgta aagtgaccgc catgaagtgt 180 tttctgctgg agctgcaggt gatttctctg gaaagcggag atgcctctat ccacgacaca 240 gtggagaatc tgatcatcct ggccaacaat agcctgagca gcaatggcaa tgtgacagag 300 tctggctgta aggagtgtga ggagctggag gagaagaaca tcaaggagtt tctgcagagc 360 2023214349

tttgtgcaca tcgtgcagat gttcatcaat acaagctctg gcggaggatc tggaggaggc 420 ggatctggag gaggaggcag tggaggcgga ggatctggcg gaggatctct gcagattaca 480 tgccctcctc caatgtctgt ggagcacgcc gatatttggg tgaagtccta cagcctgtac 540 agcagagaga gatacatctg caacagcggc tttaagagaa aggccggcac ctcttctctg 600 acagagtgcg tgctgaataa ggccacaaat gtggcccact ggacaacacc tagcctgaag 660 tgcattagag atcctgccct ggtccaccag aggcctgccc ctccatctac agtgacaaca 720 gccggagtga cacctcagcc tgaatctctg agcccttctg gaaaagaacc tgccgccagc 780 tctcctagct ctaataatac cgccgccaca acagccgcca ttgtgcctgg atctcagctg 840 atgcctagca agtctcctag cacaggcaca acagagatca gcagccacga atcttctcac 900 ggaacacctt ctcagaccac cgccaagaat tgggagctga cagcctctgc ctctcaccag 960 cctccaggag tgtatcctca gggccactct gatacaacag tggccatcag cacatctaca 1020 gtgctgctgt gtggactgtc tgccgtgtct ctgctggcct gttacctgaa gtctagacag 1080 acacctcctc tggcctctgt ggagatggag gccatggaag ccctgcctgt gacatgggga 1140 acaagcagca gagatgagga cctggagaat tgttctcacc acctgggatc cggagctact 1200 aacttcagcc tgctgaagca ggctggagac gtggaggaga accctggacc tttgagcaag 1260 ggcgaggagg acaacatggc catcatcaag gagttcatgc gcttcaaggt gcacatggag 1320 ggctccgtga acggccacga gttcgagatc gagggcgagg gcgagggccg cccctacgag 1380 ggcacccaga ccgccaagct gaaggtgacc aagggcggcc ccctgccctt cgcctgggac 1440 atcctgtccc ctcagttcat gtacggctcc aaggcctacg tgaagcaccc cgccgacatc 1500 cccgactact tgaagctgtc cttccccgag ggcttcaagt gggagcgcgt gatgaacttc 1560 gaggacggcg gcgtggtgac cgtgacccag gactcctccc tgcaggacgg cgagttcatc 1620 tacaaggtga agctgcgcgg caccaacttc ccctccgacg gccccgtaat gcagaagaag 1680 accatgggct gggaggcctc ctccgagcgg atgtaccccg aggacggcgc cctgaagggc 1740 gagatcaagc agaggctgaa gctgaaggac ggcggccact acgacgccga ggtcaagacc 1800 acctacaagg ccaagaagcc cgtgcagctg cccggcgcct acaacgtcaa catcaagctg 1860 gacatcacct cccacaacga ggactacacc atcgtggaac agtacgagcg cgccgagggc 1920 cgccactcca ccggcggcat ggacgagctg tacaagtaa 1959 3-1112 Sequences 3-1112-1 Sequence Number [ID] 1112 3-1112-2 Molecule Type 3-1112-3 Length 3-1112-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1112-5 Residues 000 3 3-1113 Sequences 3-1113-1 Sequence Number [ID] 1113 3-1113-2 Molecule Type 3-1113-3 Length 3-1113-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1113-5 Residues 000 3 3-1114 Sequences 3-1114-1 Sequence Number [ID] 1114 3-1114-2 Molecule Type AA 3-1114-3 Length 320 3-1114-4 Features REGION 1..320 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..320 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1114-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSGSVGSLNC IVAVSQNMGI GKNGDLPWPP LRNEFRYFQR MTTTSSVEGK 180

QNLVIMGKKT WFSIPEKNRP LKGRINLVLS RELKEPPQGA HFLSRSLDDA LKLTEQPELA 240 NKVDMVWIVG GSSVIKEAMN HPGHLKLFVT RIMQDFESDT FFPEIDLEKY KLLPEYPGVL 300 SDVQEEKGIK YKFEVYEKND 320 3-1115 Sequences 3-1115-1 Sequence Number [ID] 1115 11 Aug 2023

3-1115-2 Molecule Type AA 3-1115-3 Length 320 3-1115-4 Features REGION 1..320 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..320 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1115-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSGSVGSLNC IVAVSQNMGI GKNGDLPWPP LRNEFRYFQR MTTTSSVEGK 180 2023214349

QNLVIMGKKT WFSIPEKNRP LKGRINLVLS RELKEPPQGA HFLSRSLDDA LKLTEQPELA 240 NKVDMVWIVG GSSVIKEAMN HPGHLKLFVT RIMQDFESDT FFPEIDLEKY KLLPEYPGVL 300 SDVQEEKGIK YKFEVYEKND 320 3-1116 Sequences 3-1116-1 Sequence Number [ID] 1116 3-1116-2 Molecule Type AA 3-1116-3 Length 235 3-1116-4 Features REGION 1..235 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..235 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1116-5 Residues MSKGEEDNMA IIKEFMRFKV HMEGSVNGHE FEIEGEGEGR PYEGTQTAKL KVTKGGPLPF 60 AWDILSPQFM YGSKAYVKHP ADIPDYLKLS FPEGFKWERV MNFEDGGVVT VTQDSSLQDG 120 EFIYKVKLRG TNFPSDGPVM QKKTMGWEAS SERMYPEDGA LKGEIKQRLK LKDGGHYDAE 180 VKTTYKAKKP VQLPGAYNVN IKLDITSHNE DYTIVEQYER AEGRHSTGGM DELYK 235 3-1117 Sequences 3-1117-1 Sequence Number [ID] 1117 3-1117-2 Molecule Type AA 3-1117-3 Length 134 3-1117-4 Features REGION 1..134 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..134 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1117-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSGS 134 3-1118 Sequences 3-1118-1 Sequence Number [ID] 1118 3-1118-2 Molecule Type AA 3-1118-3 Length 134 3-1118-4 Features REGION 1..134 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..134 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1118-5 Residues MDWTWILFLV AAATRVHSNW VNVISDLKKI EDLIQSMHID ATLYTESDVH PSCKVTAMKC 60 FLLELQVISL ESGDASIHDT VENLIILANN SLSSNGNVTE SGCKECEELE EKNIKEFLQS 120 FVHIVQMFIN TSGS 134 3-1119 Sequences 3-1119-1 Sequence Number [ID] 1119 3-1119-2 Molecule Type AA 3-1119-3 Length 235 3-1119-4 Features REGION 1..235 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..235 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1119-5 Residues MSKGEEDNMA IIKEFMRFKV HMEGSVNGHE FEIEGEGEGR PYEGTQTAKL KVTKGGPLPF 60

AWDILSPQFM YGSKAYVKHP ADIPDYLKLS FPEGFKWERV MNFEDGGVVT VTQDSSLQDG 120 EFIYKVKLRG TNFPSDGPVM QKKTMGWEAS SERMYPEDGA LKGEIKQRLK LKDGGHYDAE 180 VKTTYKAKKP VQLPGAYNVN IKLDITSHNE DYTIVEQYER AEGRHSTGGM DELYK 235 3-1120 Sequences 3-1120-1 Sequence Number [ID] 1120 11 Aug 2023

3-1120-2 Molecule Type DNA 3-1120-3 Length 2291 3-1120-4 Features misc_feature 1..2291 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..2291 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1120-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaatgtaa taagtgattt gaaaaaaatt gaagatctta ttcaatctat gcatattgat 120 gctactttat atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 180 2023214349

tttctcttgg agttacaagt tatttcactt gagtccggag atgcaagtat tcatgataca 240 gtagaaaatc tgatcatcct agcaaacaac agtttgtctt ctaatgggaa tgtaacagaa 300 tctggatgca aagaatgtga ggaactggag gaaaaaaata ttaaagaatt tttgcagagt 360 tttgtacata ttgtccaaat gttcatcaac acttctggtt ccgttggttc gctaaactgc 420 atcgtcgctg tgtcccagaa catgggcatc ggcaagaacg gggacctgcc ctggccaccg 480 ctcaggaatg aattcagata tttccagaga atgaccacaa cctcttcagt agaaggtaaa 540 cagaatctgg tgattatggg taagaagacc tggttctcca ttcctgagaa gaatcgacct 600 ttaaagggta gaattaattt agttctcagc agagaactca aggaacctcc acaaggagct 660 cattttcttt ccagaagtct agatgatgcc ttaaaactta ctgaacaacc agaattagca 720 aataaagtag acatggtctg gatagttggt ggcagttctg ttattaagga agccatgaat 780 cacccaggcc atcttaaact atttgtgaca aggatcatgc aagactttga aagtgacacg 840 ttttttccag aaattgattt ggagaaatat aaacttctgc cagaataccc aggtgttctc 900 tctgatgtcc aggaggagaa aggcattaag tacaaatttg aagtatatga gaagaatgat 960 tgatctagat aatacgactc actagagatc ccgcccctct ccctcccccc cccctaacgt 1020 tactggccga agccgcttgg aataaggccg gtgtgcgttt gtctatatgt tattttccac 1080 catattgccg tcttttggca atgtgagggc ccggaaacct ggccctgtct tcttgacgag 1140 cattcctagg ggtctttccc ctctcgccaa aggaatgcaa ggtctgttga atgtcgtgaa 1200 ggaagcagtt cctctggaag cttcttgaag acaaacaacg tctgtagcga ccctttgcag 1260 gcagcggaac cccccacctg gcgacaggtg cctctgcggc caaaagccac gtgtataaga 1320 tacacctgca aaggcggcac aaccccagtg ccacgttgtg agttggatag ttgtggaaag 1380 agtcaaatgg ctctcctcaa gcgtattcaa caaggggctg aaggatgccc agaaggtacc 1440 ccattgtatg ggatctgatc tggggcctcg gtgcacatgc tttacatgtg tttagtcgag 1500 gttaaaaaaa cgtctaggcc ccccgaacca cggggacgtg gttttccttt gaaaaacacg 1560 atgataatat ggccacaacc atgatgagca agggcgagga ggataacatg gccatcatca 1620 aggagttcat gcgcttcaag gtgcacatgg agggctccgt gaacggccac gagttcgaga 1680 tcgagggcga gggcgagggc cgcccctacg agggcaccca gaccgccaag ctgaaggtga 1740 ccaagggtgg ccccctgccc ttcgcctggg acatcctgtc ccctcagttc atgtacggct 1800 ccaaggccta cgtgaagcac cccgccgaca tccccgacta cttgaagctg tccttccccg 1860 agggcttcaa gtgggagcgc gtgatgaact tcgaggacgg cggcgtggtg accgtgaccc 1920 aggactcctc cctgcaggac ggcgagttca tctacaaggt gaagctgcgc ggcaccaact 1980 tcccctccga cggccccgta atgcagaaga agaccatggg ctgggaggcc tcctccgagc 2040 ggatgtaccc cgaggacggc gccctgaagg gcgagatcaa gcagaggctg aagctgaagg 2100 acggcggcca ctacgacgct gaggtcaaga ccacctacaa ggccaagaag cccgtgcagc 2160 tgcccggcgc ctacaacgtc aacatcaagt tggacatcac ctcccacaac gaggactaca 2220 ccatcgtgga acagtacgaa cgcgccgagg gccgccactc caccggcggc atggacgagc 2280 tgtacaagta a 2291 3-1121 Sequences 3-1121-1 Sequence Number [ID] 1121 3-1121-2 Molecule Type DNA 3-1121-3 Length 963 3-1121-4 Features misc_feature 1..963 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..963 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1121-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaatgtaa taagtgattt gaaaaaaatt gaagatctta ttcaatctat gcatattgat 120 gctactttat atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 180 tttctcttgg agttacaagt tatttcactt gagtccggag atgcaagtat tcatgataca 240 gtagaaaatc tgatcatcct agcaaacaac agtttgtctt ctaatgggaa tgtaacagaa 300 tctggatgca aagaatgtga ggaactggag gaaaaaaata ttaaagaatt tttgcagagt 360 tttgtacata ttgtccaaat gttcatcaac acttctggtt ccgttggttc gctaaactgc 420 atcgtcgctg tgtcccagaa catgggcatc ggcaagaacg gggacctgcc ctggccaccg 480 ctcaggaatg aattcagata tttccagaga atgaccacaa cctcttcagt agaaggtaaa 540 cagaatctgg tgattatggg taagaagacc tggttctcca ttcctgagaa gaatcgacct 600 ttaaagggta gaattaattt agttctcagc agagaactca aggaacctcc acaaggagct 660 cattttcttt ccagaagtct agatgatgcc ttaaaactta ctgaacaacc agaattagca 720 aataaagtag acatggtctg gatagttggt ggcagttctg ttattaagga agccatgaat 780 cacccaggcc atcttaaact atttgtgaca aggatcatgc aagactttga aagtgacacg 840 ttttttccag aaattgattt ggagaaatat aaacttctgc cagaataccc aggtgttctc 900 tctgatgtcc aggaggagaa aggcattaag tacaaatttg aagtatatga gaagaatgat 960 11 Aug 2023 tga 963 3-1122 Sequences 3-1122-1 Sequence Number [ID] 1122 3-1122-2 Molecule Type DNA 3-1122-3 Length 708 3-1122-4 Features misc_feature 1..708 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..708 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 2023214349

3-1122-5 Residues atgagcaagg gcgaggagga taacatggcc atcatcaagg agttcatgcg cttcaaggtg 60 cacatggagg gctccgtgaa cggccacgag ttcgagatcg agggcgaggg cgagggccgc 120 ccctacgagg gcacccagac cgccaagctg aaggtgacca agggtggccc cctgcccttc 180 gcctgggaca tcctgtcccc tcagttcatg tacggctcca aggcctacgt gaagcacccc 240 gccgacatcc ccgactactt gaagctgtcc ttccccgagg gcttcaagtg ggagcgcgtg 300 atgaacttcg aggacggcgg cgtggtgacc gtgacccagg actcctccct gcaggacggc 360 gagttcatct acaaggtgaa gctgcgcggc accaacttcc cctccgacgg ccccgtaatg 420 cagaagaaga ccatgggctg ggaggcctcc tccgagcgga tgtaccccga ggacggcgcc 480 ctgaagggcg agatcaagca gaggctgaag ctgaaggacg gcggccacta cgacgctgag 540 gtcaagacca cctacaaggc caagaagccc gtgcagctgc ccggcgccta caacgtcaac 600 atcaagttgg acatcacctc ccacaacgag gactacacca tcgtggaaca gtacgaacgc 660 gccgagggcc gccactccac cggcggcatg gacgagctgt acaagtaa 708 3-1123 Sequences 3-1123-1 Sequence Number [ID] 1123 3-1123-2 Molecule Type DNA 3-1123-3 Length 1735 3-1123-4 Features misc_feature 1..1735 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..1735 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1123-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaatgtaa taagtgattt gaaaaaaatt gaagatctta ttcaatctat gcatattgat 120 gctactttat atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 180 tttctcttgg agttacaagt tatttcactt gagtccggag atgcaagtat tcatgataca 240 gtagaaaatc tgatcatcct agcaaacaac agtttgtctt ctaatgggaa tgtaacagaa 300 tctggatgca aagaatgtga ggaactggag gaaaaaaata ttaaagaatt tttgcagagt 360 tttgtacata ttgtccaaat gttcatcaac acttctggat cctgaaatct agataatacg 420 actcactaga gatcccgccc ctctccctcc ccccccccta acgttactgg ccgaagccgc 480 ttggaataag gccggtgtgc gtttgtctat atgttatttt ccaccatatt gccgtctttt 540 ggcaatgtga gggcccggaa acctggccct gtcttcttga cgagcattcc taggggtctt 600 tcccctctcg ccaaaggaat gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg 660 gaagcttctt gaagacaaac aacgtctgta gcgacccttt gcaggcagcg gaacccccca 720 cctggcgaca ggtgcctctg cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg 780 gcacaacccc agtgccacgt tgtgagttgg atagttgtgg aaagagtcaa atggctctcc 840 tcaagcgtat tcaacaaggg gctgaaggat gcccagaagg taccccattg tatgggatct 900 gatctggggc ctcggtgcac atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta 960 ggccccccga accacgggga cgtggttttc ctttgaaaaa cacgatgata atatggccac 1020 aaccatgatg agcaagggcg aggaggataa catggccatc atcaaggagt tcatgcgctt 1080 caaggtgcac atggagggct ccgtgaacgg ccacgagttc gagatcgagg gcgagggcga 1140 gggccgcccc tacgagggca cccagaccgc caagctgaag gtgaccaagg gtggccccct 1200 gcccttcgcc tgggacatcc tgtcccctca gttcatgtac ggctccaagg cctacgtgaa 1260 gcaccccgcc gacatccccg actacttgaa gctgtccttc cccgagggct tcaagtggga 1320 gcgcgtgatg aacttcgagg acggcggcgt ggtgaccgtg acccaggact cctccctgca 1380 ggacggcgag ttcatctaca aggtgaagct gcgcggcacc aacttcccct ccgacggccc 1440 cgtaatgcag aagaagacca tgggctggga ggcctcctcc gagcggatgt accccgagga 1500 cggcgccctg aagggcgaga tcaagcagag gctgaagctg aaggacggcg gccactacga 1560 cgctgaggtc aagaccacct acaaggccaa gaagcccgtg cagctgcccg gcgcctacaa 1620 cgtcaacatc aagttggaca tcacctccca caacgaggac tacaccatcg tggaacagta 1680 cgaacgcgcc gagggccgcc actccaccgg cggcatggac gagctgtaca agtaa 1735 3-1124 Sequences 3-1124-1 Sequence Number [ID] 1124 3-1124-2 Molecule Type DNA 3-1124-3 Length 405 3-1124-4 Features misc_feature 1..405 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..405 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-1124-5 Residues atggactgga catggatact cttcctggta gcagccgcca cacgagtgca cagcaactgg 60 gtgaatgtaa taagtgattt gaaaaaaatt gaagatctta ttcaatctat gcatattgat 120 gctactttat atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 180 tttctcttgg agttacaagt tatttcactt gagtccggag atgcaagtat tcatgataca 240 gtagaaaatc tgatcatcct agcaaacaac agtttgtctt ctaatgggaa tgtaacagaa 300 tctggatgca aagaatgtga ggaactggag gaaaaaaata ttaaagaatt tttgcagagt 360 tttgtacata ttgtccaaat gttcatcaac acttctggat cctga 405 3-1125 Sequences 3-1125-1 Sequence Number [ID] 1125 3-1125-2 Molecule Type DNA 3-1125-3 Length 708 3-1125-4 Features misc_feature 1..708 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..708 mol_type=other DNA organism=synthetic construct NonEnglishQualifier Value 3-1125-5 Residues atgagcaagg gcgaggagga taacatggcc atcatcaagg agttcatgcg cttcaaggtg 60 cacatggagg gctccgtgaa cggccacgag ttcgagatcg agggcgaggg cgagggccgc 120 ccctacgagg gcacccagac cgccaagctg aaggtgacca agggtggccc cctgcccttc 180 gcctgggaca tcctgtcccc tcagttcatg tacggctcca aggcctacgt gaagcacccc 240 gccgacatcc ccgactactt gaagctgtcc ttccccgagg gcttcaagtg ggagcgcgtg 300 atgaacttcg aggacggcgg cgtggtgacc gtgacccagg actcctccct gcaggacggc 360 gagttcatct acaaggtgaa gctgcgcggc accaacttcc cctccgacgg ccccgtaatg 420 cagaagaaga ccatgggctg ggaggcctcc tccgagcgga tgtaccccga ggacggcgcc 480 ctgaagggcg agatcaagca gaggctgaag ctgaaggacg gcggccacta cgacgctgag 540 gtcaagacca cctacaaggc caagaagccc gtgcagctgc ccggcgccta caacgtcaac 600 atcaagttgg acatcacctc ccacaacgag gactacacca tcgtggaaca gtacgaacgc 660 gccgagggcc gccactccac cggcggcatg gacgagctgt acaagtaa 708 3-1126 Sequences 3-1126-1 Sequence Number [ID] 1126 3-1126-2 Molecule Type AA 3-1126-3 Length 14 3-1126-4 Features REGION 1..14 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..14 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1126-5 Residues YDSLEIPPLS LPPP 14 3-1127 Sequences 3-1127-1 Sequence Number [ID] 1127 3-1127-2 Molecule Type AA 3-1127-3 Length 43 3-1127-4 Features REGION 1..43 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..43 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1127-5 Residues RYWPKPLGIR PVCVCLYVIF HHIAVFWQCE GPETWPCLLD EHS 43 3-1128 Sequences 3-1128-1 Sequence Number [ID] 1128 3-1128-2 Molecule Type AA 3-1128-3 Length 102 3-1128-4 Features REGION 1..102 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..102 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1128-5 Residues GSFPSRQRNA RSVECREGSS SSGSFLKTNN VCSDPLQAAE PPTWRQVPLR PKATCIRYTC 60 KGGTTPVPRC ELDSCGKSQM ALLKRIQQGA EGCPEGTPLY GI 102 3-1129 Sequences 3-1129-1 Sequence Number [ID] 1129 3-1129-2 Molecule Type AA

3-1129-3 Length 41 3-1129-4 Features REGION 1..41 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..41 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1129-5 Residues SGASVHMLYM CLVEVKKTSR PPEPRGRGFP LKNTMIIWPQ P 41 3-1130 Sequences 3-1130-1 Sequence Number [ID] 1130 3-1130-2 Molecule Type AA 3-1130-3 Length 24 3-1130-4 Features REGION 1..24 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..24 mol_type=protein 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-1130-5 Residues ARARRITWPS SRSSCASRCT WRAP 24 3-1131 Sequences 3-1131-1 Sequence Number [ID] 1131 3-1131-2 Molecule Type AA 3-1131-3 Length 23 3-1131-4 Features REGION 1..23 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..23 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1131-5 Residues TATSSRSRAR ARAAPTRAPR PPS 23 3-1132 Sequences 3-1132-1 Sequence Number [ID] 1132 3-1132-2 Molecule Type AA 3-1132-3 Length 24 3-1132-4 Features REGION 1..24 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..24 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1132-5 Residues PRVAPCPSPG TSCPLSSCTA PRPT 24 3-1133 Sequences 3-1133-1 Sequence Number [ID] 1133 3-1133-2 Molecule Type AA 3-1133-3 Length 9 3-1133-4 Features REGION 1..9 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..9 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1133-5 Residues STPPTSPTT 9 3-1134 Sequences 3-1134-1 Sequence Number [ID] 1134 3-1134-2 Molecule Type AA 3-1134-3 Length 12 3-1134-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1134-5 Residues SCPSPRASSG SA 12 3-1135 Sequences 3-1135-1 Sequence Number [ID] 1135 3-1135-2 Molecule Type AA 3-1135-3 Length 7 3-1135-4 Features REGION 1..7

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..7 mol_type=protein organism=synthetic construct 11 Aug 2023

NonEnglishQualifier Value 3-1135-5 Residues TSRTAAW 7 3-1136 Sequences 3-1136-1 Sequence Number [ID] 1136 3-1136-2 Molecule Type AA 3-1136-3 Length 14 3-1136-4 Features REGION 1..14 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..14 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 2023214349

3-1136-5 Residues PRTPPCRTAS SSTR 14 3-1137 Sequences 3-1137-1 Sequence Number [ID] 1137 3-1137-2 Molecule Type AA 3-1137-3 Length 12 3-1137-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1137-5 Residues SCAAPTSPPT AP 12 3-1138 Sequences 3-1138-1 Sequence Number [ID] 1138 3-1138-2 Molecule Type AA 3-1138-3 Length 21 3-1138-4 Features REGION 1..21 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..21 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1138-5 Residues CRRRPWAGRP PPSGCTPRTA P 21 3-1139 Sequences 3-1139-1 Sequence Number [ID] 1139 3-1139-2 Molecule Type AA 3-1139-3 Length 7 3-1139-4 Features REGION 1..7 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..7 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1139-5 Residues RARSSRG 7 3-1140 Sequences 3-1140-1 Sequence Number [ID] 1140 3-1140-2 Molecule Type AA 3-1140-3 Length 64 3-1140-4 Features REGION 1..64 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..64 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1140-5 Residues RTAATTTLRS RPPTRPRSPC SCPAPTTSTS SWTSPPTTRT TPSWNSTNAP RAATPPAAWT 60 SCTS 64 3-1141 Sequences 3-1141-1 Sequence Number [ID] 1141 3-1141-2 Molecule Type AA 3-1141-3 Length 7 3-1141-4 Features REGION 1..7 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..7 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 11 Aug 2023

3-1141-5 Residues NLDNTTH 7 3-1142 Sequences 3-1142-1 Sequence Number [ID] 1142 3-1142-2 Molecule Type AA 3-1142-3 Length 19 3-1142-4 Features REGION 1..19 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..19 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1142-5 Residues RSRPSPSPPP NVTGRSRLE 19 2023214349

3-1143 Sequences 3-1143-1 Sequence Number [ID] 1143 3-1143-2 Molecule Type AA 3-1143-3 Length 60 3-1143-4 Features REGION 1..60 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..60 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1143-5 Residues GRCAFVYMLF STILPSFGNV RARKPGPVFL TSIPRGLSPL AKGMQGLLNV VKEAVPLEAS 60 3-1144 Sequences 3-1144-1 Sequence Number [ID] 1144 3-1144-2 Molecule Type AA 3-1144-3 Length 29 3-1144-4 Features REGION 1..29 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..29 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1144-5 Residues RQTTSVATLC RQRNPPPGDR CLCGQKPRV 29 3-1145 Sequences 3-1145-1 Sequence Number [ID] 1145 3-1145-2 Molecule Type AA 3-1145-3 Length 58 3-1145-4 Features REGION 1..58 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..58 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1145-5 Residues DTPAKAAQPQ CHVVSWIVVE RVKWLSSSVF NKGLKDAQKV PHCMGSDLGP RCTCFTCV 58 3-1146 Sequences 3-1146-1 Sequence Number [ID] 1146 3-1146-2 Molecule Type AA 3-1146-3 Length 18 3-1146-4 Features REGION 1..18 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..18 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1146-5 Residues SRLKKRLGPP NHGDVVFL 18 3-1147 Sequences 3-1147-1 Sequence Number [ID] 1147 3-1147-2 Molecule Type AA 3-1147-3 Length 12 3-1147-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1147-5 Residues YGHNHDEQGR GG 12 3-1148 Sequences 11 Aug 2023

3-1148-1 Sequence Number [ID] 1148 3-1148-2 Molecule Type AA 3-1148-3 Length 171 3-1148-4 Features REGION 1..171 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..171 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1148-5 Residues HGHHQGVHAL QGAHGGLRER PRVRDRGRGR GPPLRGHPDR QAEGDQGWPP ALRLGHPVPS 60 VHVRLQGLRE APRRHPRLLE AVLPRGLQVG ARDELRGRRR GDRDPGLLPA GRRVHLQGEA 120 ARHQLPLRRP RNAEEDHGLG GLLRADVPRG RRPEGRDQAE AEAEGRRPLR R 171 2023214349

3-1149 Sequences 3-1149-1 Sequence Number [ID] 1149 3-1149-2 Molecule Type AA 3-1149-3 Length 56 3-1149-4 Features REGION 1..56 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..56 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1149-5 Residues GQDHLQGQEA RAAARRLQRQ HQVGHHLPQR GLHHRGTVRT RRGPPLHRRH GRAVQV 56 3-1150 Sequences 3-1150-1 Sequence Number [ID] 1150 3-1150-2 Molecule Type 3-1150-3 Length 3-1150-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1150-5 Residues 000 3 3-1151 Sequences 3-1151-1 Sequence Number [ID] 1151 3-1151-2 Molecule Type 3-1151-3 Length 3-1151-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1151-5 Residues 000 3 3-1152 Sequences 3-1152-1 Sequence Number [ID] 1152 3-1152-2 Molecule Type 3-1152-3 Length 3-1152-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1152-5 Residues 000 3 3-1153 Sequences 3-1153-1 Sequence Number [ID] 1153 3-1153-2 Molecule Type 3-1153-3 Length 3-1153-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1153-5 Residues 000 3 3-1154 Sequences 3-1154-1 Sequence Number [ID] 1154 3-1154-2 Molecule Type 3-1154-3 Length 3-1154-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1154-5 Residues 000 3 3-1155 Sequences

3-1155-1 Sequence Number [ID] 1155 3-1155-2 Molecule Type 3-1155-3 Length 3-1155-4 Features 11 Aug 2023

Location/Qualifiers NonEnglishQualifier Value 3-1155-5 Residues 000 3 3-1156 Sequences 3-1156-1 Sequence Number [ID] 1156 3-1156-2 Molecule Type 3-1156-3 Length 3-1156-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1156-5 Residues 000 3 3-1157 Sequences 2023214349

3-1157-1 Sequence Number [ID] 1157 3-1157-2 Molecule Type 3-1157-3 Length 3-1157-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1157-5 Residues 000 3 3-1158 Sequences 3-1158-1 Sequence Number [ID] 1158 3-1158-2 Molecule Type 3-1158-3 Length 3-1158-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1158-5 Residues 000 3 3-1159 Sequences 3-1159-1 Sequence Number [ID] 1159 3-1159-2 Molecule Type 3-1159-3 Length 3-1159-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1159-5 Residues 000 3 3-1160 Sequences 3-1160-1 Sequence Number [ID] 1160 3-1160-2 Molecule Type 3-1160-3 Length 3-1160-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1160-5 Residues 000 3 3-1161 Sequences 3-1161-1 Sequence Number [ID] 1161 3-1161-2 Molecule Type 3-1161-3 Length 3-1161-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1161-5 Residues 000 3 3-1162 Sequences 3-1162-1 Sequence Number [ID] 1162 3-1162-2 Molecule Type 3-1162-3 Length 3-1162-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1162-5 Residues 000 3 3-1163 Sequences 3-1163-1 Sequence Number [ID] 1163 3-1163-2 Molecule Type 3-1163-3 Length 3-1163-4 Features

Location/Qualifiers NonEnglishQualifier Value 3-1163-5 Residues 000 3 3-1164 Sequences 11 Aug 2023

3-1164-1 Sequence Number [ID] 1164 3-1164-2 Molecule Type 3-1164-3 Length 3-1164-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1164-5 Residues 000 3 3-1165 Sequences 3-1165-1 Sequence Number [ID] 1165 3-1165-2 Molecule Type 3-1165-3 Length 3-1165-4 Features 2023214349

Location/Qualifiers NonEnglishQualifier Value 3-1165-5 Residues 000 3 3-1166 Sequences 3-1166-1 Sequence Number [ID] 1166 3-1166-2 Molecule Type 3-1166-3 Length 3-1166-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1166-5 Residues 000 3 3-1167 Sequences 3-1167-1 Sequence Number [ID] 1167 3-1167-2 Molecule Type 3-1167-3 Length 3-1167-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1167-5 Residues 000 3 3-1168 Sequences 3-1168-1 Sequence Number [ID] 1168 3-1168-2 Molecule Type 3-1168-3 Length 3-1168-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1168-5 Residues 000 3 3-1169 Sequences 3-1169-1 Sequence Number [ID] 1169 3-1169-2 Molecule Type 3-1169-3 Length 3-1169-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1169-5 Residues 000 3 3-1170 Sequences 3-1170-1 Sequence Number [ID] 1170 3-1170-2 Molecule Type 3-1170-3 Length 3-1170-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1170-5 Residues 000 3 3-1171 Sequences 3-1171-1 Sequence Number [ID] 1171 3-1171-2 Molecule Type 3-1171-3 Length 3-1171-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1171-5 Residues 000 3 3-1172 Sequences

3-1172-1 Sequence Number [ID] 1172 3-1172-2 Molecule Type 3-1172-3 Length 3-1172-4 Features 11 Aug 2023

Location/Qualifiers NonEnglishQualifier Value 3-1172-5 Residues 000 3 3-1173 Sequences 3-1173-1 Sequence Number [ID] 1173 3-1173-2 Molecule Type 3-1173-3 Length 3-1173-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1173-5 Residues 000 3 3-1174 Sequences 2023214349

3-1174-1 Sequence Number [ID] 1174 3-1174-2 Molecule Type 3-1174-3 Length 3-1174-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1174-5 Residues 000 3 3-1175 Sequences 3-1175-1 Sequence Number [ID] 1175 3-1175-2 Molecule Type 3-1175-3 Length 3-1175-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1175-5 Residues 000 3 3-1176 Sequences 3-1176-1 Sequence Number [ID] 1176 3-1176-2 Molecule Type 3-1176-3 Length 3-1176-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1176-5 Residues 000 3 3-1177 Sequences 3-1177-1 Sequence Number [ID] 1177 3-1177-2 Molecule Type 3-1177-3 Length 3-1177-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1177-5 Residues 000 3 3-1178 Sequences 3-1178-1 Sequence Number [ID] 1178 3-1178-2 Molecule Type 3-1178-3 Length 3-1178-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1178-5 Residues 000 3 3-1179 Sequences 3-1179-1 Sequence Number [ID] 1179 3-1179-2 Molecule Type 3-1179-3 Length 3-1179-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1179-5 Residues 000 3 3-1180 Sequences 3-1180-1 Sequence Number [ID] 1180 3-1180-2 Molecule Type 3-1180-3 Length 3-1180-4 Features

Location/Qualifiers NonEnglishQualifier Value 3-1180-5 Residues 000 3 3-1181 Sequences 11 Aug 2023

3-1181-1 Sequence Number [ID] 1181 3-1181-2 Molecule Type 3-1181-3 Length 3-1181-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1181-5 Residues 000 3 3-1182 Sequences 3-1182-1 Sequence Number [ID] 1182 3-1182-2 Molecule Type 3-1182-3 Length 3-1182-4 Features 2023214349

Location/Qualifiers NonEnglishQualifier Value 3-1182-5 Residues 000 3 3-1183 Sequences 3-1183-1 Sequence Number [ID] 1183 3-1183-2 Molecule Type 3-1183-3 Length 3-1183-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1183-5 Residues 000 3 3-1184 Sequences 3-1184-1 Sequence Number [ID] 1184 3-1184-2 Molecule Type 3-1184-3 Length 3-1184-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1184-5 Residues 000 3 3-1185 Sequences 3-1185-1 Sequence Number [ID] 1185 3-1185-2 Molecule Type 3-1185-3 Length 3-1185-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1185-5 Residues 000 3 3-1186 Sequences 3-1186-1 Sequence Number [ID] 1186 3-1186-2 Molecule Type 3-1186-3 Length 3-1186-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1186-5 Residues 000 3 3-1187 Sequences 3-1187-1 Sequence Number [ID] 1187 3-1187-2 Molecule Type 3-1187-3 Length 3-1187-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1187-5 Residues 000 3 3-1188 Sequences 3-1188-1 Sequence Number [ID] 1188 3-1188-2 Molecule Type 3-1188-3 Length 3-1188-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1188-5 Residues 000 3 3-1189 Sequences

3-1189-1 Sequence Number [ID] 1189 3-1189-2 Molecule Type 3-1189-3 Length 3-1189-4 Features 11 Aug 2023

Location/Qualifiers NonEnglishQualifier Value 3-1189-5 Residues 000 3 3-1190 Sequences 3-1190-1 Sequence Number [ID] 1190 3-1190-2 Molecule Type 3-1190-3 Length 3-1190-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1190-5 Residues 000 3 3-1191 Sequences 2023214349

3-1191-1 Sequence Number [ID] 1191 3-1191-2 Molecule Type 3-1191-3 Length 3-1191-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1191-5 Residues 000 3 3-1192 Sequences 3-1192-1 Sequence Number [ID] 1192 3-1192-2 Molecule Type 3-1192-3 Length 3-1192-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1192-5 Residues 000 3 3-1193 Sequences 3-1193-1 Sequence Number [ID] 1193 3-1193-2 Molecule Type 3-1193-3 Length 3-1193-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1193-5 Residues 000 3 3-1194 Sequences 3-1194-1 Sequence Number [ID] 1194 3-1194-2 Molecule Type 3-1194-3 Length 3-1194-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1194-5 Residues 000 3 3-1195 Sequences 3-1195-1 Sequence Number [ID] 1195 3-1195-2 Molecule Type 3-1195-3 Length 3-1195-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1195-5 Residues 000 3 3-1196 Sequences 3-1196-1 Sequence Number [ID] 1196 3-1196-2 Molecule Type 3-1196-3 Length 3-1196-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1196-5 Residues 000 3 3-1197 Sequences 3-1197-1 Sequence Number [ID] 1197 3-1197-2 Molecule Type 3-1197-3 Length 3-1197-4 Features

Location/Qualifiers NonEnglishQualifier Value 3-1197-5 Residues 000 3 3-1198 Sequences 11 Aug 2023

3-1198-1 Sequence Number [ID] 1198 3-1198-2 Molecule Type 3-1198-3 Length 3-1198-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1198-5 Residues 000 3 3-1199 Sequences 3-1199-1 Sequence Number [ID] 1199 3-1199-2 Molecule Type 3-1199-3 Length 3-1199-4 Features 2023214349

Location/Qualifiers NonEnglishQualifier Value 3-1199-5 Residues 000 3 3-1200 Sequences 3-1200-1 Sequence Number [ID] 1200 3-1200-2 Molecule Type 3-1200-3 Length 3-1200-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1200-5 Residues 000 3 3-1201 Sequences 3-1201-1 Sequence Number [ID] 1201 3-1201-2 Molecule Type 3-1201-3 Length 3-1201-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1201-5 Residues 000 3 3-1202 Sequences 3-1202-1 Sequence Number [ID] 1202 3-1202-2 Molecule Type 3-1202-3 Length 3-1202-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1202-5 Residues 000 3 3-1203 Sequences 3-1203-1 Sequence Number [ID] 1203 3-1203-2 Molecule Type 3-1203-3 Length 3-1203-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1203-5 Residues 000 3 3-1204 Sequences 3-1204-1 Sequence Number [ID] 1204 3-1204-2 Molecule Type 3-1204-3 Length 3-1204-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1204-5 Residues 000 3 3-1205 Sequences 3-1205-1 Sequence Number [ID] 1205 3-1205-2 Molecule Type 3-1205-3 Length 3-1205-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1205-5 Residues 000 3 3-1206 Sequences

3-1206-1 Sequence Number [ID] 1206 3-1206-2 Molecule Type 3-1206-3 Length 3-1206-4 Features 11 Aug 2023

Location/Qualifiers NonEnglishQualifier Value 3-1206-5 Residues 000 3 3-1207 Sequences 3-1207-1 Sequence Number [ID] 1207 3-1207-2 Molecule Type 3-1207-3 Length 3-1207-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1207-5 Residues 000 3 3-1208 Sequences 2023214349

3-1208-1 Sequence Number [ID] 1208 3-1208-2 Molecule Type 3-1208-3 Length 3-1208-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1208-5 Residues 000 3 3-1209 Sequences 3-1209-1 Sequence Number [ID] 1209 3-1209-2 Molecule Type 3-1209-3 Length 3-1209-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1209-5 Residues 000 3 3-1210 Sequences 3-1210-1 Sequence Number [ID] 1210 3-1210-2 Molecule Type 3-1210-3 Length 3-1210-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1210-5 Residues 000 3 3-1211 Sequences 3-1211-1 Sequence Number [ID] 1211 3-1211-2 Molecule Type 3-1211-3 Length 3-1211-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1211-5 Residues 000 3 3-1212 Sequences 3-1212-1 Sequence Number [ID] 1212 3-1212-2 Molecule Type 3-1212-3 Length 3-1212-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1212-5 Residues 000 3 3-1213 Sequences 3-1213-1 Sequence Number [ID] 1213 3-1213-2 Molecule Type 3-1213-3 Length 3-1213-4 Features Location/Qualifiers NonEnglishQualifier Value 3-1213-5 Residues 000 3 3-1214 Sequences 3-1214-1 Sequence Number [ID] 1214 3-1214-2 Molecule Type 3-1214-3 Length 3-1214-4 Features

Location/Qualifiers NonEnglishQualifier Value 3-1214-5 Residues 000 3 3-1215 Sequences 11 Aug 2023

3-1215-1 Sequence Number [ID] 1215 3-1215-2 Molecule Type AA 3-1215-3 Length 604 3-1215-4 Features REGION 1..604 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..604 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1215-5 Residues MALPVTALLL PLALLLHAAR PDIQMTQTTS SLSASLGDRV TISCRASQDI SKYLNWYQQK 60 PDGTVKLLIY HTSRLHSGVP SRFSGSGSGT DYSLTISNLE QEDIATYFCQ QGNTLPYTFG 120 GGTKLEITGG GGSGGGGSGG GGSEVKLQES GPGLVAPSQS LSVTCTVSGV SLPDYGVSWI 180 2023214349

RQPPRKGLEW LGVIWGSETT YYNSALKSRL TIIKDNSKSQ VFLKMNSLQT DDTAIYYCAK 240 HYYYGGSYAM DYWGQGTSVT VSSTTTPAPR PPTPAPTIAS QPLSLRPEAC RPAAGGAVHT 300 RGLDFACDIY IWAPLAGTCG VLLLSLVITL YCKRGRKKLL YIFKQPFMRP VQTTQEEDGC 360 SCRFPEEEEG GCELRVKFSR SADAPAYKQG QNQLYNELNL GRREEYDVLD KRRGRDPEMG 420 GKPRRKNPQE GLYNELQKDK MAEAYSEIGM KGERRRGKGH DGLYQGLSTA TKDTYDALHM 480 QALPPRTRYP YDVPDYAGVQ VETISPGDGR TFPKRGQTCV VHYTGMLGDG KKVDSSRDRN 540 KPFKFMLGKQ EVIRGWEEGV AQMSVGQGAK LTISPDYAYG ATGHPGIIPP HATLVFDVEL 600 LELE 604 3-1216 Sequences 3-1216-1 Sequence Number [ID] 1216 3-1216-2 Molecule Type AA 3-1216-3 Length 9 3-1216-4 Features REGION 1..9 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..9 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1216-5 Residues MHRSAAAAT 9 3-1217 Sequences 3-1217-1 Sequence Number [ID] 1217 3-1217-2 Molecule Type AA 3-1217-3 Length 12 3-1217-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1217-5 Residues IPPPPPLSLP PP 12 3-1218 Sequences 3-1218-1 Sequence Number [ID] 1218 3-1218-2 Molecule Type AA 3-1218-3 Length 43 3-1218-4 Features REGION 1..43 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..43 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1218-5 Residues RYWPKPLGIR PVCVCLYVIF HHIAVFWQCE GPETWPCLLD EHS 43 3-1219 Sequences 3-1219-1 Sequence Number [ID] 1219 3-1219-2 Molecule Type AA 3-1219-3 Length 102 3-1219-4 Features REGION 1..102 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..102 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1219-5 Residues GSFPSRQRNA RSVECREGSS SSGSFLKTNN VCSDPLQAAE PPTWRQVPLR PKATCIRYTC 60 KGGTTPVPRC ELDSCGKSQM ALLKRIQQGA EGCPEGTPLY GI 102

3-1220 Sequences 3-1220-1 Sequence Number [ID] 1220 3-1220-2 Molecule Type AA 3-1220-3 Length 41 11 Aug 2023

3-1220-4 Features REGION 1..41 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..41 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1220-5 Residues SGASVHMLYM CLVEVKKTSR PPEPRGRGFP LKNTMIIWPQ P 41 3-1221 Sequences 3-1221-1 Sequence Number [ID] 1221 3-1221-2 Molecule Type AA 3-1221-3 Length 24 3-1221-4 Features REGION 1..24 2023214349

Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..24 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1221-5 Residues ARARRITWPS SRSSCASRCT WRAP 24 3-1222 Sequences 3-1222-1 Sequence Number [ID] 1222 3-1222-2 Molecule Type AA 3-1222-3 Length 23 3-1222-4 Features REGION 1..23 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..23 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1222-5 Residues TATSSRSRAR ARAAPTRAPR PPS 23 3-1223 Sequences 3-1223-1 Sequence Number [ID] 1223 3-1223-2 Molecule Type AA 3-1223-3 Length 24 3-1223-4 Features REGION 1..24 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..24 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1223-5 Residues PRVAPCPSPG TSCPLSSCTA PRPT 24 3-1224 Sequences 3-1224-1 Sequence Number [ID] 1224 3-1224-2 Molecule Type AA 3-1224-3 Length 9 3-1224-4 Features REGION 1..9 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..9 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1224-5 Residues STPPTSPTT 9 3-1225 Sequences 3-1225-1 Sequence Number [ID] 1225 3-1225-2 Molecule Type AA 3-1225-3 Length 12 3-1225-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1225-5 Residues SCPSPRASSG SA 12 3-1226 Sequences 3-1226-1 Sequence Number [ID] 1226

3-1226-2 Molecule Type AA 3-1226-3 Length 7 3-1226-4 Features REGION 1..7 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct 11 Aug 2023

source 1..7 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1226-5 Residues TSRTAAW 7 3-1227 Sequences 3-1227-1 Sequence Number [ID] 1227 3-1227-2 Molecule Type AA 3-1227-3 Length 14 3-1227-4 Features REGION 1..14 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..14 2023214349

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1227-5 Residues PRTPPCRTAS SSTR 14 3-1228 Sequences 3-1228-1 Sequence Number [ID] 1228 3-1228-2 Molecule Type AA 3-1228-3 Length 12 3-1228-4 Features REGION 1..12 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..12 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1228-5 Residues SCAAPTSPPT AP 12 3-1229 Sequences 3-1229-1 Sequence Number [ID] 1229 3-1229-2 Molecule Type AA 3-1229-3 Length 21 3-1229-4 Features REGION 1..21 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..21 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1229-5 Residues CRRRPWAGRP PPSGCTPRTA P 21 3-1230 Sequences 3-1230-1 Sequence Number [ID] 1230 3-1230-2 Molecule Type AA 3-1230-3 Length 7 3-1230-4 Features REGION 1..7 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..7 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1230-5 Residues RARSSRG 7 3-1231 Sequences 3-1231-1 Sequence Number [ID] 1231 3-1231-2 Molecule Type AA 3-1231-3 Length 64 3-1231-4 Features REGION 1..64 Location/Qualifiers note=Description of Artificial Sequence: Synthetic construct source 1..64 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1231-5 Residues RTAATTTLRS RPPTRPRSPC SCPAPTTSTS SWTSPPTTRT TPSWNSTNAP RAATPPAAWT 60 SCTS 64 3-1232 Sequences 3-1232-1 Sequence Number [ID] 1232 3-1232-2 Molecule Type AA

3-1232-3 Length 8 3-1232-4 Features REGION 1..8 Location/Qualifiers note=Description of Artificial Sequence: Synthetic FLAG sequence source 1..8 11 Aug 2023

mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1232-5 Residues DYKDDDDK 8 3-1233 Sequences 3-1233-1 Sequence Number [ID] 1233 3-1233-2 Molecule Type AA 3-1233-3 Length 4 3-1233-4 Features REGION 1..4 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..4 mol_type=protein 2023214349

organism=synthetic construct NonEnglishQualifier Value 3-1233-5 Residues GGGG 4 3-1234 Sequences 3-1234-1 Sequence Number [ID] 1234 3-1234-2 Molecule Type AA 3-1234-3 Length 8 3-1234-4 Features REGION 1..8 Location/Qualifiers note=Description of Artificial Sequence: Synthetic linker sequence source 1..8 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1234-5 Residues GGGGGGGG 8 3-1235 Sequences 3-1235-1 Sequence Number [ID] 1235 3-1235-2 Molecule Type AA 3-1235-3 Length 8 3-1235-4 Features REGION 1..8 Location/Qualifiers note=Description of Artificial Sequence: Synthetic peptide MOD_RES 2 note=Val or Ile MOD_RES 4 note=Any amino acid source 1..8 mol_type=protein organism=synthetic construct NonEnglishQualifier Value 3-1235-5 Residues DXEXNPGP 8

Claims

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. A composition comprising a polynucleotide encoding an effector module, said effector module comprising a stimulus response element (SRE) operably linked to at least one payload, wherein the SRE comprises a destabilizing domain (DD), said DD comprising amino acids 2 to 187 of a human dihydrofolate reductase (hDHFR; SEQ ID NO. 2) and further comprising (i) a Y 1221mutation in the amino acid at position 122 (Y122) of SEQ ID NO. 2 and a A125F mutation in the amino acid at position 125 (A125) of SEQ ID NO:2 or (ii) a Y1221 mutation in the amino acid at position 122 (Y122) of SEQ ID NO. 2, a N65F mutation in the amino acid at position 65 (N65) of SEQ ID NO. 2 and a substitution of F at the amino acid position 36 (Q36) of SEQ ID NO. 2.

2. The composition of claim 1, wherein the SRE is responsive to at least one stimulus.

3. The composition of claim 2, wherein the stimulus is selected from the group consisting of Trimethoprim (TMP) and Methotrexate (MTX).

4. The composition of any one of claims 1-3, wherein the DDstabilizes the at least one payload by a stabilization ratio of 1 or more, wherein the stabilization ratio comprises the ratio of expression, function or level of the payload in the presence of the stimulus to the expression, function or level of the payload in the absence of the stimulus.

5. The composition of any one of claims 1-3, wherein the DD destabilizes the at least one payload by a destabilization ratio between 0 and 0.09, wherein the destabilization ratio comprises the ratio of expression, function or level of the payload in the absence of the stimulus specific to the SRE to the expression, function or level of the payload that is expressed constitutively, and in the absence of the stimulus specific to the SRE.

6. The composition of any one of claims 1-5, wherein the at least one payload is an immunotherapeutic agent.

7. The composition of claim 6, wherein the immunotherapeutic agent is selected from a chimeric antigen receptor (CAR), a cytokine, and a cytokine-cytokine receptor fusion polypeptide.

8. The composition of claim 6, wherein the immunotherapeutic agent is a chimeric antigen receptor (CAR) that comprises (a) an extracellular target moiety; (b) a transmembrane domain; (c) an intracellular signaling domain; and (d) optionally, one or more co-stimulatory domains.

9. The composition of claim 7 or 8, wherein the CAR is a CD19 CAR.

10. The composition of claim 7, wherein the cytokine is IL12 or IL15.

11. The composition of claim 7, wherein the cytokine-cytokine receptor fusion polypeptide is a IL15-IL15Ra fusion polypeptide.

12. The composition of any one of claims 1-11, wherein the effector module further comprises a second payload, wherein the second payload is a chimeric antigen receptor (CAR).

13. The composition of any one of claims 1-12, wherein the effector module further comprises a signal peptide, a regulatory sequence, a linker, a protein tag, and/or a protein cleavage site.

14. The composition of any one of claims 1-13, wherein the polynucleotide is a DNA molecule or a RNA molecule.

15. The composition of claim 14, wherein the polynucleotide is an RNA molecule and said RNA molecule is a messenger RNA (mRNA).

16. The composition of any one of claims 1-15, wherein the polynucleotide is chemically modified.

17. The composition of any one of claims 1-16, wherein the polynucleotide further comprises a promoter, a linker, a signal peptide, a tag, a cleavage site and/or a targeting peptide.

18. A vector comprising the polynucleotide of any one of claims 1-17.

19. The vector of claim 18, wherein the vector is a viral vector or a plasmid.

20. The vector of claim 19, which is a viral vector and wherein the viral vector is a retroviral vector, a lentiviral vector, a gamma retroviral vector, a recombinant AAV vector, an adeno viral vector, or an oncolytic viral vector.

21. The vector of claim 20, which is a retroviral vector or a lentiviral vector.

22. A cell which expresses the effector module as defined in any one of claims 1-17, and/or is infected or transfected with the vector of any one of claims 18-21.

23. The cell of claim 22, wherein said cell is an immune cell for adoptive cell transfer (ACT).

24. The cell of claim 22 or 23, wherein said cell is a CD8+ T cell, a CD4+ T cell, a helper T cell, a natural killer (NK) cell, a NKT cell, a cytotoxic T lymphocyte (CTL), a tumor infiltrating lymphocyte (TIL), a memory T cell, a regulatory T (Treg) cell, a cytokine-induced killer (CIK) cell, a dendritic cell, a human embryonic stem cell, a mesenchymal stem cell, a hematopoietic stem cell, or a mixture thereof.

25. The cell of any one of claims 22-24, wherein said cell is a T cell modified to express a chimeric antigen receptor (CAR).

26. A pharmaceutical composition comprising: (i) the composition of any one of claims 1-17; (ii) the vector of any one of claims 18-21; or (iii) the cell of any one of claims 22-25; and a pharmaceutically acceptable excipient.

27. A method of producing a modified cell, said method comprising introducing into a cell the composition of any one of claims 1-17 or the vector of any one of claims 18-21.

28. A kit comprising a stimulus when used in modulating expression, function, and/or level of a payload in the cell of any one of claims 22-25, wherein the stimulus response element (SRE) is responsive to the stimulus; wherein the stimulus is a small molecule that binds to the SRE; and wherein the expression, function, and/or level of the payload is modulated in response to the stimulus.

29. The composition of any one of claims 1-17, a composition comprising the vector of any one of claims 18-21, or a composition comprising the cell of any one of claims 22-25, for treating a disease in a subject in need thereof, wherein the composition is used in combination with a stimulus, wherein the stimulus response element (SRE) is responsive to the stimulus; and wherein expression of the payload is modulated in response to the stimulus to thereby treat the disease.

30. The composition according to claim 29, wherein the stimulus is selected from Trimethoprim (TMP) or Methotrexate (MTX).

31. The composition of any one of claims 1-17, a composition comprising the vector of any one of claims 19-22, or a composition comprising the cell of any one of claims 23-26 for the treatment of a disease or for inducing an immune response in a subject.

32. The composition of any one of claims 1-17, a composition comprising the vector of any one of claims 18-21, or a composition comprising the cell of any one of claims 22-25 for treatment of cancer.

33. A method of modulating expression, function, and/or level of a payload in the cell of any one of claims 22-25, said method comprising administering to the cell a stimulus, wherein the stimulus response element (SRE) is responsive to the stimulus and wherein the expression, function, and/or level of the payload is modulated in response to the stimulus.

34. The composition of any one of claims 1-17, a composition comprising the vector of any one of claims 18-21, or a composition comprising the cell of any one of claims 22-25, for use in a method of treating a disease in a subject in need thereof, characterized in that the composition is administered to the subject in combination with a stimulus, wherein the SRE is responsive to the stimulus and wherein expression of the payload is modulated in response to the stimulus to thereby treat the disease.

35. The composition for use according to claim 34, wherein the stimulus is selected from Trimethoprim (TMP) or Methotrexate (MTX).