WO2024178360A2

WO2024178360A2 - Auristatin analogs and antibody conjugates thereof

Info

Publication number: WO2024178360A2
Application number: PCT/US2024/017123
Authority: WO
Inventors: Sung-Ju Moon; Sukumar Sakamuri; Jianing Wang; Ji Young Kim; Nickolas KNUDSEN
Original assignee: Ambrx Inc
Current assignee: Ambrx Inc
Priority date: 2023-02-23
Filing date: 2024-02-23
Publication date: 2024-08-29
Anticipated expiration: 2025-08-23
Also published as: WO2024178360A3

Abstract

Disclosed here are antibody-drug conjugates, drug-linkers for making antibody-drug conjugates, and methods and compositions for using antibody-drug conjugates in inhibiting, preventing or treating diseases or conditions including cancers. The antibody-drug conjugates contain at least one non-naturally-encoded amino acid. The antibodies are configured to target antigens such as CD70, PSMA, HER2, HER3 or TROP2.

Description

WSGR Ref. No 31362-825.601 AURISTATIN ANALOGS AND ANTIBODY CONJUGATES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to U.S. Provisional Application No. 63/486,558 filed on February 23, 2023, the entire contents of which are hereby incorporated herein in their entirety. REFERENCE TO A SEQUENCE LISTING The present application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy, created on February 22, 2024, is named AMBX-0240_00PCT.xml and is 79,784 bytes in size. FIELD OF THE INVENTION This invention relates to antibody-drug conjugates (ADCs), cytotoxic auristatin analog drugs and drug-linkers. In particular, the invention relates to non-natural amino acid-containing antibodies conjugated to drug-linkers containing auristatin analogs. The invention also relates to methods of using the ADCs, drugs and drug-linkers, including their use in the treatment of cancer. BACKGROUND Antibody-based therapeutics have emerged as important therapies for treating an increasing number of human malignancies. In most cases, the basis of the therapeutic function is the high degree of specificity and affinity the antibody-based drug has for its target antigen. Arming monoclonal antibodies with drugs, toxins or radionuclides is a strategy by which monoclonal antibodies may induce therapeutic effect. By combining the exquisite targeting specificity of antibody with the tumor killing power of toxic effector molecules, antibody-drug conjugates (ADCs) permit sensitive discrimination between target and normal tissue, thereby resulting in fewer side effects than most conventional chemotherapeutic drugs. However, ADCs still face challenges due to toxicity and a lack of therapeutic index. The linker technology for attachment of the cytotoxic drug to an antibody impacts the stability of ADCs during systemic circulation. Additionally, target selection and selectivity, and improved payload structures, can improve therapeutic index and reduce toxicity. Trophoblast cell surface protein 2 (also known as: trophoblast antigen 2; calcium signal transducer 2; TROP2; TROP-2; TACSTD2; GA733-1; or M1S1) is a transmembrane protein that is highly expressed on various epithelial tumors. While the physiological role of TROP2 remains under investigation, it has been shown to be involved in pathways associated with the proliferation, WSGR Ref. No 31362-825.601 migration and invasion of cancer cells, including MAPK and PI3K/AKT (Cubas R. et al., Mol Cancer, 9:253, 2010; Guan H. et al., BMC Cancer, 17:486, 2017; Guerra E. et al., Clin Cancer Res, 22:4197–205, 2016). Moreover, TROP2 overexpression has been associated with enhanced tumor aggressiveness, metastasis, drug resistance, increased tumor cell survival, reduced overall survival (OS) and reduced progression-free survival. TROP2 is highly expressed in triple negative breast cancer (TNBC), pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Overexpression of TROP2 has been correlated with poor prognosis in cancers including breast cancer and NSCLC (Lin H. et al., Exp Mol Pathol, 94:73–78, 2013; Kobayashi H. et al., Virchows Arch, 457:69–76, 2010; Muhlmann G. et al., J Clin Pathol, 62:152–158, 2009; Fong D. et al., Mod Pathol, 21:186–191, 2008). The foregoing features make TROP2 an important target for the development anti-cancer therapeutics. Challenges towards this end include the known expression of TROP2 in some normal epithelial tissues, including the skin and esophagus (Stepan L.P. et al., J Histochem Cytochem, 59:701–710, 2011). Thus, the potential for on-target toxicity in normal cells that express TROP2 must be factored into the design and development of TROP2- directed therapeutics. TROP2-directed ADCs include PF-06664178 (also known as RN927C; discontinued), which contains anti-TROP2 antibody conjugated with tubulin inhibitor Aur0101 via a cleavable linker (AcLys-VC-PABC-VC), and has a drug-to-antibody ratio of 2. PF-06664178 induced skin rash and mucosal inflammation as dose-limiting toxicities in phase I study in adult patients with advanced solid tumors (King, G.T., Invest New Drugs, 36:836-847, 2018). Datopotamab deruxtecan (Dato-DXd, DS-1062a) contains anti-TROP2 antibody conjugated with topoisomerase I inhibitor DXd via a tetrapeptide-based cleavable linker and has a drug-to-antibody ratio of 4 (Okajima, D. et al., Mol Cancer Ther, 20:2329–2340, 2021). TRODELVY (sacituzumab govitecan) is another TROP2-directed ADC and contains antibody hzRS7 (sacituzumab) conjugated with topoisomerase I inhibitor SN-38 via a hydrolyzable linker. Human epidermal growth factor receptor 3 (HER3) protein is a member of the ErbB/HER receptor tyrosine kinase family. Its role in cell proliferation, association with resistance to chemotherapy, and expression or overexpression in various tumors, including breast, ovarian, lung, colon, pancreatic, melanoma, gastric, head and neck and prostate cancers, have led to efforts towards the development of HER3-targeted therapeutic agents (see, e.g., Gandullo-Sanchez L. et al., J. Exp. Clin. Cancer Res. (2022) 41:310). One anti-HER3 ADC under clinical development is patritumab deruxtecan (U3-1402, HER3-DXd), which contains anti-HER3 antibody patritumab conjugated to drug-linker deruxtecan. Deruxtecan, which is the same drug-linker present in the anti-HER2 ADC trastuzumab deruxtecan (DS8201; ENHERTU), - contains a cleavable maleimide-GGFG peptide linker and topo-isomerase I inhibitor DXd, and is conjugated to the WSGR Ref. No 31362-825.601 antibody via thiol-maleimide linkages. This stochastic conjugation relies on random modification of reduced cysteines from interchain disulfides of the antibody. One technology which promises to overcome the current limitations of ADCs, including the need to improve therapeutic index and to circumvent heterogeneity associated with stochastic conjugation methods, involves the incorporation of non-natural amino acids into proteins; see, e.g., Wang L. et al. (2001) Science 292:498-500; Chin J. et al. (2003) Science 301:964-7; Wang L. and Schultz P.G. (2002), Chem. Comm.1:1-11; Tian F. et al. (2014) Proc. Natl. Acad. Sci. U.S.A 111(5):1766- 1771; the entire contents of each of which are hereby incorporated by reference herein in their entirety. These and other studies have demonstrated that it is possible to site- specifically introduce into a protein a non-natural amino acid containing a chemical functional group that is not found in the 20 common, genetically-encoded amino acids, that is chemically inert to all of the functional groups found in the 20 common, genetically-encoded amino acids, and that can be used to react efficiently and selectively to form stable covalent linkages with moieties, such as drug-linker moieties, that are chosen for conjugation with the protein (e.g., antibody) of interest. This unique process of conjugation allows for the precise control of the location of the cytotoxic agent on the antibody, and also the number of cytotoxic agents conjugated to each antibody. Both of these features are critical for controlling biophysical characteristics and toxicities associated with ADCs (Tian F. et al. (2014) Proc. Natl. Acad. Sci. U.S.A 111(5):1766-177). There remains a need in the art to design improved ADCs, including those with improved drug-linker payload design and target selectivity, that can lead to a wider therapeutic window, thus maximizing on-target efficacy and minimizing off-target toxicity. SUMMARY OF THE INVENTION Disclosed herein are auristatin analog payloads, ADCs containing antibody conjugated to auristatin analog payloads through one or more non-natural amino acids with one or more linker(s), methods for making auristatin analog payloads and ADCs, and use of the payloads and ADCs for treating diseases including cancer. In some general aspects, the present invention provides an antibody-drug conjugate (ADC) of Formula (I-ADC) or Formula (II-ADC):

WSGR Ref. No 31362-825.601

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence comprising one or more non-naturally encoded amino acids; L is a linker; E is a moiety joining the antibody Ab to the linker L; d is an integer from 1 to 10; V is selected from the group consisting of -CH2-, -S-, -S(O)-, -C(O)- and -C(H)(Rv)-; wherein Rv is F, CN, N3, OH, ONH2 , unsubstituted C1-C8 alkyl, or substituted C₁-C₈ alkyl; X is O or NH; Z is -CH2- or -C(O)-; R₅ is H, unsubstituted C₁-C₆ alkyl, substituted C₁-C₆ alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C3-C6 cycloalkyl; R6 is unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted cycloalkyl, substituted cycloalkyl, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; and each R7, R8 and R9 is independently H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; or R7 and R₈ are joined to form an unsubstituted heterocycloalkyl or substituted heterocycloalkyl, and R9 is H, unsubstituted C1-C8 alkyl, or optionally substituted C1-C8 alkyl; or R8 and R9 are joined to form an unsubstituted cycloalkyl, substituted cycloalkyl, an unsubstituted heterocycloalkyl, or substituted heterocycloalkyl, and R7 is H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; and R_7a is H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C₃-C₆ cycloalkyl. In some other general aspects, there is provided an antibody-drug conjugate (ADC) of Formula (I-ADC-17): WSGR Ref. No 31362-825.601

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence containing one or more non-naturally encoded amino acids; d is an integer from 1 to 10; and R_c is unsubstituted C₁-C₆ alkyl. In some other general aspects, there is provided a compound of Formula (I) or Formula (II):

or a pharmaceutically acceptable salt thereof, wherein: V is selected from the group consisting of -CH₂-, -S-, -S(O)-, -C(O)- and -C(H)(R_v)-; wherein Rv is -F, -CN, -N3, -OH, -ONH2, unsubstituted C1-C8 alkyl, or substituted C1-C8 alkyl; X is O or NH; Y is a reactive moiety; Z is -CH2- or -C(O)-; R₅ is H, unsubstituted C₁-C₆ alkyl, substituted C₁-C₆ alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C₃-C₆ cycloalkyl; R6 is unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted cycloalkyl, substituted cycloalkyl, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; each R7, R8 and R9 is independently H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl; or R7 and R8 are joined to form an unsubstituted heterocycloalkyl or a substituted heterocycloalkyl, and R₉ is H, unsubstituted C1-C8 alkyl or substituted C1-C8 alkyl; or R8 and R9 are joined to WSGR Ref. No 31362-825.601 form an unsubstituted cycloalkyl, substituted cycloalkyl, an unsubstituted heterocycloalkyl or substituted heterocycloalkyl, and R7 is H, unsubstituted C1-C8 alkyl, substituted C₁-C₈ alkyl, unsubstituted C₃-C₆ cycloalkyl or substituted C₃-C₆ cycloalkyl; R7a is H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, substituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; and L is a linker. In some embodiments, the the is selected from the of:

WSGR Ref. No 31362-825.601

and pharmaceutically acceptable salts thereof. In some other general aspects, there is provided a pharmaceutical composition comprising any of the compounds disclosed herein and at least one pharmaceutically acceptable adjuvant, binder, buffer, carrier, diluent or excipient. In some other general aspects, there is provided a method of treating a disease in a subject in need thereof, the method comprising administering to the subject an ADC of any one disclosed herein, a compound of any one of the compounds disclosed herein, or a pharmaceutical composition of any one of the pharmaceutical composition disclosed herein. In some embodiments, an ADC or composition of the present disclosure does not contain a Toll-like receptor (TLR) agonist. INCOPORATION BY REFERENCE All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings provided. FIG.1 shows the structure of monomethyl auristatin F (MMAF). FIG. 2A shows graphical illustrations of cytotoxic activity of anti-HER2 ADCs against HER2 high SK-BR-3 breast cancer cell line; FIG.2B shows graphical illustrations of cytotoxic activity of anti-HER2 ADCs against HER2 low JIMT-1 breast cancer cell line; FIG. 2C shows graphical illustrations of cytotoxic activity of anti-HER2 ADCs against HER2 positive gastric cancer cell line NCI-N87; and FIG.2D shows graphical illustrations of cytotoxic activity of anti- HER2 ADCs against HER2 negative MDA-MB-468 cell line. FIG. 3A shows graphical illustrations of cytotoxic activity of anti-CD70 ADCs against CD70 positive cancer cell line 786-O; FIG.3B shows graphical illustrations of cytotoxic activity of anti-CD70 ADCs against CD70 positive cancer cell line U-266; and FIG.3C shows graphical WSGR Ref. No 31362-825.601 illustrations of cytotoxic activity of anti-CD70 ADCs against HER2 positive and CD70 negative breast cancer cell line BT-474. FIG. 4A shows graphical illustrations of cytotoxic activity of anti-HER3 ADCs against HER3-high HCC1569 cell line; FIG.4B shows graphical illustrations of cytotoxic activity of anti- HER3 ADCs against HER3-intermediate A375 cell line; FIG.4C shows graphical illustrations of cytotoxic activity of anti-HER3 ADCs against HER3-low HC827 cell line; and FIG. 4D shows graphical illustrations of cytotoxic activity of anti-HER3 ADCs against HER3-negative SKOV-3 cell line. FIG.5A shows graphical illustrations of cytotoxic activity of anti-TROP2 ADCs against TROP2-expressing BxPC-3 cell line; FIG. 5B shows graphical illustrations of cytotoxic activity of anti-TROP2 ADCs against TROP2-expressing MDA-MB-468 cell line; FIG. 5C shows graphical illustrations of cytotoxic activity of anti-TROP2 ADCs against TROP2-expressing HCC1806 cell line; FIG. 5D shows graphical illustrations of cytotoxic activity of anti-TROP2 ADCs against TROP2-negative Calu-6 cell line; and FIG. 5E shows graphical illustrations of cytotoxic activity of anti-TROP2 ADCs against human keratinocytes. FIG.6A illustrates a possible metabolism of ADC conjugated with compound 17 via non- natural amino acid pAF; and FIG.6B illustrates a possible metabolism of ADC conjugated with compound 37 via non-natural amino acid pAF. DETAILED DESCRIPTION Before describing the present invention in detail, it is to be understood that this invention is not limited to particular methodologies, or compositions, or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. While various embodiments have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It is to be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. Definitions Unless otherwise defined herein or below in the remainder of the specification, all technical and scientific terms used herein have the same meaning as commonly understood by WSGR Ref. No 31362-825.601 those of ordinary skill in the art to which the invention belongs. As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly indicates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the inventions described herein belong. Various methods, materials, and the like, similar or equivalent to those described herein can be used in the practice or testing of the inventions described herein. All publications and patents mentioned herein are incorporated herein by reference in their entirety for the purpose of describing and disclosing, for example, the chemistry, chemical syntheses, compositions and other methodologies that are described in the publications, which might be used in connection with the presently described inventions. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. As used herein, the term “acyl,” refers to a group having the general formula -C(=O)R^XI, wherein R^XI is independently cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic: cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl. Acyl substituents include, but are not limited to, any of the substituents described herein that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, -C(O)C1-C6 alkyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halogen, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphatic thioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted). In some embodiments, an acyl is a group has the general formula -C(=O)R^XI wherein R^XI is substituted C₁-C₆ alkyl. In some embodiments, an acyl is a group has the general formula -C(=O)R^XI wherein R^XI is unsubstituted C1-C6 alkyl. In some embodiments, an acyl group as the formula -C(=O)CH3. The terms “alkoxy,” “alkylamino” and “alkylthio” (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups linked to molecules via an oxygen atom, an amino group, or a sulfur atom, respectively. The term “alkyl,” by itself or as part of another molecule means, unless otherwise stated, a straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which may be WSGR Ref. No 31362-825.601 fully saturated, mono- or polyunsaturated and can include di- and multivalent radicals, having the number of carbon atoms designated (i.e., C1-C10 means one to ten carbons). Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2- isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3- butynyl, and the higher homologs and isomers. A “lower alkyl” is a shorter chain alkyl group, generally having eight or fewer carbon atoms. Substituents for each of the above noted alkyl groups are selected from the group of acceptable substituents described herein. The term “alkylene” by itself or as part of another molecule means a divalent radical derived from an alkane, as exemplified, by (–CH₂–)_n, wherein n may be 1 to about 24. By way of example only, such groups include, but are not limited to, groups having 10 or fewer carbon atoms such as the structures –CH2CH2– and –CH2CH2CH2CH2–. The term “alkylene” as used herein includes methylene having the structure –CH₂–, unless expressly indicated otherwise. The term “alkylene,” unless otherwise noted, is also meant to include those groups described herein as “heteroalkylene.” Substituents for arylene groups are selected from the group of acceptable substituents described herein. The term “alkenylene” by itself or as part of another molecule means a divalent radical derived from an alkene, as exemplified, by (–CH=CH–)n, wherein n may be 1 to about 24. By way of example only, such groups include, but are not limited to, groups having 10 or fewer carbon atoms such as the structures –CH₌CH– and –CH₌CHCH₂CH₂–. The term “alkenylene,” unless otherwise noted, is also meant to include those groups described herein as “heteroalkenylene.” The term “alkynylene” by itself or as part of another molecule means a divalent radical derived from an alkyne, as exemplified, by (–C=C–)_n, wherein n may be 1 to about 24. By way of example only, such groups include, but are not limited to, groups having 10 or fewer carbon atoms such as the structures –C=C– and –C=CCH2CH2–. The term “alkynylene,” unless otherwise noted, is also meant to include those groups described herein as “heteroalkynylene.” In embodiments are provided novel amino acid sequences. The term “amino acid” refers to naturally occurring and non-natural or unnatural amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally encoded amino acids are the 20 common amino acids (alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, WSGR Ref. No 31362-825.601 methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine) and pyrrolysine and selenocysteine. Amino acid analogs refer to compounds that have the same basic is bound to a hydrogen, a carboxyl group, an amino group, and a functional R group. Such analogs may have modified R groups (by way of example, norleucine) or may have modified peptide backbones while still retaining the same basic chemical structure as a naturally occurring amino acid. Non-limiting examples of amino acid analogs include homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Amino acids may be referred to herein by either their name, their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Additionally, nucleotides, may be referred to by their commonly accepted single-letter codes. An “amino terminus modification group” or “a carboxy terminus modification group” refers to any molecule that can be attached to a terminal amine group or terminal carboxy group respectively. By way of example, such terminal amine groups or terminal carboxy groups may be at the end of polymeric molecules, wherein such polymeric molecules include, but are not limited to, polypeptides, polynucleotides, and polysaccharides. Terminus modification groups include but are not limited to, various water-soluble polymers, peptides or proteins. By way of example only, terminus modification groups include polyethylene glycol or serum albumin. Terminus modification groups may be used to modify therapeutic characteristics of the polymeric molecule, including but not limited to increasing the serum half-life of peptides, polypeptides or proteins. In some embodiments the disclosure provides novel antibodies and antibody variants. The term “antibody” herein refers to a protein consisting of one or more polypeptides substantially encoded by all or part of the antibody genes. The immunoglobulin genes include, but are not limited to, the kappa, lambda, alpha, gamma (IgG1, IgG2, IgG3, and IgG4), delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Antibody herein is also meant to include full-length antibodies and antibody fragments, and include antibodies that exist naturally in any organism, antibody variants, engineered antibodies and antibody fragments. Antibody herein is also meant to include intact antibody, monoclonal or polyclonal antibodies. Antibody herein also encompasses, multispecific antibodies and/or bispecific antibodies. Antibodies of the present disclosure include human antibodies. Human antibodies are usually made of two light chains and two heavy chains each comprising variable regions and constant regions. The light chain variable region comprises 3 CDRs, identified herein as CDRL1, CDRL2 and CDRL3 flanked by framework regions. The heavy chain variable region WSGR Ref. No 31362-825.601 comprises 3 CDRs, identified herein as CDRH1, CDRH2 and CDRH3 flanked by framework regions. The term “antibody fragment” herein refers to any form of an antibody other than the full- length form. Antibody fragments herein include antibodies that are smaller components that exist within full-length antibodies, and antibodies that have been engineered, such as antibody variants. Antibody fragments include but are not limited to Fv, Fc, Fab, and (Fab')2, single chain Fv (scFv), diabodies, triabodies, tetrabodies, bifunctional hybrid antibodies, CDR1, CDR2, CDR3, combinations of CDRs, variable regions, framework regions, constant regions, heavy chains, light chains, and variable regions, and alternative scaffold non-antibody molecules, bispecific antibodies, and the like (Maynard & Georgiou, Annu. Rev. Biomed. Eng.2:339-76, 2000; Hudson, Curr. Opin. Biotechnol. 9:395-402, 1998). Another functional substructure is a single chain Fv (scFv), comprised of the variable regions of the immunoglobulin heavy and light chain, covalently connected by a peptide linker (Hu et al., Cancer Research, 56, 3055-3061, 1996). These small (Mr 25,000) proteins generally retain specificity and affinity for antigen in a single polypeptide and can provide a convenient building block for larger, antigen-specific molecules. Unless specifically noted otherwise, statements and claims that use the term “antibody” or “antibodies” specifically includes “antibody fragment” and “antibody fragments.” In embodiments novel antibody drug conjugates (ADCs) are disclosed. The term “antibody-drug conjugate, or “ADC”, as used herein, refers to an antibody molecule, or fragment thereof, that is covalently bonded to one or more biologically active molecule(s). The biologically active molecule may be conjugated to the antibody through a linker, polymer, or other covalent bond. ADCs are a potent class of therapeutic constructs that allow targeted delivery of cytotoxic agents to target cells, such as cancer cells. Because of the targeting function, these compounds show a much higher therapeutic index compared to the same systemically delivered agents. ADCs have been developed as intact antibodies or antibody fragments, such as scFvs. The antibody or fragment is linked to one or more copies of drug via a linker that is stable under physiological conditions, but that may be cleaved once inside the target cell. The term "antigen-binding fragment", as used herein, refers to one or more fragments of an antibody that retain the ability to bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of an intact antibody. Examples of binding fragments encompassed within the term "antigen-binding fragment" of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment WSGR Ref. No 31362-825.601 consisting of the V_L and V_H domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., Nature 341:544-546, 1989), which consists of a VH domain; (vi) an isolated complementarity determining region (CDR), e.g., V_H CDR3 comprising or not additional sequence (linker, framework region(s) etc.) and (v) a combination of two to six isolated CDRs comprising or not additional sequence (linker, framework region(s) etc.). Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single polypeptide chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv); see e.g., Bird et al., Science 242:423-426, 1988); and (Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883, 1988). Such single chain antibodies are also intended to be encompassed within the term "antigen-binding fragment" of an antibody. Furthermore, the antigen-binding fragments include binding-domain immunoglobulin fusion proteins comprising (i) a binding domain polypeptide (such as a heavy chain variable region, a light chain variable region, or a heavy chain variable region fused to a light chain variable region via a linker peptide) that is fused to an immunoglobulin hinge region polypeptide, (ii) an immunoglobulin heavy chain CH2 constant region fused to the hinge region, and (iii) an immunoglobulin heavy chain CH3 constant region fused to the CH2 constant region. The hinge region may be modified by replacing one or more cysteine residues with serine residues to prevent dimerization. Such binding-domain immunoglobulin fusion proteins are further disclosed in US 2003/0118592 and US 2003/0133939. These antibody fragments are obtained using conventional techniques known to those with skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies. A typical antigen binding site is comprised of the variable regions formed by the pairing of a light chain immunoglobulin and a heavy chain immunoglobulin. The structure of the antibody variable regions is very consistent and exhibits very similar structures. These variable regions are typically comprised of relatively homologous framework regions (FR) interspaced with three hypervariable regions termed Complementarity Determining Regions (CDRs). The overall binding activity of the antigen binding fragment is often dictated by the sequence of the CDRs. The FRs often play a role in the proper positioning and alignment in three dimensions of the CDRs for optimal antigen binding. In fact, because CDR sequences are responsible for most antibody- antigen interactions, it is possible to express recombinant antibodies that shows the properties of specific naturally occurring antibodies by constructing expression vectors that include CDR sequences from the specific naturally occurring antibody grafted onto framework sequences from a different antibody with different properties (see, e.g., Riechmann, L. et al., Nature 332:323-327, 1998; Jones, P. et al., Nature 321:522-525, 1986; and Queen, C. et al., Proc. Natl. Acad. USA WSGR Ref. No 31362-825.601 86:10029-10033, 1989). Such framework sequences can be obtained from public DNA databases that include germline antibody gene sequences. These germline sequences will differ from mature antibody gene sequences because they will not include completely assembled variable genes, which are formed by V(D)J joining during B cell maturation. Germline gene sequences will also differ from the sequences of a high affinity secondary repertoire antibody which contains mutations throughout the variable gene but typically clustered in the CDRs. For example, somatic mutations are relatively infrequent in the amino terminal portion of framework region 1 and in the carboxy-terminal portion of framework region 4. Furthermore, many somatic mutations do not significantly alter the binding properties of the antibody. For this reason, it is not necessary to obtain the entire DNA sequence of a particular antibody in order to recreate an intact recombinant antibody having binding properties similar to those of the original antibody. Partial heavy and light chain sequence spanning the CDR regions is typically sufficient for this purpose. The partial sequence is used to determine which germline variable and joining gene segments contributed to the recombined antibody variable genes. The germline sequence is then used to fill in missing portions of the variable regions. Heavy and light chain leader sequences are cleaved during protein maturation and do not contribute to the properties of the final antibody. To add missing sequences, cloned cDNA sequences can be combined with synthetic oligonucleotides by ligation or PCR amplification. Alternatively, the entire variable region can be synthesized to create an entirely synthetic variable region clone. This process has certain advantages such as elimination or inclusion of particular restriction sites, or optimization of particular codons. Of course, the totality or portions of the framework region of the antibody described herein may be used in conjunction with the CDRs in order to optimize the affinity, specificity or any other desired properties of the antibody. The term “aromatic” or “aryl”, as used herein, refers to a closed ring structure which has at least one ring having a conjugated pi electron system and includes both carbocyclic aryl and heterocyclic aryl (or “heteroaryl” or “heteroaromatic”) groups. The carbocyclic or heterocyclic aromatic group may contain from 5 to 20 ring atoms. The term includes monocyclic rings linked covalently or fused-ring polycyclic (i.e., rings which share adjacent pairs of carbon atoms) groups. An aromatic group can be unsubstituted or substituted. Non-limiting examples of “aromatic” or “aryl”, groups include phenyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, anthracenyl, and phenanthracenyl. Non-limiting examples of “heteroaryl” groups are described herein. Substituents for each of the above noted aryl and heteroaryl ring systems are selected from the group of acceptable substituents described herein. WSGR Ref. No 31362-825.601 For brevity, the term “aromatic” or “aryl” when used in combination with other terms (including but not limited to, aryloxy, arylthioxy, aralkyl) includes both aryl and heteroaryl rings as defined above. Thus, the term “aralkyl” or “alkaryl” is meant to include those radicals in which an aryl group is attached to an alkyl group (including but not limited to, benzyl, phenethyl, pyridylmethyl and the like) including those alkyl groups in which a carbon atom (including but not limited to, a methylene group) has been replaced by a heteroatom, by way of example only, by an oxygen atom. Examples of such aryl groups include, but are not limited to, phenoxymethyl, 2-pyridyloxymethyl, 3-(1-naphthyloxy)propyl, and the like. The term “arylene”, as used herein, refers to a divalent aryl radical. Non-limiting examples of “arylene” include phenylene, pyridinylene, pyrimidinylene and thiophenylene. Substituents for arylene groups are selected from the group of acceptable substituents described herein. In some embodiments the disclosure concerns polymers such as a bifunctional polymer. A “bifunctional polymer”, also referred to as a “bifunctional linker”, refers to a polymer comprising two functional groups that are capable of reacting specifically with other moieties to form covalent or non-covalent linkages. Such moieties may include, but are not limited to, the side groups on natural or non-natural amino acids or peptides which contain such natural or non-natural amino acids. The other moieties that may be linked to the bifunctional linker or bifunctional polymer may be the same or different moieties. By way of example only, a bifunctional linker may have a functional group reactive with a group on a first peptide, and another functional group which is reactive with a group on a second peptide, whereby forming a conjugate that includes the first peptide, the bifunctional linker and the second peptide. Many procedures and linker molecules for attachment of various compounds to peptides are known. See, for example, European Patent Application No. 0188256; U.S. Patent Nos. 4,671,958, 4,659,839, 4,414,148, 4,699,784, 4,680,338, 4,569,789 and 10,550,190; PCT Application Publication Nos. WO 2012/166559 A1, WO 2012/166560 A1, WO 2013/173393 A1, WO 2013/185117 A1, WO 2013/192360 A1, WO 2016/203432 A1 and WO 2022/040596 A1; US Patent Application Publication No. US 2017/0182181 A1; Wei, BQ et al., J. Med. Chem.2018, 61, 3, 989–1000; and Jeffrey, S.C. et al., Bioconjug Chem. 2006 May-Jun;17(3):831-40; the contents of each of which are hereby incorporated by reference in their entirety. A “multi-functional polymer” also referred to as a “multi-functional linker” refers to a polymer comprising two or more functional groups that are capable of reacting with other moieties. Such moieties may include, but are not limited to, the side groups on natural or non-natural amino acids or peptides which contain such natural or non-natural amino acids (including but not limited to, amino acid side groups) to form covalent or non- covalent linkages. A bi-functional polymer or multi-functional polymer may be any desired length WSGR Ref. No 31362-825.601 or molecular weight and may be selected to provide a particular desired spacing or conformation between one or more molecules linked to a compound and molecules it binds to, or to the compound. The term “bioavailability,” as used herein, refers to the rate and extent to which a substance or its active moiety is delivered from a pharmaceutical dosage form and becomes available at the site of action or in the general circulation. Increases in bioavailability refers to increasing the rate and extent a substance or its active moiety is delivered from a pharmaceutical dosage form and becomes available at the site of action or in the general circulation. By way of example, an increase in bioavailability may be indicated as an increase in concentration of the substance or its active moiety in the blood when compared to other substances or active moieties. The term “biologically active molecule”, “biologically active moiety” or “biologically active agent” when used herein means any substance which can affect any physical or biochemical properties of a biological system, pathway, molecule, or interaction relating to an organism, including but not limited to, viruses, bacteria, bacteriophage, transposon, prion, insects, fungi, plants, animals, and humans. In particular, as used herein, biologically active molecules include but are not limited to any substance intended for diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals, or to otherwise enhance physical or mental well- being of humans or animals. Examples of biologically active molecules include, but are not limited to, peptides, proteins, enzymes, small molecule drugs, hard drugs, soft drugs, prodrugs, carbohydrates, inorganic atoms or molecules, dyes, lipids, nucleosides, radionuclides, oligonucleotides, toxins, cells, viruses, liposomes, microparticles and micelles. Classes of biologically active agents that are suitable for use with the methods and compositions described herein include, but are not limited to, drugs, prodrugs, radionuclides, imaging agents, polymers, antibiotics, fungicides, anti-viral agents, anti-inflammatory agents, anti-tumor agents, cardiovascular agents, anti-anxiety agents, hormones, growth factors, steroidal and nonsteroidal agents, microbially derived toxins, and the like. By “modulating biological activity” is meant increasing or decreasing the reactivity of a polypeptide, altering the selectivity of the polypeptide, enhancing or decreasing the substrate selectivity of the polypeptide. Analysis of modified biological activity can be performed by comparing the biological activity of the non-natural polypeptide to that of the natural polypeptide. In some embodiments the disclosure concerns amino acids that have been biosynthetically incorporated in the antibody. The term “biosynthetically,” as used herein, refers to any method utilizing a translation system (cellular or non-cellular), including use of at least one of the following components: a polynucleotide, a codon, a tRNA, and a ribosome. By way of example, WSGR Ref. No 31362-825.601 non-natural amino acids may be “biosynthetically incorporated” into non-natural amino acid polypeptides using the methods and techniques described herein and as is well known in the art. See for example, WO2010/011735 and WO2005/074650. The term “carbonyl” as used herein refers to the moiety -C(O)-. Groups containing a carbonyl include but are not limited to a ketone, an aldehyde, an ester, a carboxylic acid, a thioester and an amide. In addition, such groups may be part of linear, branched, or cyclic molecules. The term “chemically cleavable group,” also referred to as “chemically labile”, as used herein, refers to a group which breaks or cleaves upon exposure to acid, base, oxidizing agents, reducing agents, chemical initiators or radical initiators. The term “chromophore,” as used herein, refers to a molecule which absorbs light of visible wavelengths, UV wavelengths or IR wavelengths. A “comparison window,” as used herein, refers a segment of any one of contiguous positions used to compare a sequence to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Such contiguous positions include, but are not limited to a group consisting of from about 20 to about 600 sequential units, including about 50 to about 200 sequential units, and about 100 to about 150 sequential units. By way of example only, such sequences include polypeptides and polypeptides containing non-natural amino acids, with the sequential units include, but are not limited to natural and non-natural amino acids. In addition, by way of example only, such sequences include polynucleotides with nucleotides being the corresponding sequential units. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, including but not limited to, by the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math. 2:482c, by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol.48:443, by the search for similarity method of Pearson and Lipman (1988) Proc. Nat’l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e.g., Ausubel et al., Current Protocols in Molecular Biology (1995 supplement)). By way of example, an algorithm which may be used to determine percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1997) Nuc. Acids Res.25:3389-3402, and Altschul et al. (1990) J. Mol. Biol. 215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide WSGR Ref. No 31362-825.601 sequences) uses as defaults a wordlength (W) of 11, an expectation (E) or 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1992) Proc. Natl. Acad. Sci. USA 89:10915) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands. The BLAST algorithm is typically performed with the “low complexity” filter turned off. The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin and Altschul (1993) Proc. Natl. Acad. Sci. USA 90:5873-5787). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, or less than about 0.01, or less than about 0.001. The term “conservatively modified variants” applies to both natural and non-natural amino acid and natural and non-natural nucleic acid sequences, and combinations thereof. With respect to particular nucleic acid sequences, “conservatively modified variants” refers to those natural and non-natural nucleic acids which encode identical or essentially identical natural and non-natural amino acid sequences, or where the natural and non-natural nucleic acid does not encode a natural and non-natural amino acid sequence, to essentially identical sequences. By way of example, because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are “silent variations,” which are one species of conservatively modified variations. Thus, by way of example every natural or non-natural nucleic acid sequence herein which encodes a natural or non-natural polypeptide also describes every possible silent variation of the natural or non-natural nucleic acid. One of ordinary skill in the art will recognize that each codon in a natural or non-natural nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a natural and non-natural nucleic acid which encodes a natural and non-natural polypeptide is implicit in each described sequence. As to amino acid sequences, individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single natural and non-natural amino acid or a small percentage of WSGR Ref. No 31362-825.601 natural and non-natural amino acids in the encoded sequence is a “conservatively modified variant” where the alteration results in the deletion of an amino acid, addition of an amino acid, or substitution of a natural and non-natural amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar natural amino acids are well known in the art. Conservative substitution tables providing functionally similar amino acids are known to those of ordinary skill in the art. The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins: Structures and Molecular Properties (W H Freeman & Co.; 2nd edition, 1993). Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the compositions described herein. The terms “cycloalkyl” and “heterocycloalkyl”, by themselves or in combination with other terms, represent, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl”, respectively. Thus, a cycloalkyl or heterocycloalkyl includes saturated, partially unsaturated and fully unsaturated ring linkages. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. The heteroatom may include, but is not limited to, oxygen, nitrogen or sulfur. The carbocycloalkyl or heterocycloalkyl group can contain from 3 to 20 ring atoms. Examples of cycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, cyclooctynyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1– (1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3- morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3- yl, 1–piperazinyl, 2-piperazinyl, and the like. Additionally, the term encompasses multicyclic structures, including but not limited to, bicyclic and tricyclic ring structures. Similarly, the term “heterocycloalkylene” by itself or as part of another molecule means a divalent radical derived from heterocycloalkyl, and the term “cycloalkylene” by itself or as part of another molecule means a divalent radical derived from cycloalkyl. Substituents for each of the above noted cycloalkyl and heterocycloalkyl ring systems are selected from the group of acceptable substituents described herein. The term “cyclodextrin,” as used herein, refers to cyclic carbohydrates consisting of at least six to eight glucose molecules in a ring formation. The outer part of the ring contains water WSGR Ref. No 31362-825.601 soluble groups; at the center of the ring is a relatively nonpolar cavity able to accommodate small molecules. The term “diamine” as used herein, refers to groups/molecules comprising at least two amine functional groups, including, but not limited to, a hydrazine group, an amidine group, an imine group, a 1,1-diamine group, a 1,2-diamine group, a 1,3-diamine group, and a 1,4-diamine group. In addition, such groups may be part of linear, branched, or cyclic molecules. The term “detectable label,” as used herein, refers to a label which may be observable using analytical techniques including, but not limited to, fluorescence, chemiluminescence, electron-spin resonance, ultraviolet/visible absorbance spectroscopy, mass spectrometry, nuclear magnetic resonance, magnetic resonance, and electrochemical methods. The term “dicarbonyl” as used herein refers to a group containing at least two moieties selected from the group consisting of -C(O)-, -S(O)-, -S(O)2-, and –C(S)-, including, but not limited to, 1,2-dicarbonyl groups, a 1,3-dicarbonyl groups, and 1,4-dicarbonyl groups, and groups containing a least one ketone group, and/or at least one aldehyde groups, and/or at least one ester group, and/or at least one carboxylic acid group, and/or at least one thioester group. Such dicarbonyl groups include diketones, ketoaldehydes, ketoacids, ketoesters, and ketothioesters. In addition, such groups may be part of linear, branched, or cyclic molecules. The two moieties in the dicarbonyl group may be the same or different, and may include substituents that would produce, by way of example only, an ester, a ketone, an aldehyde, a thioester, or an amide, at either of the two moieties. The term “drug,” as used herein, refers to any substance used in the prevention, diagnosis, alleviation, treatment, or cure of a disease or condition. Non-limiting examples of a disease or condition to be prevented, diagnosed, alleviated, treated or cured by a drug include cancer, including but not limited to oral, colorectal, gastric, esophageal, hepatocellular, non-small-cell- lung (NSCL), small-cell lung (SCL), ovarian, breast including triple-negative breast, prostate, pancreatic, head and neck, squamous, renal, bladder, cervical, endometrial, thyroid, glioblastoma cancer. The term “drug-to-antibody ratio” (“DAR”) as used herein refers to the average (mean) number of drugs that are conjugated to an antibody in an antibody-drug conjugate (ADC) composition. The DAR value reflects the homogeneity of the ADC population in the composition, and also indicates the amount of “payload” (e.g, drug or drug-linker) that is loaded onto an antibody and can be delivered to a target (e.g., cell or diseased tissue). DAR can be determined by methods known to a person of ordinary skill in the art, for example, LC-MS (e.g., see Tang, Y. et al., Real-Time Analysis on Drug-Antibody Ratio of Antibody-Drug Conjugates for Synthesis, WSGR Ref. No 31362-825.601 Process Optimization and Quality Control, Sci Rep 7, 7763 (2017). doi: 10.1038/s41598-017- 08151-2; and Chen, Y. Drug-to-antibody ratio (DAR) by UV/Vis spectroscopy, Methods Mol. Biol., 2013;1045:267-73. doi: 10.1007/978-1-62703-541-5_16). In a non-limiting example, an ADC can have a population distribution of 20% of drug-loaded antibody, wherein the drug load is two (2) drugs per antibody; 25% of drug-loaded antibody, wherein the drug load is three (3) drugs per antibody; and 55% of drug-loaded antibody, wherein the drug load is four (4) drugs per antibody; thus, in this example, DAR is [(0.2 x 2) + (0.25 x 3) + (0.55 x 4)] = 3.35. The term “dye,” as used herein, refers to a soluble, coloring substance which contains a chromophore. The term “effective amount,” as used herein, refers to a sufficient amount of an agent, compound or composition being administered which will relieve to some extent one or more of the symptoms of the disease or condition being treated. The result can be reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. By way of example, an agent, compound or composition being administered includes, but is not limited to, a natural amino acid polypeptide, non-natural amino acid polypeptide, modified natural amino acid polypeptide, modified non-amino acid polypeptide, or an antibody or variant thereof. Compositions containing such natural amino acid polypeptides, non-natural amino acid polypeptides, modified natural amino acid polypeptides, modified non- natural amino acid polypeptides, or an antibody or variant thereof can be administered for prophylactic, enhancing, and/or therapeutic treatments. An appropriate “effective” amount in any individual case may be determined using techniques, such as a dose escalation study. The terms “enhance” or “enhancing” means to increase or prolong either in potency or duration a desired effect. By way of example, “enhancing” the effect of therapeutic agents refers to the ability to increase or prolong, either in potency or duration, the effect of therapeutic agents on during treatment of a disease, disorder or condition. An “enhancing-effective amount,” as used herein, refers to an amount adequate to enhance the effect of a therapeutic agent in the treatment of a disease, disorder or condition. When used in a patient, amounts effective for this use will depend on the severity and course of the disease, disorder or condition, previous therapy, the patient's health status and response to the drugs, and the judgment of the treating physician. As used herein, the term “eukaryote” refers to organisms belonging to the phylogenetic domain Eucarya, including but not limited to animals (including but not limited to, mammals, insects, reptiles, birds, etc.), ciliates, plants (including but not limited to, monocots, dicots, and algae), fungi, yeasts, flagellates, microsporidia, and protists. WSGR Ref. No 31362-825.601 The terms “functional group”, “active moiety”, “activating group”, “leaving group”, “reactive site”, “chemically reactive group” and “chemically reactive moiety,” as used herein, refer to portions or units of a molecule at which chemical reactions occur. The terms are somewhat synonymous in the chemical arts and are used herein to indicate the portions of molecules that perform some function or activity and are reactive with other molecules. The term “haloacyl,” as used herein, refers to acyl groups which contain halogen moieties, including, but not limited to, -C(O)CH₂F, -C(O)CF₃, -C(O)CH₂OCCl₃, and the like. The term “haloalkyl,” as used herein, refers to alkyl groups which contain halogen moieties, including, but not limited to, -CF3 and –CH2CF3 and the like. The term “halogen” as used herein includes fluorine, chlorine, bromine and iodine. In some embodiments, “halogen” may be referred to as “halo.” Non-limiting examples of halogen substituents include -F, -Cl, -Br and -I. Non-limiting examples of halogen ions include fluoride, chloride, bromide and iodide. The term “heavy atom,” as used herein, refers to a group which incorporates an ion or atom which is usually heavier than carbon. Such ions or atoms include, but are not limited to, silicon, tungsten, gold, lead, and uranium. The term “heteroalkyl,” as used herein, refers to straight or branched chain, or cyclic hydrocarbon radicals, or combinations thereof, consisting of an alkyl group and at least one heteroatom selected from the group consisting of O, N, Si and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) O, N and S and Si may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Examples include, but are not limited to, -CH₂-CH₂-O-CH₃, -CH₂-CH₂-NH-CH₃, -CH₂- CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2,-S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O- CH3, -Si(CH3)3, -CH2-CH=N-OCH3, and –CH=CH-N(CH3)-CH3. In addition, up to two heteroatoms may be consecutive, such as, by way of example, -CH₂-NH-OCH₃ and –CH₂-O- Si(CH₃)₃. Substituents for each of the above noted heteroalkyl groups are selected from the group of acceptable substituents described herein. The terms “heterocyclic-based linkage” or “heterocycle linkage” refers to a moiety formed from the reaction of a dicarbonyl group with a diamine group. The resulting reaction product is a heterocycle, including a heteroaryl group or a heterocycloalkyl group. The resulting heterocycle group serves as a chemical link between a non-natural amino acid or non-natural amino acid polypeptide and another functional group. In one embodiment, the heterocycle linkage includes a WSGR Ref. No 31362-825.601 nitrogen-containing heterocycle linkage, including by way of example only a pyrazole linkage, a pyrrole linkage, an indole linkage, a benzodiazepine linkage, and a pyrazalone linkage. Similarly, the term “heteroalkylene” refers to a divalent radical derived from heteroalkyl, as exemplified, but not limited by, -CH₂-CH₂-S-CH₂-CH₂- and –CH₂-S-CH₂-CH₂-NH-CH₂-. For heteroalkylene groups, the same or different heteroatoms can also occupy either or both of the chain termini (including but not limited to, alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, aminooxyalkylene, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. By way of example, the formula –C(O)2R’- represents both – C(O)₂R’- and –R’C(O)₂-. The term "heteroaryl" or "heteroaromatic," as used herein, refers to aryl groups which contain at least one heteroatom selected from the group consisting of N, O and S; wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized. The heteroaryl group may contain from 5 to 20 ring atoms. The term includes monocyclic rings linked covalently or fused-ring polycyclic (i.e., rings which share adjacent pairs of atoms) groups. Heteroaryl groups may be substituted or unsubstituted. A heteroaryl group may be attached to the remainder of the molecule through a ring heteroatom or a ring carbon atom. Non-limiting examples of heteroaryl groups include benzimidazolyl, benzothiazolyl, furanyl, imidazolyl, indolizinyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinolyl, quinoxalinyl, tetrazolyl, thiadiazolyl, thienyl, thiazolyl and triazolyl. Additional and more particular non-limiting examples of heteroaryl groups include 2-benzimidazolyl, 4- benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 2-benzothiazolyl, 4- benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl, 2-furanyl, 3-furanyl, 1- imidazolyl, 2-imidazolyl, 3-imidazolyl, 4-imidazolyl, 5-imidazolyl, 1-indolizinyl, 2-indolizinyl, 3-indolizinyl, 5-indolizinyl, 6-indolizinyl, 7-indolizinyl, 8-indolizinyl, 2-indolyl, 3-indolyl, 4- indolyl, 5-indolyl, 6-indolyl, 7-indolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3- isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 1,8-naphthyridinyl, 4-oxadiazolyl, 5-oxadiazolyl, 2- oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-pteridinyl, 4-pteridinyl, 6-pteridinyl, 7-pteridinyl, 2-purinyl, 6-purinyl, 7-purinyl, 8-purinyl, 2-pyrazinyl, 1-pyrazolyl, 2-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5- pyrazolyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4- pyrimidinyl, 5- pyrimidinyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 6-quinoxalinyl, 1- WSGR Ref. No 31362-825.601 tetrazolyl, 5-tetrazolyl, 4-thiadiazolyl, 5-thiadiazolyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 1-triazolyl, 2-triazolyl, 3-triazolyl, 4-triazolyl and 5-triazolyl. In some embodiments, a heteroaryl group is a 5-membered heteroaryl. In some embodiments, the 5-membered heteroaryl is substituted or unsubstituted pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl or thiodiazolyl. In some embodiments, the 5-membered heteroaryl is unsubstituted pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl or thiodiazolyl. In some embodiments, the heteroaryl is substituted or unsubstituted furanyl or thienyl. In some embodiments, the heteroaryl is unsubstituted furanyl or thienyl. In some embodiments, the heteroaryl group is substituted or unsubstituted thienyl. In some embodiments, the heteroaryl group is unsubstituted thienyl. In some embodiments, a heteroaryl group is 2-thienyl. In some embodiments, a heteroaryl group is 3-thienyl. Substituents for each of the above noted heteroaryl ring systems are selected from the group of acceptable substituents described herein. The term “homoalkyl,” as used herein refers to alkyl groups which are hydrocarbon groups. The term "humanized or chimeric antibody" refer to a molecule, generally prepared using recombinant techniques, having an antigen binding site derived from an immunoglobulin from a non-human species, (e.g., murine), and the remaining immunoglobulin structure of the molecule based upon the structure and/or sequence of a human immunoglobulin. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the framework residues/regions (FR) are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. The humanized forms of rodent antibodies will essentially comprise the same CDR sequences of the parental rodent antibodies, although certain amino acid substitutions may be included to increase affinity, increase stability of the humanized antibody, or for other reasons. However, as CDR loop exchanges do not uniformly result in an antibody with the same binding properties as the antibody of origin, changes in framework residues (FR), residues involved in CDR loop support, might also be introduced in humanized antibodies to preserve antigen binding affinity. The antigen-binding site may comprise either complete variable domains fused onto constant domains or only the complementarity determining regions (CDRs) grafted onto appropriate framework regions in the variable domains. Antigen binding sites may be wild type or modified by one or more amino acid substitutions. This eliminates the constant region as an immunogen in human individuals, but the possibility of an immune response to the foreign variable region WSGR Ref. No 31362-825.601 remains (LoBuglio, A. F. et al., "Mouse/Human Chimeric Monoclonal Antibody in Man: Kinetics and Immune Response," Proc. Natl. Acad. Sci. (USA) 86:4220-4224, 1989). Another approach focuses not only on providing human-derived constant regions but modifying the variable regions as well so as to reshape them as closely as possible to human form. It is known that the variable regions of both heavy and light chains contain three complementarity-determining regions (CDRs) which vary in response to the antigens in question and determine binding capability, flanked by four framework regions (FRs) which are relatively conserved in a given species and which putatively provide a scaffolding for the CDRs. When nonhuman antibodies are prepared with respect to a particular antigen, the variable regions can be "humanized" by grafting CDRs derived from nonhuman antibody on the FRs present in the human antibody to be modified. Application of this approach to various antibodies has been reported by Kettleborough, C. A. et al., "Humanization Of A Mouse Monoclonal Antibody By CDR-Grafting: The Importance Of Framework Residues On Loop Conformation," Protein Engineering 4:773-3783,1991; Co, M. S. et al., "Humanized Antibodies For Antiviral Therapy," Proc. Natl. Acad. Sci. (USA) 88:2869- 2873,1991; Carter, P. et al., "Humanization Of An Anti-p185her2 Antibody For Human Cancer Therapy," Proc. Natl. Acad. Sci. (USA) 89:4285-4289,1992; and Co, M. S. et al., "Chimeric And Humanized Antibodies With Specificity For The CD33 Antigen," J. Immunol. 148:1149- 1154,1992. In some embodiments, humanized antibodies preserve all CDR sequences (for example, a humanized mouse antibody which contains all six CDRs from the mouse antibodies). In other embodiments, humanized antibodies have one or more CDRs (one, two, three, four, five, six) which are altered with respect to the original antibody, which are also termed one or more CDRs "derived from" one or more CDRs from the original antibody. The term “identical,” as used herein, refers to two or more sequences or subsequences which are the same. In addition, the term “substantially identical,” as used herein, refers to two or more sequences which have a percentage of sequential units which are the same when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using comparison algorithms or by manual alignment and visual inspection. By way of example only, two or more sequences may be “substantially identical” if the sequential units are about 60% identical, about 65% identical, about 70% identical, about 75% identical, about 80% identical, about 85% identical, about 90% identical, or about 95% identical over a specified region. Such percentages describe the “percent identity” of two or more sequences. The identity of a sequence can exist over a region that is at least about 75-100 sequential units in length, over a region that is about 50 sequential units in length, or, where not specified, across the entire sequence. This definition also refers to the complement of a test sequence. By way of example only, two or WSGR Ref. No 31362-825.601 more polypeptide sequences are identical when the amino acid residues are the same, while two or more polypeptide sequences are “substantially identical” if the amino acid residues are about 60% identical, about 65% identical, about 70% identical, about 75% identical, about 80% identical, about 85% identical, about 90% identical, or about 95% identical over a specified region. The identity can exist over a region that is at least about 75 to about 100 amino acids in length, over a region that is about 50 amino acids in length, or, where not specified, across the entire sequence of a polypeptide sequence. In addition, by way of example only, two or more polynucleotide sequences are identical when the nucleic acid residues are the same, while two or more polynucleotide sequences are “substantially identical” if the nucleic acid residues are about 60% identical, about 65% identical, about 70% identical, about 75% identical, about 80% identical, about 85% identical, about 90% identical, or about 95% identical over a specified region. The identity can exist over a region that is at least about 75 to about 100 nucleic acids in length, over a region that is about 50 nucleic acids in length, or, where not specified, across the entire sequence of a polynucleotide sequence. The term “immunogenicity,” as used herein, refers to an antibody response to administration of a therapeutic drug. The immunogenicity toward therapeutic non-natural amino acid polypeptides can be obtained using quantitative and qualitative assays for detection of anti- non-natural amino acid polypeptides antibodies in biological fluids. Such assays include, but are not limited to, Radioimmunoassay (RIA), Enzyme-linked immunosorbent assay (ELISA), luminescent immunoassay (LIA), and fluorescent immunoassay (FIA). Analysis of immunogenicity toward therapeutic non-natural amino acid polypeptides involves comparing the antibody response upon administration of therapeutic non-natural amino acid polypeptides to the antibody response upon administration of therapeutic natural amino acid polypeptides. The term “isolated,” as used herein, refers to separating and removing a component of interest from components not of interest. Isolated substances can be in either a dry or semi-dry state, or in solution, including but not limited to an aqueous solution. The isolated component can be in a homogeneous state or the isolated component can be a part of a pharmaceutical composition that comprises additional pharmaceutically acceptable carriers and/or excipients. Purity and homogeneity may be determined using analytical chemistry techniques including, but not limited to, polyacrylamide gel electrophoresis or high-performance liquid chromatography. In addition, when a component of interest is isolated and is the predominant species present in a preparation, the component is described herein as substantially purified. The term “purified,” as used herein, may refer to a component of interest which is at least 85% pure, at least 90% pure, at least 95% pure, at least 99% or greater pure. By way of example only, nucleic acids or proteins are “isolated” WSGR Ref. No 31362-825.601 when such nucleic acids or proteins are free of at least some of the cellular components with which it is associated in the natural state, or that the nucleic acid or protein has been concentrated to a level greater than the concentration of its in vivo or in vitro production. Also, by way of example, a gene is isolated when separated from open reading frames which flank the gene and encode a protein other than the gene of interest. The term “label,” as used herein, refers to a substance which is incorporated into a compound and is readily detected, whereby its physical distribution may be detected and/or monitored. The term “linkage” or “adduct moiety” as used herein refers to bonds or chemical moiety formed from a chemical reaction between the functional group of one group, such as a linker of the present disclosure, and another molecule. Such bonds may include, but are not limited to, covalent linkages and non-covalent bonds, while such chemical moieties may include, but are not limited to, esters, carbonates, imines, phosphate esters, hydrazones, acetals, orthoesters, peptide linkages, oximes and oligonucleotide linkages. Hydrolytically stable linkages mean that the linkages are substantially stable in water and do not react with water at useful pH values, including but not limited to, under physiological conditions for an extended period of time, perhaps even indefinitely. Hydrolytically unstable or degradable linkages mean that the linkages are degradable in water or in aqueous solutions, including for example, blood. Enzymatically unstable or degradable linkages mean that the linkage can be degraded by one or more enzymes. By way of example only, PEG and related polymers may include degradable linkages in the polymer backbone or in the linker group between the polymer backbone and one or more of the terminal functional groups of the polymer molecule. Such degradable linkages include but are not limited to ester linkages formed by the reaction of PEG carboxylic acids or activated PEG carboxylic acids with alcohol groups on a biologically active agent, wherein such ester groups generally hydrolyze under physiological conditions to release the biologically active agent. Other hydrolytically degradable linkages include but are not limited to carbonate linkages; imine linkages resulted from reaction of an amine and an aldehyde; phosphate ester linkages formed by reacting an alcohol with a phosphate group; hydrazone linkages which are reaction product of a hydrazide and an aldehyde; acetal linkages that are the reaction product of an aldehyde and an alcohol; orthoester linkages that are the reaction product of a formate and an alcohol; peptide linkages formed by an amine group, including but not limited to, at an end of a polymer such as PEG, and a carboxyl group of a peptide; and oligonucleotide linkages formed by a phosphoramidite group, including but not limited to, at the end of a polymer, and a 5' hydroxyl group of an oligonucleotide. WSGR Ref. No 31362-825.601 The term “linker,” as used herein, refers to any multivalent group that connects, or is capable of connecting, a first group to at least one other group. Typically, a linker is a bivalent or a trivalent organic moiety that connects a drug or payload (first group) to a biologically active agent (second group), e.g., via a linkage or adduct moiety, or that connects a drug or payload (first group) to a reactive moiety (second group), wherein the reactive moiety is capable of reacting with a biologically active agent. Linkers can be susceptible to cleavage (cleavable linkers), such as, acid-induced cleavage, photo-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, and disulfide bond cleavage, and so on, at conditions under which the drug or payload and the at least one other group remains active. Alternatively, linkers can be substantially resistant to cleavage (e.g., stable linker or non-cleavable linker). The term “metabolite,” as used herein, refers to a derivative of a compound, by way of example natural amino acid polypeptide, a non-natural amino acid polypeptide, a modified natural amino acid polypeptide, or a modified non-natural amino acid polypeptide, that is formed when the compound, by way of example natural amino acid polypeptide, non-natural amino acid polypeptide, modified natural amino acid polypeptide, or modified non-natural amino acid polypeptide, is metabolized. The term “pharmaceutically active metabolite” or “active metabolite” refers to a biologically active derivative of a compound, by way of example natural amino acid polypeptide, a non-natural amino acid polypeptide, a modified natural amino acid polypeptide, or a modified non-natural amino acid polypeptide, that is formed when such a compound, by way of example a natural amino acid polypeptide, non-natural amino acid polypeptide, modified natural amino acid polypeptide, or modified non-natural amino acid polypeptide, is metabolized. The term “pharmaceutically active metabolite” or “active metabolite” also refers to biologically active derivatives of a compound, by way of example metabolizing phosphate linkages including monophosphate, diphosphate, pyrophosphate and triphosphate but not limited to such. The terms “medium” or “media,” as used herein, refer to any culture medium used to grow and harvest cells and/or products expressed and/or secreted by such cells. Such “medium” or “media” include, but are not limited to, solution, solid, semi-solid, or rigid supports that may support or contain any host cell, including, by way of example, bacterial host cells, yeast host cells, insect host cells, plant host cells, eukaryotic host cells, mammalian host cells, CHO cells, prokaryotic host cells, E. coli, or Pseudomonas host cells, and cell contents. Such “medium” or “media” includes, but is not limited to, medium or media in which the host cell has been grown into which a polypeptide has been secreted, including medium either before or after a proliferation step. Such “medium” or “media” also includes, but is not limited to, buffers or reagents that WSGR Ref. No 31362-825.601 contain host cell lysates, by way of example a polypeptide produced intracellularly and the host cells are lysed or disrupted to release the polypeptide. The term “metabolite,” as used herein, refers to a derivative of a compound, by way of example natural amino acid polypeptide, a non-natural amino acid polypeptide, a modified natural amino acid polypeptide, or a modified non-natural amino acid polypeptide, that is formed when the compound, by way of example natural amino acid polypeptide, non-natural amino acid polypeptide, modified natural amino acid polypeptide, or modified non-natural amino acid polypeptide, is metabolized. The term “pharmaceutically active metabolite” or “active metabolite” refers to a biologically active derivative of a compound, by way of example natural amino acid polypeptide, a non-natural amino acid polypeptide, a modified natural amino acid polypeptide, or a modified non-natural amino acid polypeptide, that is formed when such a compound, by way of example a natural amino acid polypeptide, non-natural amino acid polypeptide, modified natural amino acid polypeptide, or modified non-natural amino acid polypeptide, is metabolized. The term “metabolized,” as used herein, refers to the sum of the processes by which a particular substance is changed by an organism. Such processes include, but are not limited to, hydrolysis reactions and reactions catalyzed by enzymes. Further information on metabolism may be obtained from The Pharmacological Basis of Therapeutics, 9th Edition, McGraw-Hill (1996). By way of example only, metabolites of natural amino acid polypeptides, non-natural amino acid polypeptides, modified natural amino acid polypeptides, or modified non-natural amino acid polypeptides may be identified either by administration of the natural amino acid polypeptides, non-natural amino acid polypeptides, modified natural amino acid polypeptides, or modified non- natural amino acid polypeptides to a host and analysis of tissue samples from the host, or by incubation of natural amino acid polypeptides, non-natural amino acid polypeptides, modified natural amino acid polypeptides, or modified non-natural amino acid polypeptides with hepatic cells in vitro and analysis of the resulting compounds. The term “modified,” as used herein refers to the presence of a change to a natural amino acid, a non-natural amino acid, a natural amino acid polypeptide or a non-natural amino acid polypeptide. Such changes, or modifications, may be obtained by post synthesis modifications of natural amino acids, non-natural amino acids, natural amino acid polypeptides or non-natural amino acid polypeptides, or by co-translational, or by post-translational modification of natural amino acids, non-natural amino acids, natural amino acid polypeptides or non-natural amino acid polypeptides. The term “modified or unmodified” means that the natural amino acid, non-natural amino acid, natural amino acid polypeptide or non-natural amino acid polypeptide being discussed are optionally modified, that is, the natural amino acid, non-natural amino acid, natural amino acid WSGR Ref. No 31362-825.601 polypeptide or non-natural amino acid polypeptide under discussion can be modified or unmodified. As used herein, the term “modulated serum half-life” refers to positive or negative changes in the circulating half-life of a modified biologically active molecule relative to its non-modified form. By way of example, the modified biologically active molecules include, but are not limited to, natural amino acid, non-natural amino acid, natural amino acid polypeptide or non-natural amino acid polypeptide. By way of example, serum half-life is measured by taking blood samples at various time points after administration of the biologically active molecule or modified biologically active molecule and determining the concentration of that molecule in each sample. Correlation of the serum concentration with time allows calculation of the serum half-life. By way of example, modulated serum half-life may be an increased in serum half-life, which may enable an improved dosing regimen or avoid toxic effects. Such increases in serum may be at least about two-fold, at least about three-fold, at least about five-fold, or at least about ten-fold. Methods for evaluating serum half-life are known in the art and may be used for evaluating the serum half-life of antibodies and antibody drug conjugates of the present disclosure. The term “modulated therapeutic half-life,” as used herein, refers to positive or negative change in the half-life of the therapeutically effective amount of a modified biologically active molecule, relative to its non-modified form. By way of example, the modified biologically active molecules include, but are not limited to, natural amino acid, non-natural amino acid, natural amino acid polypeptide or non-natural amino acid polypeptide. By way of example, therapeutic half-life is measured by measuring pharmacokinetic and/or pharmacodynamic properties of the molecule at various time points after administration. Increased therapeutic half-life may enable a particular beneficial dosing regimen, a particular beneficial total dose, or avoids an undesired effect. By way of example, the increased therapeutic half-life may result from increased potency, increased or decreased binding of the modified molecule to its target, an increase or decrease in another parameter or mechanism of action of the non-modified molecule, or an increased or decreased breakdown of the molecules by enzymes such as, by way of example only, proteases. Methods for evaluating therapeutic half-life are known in the art and may be used for evaluating the therapeutic half-life of antibodies and antibody drug conjugates of the present disclosure. The term “nanoparticle,” as used herein, refers to a particle which has a particle size of within a range of about 0.1 nm to about 1000 nm. In some embodiments, the nanoparticle has a particle size of within a range of about 0.1 nm to about 750 nm. In some embodiments, the nanoparticle has a particle size of within a range of about 1 nm to about 500 nm. WSGR Ref. No 31362-825.601 As used herein, the term “non-eukaryote” refers to non-eukaryotic organisms. By way of example, a non-eukaryotic organism may belong to the Eubacteria, (which includes but is not limited to, Escherichia coli, Thermus thermophilus, or Bacillus stearothermophilus, Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas putida), phylogenetic domain, or the Archaea, which includes, but is not limited to, Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Archaeoglobus fulgidus, Pyrococcus furiosus, Pyrococcus horikoshii, Aeuropyrum pernix, or Halobacterium such as Haloferax volcanii and Halobacterium species NRC-1, or phylogenetic domain. A “non-natural amino acid” as used herein refers to an amino acid that is not one of the 20 common amino acids or pyrrolysine or selenocysteine. Other terms that may be used synonymously with the term “non-natural amino acid” is “non-naturally encoded amino acid,” “unnatural amino acid,” “non-naturally-occurring amino acid,” and variously hyphenated and non- hyphenated versions thereof. The term “non-natural amino acid” includes, but is not limited to, amino acids which occur naturally by modification of a naturally encoded amino acid (including but not limited to, the 20 common amino acids or pyrrolysine and selenocysteine) but are not themselves incorporated into a growing polypeptide chain by the translation complex. Examples of naturally-occurring amino acids that are not naturally-encoded include, but are not limited to, N-acetylglucosaminyl-L-serine, N-acetylglucosaminyl-L-threonine, and O-phosphotyrosine. Additionally, the term “non-natural amino acid” includes, but is not limited to, amino acids which do not occur naturally and may be obtained synthetically or may be obtained by modification of non-natural amino acids. The term “nucleic acid,” as used herein, refers to deoxyribonucleotides, deoxyribonucleosides, ribonucleosides or ribonucleotides and polymers thereof in either single- or double-stranded form. By way of example only, such nucleic acids and nucleic acid polymers include, but are not limited to, (i) analogues of natural nucleotides which have similar binding properties as a reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides; (ii) oligonucleotide analogs including, but are not limited to, PNA (peptidonucleic acid), analogs of DNA used in antisense technology (phosphorothioates, phosphoroamidates, and the like); (iii) conservatively modified variants thereof (including but not limited to, degenerate codon substitutions) and complementary sequences and sequence explicitly indicated. By way of example, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res.19:5081, 1991; Ohtsuka et al., J. Biol. Chem.260:2605-2608, 1985; and Rossolini et al., Mol. Cell. Probes 8:91-98, 1994). WSGR Ref. No 31362-825.601 The term “optionally substituted” as used herein means substituted or unsubstituted. Thus, when a substance, group or moiety is defined as optionally substituted, the substance, group or moiety can be a substituted group or an unsubstituted group. By way of example only, optionally substituted alkyl includes substituted alkyl and unsubstituted alkyl. Accordingly, the terms “substituted and unsubstituted” and “optionally substituted” may be used interchangeably. The term “oxidizing agent,” as used herein, refers to a compound or material which is capable of removing an electron from a compound being oxidized. By way of example oxidizing agents include, but are not limited to, oxidized glutathione, cystine, cystamine, oxidized dithiothreitol, oxidized erythreitol, and oxygen. A wide variety of oxidizing agents are suitable for use in the methods and compositions described herein. The term “pharmaceutically acceptable”, as used herein, refers to a material, including but not limited, to a salt, binder, adjuvant, excipient, carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively nontoxic, i.e., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. The term “photocleavable group,” as used herein, refers to a group which breaks upon exposure to light. The term “photocrosslinker,” as used herein, refers to a compound comprising two or more functional groups which, upon exposure to light, are reactive and form a covalent or non-covalent linkage with two or more monomeric or polymeric molecules. In some embodiments the disclosure concerns polymers. The term “polymer,” as used herein, refers to a molecule composed of repeated subunits. Such molecules include, but are not limited to, polypeptides, polynucleotides, or polysaccharides or polyalkylene glycols. Polymers of the disclosure can be linear or branched polymeric polyether polyols including, but are not limited to, polyethylene glycol, polypropylene glycol, polybutylene glycol, and derivatives thereof. Other exemplary embodiments are listed, for example, in commercial supplier catalogs, such as Shearwater Corporation's catalog “Polyethylene Glycol and Derivatives for Biomedical Applications” (2001). By way of example only, such polymers have average molecular weights between about 0.1 kDa to about 100 kDa. Such polymers include, but are not limited to, between about 100 Da and about 100,000 Da or more. The molecular weight of the polymer may be between about 100 Da and about 100,000 Da, including but not limited to, about 100,000 Da, about 95,000 Da, about 90,000 Da, about 85,000 Da, about 80,000 Da, about 75,000 Da, about 70,000 Da, about 65,000 Da, about 60,000 Da, about 55,000 Da, about 50,000 Da, about 45,000 Da, about 40,000 Da, about 35,000 Da, about 30,000 Da, about 25,000 Da, about 20,000 Da, about WSGR Ref. No 31362-825.601 15,000 Da, about 10,000 Da, about 9,000 Da, about 8,000 Da, about 7,000 Da, about 6,000 Da, about 5,000 Da, about 4,000 Da, about 3,000 Da, about 2,000 Da, about 1,000 Da, about 900 Da, about 800 Da, about 700 Da, about 600 Da, about 500 Da, 400 Da, about 300 Da, about 200 Da, and about 100 Da. In some embodiments molecular weight of the polymer is between about 100 Da and about 50,000 Da. In some embodiments, the molecular weight of the polymer is between about 100 Da and about 40,000 Da. In some embodiments, the molecular weight of the polymer is between about 1,000 Da and about 40,000 Da. In some embodiments, the molecular weight of the polymer is between about 2,000 to about 50,000 Da. In some embodiments, the molecular weight of the polymer is between about 5,000 Da and about 40,000 Da. In some embodiments, the molecular weight of the polymer is between about 10,000 Da and about 40,000 Da. In some embodiments, the poly(ethylene glycol) molecule is a branched polymer. The molecular weight of the branched chain PEG may be between about 1,000 Da and about 100,000 Da, including but not limited to, about 100,000 Da, about 95,000 Da, about 90,000 Da, about 85,000 Da, about 80,000 Da, about 75,000 Da, about 70,000 Da, about 65,000 Da, about 60,000 Da, about 55,000 Da, about 50,000 Da, about 45,000 Da, about 40,000 Da, about 35,000 Da, about 30,000 Da, about 25,000 Da, about 20,000 Da, about 15,000 Da, about 10,000 Da, about 9,000 Da, about 8,000 Da, about 7,000 Da, about 6,000 Da, about 5,000 Da, about 4,000 Da, about 3,000 Da, about 2,000 Da, and about 1,000 Da. In some embodiments, the molecular weight of the branched chain PEG is between about 1,000 Da and about 50,000 Da. In some embodiments, the molecular weight of the branched chain PEG is between about 1,000 Da and about 40,000 Da. In some embodiments, the molecular weight of the branched chain PEG is between about 5,000 Da and about 40,000 Da. In some embodiments, the molecular weight of the branched chain PEG is between about 5,000 Da and about 20,000 Da. In other embodiments, the molecular weight of the branched chain PEG is between about 2,000 to about 50,000 Da. The term “PEGylating” or “PEGylated” is meant to refer to the covalent bonding of the specified synthetic amino acid to a polyethylene glycol (PEG) molecule. The method can comprise contacting an isolated polypeptide comprising a synthetic amino acid with a water soluble polymer comprising a moiety that reacts with the synthetic amino acid. The method can comprise contacting an isolated anti-TROP2 ADC polypeptide, an isolated anti-HER2 polypeptide, an isolated anti-HER3 polypeptide, an isolated anti-PSMA polypeptide or an isolated CD70 polypeptide comprising a synthetic amino acid with a water soluble polymer comprising a moiety that reacts with the synthetic amino acid. The method can comprise contacting an isolated anti-HER2 ADC polypeptide comprising a synthetic amino acid with a water soluble polymer comprising a moiety that reacts with the synthetic amino acid. The method WSGR Ref. No 31362-825.601 can comprise contacting an isolated anti-CD70 ADC polypeptide comprising a synthetic amino acid with a water soluble polymer comprising a moiety that reacts with the synthetic amino acid. The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. That is, a description directed to a polypeptide applies equally to a description of a peptide and a description of a protein, and vice versa. The terms apply to naturally occurring amino acid polymers as well as amino acid polymers in which one or more amino acid residues is a non-natural amino acid. Additionally, such “polypeptides,” “peptides” and “proteins” include amino acid chains of any length, including full length proteins, wherein the amino acid residues are linked by covalent peptide bonds. In some embodiments, a “peptide” can refer to a polymer of 2 to 12 amino acids. In some embodiments, a peptide refers to a polymer containing 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 amino acids, wherein the amino acid residues are linked by covalent peptide bonds. In some embodiments, a peptide can contain 2, 3, 4, 5 or 6 amino acids. In some embodiments, a peptide can contain 2, 3 or 4 amino acids; non-limiting examples include a dipeptide, a tripeptide and a tetrapeptide. The term “post-translationally modified” refers to any modification of a natural or non- natural amino acid which occurs after such an amino acid has been translationally incorporated into a polypeptide chain. Such modifications include, but are not limited to, co-translational in vivo modifications, co-translational in vitro modifications (such as in a cell-free translation system), post-translational in vivo modifications, and post-translational in vitro modifications. In some embodiments, at least one post-translational modification at some position on a polypeptide may occur. In some embodiments the co-translational or post-translational modification occurs via the cellular machinery (e.g., glycosylation, acetylation, acylation, lipid- modification, palmitoylation, palmitate addition, phosphorylation, glycolipid-linkage modification, and the like), in many instances, such cellular-machinery-based co-translational or post-translational modifications occur at the naturally occurring amino acid sites on the polypeptide, however, in certain embodiments, the cellular-machinery-based co-translational or post-translational modifications occur on the non-natural amino acid site(s) on the polypeptide. In other embodiments, the post-translational modification does not utilize the cellular machinery, but the functionality is instead provided by attachment of a molecule (a polymer; a water-soluble polymer; a derivative of polyethylene glycol; a second protein or polypeptide or polypeptide analog; an antibody or antibody fragment; and any combination thereof) comprising a second reactive group to the at least one non-natural amino acid comprising a first reactive group (including but not limited to, non-natural amino acid containing a ketone, aldehyde, acetal, hemiacetal, alkyne, cycloalkyne, azide, oxime, aminooxy or hydroxylamine functional group) WSGR Ref. No 31362-825.601 utilizing chemistry methodology described herein, or others suitable for the particular reactive groups. In certain embodiments, the co-translational or post-translational modification is made in vivo in a eukaryotic cell or in a non-eukaryotic cell. In certain embodiments, the post-translational modification is made in vitro not utilizing the cellular machinery. Also included with this aspect are methods for producing, purifying, characterizing and using such drug or payload linker containing at least one such co-translationally or post-translationally modified non-natural amino acids. In certain embodiments, the polypeptide or non-natural amino acid linked composition includes at least one co-translational or post-translational modification that is made in vivo by one host cell, where the post-translational modification is not normally made by another host cell type. In certain embodiments, the polypeptide includes at least one co-translational or post-translational modification that is made in vivo by a eukaryotic cell, where the co-translational or post- translational modification is not normally made by a non-eukaryotic cell. Examples of such co- translational or post-translational modifications include, but are not limited to, glycosylation, acetylation, acylation, lipid-modification, palmitoylation, palmitate addition, phosphorylation, glycolipid-linkage modification, and the like. In one embodiment, the co-translational or post- translational modification comprises attachment of an oligosaccharide to an asparagine by a GlcNAc-asparagine linkage (including but not limited to, where the oligosaccharide comprises (GlcNAc-Man)2-Man-GlcNAc-GlcNAc, and the like). In another embodiment, the co- translational or post-translational modification comprises attachment of an oligosaccharide (including but not limited to, Gal-GalNAc, Gal-GlcNAc, etc.) to a serine or threonine by a GalNAc-serine, a GalNAc-threonine, a GlcNAc-serine, or a GlcNAc-threonine linkage. In certain embodiments, a protein or polypeptide can comprise a secretion or localization sequence, an epitope tag, a FLAG tag, a polyhistidine tag, a GST fusion, and/or the like. Also included with this aspect are methods for producing, purifying, characterizing and using such polypeptides containing at least one such co-translational or post-translational modification. In other embodiments, the glycosylated non-natural amino acid polypeptide is produced in a non- glycosylated form. Such a non-glycosylated form of a glycosylated non-natural amino acid may be produced by methods that include chemical or enzymatic removal of oligosaccharide groups from an isolated or substantially purified or unpurified glycosylated non-natural amino acid polypeptide; production of the non-natural amino acid in a host that does not glycosylate such a non-natural amino acid polypeptide (such a host including, prokaryotes or eukaryotes engineered or mutated to not glycosylate such a polypeptide), the introduction of a glycosylation inhibitor into the cell culture medium in which such a non-natural amino acid polypeptide is being produced WSGR Ref. No 31362-825.601 by a eukaryote that normally would glycosylate such a polypeptide, or a combination of any such methods. Also described herein are such non-glycosylated forms of normally-glycosylated non- natural amino acid polypeptides (by normally-glycosylated is meant a polypeptide that would be glycosylated when produced under conditions in which naturally-occurring polypeptides are glycosylated). Of course, such non-glycosylated forms of normally-glycosylated non-natural amino acid polypeptides (or indeed any polypeptide described herein) may be in an unpurified form, a substantially purified form, or in an isolated form. The terms “prodrug” or “pharmaceutically acceptable prodrug,” as used herein, refers to an agent that is converted into the parent drug in vivo or in vitro, which does not abrogate the biological activity or properties of the drug, and is relatively nontoxic, i.e., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. Prodrugs are generally drug precursors that, following administration to a subject and subsequent absorption, are converted to an active, or a more active species via some process, such as conversion by a metabolic pathway. Some prodrugs have a chemical group present on the prodrug that renders it less active and/or confers solubility or some other property to the drug. Once the chemical group has been cleaved and/or modified from the prodrug the active drug is generated. Prodrugs are converted into active drug within the body through enzymatic or non-enzymatic reactions. Prodrugs may provide improved physiochemical properties such as better solubility, enhanced delivery characteristics, such as specifically targeting a particular cell, tissue, organ or ligand, and improved therapeutic value of the drug. The benefits of such prodrugs include, but are not limited to, (i) ease of administration compared with the parent drug; (ii) the prodrug may be bioavailable by oral administration whereas the parent is not; and (iii) the prodrug may also have improved solubility in pharmaceutical compositions compared with the parent drug. A prodrug includes a pharmacologically inactive, or reduced activity, derivative of an active drug. Prodrugs may be designed to modulate the amount of a drug or biologically active molecule that reaches a desired site of action through the manipulation of the properties of a drug, such as physiochemical, biopharmaceutical, or pharmacokinetic properties. An example, without limitation, of a prodrug would be a non-natural amino acid polypeptide which is administered as an ester (the “prodrug”) to facilitate transmittal across a cell membrane where water solubility is detrimental to mobility and that is then metabolically hydrolyzed to the carboxylic acid, the active entity, once inside the cell where water solubility is beneficial. Prodrugs may be designed as reversible drug derivatives, for use as modifiers to enhance drug transport to site-specific tissues. WSGR Ref. No 31362-825.601 The term “prophylactically effective amount,” as used herein, refers to an amount of a composition containing at least one non-natural amino acid polypeptide or at least one modified non-natural amino acid polypeptide prophylactically applied to a patient which will relieve to some extent one or more of the symptoms of a disease, condition or disorder being treated. In such prophylactic applications, such amounts may depend on the patient's state of health, weight, and the like. It is considered well within the skill of the art for one to determine such prophylactically effective amounts by routine experimentation, including, but not limited to, a dose escalation clinical trial. The term “protected,” as used herein, refers to the presence of a “protecting group” or moiety that prevents reaction of the chemically reactive functional group under certain reaction conditions. The protecting group will vary depending on the type of chemically reactive group being protected. By way of example only, (i) if the chemically reactive group is an amine or a hydrazide, the protecting group may be selected from tert-butyloxycarbonyl (t-Boc) and 9- fluorenylmethoxycarbonyl (Fmoc); (ii) if the chemically reactive group is a thiol, the protecting group may be orthopyridyldisulfide; and (iii) if the chemically reactive group is a carboxylic acid, such as butanoic or propionic acid, or a hydroxyl group, the protecting group may be benzyl or an alkyl group such as methyl, ethyl, or tert-butyl. By way of example only, blocking/protecting groups may be selected from:

Additionally, protecting groups include, but are not limited to, photolabile groups such as Nvoc and MeNvoc and other protecting groups known in the art. Other protecting groups are described in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, which is incorporated herein by reference in its entirety. WSGR Ref. No 31362-825.601 The term “reactive compound,” as used herein, refers to a compound which under appropriate conditions is reactive toward another atom, molecule or compound. The term “recombinant host cell,” also referred to as “host cell,” refers to a cell which includes an exogenous polynucleotide, wherein the methods used to insert the exogenous polynucleotide into a cell include, but are not limited to, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells. By way of example only, such exogenous polynucleotide may be a nonintegrated vector, including but not limited to a plasmid, or may be integrated into the host genome. The term “redox-active agent,” as used herein, refers to a molecule which oxidizes or reduces another molecule, whereby the redox active agent becomes reduced or oxidized. Examples of redox active agent include, but are not limited to, ferrocene, quinones, Ru^2+/3+ complexes, Co^2+/3+ complexes, and Os^2+/3+ complexes. In some embodiments, a redox-active agent is a redox- active amino acid. The term “reducing agent,” as used herein, refers to a compound or material which is capable of adding an electron to a compound being reduced. By way of example reducing agents include, but are not limited to, dithiothreitol (DTT), 2-mercaptoethanol, dithioerythritol, cysteine, cysteamine (2-aminoethanethiol), and reduced glutathione. Such reducing agents may be used, by way of example only, to maintain sulfhydryl groups in the reduced state and to reduce intra- or intermolecular disulfide bonds. The term “resin,” as used herein, refers to high molecular weight, insoluble polymer beads. By way of example only, such beads may be used as supports for solid phase peptide synthesis, or sites for attachment of molecules prior to purification. The term “saccharide,” as used herein, refers to a series of carbohydrates including but not limited to sugars, monosaccharides, oligosaccharides, and polysaccharides. The term “safety” or “safety profile,” as used herein, refers to side effects that might be related to administration of a drug relative to the number of times the drug has been administered. By way of example, a drug which has been administered many times and produced only mild or no side effects is said to have an excellent safety profile. A non-limiting example of a method to evaluate the safety profile is given in example 26. This method may be used for evaluating the safety profile of any polypeptide. The term “subject” as used herein, refers to an animal which is the object of treatment, observation or experiment. By way of example only, a subject may be, but is not limited to, a mammal including, but not limited to, a human. WSGR Ref. No 31362-825.601 The term “substantially purified,” as used herein, refers to a component of interest that may be substantially or essentially free of other components which normally accompany or interact with the component of interest prior to purification. By way of example only, a component of interest may be “substantially purified” when the preparation of the component of interest contains less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about l% (by dry weight) of contaminating components. Thus, a “substantially purified” component of interest may have a purity level of about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or greater. By way of example only, a natural amino acid polypeptide or a non-natural amino acid polypeptide may be purified from a native cell, or host cell in the case of recombinantly produced natural amino acid polypeptides or non-natural amino acid polypeptides. By way of example a preparation of a natural amino acid polypeptide or a non-natural amino acid polypeptide may be “substantially purified” when the preparation contains less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about l% (by dry weight) of contaminating material. By way of example when a natural amino acid polypeptide or a non-natural amino acid polypeptide is recombinantly produced by host cells, the natural amino acid polypeptide or non-natural amino acid polypeptide may be present at about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, about 2%, or about 1% or less of the dry weight of the cells. By way of example when a natural amino acid polypeptide or a non-natural amino acid polypeptide is recombinantly produced by host cells, the natural amino acid polypeptide or non-natural amino acid polypeptide may be present in the culture medium at about 5g/L, about 4g/L, about 3g/L, about 2g/L, about 1g/L, about 750mg/L, about 500mg/L, about 250mg/L, about 100mg/L, about 50mg/L, about 10mg/L, or about 1mg/L or less of the dry weight of the cells. By way of example, “substantially purified” natural amino acid polypeptides or non-natural amino acid polypeptides may have a purity level of about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99% or greater as determined by appropriate methods, including, but not limited to, SDS/PAGE analysis, RP-HPLC, SEC, and capillary electrophoresis. The term “substituents” refers to groups which may be used to replace another group on a molecule. Such groups include, but are not limited to, halogen, C1-C10 alkyl, C2-C10 alkenyl, C2- C₁₀ alkynyl, C₁-C₁₀ alkoxy, substituted C₁-C₁₀ alkoxy, C₅-C₁₂ aralkyl, C₃-C₁₂ cycloalkyl, C₄-C₁₂ cycloalkenyl, C2-C12 alkoxyalkyl, C5-C12 alkoxyaryl, C5-C12 aryloxyalkyl, C7-C12 oxyaryl, C1-C6 WSGR Ref. No 31362-825.601 alkylsulfinyl, C₁-C₁₀ alkylsulfonyl, wherein m is from 1 to 8, aryl, substituted aryl (including but not limited to phenyl or substituted phenyl), haloalkyl (including but not limited to fluoroalkyl), heterocyclic radical, substituted heterocyclic radical, nitroalkyl, -SiR₃, -NO₂, -N₃, -ONH₂, -CN, - NRC(O)-(C₁-C₁₀ alkyl), -C(O)-(C₁-C₁₀ alkyl), C₂-C₁₀ alkthioalkyl, -C(O)O-(C₁-C₁₀ alkyl), -OH, - OR, -SR, -SO2, -S(O)R, -S(O)2R, -S(O)2NR2, -NRSO2R, , =NR, =N-OR, -OC(O)R, -C(O)R, - CO2R, -CONR2, -OC(O)NR2, -NRC(O)R, -NRC(O)NR2, -NR(O)2R, -NR-C(NR2)=NR, =S, - COOH, -NR₂, carbonyl (-C(O)), -C(O)-(C₁-C₁₀ alkyl)-CF₃, -C(O)-CF₃, -C(O)NR₂, -(C₁-C₁₀ aryl)- S-(C6-C10 aryl), -C(O)-(C6-C10 aryl), -(CH2)m-O-(CH2)m-O-(C1-C10 alkyl), -(CH2)m-O-(C1-C10 alkyl), -C(O)NR2, -C(S)NR2, -SO2NR2, -NRC(O)NR2, -NRC(S)NR2, a sugar; wherein each m is from 1 to 8; salts thereof, and the like. Each R group in the preceding list includes, but is not limited to, H, alkyl, substituted alkyl, aryl, substituted aryl, halogen or alkaryl. Where substituent groups are specified by their conventional chemical formulas, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left; for example, -CH2O- is equivalent to –OCH2-. The term “substituted”, when used associated with a functional group, refers to a chemical moiety that is the functional group substituted with substituents. For example, substituted alkyl refers to an alkyl group substituted with substituents. By way of example only, substituents for alkyl and heteroalkyl radicals (including those groups referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) includes, but is not limited to: -OR, =O, =NR, =N-OR, -NR2, -SR, -halogen, -SiR3, -OC(O)R, -C(O)R, -CO2R, -CONR2, -OC(O)NR2, - NRC(O)R, -NRC(O)NR2, -NR(O)2R, -NR-C(NR2)=NR, -S(O)R, -S(O)2R, -S(O)2NR2, -NRSO2R, -CN, –NO₂, -R, -N₃, -ONH₂, -CH(Ph)₂, fluoro(C₁-C₄)alkoxy, fluoro(C₁-C₄)alkyl, a sugar, in a number ranging from zero to the total number of open valences on the alkyl or heteroalkyl group, and wherein each R group in the preceding list includes, but is not limited to, hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, including but not limited to, aryl substituted with 1-3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups, or aralkyl groups. When two R groups are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5-, 6-, or 7-membered ring. For example, -NR2 is meant to include, but not be limited to, 1-pyrrolidinyl and 4-morpholinyl. By way of example, substituents for aryl and heteroaryl groups (including those groups referred to as arylene) include, but are not limited to, -OR, =O, =NR, =N-OR, -NR2, -SR, -halogen, -SiR₃, -OC(O)R, -C(O)R, -CO₂R, -CONR₂, -OC(O)NR₂, -NRC(O)R, -NRC(O)NR₂, -NR(O)₂R, - NR-C(NR2)=NR, -S(O)R, -S(O)2R, -S(O)2NR2, -NRSO2R, -CN, –NO2, -R, -N3, -ONH2, -CH(Ph)2, WSGR Ref. No 31362-825.601 fluoro(C₁-C₄)alkoxy, fluoro(C₁-C₄)alkyl, a sugar, in a number ranging from zero to the total number of open valences on the aromatic ring system; and wherein each R group in the preceding list includes, but is not limited to, and is independently selected from hydrogen, alkyl, halogen, heteroalkyl, aryl and heteroaryl. The term “therapeutically effective amount,” as used herein, refers to the amount of a composition containing at least one non-natural amino acid polypeptide and/or at least one modified non-natural amino acid polypeptide administered to a patient already suffering from a disease, condition or disorder, sufficient to cure or at least partially arrest, or relieve to some extent one or more of the symptoms of the disease, disorder or condition being treated. The effectiveness of such compositions depends on conditions including, but not limited to, the severity and course of the disease, disorder or condition, previous therapy, the patient's health status and response to the drugs, and the judgment of the treating physician. By way of example only, therapeutically effective amounts may be determined by routine experimentation, including but not limited to a dose escalation clinical trial. The term “toxic”, or “toxic moiety” or “toxic group” or “cytotoxic” or “cytotoxic payload” or “payload” or “cytotoxic drug” or “drug” as used herein, refers to a cytotoxic compound which can cause harm, disturbances, or death. Toxic moieties include, but are not limited to, a drug comprising or consisting of an aurastatin analog of the present disclosure. In other aspects the cytotoxic agent is an agent that disrupts tubulin polymerization. The terms “treat,” “treated,” “treating” or “treatment”, as used herein, include alleviating, preventing, abating or ameliorating a disease or condition symptoms, preventing additional symptoms, ameliorating or preventing the underlying metabolic causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition. The terms “treat,” “treated,” “treating” or “treatment”, include, but are not limited to, prophylactic and/or therapeutic treatments. The term “treat”, “treated,” “treating”, or “treatment” can refer to the decrease, reduction or amelioration of one or more symptoms or conditions or diseases associated with an antigen related or associated cancer. The term “treat”, “treated,” “treating”, or “treatment” can refer to the administration of an ADC of the present disclosure to a subject in need thereof to decrease, reduce, improve, alter, relieve, affect or ameliorate an antigen related or associated cancer or disease or symptom or condition, or the predisposition toward a condition. The term "capable of specific binding" refers to protein or peptide (e.g., antibody) binding to a predetermined target substance (e.g., an antigen and/or groups of antigens), e.g. a target substance WSGR Ref. No 31362-825.601 that is expressed on the surface of a cell; thus the term "binding to a target cell" or "binding to a cancer cell" is to be understand as referring to protein or peptide (e.g., antibody) binding to a predetermined target substance (e.g. antigen or antigens) that is expressed on such a cell. Typically, the protein or peptide (e.g., antibody) binds with an affinity of at least about lx10⁷ M1, and/or binds to the predetermined target substance (e.g., antigen, antigens or cell) with an affinity that is at least two-fold greater than its affinity for binding to a non-specific control substance (e.g., BSA, casein, non-cancer cells) other than the predetermined target substance or a closely-related target substance. As used herein, the term “water soluble polymer” refers to any polymer that is soluble in aqueous solvents. Such water soluble polymers include, but are not limited to, polyethylene glycol, polyethylene glycol propionaldehyde, mono C1-C10 alkoxy or aryloxy derivatives thereof (described in U.S. Patent No. 5,252,714 which is incorporated by reference herein), monomethoxy-polyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol, polyamino acids, divinylether maleic anhydride, N-(2-Hydroxypropyl)-methacrylamide, dextran, dextran derivatives including dextran sulfate, polypropylene glycol, polypropylene oxide/ethylene oxide copolymer, polyoxyethylated polyol, heparin, heparin fragments, polysaccharides, oligosaccharides, glycans, cellulose and cellulose derivatives, including but not limited to methylcellulose and carboxymethyl cellulose, serum albumin, starch and starch derivatives, polypeptides, polyalkylene glycol and derivatives thereof, copolymers of polyalkylene glycols and derivatives thereof, polyvinyl ethyl ethers, and alpha-beta-poly[(2-hydroxyethyl)-DL-aspartamide, and the like, or mixtures thereof. By way of example only, coupling of such water soluble polymers to natural amino acid polypeptides or non-natural polypeptides may result in changes including, but not limited to, increased water solubility, increased or modulated serum half-life, increased or modulated therapeutic half-life relative to the unmodified form, increased bioavailability, modulated biological activity, extended circulation time, modulated immunogenicity, modulated physical association characteristics including, but not limited to, aggregation and multimer formation, altered receptor binding, altered binding to one or more binding partners, and altered receptor dimerization or multimerization. In addition, such water soluble polymers may or may not have their own biological activity. Antibodies and Antibody Sequences The present invention provides novel ADCs comprising antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids incorporated at any desired position in the heavy and/or light chain amino acid sequence. Further, the present invention provides ADCs comprising one or more antibodies, antibody fragments or variants WSGR Ref. No 31362-825.601 thereof engineered to have one or more non-naturally encoded amino acids site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. In some embodiments, the antibody, antibody fragment or variant thereof binds to an antigen, e.g., a tumor-associated antigen (TAA). In some embodiments, the TAA is selected from the group consisting of PSMA, CD70, CD3, HER2, HER3, TROP2, PD-I, PDL-1, VEGFR, EGFR, c-Met (HGFR), CD19, CD22, CD24, CD25 (IL-2R alpha), CD30, CD33, CD37, CD38, CD44, CD46, CD47, CD48, CD52, CD56 (NCAM-1), CD71 (Transferrin R), CD74, CD79b, CD96, CD97, CD99, CD123 (IL-3R alpha), CD138 (syndecan-1), CD142, CD166 (ALCAM), CD179, CD203c (ENPP3), TIMI, CD205 (LY75), CD221 (IGF-1R), CD223, CD262 (TRAIL R2), CD276 (B7-H3), mesothelin, EpCAM, MUCI, MUC16 (CA-125), GPC3, CEA, CEACAM5, CEACAM6, CA9, DLL3, ROR1, ROR2, GPNMB, GCC, GUCY2c, NaPi2b, Flt-1, Flt-3, FOLR1 (folate receptor alpha), Tissue Factor (TF), CA6, BCMA, SLAMF7 (CS1), TIM1, CanAg, Ckit (CD117), EphA2, Nectin4, SLTRK6, FGFR2, LYPD3 (C4.4a), Cadherin 3, Cadherin 6, 5T4 (TPBG), STEAP1, PTK7, Ephrin-A4, SLC34A2, LIV-1 (SLC39A6 or ZIP6), SLC1A5, TENB2, ETBR, integrin v3, Cripto, AGS-5 (SLC44A4), LY6E, SLITRK6, AXL, LAMP1, LRRC15, TNF-alpha, CTLA-4 and MN/CA IX antibody, antibody fragment or variant. In some embodiments, the antibody, antibody fragment or variant thereof is TROP2 antibody, antibody fragment or variant. In some embodiments, the antibody, antibody fragment or variant thereof is HER2 antibody, antibody fragment or variant. In some embodiments, the antibody, antibody fragment or variant thereof is HER3 antibody, antibody fragment or variant. In some embodiments, the antibody, antibody fragment or variant thereof is PSMA antibody, antibody fragment or variant. In some embodiments, the antibody, antibody fragment or variant thereof is CD70 antibody, antibody fragment or variant. In other embodiments the invention provides anti-TROP2 ADCs comprising antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids incorporated at any desired position in the heavy and/or light chain amino acid sequence. In some embodiments, the present invention provides anti-TROP2 ADCs comprising one or more antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. In other embodiments the invention provides anti-HER2 ADCs comprising antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids incorporated at any desired position in the heavy and/or light chain amino acid sequence. In some embodiments, the present invention provides anti-HER2 ADCs comprising one or more antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids WSGR Ref. No 31362-825.601 site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. In other embodiments the invention provides anti-HER3 ADCs comprising antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids incorporated at any desired position in the heavy and/or light chain amino acid sequence. In some embodiments, the present invention provides anti-HER3 ADCs comprising one or more antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. In other embodiments the invention provides anti-PSMA ADCs comprising antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids incorporated at any desired position in the heavy and/or light chain amino acid sequence. In some embodiments, the present invention provides anti-PSMA ADCs comprising one or more antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. In other embodiments the invention provides anti-CD70 ADCs comprising antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids incorporated at any desired position in the heavy and/or light chain amino acid sequence. In some embodiments, the present invention provides anti-CD70 ADCs comprising one or more antibodies, antibody fragments or variants thereof engineered to have one or more non-naturally encoded amino acids site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. Antibody or antibody fragments or variants of the disclosure may be human, humanized, engineered, non-human, and/or chimeric antibody or antibody fragments. An antibody or antibody fragment or variant provided herein may comprise two or more amino acid sequences. A first amino acid sequence may comprise a first antibody chain and a second amino acid sequence may comprise a second antibody chain. A first antibody chain may comprise a first amino acid sequence, and a second antibody chain may comprise a second amino acid sequence. A chain of an antibody may refer to an antibody heavy chain, an antibody light chain, or a combination of a region or all of an antibody heavy chain and a region or all of an antibody light chain. As a non- limiting example, an antibody provided herein comprises a heavy chain or fragment or variant thereof, and a light chain or fragment or variant thereof. Two amino acid sequences of an antibody, including two antibody chains, may be connected, attached, or linked by one or more disulfide bonds, a chemical linker, a peptide linker, or a combination thereof. A chemical linker includes a WSGR Ref. No 31362-825.601 linker via a non-natural amino acid. A chemical linker includes a linker via one or more non- natural amino acids. A chemical linker can include a chemical conjugate. A peptide linker includes any amino acid sequence joining the two amino acid sequences. The peptide linker may comprise 1 or more, 5 or more, 10 or more, 15 or more, 20 or more, 25 or more, 30 or more, 35 or more, 40 or more, 45 or more, 50 or more, 55 or more, 60 or more, 65 or more, 70 or more, 75 or more, 80 or more, 85 or more, 90 or more, 95 or more, 100 or more amino acids. The peptide linker may comprise less than 5, less than 10, less than 15, less than 20, less than 25, less than 30, less than 35, less than 40, less than 45, less than 50, less than 75 or less than 100 amino acids. The peptide linker may be a portion of any antibody, including a domain of an antibody, such as a variable domain, CH1, CH2, CH3, and/or CL domain. In some embodiments a heavy and a light chain are connected, attached, or linked, for example, via a peptide linker. In some cases, a heavy chain and a light chain are connected, for example, by one or more disulfide bonds. Antibodies, antibody fragments and antibody variants of the disclosure may interact or engage with an antigen on an effector cell. The effector cell can include, but is not limited to, an immune cell, a genetically modified cell having increase or decrease cytotoxic activity, a cell involved in the host defense mechanism, an anti-inflammatory cell, a leukocyte, a lymphocyte, a macrophage, an erythrocyte, a thrombocyte, a neutrophil, a monocyte, an eosinophil, a basophil, a mast cell, a NK cell, a B-cell, or a T-cell. In some embodiments the immune cell may be a T cell such as a cytotoxic T cell or natural killer T cell. The antibody or antibody fragment may interact with a receptor on a T-cell such as, but not limited to a T-cell receptor (TCR). The TCR may comprise TCR alpha, TCR beta, TCR gamma, and/or TCR delta or TCR zeta. Antibody or antibody fragments of the disclosure may bind to a receptor on a lymphocyte, dendritic cell, B- cell, macrophage, monocytes, neutrophils and/or NK cells. Antibody or antibody fragments of the disclosure may bind to a cell surface receptor. Antibody or antibody fragments of the disclosure may bind to an antigen receptor, such as for example, a TROP2 antigen receptor, or a HER2 antigen receptor, or a HER3 antigen receptor, or a PSMA antigen receptor, or a CD70 antigen receptor. Antibody or antibody fragments of the disclosure can be conjugated to a T-cell surface antigen. Some cell surface antigens have a high overexpression pattern in a large number of tumors, making them excellent targets in the development of ADCs. Thus, the present disclosure provides novel anti-TROP2 antibodies, anti-HER2 antibodies, anti-HER3 antibodies, anti-PSMA antibodies, anti-CD70 antibodies, or the corresponding antibody fragments, and antibody-drug conjugates thereof for use as therapeutic agents. Disclosed herein are novel anti-TROP2 antibodies, antibody fragments or variants thereof; anti-HER2 antibodies, antibody fragments or WSGR Ref. No 31362-825.601 variants thereof; anti-HER3 antibodies, antibody fragments or variants thereof; anti-PSMA antibodies, antibody fragments or variants thereof; and anti-CD70 antibodies, antibody fragments or variants thereof; each with at least one non-naturally encoded amino acid or unnaturally encoded amino acid. The present invention provides anti-TROP2 antibodies, antibody fragments or variants thereof; anti-HER2 antibodies, antibody fragments or variants thereof; anti-HER3 antibodies, antibody fragments or variants thereof; anti-PSMA antibodies, antibody fragments or variants thereof; and anti-CD70 antibodies, antibody fragments or variants thereof; each having a non-naturally encoded amino acid that facilitate antibody conjugation to a drug (e.g., a drug, payload, toxin molecule). Antibodies, antibody fragments or variants provided in the present disclosure may be human, humanized, engineered, non-human, and/or chimeric antibody or antibody fragments that bind to the extracellular domain of the target antigen, which can be overexpressed in a number of cancers. Thus, novel antibodies, compositions and antibody drug conjugates for the treatment and/or diagnosis of antigen-expressing cancers are beneficial, including but not limited to TROP2 -expressing cancers, HER2-expressing cancers, HER3-expressing cancers, PSMA-expressing cancers and CD70-expressing cancers. Antibodies or antibody fragments or variants disclosed herein include, but are not limited to, analogs, isoforms, mimetics, fragments, or hybrids of TROP2, HER2, HER3, PSMA and CD70. Antibodies or antibody fragments or variants of TROP2, HER2, HER3, PSMA and CD70 of the present disclosure include but are not limited to Fv, Fc, Fab, and (Fab')₂, single chain Fv (scFv), diabodies, triabodies, tetrabodies, bifunctional hybrid antibodies, CDR1, CDR2, CDR3, combinations of CDRs, variable regions, framework regions, constant regions, heavy chains, light chains, alternative scaffold non-antibody molecules, bispecific antibodies and the like. Antibodies comprising non-natural amino acids are also disclosed herein. In certain embodiments, the antibody or antibody fragments or variants include but are not limited to Fv, Fc, Fab, and (Fab')₂, single chain Fv (scFv), diabodies, triabodies, tetrabodies, bifunctional hybrid antibodies, CDR1, CDR2, CDR3, combinations of CDRs, variable regions, framework regions, constant regions, heavy chains, light chains, alternative scaffold non-antibody molecules, bispecific antibodies and the like. In some embodiments, the antibody or antibody fragment or variant comprises one or more non-naturally encoded amino acids. In some embodiments, the anti-TROP2, or anti-HER2, or anti-HER3, or anti-PSMA, or anti-CD70, antibody or antibody fragment or variant comprises one or more non-naturally encoded amino acids. WSGR Ref. No 31362-825.601 Non-limiting examples of antibodies or antibody fragments or variants of the present disclosure comprise the sequences listed in Tables 1 to 5. Table 1. Anti-TROP2 amino acid sequences, including sequences with Amber sites for non-natural amino acid incorporation. Also disclosed are: all of the sequences in Table 1, wherein X is replaced by any non-natural amino acid; all of the sequences in Table 1, wherein any amino acid is replaced by any non-natural amino acid; all of the sequences in Table 1, wherein X is pAF; all of the heavy chain sequences in Table 1, wherein a non-natural amino acid is site specifically incorporated at position 114, according to Kabat numbering, as well known to the skilled artisan); and all of the heavy chain sequences in Table 1, wherein EEM is replaced with DEL. WT: Wild Type; HC: Heavy Chain; LC: Light Chain; X denotes non-natural amino acid.

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Table 2. Anti-CD70 amino acid sequences, including sequences with Amber sites for non-natural amino acid incorporation. Also disclosed are: all of the sequences in Table 2, wherein X is replaced by any non-natural amino acid; all of the sequences in Table 2, wherein any amino acid is replaced by any non-natural amino acid; all of the sequences in Table 2, wherein X is pAF; all of the heavy chain sequences in WSGR Ref. No 31362-825.601 Table 2, wherein a non-natural amino acid is site specifically incorporated at position 114, according to Kabat numbering, as well known to the skilled artisan; and all of the heavy chain sequences in Table 2, wherein EEM is replaced with DEL. WT: Wild Type; HC: Heavy Chain; LC: Light Chain; X denotes non-natural amino acid.

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Table 3. Anti-HER2 amino acid sequences, including sequences with amber sites for non-natural amino acid incorporation. Also disclosed are: all of the sequences in Table 3, wherein X is replaced by any non-natural amino acid; all of the sequences in Table 3, wherein any amino acid is replaced by any non-natural amino acid; all of the sequences in Table 3, wherein X is pAF; all of the heavy chain sequences in Table 3, wherein a non-natural amino acid is site specifically incorporated at position 114, according to Kabat numbering, as well known to the skilled artisan; and all of the heavy chain sequences in Table 3, wherein DEL is replaced with EEM. WT: Wild Type; HC: Heavy Chain; LC: Light Chain; X denotes non-natural amino acid.

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Table 4. Anti-PSMA amino acid sequences, including sequences with amber sites for non-natural amino acid incorporation. Also disclosed are: all of the sequences in Table 4, wherein X is replaced by any non-natural amino acid; all of the sequences in Table 4, wherein any amino acid is replaced by any non-natural amino acid; all of the sequences in Table 4, wherein X is pAF; all of the heavy chain sequences in Table 4, wherein a non-natural amino acid is site specifically incorporated at position 114, according to Kabat numbering, as well known to the skilled artisan; and all of the heavy chain sequences in Table 4, wherein DEL is replaced with EEM. WT: Wild Type; HC: Heavy Chain; LC: Light Chain; X denotes non-natural amino acid.

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Table 5. Anti-HER3 amino acid sequences, including sequences with amber sites for non-natural amino acid incorporation. Also disclosed are: all of the sequences in Table 5, wherein X is replaced by any non-natural amino acid; all of the sequences in Table 5, wherein any amino acid is replaced by any non-natural amino acid; all of the sequences in Table 5, wherein X is pAF; all of the heavy chain sequences in Table 5, wherein a non-natural amino acid is site specifically incorporated at position 114, according to Kabat numbering, as well known to the skilled artisan; and all of the heavy chain sequences of Table 5, wherein EEM is replaced with DEL. WT: Wild Type; HC: Heavy Chain; LC: Light Chain; X denotes non-natural amino acid.

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Non-Natural Amino Acids The present disclosure provides antibodies, antibody fragments or variants comprising at least one non-naturally encoded amino acid. Introduction of at least one non-naturally encoded amino acid into an antibody can allow for the application of conjugation chemistries that involve specific chemical reactions with one or more non-naturally encoded amino acids while not reacting with the commonly occurring 20 amino acids. Non-naturally encoded amino acid site selection was based on surface exposure/site accessibility within the antibody and hydrophobic or neutral amino acid sites were selected to maintain the charge on the antibody. Methods for introducing non-natural amino acids inserted into sites in a protein are described for example in WO2010/011735 and in WO2005/074650, the entire contents of each of which are hereby incorporated by reference herein in their entirety. The present disclosure employs such methodologies and techniques. The non-natural amino acids used in the methods and compositions described herein have at least one of the following four properties: (1) at least one functional group on the sidechain of the non-natural amino acid has at least one characteristics and/or activity and/or reactivity orthogonal to the chemical reactivity of the 20 common, genetically-encoded amino acids (i.e., alanine, arginine, asparagine, aspartic acid, WSGR Ref. No 31362-825.601 cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine), or at least orthogonal to the chemical reactivity of the naturally occurring amino acids present in the polypeptide that includes the non-natural amino acid; (2) the introduced non-natural amino acids are substantially chemically inert toward the 20 common, genetically-encoded amino acids; (3) the non-natural amino acid can be stably incorporated into a polypeptide, preferably with the stability commensurate with the naturally-occurring amino acids or under typical physiological conditions, and further preferably such incorporation can occur via an in vivo system; and (4) the non-natural amino acid includes an oxime functional group or a functional group that can be transformed into an oxime group by reacting with a reagent, preferably under conditions that do not destroy the biological properties of the polypeptide that includes the non-natural amino acid (unless of course such a destruction of biological properties is the purpose of the modification/transformation), or where the transformation can occur under aqueous conditions at a pH between about 4 and about 8, or where the reactive site on the non-natural amino acid is an electrophilic site. Any number of non-natural amino acids can be introduced into the polypeptide. Non-natural amino acids may also include protected or masked oximes or protected or masked groups that can be transformed into an oxime group after deprotection of the protected group or unmasking of the masked group. Non- natural amino acids may also include protected or masked carbonyl or dicarbonyl groups, which can be transformed into a carbonyl or dicarbonyl group after deprotection of the protected group or unmasking of the masked group and thereby are available to react with aminooxy group to form oxime groups. Oxime-based non-natural amino acids may be synthesized by methods well known in the art, (see for example WO2013/185117 and WO2005/074650; , the entire contents of each of which are hereby incorporated by reference herein in their entirety), including: (a) reaction of an aminooxy-containing non-natural amino acid with a carbonyl- or dicarbonyl-containing reagent; (b) reaction of a carbonyl- or dicarbonyl-containing non-natural amino acid with an aminooxy-containing reagent; or (c) reaction of an oxime-containing non-natural amino acid with certain carbonyl- or dicarbonyl-containing reagents. In some embodiments, non-naturally encoded amino acid site selection is based on surface exposure. Example, one possible site is an amino acid having a solvent accessible surface area ratio of 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more. In some embodiments, one possible site is an amino acid having a solvent accessible surface area ratio of about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 95%, or more. The solvent accessible surface area can be calculated based on the DSSP program [Biopolymers, 22, 2577-2637 (1983)], using a crystalline WSGR Ref. No 31362-825.601 structure analyzing data file of antibodies or antibody fragments registered in Protein Data Bank (PDB). The ratio of the solvent accessible surface area of the amino acid residues of interest can be calculated by dividing the antibody structural solvent accessible surface area calculated in the above by the solvent accessible surface area of alanine-X-alanine (X represents the amino acid residues of interest). In this connection, there is a case in which two or more PDB files are present on one species of protein, and any one of them can be used in the present invention. Alternatively, the solvent accessibility of an amino acid can be determined by a solvent accessibility test in which a functional group on the amino acid (a thiol, amino, or carbonyl group) is functionalized when treated with an electrophilic reagent or a nucleophilic reagent, or the like. Based on the test results, the functional group (i.e., the thiol, amino, or carbonyl group) can be called, for example, at least 50% solvent accessible when at least 50% of the functional group is functionalized in the test. In some embodiments, the non-naturally encoded amino acid site is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% solvent accessible. Examples of solvent accessibility test reacting with a surface thiol group, etc. None-natural amino acids that may be used in the methods and compositions described herein include, but are not limited to, amino acids comprising amino acids with novel functional groups, amino acids that covalently or noncovalently interact with other molecules, glycosylated amino acids such as a sugar substituted serine, other carbohydrate modified amino acids, keto- containing amino acids, aldehyde-containing amino acids, amino acids comprising polyethylene glycol or other polyethers, heavy atom substituted amino acids, chemically cleavable and/or photocleavable amino acids, amino acids with an elongated side chains as compared to natural amino acids, including but not limited to, polyethers or long chain hydrocarbons, including but not limited to, greater than about 5 or greater than about 10 carbons, carbon-linked sugar- containing amino acids, redox-active amino acids, amino thioacid containing amino acids, and amino acids comprising one or more toxic moiety In some embodiments disclosed herein are antibodies comprising one or more non- naturally encoded amino acids. The one or more non-natural amino acids may be encoded by a codon that does not code for one of the twenty natural amino acids. The one or more non-natural amino acids may be encoded by a nonsense codon (stop codon). The stop codon may be an amber codon. The amber codon may comprise a UAG sequence. The stop codon may be an ochre codon. The ochre codon may comprise a UAA sequence. The stop codon may be an opal or umber codon. WSGR Ref. No 31362-825.601 The opal or umber codon may comprise a UGA sequence. The one or more non-natural amino acids may be encoded by a four-base codon Non-natural amino acids of the present disclosure include, but are not limited to, 1) substituted phenylalanine and tyrosine analogues, such as 4-amino-L-phenylalanine, 4-acetyl-L- phenylalanine, 4-azido-L-phenylalanine, 4-nitro-L-phenylalanine, 3-methoxy-L-phenylalanine, 4-isopropyl-L-phenylalanine, 3-nitro-L-tyrosine, O-methyl-L-tyrosine and O-phosphotyrosine; 2) amino acids that can be photo-cross-linked, e.g., amino acids with aryl azide or benzophenone groups, such as 4-azidophenylalanine or 4-benzoylphenylalanine; 3) amino acids that have unique chemical reactivity, such as 4-acetyl-L-phenylalanine, 3-acetyl-L-phenylalanine, O-allyl-L- tyrosine, O-2-propyn-1-yl-L-tyrosine, N-(ethylthio)thiocarbonyl-L-phenylalanine and p-(3- oxobutanoyl)-L-phenylalanine; 4) heavy-atom-containing amino acids, e.g., for phasing in X-ray crystallography, such as 4-iodo-L-phenylalanine or 4-bromo-L-phenylalanine; 5) a redox-active amino acid, such as 3,4-dihydroxy-L-phenylalanine; 6) a fluorinated amino acid, such as a 2- fluorophenylalanine (e.g., 2-fluoro-L-phenylalanine), a 3-fluorophenylalanine (e.g., 3-fluoro-L- phenylalanine) or a 4-fluorophenylalanine (e.g., 4-fluoro-L-phenylalanine; 7) a fluorescent amino acid, such as an amino acid containing a naphthyl, dansyl or 7-aminocoumarin side chain; 8) a photocleavable or photoisomerizable amino acid, such as an amino acid comprising an azobenzyl 2³ amino acid); 10) a homo-amino acid, such as homoglutamine (e.g., beta- homoglutamine) or homophenylalanine (e.g., beta-homophenylalanine); 11) a proline or pyruvic acid derivative; 12) a 3-substituted alanine derivative; 14) a glycine derivative; 15) a linear core amino acid; 16) a diamino acid; 17) a D-amino acid; 18) an N-methyl amino acid; 19) a phosphotyrosine mimetic, such as a carboxymethylphenylalanine (pCmF) (e.g., 4-carboxymethyl- L-phenylalanine); 20) 2-aminooctanoic acid; and 21) an amino acid comprising a saccharide moiety, such as N-acetyl-L-glucosaminyl-L-serine, beta-N-acetylglucosamine-O-serine, N- acetyl-L-galactosaminyl-L-serine, alpha-N-acetylgalactosamine-O-serine, O-(3-O-D-galactosyl- N-acetyl-beta-D-galactosaminyl)-L-serine, N-acetyl-L-glucosaminyl-L-threonine, alpha-N- acetylgalactosamine-O-threonine, 3-O-(N-acetyl-beta-D-glucosaminyl)-L-threonine, N-acetyl-L- L-serine; an amino acid wherein the naturally-occurring N- or O- linkage between the amino acid and the saccharide is replaced by a covalent linkage not commonly found in nature, including but not limited to, an alkene, an oxime, a thioether, an amide and the like; or an amino acid containing saccharides that are not commonly found in naturally-occurring polypeptides, such as 2-deoxy- glucose, 2-deoxy-galactose and the like. Specific examples of non-natural amino acids include, WSGR Ref. No 31362-825.601 but are not limited to, a p-acetylphenylalanine (4-acetyl phenylalanine) (including 4-acetyl-L- phenylalanine, also referred to herein as p-acetyl-L-phenylalanine (pAF)), para-(2-azidoethoxy)- L-phenylalanine ((S)-2-amino-3-(4-(2-azidoethoxy)phenyl)propanoic acid), a 4- boronophenylalanine (pBoF) (e.g., 4-borono-L-phenylalanine, a 4-propargyloxyphenylalanine (pPrF) (e.g., 4-propargyloxy-L-phenylalanine), an O-methyltyrosine (e.g., O-methyl-L-tyrosine), a 3-(2-naphthyl)alanine (NapA) (e.g., 3-(2-naphthyl)-L-alanine), a 3-methylphenylalanine (e.g., 3-methyl-L-phenylalanine), an O-allyltyrosine (e.g., O-allyl-L-tyrosine), an O-isopropyltyrosine (e.g., O-isopropyl-L-tyrosine), a dopamine (e.g., L-Dopa), a 4-isopropylphenylalanine (e.g., 4- isopropyl-L-phenylalanine), a 4-azidophenylalanine (pAz) (e.g., 4-azido-L-phenylalanine), a 4- benzoylphenylalanine (pBpF) (e.g., 4-benzoyl-L-phenylalanine), an O-phosphoserine (e.g., O- phospho-L-serine), an O-phosphotyrosine (e.g., O-phospho-L-tyrosine), a 4-iodophenylalanine (pIF) (e.g., 4-iodo-L-phenylalanine, a 4-bromophenylalanine (e.g., 4-bromo-L-phenylalanine), a 4-aminophenylalanine (e.g., 4-amino-L-phenylalanine), a 4-cyanophenylalanine (pCNF) (e.g., 4- cyano-L-phenylalanine, a (8-hydroxyquinolin-3-yl)alanine (HQA) (e.g., (8-hydroxyquinolin-3- yl)-L-alanine), a (2,2-bipyridin-5-yl)alanine (BipyA) (e.g., (2,2-bipyridin-5-yl)-L-alanine), and the like. Additional non-natural amino acids are disclosed in Liu et al. (2010) Annu Rev Biochem, 79:413-44; Wang et al. (2005) Angew Chem Int Ed, 44:34-66; and Published International Application Nos.: WO 2012/166560, WO 2012/166559, WO 2011/028195, WO 2010/037062, WO 2008/083346, WO 2008/077079, WO 2007/094916, WO 2007/079130, WO 2007/070659 and WO 2007/059312, the entire contents of each of which are hereby incorporated by reference herein in their entirety. In some embodiments, the one or more non-natural amino acids can be p- acetylphenylalanine. In some more particular embodiments, the one or more non-natural amino acids can be p-acetyl-L-phenylalanine (pAF). In some embodiments, one or more non-natural amino acids is selected from the group Acetyl-D-glucosaminyl)asparagine, O-allyltyrosine, alpha-N-acetylgalactosamine-O-serine, alpha-N-acetylgalactosamine-O-threonine, 2-aminooctanoic acid, 2-aminophenylalanine, 3- aminophenylalanine, 4-aminophenylalanine, 2-aminotyrosine, 3-aminotyrosine, 4- azidophenylalanine, 4-benzoylphenylalanine, (2,2-bipyridin-5yl)alanine, 3-boronophenylalanine, 4-boronophenylalanine, 4-bromophenylalanine, p-carboxymethylphenylalanine, 4- carboxyphenylalanine, p-cyanophenylalanine, 3,4-dihydroxyphenylalanine, 4- ethynylphenylalanine, 2-fluorophenylalanine, 3-fluorophenylalanine, 4-fluorophenylalanine, O- (3-O-D-galactosyl-N-acetyl-beta-D-galactosaminyl)serine, homoglutamine, (8-hydroxyquinolin- 3-yl)alanine, 4-iodophenylalanine, 4-isopropylphenylalanine, O-i-propyltyrosine, 3- WSGR Ref. No 31362-825.601 isopropyltyrosine, O-mannopyranosylserine, 2-methoxyphenylalanine, 3-methoxyphenylalanine, 4-methoxyphenylalanine, 3-methylphenylalanine, O-methyltyrosine, 3-(2-naphthyl)alanine, 5- nitrohistidine, 4-nitrohistidine, 4-nitroleucine, 2-nitrophenylalanine, 3-nitrophenylalanine, 4- nitrophenylalanine, 4-nitrotryptophan, 5-nitrotryptophan, 6-nitrotryptophan, 7-nitrotryptophan, 2- nitrotyrosine, 3-nitrotyrosine, O-phosphoserine, O-phosphotyrosine, 4- propargyloxyphenylalanine, O-2-propyn-1-yltyrosine, 4-sulfophenylalanine, para-(2- azidoethoxy)-L-phenylalanine ((S)-2-amino-3-(4-(2-azidoethoxy)phenyl)propanoic acid) and O- sulfotyrosine. In some further embodiments, one or more non-natural amino acids is selected from the group consisting of 4-acetyl-L-phenylalanine (para-acetyl-L-phenylalanine (pAF)), 3-O-(N- allyl-L-tyrosine, alpha-N-acetylgalactosamine-O-L-serine, alpha-N-acetylgalactosamine-O-L- threonine, 2-aminooctanoic acid, 2-amino-L-phenylalanine, 3-amino-L-phenylalanine, 4-amino- L-phenylalanine, 2-amino-L-tyrosine, 3-amino-L-tyrosine, 4-azido-L-phenylalanine, 4-benzoyl- L-phenylalanine, (2,2-bipyridin-5yl)-L-alanine, 3-borono-L-phenylalanine, 4-borono-L- phenylalanine, 4-bromo-L-phenylalanine, p-carboxymethyl-L-phenylalanine, 4-carboxy-L- phenylalanine, p-cyano-L-phenylalanine, 3,4-dihydroxy-L-phenylalanine (L-DOPA), 4-ethynyl- L-phenylalanine, 2-fluoro-L-phenylalanine, 3-fluoro-L-phenylalanine, 4-fluoro-L-phenylalanine, O-(3-O-D-galactosyl-N-acetyl-beta-D-galactosaminyl)-L-serine, L-homoglutamine, (8- hydroxyquinolin-3-yl)-L-alanine, 4-iodo-L-phenylalanine, 4-isopropyl-L-phenylalanine, O-i- propyl-L-tyrosine, 3-isopropyl-L-tyrosine, O-mannopyranosyl-L-serine, 2-methoxy-L- phenylalanine, 3-methoxy-L-phenylalanine, 4-methoxy-L-phenylalanine, 3-methyl-L- phenylalanine, O-methyl-L-tyrosine, 3-(2-naphthyl)-L-alanine, 5-nitro-L-histidine, 4-nitro-L- histidine, 4-nitro-L-leucine, 2-nitro-L-phenylalanine, 3-nitro-L-phenylalanine, 4-nitro-L- phenylalanine, 4-nitro-L-tryptophan, 5-nitro-L-tryptophan, 6-nitro-L-tryptophan, 7-nitro-L- tryptophan, 2-nitro-L-tyrosine, 3-nitro-L-tyrosine, O-phospho-L-serine, O-phospho-L-tyrosine, 4- propargyloxy-L-phenylalanine, O-2-propyn-1-yl-L-tyrosine, 4-sulfo-L-phenylalanine, para-(2- azidoethoxy)-L-phenylalanine ((S)-2-amino-3-(4-(2-azidoethoxy)phenyl)propanoic acid) and O- sulfo-L-tyrosine. In some embodiments, the one or more non-natural amino acids can be p-acetyl- L-phenylalanine (pAF). Thus, in some embodiments, each and every one of the one or more non- natural amino acids is pAF. In certain embodiments of the disclosure, an antibody with at least one non-natural amino acid includes at least one post-translational modification. In one embodiment, the at least one post-translational modification comprises attachment of a molecule including but not limited to, a WSGR Ref. No 31362-825.601 water-soluble polymer, a derivative of polyethylene glycol, a drug, a drug-linker, a linker, a second protein or polypeptide or polypeptide analog, an antibody or antibody fragment, a biologically active agent, a small molecule, or any combination of the above or any other desirable compound or substance, comprising a second reactive group to at least one non-natural amino acid comprising a first reactive group utilizing chemistry methodology that is known to one of ordinary skill in the art to be suitable for the particular reactive groups. For example, the first reactive group is an alkynyl moiety (including but not limited to, the non-natural amino acid p- propargyloxyphenylalanine, where the propargyl group is also sometimes referred to as an acetylene moiety) and the second reactive group is an azido moiety, and [3+2] cycloaddition chemistry methodologies are utilized. In another example, the first reactive group is the azido moiety (including but not limited to, the non-natural amino acid p-azido-L-phenylalanine) and the second reactive group is the alkynyl moiety. In certain embodiments of the modified antibody polypeptide of the present disclosure at least one non-natural amino acid, (including but not limited to, non-natural amino acid containing a keto functional group), comprising at least one post-translational modification is used where the at least one post-translational modification comprises a saccharide moiety. In certain embodiments, the post-translational modification is made in vivo in a eukaryotic cell or in a non-eukaryotic cell. In other embodiments the post-translational modification is made in vitro. In another embodiment, the post-translational modification is made in vitro and in vivo. In some embodiments, the non-natural amino acid may be modified to incorporate a chemical group. In some embodiments the non-natural amino acid may be modified to incorporate a ketone group. The one or more non-natural amino acids may comprise at least one oxime, carbonyl, dicarbonyl, hydroxylamine group or aminooxy group, or a combination thereof. The one or more non-natural amino acids may comprise at least one carbonyl, acyl, dicarbonyl, alkoxy- amine, hydrazine, acyclic alkene, acyclic alkyne, cyclooctyne, aryl/alkyl azide, norbornene, cyclopropene, trans-cyclooctene, or tetrazine functional group or a combination thereof. In some embodiments disclosed herein the non-natural amino acid is site-specifically incorporated into the antibody, antibody fragment or variant. In some embodiments the non- natural amino acid is site-specifically incorporated into an antibody, antibody fragment or variant. Methods for incorporating a non-natural amino acid into a molecule, for example, proteins, polypeptides or peptides, are disclosed in U.S. Patent Nos.: 7,332,571; 7,928,163; 7,696,312; 8,008,456; 8,048,988; 8,809,511; 8,859,802; 8,791,231; 8,476,411; or 9,637,411, (each of which is incorporated herein by reference in its entirety), and in the Examples herein. The one or more non-natural amino acids may be incorporated by methods known in the art. For example, cell- WSGR Ref. No 31362-825.601 based or cell-free systems may be used, and auxotrophic strains may also be used in place of engineered tRNA and synthetase. In certain embodiments, orthogonal tRNA synthetase are used as disclosed in for example, WO2002085923A2; WO2002086075A2; WO2004035743A2; WO2007021297A1; WO2006068802A2; and WO2006069246A2; the contents of each of which are incorporated herein by reference in their entirety. Incorporating one or more non-natural amino acids into the antibody or antibody fragment or variant may comprise modifying one or more amino acid residues in the antibody or antibody fragment or variant. Modifying the one or more amino acid residues in the antibody or antibody fragment or variant may comprise mutating one or more nucleotides in the nucleotide sequence encoding the antibody or antibody fragment or variant. Mutating the one or more nucleotides in the nucleotide sequence encoding the antibody or antibody fragment or variant may comprise altering a codon encoding an amino acid to a nonsense codon. Incorporating one or more non-natural amino acids into the antibody or antibody fragment or variant may comprise modifying one or more amino acid residues in the antibody or antibody fragment or variant to produce one or more amber codons in the antibody or antibody fragment or variant. The one or more non-natural amino acids may be incorporated into the antibody or antibody fragment or variant in response to an amber codon. The one or more non- natural amino acids may be site-specifically incorporated into the antibody or antibody fragment or variant. Incorporating one or more non-natural amino acids into the antibody or antibody fragment or variant may comprise one or more genetically encoded non-natural amino acids with orthogonal chemical reactivity relative to the canonical twenty amino acids to site-specifically modify the biologically active molecule or targeting agent. Incorporating the one or more non- natural amino acids may comprise use of a tRNA/aminoacyl-tRNA synthetase pair to site- specifically incorporate one or more non-natural amino acids at defined sites in the biologically active molecule or targeting agent in response to one or more amber nonsense codon. Additional methods for incorporating non-natural amino acids include, but are not limited to, methods disclosed in Chatterjee et al., Biochemistry, 2013; Kazane et al., J Am Chem Soc, 135(1):340-6, 2013; Kim et al., J Am Chem Soc, 134(24):9918-21, 2012; Johnson et al., Nat Chem Biol, 7(11):779-86, 2011; and Hutchins et al., J Mol Biol, 406(4):595-603, 2011; the entire contents of each of which are hereby incorporated by reference herein in their entirety. The one or more non- natural amino acids may be produced through selective reaction of one or more natural amino acids. The selective reaction may be mediated by one or more enzymes. In non-limiting examples, the selective reaction of one or more cysteines with formylglycine generating enzyme (FGE) may produce one or more formylglycines as described in Rabuka et al., Nature Protocols 7: 1052-1067, 2012. The one or more non-natural amino acids may involve a chemical reaction to form a linker. WSGR Ref. No 31362-825.601 The chemical reaction to form the linker may include a bioorthogonal reaction. The chemical reaction to form the linker may include click chemistry. See for example WO2006/050262, the entire contents of which are hereby incorporated by reference herein in their entirety. Any position of the antibody or antibody fragment is suitable for selection to incorporate a non-natural amino acid, and selection may be based on rational design or by random selection for any or no particular desired purpose. Selection of desired sites may be based on producing a non-natural amino acid polypeptide (which may be further modified or remain unmodified) having any desired property or activity, including but not limited to a receptor binding modulators, receptor activity modulators, modulators of binding to binder partners, binding partner activity modulators, binding partner conformation modulators, dimer or multimer formation, no change to activity or property compared to the native molecule, or manipulating any physical or chemical property of the polypeptide such as solubility, aggregation, or stability. Alternatively, the sites identified as critical to biological activity may also be good candidates for substitution with a non- natural amino acid, again depending on the desired activity sought for the polypeptide. Another alternative would be to simply make serial substitutions in each position on the polypeptide chain with a non-natural amino acid and observe the effect on the activities of the polypeptide. Any means, technique, or method for selecting a position for substitution with a non-natural amino acid into any polypeptide is suitable for use in the methods, techniques and compositions described herein. The structure and activity of naturally-occurring mutants of a polypeptide that contain deletions can also be examined to determine regions of the protein that are likely to be tolerant of substitution with a non-natural amino acid. Once residues that are likely to be intolerant to substitution with non-natural amino acids have been eliminated, the impact of proposed substitutions at each of the remaining positions can be examined using methods including, but not limited to, the three-dimensional structure of the relevant polypeptide, and any associated ligands or binding proteins. X-ray crystallographic and NMR structures of many polypeptides are available in the Protein Data Bank (PDB, see world wide web for rcsb.org), a centralized database containing three-dimensional structural data of large molecules of proteins and nucleic acids, one can be used to identify amino acid positions that can be substituted with non-natural amino acids. In addition, models may be made investigating the secondary and tertiary structure of polypeptides, if three-dimensional structural data is not available. Thus, the identity of amino acid positions that can be substituted with non-natural amino acids can be readily obtained. Exemplary sites of incorporation of a non-natural amino acid include, but are not limited to, those that are excluded from potential receptor binding regions, or regions for binding to WSGR Ref. No 31362-825.601 binding proteins or ligands may be fully or partially solvent exposed, have minimal or no hydrogen-bonding interactions with nearby residues, may be minimally exposed to nearby reactive residues, and/or may be in regions that are highly flexible as predicted by the three-dimensional crystal structure of a particular polypeptide with its associated receptor, ligand or binding proteins A wide variety of non-natural amino acids can be substituted for, or incorporated into, a given position in a polypeptide. By way of example, a particular non-natural amino acid may be selected for incorporation based on an examination of the three-dimensional crystal structure of a polypeptide with its associated ligand, receptor and/or binding proteins, a preference for conservative substitutions. In some instances, incorporation of a non-natural amino acid into a polypeptide (e.g., an antibody or antibody fragment) will be combined with other additions, substitutions, or deletions within the polypeptide to affect other chemical, physical, pharmacologic and/or biological traits. In some cases, the other additions, substitutions or deletions may increase the stability (including but not limited to, resistance to proteolytic degradation) of the polypeptide or increase affinity of the polypeptide for its appropriate receptor, ligand and/or binding proteins. In some cases, the other additions, substitutions or deletions may increase the solubility (including but not limited to, when expressed in E. coli or other host cells) of the polypeptide. In some embodiments, sites are selected for substitution with a naturally encoded or non-natural amino acid in addition to another site for incorporation of a non-natural amino acid for the purpose of increasing the polypeptide solubility following expression in E. coli, or other recombinant host cells. In some embodiments, the polypeptides comprise another addition, substitution, or deletion that modulates affinity for the associated ligand, binding proteins, and/or receptor, modulates (including but not limited to, increases or decreases) receptor dimerization, stabilizes receptor dimers, modulates circulating half-life, modulates release or bio-availability, facilitates purification, or improves or alters a particular route of administration. Similarly, the non-natural amino acid polypeptide can comprise chemical or enzyme cleavage sequences, protease cleavage sequences, reactive groups, antibody- binding domains (including but not limited to, FLAG or poly-His) or other affinity based sequences (including but not limited to, FLAG, poly-His, GST, etc.) or linked molecules (including but not limited to, biotin) that improve detection (including but not limited to, GFP), purification, transport through tissues or cell membranes, prodrug release or activation, size reduction, or other traits of the polypeptide. Linkers In some aspects, the present disclosure provides linkers that are suitable for intracellular delivery of drug payloads from drug conjugates, such as ADCs. The linkers of the present WSGR Ref. No 31362-825.601 disclosure include linkers that are joined to, or that are capable of being joined to, drugs to provide drug-linker compounds. The linkers of the present disclosure also include linkers that are joined to, or are capable of being joined to, drugs and antibodies, to provide ADCs. As disclosed herein, a linker can be any multivalent group that connects, or is capable of connecting, a first group to at least one other group. The linker can serve as a spacer between the first group and the second group. A linker (or “L”) of the present disclosure can be a bivalent, trivalent or tetravalent group comprising, or consisting of, at least one moiety (“linker moiety”), In some embodiments, a linker connects a first group (e.g., a drug or payload) to a reactive moiety, wherein the reactive moiety is capable of reacting with a second group (e.g., biologically active polypeptide or protein). In some embodiments, the linker comprises the reactive moiety that is capable of reacting with the second group. In some embodiments, the biologically active polypeptide or protein contains at least one non-naturally encoded amino acid. Thus, in some embodiments, the reactive moiety is capable of reacting with a non-naturally encoded amino acid of the biologically active polypeptide or protein. In some embodiments, the biologically active polypeptide or protein is an antibody. In some embodiments, a linker connects a first group (e.g., a drug or payload) to a second group (e.g., biologically active polypeptide or protein). The linker can be connected (e.g., covalently bound) to the first group and/or the second group via a linkage or adduct moiety. In some embodiments, a linker connects a first group and a second group, wherein the first group is a drug or payload, and the second group is a biologically active polypeptide or protein. In some embodiments, the biologically active polypeptide or protein contains at least one non-naturally encoded amino acid. In some embodiments, the linker connects the drug or payload to a non- naturally encoded amino acid of the biologically active polypeptide or protein. In some embodiments, the biologically active polypeptide or protein is an antibody. Thus, the antibody connected to a drug or payload via a linker can be an antibody-drug conjugate (ADC), such as an ADC of the present disclosure. A linker of the present disclosure can be functionalized for desired utility, including payload release properties in vivo. In some aspects, linkers can be substantially resistant to cleavage (e.g., stable linkers or non-cleavable linkers). Alternatively, linkers of the present disclosure can be cleavable linkers, which can be susceptible to cleavage under conditions, including but not limited to acid-induced cleavage, photo-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, disulfide bond cleavage, and so on. In some embodiments, a cleavable linker comprises a cleavable moiety such as a disulfide, a glucuronidase-cleavable moiety, a peptide and/or a phosphate-containing moiety. In some preferred embodiments, the drug WSGR Ref. No 31362-825.601 or payload and the biologically active polypeptide or protein that are connected by the linker remain active under the linker cleavage conditions (e.g., the drug or payload retains its cytotoxic activity, and the biologically active polypeptide or protein retains its desired functionality, such as its ability to selectively bind to a target antigen). Some linkers, including but not limited to phosphate-based linkers, can have a differentiated and tunable stability in blood compared to the intracellular environment (e.g. lysosomal compartment). Thus, ADCs comprising such linkers are stable in circulation (plasma/blood) but reactive or cleavable in intracellular compartments (lysosome) making them useful for intracellular delivery of drug conjugates. Thus, the linker design, stability, pH, redox sensitivities and protease susceptibility influence circulatory stability and release of the drug or payload. Methods for designing and selecting linkers are well known in the art. Linkers may be designed de novo, including by way of example only, as part of high-throughput screening process (in which case numerous linkers may be designed, synthesized, characterized and/or tested) or based on the interests of the researcher. The linker may also be designed based on the structure of a known or partially characterized polypeptide to which the linker is connected. The principles for selecting which amino acid(s) to substitute and/or modify and the choice of which modification to employ are described in, e.g., WO2013/185117. Linkers may be designed to meet the needs of the experimenter or end user. Such needs may include, but are not limited to, manipulating the therapeutic effectiveness of the polypeptide, improving the safety profile of the polypeptide, adjusting the pharmacokinetics, pharmacologics and/or pharmacodynamics of the polypeptide, such as, by way of example only, increasing water solubility, bioavailability, increasing serum half-life, increasing therapeutic half-life, modulating immunogenicity, modulating biological activity, or extending the circulation time. In addition, such modifications include, by way of example only, providing additional functionality to the polypeptide, such as an antibody, and any combination of the aforementioned modifications. Additionally, many procedures and linker molecules for attachment of various compounds to peptides are known. See, for example, European Patent Application No. 0188256; U.S. Patent Nos. 4,671,958, 4,659,839, 4,414,148, 4,699,784, 4,680,338, 4,569,789 and 10,550,190; PCT Application Publication Nos. WO 2012/166559 A1, WO 2012/166560 A1, WO 2013/185117 A1, WO 2013/192360 A1 and WO 2022/040596 A1; and US Patent Application Publication No. US 2017/0182181 A1; the contents of each of which are hereby incorporated by reference in their entirety. In some embodiments, a linker is a bivalent linker. In some embodiments, the bivalent linker connects, or is capable of connecting, a first group and a second group. In some other embodiments, the linker is a trivalent linker. In some embodiments, the trivalent linker connects, WSGR Ref. No 31362-825.601 or is capable of connecting, a first group, a second group and a third group. In some embodiments, the linker is a tetravalent linker. In some embodiments, the tetravalent linker connects, or is capable of connecting, a first group, a second group, a third group and a fourth group. In some embodiments, a linker is a bond. In some other embodiments, a linker is not a bond. In some embodiments, a linker is linear. In other embodiments, a linker is branched. In some embodiments, the linker is a unit that is combinable with one or more additional units, thereby providing a means for the combined linker units to bond to one or more payloads. Each linker or linker unit can be comprised of one or more linker moieties, and each of the one or more linker moieties may occur one or more times within the linker or linker unit. Thus, in some embodiments, a first linker (or linker unit) is connected to a second linker (or linker unit), and the combined linkers (a composite linker) connects at least a first group and a second group. A composite linker of the present disclosure can contain 2, 3, 4, 5, 6, 7, 8, 9, 10 or more linker units. In a non-limiting example, a first, second and third linker unit are joined together to provide a composite linker that can connect multiple drugs or payloads to at least one other group, such as a biologically active polypeptide or protein (e.g., an antibody). In some embodiments, the biologically active polypeptide or protein (e.g., antibody) contains at least one non-naturally encoded amino acid. In some embodiments, a composite linker connects multiple drugs or payloads to a polypeptide or protein (e.g., antibody) via the non-naturally encoded amino acid. In some embodiments, a linker of the present disclosure is a bivalent, trivalent or tetravalent group. In some embodiments, a linker of the present disclosure comprises, or consists of, at least one linker moiety, wherein each at least one linker moiety is independently selected from the group consisting of a bond, methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, -S(O)0-2-, an amino acid, a peptide, a disulfide (-S-S-), a glucuronidase-cleavable moiety and a phosphate-containing moiety; and combinations thereof; wherein: each R_w is independently H, C₁-C₈ alkyl or a bond. In some embodiments, each phosphate-containing moiety is independently selected from the group consisting of a phosphate ester, a pyrophosphate ester, a triphosphate ester, a tetraphosphate ester, a phosphonate, a diphosphonate, a phosporamidate, a pyrophosporamidate, a triphosphoramidate, a tetraphosphoramidate, a phosphorthioate and a diphosphorthioate. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester. In some embodiments, the phosphate- containing moiety is a diphosphonate. Unless expressly indicated otherwise, the orientation of the linker or linker moiety is not limited by the direction in which the formula of the linker or linker moiety is written. By way of WSGR Ref. No 31362-825.601 example, the formula –C(O)CH₂CH₂– represents both –C(O)CH₂CH₂– and –CH₂CH₂C(O)–. In another example, the formula –C(O)CH2CH2– represents both *–C(O)CH2CH2– and – C(O)CH₂CH₂–*, wherein * denotes a point of connection, for example, connection of the linker or linker moiety to a drug or payload. In some embodiments, when a linker moiety occurs two or more times within the same linker, the two or more occurrences are not adjacent. Thus, where linker groups are specified by their conventional chemical formulas, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left; for example, -CH2O- is equivalent to –OCH2-, unless expressly indicated otherwise. In another non-limiting example, the formula –alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)_i–represents both –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i– and –(O)_i- P(=O)(OH)-O-P(=O)(OH)-O-alkylene–. In another example, the formula –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i–represents both *–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i– and –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i–*, wherein each * denotes a point of connection, for example, connection to a drug or payload. It is further understood that, when a linker comprises a linker moiety (e.g., alkylene) that is independently selected from a group of more particular linker moieties, this independent selection can be made within a given linker. By way of example only, the formula *–alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–(O-alkylene)n–, wherein each alkylene is independently -(CH2)-, -(CH2)2- or -(CH2)3-, includes but is not limited to the following: *–(CH₂)-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(CH₂)₂-(O-(CH₂)₃)_n–, *–(CH2)2-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(CH2)3-(O-CH2)n–, *–(CH2)3-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(CH2)-(O-(CH2)2)n– and *–(CH₂)₂-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(CH₂)-(O-(CH₂)₂)_n–. Furthermore, and by way of example only, the group *–alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–(O-alkylene)n–, wherein each alkylene is independently -(CH2)-, - (CH₂)₂- or -(CH₂)₃-, can be rewritten: *–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i _{n 2})-, - (CH2)2- or -(CH2)3-. Similarly, *–(alkylene–O)n-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n- J-alkylene-(alkylene–O)n–, wherein each alkylene is independently -(CH2)-, -(CH2)2- or - (CH2)₃-, and each n is independently 1, 2 or 3, can be rewritten: *–(alkylene–O)_n-P(=O)(OH)-O- P(=O)(OH)-(O)i 2)-, -(CH2)2- or -(CH2)3- independently 1, 2 or 3. In some embodiments, linker L is selected from the group consisting of a bond, –alkylene–, WSGR Ref. No 31362-825.601 –(alkylene–O)_n–alkylene–, –alkylene–C(O)–, –(alkylene–O)_n–alkylene–C(O)–, –alkylene- (alkylene–O)n-C(O)–, –alkylene-arylene-alkylene–, –alkylene–NH–, –(alkylene–O)n-alkylene- NH–, –C(O)-alkylene-NH–, –C(O)-(alkylene–O)_n–alkylene–NH–, –(alkylene–O)_n–alkylene–J–, –J-alkylene–, –alkylene-J-alkylene–, –(alkylene-O)_n-J-alkylene–, –alkylene-J-(alkylene-O)_n- alkylene-C(O)–, –alkylene–J–(alkylene–O)n–alkylene–, –(alkylene–O)n–alkylene–J–alkylene, – J–(alkylene–O)n–alkylene–, –J–(alkylene–O)n–(alkylene–O)n–alkylene–, –(alkylene–O)n– alkylene–J–(alkylene–O)_n–alkylene–J–, –C(O)-U–NH-alkylene–, –(alkylene–O)_n–alkylene- C(O)-U–NH-alkylene–C(O)–, –(alkylene–O)n–alkylene–C(O)-U-NH–alkylene–, –C(O)- alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, –alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, –alkylene-NH-U-C(O)-alkylene– and –(CH₂)_1-6– substituted with one to three groups independently selected from the group consisting of -OH, -NH2, C1-C3 alkyl, C1-C3 alkoxy and C3-C6 cycloalkyl; wherein: each U is an amino acid; each J is independently:

each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, – (CH₂)₁₀–, –(CH₂)₁₁– and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, L is not a bond. In some embodiments, arylene is phenylene. In some embodiments, linker L is selected from the group consisting of –alkylene–, – (alkylene–O)n–alkylene–, –alkylene–C(O)–, –(alkylene–O)n–alkylene–C(O)–, –alkylene-J- (alkylene-O)_n-alkylene-C(O)–, –alkylene-arylene-alkylene– and –alkylene–J–(alkylene–O)_n– alkylene–. In some embodiments, L is –(alkylene–O)_n–alkylene–. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, a linker L is selected from the group consisting of the linkers listed in Table 6. Table 6. Non-limiting examples of linkers of the present disclosure. WSGR Ref. No 31362-825.601

WSGR Ref. No 31362-825.601

In some embodiments, a linker L comprises disulfide. In some embodiments, the linker comprising the disulfide further comprises at least one additional linker moiety, wherein each at least one additional moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, -S(O)0-2- and an amino acid, wherein each Rw is independently H or C1- C8 alkyl; and combinations of any two or more of the foregoing. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, linker L is selected from the group consisting of –alkylene- C(R_e)(R_f)-S-S-C(R_g)(R_h)-alkylene–, –alkylene-C(R_e)(R_f)-S-S-C(R_g)(R_h)- alkylene–J-alkylene–, –C(O)-alkylene-C(R_e)(R_f)-S-S-C(R_g)(R_h)-alkylene–, – C(O)-alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene-J-alkylene– and –(alkylene– O)n-alkylene-J-alkylene-C(Re)(Rf)-S-S-alkylene-J-(alkylene-O)n-alkylene–; wherein: each J is independently:

each Re, Rf, Rg and Rh is independently selected from the group consisting of H and C₁-C₆ alkyl; each alkylene is independently selected from the group consisting of -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, – (CH₂)₁₀–, –(CH₂)₁₁– and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. WSGR Ref. No 31362-825.601 In some embodiments, a linker L is selected from the group consisting of the linkers listed in Table 7. Table 7. Non-limiting examples of linkers of the present disclosure.

In some embodiments, the linker L comprises a glucuronidase-cleavable moiety. In some embodiments, L further comprises at least one additional linker moiety, wherein each at least one additional linker moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, -S(O)0-2- and an amino acid, wherein each Rw is independently H or C1- C8 alkyl; and combinations of any two or more of the foregoing. In some embodiments, L is selected from the group consisting of –C(O)-O-alkylene-G-J-alkylene–, –C(O)-O-alkylene-G- NH-alkylene–, –C(O)-O-alkylene-G-J-alkylene-(O-alkylene)_n–, –C(O)-O-alkylene-G-NH- alkylene-(O-alkylene)n–, wherein: each G is a glucuronidase substrate; each J is independently: WSGR Ref. No 31362-825.601

each alkylene is independently selected from the group consisting of -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, – (CH2)10–, –(CH2)11– and –(CH2)12–; and each n is independently an integer from 1 to 100. In some embodiments, the linker L comprises linker moiety -C(O)-, and said linker moiety -C(O)- is joined to X; and Z is -CH2-. In some embodiments, G is arylene substituted with a glucuronic acid. In some embodiments, G is:

. In some further embodiments, G is:

. In some embodiments, a linker L is selected from the group consisting of the linkers listed Table 8. Table 8. Non-limiting examples of linkers of the present disclosure.

WSGR Ref. No 31362-825.601 In some embodiments, a linker, L comprises a peptide. In some embodiments, the linker L further comprises at least one additional linker moiety, wherein each at least one additional linker moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, - C(S)-, -N(Rw)-, -S(O)0-2- and an amino acid, wherein each Rw is independently H or C1-C8 alkyl; and combinations of any two or more of the foregoing. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, L is selected from the group consisting of –C(O)-O-alkylene- arylene-NH-(peptide)-C(O)–, –C(O)-O-alkylene-arylene-NH-(peptide)-C(O)-alkylene–, –C(O)- O-alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)n–, –C(O)-O-alkylene-arylene-NH- (peptide)-(alkylene-O)n-alkylene–, –C(O)-(alkylene-O)n-alkylene-NH-(peptide)-C(O)-alkylene–, –alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)_n–, –alkylene-arylene-NH-(peptide)- C(O)-alkylene–, –alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-C(O)-O- alkylene-arylene-NH-(peptide)-C(O)–, –(alkylene–O)n-alkylene-C(O)-O-alkylene-arylene-NH- (peptide)-C(O)–, –J-(alkylene-N(CH₃))_n-alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J–alkylene–N(CH₃)–alkylene–N(CH₃)–alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-J-(alkylene–N(CH3))n-alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)– and – alkylene–J–alkylene–N(CH3)–alkylene–N(CH3)–alkylene-C(O)-O-alkylene-arylene-NH- (peptide)-C(O)–; wherein: each J is independently:

each peptide is independently a dipeptide, tripeptide or tetrapeptide; each alkylene is independently selected from the group consisting of -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH₂)₈–, –(CH₂)₉–, – (CH2)10–, –(CH2)11– and –(CH2)12–; and each n is independently an integer from 1 to 100. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, each arylene is phenylene. In some embodiments, linker L is selected from the group consisting of –C(O)-O-alkylene- arylene-NH-(peptide)-alkylene-(O-alkylene)n–, –C(O)-O-alkylene-arylene-NH-(peptide)-C(O)- WSGR Ref. No 31362-825.601 alkylene–, –alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)_n–, –alkylene-arylene-NH- (peptide)-C(O)-alkylene– and –C(O)-(alkylene-O)n-alkylene-NH-(peptide)-C(O)-alkylene–. In some embodiments, each -C(O)-O-alkylene-arylene-NH- is:

. In some embodiments, each peptide is independently selected from the group consisting of -P1-P2-, -P1-P2-P3- and -P1-P2-P3-P4-, In some embodiments, each P1, P2, P3 and P4 is independently selected from the group consisting of alanine (ala), arginine (arg), asparagine (asn), aspartic acid (asp), cysteine (cys), glutamine (gln), glutamic acid (glu), glycine (gly), histidine (his), isoleucine (ile), leucine (leu), lysine (lys), methionine (met), phenylalanine (phe), proline (pro), serine (ser), threonine (thr), tryptophan (trp), tyrosine (tyr), valine (val), pyrrolysine, selenocysteine, N -methyl-lysine, N ,N -dimethyl-lysine, citrulline (cit)

. In some embodiments, -P1-P2- is -ala-val- or -cit-val-. In some embodiments, -P1-P2- is -cit-val- and –C(O)-O-alkylene-arylene-NH-(peptide)- C(O)– has the following structure:

. In some embodiments, -P1-P2- has the following structure, wherein P1 is cit:

. In some embodiments, -P1-P2-P3- is -ala-val-glu-, -cit-val-glu- or -asn-ala-ala. In some embodiments, -P1-P2-P3-P4- is -gly-phe-gly-gly-. In some embodiments, L is *–alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)n– or *–alkylene-arylene-NH-(peptide)-C(O)-alkylene–; wherein: * denotes connection to drug. WSGR Ref. No 31362-825.601 In some embodiments, R₇ is not H, and -N(R₇) is quaternized via further substitution with C1-C6 alkyl. In some embodiments, R7 is methyl. In some embodiments, a linker L is selected from the group consisting of the linkers listed Table 9. Table 9. Non-limiting examples of linkers of the present disclosure.

WSGR Ref. No 31362-825.601 In some embodiments, a linker of the present disclosure is a phosphate-based linker. Phosphate-based linkers of the present disclosure can comprise a phosphate ester, a pyrophosphate ester, a triphosphate ester, a tetraphosphate ester, a phosphonate, a diphosphonate, a phosporamidate, a pyrophosporamidate, a triphosphoramidate, a tetraphosphoramidate, a phosphorthioate and/or a diphosphorthioate. Thus, a phosphate-based linkers of the present disclosure can comprise:

a phosphate ester having the structure ; a phosphonate having the structure

a pyrophosphate ester having the structure ; a diphosphonate having the structure

; a triphosphate ester having the structure

;

a tetraphosphate ester having the structure ;

a phosphorthioate having the structure ; a diphosphorthioate having the structure

a phosphoramidate having the structure

WSGR Ref. No 31362-825.601 a pyrophosphoramidate having the structure

; a triphosphoramidate having the structure

and/or a tetraphosphoramidate having the structure

. In some embodiments, a phosphate-based linker of the present disclosure comprises a phosphate-containing moiety and at least one additional linker moiety, wherein each at least one linker moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, -S(O)0-2-, an amino acid, a peptide, a glucuronidase-cleavable moiety and a disulfide (-S-S); and combinations thereof; wherein: each R_w is independently H or C₁-C₈ alkyl; and each phosphate-containing moiety is independently selected from the group consisting of a phosphate ester, a pyrophosphate ester, a triphosphate ester, a tetraphosphate ester, a phosphonate, a diphosphonate, a phosporamidate, a pyrophosporamidate, a triphosphoramidate, a tetraphosphoramidate, a phosphorthioate and a diphosphorthioate. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester or a diphosphonate. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, each at least one additional linker moiety is independently selected from the group consisting of unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(R_w)-, -S(O)_0-2- and an amino acid, wherein each R_w is independently H or C1-C8 alkyl; and combinations of any two or more of the foregoing. In some further embodiments, a phosphate-based linker of the present disclosure is selected from the group consisting of *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–, *–P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)i–alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i–alkylene-J–, *–P(=O)(OH)- O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-(O-alkylene)n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i- WSGR Ref. No 31362-825.601 (alkylene-O)_n-alkylene-C(O)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n-alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i–alkylene–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i– (alkylene-O)_n–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-(O-alkylene)_n-J- alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–alkylene–J-(alkylene-O)_n–alkylene–, *– P(=O)(OH)-O-P(=O)(OH)-(O)i–alkylene–U–alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-J- alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-(O-alkylene)_n–, – alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i–, – alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)- (O)_i-alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–J-alkylene–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)- (O)i-(alkylene-O)n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene– (O-alkylene)n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–(O-alkylene)n–, – (alkylene–O)_n-P(=O)(OH)-O-P(=O)(OH)-(O)_i–, –(alkylene–O)_n-P(=O)(OH)-O-P(=O)(OH)-(O)_i- alkylene–, –(alkylene–O)_n-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, –(alkylene–O)_n- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –(alkylene–O)n–alkylene-P(=O)(OH)- O-P(=O)(OH)-(O)i–, –(alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –(alkylene– O)_n–alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n–alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –(alkylene–O)n–alkylene-P(=O)(OH)-O-P(=O)(OH)- (O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)_n–alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene– and – (alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–; wherein: each U is an amino acid; each J is independently:

each alkylene is independently selected from the group consisting of -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, – (CH2)10–, –(CH2)11– and –(CH2)12–; each n is independently an integer from 1 to 100; each i is independently 0 or 1; and *, when present, denotes connection to drug. WSGR Ref. No 31362-825.601 In some embodiments, the phosphate-containing moiety is a pyrophosphate ester or a diphosphonate. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, each U is independently:

. In some embodiments, the linker is selected from the group consisting of the linkers listed in Table 10. Table 10. Non-limiting examples of linkers of the present disclosure.

WSGR Ref. No 31362-825.601

WSGR Ref. No 31362-825.601

In some embodiments, the linker is selected from the group consisting of:

wherein: each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each i is independently 0 or 1; * denotes connection to drug; and the wavy line denotes connection to a reactive moiety or an antibody. In some embodiments, the linker has the following structure:

wherein * denotes connection to drug; and the wavy line denotes connection to a reactive moiety or an antibody. In some preferred embodiments, the linker has the following structure: WSGR Ref. No 31362-825.601

wherein Y is a reactive moiety; and * denotes connection to a drug. In some embodiments, Y is -ONH2. In some embodiments, when a linker of the present disclosure comprises an amino acid, or when a linker moiety is an amino acid, the amino acid is at least one amino acid. In some embodiments, the at least one amino acid is independently selected from the group consisting of alanine (ala), arginine (arg), asparagine (asn), aspartic acid (asp), cysteine (cys), glutamine (gln), glutamic acid (glu), glycine (gly), histidine (his), isoleucine (ile), leucine (leu), lysine (lys), methionine (met), phenylalanine (phe), proline (pro), serine (ser), threonine (thr), tryptophan (trp), tyrosine (tyr), valine (val), pyrrolysine, selenocysteine, N -methyl-lysine, N ,N - dimethyl-lysine, citrulline (cit) and

. In some embodiments, each of the at least one amino acid is independently:

. In some embodiments, a linker of the present disclosure is a non-cleavable linker. In some preferred embodiments, the non-cleavable linker comprises one or more linker moieties, wherein each of the one or more linker moieties is independently selected from the group consisting of unsubstituted alkylene and –(O-alkylene)_n–, wherein each n is independently an integer from 1 to 100. In some embodiments, the non-cleavable linker further comprises a reactive moiety. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, each unsubstituted alkylene is independently selected from the group consisting of -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5- and -(CH2)6-. In some embodiments, each –(O-alkylene)_n– is –(O-CH₂CH₂)_n–. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, WSGR Ref. No 31362-825.601 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, the non-cleavable linker comprises the reactive moiety. In some embodiments, the reactive moiety is any reactive moiety of the present disclosure. In some embodiments, the reactive moiety is -ONH2. In some embodiments, the non-cleavable linker is selected from the group consisting of: and

wherein each wavy line indicates connection to a reactive moiety or an antibody, and each * indicates connection to a drug. In some embodiments, the linker further comprises the reactive moiety. In some embodiments, the reactive moiety is -ONH₂. In some further embodiments, a linker of the present disclosure is selected from the group consisting of:

wherein each wavy line indicates connection to a reactive moiety or an antibody, each * indicates connection to a drug, and each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, the linker further comprises the reactive moiety. In some embodiments, the reactive moiety is -ONH2. In some other embodiments, a linker is selected from the group consisting of:

; wherein each wavy line indicates connection to a reactive moiety or an antibody, each * indicates connection to a drug, and each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, the linker further comprises the reactive moiety. In some embodiments, the reactive moiety is -ONH₂. WSGR Ref. No 31362-825.601 In some embodiments, a linker is selected from the group consisting of:

wherein each wavy line indicates connection to a reactive moiety or an antibody, each * indicates connection to a drug, and each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, the linker further comprises the reactive moiety. In some embodiments, the reactive moiety is -ONH₂. In some other embodiments, a linker is selected from the group consisting of:

wherein each wavy line indicates connection to a reactive moiety or an antibody, each * indicates connection to a drug, and each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, the linker further comprises the reactive moiety. In some embodiments, the reactive moiety is -ONH2. Drugs and Drug-linkers The present disclosure provides drugs and drug-linker compounds. A drug-linker can contain any drug of the present disclosure covalently bound to any linker, such as any linker of the present disclosure. In some aspects, the drug and drug-linker compounds can be used alone, e.g., for the treatment of a disease or condition in a subject. In some other aspects, the drug and drug-linker compounds can be conjugated to an antibody to provide an ADC (e.g., an ADC of the present disclosure). The drug or drug-linker can be released from an ADC in a desired location, such as a cancer cell, where the delivered drug- or drug-linker “payload” can induce cancer cell death. Thus, in some embodiments, the drug or drug-linker is a cytotoxic drug or agent. In some aspects, the cytotoxic drug or drug-linker is an agent that disrupts tubulin polymerization. WSGR Ref. No 31362-825.601 In some aspects, a cytotoxic drug of the present disclosure is an auristatin analog. In some embodiments, the cytotoxic drug is monomethyl auristatin F. Monomethyl auristatin F (MMAF) is a highly potent synthetic analog of auristatin having the structure shown in FIG. 1. MMAF inhibits cell proliferation by disrupting tubulin polymerization and relatively membrane impermeable (Skidmore, L. et al., Mol. Cancer Ther., 19, pp.1833-1843 (2020); the entire contents of which are hereby incorporated by reference in their entirety). In some embodiments, the cytotoxic drug is MMAF. In some embodiments, the drug- linker compound is amberstatin 269 (AS269) having the following structure:

. In some other embodiments, a cytotoxic drug of the present disclosure is a compound of Formula (I-C):

wherein: V is selected from the group consisting of -CH2-, -S-, -S(O)-, -C(O)- and -C(H)(Rv)-; wherein Rv is -F, -CN, -N3, -OH, -ONH2 or optionally substituted C1-C8 alkyl; X is O or NH; Z is -CH₂- or -C(O)-; R5 is H, optionally substituted C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl; R₆ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; R7, R8 and R9 are each independently H, optionally substituted C1-C8 alkyl or optionally substituted C3-C6 cycloalkyl; or R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R₉ is H or optionally substituted C₁-C₈ alkyl; or R₈ and R9 are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R7 is H, optionally substituted C1-C8 alkyl or optionally substituted C₃-C₆ cycloalkyl; and R_7a is H, optionally substituted C₁-C₆ alkyl or optionally substituted C3-C6 cycloalkyl; or a pharmaceutically acceptable salt thereof. WSGR Ref. No 31362-825.601 In some embodiments, V is CH₂. In some embodiments, X is O. In some other embodiments, X is NH. In some embodiments, Z is -C(O)-. In some other embodiments, Z is -CH₂-. In some embodiments, R₅ is H or unsubstituted C₁-C₆ alkyl. In some embodiments, R₅ is H or methyl. In some embodiments, R5 is H. In some embodiments, R6 is optionally substituted aryl or optionally substituted heteroaryl. In some embodiments, R₆ is unsubstituted aryl or unsubstituted heteroaryl. In some embodiments, R7 is H or methyl. In some embodiments, R7 is methyl. In some embodiments, R7a is H or optionally substituted C1-C6 alkyl. In some embodiments, R_7a is H or methyl. In some embodiments, R_7a is methyl. In some embodiments, R7 and R7a are each methyl. In some embodiments, R8 and R9 are each methyl. In some other embodiments, R8 is H and R₉ is C₁-C₆ alkyl. In some embodiments, R₉ is methyl, ethyl, propyl or isopropyl. In some embodiments, R9 is isopropyl. In some embodiments, R6 is optionally substituted aryl. In some embodiments, R6 is unsubstituted aryl. In some embodiments, R₆ is phenyl. In some embodiments, the cytotoxic drug is a compound selected from the group consisting of:

and pharmaceutically acceptable salts thereof. In some embodiments, V is -CH₂-; Z is -CH₂- or -C(O)-; R₅ is H or unsubstituted C₁-C₆ alkyl; R6 is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R7 is H or unsubstituted C₁-C₆ alkyl; R_7a is H or unsubstituted C₁-C₆ alkyl; and R₈ and R₉ are each independently H or C₁-C₆ alkyl. In some embodiments, R6 is optionally substituted heteroaryl. In some embodiments, said optionally substituted heteroaryl is an optionally substituted 5-membered heteroaryl. In some embodiments, R₆ is optionally substituted 5-membered heteroaryl selected from the group consisting of pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl and thiodiazolyl. In some embodiments, R6 is WSGR Ref. No 31362-825.601 optionally substituted furanyl or thienyl. In some embodiments, R₆ is unsubstituted heteroaryl. In some embodiments, R6 is unsubstituted furanyl or thienyl. In some embodiments, R6 is unsubstituted 2-thienyl. In some other embodiments, R₆ is unsubstituted 3-thienyl. In some embodiments, Z is -C(O)-. In some embodiments, the cytotoxic drug is a compound selected from the group consisting of:

and pharmaceutically acceptable salts thereof. In some other embodiments, Z is -CH2-. In some embodiments, the cytotoxic drug is a compound selected from the group consisting of:

WSGR Ref. No 31362-825.601

and pharmaceutically acceptable salts thereof. In some embodiments, the cytotoxic drug is a compound having the following structure:

wherein R_7a is H or methyl; or a pharmaceutically acceptable salt thereof. In some embodiments, R7a is H. In some other embodiments, R7a is methyl. In some aspects, a cytotoxic drug of the present disclosure is a drug-linker compound, or more particularly, an auristatin analog comprising a linker. The linker can further contain a reactive moiety, or another moiety. In some embodiments, a drug-linker is a compound of Formula (I) or Formula (II):

wherein: V is selected from the group consisting of -CH₂-, -S-, -S(O)-, -C(O)- and -C(H)(R_v)-; wherein Rv is -F, -CN, -N3, -OH, -ONH2 or optionally substituted C1-C8 alkyl; X is O or NH; Y is a reactive moiety; Z is -CH₂- or -C(O)-; R5 is H, optionally substituted C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl; R₆ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; R7, R8 and R9 are each independently H, optionally substituted C1-C8 alkyl or optionally substituted C3-C6 cycloalkyl; or R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R₉ is H or optionally substituted C₁-C₈ alkyl; or WSGR Ref. No 31362-825.601 R₈ and R₉ are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R7 is H, optionally substituted C1-C8 alkyl or optionally substituted C₃-C₆ cycloalkyl; and R_7a is H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; and L is a linker; or a pharmaceutically acceptable salt thereof. In some embodiments, the reactive moiety Y comprises -N3, -OH, -SH, -NHRb, -C(O)Rc, -C(O)ORd, -C(O)CH2NH2, an activated ester, –O–NH2, a maleimide, a tetrazine, an alkyne, a cyclooctyne or an (E)-cyclooctene; wherein: Rb is H or unsubstituted C1-C6 alkyl, Rc is unsubstituted C1-C6 alkyl, and R_d is H, unsubstituted C₁-C₆ alkyl or a carboxylic acid protecting group. In some embodiments, V is CH2. In some embodiments, X is O. In some other embodiments, X is NH. In some embodiments, Z is -C(O)-. In some embodiments, Z is -C(O)- and X is O. In other embodiments, Z is -C(O)- and X is NH. In some other embodiments, Z is -CH2-. In some embodiments, Z is -CH2- and X is O. In some embodiments, R5 is H or unsubstituted C1-C6 alkyl. In some embodiments, R5 is H or methyl. In some embodiments, R₅ is H. In some embodiments, R6 is optionally substituted aryl or optionally substituted heteroaryl. In some embodiments, R6 is unsubstituted aryl or unsubstituted heteroaryl. In some embodiments, R₇ is H or methyl. In some embodiments, R₇ is methyl. In some embodiments, R8 and R9 are each methyl. In some other embodiments, R8 is H and R9 is C1-C6 alkyl. In some embodiments, R9 is methyl, ethyl, propyl or isopropyl. In some embodiments, R₉ is isopropyl. In some embodiments, R_7a is H or optionally substituted C₁-C₆ alkyl. In some embodiments, R7a is H or methyl. In some embodiments, R7a is methyl. In some embodiments, R7 and R7a are each methyl. In some embodiments, Y is selected from the group consisting of:

, -N₃, -OH, -SH, -NHR_b, -C(O)R_c, -C(O)OR_d, an activated WSGR Ref. No 31362-825.601 ester, –O–NH₂ and an optionally substituted monocyclic or polycyclic group comprising a cyclooctyne; wherein: R_b is H or unsubstituted C₁-C₆ alkyl, R_c is unsubstituted C₁-C₆ alkyl, Rd is H, unsubstituted C1-C6 alkyl or a carboxylic acid protecting group, Rt is H or unsubstituted C1-C6 alkyl, s is 0, 1, 2, 3, 4, 5 or 6, t is 0, 1, 2, 3, 4, 5 or 6, and *, when present, denotes connection to L. In some embodiments, when Y is a monocyclic or polycyclic group comprising cyclooctyne, the monocyclic or polycyclic group comprising the cyclooctyne is selected from the group consisting of:

In some embodiments, Y is -O-NH2. In some embodiments, V is -CH2-, Z is -CH2- or -C(O)-; R5 is H or unsubstituted C1-C6 alkyl; R₆ is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R₇ is H or unsubstituted C₁-C₆ alkyl; R₈ and R₉ are each independently H or C₁-C₆ alkyl; Y is -ONH₂; and L is the linker. In some embodiments, V is -CH₂-, Z is -CH₂-, X is -O-; Y is -ONH₂; R₆ is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R₇ is H or unsubstituted C₁-C₆ alkyl; R7a is H or unsubstituted C1-C6 alkyl; R8 and R9 are each independently H or C1-C6 alkyl; and L is the linker. In some embodiments, the linker L is any linker of the present disclosure. In some embodiments, the linker is a bivalent, trivalent or tetravalent group. In some embodiments, the linker is a bivalent group. In some embodiments, the linker comprises, or consists of, at least one linker moiety, wherein each at least one linker moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, -S(O)0-2-, an amino acid, a peptide, a disulfide (-S-S-), a glucuronidase-cleavable moiety and a phosphate-containing moiety; and combinations thereof; wherein: each R_w is independently H, C₁-C₈ alkyl or a bond. In some embodiments, each phosphate-containing moiety is independently selected from the group consisting of a phosphate ester, a pyrophosphate ester, a triphosphate ester, a tetraphosphate ester, WSGR Ref. No 31362-825.601 a phosphonate, a diphosphonate, a phosporamidate, a pyrophosporamidate, a triphosphoramidate, a tetraphosphoramidate, a phosphorthioate and a diphosphorthioate. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester. In some embodiments, the phosphate- containing moiety is a diphosphonate. In some embodiments, the linker L is selected from the group consisting of the linkers listed in Table 6. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 7. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 8. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 9. In some other embodiments, the linker is selected from the group consisting of the linkers listed in Table 10. In some embodiments, L is a non-cleavable linker. In some embodiments, the non- cleavable linker comprises one or more linker moieties, wherein each of the one or more linker moieties is independently selected from the group consisting of methine (-CH-), unsubstituted alkylene and –(O-alkylene)n–, wherein each n is independently an integer from 1 to 100. In some embodiments, each unsubstituted alkylene is independently selected from the group consisting of -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅- and -(CH₂)₆-. In some embodiments, each –(O- alkylene)_n– is –(O-CH₂CH₂)_n–. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, L is a non-cleavable linker selected from the group consisting of: and

wherein each wavy line indicates connection to the reactive moiety Y, and each * indicates connection to -N(R₇) of Formula (I). In some embodiments, R₆ is optionally substituted aryl. In some embodiments, R₆ is unsubstituted aryl. In some embodiments, R6 is phenyl. In some embodiments, the drug-linker is a compound of Formula (I). In some embodiments, the drug-linker is a compound of Formula (I) selected from the group consisting of: WSGR Ref. No 31362-825.601

and pharmaceutically acceptable salts thereof. In some embodiments, R6 is optionally substituted heteroaryl. In some embodiments, said optionally substituted heteroaryl is an optionally substituted 5-membered heteroaryl. In some embodiments, R₆ is optionally substituted 5-membered heteroaryl selected from the group consisting of pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl and thiodiazolyl. In some embodiments, R₆ is optionally substituted furanyl or thienyl. In some embodiments, R₆ is unsubstituted heteroaryl. In some embodiments, R6 is unsubstituted furanyl or thienyl. In some embodiments, R6 is unsubstituted 2-thienyl. In some other embodiments, R6 is unsubstituted 3-thienyl. In some embodiments, Z is -C(O)-. In some embodiments, the drug-linker is a compound of Formula (I) selected from the group consisting of:

, WSGR Ref. No 31362-825.601

In some other embodiments, Z is -CH₂-. In some embodiments, the drug-linker is a compound of Formula (I) selected from the group consisting of:

and pharmaceutically acceptable salts thereof. In some embodiments, the compound is a compound of Formula (II). In some embodiments, when the compound is a compound of Formula (II), the linker is a phosphate-based linker of the present disclosure. Thus, in some embodiments, L comprises a phosphate-containing moiety and at least one additional linker moiety, wherein each at least one linker moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, – (alkylene–O)n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, - S(O)_0-2-, an amino acid, a peptide, a glucuronidase-cleavable moiety and a disulfide (-S-S); and combinations thereof; wherein: each Rw is independently H or C1-C8 alkyl; and WSGR Ref. No 31362-825.601 each phosphate-containing moiety is independently selected from the group consisting of a phosphate ester, a pyrophosphate ester, a triphosphate ester, a tetraphosphate ester, a phosphonate, a diphosphonate, a phosporamidate, a pyrophosporamidate, a triphosphoramidate, a tetraphosphoramidate, a phosphorthioate and a diphosphorthioate. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester or a diphosphonate. In some embodiments, each n is independently an integer from 1 to 100. In some embodiments, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each n is independently 1, 2 or 3. In some embodiments, each at least one additional linker moiety is independently selected from the group consisting of unsubstituted alkylene, substituted alkylene, –(alkylene–O)n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(R_w)-, -S(O)_0-2- and an amino acid, wherein each R_w is independently H or C1-C8 alkyl; and combinations of any two or more of the foregoing. In some embodiments, L is *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–; wherein * denotes the connection to X of Formula (II). In some embodiments, L has the following structure:

; wherein Y is a reactive moiety; and * denotes the connection to X of Formula (II). In some embodiments, X is O. In some embodiments, Y is -ONH₂. In some embodiments, R6 is optionally substituted aryl. In some embodiments, R6 is unsubstituted aryl. In some embodiments, R6 is phenyl. In some embodiments, the drug-linker is a compound of Formula (II) selected from the group consisting of:

and pharmaceutically acceptable salts thereof. In some embodiments, R_7a is H or methyl. In some embodiments, R7a is H. In some embodiments, R7a is methyl. In some embodiments, R6 is optionally substituted heteroaryl. In some embodiments, said optionally substituted heteroaryl is an optionally substituted 5-membered heteroaryl. In some embodiments, R6 is optionally substituted 5-membered heteroaryl selected from the group consisting of pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, WSGR Ref. No 31362-825.601 isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl and thiodiazolyl. In some embodiments, R₆ is optionally substituted furanyl or thienyl. In some embodiments, R6 is unsubstituted heteroaryl. In some embodiments, R₆ is unsubstituted furanyl or thienyl. In some embodiments, R₆ is unsubstituted 2-thienyl. In some other embodiments, R₆ is unsubstituted 3-thienyl. In some embodiments, the drug-linker compound is a compound of Formula (II) selected from the group consisting of:

and pharmaceutically acceptable salts thereof. In some embodiments, R_7a is H or methyl. In some embodiments, R_7a is H. In some embodiments, R_7a is methyl. Table 11 provides non-limiting, exemplary drug-linker compounds that can be employed or conjugated with any targeting ligand such as an antibody or antibody fragment, that is selected based in its specificity for an antigen expressed on a target cell or at a target site of interest. Synthesis of such payload or drug linkers are well known to the skilled artisan. See for example EP14874745, Dubowchik et al., Bioconjugate Chem.13: 855-869, (2002); Doronina et al., Nature Biotechnology 21(7): 778-784, (2003); WO2012/166560; WO2013/185117 each incorporated herein by reference. Table 11. Non-limiting Drug-linker Compounds of the Invention.

WSGR Ref. No 31362-825.601

In some aspects, the present disclosure provides branched drug-linker compounds. In some embodiments, there is provided a compound of Formula (III) or (IV):

WSGR Ref. No 31362-825.601

wherein: each V is selected from the group consisting of -CH₂-, -S-, -S(O)-, -C(O)- and - C(H)(R_v)-; wherein R_v is F, CN, N₃, OH, ONH₂ or optionally substituted C₁-C₈ alkyl; Y is a reactive moiety, optionally, wherein the reactive moiety comprises -N3, -OH, -SH, -NHR_b, -C(O)R_c, -C(O)OR_d, -C(O)CH₂NH₂, an activated ester, –O–NH₂, a maleimide, a tetrazine, an alkyne, a cyclooctyne or an (E)-cyclooctene; wherein: Rb is H or unsubstituted C1-C6 alkyl, R_c is unsubstituted C₁-C₆ alkyl, R_d is H, unsubstituted C₁-C₆ alkyl or a carboxylic acid protecting group, s is 0, 1, 2, 3, 4, 5 or 6 and t is 0, 1, 2, 3, 4, 5 or 6; each X is O or NH; each Z is -CH2- or -C(O)-; each R5 is H, optionally substituted C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl; each R6 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; each R_7, R₈ and R₉ are each independently H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R9 is H or optionally substituted C1-C8 alkyl; or R₈ and R₉ are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R7 is H, optionally substituted C1-C8 alkyl or optionally substituted C3-C6 cycloalkyl; each R_7a is H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; F1 is N or CH; and L₁, L₂ and L₃ are each independently a linker; WSGR Ref. No 31362-825.601 or a pharmaceutically acceptable salt thereof. In some embodiments, R6 is optionally substituted heteroaryl. In some embodiments, R6 is unsubstituted 2-thienyl or unsubstituted 3-thienyl. In some embodiments, Y is -ONH₂. In some embodiments, each linker is independently a linker of any one of Tables 6 to 10. In some other aspects, the cytotoxic drug is monomethyl auristatin E (MMAE), and the drug-linker is MMAE linked to a phosphate-based linker. In some embodiments, the present disclosure provides a compound of Formula (V):

wherein: L is a linker comprising a phosphate-containing moiety; and Y is a reactive moiety, or a pharmaceutically acceptable salt thereof. In some embodiments, the reactive moiety comprises -N3, -OH, -SH, -NHRb, -C(O)Rc, - C(O)OR_d, -C(O)CH₂NH₂, an activated ester, –O–NH₂, a maleimide, a tetrazine, an alkyne, a cyclooctyne or an (E)-cyclooctene; wherein Rb is H or unsubstituted C1-C6 alkyl, Rc is unsubstituted C1-C6 alkyl, Rd is H, unsubstituted C1-C6 alkyl or a carboxylic acid protecting group, s is 0, 1, 2, 3, 4, 5 or 6 and t is 0, 1, 2, 3, 4, 5 or 6. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester moiety. In some embodiments, Y is -ONH2. In some embodiments, the compound is selected from the group consisting of:

WSGR Ref. No 31362-825.601

pharmaceutically acceptable salts thereof. In some other embodiments, there is a of Formula (VI):

wherein: R_7a is H, optionally substituted C₁-C₆ alkyl or optionally substituted C₃-C₆ cycloalkyl; L is a linker comprising a phosphate-containing moiety; and Y is a reactive moiety, or a pharmaceutically acceptable salt thereof. In some embodiments, the reactive moiety comprises -N3, -OH, -SH, -NHRb, -C(O)Rc, - C(O)ORd, -C(O)CH2NH2, an activated ester, –O–NH2, a maleimide, a tetrazine, an alkyne, a cyclooctyne or an (E)-cyclooctene; wherein R_b is H or unsubstituted C₁-C₆ alkyl, R_c is unsubstituted C₁-C₆ alkyl, R_d is H, unsubstituted C₁-C₆ alkyl or a carboxylic acid protecting group, s is 0, 1, 2, 3, 4, 5 or 6 and t is 0, 1, 2, 3, 4, 5 or 6. In some embodiments, R7a is H or methyl. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester moiety. In some embodiments, Y is -ONH2. In some embodiments, the compound is selected from the group consisting of:

WSGR Ref. No 31362-825.601

wherein: R_7a is H, optionally substituted C₁-C₆ alkyl or optionally substituted C₃-C₆ cycloalkyl; or a pharmaceutically acceptable salt thereof. In some embodiments, R7a is H or methyl. In some embodiments the present invention provides additional drug-linkers prepared using similar procedures as described herein, including the schemes disclosed in the Examples. Additional drug-linker compounds are engineered by linkage of any possible linker group known in the art or elsewhere. The drug-linker compounds are engineered by linkage of one or more linkers via any chemical or functional reactive positions in the drug, for example a nitrogen, halogen, boron, phosphorus, silicon, carbon, carbonyl or oxygen of the cytotoxic agent. Selection of the nitrogen, halogen, boron, phosphorus, silicon, sulfur, carbon or oxygen position in the drug for linkage to a linker is assessed as disclosed elsewhere herein, based on structure of the cytotoxic agent, and using the process known in the art or elsewhere to generate a drug linkage. In some embodiments, drug-linkers of the invention include a linker attached or linked at a hydroxyl group of the cytotoxic agent or analogue thereof, such as an auristatin analog of the present disclosure. In some embodiments, drug-linkers of the invention include a linker attached or linked at an N-terminal group of the cytotoxic agent or analogue thereof, such as an auristatin analog of the present disclosure. In some embodiments, drug-linkers of the invention include a linker attached or linked at a C-terminal group of the cytotoxic agent or analogue thereof, such as an auristatin analog of the present disclosure. In other embodiments, drug-linkers of the invention include a linker attached or linked at a methyl or methylene group of the cytotoxic agent or analogue thereof, such as an auristatin analog of the present disclosure. In some embodiments, such additional drug- linker compounds can comprise a branched linkers, which connects to two identical or different drug/payload. In some embodiments, drug-linkers of the present invention include drug-linkers generated via linkage of one or more linkers at one or more a nitrogen, halogen, boron, phosphorus, silicon, sulfur, carbon, carbonyl or oxygen of the cytotoxic agent. Also included within the scope of the methods, compositions, strategies and techniques described herein are reagents capable of reacting with a drug or payload linker (e.g., containing a carbonyl, dicarbonyl, alkyne, cycloalkyne, azide, aminooxy or hydroxylamine group, or masked or protected forms thereof) that is part of a polypeptide so as to produce any post-translational modification disclosed herein. In certain embodiments, the resulting post-translationally modified WSGR Ref. No 31362-825.601 drug or payload linker will contain at least one oxime group; the resulting modified oxime- containing drug or payload linker may undergo subsequent modification reactions. Also included with this aspect are methods for producing, purifying, characterizing and using such reagents that are capable of any such post-translational modifications of such drug or payload linkers. Antibody Drug Conjugates Antibody drug conjugates (ADCs) of the present disclosure provide novel therapeutics or anti-cancer drugs by combining the selectivity of antibodies comprising one or more non-natural amino acids conjugated and a cytotoxic agent. Targeted cytotoxic drug delivery into tumor tissue increases the therapeutic window of these agents considerably. ADCs of the present disclosure comprise of an antibody bound to a cytotoxic drug or payload via a linker. Stability of the linker between the antibody and the cytotoxic drug is essential for the ADC integrity in circulation. The successful ADC development for a given target antigen depends on optimization of antibody selection, linker design and stability, drug potency and mode of drug and linker conjugation to the antibody. Linker properties of pH and redox sensitivities and protease susceptibility influence circulatory stability and release of the drug moiety. Thus, the present disclosure provides drug or payload moieties with linkers that reduce the toxicity of the moiety in vivo while retaining pharmacological activity. In some embodiments, the toxicity of the linked drug or payload group, when administered to an animal or human, is reduced or eliminated compared to the free toxic group or toxic group derivatives comprising labile linkages, while retaining pharmacological activity. In some embodiments, increased doses of the linked toxic group may be administered to animals or humans with greater safety. In certain embodiments, the non-natural amino acid-containing antibodies linked to a drug moiety (e.g., an auristatin analog) provides in vitro and in vivo stability. In some embodiments, the non-natural amino acid-containing antibodies linked to a drug moiety are efficacious and less toxic compared to the free drug moiety. In some embodiments of the disclosure, the antibody of the ADC comprises a full length antibody or fragment thereof that binds to an antigen, and is conjugated to a cytotoxic agent or an immunosuppressive agent, wherein the antibody-drug conjugate exerts: (a) a cytotoxic or cytostatic effect on the antigen-expressing or antigen targeting cell line, or (b) a cytotoxic, cytostatic, or immunosuppressive/immune activating effect on an antigen-expressing immune cell, wherein the conjugation occurs at a non-naturally encoded amino acid in the antibody. In some embodiments, the antigen, or the antigen of the antigen-expressing cell, or antigen-targeting cell, or antigen-expressing immune cell, is PSMA, CD70, CD3, HER2, HER3, TROP2, PD-I, PDL-1, VEGFR, EGFR, c-Met (HGFR), CD19, CD22, CD24, CD25 (IL-2R alpha), CD30, CD33, CD37, WSGR Ref. No 31362-825.601 CD38, CD44, CD46, CD47, CD48, CD52, CD56 (NCAM-1), CD71 (Transferrin R), CD74, CD79b, CD96, CD97, CD99, CD123 (IL-3R alpha), CD138 (syndecan-1), CD142, CD166 (ALCAM), CD179, CD203c (ENPP3), TIMI, CD205 (LY75), CD221 (IGF-1R), CD223, CD262 (TRAIL R2), CD276 (B7-H3), mesothelin, EpCAM, MUCI, MUC16 (CA-125), GPC3, CEA, CEACAM5, CEACAM6, CA9, DLL3, ROR1, ROR2, GPNMB, GCC, GUCY2c, NaPi2b, Flt-1, Flt-3, FOLR1 (folate receptor alpha), Tissue Factor (TF), CA6, BCMA, SLAMF7 (CS1), TIM1, CanAg, Ckit (CD117), EphA2, Nectin4, SLTRK6, FGFR2, LYPD3 (C4.4a), Cadherin 3, Cadherin 6, 5T4 (TPBG), STEAP1, PTK7, Ephrin-A4, SLC34A2, LIV-1 (SLC39A6 or ZIP6), SLC1A5, TENB2, ETBR, integrin v3, Cripto, AGS-5 (SLC44A4), LY6E, SLITRK6, AXL, LAMP1, LRRC15, TNF-alpha, CTLA-4 and MN/CA IX, but is not limited to such. In some embodiments, the antigen, antigen-expressing cell, or antigen-targeting cell, or antigen-expressing immune cell is a TROP2, HER2, HER3, PSMA or CD70 antigen, or antigen-targeting cell, or antigen- expressing cell or antigen-expressing immune cell. In some embodiments of the disclosure, the antibody of the ADC comprises a full length antibody or fragment thereof that: binds to TROP2, HER2, HER3, PSMA or CD70 and is conjugated to a cytotoxic agent or an immunosuppressive agent, wherein the antibody-drug conjugate exerts: (a) a cytotoxic or cytostatic effect on a TROP2- expressing cancer cell line, a HER2-expressing cancer cell line, a HER3-expressing cancer cell line, a PSMA-expressing cancer cell line or a CD70-expressing cancer cell line, or (b) a cytotoxic, cytostatic, or immunosuppressive/immune activating effect on a TROP2-expressing immune cell, a HER2-expressing immune cell, a HER3-expressing immune cell, a PSMA-expressing immune cell or a CD70-expressing immune cell, wherein the conjugation occurs at a non-naturally encoded amino acid in the antibody. In some embodiments, the antibody, variant, or composition of the present disclosure may be an antibody, variant, or composition that binds to an antigen receptor. In other embodiments the antibody, variant, or composition may be an antibody, variant, or composition that binds to extracellular surface of an antigen receptor. In some embodiments the antibody, variant, or composition of the present disclosure may be an antibody, variant, or composition that has CDRs grafted onto the framework region of the variable region. In other embodiments the antibody, variant, or composition of the present disclosure may be an antibody, variant, or composition that has a non-naturally encoded amino acid. In some embodiments the antibody, variant, or composition may be an antibody, variant, or composition that is described by more than one of the embodiments elsewhere herein the present disclosure. In some embodiments the antibody, antibody variant or antibody composition(s) disclosed herein may be fully humanized. In other embodiments the antibody, antibody variant or antibody composition(s) disclosed herein may be WSGR Ref. No 31362-825.601 chimeric. In some embodiments the antibody may be an antibody that is full length antibody (Variable + Fc regions), Fab, bispecific, Fab-dimers, Fab-bispecific, Fab-trispecific, bispecific T- cell engagers, dual-affinity re-targeting antibody, IgG1/IgG3 bispecific antibody, diabody, bispecific diabody, scFv-Fc, minibody. In one embodiment, the ADC comprises an antibody conjugated to a drug wherein the conjugation occurs via a non-naturally encoded amino acid in the antibody. In one embodiment, the ADC comprises an antibody conjugated to a drug wherein the conjugation occurs via a non- naturally encoded amino acid in the heavy chain of the antibody. In one embodiment, the ADC comprises an antibody conjugated to a drug wherein the conjugation occurs via a non-naturally encoded amino acid in the light chain of the antibody. In one embodiment, the ADC comprises a full-length antibody conjugated to a drug wherein the conjugation occurs via a non-naturally encoded amino acid in the antibody. In one embodiment, the ADC comprises a full-length antibody conjugated to a drug wherein the conjugation occurs via a non-naturally encoded amino acid in the heavy chain of the antibody. In one embodiment, the ADC comprises a full-length antibody conjugated to a drug wherein the conjugation occurs via a non-naturally encoded amino acid in the light chain of the antibody. In some embodiments a payload or drug moiety is employed in the ADCs of the present disclosure. In some aspects of the invention, the cytotoxic drug or payload is MMAF or a derivative or analog thereof. In some embodiments, the cytotoxic drug or payload is an agent that disrupts tubulin polymerization. In some embodiments the payload or drug is a drug or payload generated as described in the Examples herein. In some embodiments the payload or drug is compound 6, 17, 24, 27, 33, 37 or 43 or analogs or derivatives thereof. In some embodiments the payload or drug is compound 6, 17, 24, 27, 33 or 37, or analogs or derivatives thereof. In some embodiments, the ADC comprises an antibody, antibody fragment or variant thereof engineered to have one or more non-naturally encoded amino acids site specifically incorporated in the heavy and/or light chain amino acid sequence conjugated to drug or payload via a linker. In some embodiments, the linker L is any linker of the present disclosure. In some embodiments, the linker is a bivalent, trivalent or tetravalent group. In some embodiments, the linker is a bivalent group. In some embodiments, the linker comprises, or consists of, at least one linker moiety, wherein each at least one linker moiety is independently selected from the group consisting of methine (-CH)-, unsubstituted alkylene, substituted alkylene, –(alkylene–O)_n–, optionally substituted arylene, -O-, -C(O)-, -C(S)-, -N(Rw)-, -S(O)0-2-, an amino acid, a peptide, a WSGR Ref. No 31362-825.601 disulfide (-S-S-), a glucuronidase-cleavable moiety and a phosphate-containing moiety; and combinations thereof; wherein: each Rw is independently H, C1-C8 alkyl or a bond. In some embodiments, each phosphate-containing moiety is independently selected from the group consisting of a phosphate ester, a pyrophosphate ester, a triphosphate ester, a tetraphosphate ester, a phosphonate, a diphosphonate, a phosporamidate, a pyrophosporamidate, a triphosphoramidate, a tetraphosphoramidate, a phosphorthioate and a diphosphorthioate. In some embodiments, the phosphate-containing moiety is a pyrophosphate ester. In some embodiments, the phosphate- containing moiety is a diphosphonate. In some embodiments, the linker L is selected from the group consisting of the linkers listed in Table 6. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 7. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 8. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 9. In some other embodiments, the linker is selected from the group consisting of the linkers listed in Table 10. In some embodiments, a drug linker compound containing a reactive moiety is conjugated to an antibody or antibody fragment by reacting a drug-linker compound with an antibody, antibody fragment or variant thereof (or simply “antibody”) containing one or more natural or non-natural amino acids. The conjugation reaction provides an ADC, wherein drug-linker is conjugated to a natural or non-natural amino acid of the antibody via a covalent linkage. The covalent linkage can be a product of the reactive moiety of the drug-linker and an additional moiety present in the natural or non-natural amino acid, wherein the additional moiety can react to form the covalent linkage with the reactive moiety. Methods of conjugating drug-linkers to antibodies are known to a person of ordinary skill in the art, and the present disclosure provides for such methods, including methods disclosed in the Examples herein. Also see, e.g., Johann, K. et al., Polymer Chemistry, 27(11):4396-4407 (2020); Bioconjug Chem., 27(12):2791–2807 (2016); Northrop, B. H. et al., Polymer Chemistry, 18(6):3415-3430 (2015); Axup, J.Y. et al., Proc. Natl. Acad. Sci., 109(40):16101-16016 (2012); Hartmuth, C. et al., Angew. Chem. Int. Ed., 40(11):2004–2021 (2001); Sletten, E.M. and Bertozzi, C. R., Angew. Chem. Int. Ed., 48(38):6974- 6998 (2009); WO2006/050262A2; and WO2013/185177A1; the contents of each of which are hereby incorporated by reference in their entirety. In some embodiments, a drug-linker is conjugated to an antibody of the present disclosure by reacting a drug-linker containing a reactive group with an antibody containing one or more natural or non-natural amino acids. The conjugation reaction provides an antibody-drug conjugate, wherein the drug-linker is conjugated to a natural amino acid or a non-natural amino acid of the antibody via a covalent linkage. The WSGR Ref. No 31362-825.601 covalent linkage can be a product of the reactive group of the drug-linker and a different reactive group present in the natural amino acid or the non-natural amino acid. Non-limiting examples of reactions and linkages formed between payloads and natural amino acids or non-natural amino acids (collectively, “target conjugation site(s)”), that can be present in an antibody of the present disclosure, include those disclosed in the following paragraphs A to I. A. (i) Reaction of a drug-linker comprising reactive group -N3 with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising an alkynyl group, thereby providing a linkage comprising a 1,2,3-triazolyl moiety; or (ii) reaction of a drug-linker comprising a reactive alkynyl group with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising -N₃, thereby providing a linkage comprising a 1,2,3-triazolyl moiety. In some embodiments, the alkynyl group is a cyclooctynyl group. In some embodiments, the target conjugation site comprising -N3 is non- natural amino acid p-azido-L-phenylalanine. In some embodiments, the linkage comprising the 1,2,3-triazolyl moiety has the following structure:

; wherein: each s is independently 0 or an integer from 1 to 50; optionally, wherein each s is independently 0, 1, 2, 3, 4, 5 or 6; each t is independently 0 or an integer from 1 to 50; optionally, wherein each t is independently 0, 1, 2, 3, 4, 5 or 6; each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. B. (i) Reaction of a drug-linker comprising a reactive tetrazinyl group with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising an (E)-cyclooctenyl group, thereby providing a linkage comprising a 1,4-dihydropyridazinyl WSGR Ref. No 31362-825.601 moiety; or (ii) reaction of a drug-linker comprising a tetrazinyl group with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising an (E)- cyclooctenyl, thereby providing a linkage comprising a 1,4-dihydropyridazinyl moiety. In some embodiments, the linkage comprising the 1,4-dihydropyridazinyl moiety has the following structure:

wherein: each R^f is independently H or alkyl, optionally unsubstituted C1-C6 alkyl; each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. C. (i) Reaction of a drug-linker comprising an -ONH2 group with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid, such as para-acetyl-L- phenylalanine)) comprising a carbonyl-containing group (e.g., a ketone group), thereby providing a linkage comprising an oxime moiety; or (ii) reaction of a drug-linker comprising a carbonyl- containing group (e.g., a ketone group) with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising an -ONH₂ group, thereby providing a linkage comprising an oxime moiety. In some embodiments, the carbonyl containing group (e.g., ketone group) is -C(O)R^c, wherein R^c is unsubstituted C1-C6 alkyl. In some embodiments, R^c is methyl. In some embodiments, the linkage comprising the oxime moiety has the following structure:

optionally, each R^c is methyl; each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. D. (i) Reaction of a drug-linker comprising a maleimide group with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a thiol (-SH), thereby providing a linkage comprising a pyrrolidine-2,5-dione moiety, a thiol (-SH) group with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising a maleimide group, thereby providing a linkage comprising embodiments, the natural amino acid is cysteine. In some embodiments, the linkage comprising WSGR Ref. No 31362-825.601 the following structure:

wherein: each + denotes connection to a linker of the drug- linker; and each wavy line denotes connection to the antibody. E. (i) Reaction of a drug-linker comprising a primary or secondary amine with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group, thereby providing a linkage comprising an amide moiety; or (ii) reaction of a drug-linker comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a primary or secondary amine group, thereby providing a linkage comprising a amide moiety. In some embodiments, the natural amino acid is aspartic acid or glutamic acid. In some other embodiments, the natural amino acid is lysine. In some embodiments, the reaction is a peptide coupling reaction or other well-known method of forming an amide, each of which can be performed using methods readily understood by a person of ordinary skill in the art. In some embodiments, the linkage comprising the amide moiety has the following structure:

wherein: each R^j is independently H or alkyl; optionally unsubstituted C₁-C₆ alkyl; each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. F. (i) Reaction of a drug-linker comprising a hydroxyl group (-OH) with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group, thereby providing a linkage comprising an ester moiety; or (ii) reaction of a drug-linker comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a hydroxyl group (-OH), thereby providing a linkage comprising an ester moiety. In some embodiments, the natural amino acid is aspartic acid or glutamic acid. In some other embodiments, the natural amino acid is serine, threonine or tyrosine. Methods of forming such esters linkages can be performed using methods readily understood by a person of ordinary skill WSGR Ref. No 31362-825.601 in the art. In some embodiments, the linkage comprising the ester moiety has the following structure:

; wherein: each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. G. (i) Reaction of a drug-linker comprising a thiol group (-SH) with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group, thereby providing a linkage comprising a thioester moiety; or (ii) reaction of a drug-linker comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a thiol group (-SH), thereby providing a linkage comprising a thioester moiety. In some embodiments, the natural amino acid is aspartic acid or glutamic acid. In some other embodiments, the natural amino acid is cysteine. Methods of forming such thioesters linkages can be performed using methods readily understood by a person of ordinary skill in the art. In some embodiments, the linkage comprising the ester moiety has the following structure:

; wherein: each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. H. Reaction of a drug-linker comprising a -C(O)CH2NH2 group with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group, thereby providing a linkage comprising a -C(O)CH2NHC(O)- moiety; or (ii) reaction of a drug- linker comprising a carboxylic acid group, a protected carboxylic acid, or an activated ester group with an antibody, wherein the antibody contains a target conjugation site (e.g., a non-natural amino acid) comprising a -C(O)CH2NH2 group, thereby providing a linkage comprising a - C(O)CH2NHC(O)- moiety. In some embodiments, the natural amino acid is aspartic acid or glutamic acid. Methods of forming such linkages can be performed using methods readily understood by a person of ordinary skill in the art. In some embodiments, the linkage has the following structure:

; wherein: each + denotes connection to a linker of the drug-linker; and each wavy line denotes connection to the antibody. WSGR Ref. No 31362-825.601 I. Reaction of a drug-linker comprising a thiol group (-SH) with an antibody, wherein the antibody contains a target conjugation site (e.g., a natural or non-natural amino acid) comprising a thiol group, thereby providing a linkage comprising a disulfide. In some embodiments, the natural amino acid is cysteine. Methods of forming disulfide linkages can be performed using methods readily understood by a person of ordinary skill in the art. In some embodiments, an ADC of the present invention comprises an antibody and a drug, and is represented by the general formula (A) or (B):

wherein Ab is the antibody, wherein the antibody comprises one or more non-naturally encoded amino acids; L is a linker; E is a moiety joining the antibody Ab and the linker L; the drug is an auristatin analog having an N-terminus and a C-terminus; and d is an integer from 1 to 10. In some embodiments, the auristatin analog contains a 5-membered heteroaryl group at the C-terminal amino acid side chain. In some embodiments, the heteroaryl group is thienyl. In some embodiments, the ADC is an ADC of Formula (A), wherein linker L is joined to the auristatin analog N-terminus. In some other embodiments, the ADC is an ADC of Formula (B), wherein the linker L is joined to the auristatin analog C-terminus. In some embodiments, the linker L is selected from the linkers listed in Table 6, Table 7, Table 8, Table 9 or Table 10. In some embodiments, the antibody (Ab) comprises an amino acid sequence selected from the sequences listed in Table 1, Table 2, Table 3, Table 4 or Table 5. In some embodiments, there is provided an ADC of Formula (I-ADC) or Formula (II-

wherein: WSGR Ref. No 31362-825.601 Ab is an antibody, wherein the antibody comprises an amino acid sequence containing one or more non-naturally encoded amino acids; L is a linker; E is a moiety joining the antibody Ab to the linker L; d is an integer from 1 to 10; V is selected from the group consisting of -CH2-, -S-, -S(O)-, -C(O)- and -C(H)(Rv)-; wherein R_v is F, CN, N₃, OH, ONH₂ or optionally substituted C₁-C₈ alkyl; X is O or NH; Z is -CH2- or -C(O)-; R₅ is H, optionally substituted C₁-C₆ alkyl or optionally substituted C₃-C₆ cycloalkyl; R6 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; and R_7, R₈ and R₉ are each independently H, optionally substituted C₁-C₈ alkyl or optionally substituted C3-C6 cycloalkyl; R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R9 is H or optionally substituted C1- C₈ alkyl; or R₈ and R₉ are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R₇ is H, optionally substituted C₁- C8 alkyl or optionally substituted C3-C6 cycloalkyl; and R7a is H, optionally substituted C1-C8 alkyl or optionally substituted C3-C6 cycloalkyl; or a pharmaceutically acceptable salt thereof. In some embodiments, the ADC is an ADC of Formula (I-ADC). In some other embodiments, the ADC is an ADC of Formula (II-ADC). In some embodiments, the antibody (Ab) is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 1. In some embodiments, the antibody (Ab) is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 2. In some embodiments, the antibody (Ab) is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 3. In some embodiments, the antibody (Ab) is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 4. In some embodiments, the antibody (Ab) is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 5. In some embodiments, d is 1, 2, 3 or 4. In some embodiments, d is 2. In some embodiments, d is 3. In some embodiments, d is 4. WSGR Ref. No 31362-825.601 In some embodiments, V is selected from the group consisting of -CH₂-, -S-, -S(O)-, - C(O)- and -C(H)(Rv)-; wherein Rv is F, CN, N3, OH, ONH2 or optionally substituted C1-C8 alkyl. In some embodiments, V is -CH₂- or -C(H)(R_v)-. In some embodiments, V is CH₂. In some embodiments, X is O. In some other embodiments, X is NH. In some embodiments, Z is -CH2- or -C(O)-. In some embodiments, Z is -CH2-. In some other embodiments, Z is -C(O)-. In some embodiments, Z is -C(O)- and X is O. In other embodiments, Z is -C(O)- and X is NH. In some other embodiments, Z is -CH2- and X is O. In some embodiments, V is -CH2-, Z is -CH2- and X is -O-. In some embodiments, R₅ is H, optionally substituted C₁-C₆ alkyl or optionally substituted C3-C6 cycloalkyl. In some embodiments, R5 is H. In other embodiments, R5 is optionally substituted C1-C6 alkyl. In some more particular embodiments, R5 is methyl, ethyl, isopropyl or t-butyl. In some embodiments, R₅ is methyl. In some embodiments, when the ADC is an ADC of Formula (I-ADC), R5 is H or unsubstituted C1-C6 alkyl. In some further embodiments, R5 is H or methyl. In yet some further embodiments, R5 is H. In some embodiments, R₆ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl. In some embodiments, R6 is optionally substituted aryl or optionally substituted heteroaryl. In some embodiments, R6 is optionally substituted heteroaryl. In some embodiments, R6 is optionally substituted 5-membered heteroaryl. In some embodiments, said optionally substituted heteroaryl or optionally substituted 5-membered heteroaryl is selected from the group consisting of pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl and thiodiazolyl. In some embodiments, R₆ is unsubstituted heteroaryl. In some embodiments, R6 is unsubstituted 2-thienyl or unsubstituted 3-thienyl. In some embodiments, R6 is optionally substituted furanyl or thienyl. In some embodiments, R6 is unsubstituted 2-thienyl or unsubstituted 3-thienyl. In some embodiments, R₆ is unsubstituted 2-thienyl. In some embodiments, R₆ is unsubstituted 3-thienyl. In some embodiments, R7, R8 and R9 are each independently H, optionally substituted C1- C8 alkyl or optionally substituted C3-C6 cycloalkyl. In some other embodiments, R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R₉ is H or optionally substituted C₁- C8 alkyl. In some other embodiments, R8 and R9 are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R7 is H, optionally substituted C1-C8 alkyl or optionally substituted C₃-C₆ cycloalkyl. WSGR Ref. No 31362-825.601 In some other embodiments, R_7, R₈ and R₉ are each independently H, optionally substituted C1-C8 alkyl or optionally substituted C3-C6 cycloalkyl. In some embodiments, R7, R8 and R9 are each independently H or optionally substituted C₁-C₈ alkyl. In some embodiments, R₇ is H or methyl. In some embodiments, R₇ is methyl. In some embodiments, R8 is H. In some other embodiments, R8 is methyl. In some embodiments, R9 is C1-C6 alkyl. In some embodiments, R9 is methyl, ethyl, propyl or isopropyl. In some embodiments, R₉ is isopropyl. In some embodiments, R8 and R9 are each methyl. In some embodiments, R8 is H and R9 is C1-C6 alkyl. In some further embodiments, R8 is H and R₉ is methyl, ethyl, propyl or isopropyl. In some embodiments, R₈ is H and R₉ is isopropyl. In some embodiments, R7a is H, optionally substituted C1-C8 alkyl or optionally substituted C3-C6 cycloalkyl. In some embodiments, R7a is H or optionally substituted C1-C8 alkyl. In some embodiments, R_7a is H. In other embodiments, R_7a is optionally substituted C₁-C₆ alkyl. In some more particular embodiments, R7a is methyl, ethyl, isopropyl or t-butyl. In some embodiments, R7a is methyl. In some embodiments, when the ADC is an ADC of Formula (II-ADC), R7a is H or methyl. In some further embodiments, R₇ and R_7a are each methyl. In some embodiments, V is -CH₂-; Z is -CH₂-; X is -O-; R₆ is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R7 is H or unsubstituted C1-C6 alkyl; R7a is H or unsubstituted C1-C6 alkyl; R8 and R9 are each independently H or C1-C6 alkyl; and L is the linker. In some embodiments, R₅ is H In some other embodiments, V is -CH2-; Z is -C(O)-; X is -O-; R6 is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R7 is H or unsubstituted C1-C6 alkyl; R7a is H or unsubstituted C₁-C₆ alkyl; R₈ and R₉ are each independently H or C₁-C₆ alkyl; and L is the linker. In some embodiments, R5 is H. In some embodiments, E comprises an amide, an ester, a thioester, a pyrrolidine-2,5-dione, an oxime, a 1,2,3-triazole or a 1,4-dihydropyridazine. In some embodiments, the 1,2,3-triazole and the 1,4-dihydropyridazine are each optionally fused to an 8-membered ring. In some embodiments, E is selected from the group consisting of:

WSGR Ref. No 31362-825.601

wherein: each Rb is independently H or unsubstituted C1-C6 alkyl; each Rc is independently unsubstituted C1-C6 alkyl; each R_t is independently H or unsubstituted C₁-C₆ alkyl, each s is independently 0, 1, 2, 3, 4, 5 or 6, each t is independently 0, 1, 2, 3, 4, 5 or 6; each + denotes connection to L; and each wavy line denotes connection to Ab. In some embodiments, E comprises an oxime. In some embodiments, E is oxime. In some embodiments, E has the following structure: ; wherein Rc is unsubstituted C1-C6 alkyl; + denotes connection to linker L; and the wavy line denotes connection to Ab. In some embodiments, Rc is methyl. In some embodiments, each of the one or more non-naturally encoded amino acids is independently selected from the group consisting of 4-acetyl-L-phenylalanine (para-acetyl-L- glucosaminyl)-L-asparagine, O-allyl-L-tyrosine, alpha-N-acetylgalactosamine-O-L-serine, WSGR Ref. No 31362-825.601 alpha-N-acetylgalactosamine-O-L-threonine, 2-aminooctanoic acid, 2-amino-L-phenylalanine, 3- amino-L-phenylalanine, 4-amino-L-phenylalanine, 2-amino-L-tyrosine, 3-amino-L-tyrosine, 4- azido-L-phenylalanine, 4-benzoyl-L-phenylalanine, (2,2-bipyridin-5yl)-L-alanine, 3-borono-L- phenylalanine, 4-borono-L-phenylalanine, 4-bromo-L-phenylalanine, p-carboxymethyl-L- phenylalanine, 4-carboxy-L-phenylalanine, p-cyano-L-phenylalanine, 3,4-dihydroxy-L- phenylalanine (L-DOPA), 4-ethynyl-L-phenylalanine, 2-fluoro-L-phenylalanine, 3-fluoro-L- phenylalanine, 4-fluoro-L-phenylalanine, O-(3-O-D-galactosyl-N-acetyl-beta-D- galactosaminyl)-L-serine, L-homoglutamine, (8-hydroxyquinolin-3-yl)-L-alanine, 4-iodo-L- phenylalanine, 4-isopropyl-L-phenylalanine, O-i-propyl-L-tyrosine, 3-isopropyl-L-tyrosine, O- mannopyranosyl-L-serine, 2-methoxy-L-phenylalanine, 3-methoxy-L-phenylalanine, 4-methoxy- L-phenylalanine, 3-methyl-L-phenylalanine, O-methyl-L-tyrosine, 3-(2-naphthyl)-L-alanine, 5- nitro-L-histidine, 4-nitro-L-histidine, 4-nitro-L-leucine, 2-nitro-L-phenylalanine, 3-nitro-L- phenylalanine, 4-nitro-L-phenylalanine, 4-nitro-L-tryptophan, 5-nitro-L-tryptophan, 6-nitro-L- tryptophan, 7-nitro-L-tryptophan, 2-nitro-L-tyrosine, 3-nitro-L-tyrosine, O-phospho-L-serine, O- phospho-L-tyrosine, 4-propargyloxy-L-phenylalanine, O-2-propyn-1-yl-L-tyrosine, 4-sulfo-L- phenylalanine, para-(2-azidoethoxy)-L-phenylalanine ((S)-2-amino-3-(4-(2- azidoethoxy)phenyl)propanoic acid) and O-sulfo-L-tyrosine. In some embodiments, the non-naturally encoded amino acid is para-acetyl-L- phenylalanine (pAF). In some embodiments, the antibody comprises at least two non-naturally encoded amino acids. In some embodiments, the antibody comprises 1, 2, 3, 4, 5, 6, 7 or 8 non-naturally encoded amino acids. In some embodiments, the antibody comprises 1, 2, 3 or 4 non-naturally encoded amino acids. In some embodiments, each of the one or more non-naturally encoded amino acids is the same. In some embodiments, each of the one or more non-naturally encoded amino acids is pAF. In some other embodiments, at least two of the non-naturally encoded amino acids are different. In some embodiments, at least one of the non-naturally occurring amino acids is pAF. In some embodiments, the linker comprises at least one linker moiety. In some embodiments, the linker L is selected from the group consisting of the linkers listed in Table 6. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 7. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 8. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 9. In some other embodiments, the linker is selected from the group consisting of the linkers listed in Table 10. WSGR Ref. No 31362-825.601 In some embodiments, the ADC is an ADC of Formula (I-ADC), and the linker is a non- cleavable linker. In some embodiments, the non-cleavable linker comprises one or more linker moieties selected from the group consisting of unsubstituted alkylene and –(O-alkylene)_n–, wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some other embodiments, the ADC is an ADC of Formula (II-ADC), and the linker is a cleavable linker. In some embodiments, the cleavable linker comprises a pyrophosphate ester. In some further embodiments, the ADC is an ADC of Formula (I-ADC-1) and Formula

Ab is an antibody, wherein the antibody comprises an amino acid sequence containing one or more non-naturally encoded amino acids; L is a linker; d is an integer from 1 to 10; V is selected from the group consisting of -CH2-, -S-, -S(O)-, -C(O)- and -C(H)(Rv)-; wherein R_v is F, CN, N₃, OH, ONH₂ or optionally substituted C₁-C₈ alkyl; X is O or NH; Z is -CH2- or -C(O)-; Rc is unsubstituted C1-C6 alkyl; R₅ is H, optionally substituted C₁-C₆ alkyl or optionally substituted C₃-C₆ cycloalkyl; R₆ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; and R_7, R₈ and R₉ are each independently H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; R₇ and R₈ are joined to form an optionally substituted heterocycloalkyl, and R9 is H or optionally substituted C1- C₈ alkyl; or R₈ and R₉ are joined to form an optionally substituted cycloalkyl or WSGR Ref. No 31362-825.601 an optionally substituted heterocycloalkyl, and R₇ is H, optionally substituted C₁- C8 alkyl or optionally substituted C3-C6 cycloalkyl; and R_7a is H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; or a pharmaceutically acceptable salt thereof. In some embodiments, the antibody (Ab) is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 1. In some embodiments, the antibody (Ab) is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 2. In some embodiments, the antibody (Ab) is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 3. In some embodiments, the antibody (Ab) is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 4. In some embodiments, the antibody (Ab) is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 5. In some embodiments, the non-naturally encoded amino acid is para-acetyl-L- phenylalanine (pAF). In some embodiments, R_c is methyl. In some embodiments, d is 1, 2, 3 or 4. In some embodiments, d is 2. In some embodiments, d is 3. In some embodiments, d is 4. In some embodiments, V is selected from the group consisting of -CH2-, -S-, -S(O)-, - C(O)- and -C(H)(R_v)-; wherein R_v is F, CN, N₃, OH, ONH₂ or optionally substituted C₁-C₈ alkyl. In some embodiments, V is -CH2- or -C(H)(Rv)-. In some embodiments, V is CH2. In some embodiments, X is O. In some other embodiments, X is NH. In some embodiments, Z is -CH₂- or -C(O)-. In some embodiments, Z is -CH₂-. In some other embodiments, Z is -C(O)-. In some embodiments, Z is -C(O)- and X is O. In other embodiments, Z is -C(O)- and X is NH. In some other embodiments, Z is -CH₂- and X is O. In some embodiments, V is -CH₂-, Z is -CH₂- and X is -O-. In some embodiments, R5 is H, optionally substituted C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl. In some embodiments, R5 is H. In other embodiments, R5 is optionally substituted C₁-C₆ alkyl. In some more particular embodiments, R₅ is methyl, ethyl, isopropyl or t-butyl. In some embodiments, R5 is methyl. In some embodiments, when the ADC is an ADC of Formula (I-ADC-1), R5 is H or unsubstituted C1-C6 alkyl. In some further embodiments, R5 is H or methyl. In yet some further embodiments, R₅ is H. WSGR Ref. No 31362-825.601 In some embodiments, R₆ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl. In some embodiments, R₆ is optionally substituted aryl or optionally substituted heteroaryl. In some embodiments, R₆ is optionally substituted heteroaryl. In some embodiments, R₆ is optionally substituted 5-membered heteroaryl. In some embodiments, said optionally substituted heteroaryl or optionally substituted 5-membered heteroaryl is selected from the group consisting of pyrrolyl, thienyl, furanyl, imidazolyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, isothiazolyl and thiodiazolyl. In some embodiments, R6 is unsubstituted heteroaryl. In some embodiments, R6 is unsubstituted 2-thienyl or unsubstituted 3-thienyl. In some embodiments, R6 is optionally substituted furanyl or thienyl. In some embodiments, R₆ is unsubstituted 2-thienyl or unsubstituted 3-thienyl. In some embodiments, R6 is unsubstituted 2-thienyl. In some embodiments, R6 is unsubstituted 3-thienyl. In some embodiments, R_7, R₈ and R₉ are each independently H, optionally substituted C₁- C8 alkyl or optionally substituted C3-C6 cycloalkyl. In some other embodiments, R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R9 is H or optionally substituted C1- C₈ alkyl. In some other embodiments, R₈ and R₉ are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R₇ is H, optionally substituted C₁-C₈ alkyl or optionally substituted C3-C6 cycloalkyl. In some other embodiments, R7, R8 and R9 are each independently H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl. In some embodiments, R_7, R₈ and R₉ are each independently H or optionally substituted C1-C8 alkyl. In some embodiments, R7 is H or methyl. In some embodiments, R7 is methyl. In some embodiments, R₈ is H. In some other embodiments, R₈ is methyl. In some embodiments, R9 is C1-C6 alkyl. In some embodiments, R9 is methyl, ethyl, propyl or isopropyl. In some embodiments, R9 is isopropyl. In some embodiments, R₈ and R₉ are each methyl. In some embodiments, R₈ is H and R₉ is C₁-C₆ alkyl. In some further embodiments, R₈ is H and R9 is methyl, ethyl, propyl or isopropyl. In some embodiments, R8 is H and R9 is isopropyl. In some embodiments, R7a is H, optionally substituted C1-C8 alkyl or optionally substituted C₃-C₆ cycloalkyl. In some embodiments, R_7a is H or optionally substituted C₁-C₈ alkyl. In some embodiments, R7a is H. In other embodiments, R7a is optionally substituted C1-C6 alkyl. In some more particular embodiments, R7a is methyl, ethyl, isopropyl or t-butyl. In some embodiments, R_7a is methyl. In some embodiments, when the ADC is an ADC of Formula (II-ADC), R_7a is H or methyl. In some further embodiments, R7 and R7a are each methyl. WSGR Ref. No 31362-825.601 In some embodiments, V is -CH₂-; Z is -CH₂-; X is -O-; R₆ is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R7 is H or unsubstituted C1-C6 alkyl; R7a is H or unsubstituted C₁-C₆ alkyl; R₈ and R₉ are each independently H or C₁-C₆ alkyl; and L is the linker. In some embodiments, R₅ is H In some other embodiments, V is -CH2-; Z is -C(O)-; X is -O-; R6 is optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R7 is H or unsubstituted C1-C6 alkyl; R7a is H or unsubstituted C₁-C₆ alkyl; R₈ and R₉ are each independently H or C₁-C₆ alkyl; and L is the linker. In some embodiments, R5 is H. In some embodiments, the linker comprises at least one linker moiety. In some embodiments, the linker L is selected from the group consisting of the linkers listed in Table 6. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 7. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 8. In some other embodiments, the linker L is selected from the group consisting of the linkers listed in Table 9. In some other embodiments, the linker is selected from the group consisting of the linkers listed in Table 10. In some embodiments, the ADC is an ADC of Formula (I-ADC), and the linker is a non- cleavable linker. In some embodiments, the non-cleavable linker comprises one or more linker moieties selected from the group consisting of unsubstituted alkylene and –(O-alkylene)n–, wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some other embodiments, the ADC is an ADC of Formula (II-ADC), and the linker is a cleavable linker. In some embodiments, the cleavable linker comprises a pyrophosphate ester. In some embodiments, the ADC is an ADC of Formula (I-ADC-1). In some embodiments, the ADC of Formula (I-ADC-1) selected from the group consisting of:

WSGR Ref. No 31362-825.601 ,

wherein each unspecified variable group is as defined for Formula (I-ADC-1); and pharmaceutically acceptable salts thereof. In some embodiments, d is 1, 2, 3 or 4, and Rc is methyl. In some other embodiments, the ADC is an ADC of Formula (II-ADC-1). In some embodiments, the ADC of Formula (II-ADC-1) is selected from the group consisting of:

WSGR Ref. No 31362-825.601

wherein each unspecified variable group is as defined for Formula (II-ADC-1); and pharmaceutically acceptable salts thereof. In some embodiments, d is 1, 2, 3 or 4, and R7a is H or methyl. In some aspects, an ADC of the present disclosure, including but not limited to an ADC of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1), can comprise a heavy chain, wherein the heavy chain is characterized as having a heavy chain amino acid sequence; a light chain, wherein the light chain is characterized as having a light chain amino acid sequence; or both. In some embodiments, the heavy chain amino acid sequence comprises at least one non-naturally encoded amino acid. In some embodiments, the light chain amino acid sequence does not contain a non-naturally encoded amino acid. In some other embodiments, the light chain amino acid sequence comprises at least one non-naturally encoded amino acid. In some embodiments, the heavy chain amino acid sequence comprises a first non-naturally encoded amino acid, and the light chain amino acid sequence comprises a second non-naturally encoded amino acid. In some embodiments, the first non-naturally encoded amino acid and the second non-naturally encoded amino acid are the same. In some embodiments, the first non-naturally encoded amino acid and the second non-naturally encoded amino acid is pAF. In some aspects, an ADC of the present disclosure, including but not limited to an ADC of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1), can comprise two heavy chains, wherein each heavy chain is characterized as having a heavy chain amino acid sequence; and two light chains, wherein each light chain is characterized as having a light chain amino acid sequence. In some embodiments, each heavy chain amino acid sequence comprises at least one non-naturally encoded amino acid. In some embodiments, each light chain amino acid sequence does not contain a non-naturally encoded amino acid. In some other embodiments, each light chain amino acid sequence comprises at least one non-naturally encoded amino acid. In some embodiments, the antibody comprises two heavy chains and two light chains, wherein each heavy chain amino acid sequence and each light chain amino acid sequence comprises at least one non-naturally encoded amino acid. In some embodiments, each heavy chain amino acid sequence and each light chain amino acid sequence comprises one non- WSGR Ref. No 31362-825.601 naturally encoded amino acid. In some embodiments, each non-naturally encoded amino acid is the same. In some embodiments, each non-naturally encoded amino acid is pAF. In some embodiments, the antibody (e.g., an antibody Ab of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1)) is configured to bind to an antigen. In some embodiments, the antibody binds to a tumor-associated antigen (TAA), as disclosed herein. In some embodiments, the antibody (e.g., Ab of Formula (A), Formula (B), Formula (I- ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1)) is an anti-trophoblast antigen 2 (anti-TROP2) antibody. In some embodiments, the anti-TROP2 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 17 (see Table 1). In some embodiments, the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 1, 2, 5 and 6, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NO: 4, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17. In some embodiments, the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 1, 2, 5 and 6, and the light chain amino acid sequence is SEQ ID NO: 4. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 1, and the light chain amino acid sequence is SEQ ID NO: 4. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 5, and the light chain amino acid sequence is SEQ ID NO: 4. In some embodiments, the heavy chain amino acid sequence comprises the one or more non-naturally encoded amino acids. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 5, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some other embodiments, the antibody (e.g., Ab of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1)) is an anti-CD70 antibody. In some embodiments, the anti-CD70 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 18 to 24 (see Table 2). In some embodiments, the anti-CD70 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 18 and 20, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 19, 21, 22, 23 and 24. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 20, and the light chain amino acid sequence is SEQ ID NO: 19. In some embodiments, the heavy chain amino acid sequence comprises the one or more non-naturally encoded amino acids. In some embodiments, WSGR Ref. No 31362-825.601 the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 20, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some other embodiments, the antibody (e.g., Ab of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1)) is an anti-HER2 antibody. In some embodiments, the anti-HER2 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 25, 26, 27 and 28 (see Table 3). In some embodiments, the anti-HER2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 25 and 26, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 27 and 28. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 26, and the light chain amino acid sequence is SEQ ID NO: 27. In some embodiments, the heavy chain amino acid sequence comprises the one or more non-naturally encoded amino acids. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 26, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some other embodiments, the antibody (e.g., Ab of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1)) is an anti-PSMA antibody. In some embodiments, the anti-PSMA antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 29 to 45 (see Table 4). In some embodiments, the anti-PSMA antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 36, 38, 40, 42 and 44, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 37, 39, 41, 43 and 45. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 36, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 37, 39, 41, 43 and 45. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 36, and the light chain amino acid sequence is SEQ ID NO: 37. In some embodiments, the heavy chain amino acid sequence comprises the one or more non-naturally encoded amino acids. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 36, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some other embodiments, the antibody (e.g., Ab of Formula (A), Formula (B), Formula (I-ADC), Formula (II-ADC), Formula (I-ADC-1) or Formula (II-ADC-1)) is an anti-HER3 antibody. In some embodiments, the anti-HER3 antibody comprises an amino acid sequence WSGR Ref. No 31362-825.601 selected from the group consisting of SEQ ID NOs: 46 to 58 (see Table 5). In some embodiments, the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 46 or 58, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 47 to 57. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. In some other embodiments, the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. In some embodiments, the heavy chain amino acid sequence comprises the one or more non-naturally encoded amino acids. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 58, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some embodiments, the ADC is an ADC of Formula (I-ADC-17):

wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence containing one or more non-naturally encoded amino acids; d is an integer from 1 to 10; and R_c is unsubstituted C₁-C₆ alkyl; or a pharmaceutically acceptable salt thereof. In some embodiments, the antibody (Ab) is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 1. In some embodiments, the antibody (Ab) is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 2. In some embodiments, the antibody (Ab) is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 3. In some embodiments, the antibody (Ab) is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 4. In some embodiments, the antibody (Ab) is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 5. In some embodiments, the non-naturally encoded amino acid is para-acetyl-L- phenylalanine (pAF). In some embodiments, Rc is methyl. WSGR Ref. No 31362-825.601 In some embodiments, d is 1, 2, 3 or 4. In some embodiments, d is 2. In some embodiments, d is 3. In some embodiments, d is 4. In some embodiments, Ab is an anti-HER3 antibody. In some embodiments, the anti- HER3 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 46 to 58 (see Table 5). In some embodiments, the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 46 or 58, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 47 to 57. In some embodiments, the anti-HER3 antibody heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 58, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some other embodiments, the anti-HER3 antibody heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid, and the light chain amino acid sequence comprises one non-naturally encoded amino acid. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 58, according to Kabat numbering; and the light chain comprises one non-naturally encoded amino acid at position 121. In some embodiments, each non-naturally encoded amino acid is pAF. In some other embodiments, Ab is an anti-TROP2 antibody. In some embodiments, the anti-TROP2 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 17 (see Table 1). In some embodiments, the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 1, 2, 5 and 6, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NO: 4, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17. In some embodiments, the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 1, 2, 5 and 6, and the light chain amino acid sequence is SEQ ID NO: 4. In some embodiments, the heavy chain amino acid sequence is SEQ ID NO: 5, and the light chain amino acid sequence is SEQ ID NO: 4. In some embodiments, the heavy chain amino acid sequence comprises one or more non- naturally encoded amino acid. In some embodiments, the heavy chain amino acid sequence WSGR Ref. No 31362-825.601 comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 5, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. The present disclosure also provides ADCs comprising branched linkers. In some embodiments, there is provided an ADC of Formula (III-ADC) or (IV-ADC)):

wherein: each V is selected from the group consisting of -CH2-, -S-, -S(O)-, -C(O)- and - C(H)(R_v)-; wherein R_v is F, CN, N₃, OH, ONH₂ or optionally substituted C₁-C₈ alkyl; Ab is an antibody, wherein the antibody comprises one or more non-naturally encoded amino acids; E is a moiety joining Ab and L1; each X is O or NH; each Z is -CH2- or -C(O)-; each R5 is H, optionally substituted C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl; each R₆ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; each R_7, R₈ and R₉ are each independently H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; R7 and R8 are joined to form an optionally substituted heterocycloalkyl, and R9 is H or optionally substituted C₁-C₈ alkyl; or WSGR Ref. No 31362-825.601 R₈ and R₉ are joined to form an optionally substituted cycloalkyl or an optionally substituted heterocycloalkyl, and R7 is H, optionally substituted C1-C8 alkyl or optionally substituted C₃-C₆ cycloalkyl; each R_7a is H, optionally substituted C₁-C₈ alkyl or optionally substituted C₃-C₆ cycloalkyl; F1 is N or CH; and L₁, L₂ and L₃ are each independently a linker; or a pharmaceutically acceptable salt thereof. In some embodiments, R6 is optionally substituted heteroaryl. In some embodiments, R6 is unsubstituted 2-thienyl or unsubstituted 3-thienyl. In some embodiments, E comprises an oxime. In some embodiments, E is oxime. In some embodiments, E has the following structure:

; wherein R_c is unsubstituted C₁-C₆ alkyl; + denotes connection to linker L; and the wavy line denotes connection to Ab. In some embodiments, Rc is methyl. In some embodiments, the antibody (Ab) is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 1. In some embodiments, the antibody (Ab) is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 2. In some embodiments, the antibody (Ab) is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 3. In some embodiments, the antibody (Ab) is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 4. In some embodiments, the antibody (Ab) is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 5. In some embodiments, each linker is independently selected from the group consisting of the linkers listed in Table 6. In some other embodiments, each linker is independently selected from the group consisting of the linkers listed in Table 7. In some other embodiments, each linker is independently selected from the group consisting of the linkers listed in Table 8. In some other embodiments, each linker is independently selected from the group consisting of the linkers listed in Table 9. In some other embodiments, each linker is independently selected from the group consisting of the linkers listed in Table 10. The present disclosure also provides ADCs comprising the drug MMAE. In some aspects, the present disclosure provides an ADC of Formula (V-ADC) or Formula (VI-ADC): WSGR Ref. No 31362-825.601

wherein: the ADC comprises drug MMAE conjugated to an antibody via a linker and an oxime; Ab is the antibody; d is an integer from 1 to 10; R7a is H, optionally substituted C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl; optionally, R_7a is H or methyl; R_c is unsubstituted C₁-C₆ alkyl; and L is the linker. In some embodiments, Rc is methyl. In some embodiments, the antibody (Ab) is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 1. In some embodiments, the antibody (Ab) is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 2. In some embodiments, the antibody (Ab) is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 3. In some embodiments, the antibody (Ab) is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 4. In some embodiments, the antibody (Ab) is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of the sequences listed in Table 5. In some embodiments, each linker is independently a linker of any one of Tables 6 to 10. In some embodiments, the ADC is an ADC of Formula (VI-ADC), and the linker is selected from the group consisting of: WSGR Ref. No 31362-825.601

wherein: each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each i is independently 0 or 1; * denotes connection to drug; and the wavy line denotes connection to the antibody. In some embodiments, the linker has the following structure:

; wherein * denotes connection to drug; and the wavy line denotes connection to the antibody. The present disclosure also provides ADCs comprising the drug-linker compound AS269.

wherein Ab is an anti-HER3 antibody comprising at least one non-natural amino acid. In some embodiments, the anti-HER3 antibody comprises an amino acid sequence selected from the group consisting of the amino acid sequences listed in Table 5. In some embodiments, the anti-HER3 antibody comprises an amino acid sequence selected from the group consisting of WSGR Ref. No 31362-825.601 SEQ ID NOs: 46 to 58 (see Table 5). In some embodiments, the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 46 or 58, and the light chain amino acid sequence is selected from the group consisting of SEQ ID NOs: 47 to 57. In some embodiments, the anti-HER3 antibody heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 58, according to Kabat numbering. In some embodiments, the one non-naturally encoded amino acid is pAF. In some other embodiments, the anti-HER3 antibody heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid, and the light chain amino acid sequence comprises one non-naturally encoded amino acid. In some embodiments, the heavy chain amino acid sequence comprises one non-naturally encoded amino acid at amino acid sequence position 114 of SEQ ID NO: 58, according to Kabat numbering; and the light chain comprises one non-naturally encoded amino acid at position 121. In some embodiments, each non-naturally encoded amino acid is pAF. In some embodiments, ADC, or a composition, of the present disclosure does not contain a Toll-like receptor (TLR) agonist. It is understood that an ADC is typically produced as a composition containing a population of ADCs, i.e., a mixture of ADCs that are essentially identical, except for the drug load. As disclosed herein, an ADC composition can be characterized by a drug-to-antibody ratio (DAR), which reports on the average number of drugs conjugated to antibody in the ADC composition. Thus, in some aspects, the present disclosure provides an ADC composition comprising a mixture of ADCs, wherein each ADC in the mixture is identical, except that the number of drugs or drug- linkers that are conjugated to each antibody can vary. In a non-limiting example, an ADC of the present disclosure comprises a first ADC, a second ADC, a third ADC and a fourth ADC, wherein the first ADC, the second ADC, the third ADC and the fourth ADC are identical, except that the first ADC comprises one drug or drug-linker, the second ADC comprises two drugs or drug- linkers, the third ADC comprises three drugs or drug-linkers, and the fourth ADC comprises four drugs or drug-linkers. In some embodiments, an ADC composition of the present disclosure is characterized as having a DAR of at least about 1 and at most about 8. In some embodiments, the ADC WSGR Ref. No 31362-825.601 composition is characterized as having a DAR of at least about 2 and at most about 8, at least about 2 and at most about 6, or at least about 2 and at most about 4. In some embodiments, the ADC composition is characterized as having a DAR of at least about 3 and at most about 4. In some embodiments, the ADC composition is characterized as having a DAR of at least about 1 and at most about 2. In some embodiments, the ADC composition is characterized as having a DAR of at least about 1 and at most about 3. In some embodiments, the ADC composition is characterized as having a DAR of at least about 2 and at most about 4. In some embodiments, the ADC composition is characterized as having a DAR of at least about 3 and at most about 4. In some aspects of the disclosure, antibody, antibody fragments, variant or drug conjugate with increased serum half-life, water solubility, bioavailability, therapeutic half-life, or circulation time, or to modulate immunogenicity, or biological activity is desired. One method of achieving such desired features of the compositions disclosed herein, is by covalent attachment of the polymer polyethylene glycol, (PEG). To maximize the desired properties of PEG, the total molecular weight and hydration state of the polymer or polymers attached to the biologically active molecule must be sufficiently high to impart the advantageous characteristics typically associated with such polymer attachment, such as increased water solubility and circulating half- life, while not adversely impacting the bioactivity of the molecule to which the PEG is attached. PEG derivatives are frequently linked to biologically active molecules through reactive chemical functionalities, such as amino acid residues, the N-terminus, and/or carbohydrate moieties. In some aspects of the present invention, PEG derivatives are linked to biologically active molecules through reactive chemical functionalities to improve biophysical properties of the resulting ADC. WO99/67291 discloses a process for conjugating a protein with PEG, wherein at least one amino acid residue on the protein is substituted with a synthetic amino acid and the protein is contacted with PEG under conditions sufficient to achieve conjugation to the protein. In some aspects of the disclosure antibody, antibody fragments, variant or drug conjugate with increase serum half-life, water solubility, bioavailability, therapeutic half-life, or circulation time, or to modulate immunogenicity, or biological activity is desired. One method of achieving such desired features of the composition disclosed herein, is by covalent attachment of the polymer polyethylene glycol, (PEG). To maximize the desired properties of PEG, the total molecular weight and hydration state of the polymer or polymers attached to the biologically active molecule must be sufficiently high to impart the advantageous characteristics typically associated with such polymer attachment, such as increased water solubility and circulating half-life, while not adversely impacting the bioactivity of the molecule to which the PEG is attached. PEG derivatives are frequently linked to biologically active molecules through reactive chemical functionalities, WSGR Ref. No 31362-825.601 such as amino acid residues, the N-terminus, and/or carbohydrate moieties. In some aspects of the present invention, PEG derivatives are linked to biologically active molecules through reactive chemical functionalities to improve biophysical properties of the resulting ADC. WO99/67291 discloses a process for conjugating a protein with PEG, wherein at least one amino acid residue on the protein is substituted with a synthetic amino acid and the protein is contacted with PEG under conditions sufficient to achieve conjugation to the protein. Proteins and other molecules often have a limited number of reactive sites available for polymer attachment. The sites most suitable for modification via polymer attachment may play a significant role in receptor binding, and such sites may be necessary for retention of the biological activity of the molecule therefore making them inappropriate for polymer attachment. As a result, indiscriminate attachment of polymer chains to such reactive sites on a biologically active molecule often leads to a significant reduction or even total loss of biological activity of the polymer-modified molecule, PEG attachment can be directed to a particular position within a protein such that the PEG moiety does not interfere with the function of that protein. One method of directing PEG attachment is to introduce a synthetic amino acid into the protein sequence. The protein biosynthetic machinery of the prokaryote Escherichia coli (E. coli) can be altered in order to incorporate synthetic amino acids efficiently and with high fidelity into proteins in response to the amber codon, UAG. See, e.g., J. W. Chin et al., J. Amer. Chem. Soc.124: 9026-9027, 2002; J. W. Chin, & P. G. Schultz, ChemBioChem 3(11): 1135-1137, 2002; J. W. Chin, et al., PNAS USA 99: 11020-11024, 2002; and, L. Wang, & P. G. Schultz, Chem. Comm., 1: 1-11, 2002. A similar method can be accomplished with the eukaryote, Saccharomyces cerevisiae (S. cerevisiae) (e.g., J. Chin et al., Science 301: 964-7, 2003). Using this method, a non-naturally encoded amino acid can be incorporated into an antibody, variant or drug conjugate of the present disclosure, providing an attachment site for PEG. See, for example WO2010/011735 and WO2005/074650. Methodology and Techniques The present disclosure encompasses methodologies and technologies well known in the art. These include conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques and pharmacology, within the skill of the art. Compounds of the present disclosure can be synthesized using several processes or schemes employed in the art. See for example, Dubowchik et al., Bioconjugate Chem.13: 855-869, 2002; Doronina et al., Nature Biotechnology 21(7): 778-784, 2003; WO2012/166560; WO2013/185117, each incorporated herein by reference. Many methodologies and techniques for synthesis of pharmaceutical, diagnostic or therapeutic compounds are well known to one of ordinary skill in the art. WSGR Ref. No 31362-825.601 The present disclosure, unless otherwise indicated, also encompass conventional techniques of molecular biology (including recombinant techniques), cell biology, biochemistry and immunology, all within the skill of the art. Such techniques are explained fully in the literature, such as, Molecular Cloning: A Laboratory Manual, Third Edition, Cold Spring Harbor Press, Cold Spring Harbor, NY (Sambrook et al. Eds., 2001); Oligonucleotide Synthesis: Methods And Applications (Methods in Molecular Biology), Herdewijn, P., Ed., Humana Press, Totowa, NJ; Oligonucleotide Synthesis (Gait, M. J., Ed., 1984); Methods In Molecular Biology, Humana Press, Totowa, NJ; Cell Biology: A Laboratory Notebook ,Academic Press, New York, NY (Cellis, J. E., Ed., 1998); Animal Cell Culture (Freshney, R. I., Ed., 1987); Introduction To Cell And Tissue Culture Plenum Press, New York, NY, (Mather, J. P. and Roberts, P. E., Eds., 1998); Cell And Tissue Culture: Laboratory Procedures John Wiley and Sons, Hoboken, NJ, (Doyle, A. et al., Eds., 1993-8); Methods In Enzymology (Academic Press, Inc.) New York, NY; Weir's Handbook Of Experimental Immunology Wiley-Blackwell Publishers, New York, NY, (Herzenberg, L. A. et al. Eds., 1997); Gene Transfer Vectors For Mammalian Cells Cold Spring Harbor Press, Cold Spring Harbor, NY, (Miller, J. M. et al. Eds., 1987); Current Protocols In Molecular Biology, Greene Pub. Associates, New York, NY, (Ausubel, F. M. et al., Eds., 1987); PCR: The Polymerase Chain Reaction, Birkhauser, Boston, MA, (Mullis, K. et al., Eds., 1994); Current Protocols In Immunology, John Wiley and Sons, Hoboken, NJ, (Coligan, J. E. et al., eds., 1991); Short Protocols In Molecular Biology, Hoboken, NJ, (John Wiley and Sons, 1999); Immunobiology 7 Garland Science, London, UK, (Janeway, C. A. et al., 2007); Antibodies. Stride Publications, Devoran, UK, (P. Finch, 1997); Antibodies: A Practical Approach Oxford University Press, USA, New York, NY, (D. Catty., ed., 1989); Monoclonal Antibodies: A Practical Approach Oxford University Press, USA, New York NY, (Shepherd, P. et al. Eds., 2000); Using Antibodies: A Laboratory Manual Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, (Harlow, E. et al. Eds., 1998); The Antibodies Harwood Academic Publishers, London, UK, (Zanetti, M. et al. Eds.1995). Therapeutic Uses of ADCs The antibodies or ADCs of the disclosure are useful for treating a wide range of diseases. disorders, conditions, or cancers. Compositions disclosed herein may be used to modulate an immune response. Modulation of an immune response may comprise stimulating, activating, increasing, enhancing, or up-regulating an immune response. Modulation of an immune response may comprise suppressing, inhibiting, preventing, reducing, or downregulating an immune response. In some embodiments, the ADCs of the present invention may be used for reducing or WSGR Ref. No 31362-825.601 inhibiting tumor growth or progression in an antigen-expressing cancer or cancer cell comprising an effective amount of the ADC. Disclosed herein are methods of treating a subject for a condition with an ADC or pharmaceutical composition of the disclosure. In some cancers, overexpression of specific cell surface receptors can allow selective targeting of cancerous cells with small molecules or drugs, while minimizing effects on healthy cells. The invention provides a method of treating cancer by administering to a patient a therapeutically-effective amount of an ADC of the invention comprising an antibody or antibody fragment conjugated to a payload-linker disclosed herein. The cancer to be treated by an ADC of the present invention may be, a breast cancer including triple negative breast cancer (TNBC), a brain cancer, a pancreatic cancer, a skin cancer, a lung cancer, a liver cancer, a gall bladder cancer, a colon cancer, an ovarian cancer, a prostate cancer, a uterine cancer, a bone cancer, and a blood cancer (leukemic) cancer or a cancer or disease or conditions related to any of these cancers. In some embodiments, the invention provides a method of treating cancer by administering to a patient a therapeutically-effective amount of an ADC of the invention. The cancer may be an antigen expressing cancer. The cancer may be ovarian cancer including, but not limited to, an epithelial, stromal and germ cell tumor. The ovarian cancer may comprise a fallopian tube cancer or primary peritoneal carcinoma. The cancer may be characterized by high expression of an antigen receptor. The cancer may be treated by recruiting cytotoxic T cells to the antigen receptor expressing tumor cells. In some embodiments, the disclosure provides a method of treating any cancer, disease or condition associated with high expression of antigen receptors by administering to a patient a therapeutically-effective amount of an antibody or ADC of the disclosure. In some embodiments, the invention provides a method of treating a disorder, or condition, or disease, or cancer by administering to a patient a therapeutically-effective amount of an antibody or ADC of the invention. In some embodiments, the antibody, antibody fragment or variant thereof binds to a tumor-associated antigen (TAA), as disclosed herein. In some embodiments, the invention provides a method of treating a disorder, or condition, or disease, or cancer by administering to a patient a therapeutically-effective amount of an anti-TROP2 antibody or ADC of the invention. In some embodiments, the invention provides a method of treating a disorder, or condition, or disease, or cancer by administering to a patient a therapeutically- effective amount of an anti-HER2 antibody or ADC of the invention. In some embodiments, the invention provides a method of treating a disorder, or condition, or disease, or cancer by administering to a patient a therapeutically-effective amount of an anti-HER3 antibody or ADC of the invention. In some embodiments, the invention provides a method of treating a disorder, or condition, or disease, or cancer by administering to a patient a therapeutically-effective amount of WSGR Ref. No 31362-825.601 an anti-PSMA antibody or ADC of the invention. In some embodiments, the invention provides a method of treating a disorder, or condition, or disease, or cancer by administering to a patient a therapeutically-effective amount of an anti-CD70 antibody or ADC of the invention. In some aspects, the disclosure provides ADCs for use in treating a disease or condition in a cell expressing high TROP2 receptor number. In some aspects, the disclosure provides ADCs for use in treating a disease or condition in a cell expressing high HER2 receptor number. In some aspects, the disclosure provides ADCs for use in treating a disease or condition in a cell expressing high HER3 receptor number. In some aspects, the disclosure provides ADCs for use in treating a disease or condition in a cell expressing high PSMA receptor number. In some aspects, the disclosure provides ADCs for use in treating a disease or condition in a cell expressing high CD70 receptor number. The antibodies and ADCs of the disclosure are for use in treating cancer including, but not limited to, ovarian cancer ovarian cancer including, but not limited to, an epithelial, stromal and germ cell tumor. The ovarian cancer may comprise a fallopian tube cancer or primary peritoneal carcinoma. The cancer may be characterized by high expression of antigen receptors, such as ovarian cancer, for example. The cancer may be treated by recruiting cytotoxic T cells to high expressing antigen receptor tumor cells. The antibodies of the disclosure are for use in treating inherited diseases, AIDS, or diabetes but is not limited to such. The antibodies, compounds or composition or conjugates of the disclosure can be used in the manufacture of a medicament for treating a disease or condition in a cell expressing high receptor number. The antibodies, compounds or composition or conjugates of the disclosure can be used in the manufacture of a medicament for treating cancer including, but not limited to, breast cancer including triple negative breast cancer, ovarian cancer including, but not limited to, an epithelial, stromal and germ cell tumor. The antibodies of the invention can be used in the manufacture of a medicament for treating diseases, conditions or cancers related to or associated with expression of an antigen receptor such as TROP2, or HER2, or HER3, or PSMA, or CD70, antigen receptor for example. The anti-TROP2 antibodies of the invention can be used in the manufacture of a medicament for treating diseases, conditions or cancers related to or associated with high TROP2 receptor numbers. In other embodiments, the anti-HER2 antibodies of the disclosure can be used in the manufacture of a medicament for treating diseases, conditions or cancers related to or associated with HER2 expression. In other embodiments, the anti-HER3 antibodies of the disclosure can be used in the manufacture of a medicament for treating diseases, conditions or cancers related to or associated with HER3 expression. In other embodiments, the anti-PSMA antibodies of the disclosure can be used in the manufacture of a medicament for treating diseases, conditions or cancers related to or associated with PSMA expression. In other embodiments, the WSGR Ref. No 31362-825.601 anti-CD70 antibodies of the disclosure can be used in the manufacture of a medicament for treating diseases, conditions or cancers related to or associated with CD70 expression. In some embodiments the condition to be treated is a cancer. The cancer may be, but is non-limited to, a breast cancer including triple negative breast cancer (TNBC), a brain cancer, a pancreatic cancer, a skin cancer, a lung cancer, a liver cancer, a gall bladder cancer, a colon cancer, an ovarian cancer, a prostate cancer, a uterine cancer, a bone cancer, and a blood cancer (leukemic) cancer or a cancer or disease or conditions related to any of these cancers. Carcinomas are cancers that begin in the epithelial cells, which are cells that cover the surface of the body, produce hormones, and make up glands. By way of non-limiting example, carcinomas include breast cancer, pancreatic cancer, lung cancer, colon cancer, colorectal cancer, rectal cancer, kidney cancer, bladder cancer, stomach cancer, prostate cancer, liver cancer, ovarian cancer, brain cancer, vaginal cancer, vulvar cancer, uterine cancer, oral cancer, penile cancer, testicular cancer, esophageal cancer, skin cancer, cancer of the fallopian tubes, head and neck cancer, gastrointestinal stromal cancer, adenocarcinoma, cutaneous or intraocular melanoma, cancer of the anal region, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, cancer of the urethra, cancer of the renal pelvis, cancer of the ureter, cancer of the endometrium, cancer of the cervix, cancer of the pituitary gland, neoplasms of the central nervous system (CNS), primary CNS lymphoma, brain stem glioma, and spinal axis tumors. In some instances, the cancer is a skin cancer, such as a basal cell carcinoma, squamous, melanoma, nonmelanoma, or actinic (solar) keratosis. In some embodiments the cancer is any cancer with highly expressed antigen receptor numbers such as, for example, TROP2 antigen receptor numbers, HER2 antigen receptor numbers, HER3 antigen receptor numbers, PSMA antigen receptor numbers or CD70 antigen receptor numbers. In some embodiments the condition to be treated is a disease or condition associated with or having a high antigen receptor number such as, for example, TROP2 antigen receptor number, HER2 antigen receptor number, HER3 antigen receptor number, PSMA antigen receptor numbers or CD70 antigen receptor number. The disease or condition may be a pathogenic infection. The pathogenic infection may be a bacterial infection. The pathogenic infection may be a viral infection. The disease or condition may be an inflammatory disease. The disease or condition may be an autoimmune disease. The autoimmune disease may be diabetes. The disease or condition may be a cancer. In some embodiments the disease or condition is any disease or condition with highly expressed antigen receptor numbers such as, for example, TROP2 antigen receptor numbers, HER2 antigen receptor numbers, HER3 antigen receptor numbers, PSMA antigen receptor numbers or CD70 antigen receptor numbers. The disease or condition may be a pathogenic WSGR Ref. No 31362-825.601 infection. The biologically active molecule may interact with a cell surface molecule on an infected cell. The biologically active molecule may interact with a molecule on a bacterium, a virus, or a parasite. Pathogenic infections may be caused by one or more pathogens. In some instances, the pathogen is a bacterium, fungi, virus, or protozoan. Exemplary pathogens include but are not limited to: Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Chlamydophila, Clostridium, Corynebacterium, Enterococcus, Escherichia, Francisella, Haemophilus, Helicobacter, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Pseudomonas, Rickettsia, Salmonella, Shigella, Staphylococcus, Streptococcus, Treponema, Vibrio, or Yersinia. The pathogen may be a virus. Examples of viruses include, but are not limited to, adenovirus, coxsackievirus, Epstein-Barr virus, Hepatitis virus (e.g., Hepatitis A, B, and C), herpes simplex virus (type 1 and 2), cytomegalovirus, herpes virus, HIV, influenza virus, measles virus, mumps virus, papillomavirus, parainfluenza virus, poliovirus, respiratory syncytial virus, rubella virus, and varicella-zoster virus. Examples of diseases or conditions caused by viruses include, but are not limited to, cold, flu, hepatitis, AIDS, chicken pox, rubella, mumps, measles, warts, and poliomyelitis. The disease or condition may be an autoimmune disease or autoimmune related disease. An autoimmune disorder may be a malfunction of the body's immune system that causes the body to attack its own tissues. Examples of autoimmune diseases and autoimmune related diseases include, but are not limited to, Addison's disease, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome (APS), autoimmune aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune myocarditis, Behcet’s disease, celiac sprue, Crohn’s disease, dermatomyositis, eosinophilic fasciitis, erythema nodosum, giant cell arteritis (temporal arteritis), Goodpasture’s syndrome, Graves' disease, Hashimoto’s disease, idiopathic thrombocytopenic purpura (ITP), IgA nephropathy, juvenile arthritis, diabetes, juvenile diabetes, Kawasaki syndrome, Lambert-Eaton syndrome, lupus (SLE), mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, pemphigus, polyarteritis nodosa, type I, II, & III autoimmune polyglandular syndromes, polymyalgia rheumatica, polymyositis, psoriasis, psoriatic arthritis, Reiter’s syndrome, relapsing polychondritis, rheumatoid arthritis, sarcoidosis, scleroderma, Sjogren's syndrome, sperm & testicular autoimmunity, stiff person syndrome, Takayasu’s arteritis, temporal arteritis/giant cell arteritis, ulcerative colitis, uveitis, vasculitis, vitiligo, and Wegener’s granulomatosis. The disease or condition may be an inflammatory disease. Examples of inflammatory diseases include, but are not limited to, alveolitis, amyloidosis, angiitis, ankylosing spondylitis, avascular necrosis, Basedow's disease, Bell's palsy, bursitis, carpal tunnel syndrome, celiac disease, cholangitis, chondromalacia patella, chronic active hepatitis, chronic fatigue syndrome, WSGR Ref. No 31362-825.601 Cogan's syndrome, congenital hip dysplasia, costochondritis, Crohn's Disease, cystic fibrosis, De Quervain’s tendinitis, diabetes associated arthritis, diffuse idiopathic skeletal hyperostosis, discoid lupus, Ehlers-Danlos syndrome, familial mediterranean fever, fascitis, fibrositis/fibromyalgia, frozen shoulder, ganglion cysts, giant cell arteritis, gout, Graves' Disease, HIV-associated rheumatic disease syndromes, hyperparathyroid associated arthritis, infectious arthritis, inflammatory bowel syndrome/ irritable bowel syndrome, juvenile rheumatoid arthritis, Lyme disease, Marfan’s Syndrome, Mikulicz's Disease, mixed connective tissue disease, multiple sclerosis, myofascial pain syndrome, osteoarthritis, osteomalacia, osteoporosis and corticosteroid- induced osteoporosis, Paget's Disease, palindromic rheumatism, Parkinson's Disease, Plummer's Disease, polymyalgia rheumatica, polymyositis, pseudogout, psoriatic arthritis, Raynaud's Phenomenon/Syndrome, Reiter's Syndrome, rheumatic fever, rheumatoid arthritis, sarcoidosis, sciatica (lumbar radiculopathy), scleroderma, scurvy, sickle cell arthritis, Sjogren's Syndrome, spinal stenosis, spondyloisthesis, Still's Disease, systemic lupus erythematosis, Takayasu's (Pulseless) Disease, Tendinitis, tennis elbow/golf elbow, thyroid associated arthritis, trigger finger, ulcerative colitis, Wegener's Granulomatosis, and Whipple's Disease. The pharmaceutical compositions containing an antibody or ADC of the invention may be formulated at a strength effective for administration by various means to a human patient experiencing disorders that may be affected by antibody agonists or antagonists, such as but not limited to, anti-proliferatives, anti-inflammatory, or anti-virals are used, either alone or as part of a condition or disease. Average quantities of an antibody or ADC may vary and in particular should be based upon the recommendations and prescription of a qualified physician. The exact amount of an antibody or ADC is a matter of preference subject to such factors as the exact type of condition being treated, the condition of the patient being treated, as well as the other ingredients in the composition. The disclosure also provides for administration of a therapeutically effective amount of another active agent such as an anti-cancer chemotherapeutic agent or immunotherapeutic agent but is not limited to such. The amount to be given may be readily determined by one skilled in the art based upon therapy with the antibody or ADCs of the invention. Pharmaceutical Composition In other aspects of the present invention the antibody, antibody fragments, variants or ADCs further comprise a pharmaceutical composition or formulation. Such a pharmaceutical composition can employ various pharmaceutically acceptable excipients, stabilizers, buffers, and other components for administration to animals. See, for example, Remington, The Science and Practice of Pharmacy, 19th ed., Gennaro, ed., Mack Publishing Co., Easton, PA, 1995. WSGR Ref. No 31362-825.601 Identifying suitable composition or formulations for stability, administration to a subject, and activity varies with each compound as a number of components, (for example, purifying, stabilizing components), need to be considered. Suitable salts for inclusion into the composition or formulation can include, but not limited to, sodium chloride, potassium chloride or calcium chloride. Buffering and/or stabilizing agents such as sodium acetate can be used. Suitable buffers can include phosphate-citrate buffer, phosphate buffer, citrate buffer, L-histidine, L-arginine hydrochloride, bicarbonate buffer, succinate buffer, citrate buffer, and TRIS buffer, either alone or in combination. Surfactants can also be employed, including polysorbates (e.g., polysorbate 80), dodecyl sulfate (SDS), lecithin either alone or in combination. In some aspects of the present invention, the pharmaceutical composition or formulation can be an aqueous composition or in the form of a reconstituted liquid composition or as a powder. The composition or formulation can have a pH range from about 4.0 to about 7.0 or from about 4.5 to about 6.5 when the formulation is in a liquid form. However, the pH can be adjusted to provide acceptable stability and administration by the skilled medical practitioner. The composition can be stored in a vial or cartridge, a pen delivery device, a syringe, intravenous administration tubing or an intravenous administration bag but is not limited to such. In other embodiments a pharmaceutical composition of the invention can be administered as a single dose or followed by one or more subsequent dose(s) minutes, days, or weeks after the first dose. Further administrations may be contemplated as needed to treat, reduce or prevent a cancer, condition, disorder or disease. In some instances, the antibodies, antibody fragments, variants, or ADCs of the present invention disclosure may be used in conjunction with an additional therapy or treatment including but not limited to surgery, radiation, cryosurgery, thermotherapy, hormone treatment, chemotherapy, vaccines and other immunotherapies. In some embodiments such additional treatment can include a therapeutic agent such as chemotherapeutic agent, hormonal agent, antitumor agent, immunostimulatory agent, immunomodulator, corticosteroid or combination thereof. In other embodiments the antibodies, antibody fragments, variants, or ADCs of the invention can be administered with one or more immunostimulatory agents to induce or enhance an immune response. Immunostimulatory agents that can stimulate specific arms of the immune system, such as natural killer (NK) cells that mediate antibody-dependent cell cytotoxicity (ADCC). Such immunostimulatory agents include, but are not limited to, IL-2, WSGR Ref. No 31362-825.601 administered with one or more immunomodulators including, but not limited to, cytokines, combinations thereof). Other therapeutic agents can be a vaccine that immunizes a subject against an antigen such as, for example, TROP2, HER2, HER3, PSMA or CD70. Such vaccines, in some embodiments, include antigens, with, optionally, one or more adjuvants to induce or enhance an immune response. Adjuvants of many kinds are well known in the art. The chemotherapeutic agent or any agent involved in treating, reducing or preventing a disease, condition or cancer in a subject in need thereof can also be administered in combination with an ADC of the invention disclosure. Chemotherapeutic agents may include, but are not limited to, erlotinib (TARCEVA®, Genentech/OSI Pharm.), bortezomib (VELCADE®, Millennium Pharm.), fulvestrant (FASLODEX®, AstraZeneca), sutent (SU11248, Pfizer), letrozole (FEMARA®, Novartis), imatinib mesylate (GLEEVEC®, Novartis), PTK787/ZK 222584 (Novartis), oxaliplatin (Eloxatin®, Sanofi), 5-FU (5-fluorouracil), leucovorin, Rapamycin (Sirolimus, RAPAMUNE®, Wyeth), lapatinib (TYKERB®, GSK572016, GlaxoSmithKline), lonafarnib (SCH 66336), sorafenib (BAY43-9006, Bayer Labs.), and gefitinib (IRESSA®, AstraZeneca), AG1478, AG1571 (SU 5271; Sugen), alkylating agents such as thiotepa and CYTOXAN® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; antifolate antineoplastic such as pemetrexed (ALIMTA®, Eli Lilly), aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics, calicheamicin, calicheamicin gamma and calicheamicin omega; dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores, aclacinomysins, actinomycin, anthramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, WSGR Ref. No 31362-825.601 ADRIAMYCIN® doxorubicin (including morpholino-doxorubicin, cyanomorpholino- doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5- fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; antiandrogens or androgen deprivation therapy; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elformithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2- ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2''- trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids, e.g., paclitaxel (TAXOL®, Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE Cremophor-free, albumin, nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, Ill.), and TAXOTERE® doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; GEMZAR® gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE® vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine; and pharmaceutically acceptable salts, acids or derivatives of any of the above. The term “about” will be understood by persons of ordinary skill in the art and will vary to some extent depending on the context in which it is used. Examples WSGR Ref. No 31362-825.601 It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. NUMBERED EMBODIMENTS Embodiment 1. An antibody-drug conjugate (ADC) of Formula (I-ADC) or Formula (II-ADC):

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence comprising one or more non-naturally encoded amino acids; L is a linker; E is a moiety joining the antibody Ab to the linker L; d is an integer from 1 to 10; V is selected from the group consisting of -CH₂-, -S-, -S(O)-, -C(O)- and -C(H)(R_v)-; wherein Rv is F, CN, N3, OH, ONH2 , unsubstituted C1-C8 alkyl, or substituted C₁-C₈ alkyl; X is O or NH; Z is -CH2- or -C(O)-; R5 is H, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C₃-C₆ cycloalkyl; R₆ is unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted cycloalkyl, substituted cycloalkyl, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; and each R_7, R₈ and R₉ is independently H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; or R7 and R₈ are joined to form an unsubstituted heterocycloalkyl or substituted WSGR Ref. No 31362-825.601 heterocycloalkyl, and R₉ is H, unsubstituted C₁-C₈ alkyl, or optionally substituted C1-C8 alkyl; or R8 and R9 are joined to form an unsubstituted cycloalkyl, substituted cycloalkyl, an unsubstituted heterocycloalkyl, or substituted heterocycloalkyl, and R₇ is H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; and R7a is H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C₃-C₆ cycloalkyl. Embodiment 2. The ADC of Embodiment 1, wherein the ADC is according to Formula (I- ADC). Embodiment 3. The ADC of Embodiment 1, wherein the ADC is according to Formula (II- ADC). Embodiment 4. The ADC of any one of Embodiments 1 to 3, wherein Ab is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 46 to 58. Embodiment 5. The ADC of Embodiment 4, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. Embodiment 6. The ADC of Embodiment 4, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. Embodiment 7. The ADC of any one of Embodiments 1 to 3, wherein Ab is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 17. Embodiment 8. The ADC of Embodiment 7, wherein the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 5, and the light chain amino acid sequence is SEQ ID NO: 4. Embodiment 9. The ADC of any one of Embodiments 1 to 3, wherein Ab is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 18 to 24. Embodiment 10. The ADC of Embodiment 9, wherein the anti-CD70 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 20, and the light chain amino acid sequence is SEQ ID NO: 19. Embodiment 11. The ADC of any one of Embodiments 1 to 3, wherein Ab is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 25 to 28. WSGR Ref. No 31362-825.601 Embodiment 12. The ADC of Embodiment 11, wherein the anti-HER2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 26, and the light chain amino acid sequence is SEQ ID NO: 27. Embodiment 13. The ADC of any one of Embodiments 1 to 3, wherein Ab is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 29 to 45. Embodiment 14. The ADC of Embodiment 13, wherein the anti-PSMA antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 36, and the light chain amino acid sequence is SEQ ID NO: 37. Embodiment 15. The ADC of any one of Embodiments 1 to 14, wherein d is 1, 2, 3 or 4. Embodiment 16. The ADC of any one of Embodiments 1 to 15, wherein V is -CH2-. Embodiment 17. The ADC of any one of Embodiments 1 to 16, wherein R6 is unsubstituted heteroaryl or substituted heteroaryl. Embodiment 18. The ADC of Embodiment 17, wherein the unsubstituted heteroaryl is unsubstituted 2-thienyl. Embodiment 19. The ADC of Embodiment 17, wherein the unsubstituted heteroaryl is unsubstituted 3-thienyl. Embodiment 20. The ADC of any one of Embodiments 1 to 19, wherein each of the one or more non-naturally encoded amino acids is independently selected from the group consisting of 4- acetyl-L-phenylalanine (para-acetyl-L-phenylalanine (pAF)), 3-O-(N-acetyl-beta-D- alpha-N-acetylgalactosamine-O-L-serine, alpha-N-acetylgalactosamine-O-L-threonine, 2- aminooctanoic acid, 2-amino-L-phenylalanine, 3-amino-L-phenylalanine, 4-amino-L- phenylalanine, 2-amino-L-tyrosine, 3-amino-L-tyrosine, 4-azido-L-phenylalanine, 4-benzoyl-L- phenylalanine, (2,2-bipyridin-5yl)-L-alanine, 3-borono-L-phenylalanine, 4-borono-L- phenylalanine, 4-bromo-L-phenylalanine, p-carboxymethyl-L-phenylalanine, 4-carboxy-L- phenylalanine, p-cyano-L-phenylalanine, 3,4-dihydroxy-L-phenylalanine (L-DOPA), 4-ethynyl- L-phenylalanine, 2-fluoro-L-phenylalanine, 3-fluoro-L-phenylalanine, 4-fluoro-L-phenylalanine, O-(3-O-D-galactosyl-N-acetyl-beta-D-galactosaminyl)-L-serine, L-homoglutamine, (8- hydroxyquinolin-3-yl)-L-alanine, 4-iodo-L-phenylalanine, 4-isopropyl-L-phenylalanine, O-i- propyl-L-tyrosine, 3-isopropyl-L-tyrosine, O-mannopyranosyl-L-serine, 2-methoxy-L- phenylalanine, 3-methoxy-L-phenylalanine, 4-methoxy-L-phenylalanine, 3-methyl-L- phenylalanine, O-methyl-L-tyrosine, 3-(2-naphthyl)-L-alanine, 5-nitro-L-histidine, 4-nitro-L- histidine, 4-nitro-L-leucine, 2-nitro-L-phenylalanine, 3-nitro-L-phenylalanine, 4-nitro-L- WSGR Ref. No 31362-825.601 phenylalanine, 4-nitro-L-tryptophan, 5-nitro-L-tryptophan, 6-nitro-L-tryptophan, 7-nitro-L- tryptophan, 2-nitro-L-tyrosine, 3-nitro-L-tyrosine, O-phospho-L-serine, O-phospho-L-tyrosine, 4- propargyloxy-L-phenylalanine, O-2-propyn-1-yl-L-tyrosine, 4-sulfo-L-phenylalanine, para-(2- azidoethoxy)-L-phenylalanine ((S)-2-amino-3-(4-(2-azidoethoxy)phenyl)propanoic acid) and O- sulfo-L-tyrosine. Embodiment 21. The ADC of any one of Embodiments 1 to 20, wherein E comprises an amide, an ester, a thioester, a pyrrolidine-2,5-dione, an oxime, a 1,2,3-triazole or a 1,4-dihydropyridazine, or a combination thereof. Embodiment 22. The ADC of Embodiment 21, wherein the 1,2,3-triazole is fused to an 8- membered ring, and the 1,4-dihydropyridazine is fused to an 8-membered ring. Embodiment 23 The ADC of any one of Embodiments 1 to 22, wherein each of the one or more non-naturally encoded amino acids is para-acetyl-L-phenylalanine (pAF), and E has the following structure:

; wherein R_c is methyl; + denotes a connection to linker L; and the wavy line ( ) denotes a connection to antibody Ab. Embodiment 24. The ADC of any one of Embodiments 1 to 23, wherein Z is -C(O)-, and X, when present, is O. Embodiment 25. The ADC of any one of Embodiments 1 to 24, wherein R₅, when present, is H; each R7, R8 and R9 is independently H or unsubstituted C1-C8 alkyl; and R7a, when present, is H or unsubstituted C1-C8 alkyl. Embodiment 26. The ADC of any one of Embodiments 1 to 25, wherein the linker L is selected from the group consisting of a bond, –alkylene–, –(alkylene–O)n–alkylene–, –alkylene–C(O)–, – (alkylene–O)n–alkylene–C(O)–, –alkylene-(alkylene–O)n-C(O)–, –alkylene-arylene-alkylene–, – alkylene–NH–, –(alkylene–O)_n-alkylene-NH–, –C(O)-alkylene-NH–, –C(O)-(alkylene–O)_n– alkylene–NH–, –(alkylene–O)_n–alkylene–J–, –J-alkylene–, –alkylene-J-alkylene–, –(alkylene- O)n-J-alkylene–, –alkylene-J-(alkylene-O)n-alkylene-C(O)–, –alkylene–J–(alkylene–O)n– alkylene–, –(alkylene–O)_n–alkylene–J–alkylene, –J–(alkylene–O)_n–alkylene–, –J–(alkylene– O)_n–(alkylene–O)_n–alkylene–, –(alkylene–O)_n–alkylene–J–(alkylene–O)_n–alkylene–J–, –C(O)- U–NH-alkylene–, –(alkylene–O)n–alkylene-C(O)-U–NH-alkylene–C(O)–, –(alkylene–O)n– alkylene–C(O)-U-NH–alkylene–, –C(O)-alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, – alkylene-C(O)-U-NH-(alkylene-O)_n-alkylene–, –alkylene-NH-U-C(O)-alkylene–, and –(CH₂)_1- 6– substituted with one to three groups independently selected from the group consisting of -OH, -NH2, C1-C3 alkyl, C1-C3 alkoxy and C3-C6 cycloalkyl; wherein: WSGR Ref. No 31362-825.601 each U is independently an amino acid; each J is independently:

each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. Embodiment 27. The ADC of any one of Embodiments 1 to 25, wherein the linker L is selected from the group consisting of –alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene–, –alkylene-C(Re)(Rf)- S-S-C(Rg)(Rh)-alkylene–J-alkylene–, –C(O)-alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene–, – C(O)-alkylene-C(R_e)(R_f)-S-S-C(R_g)(R_h)-alkylene-J-alkylene–, –(alkylene–O)_n-alkylene-J- alkylene-C(Re)(Rf)-S-S-alkylene-J-(alkylene-O)n-alkylene–; wherein: each J is independently:

; each R_e, R_f, R_g and R_h is independently selected from the group consisting of H and C1-C6 alkyl; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. Embodiment 28. The ADC of any one of Embodiments 1 to 25, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-G-J-alkylene–, –C(O)-O-alkylene-G-NH- alkylene–, –C(O)-O-alkylene-G-J-alkylene-(O-alkylene)n–, –C(O)-O-alkylene-G-NH-alkylene- (O-alkylene)_n–, wherein: each G is a glucuronidase substrate; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁–, and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. WSGR Ref. No 31362-825.601 Embodiment 29. The ADC of any one of Embodiments 1 to 25, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –C(O)-O-alkylene- arylene-NH-(peptide)-C(O)-alkylene–, –C(O)-O-alkylene-arylene-NH-(peptide)-alkylene-(O- alkylene)_n–, –C(O)-O-alkylene-arylene-NH-(peptide)-(alkylene-O)_n-alkylene–, –C(O)- (alkylene-O)n-alkylene-NH-(peptide)-C(O)-alkylene–, –alkylene-arylene-NH-(peptide)-alkylene- (O-alkylene)n–, –alkylene-arylene-NH-(peptide)-C(O)-alkylene–, –alkylene-C(O)-O-alkylene- arylene-NH-(peptide)-C(O)–, –alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, – (alkylene–O)n-alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J-(alkylene-N(CH3))n- alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J–alkylene–N(CH3)–alkylene– N(CH₃)–alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-J-(alkylene– N(CH3))n-alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene–J–alkylene– N(CH3)–alkylene–N(CH3)–alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–; wherein: each J is independently:

; each peptide is independently a dipeptide, tripeptide or tetrapeptide; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11– and –(CH2)12–; and each n is independently an integer from 1 to 100. Embodiment 30. The ADC of any one of Embodiments 1 to 25, wherein the linker L is selected from the group consisting of the linkers listed in Table 10. *–P(=O)(OH)-O-P(=O)(OH)-(O)i–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)_i–alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–alkylene-J–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i- (alkylene-O)_n-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-(O-alkylene)_n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n-alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i– alkylene–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–(alkylene-O)_n–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-(O-alkylene)_n-J-alkylene–, *– P(=O)(OH)-O-P(=O)(OH)-(O)i–alkylene–J-(alkylene-O)n–alkylene–, *–P(=O)(OH)- O-P(=O)(OH)-(O)i–alkylene–U–alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)_i-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i- WSGR Ref. No 31362-825.601 alkylene-J-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene- (O-alkylene)n–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)_i–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i- alkylene–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i- (alkylene-O)_n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, – alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)_i-alkylene–(O-alkylene)_n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)- (O)i-alkylene–(O-alkylene)n–, –(alkylene–O)n-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –(alkylene–O)n-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –(alkylene–O)n- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, –(alkylene–O)_n-P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –(alkylene–O)n–alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)i–, –(alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i–, – (alkylene–O)_n–alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n– alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –(alkylene–O)_n–alkylene- O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–; wherein: each U is an amino acid; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁–, and –(CH₂)₁₂–; each n is independently an integer from 1 to 100; each i is independently 0 or 1; and *, when present, denotes a connection to drug in the ADC. Embodiment 31. The ADC of any one of Embodiments 26-30, wherein arylene is phenylene. Embodiment 32. The ADC of any one of Embodiments 1 to 25, wherein the ADC is according to Formula (I-ADC), and the linker L is a non-cleavable linker. WSGR Ref. No 31362-825.601 Embodiment 33. The ADC of Embodiment 32, wherein the non-cleavable linker comprises one or more linker moieties selected from the group consisting of unsubstituted alkylene and unsubstituted –(O-alkylene)_n–, wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. Embodiment 34. The ADC of any one of Embodiments 1 to 25, wherein the ADC is according to Formula (II-ADC), and the linker L is a cleavable linker. Embodiment 35. The ADC of Embodiment 34, wherein the cleavable linker comprises a pyrophosphate ester or diphosphonate. Embodiment 36. An antibody-drug conjugate (ADC) of Formula (I-ADC-17):

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence containing one or more non-naturally encoded amino acids; d is an integer from 1 to 10; and Rc is unsubstituted C1-C6 alkyl. Embodiment 37. The ADC of Embodiment 36, wherein each non-naturally encoded amino acid is para-acetyl-L-phenylalanine (pAF), and Rc is methyl. Embodiment 38. The ADC of Embodiment 36 or 37, wherein d is 1, 2, 3 or 4. Embodiment 39. The ADC of any one of Embodiments 36-38, wherein Ab is an anti-HER3 antibody. Embodiment 40. The ADC of Embodiment 39, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. Embodiment 41. The ADC of Embodiment 39, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. Embodiment 42. The ADC of any one of Embodiments 36-38, wherein Ab is an anti-TROP2 antibody. Embodiment 43. The ADC of Embodiment 42, wherein the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 5, and the light chain amino acid sequence is SEQ ID NO: 4. WSGR Ref. No 31362-825.601 Embodiment 44. The ADC of any one of Embodiments 36-38, wherein Ab is an anti-CD70 antibody. Embodiment 45. The ADC of Embodiment 44, wherein the anti-CD70 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 20, and the light chain amino acid sequence is SEQ ID NO: 19. Embodiment 46. The ADC of any one of Embodiments 36-38, wherein Ab is an anti-HER2 antibody. Embodiment 47. The ADC of Embodiment 46, wherein the anti-HER2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 26, and the light chain amino acid sequence is SEQ ID NO: 27. Embodiment 48. The ADC of any one of Embodiments 36-38, wherein Ab is an anti-PSMA antibody. Embodiment 49. The ADC of Embodiment 48, wherein the anti-PSMA antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 36, and the light chain amino acid sequence is SEQ ID NO: 37. Embodiment 50. A pharmaceutical composition comprising the ADC of any one of Embodiments 1 to 49 and at least one pharmaceutically acceptable adjuvant, binder, buffer, carrier, diluent or excipient. Embodiment 51. The pharmaceutical composition of Embodiment 50, wherein the pharmaceutical composition comprises a therapeutically effective amount of the ADC. Embodiment 52. The pharmaceutical composition of Embodiment 50 or 51, further comprising a chemotherapeutic agent, hormonal agent, antitumor agent, immunostimulatory agent, immunomodulator or corticosteroid; or any combination thereof. Embodiment 53. A of Formula (I) or Formula (II):

or a pharmaceutically acceptable salt thereof, wherein: V is selected from the group consisting of -CH₂-, -S-, -S(O)-, -C(O)- and -C(H)(R_v)-; wherein R_v is -F, -CN, -N₃, -OH, -ONH₂, unsubstituted C₁-C₈ alkyl, or substituted C1-C8 alkyl; WSGR Ref. No 31362-825.601 X is O or NH; Y is a reactive moiety; Z is -CH₂- or -C(O)-; R₅ is H, unsubstituted C₁-C₆ alkyl, substituted C₁-C₆ alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C3-C6 cycloalkyl; R6 is unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted cycloalkyl, substituted cycloalkyl, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; each R7, R8 and R9 is independently H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C₃-C₆ cycloalkyl, substituted C₃-C₆ cycloalkyl; or R₇ and R₈ are joined to form an unsubstituted heterocycloalkyl or a substituted heterocycloalkyl, and R9 is H, unsubstituted C1-C8 alkyl or substituted C1-C8 alkyl; or R8 and R9 are joined to form an unsubstituted cycloalkyl, substituted cycloalkyl, an unsubstituted heterocycloalkyl or substituted heterocycloalkyl, and R7 is H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C3-C6 cycloalkyl or substituted C3-C6 cycloalkyl; R_7a is H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, substituted C₃-C₆ cycloalkyl, or substituted C3-C6 cycloalkyl; and L is a linker. Embodiment 54. The compound of Embodiment 53, wherein the reactive moiety Y comprises - N3, -OH, -SH, -NHRb, -C(O)Rc, -C(O)ORd, -C(O)CH2NH2, an activated ester, –O–NH2, a maleimide, a tetrazine, an alkyne, a cyclooctyne or an (E)-cyclooctene; wherein: R_b is H or unsubstituted C₁-C₆ alkyl, Rc is unsubstituted C1-C6 alkyl, and Rd is H, unsubstituted C1-C6 alkyl or a carboxylic acid protecting group. Embodiment 55. The compound of Embodiment 54, wherein Y is -O-NH₂. Embodiment 56. The compound of Embodiment 53-55, wherein V is -CH₂-. Embodiment 57. The compound of any one of Embodiments 53 to 56, wherein R6 is unsubstituted heteroaryl or substituted heteroaryl. Embodiment 58. The compound of Embodiment 57, wherein the unsubstituted heteroaryl is unsubstituted 2-thienyl. Embodiment 59. The compound of Embodiment 57, wherein the unsubstituted heteroaryl is unsubstituted 3-thienyl. WSGR Ref. No 31362-825.601 Embodiment 60. The compound of any one of Embodiments 53 to 59, wherein the linker L is selected from the group consisting of a bond, –alkylene–, –(alkylene–O)n–alkylene–, –alkylene– C(O)–, –(alkylene–O)_n–alkylene–C(O)–, –alkylene-(alkylene–O)_n-C(O)–, –alkylene-arylene- alkylene–, –alkylene–NH–, –(alkylene–O)_n-alkylene-NH–, –C(O)-alkylene-NH–, –C(O)- (alkylene–O)n–alkylene–NH–, –(alkylene–O)n–alkylene–J–, –J-alkylene–, –alkylene-J- alkylene–, –(alkylene-O)n-J-alkylene–, –alkylene-J-(alkylene-O)n-alkylene-C(O)–, –alkylene–J– (alkylene–O)_n–alkylene–, –(alkylene–O)_n–alkylene–J–alkylene, –J–(alkylene–O)_n–alkylene–, – J–(alkylene–O)n–(alkylene–O)n–alkylene–, –(alkylene–O)n–alkylene–J–(alkylene–O)n– alkylene–J–, –C(O)-U–NH-alkylene–, –(alkylene–O)n–alkylene-C(O)-U–NH-alkylene–C(O)–, – (alkylene–O)_n–alkylene–C(O)-U-NH–alkylene–, –C(O)-alkylene-C(O)-U-NH-(alkylene-O)_n- alkylene–, –alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, –alkylene-NH-U-C(O)-alkylene–, and –(CH2)1-6– substituted with one to three groups independently selected from the group consisting of -OH, -NH₂, C₁-C₃ alkyl, C₁-C₃ alkoxy and C₃-C₆ cycloalkyl; wherein: each U is independently an amino acid; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. Embodiment 61. The compound of any one of Embodiments 53 to 59, wherein the linker L is selected from the group consisting of –alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene–, –alkylene- C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene–J-alkylene–, –C(O)-alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)- alkylene–, –C(O)-alkylene-C(R_e)(R_f)-S-S-C(R_g)(R_h)-alkylene-J-alkylene–, –(alkylene–O)_n- alkylene-J-alkylene-C(R_e)(R_f)-S-S-alkylene-J-(alkylene-O)_n-alkylene–; wherein: each J is independently:

; each R_e, R_f, R_g and R_h is independently selected from the group consisting of H and C1-C6 alkyl; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and WSGR Ref. No 31362-825.601 each n is independently an integer from 1 to 100. Embodiment 62. The compound of any one of Embodiments 53 to 59, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-G-J-alkylene–, –C(O)-O-alkylene-G- NH-alkylene–, –C(O)-O-alkylene-G-J-alkylene-(O-alkylene)_n–, –C(O)-O-alkylene-G-NH- alkylene-(O-alkylene)n–, wherein: each G is a glucuronidase substrate; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. Embodiment 63. The compound of any one of Embodiments 53 to 59, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –C(O)-O- alkylene-arylene-NH-(peptide)-C(O)-alkylene–, –C(O)-O-alkylene-arylene-NH-(peptide)- alkylene-(O-alkylene)n–, –C(O)-O-alkylene-arylene-NH-(peptide)-(alkylene-O)n-alkylene–, – C(O)-(alkylene-O)n-alkylene-NH-(peptide)-C(O)-alkylene–, –alkylene-arylene-NH-(peptide)- alkylene-(O-alkylene)_n–, –alkylene-arylene-NH-(peptide)-C(O)-alkylene–, –alkylene-C(O)-O- alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –(alkylene–O)n-alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J-(alkylene-N(CH3))n- alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J–alkylene–N(CH3)–alkylene– N(CH₃)–alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-J-(alkylene– N(CH3))n-alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene–J–alkylene– N(CH3)–alkylene–N(CH3)–alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–; wherein: each J is independently:

; each peptide is independently a dipeptide, tripeptide or tetrapeptide; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11– and –(CH2)12–; and each n is independently an integer from 1 to 100. WSGR Ref. No 31362-825.601 Embodiment 64. The compound of any one of Embodiments 53 to 59, wherein the linker L is selected from the group consisting of the linkers listed in Table 10. *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)i–alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i–alkylene-J–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i- (alkylene-O)_n-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-(O-alkylene)_n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n-alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i– alkylene–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–(alkylene-O)_n–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-(O-alkylene)n-J-alkylene–, *– P(=O)(OH)-O-P(=O)(OH)-(O)i–alkylene–J-(alkylene-O)n–alkylene–, *–P(=O)(OH)- O-P(=O)(OH)-(O)_i–alkylene–U–alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i- alkylene-J-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene- (O-alkylene)_n–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)_i–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i- alkylene–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)_i-alkylene–J-alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i- (alkylene-O)n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, – alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–(O-alkylene)n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)- (O)i-alkylene–(O-alkylene)n–, –(alkylene–O)n-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –(alkylene–O)_n-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, –(alkylene–O)_n-P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –(alkylene–O)n–alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)i–, –(alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i–, – (alkylene–O)_n–alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n– alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –(alkylene–O)n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, –(alkylene–O)_n–alkylene- WSGR Ref. No 31362-825.601 P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –(alkylene–O)_n–alkylene- O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–; wherein: each U is an amino acid; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; each n is independently an integer from 1 to 100; each i is independently 0 or 1; and *, when present, denotes a connection to drug in the ADC. Embodiment 65. The ADC of any one of Embodiments 60-64, wherein arylene is phenylene. Embodiment 66. The compound of any one of Embodiments 53 to 59, wherein the compound is a compound of Formula (I), and the linker is a non-cleavable linker. Embodiment 67. The compound of Embodiment 66, wherein the non-cleavable linker comprises one or more linker moieties selected from the group consisting of unsubstituted alkylene and unsubstituted –(O-alkylene)_n–, wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. Embodiment 68. The compound of any one of Embodiments 53 to 59, wherein the compound is a compound of Formula (II), and the linker is a cleavable linker. Embodiment 69. The compound of Embodiment 67, wherein the cleavable linker comprises a pyrophosphate ester or diphosphonate. Embodiment 70. The compound of any one of Embodiments 53 to 69, wherein Z is -C(O); R_7, R₈ and R₉ are each independently H or unsubstituted C₁-C₈ alkyl; X, when present, is O; R₅, when present, is H; and R7a, when present, is H or unsubstituted C1-C8 alkyl. Embodiment 71. The compound of any one of Embodiments 53 to 69, wherein Z is -CH₂-; R_7, R₈ and R₉ are each independently H or unsubstituted C₁-C₈ alkyl; X, when present, is O; R₅, when present, is H; and R7a, when present, is H or unsubstituted C1-C8 alkyl. Embodiment 72. The compound of Embodiment 53, wherein the compound is selected from the of:

, WSGR Ref. No 31362-825.601

and pharmaceutically acceptable salts thereof. Embodiment 73. A pharmaceutical composition comprising a compound of any one of Embodiments 53 to 72 and at least one pharmaceutically acceptable adjuvant, binder, buffer, carrier, diluent or excipient. Embodiment 74. The pharmaceutical composition of Embodiment 73, wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound. Embodiment 75. A method of treating a disease in a subject in need thereof, the method comprising administering to the subject an ADC of any one of Embodiments 1 to 49, a compound WSGR Ref. No 31362-825.601 of any one of Embodiments 53 to 72, or a pharmaceutical composition of any one of Embodiments 50 to 52, 73 and 74. Embodiment 76. The method of Embodiment 75, wherein the disease is cancer. EXAMPLES Example 1 - General Experimental Procedures All commercially available anhydrous solvents were used without further purification and were stored under a nitrogen atmosphere. TLC was performed on Merck Silica gel 60 F254 plates using UV light and/or staining with aqueous KMnO4 solution or other staining reagents as needed for visualization. Chromatographic purification was performed on CombiFlash Rf from Teledyne ISCO using conditions detailed in the experimental procedure. Analytical HPLC was performed on Shimadzu system using Phenomenex Gemini–NX C185µm 50 x 4.6 mm column, which was eluted at 1 ml/min with a linear gradient of acetonitrile in water containing 0.05% TFA. (Mobile phase A: 0.05% trifluoroacetic acid in water; mobile phase B: 0.05% trifluoroacetic acid in 90% acetonitrile (ACN) aqueous solution) or Waters BEH 1.7µm v2.1X50 mm column. Analytic Methods - Method 1: 0% B in 1min, 0-50% B in 11min, 50-100% B in 0.5 min, 100% B for 1.5 min, 100-0% B in 1 min, 0% B for 2 min; Method 2: 10-20% B in 1min, 20-70% B in 11min, 70-100% B in 0.5 min, 100% B for 1.5 min, 100-10% B in 1 min, 10% B for 2 min; Method 3: 0-40% B in 1min, 40-90% B in 11min, 90-100% B in 0.5 min, 100% B for 1.5 min, 100-10% B in 1 min, 10% B for 2 min. Method 4: 5% B in 0.3 min, 5-100% B from 0.3 to 1.5 min.100% B from 1.5 min to 1.8 min. flow rate from 0.8 ml/min to 1.1 min/min from 0 min to 1.8 min. Preparative HPLC was performed on Shimadzu system using Gemini–NX C185 µm 100 x 30 mm, 150 x 30 mm or 250 x 50 mm column, depending on the scale. Mass spectra (MS) were recorded on a Shimadzu LCMS-2020 system and data were processed using Shimadzu LabSolutions software. Agilent 1260 Infinity Binary LC coupled with 6230 Accurate-Mass TOFMS system was used for HR-ESI-TOF analysis. NMR spectral data were collected on a 500 deuterium solvent signal. Coupling constants (J) are reported in hertz (Hz). Spin multiplicities are described as: s (singlet), br (broad), d (doublet), dd (doublet of doublets), t (triplet), q (quartet), or m (multiplet). Abbreviations used in the Examples herein: Boc: Tert-butyloxycarbonyl, Boc-Dap-OH: methylpyridinium iodide, DIEA: N,N-Diisopropylethylamine, DCM: Dichloromethane, DIAD: Diisopropyl azodicarboxylate, DMF: Dimethylformamide, DMSO: Dimethyl sulfoxide, WSGR Ref. No 31362-825.601 DMTMMT: 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Tetrafluoroborate, EDC: 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide HCl, Fmoc: fluorenylmethoxycarbonyl, EtOAc: Ethyl acetate, HATU: 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate, HOBt: Hydroxybenzotriazole, MeOH: Methanol, MTBE: Methyl tert-butyl ether, TEA: Triethylamine, TFA: Trifluoroacetic acid, TLE: L-tert- Leucine, TMSCl: Trimethylsilyl chloride. Example 2 – Synthesis of Compound 6 Scheme for of 6

tert-Butyl (3R,4S,5S)-4-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N,3,3- trimethylbutanamido)-3-methoxy-5-methylheptanoate (1): To a solution of Fmoc-Tle (200 mg, 0.566 mmol) in DCM (5 mL) was added CMPI (300 mg, 1.174 mmol) at 23 °C. After 5 min, to this mixture was added a solution of Na₂CO₃ (120 mg, 1.132 mmol), NaHCO₃ (150 mg, 1.786 mmol), and Dil-OtBu^.HCl (170 mg, 0.572 mmol) in water (5 mL) at 23 °C. After 1h of stirring, the organic layer was separated, and then diluted with 120 ml of EtOAc. The solution was washed WSGR Ref. No 31362-825.601 with1N HCl (50 mL), saturated sodium bicarbonate (50 mL) and brine (20 mL). The organic layer was dried over MgSO4, followed by filtration. The liquid was removed in vacuo. The residue was purified by flash chromatography (SiO₂) to give compound 1 (268 mg, 0.451 mmol, 80%) as colorless glassy form. MS m/z 617 (M+Na)⁺. (tert-Butyl (3R,4S,5S)-4-((S)-2-amino-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoate (2): To a solution of compound 1 (268 mg, 0.451 mmol) in DCM (10 mL) was added thiomalic acid (270 mg, 1.798 mmol) and DBU (540 µL, 3.611 mmol) at 23 °C. After 1 h, the mixture was washed with Na2CO3 (50 mL, 2 times) and brine (50 mL), followed by drying over MgSO4 and filtration. The organic layer was combined, evaporated in vacuo. The residue was purified by Prep-LC to give compound 2 (90 mg, 0.185 mmol, 41%) as TFA salt of colorless glassy solid. MS m/z 373 (M+H)⁺. (3R,4S,5S)-4-((S)-2-((S)-2-(Dimethylamino)-3-methylbutanamido)-N,3,3- trimethylbutanamido)-3-methoxy-5-methylheptanoic acid (3): To the solution of compound 2 (42 mg, 0.113 mmol) and dimethyl-L-valine (24 mg, 0.165 mmol) in DMF (2 mL) was added HATU (60 mg, 0.158 mmol) and DIEA (80 µL, 0.459 mmol) at 23 °C. After 10 min, the liquid was removed in vacuo, and then to the residue was added DCM (1 mL) and TFA (1 mL) at 23 °C. After 10 min, the liquid was removed in vacuo. The residue was purified by Prep-LC to give target compound 3 (30 mg, 0.054 mmol, 48%) as colorless glassy solid. MS m/z 444 (M+H). tert-Butyl (S)-2-((1R,2R)-3-(((S)-1-hydroxy-3-(thiophen-2-yl)propan-2-yl)amino)-1- methoxy-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylate (4): To a solution of (2R,3R)-3- ((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoic acid (310 mg, 1.079 mmol) and (S)-2-amino-3-(thiophen-2-yl)propan-1-ol (180 mg, 1.145 mmol) in DCM (20 mL) was added HATU (570 mg, 1.499 mmol) and DIEA (360 µL, 2.786 mmol) at 23 °C. After 40 min of stirring, the solution was diluted with EtOAc (120 mL) and washed with 1N HCl (50 mL), saturated sodium bicarbonate (50 mL) and brine (20 mL). The organic layer was dried over MgSO4, followed by filtration. The solvent was removed in vacuo. The residue was purified by flash chromatography to give target compound 4 (315 mg, 0.738 mmol, 68 %) as white solid. MS m/z 427 (M+H). (2R,3R)-N-((S)-1-Hydroxy-3-(thiophen-2-yl)propan-2-yl)-3-methoxy-2-methyl-3- ((S)-pyrrolidin-2-yl)propanamide (5): To compound 4 (315 mg, 0.738 mmol) was added 4M HCl in dioxane (5 mL) at 23 °C. After 30 min, the volatiles were removed in vacuo, dried in high vacuum to give target compound 5 (280 mg, 0.773 mmol, quant.) as white solid. MS m/z 327 (M+H). WSGR Ref. No 31362-825.601 (S)-2-((S)-2-(Dimethylamino)-3-methylbutanamido)-N-((3R,4S,5S)-1-((S)-2- ((1R,2R)-3-(((S)-1-hydroxy-3-(thiophen-2-yl)propan-2-yl)amino)-1-methoxy-2-methyl-3- oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)-N,3,3- trimethylbutanamide (6): To a solution of compound 3 TFA salt (30 mg, 0.054 mmol) in DMF (2 mL) was added EDC (15 mg, 0.078 mmol) and HOBt (8 mg, 0.059 mmol). After 5 min, to this mixture was added compound 5 (25 mg, 0.057 mmol) and DIEA (50 µL, 0.287 mmol) at 23 °C. After 24 h, the liquid was removed in vacuo, and then the residue was purified by Prep-LC to give compound 6 (4 mg, 0.005 mmol, 9%) as TFA salt of white solid. MS m/z 752 (M+H). Example 3 – Synthesis of Compound 17 Synthetic Scheme for synthesis of Compound 17

WSGR Ref. No 31362-825.601

2-(2-(2-(2-(2-Hydroxyethoxy)ethoxy)ethoxy)ethoxy)isoindoline-1,3-dione (7): To a solution of HO-PEG4-OH (1785 mg, 9.190 mmol) and N-hydroxyphthalimide (755 mg, 4.629 mmol) in DCM (10 mL) at 23 °C was added PPh3 (1320 mg, 5.033 mmol). After 10 min, temperature was reduced to 0 °C, and then to this mixture was added DIAD (1050 µL, 5.333 mmol) at 0 °C over 5-minute period. The mixture was stirred at 0 °C for 1h, and then at 23 °C. After 20 h, to the mixture was added water (50 mL), and then organic phase was separated, and then concentrated in vacuo. To the oily residue was added MTBE (50 mL). The precipitate formed at 0 °C was removed by filtration. The organic solvent was removed in vacuo and the residues was purified by flash chromatography (SiO2) to give compound 7 (1343 mg, 3.958 mmol, 43%) as colorless glassy solid. MS m/z 340 (M+H)⁺. WSGR Ref. No 31362-825.601 2-(2-(2-(2-((1,3-Dioxoisoindolin-2-yl)oxy)ethoxy)ethoxy)ethoxy)acetaldehyde (8): To a solution of compound 7 (1343 mg, 3.958 mmol) in DCM (20 mL) was added Dess-Martin periodinate (2500 mg, 5 mmol) at 23 °C and stirred for 1 hr. The mixture was washed by saturated sodium bicarbonate (2X 50 mL) and brine (50 mL), followed by drying over MgSO₄ and filtration. The solvent was removed in vacuo to give a mixture of starting material and compound 8 (1400 mg, crude, ~50% mixture) as light-yellow oil. The product was used for next step without further purification. MS m/z 338 (M+H)⁺. (S)-14-((1,3-Dioxoisoindolin-2-yl)oxy)-2-isopropyl-3-methyl-6,9,12-trioxa-3- azatetradecanoic acid (9): To a solution of compound 8 (1400 mg, 4.151 mmol, crude (~50%)), N-Methyl valine (550 mg, 4.195 mmol) and MgSO₄ (535 mg, 4.445 mmol) in DMF (5 mL) was added TFA (10 µL, cat) at 23 °C. After 30 min, to this mixture was added NaCNBH3 (400 mg, 6.365 mmol) at 23 °C. After 20 h, the reaction mixture transferred to 15 mL conical tube and the precipitate was removed by centrifuge (400 rpm, 10 min). The liquid was removed in vacuo. To the residue was added 1N HCl (5 mL) and DMSO (3 mL), and the mixture was purified by Prep- LC to give compound 9 (202 mg, 0.357 mmol, 9 %) as white solid. MS m/z 453 (M+H). (3R,4S,5S)-4-((S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-N,3,3- trimethylbutanamido)-3-methoxy-5-methylheptanoic acid (10): To a solution of compound 1 (887 mg, 1.491 mmol) in DCM (2 mL) was added TFA (2 mL ) at 23 °C. After 30 min, the liquid was removed in vacuo, and then dried under high vacuum to give compound 10 (887 mg, 1.647 mmol, crude) as colorless glassy form. The product was used in the next reaction without further purification. MS m/z 539 (M+H). Methyl (S)-2-amino-3-(thiophen-3-yl)propanoate (11): In a 100 mL round-bottomed flask equipped with a magnetic stirrer was placed an Boc-L-3-thienylalanine (990 mg, 3.646 mmol) and methanol (10 mL). To the mixture was added TMSCl (2000 µL, 18.416 mmol) at 23 °C. After 1 h, the liquid was removed in vacuo. To the residue was added anhydrous ether (60 mL). The slurry was stirred for 15 min and then filtered. The cake was washed with ether (5 mL) and dried to give compound 11 (710 mg, 2.206 mmol, 60 %) as white solid. MS m/z 286 (M+H). tert-Butyl (S)-2-((1R,2R)-1-methoxy-3-(((S)-1-methoxy-1-oxo-3-(thiophen-3- yl)propan-2-yl)amino)-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylate (12): To a solution of Boc-Dap-OH (342 mg, 1.190 mmol) and compound 11, HCl (270 mg, 1.458 mmol) in DCM (10 mL) was added DMTMMT (445 mg, 1.844 mmol) and DIEA (800 µL, 6.190 mmol) at 23 °C. After 1 h of stirring, the solution was diluted with 120 ml of EtOAc and washed with1N HCl (50 mL), saturated sodium bicarbonate (50 mL) and brine (20 mL). The organic layer was dried over MgSO4, followed by filtration. The volatiles were removed in vacuo and the residue was purified WSGR Ref. No 31362-825.601 by flash chromatography (SiO₂) to give compound 12 (527 mg, 1.159 mmol, 97 %) as white solid. MS m/z 455 (M+H). Methyl (S)-2-((2R,3R)-3-methoxy-2-methyl-3-((S)-pyrrolidin-2-yl)propanamido)-3- (thiophen-3-yl)propanoate (13): Compound 13 was prepared using compound 12 as starting material with similar procedure as described for compound 10 to get target compound (550 mg, 1.174 mmol, crude). MS m/z 355 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-3- yl)propanoate (14): Compound 14 was prepared using compound 10 and compound 13 as starting materials with similar procedure as described for compound 6 to get the target compound 14 (700 mg, 0.800 mmol, 70 %). MS m/z 875 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-amino-N,3,3- trimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2- methylpropanamido)-3-(thiophen-3-yl)propanoate (15): To a solution of compound 14 (360 mg, 0.413 mmol) in DCM (10 mL) was added dodecanethiol (380 µL, 1.877 mmol) and DBU (15 µL, 0.100 mmol) at 23 °C. After 1 h, the solvent was removed in vacuo. To the residue was added Hexane (100 mL) to precipitate the product. The hexane was decanted, and the precipitate was purified by Prep-LC to give compound 15 (350 mg, 0.456 mmol, 57%) as white solid. MS m/z 655 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-((S)-1-((13S,16S,19S,20R)-1-(aminooxy)-19-((S)-sec-butyl)- 16-(tert-butyl)-13-isopropyl-20-methoxy-12,18-dimethyl-14,17-dioxo-3,6,9-trioxa-12,15,18- triazadocosan-22-oyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-3- yl)propanoate (16): To a solution of compound 9 (180 mg, 0.398 mmol) and compound 15 (240 mg, 0.313 mmol) in DMF (3 mL) was added DMTMMT (100 mg, 0.414 mmol) and DIEA (220 m/z 1087 (M+H)⁺). To the mixture was added hydrazine hydrate (120 µL, 2.47 mmol) at 23 °C. After 40 min, the liquid was removed in vacuo (precipitate). To the precipitate was added DMSO (3 ml), and water 3 ml. The precipitate was removed by filtration, and the solution was purified by prep-LC to give compound 16 (169 mg, 0.146 mmol, 46%) as TFA salt of white powder. MS m/z 979 (M+Na)⁺. (S)-2-((2R,3R)-3-((S)-1-((13S,16S,19S,20R)-1-(Aminooxy)-19-((S)-sec-butyl)-16- (tert-butyl)-13-isopropyl-20-methoxy-12,18-dimethyl-14,17-dioxo-3,6,9-trioxa-12,15,18- triazadocosan-22-oyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-3- WSGR Ref. No 31362-825.601 yl)propanoic acid, 2TFA (17): To a solution of compound 16 (120 mg, 0.398 mmol) in water (3 ml) and MeOH (3 mL) was added LiOH (10 mg, 0.418 mmol) at 23 °C. After 20 min, the liquid was reduced to ~1 ml in vacuo, and then the mixture was purified by prep-LC to give compound 17 (40 mg, 0.034 mmol.34%) as TFA salt of white solid. MS m/z 943 (M+H)⁺. Example 4 – Synthesis of Compound 24 Synthetic Scheme for synthesis of Compound 24

. Methyl (S)-2-amino-3-(thiophen-2-yl)propanoate (18): Compound 18 was prepared using Boc-L-2-thienylalanine as starting material with similar procedure as described for compound 11 to get the target compound 18 (450 mg, 2.030 mmol, 94%), MS m/z 186 (M+H)⁺. tert-Butyl (S)-2-((1R,2R)-1-methoxy-3-(((S)-1-methoxy-1-oxo-3-(thiophen-2- yl)propan-2-yl)amino)-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylate (19): Compound 19 WSGR Ref. No 31362-825.601 was prepared using compound 18 and Boc-Dap as starting materials with similar procedure as described for compound 12 to get the target compound 19 (440 mg, 0.968 mmol, 92 %). MS m/z 455 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-methoxy-2-methyl-3-((S)-pyrrolidin-2-yl)propanamido)-3- (thiophen-2-yl)propanoate (20): Compound 20 was prepared using compound 19 as starting material with similar procedure as described for compound 10 to get the target compound 20 (460 mg, 0.982 mmol, quant.). MS m/z 355 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propanoate (21): Compound 21 was prepared using compound 20 as starting material with similar procedure as described for compound 6 to get the target compound 21 (675 mg, 0.771 mmol, 78 %). MS m/z 875 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-amino-N,3,3- trimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2- methylpropanamido)-3-(thiophen-2-yl)propanoate (22): Compound 22 was prepared using compound 21 as starting material with similar procedure as described for compound 15 to get the target compound 22 (321 mg, 0.419 mmol, 54%MS m/z 654 (M+H)⁺. Methyl (S)-2-((2R,3R)-3-((S)-1-((13S,16S,19S,20R)-1-(aminooxy)-19-((S)-sec-butyl)- 16-(tert-butyl)-13-isopropyl-20-methoxy-12,18-dimethyl-14,17-dioxo-3,6,9-trioxa-12,15,18- triazadocosan-22-oyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propanoate (23): Compound 23 was prepared using compound 9 and compound 22 as starting materials with similar procedure as described for compound 16 to get the target compound 23 (321 mg, 0.419 mmol, 54%) as TFA salt of white solid. MS m/z 957 (M+H)⁺. (S)-2-((2R,3R)-3-((S)-1-((13S,16S,19S,20R)-1-(Aminooxy)-19-((S)-sec-butyl)-16- (tert-butyl)-13-isopropyl-20-methoxy-12,18-dimethyl-14,17-dioxo-3,6,9-trioxa-12,15,18- triazadocosan-22-oyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propanoic acid (24): Compound 24 was prepared using compound 23 as starting material with similar procedure as described for compound 17 to get the target compound 24 (8 mg, 0.050 mmol, 95%) as TFA salt of white solid . MS m/z 943 (M+H)⁺. Example 5 – Synthesis of Compound 27 Synthetic Scheme for synthesis of Compound 27 WSGR Ref. No 31362-825.601

. 14-((1,3-dioxoisoindolin-2-yl)oxy)-2,2,3-trimethyl-6,9,12-trioxa-3-azatetradecanoic acid (25): Compound 25 was prepared using compound 8 and 2-methyl-2- (methylamino)propanoic acid as starting materials with similar procedure as described for compound 9 to get the target compound 25 (46 mg,0.083 mmol, 11%) as white solid. MS m/z 439 (M+H)⁺. methyl (S)-2-((2R,3R)-3-((S)-1-((16S,19S,20R)-1-(aminooxy)-19-((S)-sec-butyl)-16- (tert-butyl)-20-methoxy-12,13,13,18-tetramethyl-14,17-dioxo-3,6,9-trioxa-12,15,18- triazadocosan-22-oyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propanoate (26): Compound 26 was prepared using compound 22 and compound 25 as starting materials with similar procedure as described for compound 16 to get the target compound 26 (44 mg, 0.038 mmol, 45%) as TFA salt of white solid. MS m/z 943 (M+H)⁺. (S)-2-((2R,3R)-3-((S)-1-((16S,19S,20R)-1-(aminooxy)-19-((S)-sec-butyl)-16-(tert- butyl)-20-methoxy-12,13,13,18-tetramethyl-14,17-dioxo-3,6,9-trioxa-12,15,18- triazadocosan-22-oyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propanoic acid (27): Compound 27 was prepared using compound 26 as starting material with similar procedure as described for compound 17 to get the target compound 27 (33 mg, 0.029 mmol, 76 %) as TFA salt of white solid. MS m/z 929 (M+H)⁺. Example 6 – Synthesis of Compound 33 Synthetic Scheme for synthesis of Compound 33 WSGR Ref. No 31362-825.601

. tert-Butyl (S)-2-((1R,2R)-1-methoxy-3-(((S)-1-methoxy-1-oxo-3-phenylpropan-2- yl)amino)-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylate (28): Compound 28 was prepared using Boc-Dap-OH and L-Phe-OMe^.HCl as starting materials with similar procedure as described for compound 12 to get the target compound 28 (155 mg, 0.346 mmol, 98 %) as white solid. MS m/z 448 (M+H)⁺. Methyl ((2R,3R)-3-methoxy-2-methyl-3-((S)-pyrrolidin-2-yl)propanoyl)-L- phenylalaninate, TFA (29): Compound 29 was prepared using compound 28 as starting material with similar procedure as described for compound 10 to get the target compound 29 (160 mg, 0.346 mmol, quantitative) as TFA salt of white solid. MS m/z 349 (M+H)⁺. Methyl ((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L-phenylalaninate (30): Compound 30 was prepared using compound 29 and compound 10 as starting materials with WSGR Ref. No 31362-825.601 similar procedure as described for compound 6 to get the target compound 30 (90 mg, 0.104 mmol, 31%) as white solid. MS m/z 869 (M+H)⁺. Methyl ((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-amino-N,3,3-trimethylbutanamido)-3- methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L- phenylalaninate (31): Compound 31 was prepared using compound 30 as starting material with similar procedure as described for compound 15 to get the target compound 31 (30 mg, 0.039 mmol, 38%) as white solid. MS m/z 647 (M+H)⁺. Methyl ((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-14-(aminooxy)-2-isopropyl-3- methyl-6,9,12-trioxa-3-azatetradecanamido)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L-phenylalaninate (32): Compound 32 was prepared using compound 9 and compound 31 as starting materials with similar procedure as described for compound 16 to get the target compound 32 (25 mg, 0.021 mmol, 54%) as TFA salt of white solid. MS m/z 951 (M+H)⁺. ((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-14-(Aminooxy)-2-isopropyl-3-methyl- 6,9,12-trioxa-3-azatetradecanamido)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L-phenylalanine (33): Compound 33 was prepared using compound 32 as starting material with similar procedure as described for compound 17 to get the target compound 33 (24 mg, 0.021 mmol, 97%) as TFA salt of white solid. MS m/z 937 (M+H)⁺. Example 7 – Synthesis of Compound 37 Synthetic Scheme for synthesis of Compound 37

WSGR Ref. No 31362-825.601

. (3R,4S,5S)-4-((S)-2-(2-(Dimethylamino)-2-methylpropanamido)-N,3,3- trimethylbutanamido)-3-methoxy-5-methylheptanoic acid (34): Compound 34 was prepared using compound 2 and 2-(Dimethylamino)-2-methylpropanoic acid as starting materials with similar procedure as described for compound 3 to get the target compound 34 (27 mg, 0.050 mmol, 75%) as TFA salt of white solid. MS m/z 430 (M+H)⁺. (S)-2-(2-(Dimethylamino)-2-methylpropanamido)-N-((3R,4S,5S)-1-((S)-2-((1R,2R)- 3-(((S)-1-hydroxy-3-(thiophen-2-yl)propan-2-yl)amino)-1-methoxy-2-methyl-3- oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)-N,3,3- trimethylbutanamide (35): Compound 35 was prepared using compound 34 and compound 5 as starting materials with similar procedure as described for compound 6 to get the target compound 35 (28 mg, 0.038 mmol, 76 %) as TFA salt of white solid. MS m/z 738 (M+H)⁺. (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-(2-(Dimethylamino)-2- methylpropanamido)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propyl dihydrogen phosphate (36): To a solution of compound 35 (28 mg, 0.033 mmol) in acetonitrile (1 mL) was added trichloroacetonitrile (10 µL, 0.100 mmol), followed by drop wise addition of tetrabutylammonium phosphate monobasic (35 mg, 0.103 mmol) in acetonitrile (2 mL) WSGR Ref. No 31362-825.601 at 23 °C. After 22 h, the solvent was removed in vacuo. The residue was purified by Prep-LC to give compound 36 (25 mg, 0.027 mmol, 82 %) as TFA salt of white solid. MS m/z 818 (M+H)⁺. 2-(Aminooxy)ethyl ((S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-(2-(dimethylamino)- 2-methylpropanamido)-N,3,3-trimethylbutanamido)-3-methoxy-5- methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-(thiophen-2- yl)propyl) hydrogen phosphate (37): tert-Butyl 2-(phosphonooxy)ethoxycarbamate, TEA (25 mg, 0.070 mmol) was dissolved in DMF (1 mL) and treated with CDI (25 mg, 0.154 mmol) at 23 °C for 30 min. After quenched with MeOH (5 µL, 0.124 mmol) for 15 min, all the volatiles were removed in vacuo to give a syrup. To the syrup was added compound 36 (25 mg, 0.027 mmol) in DMF (2 mL) solution. After 22 h, the solvent was removed in vacuo, and then to the residue (MS m/z 1057 (M+H)⁺) was added DCM (1 mL) and TFA (1 mL). After 10 min, the solvent was removed in vacuo. The residue was purified by Prep-LC to give compound 37 (17 mg, 0.014 mmol, 53 %) as TFA salt of white solid. MS m/z 957 (M+H)⁺. Example 8 – Synthesis of Compound 43 Monomethyl auristatin E (MMAE) starting material is available from commercial suppliers including MedChemExpress, located at 1 Deerpark Dr # Q, Monmouth Junction, NJ 08852, as Catalog No.: HY-15162; and BroadPharm, located at 6625 Top Gun Street, Suite 103 San Diego, CA 92121, as Catalog No.: BP-22278. Compound 43 was obtained using the scheme as below. MS m/z 1009.5 (M-H)-, ³¹P NMR -11.48– -12.06 (m, 1P), -13.88– -14.07 (m, 1P). Synthetic Scheme for synthesis of Compound 43

WSGR Ref. No 31362-825.601

. Example 9 - Synthesis of Additional Drug-Linker Compounds The above schemes are further utilized in synthesizing drug linker compounds in engineering ADCs using the methods and procedures disclosed herein. Drug-linker compounds are prepared using similar procedures, protocols, and methods disclosed herein. Methods for the synthesis of additional drug-linker compounds are disclosed in WO2013/185117A1, the contents of which is hereby incorporated herein in its entirety, including the synthesis of amberstatin 269 (AS269). Additional drug-linker compounds are engineered by linkage of any possible linker group known in the art or elsewhere. The compounds of the present disclosure (e.g. compounds and ADCs disclosed herein) are engineered by linkage of one or more linkers via any chemical or functional reactive positions in the drug/payload, for example a nitrogen, halogen, boron, WSGR Ref. No 31362-825.601 phosphorus, silicon, sulfur, carbon or oxygen of the cytotoxic agent. Selection of the nitrogen, halogen, boron, phosphorus, silicon, sulfur, carbon or oxygen position in the drug/payload for linkage to a linker is assessed as disclosed elsewhere herein, based on structure of the cytotoxic agent, and using the process known in the art or elsewhere to generate a drug linkage. Further payload/drug-linkers contemplated in the present invention include linkage of one or more linkers at one or more nitrogen, halogen, boron, phosphorus, silicon, sulfur, carbon or oxygen of the cytotoxic agent. In some embodiments, such additional drug-linker compounds can comprise a branched linkers, which connect to two or more identical or different drug/payload. Example 10 – Site Specific Conjugation of Drug-Linker Payloads The synthesized drug or payload linker compounds generated by the above schemes were utilized in engineering ADCs. Briefly, anti-CD70 antibody (heavy chain SEQ ID NO: 20 containing para-acetyl-L-phenylalanine (pAF) at amino acid position 114 (Kabat numbering); and light chain SEQ ID NO: 19), or anti-HER2 antibody (heavy chain SEQ ID NO: 26 containing pAF at amino acid position 114 (Kabat numbering); and light chain SEQ ID NO: 27), were buffer exchanged into 30 mM sodium acetate; 2.5% trehalose, pH 4.0-4.3 and concentrated to 10-20 mg/mL. Acetic hydrazide (100mM) and amino-oxy functionalized drug-linker compounds 17, 24, 27, 33 and 37 (10-15 molar equivalents) were added and reacted for 16-48 hours at 30 °C. The resulting ADCs (anti-CD70-17, anti-CD70-24, anti-CD70-27, anti-CD70-33, anti-CD70-37, anti- HER2-17, anti-HER2-24, anti-HER2-27, anti-HER2-33 and anti-HER2-37) were purified over a cation exchange column (Capto SP Impres, Cytiva) to remove excess reagents. The purified ADCs were buffer exchanged into formulation buffer (50 mM histidine, 100 mM NaCl, 2.5% Calculated conjugation efficiencies based on LC-MS chromatograms (data not shown) and DAR values are reported in Table 12 for ADCs anti-CD70-17, anti-CD70-24, anti-CD70-27, anti- CD70-33, anti-CD70-37, anti-HER2-17, anti-HER2-24, anti-HER2-27, anti- HER2-33 and anti- HER2-37. Table 12. Conjugation efficiency and DAR values for exemplary ADCs of the invention.

WSGR Ref. No 31362-825.601

Anti-TROP2 antibody (heavy chain SEQ ID NO: 5 containing pAF at amino acid position 114 (Kabat numbering); and light chain SEQ ID NO: 4) was buffer exchanged into 50 mM sodium acetate, pH 4.0-4.3, and concentrated to 5-25 mg/mL.1.5 M acetohydrazide (AHZ), pH 4.0, was added to the concentrated antibody at a final concentration of 100 mM. A stock solution of drug- linker compound 17 in water for injection (WFI) or DMSO was then added to the anti-TROP2 mAb solution at 8-15 molar equivalents drug-linker to mAb. The conjugation reactions were allowed to react for 16-72 hours at 30 °C. The antibody conjugates were purified over a Capto SP Impres column (Cytiva) to remove excess reagents. ADCs were then formulated into 50 mM histidine, 2.5% trehalose, pH 6.0 and 0.22 µm filtered. Reverse Phase (RP) chromatography was used to monitor the final drug-to-antibody ratio (DAR) under reducing conditions. RP-HPLC analysis was performed on an Agilent 1200 series HPLC system using an Agilent Stablebond SB- C8, 5 µm, 4.6 x 150 mm column. Mobile phase A consisted of 0.1% TFA in water and mobile phase B consisted of 0.1% TFA in acetonitrile. The flow rate was 1 mL/minute, the column temperature was 75 °C, and detection was recorded at A214 nm. Elution of the reduced heavy and light chain of the mAb and ADC elution occurred during a 30-60% gradient increase of mobile phase B. Anti-HER3 antibody (heavy chain SEQ ID NO: 58 containing para-acetyl-L- phenylalanine (pAF) at amino acid position 114 (Kabat numbering); and light chain SEQ ID NO: 51 containing pAF at amino acid position 121 was conjugated with each of compounds 17, 27 and 37 to provide ADCs referred to herein as anti-HER3-17, anti-HER3-27 and anti-HER3-37, respectively, essentially as described above for the anti-CD70 and anti-HER2 ADCs. Example 11 - In vitro Cytotoxicity. In vitro testing of anti-HER2 and anti-CD70 ADCs. Cancer cells were seeded into 96-well white plate at 3,000 cells/well and incubated overnight in a 37 °C and 5% CO2 incubator. The next day, serially diluted anti-HER2 ADCs or anti-CD70 ADCs were added to the wells and the plates were incubated for 3 days. At the end of incubation, luminescence was measured by the addition of CellTiter-Glo2.0 (Promega, Madison, WI) and the relative cell viability was calculated as a percentage of untreated control. The half- WSGR Ref. No 31362-825.601 maximal inhibitory concentration (IC₅₀) was determined by a sigmoidal 4PL curve fitting using Prism (GraphPad Software, San Diego, CA). Anti-HER2-17, anti-HER2-24, and anti-HER2-33 showed cytotoxic activity with comparable IC₅₀s in HER2 high SK-BR-3 breast cancer cell line (FIG. 2A), HER2 low JIMT-1 breast cancer cell line (FIG.2B), and NCI-N87 gastric cancer cell line (FIG.2C) while anti-HER2- 37 and anti-HER2-27 showed reduced cytotoxic activity in these assays (Table 13). All anti-HER2 ADCs had no cell killing effect on HER2 negative MDA-MB-468 cell line (FIG.2D). Table 13. IC50 (nM) of anti-HER2 ADCs

Anti-CD70-17, anti-CD70-24, and anti-CD70-33 showed cytotoxic activity in CD70 positive 788-O and U-266 cell lines (FIGS.3A and 3B). The anti-CD70 ADCs did not show cell killing effect against HER2 positive/CD70 negative breast cancer cell line BT-474 (FIG.3C). In vitro testing of anti-HER3 ADCs. For the 2D-culture cytotoxicity assay, cells were seeded into 96-well clear bottom white plate at 1,000 cells/well and incubated overnight in a 37 °C and 5% CO2 incubator. The next day, serially diluted anti-HER3 ADCs (anti-HER3-17, anti-HER3-27 and anti-HER3-37) were added to the wells and the plates were incubated for 7 days. At the end of incubation, CellTiter-Glo2.0 Reagent (Promega, Madison, WI) was added to the room temperature equilibrated plates and luminescence was measured in a SpectraMax M5E luminometer. For the 3D-culture cytotoxicity assay, cells were seeded at 1,000 cells/well into 96-well clear round bottom Ultra-low attachment microplate and cultured for 3 days. The serially diluted anti-HER3 ADCs (anti-HER3-17, anti-HER3-27 and anti-HER3-37) were added to the wells and the plates were incubated for 7 days. At the end of incubation, CellTiter-Glo 3D Reagent (Promega, Madison, WI) was added to the room temperature equilibrated plates, mixed for 5 minutes, and allowed the luminescent signal stabilized for 25 minutes. The media were transferred to new 96- well white plates and luminescence was measured in a SpectraMax M5E luminometer. The relative viability of each cell line was calculated based on untreated cells as 100% viability. The half-maximal inhibitory concentration (IC50) was determined by a nonlinear 4-parameter dose- WSGR Ref. No 31362-825.601 response curve fitting using GraphPad Prism (GraphPad Software, San Diego, CA). The maximal killing (Emax) was determined by subtracting the % viability from 100%. Cytotoxicity of anti-HER3-17, anti-HER3-27 and anti-HER3-37 against HCC1569, A375, HC827 and SKOV-3 cell lines is shown in FIGS.4A, 4B, 4C and 4D, respectively. The DAR of each anti-HER3 ADC, together with the IC50 (nM) and Emax (%) at 100 nM treatment in the HCC1569 cell line, are shown in Table 14. Anti-HER3-Compound-17 showed cytotoxic activity with an IC₅₀ value of 2.91 nM and efficacy with Emax of 61.5% in HER3-high HCC1569 cell line, and an IC50 value of 22.38 nM in HER3-intermediate A375. The anti-HER3 ADCs showed minimal cytotoxic activities in HER3-low HCC827 or HER3-negative SKOV-3 cell lines. Anti- HER3-mcVC-MMAE represents a control ADC using MMAE payload with a cathepsin cleavable linker maleimido-caproyl-valine-citruline (mcVC). Table 14. IC50 (nM) and Emax (%) in HCC1569 cell line.

In vitro testing of anti-TROP2 ADCs. Cells were seeded into 96-well clear bottom white plate at 2,500 cells/well for BxPC-3, MDA-MB-468, and Calu-6 cells or at 2,000 cells/well for HCC1806 cells and incubated overnight in a 37 °C, 5% CO₂ incubator. The next day, serially diluted anti-TROP2-17 ADC (DAR2; “TROP2-compound-17”), an anti-TROP2-auristatin-0101 ADC (also referred to herein as “Benchmark-Aur0101”) or monomethyl auristatin E (MMAE; MedChemExpress, CAS No.: 474645-27-7) were added to the wells, and the plates were incubated for 4 days. At the end of incubation, luminescence was measured by addition of CellTiter-Glo2.0 Reagent (Promega, Madison, WI) to the room temperature equilibrated plates. The relative cell viability was calculated as a percentage of an untreated control. The half-maximal inhibitory concentration (IC50) was determined by a nonlinear 4-parameter dose-response curve fitting using GraphPad Prism (GraphPad Software, San Diego, CA). The maximal killing (Emax) was determined by subtracting the % viability from 100%. The results are shown in FIGS.5A-5D). Cytotoxicity in human keratinocytes was assessed as follows. Cells were seeded at 2,500 cells/well into 96-well clear bottom white plate and treated the next day with serially diluted anti- WSGR Ref. No 31362-825.601 TROP2-17 ADC (DAR2; “TROP2-compound-17”), Benchmark-Aur0101 or MMAE. The relative viability of the cells was measured using CellTiter-Glo2.0 Reagent 4 days after treatment. The results are shown in FIG. 5E. TROP2-compound-17 was more potent than Benchmark- Aur0101 in BxPC-3 and HCC1806 cells and showed less cytotoxicity than Benchmark-Aur0101 in keratinocytes. No cytotoxicity was observed when TROP2-negative Calu-6 cells were treated with up to 100 nM concentrations of TROP2-compound-17. Example 12 – Metabolism of ADCs ADCs of the present disclosure can be metabolized in vitro or in vivo. Exemplary payload- linker metabolism of ADCs containing antibody conjugated to drug via non-natural amino acid pAF are illustrated in FIG. 6A (metabolism of ADC containing compound 17) and FIG. 6B (metabolism of antibody containing compound 37). After binding to target antigens on tumor cells, the ADC can be internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. Example 13 Methods of generating cell lines to promote non-natural amino acid-containing protein production using genome engineering technology, essentially as described in WO2018/223108, the entire contents of which are hereby incorporated by reference in their entirety, can be applied to generate antibodies (including anti-CD70 antibodies, anti-HER2 antibodies, anti-PSMA antibodies, anti-HER3 antibodies and anti-TROP2 antibodies) containing non-naturally encoded amino acids of the present disclosure. Molecular Cloning for Antibody Expression. CHO cell codon-optimized antibody heavy chain and light chain cDNA sequences were obtained from a commercial DNA synthesis service (Integrated DNA Technologies (IDT), San Diego, CA). The synthesized DNA fragments were digested with Hind III and EcoR I (both from New England BioLabs, (NEB), Ipswich, MA) and purified using a PCR purification kit (Qiagen, Valencia, CA). Then the digested antibody gene fragments were ligated into the expression vector via a quick ligation kit (NEB) to yield the constructs for expression of wild type antibody heavy chain and light chain. The resulting plasmids were propagated in E. coli and verified by a DNA sequencing service (Eton Biosciences, San Diego, CA). Generation of amber codon-containing mutants. The genetic codon of each site chosen for genetic incorporation of non-natural amino acid pAF was mutated to amber codon (TAG) via site-directed mutagenesis to generate an expression plasmid for that antibody mutant. Primers were purchased from IDT. All site-directed mutagenesis experiments were carried out using Q5 site-directed mutagenesis kit following the instruction manuals (NEB). The expression plasmids for the mutants were propagated in E. coli and verified by a DNA sequencing service (Eton Biosciences). WSGR Ref. No 31362-825.601 Protocols for Production of Anti-CD70 Antibodies Containing pAF at Heavy Chain Position 114 Transient expression. Platform cell line was maintained in EX-Cell 302 (Sigma) supplemented with 3 mM L-glutamine (Gibco) and 3 mM GlutaMAX (Gibco). Cells were passaged every 3 to 4 days seeded at a density of 0.4 million cells per ml. One day prior to transfection, cells were seeded at 0.6 million cells per ml. On day 0, cells were transfected with antibody expression plasmids encoding the light chain and heavy chain using MaxCyte electroporation platform following the instruction manual. After transfection, cells were rested in an empty 125 ml shake flask and incubated at 37 °C in a static incubator for 30 mins. The transfected cells were then inoculated into basal expression media (50% Dynamis:50% ExCell 302 supplemented with 3 mM L-glutamine and 3 mM GlutaMAX) at a density of 3 x 10⁶/ml in shake flask. The transfected cells were incubated at 37 °C, 5% CO2 on an orbital shaker set to 140 rpm. The following were added to the culture on day 1: pAF (final concentration in culture: 1 mM), Cell Boost 5 (GE Healthcare; final concentration in culture: 7 g/L), Long R3 IGF-1 (Sigma; final concentration in culture: 120 µg/L) and GlutaMAX (final concentration in culture: 2 mM). The temperature was shifted from 37 °C to 32 °C inside the incubator. Additional Cell Boost 5 (final concentration: 7 g/L) and GlutaMAX (final concentration: 2 mM) was added on day 3 and supernatant was collected on day 5. The culture media glucose level was monitored using glucose meters, and additional glucose was added to the culture when the glucose level was below 2 g/L. Viable cell count and viability were measured by Vi-Cell instrument. Antibody production was measured by Octet using Protein G sensors. Stable bulk pool generation. The expression plasmid was linearized using Pvu I (NEB) digestion for four hours. After linearization, the DNA was purified using phenol:chloroform:isoamyl alcohol extraction and dissolved in endotoxin-free water at the concentration of 2.5 µg/µl. Platform cell line was maintained in EX-Cell 302 supplemented with 3 mM L-glutamine and 3 mM GlutaMAX. Cells were passaged every 3 to 4 days seeded at a density of 0.3 x 10⁶/ml. One day prior to transfection, cells were seeded at 0.6 x 10⁶/ml. On day 0, 15 x 10⁶ cells were transfected with 25 µg of linearized antibody expression plasmids using MaxCyte electroporation (OC-100) platform following the instruction manual. After transfection, cells were rested in an empty 125 ml shake flask and incubated at 37 °C in a static incubator for 30 mins. Then 30 ml recovery media (50% Ex-302:50% CD-CHO supplemented with 3 mM L-glutamine and 3mM GlutaMAX) was added into the flask and shaked overnight. On day one, transfected cells were counted, spun down, washed and re-suspended in selection media (50% EXCELL 302:50% CD- CHO with 50 µM MSX) for stable bulk pool generation. The viable cell numbers and viability were monitored, and media was changed every 3 to 4 days until the viability of the stable bulk WSGR Ref. No 31362-825.601 pool returned to 90%. When selection ended, frozen cell stocks were made, and the resulting stable bulk pool was used to generate material for fed-batch expression. Fed-batch expression. Previously generated antibody stable bulk pools were inoculated into basal expression media (50% Dynamis:50% ExCell 302 supplemented with 50 µM MSX) at a density of 0.5 x 10⁶/ml in a shake flask on day 0. The transfected cells were incubated at 37 °C, 5% CO2 on an orbital shaker set to 150 rpm. The following were added to the culture on day 3: pAF (final concentration in culture: 0.5 mM), Cell Boost 4 (GE Healthcare; final concentration in culture: 10 g/L) and Cell Boost 7b (GE Healthcare; final concentration in culture: 0.52 g/L). Long R3 IGF-1 (final concentration in culture: 120 µg/L) was added to the culture on day 5. The culture media glucose level was monitored using glucose meters, and additional glucose was added to the culture when the glucose level was below 2 g/L. Viable cell count and viability were measured by Vi-Cell instrument. The supernatant was collected for purification on day 7. Antibody production was measured by Octet using Protein G sensors. Protocols for Production of Anti-HER3 Antibodies Containing pAF at Heavy Chain Position 114 and Light Chain Position 121 Transient expression - Platform cell line was maintained in EX-CELL 302 (Sigma) supplemented with 3 mM L-glutamine (Gibco) and 3 mM GlutaMAX (Gibco). Cells were passaged every 3 to 4 days seeded at a density of 0.4 million cells per ml. One day prior to transfection, cells were seeded at 0.6 million cells per ml. On day 0, cells were transfected with antibody expression plasmids encoding the light chain and heavy chain using MaxCyte electroporation platform following the instruction manual. After transfection, cells were rested in an empty 125 ml shake flask and incubated at 37 °C in a static incubator for 30 min. Basal expression media (50% Dynamis : 50% EX-CELL 302 supplemented with 3 mM L-glutamine and 3 mM GlutaMAX) was added to the transfected cells in the shake flask for a final density of 3 x 10⁶ cells per ml. The transfected cells were incubated at 37 °C, 5% CO2 on an orbital shaker set to 155 RPM. The following were added to the culture on day 1: pAF (final concentration in culture: 1 mM), Cell Boost 4 (GE Healthcare; final concentration in culture: 3.75 g/L), Cell Boost 7b (GE Healthcare; final concentration in culture: 0.2 g/L), Long R3 IGF-1 (Sigma; final concentration in culture: 120 µg/L) and GlutaMAX (final concentration in culture: 2 mM). The incubator temperature was shifted from 37 °C to 32 °C. Additional Cell Boost 4 (final concentration: 2 g/L), Cell Boost 7b (final concentration: 0.1 g/L), and GlutaMAX (final concentration: 2 mM) was added on days 3 and 5, and supernatant was collected on day 7. The culture media glucose level was monitored using glucose meters, and additional glucose was added to the culture when the glucose level was WSGR Ref. No 31362-825.601 below 2 g/L. Viable cell count and viability were measured by Vi-Cell instrument. Antibody production was measured by Octet using Protein G sensors. Stable bulk pool generation - The expression plasmid was linearized using Pvu I (NEB) digestion for four hours. After linearization, the DNA was purified using phenol:chloroform:isoamyl alcohol extraction and dissolved in endotoxin-free water at the concentration of 2.5 µg/µl. Platform cell line was maintained in EX-CELL 302 supplemented with 3 mM L-glutamine and 3 mM GlutaMAX. Cells were passaged every 3 to 4 days seeded at a density of 0.3 x 10⁶/ml. One day prior to transfection, cells were seeded at 0.6 x 10⁶/ml. On day 0, 15 x 10⁶ cells were transfected with 25 µg of linearized antibody expression plasmids using MaxCyte electroporation (OC-100) platform following the instruction manual. After transfection, cells were rested in an empty 125 ml shake flask and incubated at 37 °C in a static incubator for 30 min. Then 30 ml recovery media (50% EX-CELL: 50% CD-CHO supplemented with 3 mM L-glutamine and 3mM GlutaMAX) was added into the flask and shaken overnight. On day one, transfected cells were counted, spun down, washed and re-suspended in selection media (50% EX-CELL 302 : 50% CD- CHO with 25 µM MSX) for stable bulk pool generation. The viable cell numbers and viability were monitored, and media was changed every 3 to 4 days until the viability of the stable bulk pool returned to 90%. When selection ended, frozen cell stocks were made, and the resulting stable bulk pool was used to generate material for fed-batch expression. Fed-batch expression - Previously generated antibody stable bulk pools were inoculated into basal expression media (50% Dynamis : 50% EX-CELL 302 supplemented with 1x GS, 2 µg/ml insulin, 0.5 mM ornithine, 2 g/L glucose and 1 x anti clumping agent and 25 µM MSX) at a density of 0.5 x 10⁶/ml in a shake flask on day 0. The transfected cells were incubated at 37 °C, 5% CO2 on an orbital shaker set to 150 rpm. The following were added to the culture on day 3: pAF (final concentration in culture: 0.5 mM), Cell Boost 4 (GE Healthcare; final concentration in culture: 10 g/L) and Cell Boost 7b (GE Healthcare; final concentration in culture: 0.52 g/L). Long R3 IGF- 1 (final concentration in culture: 120 µg/L) was added to the culture on day 5. The culture media glucose level was monitored using glucose meters, and additional glucose was added to the culture up to 6g/L when the glucose level was below 2 g/L. Viable cell count and viability were measured by Vi-Cell instrument. The supernatant was collected for purification on day 10. Antibody production was measured by Octet using Protein G sensors. Protocols for Production of Anti-TROP2 Antibodies Containing pAF at Heavy Chain Position 114 Engineering of Expression Vectors – Anti-TROP2 antibody expression plasmids were engineered by recombination-based cloning method using Gibson Assembly kit (New England Biolabs, MA) WSGR Ref. No 31362-825.601 in E. coli E. coli cloning host used in this study and its genotypes. Table 15. Escherichia coli cloning host strain and genotype.

Gibson Assembly – Anti-TROP2 light chain and heavy chain gBlocks (GOIs) were synthesized at Genewiz (Azanta, South Plainfield, NJ, 07080). The primers for amplifying various GOIs with the acceptor vector sequences for homologous recombination and were synthesized at Integrated DNA Technologies ((IDT), San Diego, CA)). The PCR fragments were amplified using high fidelity DNA polymerase mix, Pfu Ultra II Hotstart PCR Master Mix (Agilent Technologies, CA). The PCR products were digested with Dpn1 restriction enzyme (NEB) for 2 hours at 37 °C to remove plasmid background followed by column purification using Qiagen PCR column purification kit (Qiagen) and quantitated by Nanodrop (ThermoFisher). The acceptor vectors were linearized by digesting with unique restriction enzymes: HindIII and EcoR1 (NEB, MA) for 4 to 5 hours at supplier’s recommended temperatures, PCR column purified and quantitated. The donor inserts and appropriately prepared acceptor vectors were mixed at a 3:1 molar ratio, incubated at 50 °C for 15 min, using Gibson Assembly kit (NEB), and then used for transformation into E. coli The recombinants were recovered by plating transformed cells on to 2xYT+ 2% Glucose agar plates (Teknova) containing antibiotic carbenicillin, 100 µg/mL. The next day, 4 to 6 well- isolated single colonies were inoculated into 5 mL Super broth + carbenicillin 100 µg/mL (Teknova) media and grown overnight at 37 ^oC. The recombinant plasmids were isolated using Qiagen’s plasmid DNA mini-prep kit (Qiagen) and verified by DNA sequencing (Eton Biosciences, CA). The complete GOI region plus 200 bp upstream and 200 bp downstream sequences were verified by using gene-specific sequencing primers. CHO cells transient transfection grade high-quality large-scale DNA (10 mg or higher) was manufactured at Aldevron (Fargo, North Dakota 58103). Transient expression – Platform cell line was maintained in CD CHO Fusion (SAFC) supplemented with 8 mM L-glutamine (Gibco). Cells were passaged every 3 to 4 days at density of 0.4 million cells per ml. Cells were expanded to large scale to meet transfection volume. WSGR Ref. No 31362-825.601 On the day of transfection, cells were collected for transfection volume at Viable Cell Density of 4 x 10⁶/ml. Cells were then spun at 2000 RPM, for 4 min. at room temperature. The liquid was aspirated by vacuum and the cell pellet was re-suspended with transfection volume of TransFX (Cytiva) supplemented with 8 mM L-glutamine (Gibco), 0.05% Poloxamer 188 (Sigma), 0.125% Dimethyl Acetamide (Sigma Aldrich). Non-Linearized DNA at the ratio of 2:1 (HC:LC) at the total amount of 3.2 mgs/L were added to the cells in shake flask. The culture was shaking at 190 RPM, 37C, 5% CO₂, 80% humidity in incubator (Kuhner) for 5 min. PEI Max (liquid, Polysciences) was added to culture/DNA at the concentration of 4.8 mgs/L, and immediately, the culture shake flask was placed back into same incubator for 24 hr. The following were added to the culture on day 1: pAF (final concentration in culture: 1 mM), Cell Boost 4 (GE Healthcare; final concentration in culture: 3.75 g/L), Cell Boost 7b (GE Healthcare; final concentration in culture: 0.2 g/L), Long R3 IGF-1 (Sigma; final concentration in culture: 120 µg/L). The incubator temperature was shifted from 37 °C to 32 °C, and the shake speed reduced to 160 RPM. Additional Cell Boost 4 (final concentration: 2 g/L), Cell Boost 7b (final concentration: 0.1 g/L), and glucose (final concentration: 2 mM) were added on days 3, and 5. The culture media glucose level was monitored using glucose meters, and additional glucose was added to the culture when the glucose level was below 2 g/L. Viable cell count and viability were measured by Vi-Cell instrument. Antibody production was measured by Octet using Protein G sensors. The culture was collected on day 7, by spinning at 4000RPM, 20min. in centrifuge. The supernatant was then filtered by 0.2 µm filtration. The foregoing transient expression method can also be used to generate light chain mutants, such as light chain having amber mutation at V110, A112 or S114, each of which were generated as transients. Master-well generation - The expression plasmid was linearized using Pvu I (NEB) digestion for 24 hours. After linearization, the DNA was purified using phenol:chloroform:isoamyl alcohol extraction and dissolved in endotoxin-free water at the concentration of 2.5 µg/µl. Platform cell line was maintained in EX-CELL 302 supplemented with 3 mM L-glutamine and 3 mM GlutaMAX. Cells were passaged every 3 to 4 days seeded at density of 0.3 x 10⁶/ml. One day prior to transfection, cells were seeded at 0.6 x 10⁶/ml. On day 0, 15 x 10⁶ cells were transfected with 25 µg of total linearized antibody expression plasmids using MaxCyte electroporation (OC- 100) platform following instruction manual. After transfection, cells were rested in an empty 125 ml shake flask and incubated in 37 °C static incubator for 20 min. Then 30 ml recovery media (50% EX-CELL 302 (SAFC) - 50% CD-CHO (GIBCO) supplemented with 3mM glutamine and 3mM GlutaMAX) was added into the flask and shaken in incubator. After 48 hours, transfected WSGR Ref. No 31362-825.601 cells were counted, spun down, washed and re-suspended in selection media (50% EX-CELL 302 – 50% CD-CHO with 37.5 µM MSX (Millipore)) for Master-well generation. Limited dilution of cells was performed. Cells were then plated into 96-well flat bottom plate (Corning) at volume of 200uL and at cell density of 2500 cells/well. Five 96-well plates were plated and placed into static 37 °C, 5% CO2, high humidity incubator (Panasonic) for 3 weeks. Confluent wells were selected and transferred to new “Master” 96-well plate by diluting 100 µL of old culture with 100 µL of fresh media (50% EX-CELL 302 + 50% CD CHO + 37.5 µM MSX). The plates were plated and placed into static 37 °C, 5% CO2, high humidity incubator for 4 days. On day 4, 100 µL of cells from each well of “Master” plate were transferred into new “assay” plate which contained 100 µL of 50% EX-CELL 302 + 50% CD CHO + 37.5uM MSX + 1mM pAF. The final concentration of pAF is 0.5 mM. After incubating for 4 days, the “assay” plate was spun at 2000 RPM, 4 minutes. The supernatants were subjected to ELISA with capturing (Southern Biotech). Top 24 clones, based upon ELISA data, were selected and transferred from the “master” plate into 24 Well plate (Corning) by diluting 180 µL of old culture from each well into 500 µL of same selection media. The 24-well plate was placed into static incubator at 37 °C, 5% CO₂, 80% humidity (Panasonic) for 4 days. Cells from each well (24 well static) were transferred to 24- Deep Well plate (Thomson Instrument) by dilution of 600 µL of cells into 1400 µL of fresh selection media per well. The plate was incubated in shaking incubator (250 RPM, 37 °C, 5% CO2, 80% humidity). After 7 days, cells from each well were diluted with PBS (0.5 mL cells + 0.5 mL PBS) to count by Vicel. Each “master-well” were transferred to 125 mL shake flask (Corning). The dilution was 1.5 mL of cultures into 20 mL of same selection media. The shake flasks were shaking in Kuhner incubator (37 °C, 5% CO2, 80% humidity, 155 RPM) for 5 days. Each of the master-well clones was passaged at least 1 passage, and 2 freeze vials were frozen. The cultures then being subjected to Fed-batch expression to finalize top 2 master wells. Fed-batch expression - Generated master-well clones were inoculated into basal expression media (50% Dynamis – 50% EX-CELL 302 supplemented with 25 µM MSX, ornithine 0.5 mM, glucose 2 g/L) at density of 0.5 x 10⁶/ml in a shake flask on day 0. The transfected cells were incubated at 37 °C, 5% CO₂ on orbital shaker set to 150 rpm. The following were added to the culture on day 3: pAF (final concentration in culture: 0.5 mM), Cell Boost 4 (GE Healthcare; final concentration in culture: 10 g/L) and Cell Boost 7b (GE Healthcare; final concentration in culture: 0.52 g/L). Long R3 IGF-1 (final concentration in culture: 120 µg/L) was added to the culture on day 5. The culture media glucose level was monitored using glucose meters, and additional glucose was WSGR Ref. No 31362-825.601 added to the culture up to 6 g/L when the glucose level was below 2 g/L. Viable cell count and viability were measured by Vi-Cell instrument. The supernatant was collected for purification on day 10. Antibody production was measured by Octet using Protein G sensors. Example 14 - Purification of Antibodies Containing nnAAs from EuCODE Expression System. Clarified Cell culture media containing the target antibody containing non-naturally encoded amino acid was loaded over a protein A ProSep Ultra column (EMD Millipore) equilibrated in 20 mM sodium phosphate, 100 mM sodium chloride, pH 7.5. After loading, the column was washed with buffer A (20 mM sodium phosphate, 100 mM sodium chloride, pH 7.5) followed by wash buffer B (5 mM succinic acid, pH 5.8) to remove host cell contaminants. The target antibody was eluted from the column with elution buffer C (50 mM glycine, 10 mM succinic acid, pH 3.2). The target antibody was pooled, and pH adjusted to pH 5.0 with 2.0 M tris base. The target antibody was further purified by loading the conditioned protein A pool over a Capto SP Impres column (GE Healthcare) equilibrated in 30 mM sodium acetate, pH 5.0. The target antibody was eluted from the column with a linear gradient to 100% buffer B (30 mM sodium acetate, 0.5 M sodium chloride, pH 5.0) and fractions containing monomeric antibody were pooled, It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to those of ordinary skill in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, patent applications, and/or other documents cited in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, patent application, and/or other document were individually indicated to be incorporated by reference for all purposes.

Claims

WSGR Ref. No 31362-825.601 CLAIMS WHAT IS CLAIMED IS: 1. An antibody-drug conjugate (ADC) of Formula (I-ADC) or Formula (II-ADC):

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence comprising one or more non-naturally encoded amino acids; L is a linker; E is a moiety joining the antibody Ab to the linker L; d is an integer from 1 to 10; V is selected from the group consisting of -CH₂-, -S-, -S(O)-, -C(O)- and -C(H)(R_v)-; wherein Rv is F, CN, N3, OH, ONH2 , unsubstituted C1-C8 alkyl, or substituted C₁-C₈ alkyl; X is O or NH; Z is -CH2- or -C(O)-; R₅ is H, unsubstituted C₁-C₆ alkyl, substituted C₁-C₆ alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C₃-C₆ cycloalkyl; R6 is unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted cycloalkyl, substituted cycloalkyl, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; and each R_7, R₈ and R₉ is independently H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; or R7 and R₈ are joined to form an unsubstituted heterocycloalkyl or substituted heterocycloalkyl, and R₉ is H, unsubstituted C₁-C₈ alkyl, or optionally substituted C1-C8 alkyl; or R8 and R9 are joined to form an unsubstituted cycloalkyl, WSGR Ref. No 31362-825.601 substituted cycloalkyl, an unsubstituted heterocycloalkyl, or substituted heterocycloalkyl, and R7 is H, unsubstituted C1-C8 alkyl, substituted C1-C8 alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C₃-C₆ cycloalkyl; and R_7a is H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, unsubstituted C₃-C₆ cycloalkyl, or substituted C3-C6 cycloalkyl. 2. The ADC of claim 1, wherein the ADC is according to Formula (I-ADC). 3. The ADC of claim 1, wherein the ADC is according to Formula (II-ADC). 4. The ADC of any one of claims 1 to 3, wherein Ab is an anti-HER3 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 46 to 58. 5. The ADC of claim 4, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. 6. The ADC of claim 4, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. 7. The ADC of any one of claims 1 to 3, wherein Ab is an anti-TROP2 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 17. 8. The ADC of claim 7, wherein the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 5, and the light chain amino acid sequence is SEQ ID NO: 4. 9. The ADC of any one of claims 1 to 3, wherein Ab is an anti-CD70 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 18 to 24. 10. The ADC of claim 9, wherein the anti-CD70 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 20, and the light chain amino acid sequence is SEQ ID NO: 19. 11. The ADC of any one of claims 1 to 3, wherein Ab is an anti-HER2 antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 25 to 28. 12. The ADC of claim 11, wherein the anti-HER2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 26, and the light chain amino acid sequence is SEQ ID NO: 27. 13. The ADC of any one of claims 1 to 3, wherein Ab is an anti-PSMA antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 29 to 45. WSGR Ref. No 31362-825.601 14. The ADC of claim 13, wherein the anti-PSMA antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 36, and the light chain amino acid sequence is SEQ ID NO: 37. 15. The ADC of any one of claims 1 to 14, wherein d is 1, 2, 3 or 4. 16. The ADC of any one of claims 1 to 15, wherein V is -CH2-. 17. The ADC of any one of claims 1 to 16, wherein R6 is unsubstituted heteroaryl or substituted heteroaryl. 18. The ADC of claim 17, wherein the unsubstituted heteroaryl is unsubstituted 2-thienyl. 19. The ADC of claim 17, wherein the unsubstituted heteroaryl is unsubstituted 3-thienyl. 20. The ADC of any one of claims 1 to 19, wherein each of the one or more non-naturally encoded amino acids is independently selected from the group consisting of 4-acetyl-L-phenylalanine N-Acetyl-D-glucosaminyl)-L-asparagine, O-allyl-L-tyrosine, alpha-N-acetylgalactosamine-O-L- serine, alpha-N-acetylgalactosamine-O-L-threonine, 2-aminooctanoic acid, 2-amino-L- phenylalanine, 3-amino-L-phenylalanine, 4-amino-L-phenylalanine, 2-amino-L-tyrosine, 3- amino-L-tyrosine, 4-azido-L-phenylalanine, 4-benzoyl-L-phenylalanine, (2,2-bipyridin-5yl)-L- alanine, 3-borono-L-phenylalanine, 4-borono-L-phenylalanine, 4-bromo-L-phenylalanine, p- carboxymethyl-L-phenylalanine, 4-carboxy-L-phenylalanine, p-cyano-L-phenylalanine, 3,4- dihydroxy-L-phenylalanine (L-DOPA), 4-ethynyl-L-phenylalanine, 2-fluoro-L-phenylalanine, 3- fluoro-L-phenylalanine, 4-fluoro-L-phenylalanine, O-(3-O-D-galactosyl-N-acetyl-beta-D- galactosaminyl)-L-serine, L-homoglutamine, (8-hydroxyquinolin-3-yl)-L-alanine, 4-iodo-L- phenylalanine, 4-isopropyl-L-phenylalanine, O-i-propyl-L-tyrosine, 3-isopropyl-L-tyrosine, O- mannopyranosyl-L-serine, 2-methoxy-L-phenylalanine, 3-methoxy-L-phenylalanine, 4-methoxy- L-phenylalanine, 3-methyl-L-phenylalanine, O-methyl-L-tyrosine, 3-(2-naphthyl)-L-alanine, 5- nitro-L-histidine, 4-nitro-L-histidine, 4-nitro-L-leucine, 2-nitro-L-phenylalanine, 3-nitro-L- phenylalanine, 4-nitro-L-phenylalanine, 4-nitro-L-tryptophan, 5-nitro-L-tryptophan, 6-nitro-L- tryptophan, 7-nitro-L-tryptophan, 2-nitro-L-tyrosine, 3-nitro-L-tyrosine, O-phospho-L-serine, O- phospho-L-tyrosine, 4-propargyloxy-L-phenylalanine, O-2-propyn-1-yl-L-tyrosine, 4-sulfo-L- phenylalanine, para-(2-azidoethoxy)-L-phenylalanine ((S)-2-amino-3-(4-(2- azidoethoxy)phenyl)propanoic acid) and O-sulfo-L-tyrosine. 21. The ADC of any one of claims 1 to 20, wherein E comprises an amide, an ester, a thioester, a pyrrolidine-2,5-dione, an oxime, a 1,2,3-triazole or a 1,4-dihydropyridazine, or a combination thereof. WSGR Ref. No 31362-825.601 22. The ADC of claim 21, wherein the 1,2,3-triazole is fused to an 8-membered ring, and the 1,4- dihydropyridazine is fused to an 8-membered ring. 23. The ADC of any one of claims 1 to 22, wherein each of the one or more non-naturally encoded amino acids is para-acetyl-L-phenylalanine (pAF), and E has the following structure:

; wherein Rc is methyl; + denotes a connection to linker L; and the wavy line ( ) denotes a connection to antibody Ab. 24. The ADC of any one of claims 1 to 23, wherein Z is -C(O)-, and X, when present, is O. 25. The ADC of any one of claims 1 to 24, wherein R5, when present, is H; each R7, R8 and R9 is independently H or unsubstituted C₁-C₈ alkyl; and R_7a, when present, is H or unsubstituted C₁-C₈ alkyl. 26. The ADC of any one of claims 1 to 25, wherein the linker L is selected from the group consisting of a bond, –alkylene–, –(alkylene–O)_n–alkylene–, –alkylene–C(O)–, –(alkylene–O)_n– alkylene–C(O)–, –alkylene-(alkylene–O)_n-C(O)–, –alkylene-arylene-alkylene–, –alkylene–NH–, –(alkylene–O)n-alkylene-NH–, –C(O)-alkylene-NH–, –C(O)-(alkylene–O)n–alkylene–NH–, – (alkylene–O)n–alkylene–J–, –J-alkylene–, –alkylene-J-alkylene–, –(alkylene-O)n-J-alkylene–, – alkylene-J-(alkylene-O)_n-alkylene-C(O)–, –alkylene–J–(alkylene–O)_n–alkylene–, –(alkylene– O)n–alkylene–J–alkylene, –J–(alkylene–O)n–alkylene–, –J–(alkylene–O)n–(alkylene–O)n– alkylene–, –(alkylene–O)n–alkylene–J–(alkylene–O)n–alkylene–J–, –C(O)-U–NH-alkylene–, – (alkylene–O)_n–alkylene-C(O)-U–NH-alkylene–C(O)–, –(alkylene–O)_n–alkylene–C(O)-U-NH– alkylene–, –C(O)-alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, –alkylene-C(O)-U-NH- (alkylene-O)n-alkylene–, –alkylene-NH-U-C(O)-alkylene–, and –(CH2)1-6– substituted with one to three groups independently selected from the group consisting of -OH, -NH₂, C₁-C₃ alkyl, C₁- C₃ alkoxy and C₃-C₆ cycloalkyl; wherein: each U is independently an amino acid; each J is independently:

^; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. 27. The ADC of any one of claims 1 to 25, wherein the linker L is selected from the group consisting of –alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene–, –alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)- WSGR Ref. No 31362-825.601 alkylene–J-alkylene–, –C(O)-alkylene-C(R_e)(R_f)-S-S-C(R_g)(R_h)-alkylene–, –C(O)-alkylene- C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene-J-alkylene–, –(alkylene–O)n-alkylene-J-alkylene-C(Re)(Rf)-S- S-alkylene-J-(alkylene-O)_n-alkylene–; wherein: each J is independently:

; each Re, Rf, Rg and Rh is independently selected from the group consisting of H and C₁-C₆ alkyl; each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁–, and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. 28. The ADC of any one of claims 1 to 25, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-G-J-alkylene–, –C(O)-O-alkylene-G-NH-alkylene–, –C(O)-O- alkylene-G-J-alkylene-(O-alkylene)_n–, –C(O)-O-alkylene-G-NH-alkylene-(O-alkylene)_n–, wherein: each G is a glucuronidase substrate; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. 29. The ADC of any one of claims 1 to 25, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –C(O)-O-alkylene-arylene-NH- (peptide)-C(O)-alkylene–, –C(O)-O-alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)_n–, – C(O)-O-alkylene-arylene-NH-(peptide)-(alkylene-O)_n-alkylene–, –C(O)-(alkylene-O)_n-alkylene- NH-(peptide)-C(O)-alkylene–, –alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)n–, – alkylene-arylene-NH-(peptide)-C(O)-alkylene–, –alkylene-C(O)-O-alkylene-arylene-NH- (peptide)-C(O)–, –alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –(alkylene–O)_n- alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J-(alkylene-N(CH3))n-alkylene-C(O)- O-alkylene-arylene-NH-(peptide)-C(O)–, –J–alkylene–N(CH3)–alkylene–N(CH3)–alkylene- C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-J-(alkylene–N(CH₃))_n-alkylene-C(O)- WSGR Ref. No 31362-825.601 O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene–J–alkylene–N(CH₃)–alkylene–N(CH₃)– alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–; wherein: each J is independently:

; each peptide is independently a dipeptide, tripeptide or tetrapeptide; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁– and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. 30. The ADC of any one of claims 1 to 25, wherein the linker L is selected from the group consisting of the linkers listed in Table 10. *–P(=O)(OH)-O-P(=O)(OH)-(O)i–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)_i–alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–alkylene-J–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i- (alkylene-O)n-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-(O-alkylene)n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n-alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i– alkylene–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i–(alkylene-O)n–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene-(O-alkylene)_n-J-alkylene–, *– P(=O)(OH)-O-P(=O)(OH)-(O)_i–alkylene–J-(alkylene-O)_n–alkylene–, *–P(=O)(OH)- O-P(=O)(OH)-(O)i–alkylene–U–alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)_i-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i- alkylene-J-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene- (O-alkylene)n–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i- alkylene–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i- (alkylene-O)_n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, – alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –alkylene-P(=O)(OH)-O- WSGR Ref. No 31362-825.601 P(=O)(OH)-(O)_i-alkylene–(O-alkylene)_n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)- (O)i-alkylene–(O-alkylene)n–, –(alkylene–O)n-P(=O)(OH)-O-P(=O)(OH)-(O)i–, –(alkylene–O)_n-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, –(alkylene–O)_n-P(=O)(OH)-O- P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –(alkylene–O)n–alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)i–, –(alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i–, – (alkylene–O)_n–alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n– alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –(alkylene–O)n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, –(alkylene–O)_n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –(alkylene–O)n–alkylene- O-P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–; wherein: each U is an amino acid; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; each n is independently an integer from 1 to 100; each i is independently 0 or 1; and *, when present, denotes a connection to drug in the ADC. 31. The ADC of any one of claims 26-30, wherein arylene is phenylene. 32. The ADC of any one of claims 1 to 25, wherein the ADC is according to Formula (I-ADC), and the linker L is a non-cleavable linker. 33. The ADC of claim 32, wherein the non-cleavable linker comprises one or more linker moieties selected from the group consisting of unsubstituted alkylene and unsubstituted –(O- alkylene)_n–, wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. 34. The ADC of any one of claims 1 to 25, wherein the ADC is according to Formula (II-ADC), and the linker L is a cleavable linker. 35. The ADC of claim 34, wherein the cleavable linker comprises a pyrophosphate ester or diphosphonate. 36. An antibody-drug conjugate (ADC) of Formula (I-ADC-17): WSGR Ref. No 31362-825.601

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, wherein the antibody comprises an amino acid sequence containing one or more non-naturally encoded amino acids; d is an integer from 1 to 10; and R_c is unsubstituted C₁-C₆ alkyl. 37. The ADC of claim 36, wherein each non-naturally encoded amino acid is para-acetyl-L- phenylalanine (pAF), and R_c is methyl. 38. The ADC of claim 36 or 37, wherein d is 1, 2, 3 or 4. 39. The ADC of any one of claims 36-38, wherein Ab is an anti-HER3 antibody. 40. The ADC of claim 39, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 51. 41. The ADC of claim 39, wherein the anti-HER3 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 58, and the light chain amino acid sequence is SEQ ID NO: 47. 42. The ADC of any one of claims 36-38, wherein Ab is an anti-TROP2 antibody. 43. The ADC of claim 42, wherein the anti-TROP2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 5, and the light chain amino acid sequence is SEQ ID NO: 4. 44. The ADC of any one of claims 36-38, wherein Ab is an anti-CD70 antibody. 45. The ADC of claim 44, wherein the anti-CD70 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 20, and the light chain amino acid sequence is SEQ ID NO: 19. 46. The ADC of any one of claims 36-38, wherein Ab is an anti-HER2 antibody. 47. The ADC of claim 46, wherein the anti-HER2 antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 26, and the light chain amino acid sequence is SEQ ID NO: 27. 48. The ADC of any one of claims 36-38, wherein Ab is an anti-PSMA antibody. WSGR Ref. No 31362-825.601 49. The ADC of claim 48, wherein the anti-PSMA antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence is SEQ ID NO: 36, and the light chain amino acid sequence is SEQ ID NO: 37. 50. A pharmaceutical composition comprising the ADC of any one of claims 1 to 49 and at least one pharmaceutically acceptable adjuvant, binder, buffer, carrier, diluent or excipient. 51. The pharmaceutical composition of claim 50, wherein the pharmaceutical composition comprises a therapeutically effective amount of the ADC. 52. The pharmaceutical composition of claim 50 or 51, further comprising a chemotherapeutic agent, hormonal agent, antitumor agent, immunostimulatory agent, immunomodulator or corticosteroid; or any combination thereof. 53. A of Formula (I) or Formula (II):

or a pharmaceutically acceptable salt thereof, wherein: V is selected from the group consisting of -CH2-, -S-, -S(O)-, -C(O)- and -C(H)(Rv)-; wherein R_v is -F, -CN, -N₃, -OH, -ONH₂, unsubstituted C₁-C₈ alkyl, or substituted C₁-C₈ alkyl; X is O or NH; Y is a reactive moiety; Z is -CH₂- or -C(O)-; R5 is H, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C3-C6 cycloalkyl, or substituted C3-C6 cycloalkyl; R₆ is unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted cycloalkyl, substituted cycloalkyl, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; each R_7, R₈ and R₉ is independently H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, unsubstituted C₃-C₆ cycloalkyl, substituted C₃-C₆ cycloalkyl; or R₇ and R₈ are joined to form an unsubstituted heterocycloalkyl or a substituted heterocycloalkyl, and R9 is H, unsubstituted C₁-C₈ alkyl or substituted C₁-C₈ alkyl; or R₈ and R₉ are joined to form an unsubstituted cycloalkyl, substituted cycloalkyl, an unsubstituted WSGR Ref. No 31362-825.601 heterocycloalkyl or substituted heterocycloalkyl, and R₇ is H, unsubstituted C₁-C₈ alkyl, substituted C1-C8 alkyl, unsubstituted C3-C6 cycloalkyl or substituted C3-C6 cycloalkyl; R_7a is H, unsubstituted C₁-C₈ alkyl, substituted C₁-C₈ alkyl, substituted C₃-C₆ cycloalkyl, or substituted C3-C6 cycloalkyl; and L is a linker. 54. The compound of claim 53, wherein the reactive moiety Y comprises -N₃, -OH, -SH, - NHRb, -C(O)Rc, -C(O)ORd, -C(O)CH2NH2, an activated ester, –O–NH2, a maleimide, a tetrazine, an alkyne, a cyclooctyne or an (E)-cyclooctene; wherein: R_b is H or unsubstituted C₁-C₆ alkyl, Rc is unsubstituted C1-C6 alkyl, and Rd is H, unsubstituted C1-C6 alkyl or a carboxylic acid protecting group. 55. The compound of claim 54, wherein Y is -O-NH₂. 56. The compound of claim 53-55, wherein V is -CH2-. 57. The compound of any one of claims 53 to 56, wherein R6 is unsubstituted heteroaryl or substituted heteroaryl. 58. The compound of claim 57, wherein the unsubstituted heteroaryl is unsubstituted 2-thienyl. 59. The compound of claim 57, wherein the unsubstituted heteroaryl is unsubstituted 3-thienyl. 60. The compound of any one of claims 53 to 59, wherein the linker L is selected from the group consisting of a bond, –alkylene–, –(alkylene–O)_n–alkylene–, –alkylene–C(O)–, – (alkylene–O)n–alkylene–C(O)–, –alkylene-(alkylene–O)n-C(O)–, –alkylene-arylene-alkylene–, – alkylene–NH–, –(alkylene–O)n-alkylene-NH–, –C(O)-alkylene-NH–, –C(O)-(alkylene–O)n– alkylene–NH–, –(alkylene–O)_n–alkylene–J–, –J-alkylene–, –alkylene-J-alkylene–, –(alkylene- O)n-J-alkylene–, –alkylene-J-(alkylene-O)n-alkylene-C(O)–, –alkylene–J–(alkylene–O)n– alkylene–, –(alkylene–O)n–alkylene–J–alkylene, –J–(alkylene–O)n–alkylene–, –J–(alkylene– O)_n–(alkylene–O)_n–alkylene–, –(alkylene–O)_n–alkylene–J–(alkylene–O)_n–alkylene–J–, –C(O)- U–NH-alkylene–, –(alkylene–O)_n–alkylene-C(O)-U–NH-alkylene–C(O)–, –(alkylene–O)_n– alkylene–C(O)-U-NH–alkylene–, –C(O)-alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, – alkylene-C(O)-U-NH-(alkylene-O)n-alkylene–, –alkylene-NH-U-C(O)-alkylene–, and –(CH2)1- ₆– substituted with one to three groups independently selected from the group consisting of -OH, -NH2, C1-C3 alkyl, C1-C3 alkoxy and C3-C6 cycloalkyl; wherein: each U is independently an amino acid; each J is independently: ; WSGR Ref. No 31362-825.601 each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁–, and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. 61. The compound of any one of claims 53 to 59, wherein the linker L is selected from the group consisting of –alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene–, –alkylene-C(Re)(Rf)-S-S-C(Rg)(Rh)- alkylene–J-alkylene–, –C(O)-alkylene-C(R_e)(R_f)-S-S-C(R_g)(R_h)-alkylene–, –C(O)-alkylene- C(Re)(Rf)-S-S-C(Rg)(Rh)-alkylene-J-alkylene–, –(alkylene–O)n-alkylene-J-alkylene-C(Re)(Rf)-S- S-alkylene-J-(alkylene-O)n-alkylene–; wherein: each J is independently:

; each Re, Rf, Rg and Rh is independently selected from the group consisting of H and C₁-C₆ alkyl; each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. 62. The compound of any one of claims 53 to 59, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-G-J-alkylene–, –C(O)-O-alkylene-G-NH-alkylene–, –C(O)-O- alkylene-G-J-alkylene-(O-alkylene)_n–, –C(O)-O-alkylene-G-NH-alkylene-(O-alkylene)_n–, wherein: each G is a glucuronidase substrate; each J is independently:

^; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH2)8–, –(CH2)9–, –(CH2)10–, –(CH2)11–, and –(CH2)12–; and each n is independently an integer from 1 to 100. 63. The compound of any one of claims 53 to 59, wherein the linker L is selected from the group consisting of –C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –C(O)-O-alkylene-arylene-NH- (peptide)-C(O)-alkylene–, –C(O)-O-alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)n–, – C(O)-O-alkylene-arylene-NH-(peptide)-(alkylene-O)_n-alkylene–, –C(O)-(alkylene-O)_n-alkylene- WSGR Ref. No 31362-825.601 NH-(peptide)-C(O)-alkylene–, –alkylene-arylene-NH-(peptide)-alkylene-(O-alkylene)_n–, – alkylene-arylene-NH-(peptide)-C(O)-alkylene–, –alkylene-C(O)-O-alkylene-arylene-NH- (peptide)-C(O)–, –alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –(alkylene–O)_n- alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –J-(alkylene-N(CH₃))_n-alkylene-C(O)- O-alkylene-arylene-NH-(peptide)-C(O)–, –J–alkylene–N(CH3)–alkylene–N(CH3)–alkylene- C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene-J-(alkylene–N(CH3))n-alkylene-C(O)- O-alkylene-arylene-NH-(peptide)-C(O)–, –alkylene–J–alkylene–N(CH₃)–alkylene–N(CH₃)– alkylene-C(O)-O-alkylene-arylene-NH-(peptide)-C(O)–; wherein: each J is independently:

^; each peptide is independently a dipeptide, tripeptide or tetrapeptide; each alkylene is independently selected from the group consisting of: -(CH₂)-, -(CH₂)₂-, -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅-, -(CH₂)₆-, -(CH₂)₇-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁– and –(CH₂)₁₂–; and each n is independently an integer from 1 to 100. 64. The compound of any one of claims 53 to 59, wherein the linker L is selected from the group consisting of the linkers listed in Table 10. *–P(=O)(OH)-O-P(=O)(OH)-(O)i–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)_i–alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i–alkylene-J–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i- (alkylene-O)n-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-(O-alkylene)n–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n-alkylene-C(O)–, *–P(=O)(OH)-O- P(=O)(OH)-(O)_i-(alkylene-O)_n-alkylene-N(H)–, *–P(=O)(OH)-O-P(=O)(OH)-(O)_i– alkylene–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i–(alkylene-O)n–J-alkylene–, *–P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene-(O-alkylene)n-J-alkylene–, *– P(=O)(OH)-O-P(=O)(OH)-(O)_i–alkylene–J-(alkylene-O)_n–alkylene–, *–P(=O)(OH)- O-P(=O)(OH)-(O)i–alkylene–U–alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i- alkylene-J-alkylene–, –C(O)-O-alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene- (O-alkylene)_n–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i- alkylene–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –alkylene- WSGR Ref. No 31362-825.601 P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–J-alkylene–, –alkylene-O-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–J-alkylene–, –alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i- (alkylene-O)_n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–, – alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–alkylene–, –alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)i-alkylene–(O-alkylene)n–, –alkylene-O-P(=O)(OH)-O-P(=O)(OH)- (O)_i-alkylene–(O-alkylene)_n–, –(alkylene–O)_n-P(=O)(OH)-O-P(=O)(OH)-(O)_i–, –(alkylene–O)n-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –(alkylene–O)n- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n-P(=O)(OH)-O- P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –(alkylene–O)_n–alkylene-P(=O)(OH)-O- P(=O)(OH)-(O)i–, –(alkylene–O)n–alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)i–, – (alkylene–O)n–alkylene-P(=O)(OH)-O-P(=O)(OH)-(O)i-alkylene–, –(alkylene–O)n– alkylene-O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-alkylene–, –(alkylene–O)_n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene-O- P(=O)(OH)-O-P(=O)(OH)-(O)i-(alkylene-O)n–, –(alkylene–O)n–alkylene- P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–, –(alkylene–O)_n–alkylene- O-P(=O)(OH)-O-P(=O)(OH)-(O)_i-(alkylene-O)_n–alkylene–; wherein: each U is an amino acid; each J is independently:

; each alkylene is independently selected from the group consisting of: -(CH2)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH₂)₈–, –(CH₂)₉–, –(CH₂)₁₀–, –(CH₂)₁₁–, and –(CH₂)₁₂–; each n is independently an integer from 1 to 100; each i is independently 0 or 1; and *, when present, denotes a connection to drug in the ADC. 65. The ADC of any one of claims 60-64, wherein arylene is phenylene. 66. The compound of any one of claims 53 to 59, wherein the compound is a compound of Formula (I), and the linker is a non-cleavable linker. 67. The compound of claim 66, wherein the non-cleavable linker comprises one or more linker moieties selected from the group consisting of unsubstituted alkylene and unsubstituted –(O- alkylene)n–, wherein each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. WSGR Ref. No 31362-825.601 68. The compound of any one of claims 53 to 59, wherein the compound is a compound of Formula (II), and the linker is a cleavable linker. 69. The compound of claim 67, wherein the cleavable linker comprises a pyrophosphate ester or diphosphonate. 70. The compound of any one of claims 53 to 69, wherein Z is -C(O); R7, R8 and R9 are each independently H or unsubstituted C1-C8 alkyl; X, when present, is O; R5, when present, is H; and R_7a, when present, is H or unsubstituted C₁-C₈ alkyl. 71. The compound of any one of claims 53 to 69, wherein Z is -CH2-; R7, R8 and R9 are each independently H or unsubstituted C1-C8 alkyl; X, when present, is O; R5, when present, is H; and R_7a, when present, is H or unsubstituted C₁-C₈ alkyl. 72. The of claim 53, wherein the is selected from the of: ,

WSGR Ref. No 31362-825.601

and pharmaceutically acceptable salts thereof. 73. A pharmaceutical composition comprising a compound of any one of claims 53 to 72 and at least one pharmaceutically acceptable adjuvant, binder, buffer, carrier, diluent or excipient. 74. The pharmaceutical composition of claim 73, wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound. 75. A method of treating a disease in a subject in need thereof, the method comprising administering to the subject an ADC of any one of claims 1 to 49, a compound of any one of claims 53 to 72, or a pharmaceutical composition of any one of claims 50 to 52, 73 and 74. 76. The method of claim 75, wherein the disease is cancer.