[go: up one dir, main page]

WO2025137523A2 - Pharmaceutical formulations of antibodies that bind interleukin 13 - Google Patents

Pharmaceutical formulations of antibodies that bind interleukin 13 Download PDF

Info

Publication number
WO2025137523A2
WO2025137523A2 PCT/US2024/061395 US2024061395W WO2025137523A2 WO 2025137523 A2 WO2025137523 A2 WO 2025137523A2 US 2024061395 W US2024061395 W US 2024061395W WO 2025137523 A2 WO2025137523 A2 WO 2025137523A2
Authority
WO
WIPO (PCT)
Prior art keywords
seq
cdr
set forth
formulation
antibody
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/061395
Other languages
French (fr)
Other versions
WO2025137523A3 (en
Inventor
Holly Prentice
Gayathri Ratnaswamy
Rebecca Lucille DABORA
Aaron Noyes
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Apogee Therapeutics Inc
Original Assignee
Apogee Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Apogee Therapeutics Inc filed Critical Apogee Therapeutics Inc
Publication of WO2025137523A2 publication Critical patent/WO2025137523A2/en
Publication of WO2025137523A3 publication Critical patent/WO2025137523A3/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Definitions

  • CDR-H1 comprises the sequence set forth in SEQ ID NO: 58 or 67; b. CDR-H2 comprises the sequence set forth in SEQ ID NO: 100 or 104; c. CDR-H3 comprises the sequence set forth in SEQ ID NO: 112; d. CDR-L1 comprises the sequence set forth in SEQ ID NO: 141 or 149; e. CDR-L2 comprises the sequence set forth in SEQ ID NO: 153 or 596; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165.
  • the formulation further comprises a metal ion chelator.
  • the metal ion chelator is EDTA or salt thereof.
  • the antibody is at a concentration of about 160-200 mg/mL.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 5 mM and 20 mM. In certain embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 10 mM.
  • the histidine buffer comprises a histidine and a histidine salt. In certain embodiments, the histidine is L-histidine. In certain embodiments, the histidine salt is L-histidine HCl monohydrate.
  • the formulation comprises methionine, and wherein the methionine is L-methionine. In certain embodiments, the L-methionine is at a concentration between 1 mM and 20 mM. In certain embodiments, the L-methionine is at a concentration of about 10 mM. [0015] In certain embodiments, the formulation comprises arginine, and wherein the arginine is L-arginine. In certain embodiments, the formulation comprises an L-arginine salt solution. In certain embodiments, the L-arginine salt solution salt solution comprises HCl monohydrate. In certain embodiments, wherein the L-arginine salt solution is at a concentration between 40 mM and 250 mM.
  • the L-arginine salt solution is at a concentration of about 80 mM. In certain embodiments, the L-arginine salt solution is at a concentration of about 120 mM. [0016] In certain embodiments, the formulation further comprises a surfactant. [0017] In certain embodiments, the formulation comprises a polysorbate. In certain embodiments the polysorbate is at a concentration between 0.005% w/v and 0.15% w/v, e.g., 0.01% w/v-0.10% w/v. In certain embodiments, the polysorbate is at a concentration of about 0.05% w/v. In certain embodiments, the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80.
  • the pH is between 5.5 and 6.5, such as at about 6.0. In certain embodiments, the pH is 5.8. In certain embodiments, the pH is 6.0.
  • a formulation comprising: (a) an IL-13 antibody at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • a formulation comprising: (a) an IL-13 antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L- histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 80 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • a formulation comprising: (a) an IL-13 antibody present at a concentration of about 200 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L- histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • a formulation comprising: (a) an IL-13 antibody at a concentration of about 180-200 mg/mL (e.g., at 180 mg/mL or 200 mg/mL); (b) a histidine buffer at a concentration of about 10 mM (e.g., at 10 mM), wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); (e) polysorbate 80 at a concentration of about 0.05% w/v Attorney Docket No.: AOJ-017PC AOE-003WO (e.g., at 0.05% polysorbate 80), (f) EDTA or a salt thereof (e.g., EDTA-2Na
  • a formulation comprising: (a) an IL-13 antibody at a concentration of about 180-200 mg/mL (e.g., at 180 mg/mL or 200 mg/mL); (b) a histidine buffer at a concentration of about 10 mM (e.g., at 10 mM), wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); and (e) poloxamer 188 at a concentration of about 0.5 mg/ml (e.g., at 0.5 mg/ml), at pH of about 5.8-6.0 (e.g., at a pH of 5.8 or a pH of 6.0).
  • an IL-13 antibody at a concentration of about 180-200 mg/mL (e.
  • the formulation further comprises: (f) a sugar or sugar alcohol.
  • the sugar or sugar alcohol is at a concentration between 1% w/v and 8% w/v. In certain embodiments, the sugar or sugar alcohol is at a concentration of about 3% w/v.
  • the sugar or sugar alcohol is a disaccharide. In certain embodiments, the disaccharide is sucrose.
  • the IL-13 antibody comprises: (a) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR- H3; and (b) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (i) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (ii) CDR- H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; (iii) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (iv) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, (v) CDR
  • the (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85;
  • CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108;
  • CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130,
  • CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ Attorney Docket No.: AOJ-017PC AOE-003WO ID NO: 141 and SEQ ID NO: 149,
  • CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164;
  • CDR-L3 comprises the sequence set forth in SEQ ID NO:
  • the IL-13 antibody comprises: (a) CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-66; (b) CDR- H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-103; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172.
  • the IL-13 antibody comprises: (a) CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 67-83; (b) CDR- H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 104-107; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172.
  • CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, e.
  • CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and f.
  • CDR-L3 comprises the sequence set forth in SEQ ID NO: 165.
  • the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises the sequence set forth in SEQ ID NO: 58 or 67; b. CDR-H2 comprises the sequence set forth in SEQ ID NO: 100 or 104; c.
  • the IL-13 antibody comprises a means for extending the half-life of the IL-13 antibody.
  • the means comprises at least one amino acid modification in the IL-13 antibody, as described further herein.
  • the formulation further comprises a sugar or sugar alcohol.
  • FIG.2 is a graph depicting the average gliding force in Newtons (N) (y-axis) at room temperature of a formulation with varied concentrations of an IL-13 antibody (x-axis) and including 150 mM Arg-HCl, 80 mM Arg-HCl and 3% w/v sucrose, or 120 mM Arg-HCl injected through a pre-filled syringe (PFS).
  • N Newtons
  • x-axis concentrations of an IL-13 antibody
  • PFS pre-filled syringe
  • FIG.7A-7B show bar graphs of CE-SDS-NR (FIG.7A) and CE-SDS-R (FIG.7B) results in samples tested with different combinations of syringes (C and D) and plungers (A and B).
  • FIG.8 shows a bar graph of ELISA results for container closure compatibility for samples tested with different combinations of syringes (C and D) and plungers (A and B).
  • compositions described herein can either comprise the listed components or steps, or can “consist essentially of” the listed components or steps.
  • composition when a composition is described as “consisting essentially of” the listed components, the composition contains the components listed, and may contain other components which do not substantially affect the condition being treated, but do not contain any other components which substantially affect the condition being treated other than those components expressly listed; or, if the composition does contain extra components other than those listed which substantially affect the condition being treated, the composition does not contain a sufficient concentration or amount of the extra components to substantially affect the condition being treated.
  • a method is described as “consisting essentially of” the listed steps, the method contains the steps listed, and may contain other steps that do not substantially affect the condition being treated, but the method does not contain any other steps which substantially affect the condition being treated other than those steps expressly listed.
  • an “effective amount” or “therapeutically effective amount” as used herein refers to an amount of therapeutic compound, such as an IL-13 antibody, administered to an individual, either as a single dose or as part of a series of doses, which is effective to produce or contribute to a desired therapeutic effect, either alone or in combination with another therapeutic modality. Examples of a desired therapeutic effect is enhancing an immune response, slowing or delaying tumor development; stabilization of disease; amelioration of one or more symptoms.
  • treating refers to clinical intervention in an attempt to alter the natural course of a disease or condition in a subject in need thereof. Treatment can be performed during the course of clinical pathology. Desirable effects of treatment include preventing recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, Attorney Docket No.: AOJ-017PC AOE-003WO preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.
  • the term “sufficient amount” means an amount sufficient to produce a desired effect, e.g., an amount sufficient to modulate an immune response in a subject.
  • the terms “subject”, “patient”, and “individual” are used interchangeably herein.
  • the term “subject”, “patient”, or “individual” means a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, and sheep. In certain embodiments, the subject is a human. In certain embodiments the subject has a disease or condition that can be treated with an antibody provided herein.
  • composition refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective in treating a subject, and which contains no additional components which are unacceptably toxic to the subject in the amounts provided in the pharmaceutical composition.
  • modulate and “modulation” refer to reducing or inhibiting or, alternatively, activating or increasing, a recited variable.
  • the terms “increase” and “activate” refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable.
  • the terms “reduce” and “inhibit” refer to a decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable.
  • Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), Attorney Docket No.: AOJ-017PC AOE-003WO glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).
  • an amino acid described herein may refer to its L-isomer form.
  • methionine may refer to L-methionine
  • proline may refer to L-proline
  • arginine may refer to L-arginine.
  • affinity refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or epitope).
  • affinity refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen or epitope).
  • KD Kd/ka. In certain embodiments, the affinity of an antibody is described in terms of the KD for an interaction between such antibody and its antigen.
  • KA ka/kd.
  • antibody is used herein in its broadest sense and includes certain types of immunoglobulin molecules comprising one or more antigen-binding domains that specifically bind to an antigen or epitope. An antibody specifically includes intact antibodies (e.g., intact immunoglobulins), antibody fragments, and multi-specific antibodies.
  • a “anti-IL-13 antibody,” “IL-13 antibody,” or “IL-13 specific antibody” is an antibody, as provided herein, which specifically binds to the antigen IL-13.
  • the term “epitope” means a portion of an antigen that specifically binds to an antibody.
  • the term “hypervariable region” or “HVR,” as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and/or form structurally defined loops (“hypervariable loops”). Attorney Docket No.: AOJ-017PC AOE-003WO [00106]
  • the term “antigen-binding domain” means the portion of an antibody that is capable of specifically binding to an antigen or epitope.
  • chimeric antibody refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species.
  • human antibody refers to an antibody which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.
  • humanized antibody refers to a protein having a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject.
  • multispecific antibody refers to an antibody that comprises two or more different antigen-binding domains that collectively specifically bind two or more different epitopes.
  • a “monospecific antibody” is an antibody that comprises one or more binding sites that specifically bind to a single epitope.
  • a monospecific antibody is a naturally occurring IgG molecule which, while divalent (i.e., having two antigen-binding domains), recognizes the same epitope at each of the two antigen-binding domains.
  • the binding specificity may be present in any suitable valency.
  • the term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies.
  • a population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts.
  • a monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies.
  • the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones.
  • the selected antibody can be further altered, for Attorney Docket No.: AOJ-017PC AOE-003WO example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject.
  • affinity maturation affinity for the target
  • the term “single-chain” refers to a molecule comprising amino acid monomers linearly linked by peptide bonds.
  • an scFv has a variable domain of light chain (VL) connected from its C-terminus to the N-terminal end of a variable domain of heavy chain (VH) by a polypeptide chain.
  • VL variable domain of light chain
  • VH variable domain of heavy chain
  • the scFv comprises of polypeptide chain where in the C-terminal end of the VH is connected to the N-terminal end of VL by a polypeptide chain.
  • the “Fab fragment” (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CH1) of the heavy chain along with the variable domains VL and VH on the light and heavy chains respectively.
  • the variable domains comprise the complementarity determining loops (CDR, also referred to as hypervariable region) that are involved in antigen-binding.
  • CDR complementarity determining loops
  • Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region.
  • “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds.
  • F(ab’)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody.
  • the F(ab’) fragments can be dissociated, for example, by treatment with ß-mercaptoethanol.
  • “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.
  • Single-chain Fv or “sFv” or “scFv” includes the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain.
  • the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding.
  • a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding.
  • an Fc domain may be attached to the C-terminal of the scFv.
  • the Fc domain may follow the VH Attorney Docket No.: AOJ-017PC AOE-003WO or VL, depending on the orientation of the variable domains in the scFv (i.e., VH -VL or VL - VH). Any suitable Fc domain known in the art or described herein may be used.
  • the Fc domain comprises an IgG4 Fc domain.
  • the term “single domain antibody” or “sdAb” refers to a molecule in which one variable domain of an antibody specifically binds to an antigen without the presence of the other variable domain.
  • Single domain antibodies are described in Arabi Ghahroudi et al., FEBS Letters, 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sci., 2001, 26:230-245, each of which is incorporated by reference in its entirety.
  • Single domain antibodies are also known as sdAbs or nanobodies. Sdabs are fairly stable and easy to express as fusion partner with the Fc chain of an antibody (Harmsen MM, De Haard HJ (2007). “Properties, production, and applications of camelid single-domain antibody fragments”. Appl. Microbiol Biotechnol.77(1): 13-22).
  • full length antibody “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a naturally occurring antibody structure and having heavy chains that comprise an Fc region.
  • a “full length antibody” is an antibody that comprises two heavy chains and two light chains.
  • antibody fragment refers to an antibody that comprises a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody.
  • Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, and scFv-Fc fragments.
  • Fc domain or “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions.
  • percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill) or by visual inspection.
  • sequence comparison algorithms e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill
  • sequence comparison typically one sequence acts as a reference sequence to which test sequences are compared.
  • test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence comparison algorithm calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.
  • Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci.
  • a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50.
  • stable formulation refers to a formulation in which the protein of interest (here an antibody or an antigen binding fragment thereof) essentially retains its physical, chemical and/or biological properties upon storage.
  • the protein of interest here an antibody or an antigen binding fragment thereof
  • various analytical methods are well within the knowledge of the skilled person (see some examples in the Example section). Stability is typically assessed at a selected temperature (for instance ⁇ 70 °C, -40° C, -20° C, 2-8 °C, 25 °C, 35 °C, or more) for a selected time period (e.g., 3 months, 6 months, 12 months, or more).
  • an antibody once formulated, it may be stored frozen (-20 °C to -70 °C) , under refrigerated conditions (typically 2-8° C), or at room temperature (typically 20-26° C) before being prepared for administration to a patient. It is important that the formulated antibody is stable over time at least at 2-25° C or under frozen conditions (-20 to -70° C), as shown for example at 2-8° C, 25° C, -20° C, -40° C, and -70° C.
  • Various values can be used to conclude about stability over a given time period (in comparison of the initial data), such as (and not limited to): 1) no more than 10% of alteration of the monomeric form of the antibody, 2) no more than 10% of increase in High Molecular Weight Species (HMW; also herein referred to as aggregates), 3) no more than 10% of increase in Low Molecular Weight species (LMW), 4) no more than +1-0.3 unit variation of the pH, 5) changes in charge variation, 6) changes in potency, or 7) changes in particulates, the relevant changed ranges of which one of skill in the art could determine.
  • HMW High Molecular Weight Species
  • LMW Low Molecular Weight species
  • amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol.262:732- 745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol.
  • Table 1 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR- H2, and CDR-H3 as identified by the Kabat and Chothia schemes.
  • residue numbering is provided using both the Kabat and Chothia numbering schemes.
  • CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available at www.bioinf.org.uk/abs/abnum/, and described in Abhinandan and Martin, Immunology, 2008, 45:3832-3839, incorporated by reference in its entirety. Table 1.
  • an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer of an antibody.
  • Another example of an antigen-binding domain is an antigen-binding domain formed by diversification of certain loops from the tenth fibronectin type III domain of an Adnectin.
  • An antigen-binding domain can include CDRs 1, 2, and 3 from a heavy chain in that order; and CDRs 1, 2, and 3 from a light chain in that order.
  • Epitopes frequently consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics.
  • Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter may be lost in the presence of denaturing solvents.
  • An epitope may comprise amino acid residues that are directly involved in the binding and other amino acid residues, which are not directly involved in the binding.
  • the epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to IL-13 variants with different point-mutations or to chimeric IL-13 variants.
  • a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed.
  • epitope mapping can be performed by methods known in the art.
  • AOJ-017PC AOE-003WO [00151] Chimeric antibodies are antibodies in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species.
  • Human antibodies are antibodies which possess an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.
  • a humanized antibody has a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non- human species antibody, when it is administered to a human subject.
  • certain amino acids in the framework and constant domains of the heavy and/or light chains of the non-human species antibody are mutated to produce the humanized antibody.
  • the constant domain(s) from a human antibody are fused to the variable domain(s) of a non-human species.
  • one or more amino acid residues in one or more CDR sequences of a non-human antibody are changed to reduce the likely immunogenicity of the non-human antibody when it is administered to a human subject, wherein the changed amino acid residues either are not critical for immunospecific binding of the antibody to its antigen, or the changes to the amino acid sequence that are made are conservative changes, such that the binding of the humanized antibody to the antigen is not significantly worse than the binding of the non-human antibody to the antigen. Examples of how to make humanized antibodies can be found in U.S. Pat. Nos.6,054,297, 5,886,152 and 5,877,293.
  • the two or more different epitopes may be epitopes on the same antigen (e.g., a single IL-13) or on different antigens (e.g., different IL-13 molecules, or a IL-13 molecule and a non- IL-13 molecule).
  • a multi-specific antibody binds two different epitopes (i.e., a “bispecific antibody”).
  • a multi-specific antibody binds three different epitopes (i.e., a “trispecific antibody”).
  • a trispecific antibody can include those described herein such as the clones set forth in the drawings and/or tables.
  • the antibody comprises an alternative scaffold.
  • the antibody consists of an alternative scaffold.
  • the antibody consists essentially of an alternative scaffold.
  • the antibody comprises an antibody fragment.
  • the antibody consists of an antibody fragment.
  • the antibody consists essentially of an antibody fragment.
  • the antibodies are monoclonal antibodies.
  • the antibodies are polyclonal antibodies.
  • the antibodies are produced by hybridomas.
  • the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains.
  • the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof.
  • the antibodies may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof.
  • the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab′2 fragment, a CDR, and ScFv.
  • the antibodies are capable of forming an immune complex.
  • an immune complex can be a tumor cell covered by antibodies.
  • Sequences of IL-13 Antibodies VH Domains [00162]
  • the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0.
  • a histidine buffer e.g., combination L-hist
  • the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence Attorney Docket No.: AOJ-017PC AOE-003WO comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-
  • the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration, e.g., between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0.
  • a histidine buffer e.g., combination L-histidine and L-histidine HCl buffer
  • an acetate buffer e.g., combination acetic acid and sodium acetate trihydrate
  • succinate buffer
  • the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID
  • an antibody provided herein comprises a VH sequence selected from SEQ ID NOs: 1-32.
  • an antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VH sequence provided in SEQ ID NOs: 1-32.
  • an antibody provided herein comprises a VH sequence provided in SEQ ID NOs: 1-32, with up Attorney Docket No.: AOJ-017PC AOE-003WO to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • VL Domains [00166]
  • an antibody provided herein comprises a VL sequence selected from SEQ ID NOs: 33-57.
  • an antibody provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VL sequence provided in SEQ ID NOs: 33-57.
  • an antibody provided herein comprises a VL sequence provided in SEQ ID NOs: 33-57 with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a VH sequence selected from SEQ ID NOs: 1-32; and a VL sequence selected from SEQ ID NOs: 33-57, such as any of the VH-VL combinations set forth for Constructs 3-127 and 132-144 in Table 2, below. [00169] In certain aspects, any of SEQ ID NOs: 1-32 can be combined with any of SEQ ID NOs: 33-57. [00170] In certain embodiments, the antibody comprises a VH sequence selected from the sequences set forth in SEQ ID NOs: 1-32 and a VL sequence set forth in SEQ ID NO: 39.
  • the antibody comprises the VH sequence set forth in SEQ ID NO: 3 and the VL sequence set forth in SEQ ID NO: 39. [00172] In certain embodiments, the antibody comprises a VH sequence selected from the sequences set forth in SEQ ID NOs: 1-32 and a VL sequence set forth in SEQ ID NO: 51.
  • an antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VH sequence provided in SEQ ID NOs: 1-32; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VL sequence provided in SEQ ID NOs: 33-57.
  • an antibody provided herein comprises a VH sequence provided in SEQ ID NOs: 1-32, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions; and a VL sequence provided in SEQ ID NOs: 33-57, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody provided herein comprises a VH sequence and a VL sequence selected from combinations set forth for Constructs 3-127 and 132-144 in Table 2, below.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 33. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 2 and a VL sequence set forth in SEQ ID NO: 33. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 35.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the Attorney Docket No.: AOJ-017PC AOE-003WO antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 36.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 39.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 40.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 8 and a VL sequence set forth in SEQ ID NO: 42. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 9 and a VL sequence set forth in SEQ ID NO: 43.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 44. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 45. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 47.
  • the Attorney Docket No.: AOJ-017PC AOE-003WO antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 48. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 49. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 50. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 51.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 52. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 53. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 54. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 55. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 56.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 57. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 10 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 11 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 12 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 13 and a VL sequence set forth in SEQ ID NO: 39.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 14 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 15 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 16 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 17 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 18 and a VL sequence set forth in SEQ ID NO: 39.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 19 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 20 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 21 and a VL sequence set forth in SEQ ID NO: 39. In Attorney Docket No.: AOJ-017PC AOE-003WO certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 22 and a VL sequence set forth in SEQ ID NO: 39.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 23 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 24 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 25 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 26 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 27 and a VL sequence set forth in SEQ ID NO: 39.
  • the antibody comprises a VH sequence set forth in SEQ ID NO: 28 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 28 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 29 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 30 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 31 and a VL sequence set forth in SEQ ID NO: 39.
  • the IL-13 antibody comprises a heavy chain variable domain comprising a framework region sequence selected from a sequence set forth in SEQ ID NOs: 198-229, 255-256, 258-259, 261-285, 311-315, 317-342, 368-369, 371-399, and 540-580.
  • the IL-13 antibody comprises a heavy chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 198-229, 255-256, 258-259, 261-285, 311-315, 317-342, 368-369, 371-399, and 540-580.
  • the IL-13 antibody comprises a light chain variable domain comprising a framework region sequence selected from a sequence set forth in SEQ ID NOs: 230-231, 233-235, 239, 241-254, 286, 288, 290-291, 293, 296-310, 343-345, 347, Attorney Docket No.: AOJ-017PC AOE-003WO 400-424, and 581-609.
  • the IL-13 antibody comprises a light chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 230-231, 233-235, 239, 241-254, 286, 288, 290-291, 293, 296-310, 343-345, 347, 400-424, and 581-609.
  • the IL-13 antibody comprises a heavy chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 198-229, 255-256, 258-259, 261-285, 311-315, 317-342, 368-369, 371-399, and 540-580, and comprises a light chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 230-231, 233-235, 239, 241-254, 286, 288, 290-291, 293, 296-310, 343-345, 347, 400-424, and 581- 609. Table 2.
  • Anti-interleukin (IL)-13 antibody VH-VL sequences Construc VH; VL; HC VH sequence VL sequence t ID t t R F Y S T R F Y S Attorney Docket No.: AOJ-017PC AOE-003WO Human kappa CAGDGYYPYAMDNW YYCQQNNEDPRTFGGGT LC GQGSLVTVSS (SEQ ID KVEIK (SEQ ID NO: 471) R F Y S S T R F Y S S T F Y Y K F Y Attorney Docket No.: AOJ-017PC AOE-003WO YTE; Human WLGMIWGDGKIVYNS LASNLESGVPSRFSGSGS kappa LC ALKSRLTITKDSSTSTV RTDFTLTISSLQPEDFATY K F Y Y K F Y Y K F Y Y K Attorney Docket No.: AOJ-017PC AOE-003WO HC
  • an IL-13 antibody comprises a VH domain selected from any one the VH domains of Constructs 3-127 and 132-144 in Table 2 or a VH domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and a HC domain comprising a sequence selected from any one of SEQ ID NOs: 425-468, 484-539, and 610-709 or an HC domain having at least about 80%, 90%, 91%, 92%, 93%, Attorney Docket No.: AOJ-017PC AOE-003WO 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • a VH domain listed for any one of Constructs 3-127 and 132-144 in Table 2 can be combined with a heavy chain constant (HC) domain provided herein.
  • an IL-13 antibody comprises a VH domain selected from any one the VH domains of Constructs 3-127 and 132- 144 in Table 2 or a VH domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and a HC domain comprising a sequence selected from any one of SEQ ID NOs: 610, 615-641, and 654-709 or an HC domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.
  • the HC domain is an IgG1 HC domain.
  • the HC domain includes IgG4-SP, hIgG1-LALA-YTE, hIgG1-LAGA YTE, hIgG1-LALA-LS, IgG4-YTE HC, and IgG4-LS.
  • such an IgG4-SP HC constant domain has the sequence: ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 427).
  • such a hIgG1-LALA-YTE HC constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP EAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSPG (SEQ ID NO: 439).
  • such a hIgG1-LAGA YTE HC constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELAGAPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT Attorney Docket No.: AOJ-017PC AOE-003WO KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSPG (SEQ ID NO: 440).
  • such a hIgG1-LALA-LS HC constant domain has the sequence: [00184] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSPG (SEQ ID NO: 446).
  • such an IgG4-LS HC constant domain has the sequence: ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVLHEALHSYTQKSLSLSLGK (SEQ ID NO: 460).
  • such a hIgG1-LALA-YTE HC C-terminal lysine variant constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP EAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG Attorney Docket No.: AOJ-017PC AOE-003WO SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS
  • such a hIgG1-LAGA YTE HC C-terminal lysine variant constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELAGAPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSPGK (SEQ ID NO: 625).
  • such a hIgG1-LALA-LS HC C-terminal lysine variant constant domain has the sequence: [00190] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSPGK (SEQ ID NO: 631).
  • a VL domain listed for Constructs 3-127 and 132-144 in Table 2 can be combined with a light chain constant (LC) domain provided herein.
  • the LC domain is a human kappa LC constant domain.
  • such a human kappa LC constant domain has the sequence: RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 469).
  • an antibody provided herein comprises one to three CDRs of a VH domain selected from SEQ ID NOs: 1-32, such as any of the CDRs listed in Table 3, Table 4, or Table 5, below. In some embodiments, an antibody provided herein comprises two to three CDRs of a VH domain selected from SEQ ID NOs: 1-32. In some embodiments, an antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1-32. In some embodiments, the CDRs are Exemplary CDRs. In some embodiments, Attorney Docket No.: AOJ-017PC AOE-003WO the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs. In some embodiments, the CDRs are IMGT CDRs. In some embodiments, the CDRs are AbM CDRs. In some embodiments, the CDRs are Contact CDRs. [00193] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with a CDR-H1, CDR-H2, or CDR-H3 of SEQ ID NOs: 58-140.
  • the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 1-32, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-H2 is a CDR-H2 of a VH domain of SEQ ID NO: 1-32, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 1-32, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • an antibody provided herein comprises one to three CDRs of a VL domain of SEQ ID NOs: 33-57, such as any of the CDRs listed in Table 6, Table 7, or Table 8, below.
  • an antibody provided herein comprises two to three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, the CDRs are Exemplary CDRs. In some embodiments, the CDRs are Kabat CDRs. In some embodiments, the CDRs are Chothia CDRs. In some embodiments, the CDRs are IMGT CDRs. In some embodiments, the CDRs are AbM CDRs. In some embodiments, the CDRs are Contact CDRs.
  • the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with a CDR-L1, CDR-L2, or CDR-L3 of SEQ ID NOs: 141-188.
  • the CDR-L1 is a CDR-L1 of a VL domain of SEQ ID NOs: 33-57, with up to 1, 2, 3, 4, or 5 amino acid substitutions.
  • the CDR-L2 is a CDR-L2 of a VL domain of SEQ ID NOs: 33-57 , with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the CDR-L3 is a CDR- Attorney Docket No.: AOJ-017PC AOE-003WO L3 of a VL domain of SEQ ID NOs: 33-57, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • an antibody provided herein comprises one to three CDRs of a VH domain selected from SEQ ID NOs: 1-32 and one to three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises two to three CDRs of a VH domain selected from SEQ ID NOs: 1-32 and two to three CDRs of a VL domain of SEQ ID NOs: 33-57.
  • an antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1-32 and three CDRs of a VL domain of SEQ ID NOs: 33-57.
  • the CDRs are Exemplary CDRs.
  • the CDRs are Kabat CDRs.
  • the CDRs are Chothia CDRs.
  • the CDRs are IMGT CDRs.
  • the CDRs are AbM CDRs.
  • the CDRs are Contact CDRs.
  • an antibody provided herein comprises a CDR-H3 selected of SEQ ID NOs: 112-120 and 130-40.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112-120 or 130-40.
  • the CDR-H3 is a CDR-H3 selected of SEQ ID NOs: 112-120 and 130-40, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a CDR-H1 of SEQ ID NOs: 58-99 and 121.
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58-99 or 121.
  • the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58-99 or 121, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a CDR-H2 of any one of SEQ ID NOs: 100-111.
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of any one of SEQ ID NOs: 100-111.
  • the CDR-H2 is a CDR-H2 of any one of SEQ ID NOs: 100-111, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a CDR-L3 selected from SEQ ID NOs: 165-172.
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NOs: 165-172.
  • the CDR-L3 is a CDR-L3 of SEQ ID NOs: 165- 172, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method Attorney Docket No.: AOJ-017PC AOE-003WO known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS.
  • the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS.
  • the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152.
  • the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR- L1 selected from SEQ ID NOs: 141-144 and 149-152.
  • the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions.
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this paragraph are referred to herein as “variants.”
  • such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • an antibody provided herein comprises a CDR-H3 selected from SEQ ID NOs: 112-120 and 130-140, a CDR-H2 of SEQ ID NOs: 100-111, a CDR-H1 selected from SEQ ID NOs: 58-99 and 121, a CDR-L3 selected from SEQ ID NOs: 165-172, a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, and a Attorney Docket No.: AOJ-017PC AOE-003WO CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152.
  • the CDR- H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 selected from SEQ ID NOs: 112-120 and 130-140
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100-111
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 selected from SEQ ID NOs: 58-99 and 121
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 selected from SEQ ID NOs
  • the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 112-120 and 130-140, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions;
  • the CDR-H2 is a CDR- H2 of SEQ ID NOs: 100-111, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions;
  • the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 58-99 and 121, with up to 1, 2, 3, 4, or 5 amino acid substitutions;
  • the CDR-L3 is a CDR-L3 selected from SEQ ID NOs: 165-172, with up to 1, 2, 3, 4, or 5 amino acid substitutions;
  • the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions;
  • the CDR-L1 is a CDR-L1 selected from SEQ ID NOs:
  • an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112, 121, and 130, a CDR-H2 of SEQ ID NOs: 100, 104, and 108, a CDR-H1 of SEQ ID NOs: 58, 68, and 85, a CDR-L3 of SEQ ID NOs: 168, 173, and 181, a CDR-L2 of SEQ ID NOs: 153 and the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 and 149.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104 or 108
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 68 or 85
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 168
  • the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104 or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 68 or 85, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 168 with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L2 is a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions
  • the CDR-L1 is a CDR-L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6
  • an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112, 121 or 130, a CDR-H2 of SEQ ID NOs: 100, 104 or 108, a CDR-H1 of SEQ ID NOs: 58, 68, or 85, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104 or 108
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 68 or 85
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 165
  • the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104 or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 68 or 85, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L2 is a CDR-L2 of SEQ ID NO: 153 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions
  • the CDR-L1 is a CDR-L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6
  • an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112 or 130, a CDR-H2 of SEQ ID NOs: 100, 104, or 108, a CDR-H1 of SEQ ID NOs: 58, 68, or 85, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104, or108
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 68 or 85
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 165
  • the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104, or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 68, or 85, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L2 is a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions
  • the CDR-L1 is a CDR- L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5,
  • an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112, 121 or 130, a CDR-H2 of SEQ ID NOs: 100, 104 or 108, a CDR-H1 of SEQ ID NOs: 58, 67, or 84, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104 or 108
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 67 or 84
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO:
  • the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104 or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 67 or 84, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L2 is a CDR-L2 of SEQ ID NO: 153 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions
  • the CDR-L1 is a CDR-L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or
  • an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112 or 130, a CDR-H2 of SEQ ID NOs: 100, 104, or 108, a CDR-H1 of SEQ ID NOs: 58, 67, or 84, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149.
  • the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130
  • the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104, or108
  • the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 67 or 84
  • the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO:
  • the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104, or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions
  • the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 67, or 84, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions
  • the CDR-L2 is a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions
  • the CDR-L1 is a CDR- L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4,
  • the amino acid substitutions are conservative amino acid substitutions.
  • the antibodies described in this disclosure are referred to herein as “variants” or “clones”.
  • such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein.
  • such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.
  • the antibodies disclosed herein do not include antibodies disclosed in US Patent number 9,067,994.
  • IL-13 antibody does not comprise any combination of: (a) a CDR-H1 set forth in any of SEQ ID NOs: 58, 67, or 84; (b) a CDR-H2 set forth in any of SEQ ID NOs: 100, 104, or 108; (c) a CDR-H3 set forth in any of SEQ ID NOs: 112 or 130; (d) a CDR-L1 set forth in any of SEQ ID NOs: 141 or 149; (e) a CDR-L2 set forth in any of SEQ ID NOs: 153 or 154; and (f) a CDR-L3 set forth in SEQ ID NO: 165.
  • Fc Region [00213] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder and Cavacini, J. Allergy Clin. Immunol., 2010, 125:S41-52, incorporated by reference in its entirety.
  • the Fc region may be a naturally occurring Fc region, or an Fc region modified as described in the art or elsewhere in this disclosure.
  • numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al, Sequences of Proteins of Immunological Interest, 5th Ed.
  • an “Fc polypeptide” of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e., a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association.
  • an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence.
  • An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.
  • 125 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00215]
  • the terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody.
  • an FcR can be a native sequence human FcR.
  • an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
  • Fc ⁇ RII receptors include Fc ⁇ RIIA (an “activating receptor”) and Fc ⁇ RIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
  • Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)).
  • Activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain.
  • Inhibiting receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Da ⁇ ron, Annu. Rev. Immunol. 15:203-234 (1997)).
  • FcRs are reviewed in Ravetch and Kinet, Annu. Rev.
  • FcR neonatal receptor
  • Modifications in the CH2 domain can affect the binding of FcRs to the Fc.
  • a number of amino acid modifications in the Fc region are known in the art for selectively altering the affinity of the Fc for different Fcgamma receptors.
  • the Fc comprises one or more modifications to promote selective binding of Fc-gamma receptors.
  • Exemplary mutations that alter the binding of FcRs to the Fc are listed below: [00218] S298A/E333A/K334A, S298A/E333A/K334A/K326A (Lu Y, Vernes JM, Chiang N, et al. J Immunol Methods.
  • an antibody described herein includes modifications designed to improve its ability to mediate effector function. Such modifications are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC.
  • FCGR3a for ADCC
  • C1q for CDC
  • an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in Table 9 that confer improved 127 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR effector function.
  • the antibody can be afucosylated to improve effector function.
  • Table 9. CH2 domains and effector function engineering Reference Mutations Effect C C C C C C C C C C C C C C C C C [00227] Fc modifications designed to reduce FcgR and/or complement binding and/or effector function are known in the art.
  • Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D- lyxo-4-hexylose reductase (RMD) (see Henning von Horsten et al., Glycobiol 2010, 20:1607- 1618) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al., Arch. Biochem. Biophys., 1986, 249:533-545; U.S. Pat. Pub. No.
  • Examples of cell lines capable of producing defucosylated antibody include CHO- DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4- hexylose reductase (RMD) (see Henning von Horsten et al., Glycobiol 2010, 20:1607-1618) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al., Arch. Biochem. Biophys., 1986, 249:533-545; U.S. Pat. Pub. No.
  • knockout cell lines such as alpha-1,6- fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane-Ohnuki et al., Biotech. Bioeng., 2004, 87: 614-622; Kanda et al., Biotechnol. Bioeng., 2006, 94:680-688; and WO 2003/085107; each of which is incorporated by reference in its entirety).
  • Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system.
  • an antibody provided herein comprises an IgG1 domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgG1 domain. Such Fc domains are known to have improved ADCC. See Shields et al., J.
  • an antibody provided herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region.
  • an antibody provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al., Proc. Natl. Acad. Sci. USA, 2006,103:4005-4010, incorporated by reference in its entirety.
  • Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub. Nos. 2003/0157108, 2004/0093621, 2003/0157108, 2003/0115614, 2002/0164328, 2004/0093621, 2004/0132140, 2004/0110704, 2004/0110282, 2004/0109865; International Pat. Pub. Nos.
  • an antibody provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region.
  • Such antibody variants may have improved CDC function.
  • an antibody provided herein comprises one or more alterations that improves or diminishes C1q binding and/or CDC. See U.S. Pat. No. 6,194,551; WO 99/51642; and Idusogie et al., J. Immunol., 2000, 164:4178-4184; each of which is incorporated by reference in its entirety.
  • an antibody provided herein comprises a heavy chain comprising a constant heavy chain (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or SEQ ID NO: 624.
  • an antibody provided herein comprises a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469.
  • an antibody provided herein comprises (1) a constant heavy chain (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or SEQ ID NO: 624 or a HC region comprising sequence comprising an amino acid sequence having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 439 or SEQ ID NO: 624 (2) a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469, or a LC region comprising sequence comprising an amino acid sequence having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 469 (3) a VH comprising an amino acid sequence set forth in SEQ ID NO: 3 or a VH having at least 95%, 96%, 97%, 98%, 99% or 100% sequence
  • the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a light chain constant (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469, wherein the antibody further comprises a VH comprising an amino acid sequence having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 3 and a VL comprising an amino acid sequence at least 95% 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 39, wherein the VH comprises a HCDR1 comprising SEQ ID NO: 58, SEQ ID NO: 68, or SEQ ID NO: 85; a HCDR2 comprising SEQ ID NO: 100, SEQ ID NO: 104, or SEQ ID NO: 108; and a HCDR3 comprising SEQ ID NO: 112 or SEQ ID NO: 130; and the VL comprises a LCDR1 comprising SEQ ID NO: 58
  • the isolated antibody comprises a HCDR1 comprising SEQ ID NO: 58, a HCDR2 comprising SEQ ID NO: 100, a HCDR3 comprising SEQ ID NO: 112, a LCDR1 comprising SEQ ID NO: 141, a LCDR2 comprising SEQ ID NO: 153, and a LCDR3 comprising SEQ ID NO: 165.
  • the isolated antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO:3.
  • the isolated antibody comprises a VL comprising an amino acid sequence set forth in SEQ ID NO:39.
  • the isolated antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO:3 and a VL comprising an amino acid sequence set forth in SEQ ID NO:39.
  • the isolated antibody comprises a heavy chain 132 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439.
  • the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 624.
  • the isolated antibody comprises a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469.
  • the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469.
  • the isolated antibody comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of Construct 133.
  • the isolated antibody comprises the VH of Construct 133.
  • the isolated antibody comprises the VL of Construct 133.
  • the isolated antibody comprises the VH and VL of Construct 133.
  • the isolated antibody comprises the heavy chain constant (HC) region of Construct 133.
  • the isolated antibody comprises the constant light chain (LC) region of Construct 133. In certain embodiments, the isolated antibody comprises the heavy chain constant (HC) region and constant light chain (LC) region of Construct 133. [00243] In certain embodiments, the isolated antibody comprises Construct 133, i.e., comprising a HCDR1 comprising SEQ ID NO: 58, a HCDR2 comprising SEQ ID NO: 100, a HCDR3 comprising SEQ ID NO: 112, a LCDR1 comprising SEQ ID NO: 141, a LCDR2 comprising SEQ ID NO: 153, a LCDR3 comprising SEQ ID NO: 165, a VH comprising SEQ ID NO:3, a VL comprising SEQ ID NO:39, a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469.
  • Construct 133 i
  • the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in increased antibody half-life, increased ADCC activity, increased ADCP activity, or increased CDC activity compared with the Fc without the one or more substitutions.
  • the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the one or more amino acid substitutions is selected from the group consisting of S228P (SP); M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W.
  • SP S228P
  • the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS); M252Y/S254T/T256E (YTE); T250Q/M428L; T307A/E380A/N434A; T256D/T307Q (DQ); T256D/T307W (DW); M252Y/T256D (YD); T307Q/Q311V/A378V (QVV); T256D/H285D/T307R/Q311V/A378V (DDRVV); L309D/Q311H/N434S (DHS); S228P/L235E (SPLE); L234A/L235A (LA), M428L/N434A L234A/G237A (LALA), L234A/L235A/G237A, L234A/L235A/P329G
  • the antibodies described herein comprise an Fc region with YTE mutations at positions 253, 255, and 257. In certain embodiments, the antibodies described herein comprise an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, the antibodies described herein comprise an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236. In certain embodiments, the antibodies described herein comprise the heavy and light chain variable regions (VH and VL) as set forth in SEQ ID NOs: 3 and 39, respectively, and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively.
  • VH and VL heavy and light chain variable regions
  • the antibodies described herein comprise a human IgG1 Fc with LALA mutations. In certain embodiments, the antibodies described herein comprise a human IgG1 Fc with YTE mutations. In certain embodiments, the antibodies described herein comprise a human IgG1 Fc with LALA and YTE mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers.
  • the human Fc region comprises a human IgG1 Fc with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E.
  • the Fc region binds an Fc ⁇ Receptor selected from the group consisting of: Fc ⁇ RI, Fc ⁇ RIIa, Fc ⁇ RIIb, Fc ⁇ RIIc, Fc ⁇ RIIIa, and Fc ⁇ RIIIb.
  • the Fc region binds an Fc ⁇ Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.
  • the fragment crystallizable region (Fc region) of the IL-13 antibody described herein carries a triple substitution M252Y/S254T/T256E (YTE) designed to increase the half-life of the IgG.
  • the Fc region of the anti-IL-13 antibody described herein carries a triple substitution M253Y/S255T/T257E (YTE) designed to increase the half-life of the IgG.
  • YTE substitutions increase the binding of the modified IgG to the human neonatal Fc receptor (FcRn). FcRn-bound IgG is recycled via lysosomal salvage, resulting in the IgG returning to the circulation.
  • the YTE substitutions confer greater FcRn-IgG binding, prolonging the IgG serum half-life compared to an unmodified IgG.
  • LALA Modification [00250]
  • the IL-13 antibodies described herein additionally carries Fc region amino acid modifications L234A/L235A or L235A/L236A in the IgG1 heavy chain, commonly called LALA mutations. These changes can impair Fc receptor binding to IgG and prevent undesired effector cell activation.
  • an IL-13 antibody described herein is a high-affinity IgG1 humanized monoclonal antibody (mAb) that binds IL-13.
  • the IL-13 antibody described herein contains YTE and LALA modifications and is built on an IgG1 backbone.
  • the binding of the IL-13 antibodies described herein to IL-13 prevent the formation of the IL-13R ⁇ 1/IL-4R ⁇ active receptor heterodimer and subsequent IL-13-mediated signaling.
  • the direct consequences of IL-13 signaling in atopic dermatitis (AD) pathology include dermal thickening, increased CD4 + T cell infiltration, and dermal barrier disruption. Consequently, preventing receptor heterodimer formation is believed to decrease the clinical severity of AD.
  • the affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (KD).
  • KD dissociation equilibrium constant
  • the kinetic components that contribute to the dissociation equilibrium constant are described in more detail below.
  • Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®).
  • the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non- target molecule).
  • Specific binding can be measured, for example, by measuring binding to a target molecule (i.e., IL-13) and comparing it to binding to a non-target molecule.
  • Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule.
  • the affinity of an IL-13 antibody for a non-target molecule is less than about 50% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non- target molecule is less than about 40% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non-target molecule is less than about 30% of the affinity for IL-13.
  • the affinity of an IL-13 antibody for a non-target molecule is less than about 20% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 136 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR antibody for a non-target molecule is less than about 10% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non-target molecule is less than about 1% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non- target molecule is less than about 0.1% of the affinity for IL-13.
  • the term “competes with” or “cross-competes with” indicates that the two or more antibodies compete for binding to an antigen (e.g., IL-13).
  • an antigen e.g., IL-13
  • IL-13 is coated on a surface and contacted with a first IL-13 antibody, after which a second IL-13 antibody is added.
  • a first IL-13 antibody is coated on a surface and contacted with IL-13, and then a second IL-13 antibody is added. If the presence of the first IL-13 antibody reduces binding of the second IL-13 antibody, in either assay, then the antibodies compete with each other.
  • the term “competes with” also includes combinations of antibodies where one antibody reduces binding of another antibody, but where no competition is observed when the antibodies are added in the reverse order.
  • the first and second antibodies inhibit binding of each other, regardless of the order in which they are added.
  • one antibody reduces binding of another antibody to its antigen by at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% as measured in a competitive binding assay.
  • concentrations of the antibodies used in the competition assays based on the affinities of the antibodies for IL-13 and the valency of the antibodies.
  • the assays described in this definition are illustrative, and a skilled artisan can utilize any suitable assay to determine if antibodies compete with each other. Suitable assays are described, for example, in Cox et al., “Immunoassay Methods,” in Assay Guidance Manual [Internet], Updated December 24, 2014 (ncbi.nlm.nih.gov/books/NBK92434/; accessed September 29, 2015); Silman et al., Cytometry, 2001, 44:30-37; and Finco et al., J. Pharm. Biomed. Anal., 2011, 54:351-358; each of which is incorporated by reference in its entirety.
  • test antibody competes with a reference antibody if an excess of a test antibody (e.g., at least 2x, 5x, 10x, 20x, or 100x) inhibits or blocks binding of the reference antibody by, e.g., at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% as measured in a competitive binding assay.
  • a test antibody e.g., at least 2x, 5x, 10x, 20x, or 100x
  • Antibodies identified by competition assay include antibodies binding to the same epitope as the reference antibody and antibodies binding to an adjacent epitope sufficiently proximal to the epitope bound by the reference antibody for steric 137 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR hindrance to occur.
  • a second, competing antibody can be identified that competes for binding to IL-13 with a first antibody described herein.
  • the second antibody can block or inhibit binding of the first antibody by, e.g., at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% as measured in a competitive binding assay.
  • the second antibody can displace the first antibody by greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%.
  • the antibody binds an IL-13 sequence set forth in SEQ ID NOs: 472-475.
  • the antibody binds to an IL-13 sequence set forth in SEQ ID NOs: 472-475 with a K D of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10 -9 M, as measured by surface plasmon resonance (SPR).
  • the antibody binds to an IL-13 sequence set forth in SEQ ID NOs: 472-475 with a KD of less than or equal to about 1 x 10 -10 M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody binds to human IL-13 with a K D of less than or equal to about 1 x 10 -9 M, as measured by surface plasmon resonance (SPR).
  • an antibody provided herein binds IL-13 with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10 -8 M, as measured by ELISA or any other suitable method known in the art.
  • an antibody provided herein binds IL-13 with a K D of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10 -9 M, as measured by ELISA or any other suitable method known in the art.
  • the K D of an antibody provided herein for the binding of IL- 13 is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2-1.3, 1.3-1.4, 1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10 -8 M, as measured by ELISA or any other suitable method known in the art.
  • an antibody provided herein binds IL-13 with a KD of less than or equal to about 1 x 10 -8 M, or less than or equal to above 1 x 10 -9 M as measured by ELISA or any other suitable method known in the art.
  • an antibody provided herein binds IL-13 with a K D of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10 -8 M, or less, as measured by ELISA or any other suitable method known in the art .
  • an antibody provided herein binds IL-13 with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8-1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10 -8 M as measured by ELISA or any other suitable method known in the art.
  • Pharmaceutical Formulations and Methods of Manufacture Thereof [00262]
  • the present disclosure provides pharmaceutical formulations that comprise a therapeutically effective amount of an IL-13 antibody disclosed herein.
  • the pharmaceutical formulation comprises one or more excipients and/or surfactants and is maintained at a certain pH.
  • excipient include any non-therapeutic agent added to the formulation to provide a desired physical or chemical property, for example, pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption, or penetration.
  • Methods of manufacturing pharmaceutical formulations of the disclosure are also contemplated.
  • the method can include adjusting the matrix of an intermediate preparation of the disclosure (e.g., changing the buffer composition and/or the concentration of a purified preparation of an IL-13 antibody), such as by Ultrafiltration and Diafiltration (UFDF), to increase a concentration of an IL-13 antibody.
  • a method of manufacturing an intermediate preparation of an interleukin 13 (IL-13) antibody comprising: (a) obtaining a purified preparation of the IL-13 antibody; and (b) adjusting the matrix of the purified preparation of step (a), wherein adjusting the matrix of comprises performing Ultrafiltration and Diafiltration (UFDF) with the diafiltration buffer of the above described aspect or any one of the embodiments thereof, thereby obtaining the intermediate preparation of the IL-13 antibody.
  • the intermediate preparation (e.g., a UFDF intermediate preparation) can be used to prepare a final preparation through the addition of excipients and/or dilution.
  • 139 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR
  • the intermediate preparation of the IL-13 antibody has a higher concentration of the IL-13 antibody relative to the purified preparation.
  • the method of manufacturing further comprises: (c) formulating the intermediate preparation to obtain a formulation of the IL-13 antibody.
  • the formulation of the IL-13 antibody comprises a formulation described herein.
  • a diafiltration buffer comprising: (a) a histidine buffer; and (b) arginine or a salt solution thereof, at pH of from 5.4 to 7.0, e.g., from 5.5-6.5. In some embodiments, the pH is from about 5.7 to about 6.5. In some embodiments, the pH is about 5.8 or about 6.0.
  • the histidine buffer comprises a histidine and a histidine salt. In some embodiments, the histidine is L-histidine. In some embodiments, the histidine salt is L- histidine HCl monohydrate.
  • Histidine buffer can be present in an amount of about 15-20 mM, for example, at about 18 mM.
  • the diafiltration buffer comprises arginine, and wherein the arginine is L-arginine.
  • the diafiltration buffer comprises an L-arginine salt solution.
  • the L-arginine salt solution salt solution comprises HCl monohydrate.
  • the L-arginine salt solution is at a concentration between 40 mM and 200 mM.
  • the L-arginine salt solution is at a concentration of about 50 mM.
  • the L-arginine salt solution is at a concentration of about 100 mM.
  • the L-arginine salt solution is at a concentration of about 120 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 170 mM.
  • Excipients, Surfactants, and pH may be selected for their suitability for intravenous or subcutaneous administration, providing the necessary stabilizing, buffering capacity, viscosity, and tonicity. The formulation can improve the stability of the IL-13 antibody and can provide a sterile solution suitable for subcutaneous or intravenous administration.
  • the excipients and/or surfactants contained in the formulation are pharmacopoeial grade excipients.
  • the excipients in the formulation comprise a histidine buffer (also referred 140 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR to as a His buffer) (e.g., a combination L-histidine and L-histidine HCl buffer, also referred to as L-His and L-His HCl), an acetate buffer, or a succinate buffer; arginine (Arg) and/or methionine (Met) (e.g., L-arginine (L-Arg) and/or L-methionine (L-Met)) or a salt solution thereof; and a polysorbate or a poloxamer.
  • a histidine buffer also referred 140 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Dock
  • the formulation further comprises a sugar or sugar alcohol.
  • the one or more excipients in the pharmaceutical formulation of the present invention can comprise a buffering agent.
  • buffering agent refers to one or more components that when added to an aqueous solution is able to protect the solution against variations in pH when adding acid or alkali, or upon dilution with a solvent.
  • histidine buffers, acetate buffers, and succinate buffers in certain embodiments, phosphate buffers, glycinate buffers, carbonate buffers, citrate buffers and the like can be used.
  • sodium, potassium or ammonium ions can serve as counterion.
  • the buffer or buffer system such as a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer), acetate buffer, or succinate buffer, comprises at least one buffer that has a buffering range that overlaps fully or in part with the range of between 5.5 and 7.0 (e.g., between 5.6 and 6.5, and 5.7 and 6.2).
  • the pH is between 5.6 and 6.5.
  • the pH is between 5.8 and 6.0.
  • the buffer has a pH of about 5.5.
  • the buffer has a pH of about 5.6.
  • the buffer has a pH of about 5.7.
  • the buffer has a pH of about 5.8. In some embodiments, the buffer has a pH of about 5.9. In some embodiments, the buffer has a pH of about 6.0. In some embodiments, the buffer has a pH of about 6.1. In some embodiments, the buffer has a pH of about 6.2. In some embodiments, the buffer has a pH of about 6.3. In some embodiments, the buffer has a pH of about 6.4. In some embodiments, the buffer has a pH of about 6.5. In some embodiments, the buffer has a pH of about 5.9-6.3. In some embodiments, the buffer has a pH of about 6.0.
  • the histidine buffer e.g., a combination L-histidine and L- histidine HCl buffer
  • acetate buffer e.g., acetate buffer
  • succinate buffer is at a concentration between 5 mM and 20 mM (e.g., between 6 mM and 19 mM, 7 mM and 18 mM, 8 mM and 17 mM, 9 mM and 16 mM, and 10 mM and 15 mM).
  • the histidine buffer, acetate buffer, or 141 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR succinate buffer is at a concentration between 6 mM and 19 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 7 mM and 18 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 8 mM and 17 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 9 mM and 16 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 10 mM and 15 mM.
  • the histidine buffer e.g., a combination L-histidine and L- histidine HCl buffer
  • acetate buffer, or succinate buffer is at a concentration of about 1 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 2 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 3 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 4 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 5 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 6 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 7 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 8 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 9 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 10 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 11 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 12 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 13 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 14 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 15 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 16 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 17 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 18 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 19 mM.
  • the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 20 mM.
  • the formulation comprises a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer), acetate buffer, or succinate buffer.
  • the formulation comprises a histidine buffer.
  • the histidine buffer comprises L-histidine and L-histidine HCl.
  • the formulation comprises an acetate buffer.
  • the formulation comprises a succinate buffer.
  • a histidine buffer acts as a buffering agent.
  • the histidine buffer comprises a histidine and a histidine salt.
  • the histidine is L-histidine.
  • the histidine salt is L-histidine HCl monohydrate.
  • the formulation comprises methionine. In some embodiments, the methionine is L-methionine.
  • the methionine (e.g., L-methionine) is at a concentration between 1 mM and 20 mM (e.g., between 2 mM and 19 mM, 3 mM and 18 mM, 4 mM and 17 mM, 5 mM and 16 mM, and 5 mM and 15 mM).
  • the L-methionine is at a concentration between 1 mM and 19 mM.
  • the L-methionine is at a concentration between 2 mM and 18 mM.
  • the L-methionine is at a concentration between 3 mM and 17 mM.
  • the L-methionine is at a concentration between 4 mM and 16 mM. In some embodiments, the L-methionine is at a concentration between 5 mM and 15 mM. [00281] In some embodiments, the methionine (e.g., L-methionine) is at a concentration of about 1 mM. In some embodiments, the L-methionine is at a concentration of about 2 mM. In some embodiments, the L-methionine is at a concentration of about 3 mM. In some embodiments, the L-methionine is at a concentration of about 4 mM. In some embodiments, the L-methionine is at a concentration of about 5 mM.
  • the methionine e.g., L-methionine
  • the methionine is at a concentration of about 1 mM. In some embodiments, the L-methionine is at a concentration of about 2 mM. In some embodiments,
  • the L-methionine is at a concentration of about 6 mM. In some embodiments, the L-methionine is at a concentration of about 7 mM. In some embodiments, the L-methionine is at a concentration of about 8 mM. In some embodiments, the L-methionine is at a concentration of about 9 mM. In some embodiments, the L-methionine is at a concentration of about 10 mM. In some embodiments, the L-methionine is at a concentration of about 11 mM.
  • the L-methionine is 143 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR at a concentration of about 12 mM. In some embodiments, the L-methionine is at a concentration of about 13 mM. In some embodiments, the L-methionine is at a concentration of about 14 mM. In some embodiments, the L-methionine is at a concentration of about 15 mM. In some embodiments, the L-methionine is at a concentration of about 16 mM. In some embodiments, the L-methionine is at a concentration of about 17 mM.
  • the L-methionine is at a concentration of about 18 mM. In some embodiments, the L-methionine is at a concentration of about 19 mM. In some embodiments, the L-methionine is at a concentration of about 20 mM.
  • the formulation comprises arginine. In some embodiments, the arginine is L-arginine. In some embodiments, the formulation comprises an L-arginine salt solution. In some embodiments, the L-arginine or L-arginine salt solution acts as a viscosity modulator. In some embodiments, the L-arginine salt solution salt solution comprises HCl monohydrate.
  • the arginine (e.g., L-arginine) salt solution is at a concentration between 40 mM and 250 mM (e.g., between 50 mM and 200 mM, 60 mM and 150 mM, 70 mM and 125 mM, 80 mM and 100 mM, and about 90 mM).
  • the arginine (e.g., L-arginine) salt solution is at a concentration between 70 mM and 130 mM.
  • the L-arginine salt solution is at a concentration of about 40 mM.
  • the L-arginine salt solution is at a concentration of about 50 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 60 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 70 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 80 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 90 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 100 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 120 mM.
  • the L-arginine salt solution is at a concentration of about 125 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 150 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 170 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 200 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 250 mM. 144 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00285]
  • the one or more excipients in the pharmaceutical formulation disclosed herein further comprises a surfactant.
  • surfactant refers to a surface active molecule containing both a hydrophobic portion (e.g., alkyl chain) and a hydrophilic portion (e.g., carboxyl and carboxylate groups). Surfactants are useful in pharmaceutical formulations for reducing aggregation of a therapeutic protein.
  • Surfactants suitable for use in the pharmaceutical formulations are generally non-ionic surfactants and include, but are not limited to, polysorbates (e.g., polysorbates 20 or 80); poloxamers (e.g., poloxamer 188); sorbitan esters and derivatives; Triton; sodium laurel sulfate; sodium octyl glycoside; lauryl-, myristyl-, linoleyl-, or stearyl- sulfobetadine; lauryl-, myristyl-, linoleyl- or stearyl-sarcosine; linoleyl-, myristyl-, or cetyl- betaine; lauramidopropyl-cocamidopropyl-, linoleamidopropyl-, myristamidopropyl-, palmidopropyl-, or isostearamidopropylbetaine (e.g.
  • the surfactant is a polysorbate. In certain embodiments, the surfactant is polysorbate 80. In certain embodiments, the surfactant is a poloxamer. In certain embodiments, the surfactant is poloxamer 188. [00286] In some embodiments, a polysorbate or poloxamer acts as a stabilizer. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.005% w/v and 0.15% w/v or between 0.01% w/v and 0.15% w/v (e.g., between 0.02% and 0.14%, 0.03% and 0.13%, 0.04% and 0.12%, 0.05% and 0.11%, or about 0.1%).
  • the polysorbate or poloxamer is at a concentration between 0.02% and 0.14%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.03% and 0.13%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.04% and 0.12%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.05% and 0.11%.
  • the polysorbate or poloxamer is at a concentration between 0.005% w/v and 0.10% w/v, or between 0.005% w/v and 0.05% w/v or between 0.05% w/v and 0.10 w/v, or at about 0.05% w/v or at 0.05% w/v. [00287] In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.005% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.01% w/v.
  • the polysorbate or poloxamer is at a concentration of about 145 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 0.02% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.03% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.04% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.05% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.06% w/v.
  • the polysorbate or poloxamer is at a concentration of about 0.07% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.08% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.09% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.1% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.11% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.12% w/v.
  • the polysorbate or poloxamer is at a concentration of about 0.13% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.14% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.15% w/v. [00288] In some embodiments, the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In some embodiments, the polysorbate is polysorbate 20. In some embodiments, the polysorbate is polysorbate 40. In some embodiments, the polysorbate is polysorbate 60. In some embodiments, the polysorbate is polysorbate 80.
  • the poloxamer is poloxamer 188, also referred to herein as P188.
  • P188 is included in the formulation at a concentration in a range of, for example 0.1-2.0 mg/ml, 0.25-1.5 mg/ml or 0.5-1.0 mg/ml, or at a concentration of 0.25 mg/ml, 0.5 mg/ml, 0.75 mg/ml or 1.0 mg/ml.
  • the formulation comprises P188 at a concentration of 0.5 mg/ml.
  • the one or more excipients in the pharmaceutical formulation of the present invention can further comprise a metal ion chelator.
  • Metal ion chelators also known as chelating agents, bind metal ions to form water soluble complexes and thus can be used to remove metal ions from a formulation.
  • the metal ion chelator is ethylenediaminetetraacetic acid (EDTA), or a salt thereof (e.g., disodium EDTA, sodium calcium edetate, tetrasodium EDTA).
  • the metal ion chelator is EDTA disodium salt (EDTA-2Na).
  • the metal ion chelator is EDTA-2Na, which is included in the formulation at a concentration in a range of, for example, 0.001-1 mM or 0.01-1mM or 0.001-0.5 mM or 0.01-0.5 mM or at a 146 4925-0461-2873 v.1 4925-0461-2873 v.1
  • the formulation comprises EDTA (e.g., EDTA-2Na) at a concentration of 0.05 mM.
  • EDTA e.g., EDTA-2Na
  • Other metal ion chelators are known in the art, non-limiting examples of which include ethylenediamine (1,2-diaminoethane), diethylenetriaminepentaacetic acid (DTPA), ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), succimer (dimercaptonol), dimercaprol (BAL), nitrilotriacetic acid (NTA), iminodisuccinic acid (IDS), polyaspartic acid, S,S-ethylenediamine-N,N′-disuccinic acid (EDDS), methylglycinediacetic acid (MGDA), L-Glutamic acid N,N-diacetic acid, t
  • the one or more excipients in the pharmaceutical formulation of the present invention can further comprise a sugar or sugar alcohol.
  • Sugars and sugar alcohols are useful in pharmaceutical formulations as a thermal stabilizer.
  • the pharmaceutical formulation comprises a sugar, for example, a monosaccharide (glucose, xylose, or erythritol), a disaccharide (e.g., sucrose, trehalose, maltose, or galactose), or an oligosaccharide (e.g., stachyose).
  • the pharmaceutical formulation comprises sucrose.
  • the pharmaceutical composition comprises a sugar alcohol, for example, a sugar alcohol derived from a monosaccharide (e.g., mannitol, sorbitol, or xylitol), a sugar alcohol derived from a disaccharide (e.g., lactitol or maltitol), or a sugar alcohol derived from an oligosaccharide.
  • the pharmaceutical formulation comprises sucrose.
  • a sugar or sugar alcohol acts as a stabilizer.
  • the sugar or sugar alcohol is at a concentration between 1% w/v and 5% w/v (e.g., between 2% w/v and 4% w/v, or about 3% w/v). In some embodiments, the sugar or sugar alcohol is at a concentration between 2% w/v and 4% w/v. [00294] In some embodiments, the sugar or sugar alcohol is at a concentration of about 1% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 2% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 3% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 4% w/v.
  • the sugar or sugar alcohol is at a concentration of about 5% w/v. 147 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR
  • the sugar or sugar alcohol is a disaccharide.
  • the disaccharide is sucrose.
  • the formulation is adjusted to final volume in water for injection (WFI).
  • WFI water for injection
  • the drug product is diluted in an aqueous carrier suitable for the route of administration, e.g., intravenous administration.
  • Exemplary carriers include sterile water for injection (SWFI), bacteriostatic water for injection (BWFI), a pH buffered solution (e.g., phosphate-buffered saline), sterile saline solution, Ringer's solution, or dextrose solution.
  • SWFI sterile water for injection
  • BWFI bacteriostatic water for injection
  • a pH buffered solution e.g., phosphate-buffered saline
  • sterile saline solution e.g., Ringer's solution
  • Ringer's solution e.g., Ringer's solution
  • dextrose solution e.g., sterile saline solution
  • D5W 5% dextrose solution
  • the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0.
  • a histidine buffer e.g., combination L-histidine and L-histidine HCl buffer
  • an acetate buffer e.g., combination acetic acid and sodium acetate trihydrate
  • a succinate buffer e.g.,
  • the pharmaceutical formulation of the present invention comprises: (a) IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0.
  • a histidine buffer e.g., combination L-histidine and L-histidine HCl buffer
  • an acetate buffer e.g., combination acetic acid and sodium acetate trihydrate
  • a succinate buffer e.g., combination
  • the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; 148 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (d) CDR-L1 comprises a sequence selected from
  • the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody at a concentration, e.g., between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer), an acetate buffer, or a succinate buffer; (c) arginine and/or methionine (e.g., L-arginine and/or L- methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0.
  • a histidine buffer e.g., a combination L-histidine and L-histidine HCl buffer
  • an acetate buffer e.g., acetate buffer, or a succinate buffer
  • arginine and/or methionine e.g., L-arginine and/or L- methionine
  • a salt solution thereof e
  • the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR- L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID
  • the pharmaceutical formulation of the present invention comprises: (a) an IL-13 present at a concentration of, e.g., about 180 mg/mL; (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • a histidine buffer e.g., a combination L-histidine and L-histidine HCl buffer
  • an L-arginine salt solution at a concentration of about 120 mM
  • L-methionine at a concentration of about 10 mM
  • polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • the pharmaceutical formulation of the present invention comprises: (a) IL-13 antibody present at a concentration of, e.g., about 180 mg/mL; (b) a 149 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR histidine buffer (e.g.,, a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 80 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • AOE-003PR histidine buffer e.g.,, a combination L-histidine and L-histidine HCl buffer
  • an L-arginine salt solution at a concentration of about 80 mM
  • the pharmaceutical formulation of the present invention comprises: (a) IL-13 antibody present at a concentration of, e.g., about 200 mg/mL; (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • a histidine buffer e.g., a combination L-histidine and L-histidine HCl buffer
  • an L-arginine salt solution at a concentration of about 120 mM
  • L- methionine at a concentration of about 10 mM
  • polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8.
  • the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody present at a concentration of, e.g., about 180 mg/mL (e.g., at 180 mg/ml); (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM (e.g., at 10 mM); (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); (e) polysorbate 80 at a concentration of about 0.05% w/v (e.g., at 0.05% w/v); and (f) EDTA or a salt thereof (e.g., EDTA-2Na) at a concentration of about 0.05 mM (e.g.,
  • the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody present at a concentration of, e.g., about 180 mg/mL (e.g., at 180 mg/ml); (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM (e.g., at 10 mM); (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); (e) poloxamer 188 at a concentration of about 0.5 mg/ml (e.g., at 0.5 mg/ml), at pH of about 5.8-6.0 (e.g., at pH 5.8 or pH 6.0).
  • a histidine buffer e.g., a combination L-histidine and L-hist
  • the formulation comprises a sugar, for example, sucrose at a concentration between about 2% w/v and 8% w/v, such as a concentration of about 3% w/v or about 5% w/v.
  • a sugar for example, sucrose at a concentration between about 2% w/v and 8% w/v, such as a concentration of about 3% w/v or about 5% w/v.
  • the pharmaceutical formulations of the present invention exhibit high levels of stability.
  • a pharmaceutical formulation is stable when the IL-13 antibody within the formulation retains an acceptable degree of physical property, chemical structure, and/or biological function after storage under defined conditions.
  • the pharmaceutical formulation can be prepared and stored as a liquid formulation.
  • the pharmaceutical formulation is a liquid formulation for storage frozen (-20 to -70° C), under refrigerated conditions (typically 2-8° C), or at room temperature (typically 20-26° C) before preparation for administration.
  • the pharmaceutical formulation is a liquid formulation for storage at a suitable temperature and protected from light.
  • Antibody 180 mg/mL or 200 mg/mL concentrate for injection is suitable for subcutaneous administration with disposable syringes, without dilution or with dilution in a carrier buffer.
  • Materials found to be compatible with an antibody herein comprise injection syringes composed of polypropylene or polycarbonate, and needles for injection composed of stainless steel. Compatibility of antibody concentrate for solution for injection has been demonstrated with pre- filled syringes for an antibody concentration of from 160 mg/mL and 250 mg/mL.
  • the pharmaceutical formulation Prior to pharmaceutical use, can be diluted in an aqueous carrier if suitable for the route of administration.
  • a IL-13 antibody is fully formulated for subcutaneous administration (i.e., no diluents are added), and thus is identical in composition to the formulation described herein.
  • the IL-13 antibody may be further diluted in an appropriate carrier prior to pharmaceutical use.
  • suitable carriers include sterile water for injection (SWFI), bacteriostatic water for injection (BWFI), a pH buffered solution (e.g., phosphate- buffered saline), sterile saline solution, Ringer’s solution, or dextrose solution.
  • SWFI sterile water for injection
  • BWFI bacteriostatic water for injection
  • a pH buffered solution e.g., phosphate- buffered saline
  • sterile saline solution e.g., Ringer’s solution
  • dextrose solution e.g., phosphate- buffered saline
  • Ringer’s solution e.g., Ringer’s solution
  • dextrose solution e.g., sterile saline solution
  • Ringer sterile saline solution
  • dextrose solution e.g., phosphate- buffered saline
  • Ringer sterile saline solution
  • the diluted pharmaceutical formulation is isotonic and suitable for administration by intravenous infusion, e.g., D5W.
  • the formulation is diluted in about 50 mL D5W, 100 mL D5W, 150 mL D5W, 200 mL D5W, 250 mL D5W, 300 mL D5W, 350 mL D5W, 400 mL D5W, 450 mL D5W, 500 mL D5W, or 1 L D5W.
  • the pharmaceutical formulation comprises the IL-13 antibody at a concentration suitable for storage.
  • the pharmaceutical formulation comprises the IL-13 antibody at a concentration between 160 mg/mL and 250 mg/mL (e.g., between 170 mg/mL and 210 mg/mL, 180 mg/mL and 200 mg/mL, or about 190 mg/mL).
  • the IL- 13 antibody is at a concentration between 170 mg/mL and 210 mg/mL.
  • the IL-13 antibody is at a concentration between 180 mg/mL and 200 mg/mL.
  • the IL-13 antibody is at a concentration of about 160 mg/mL.
  • the IL-13 antibody is at a concentration of about 170 mg/mL.
  • the IL-13 antibody is at a concentration of about 180 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 190 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 200 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 210 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 220 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 230 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 240 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 250 mg/mL.
  • the IL-13 antibody is at a concentration of 160 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 170 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 180 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 190 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 200 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 210 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 220 mg/mL.
  • the IL-13 antibody is at a concentration of 230 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 240 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 250 mg/mL.
  • Formulations described herein may be included in e.g., a vial, bag, bottle or on-body device. In some embodiments, the vial is a syringe. In some embodiments, the vial is a glass syringe.
  • the syringe is a prefilled syringe. In some embodiments, the prefilled syringe is a prefilled glass syringe. Additionally, formulations herein may be included in and administered by pens, autoinjectors, including autoinjector syringes and cartridges, and on-body devices. In some embodiments, when an on-body device is used for administration, up to 5 mL of the formulation may be present in the device.
  • an extractable volume of the vial is between 1.0 mL and 10.0 mL, e.g., between 1.0 mL and 3.0 mL or between 3.0 mL and 10.0 mL. In some embodiments, the extractable volume of the vial is about 1.0, 2.0 mL, 3.0 mL, 4.0 mL, 5.0 mL, 6.0 mL, 7.0 mL, 8.0 mL, 9.0 mL or 10.0 mL. As used herein, the “extractable volume” of the vial is the amount that can be withdrawn from the receptacle.
  • the pharmaceutical formulation is packaged in a vial (e.g., a pen or syringe).
  • the vial comprises an overfill to allow for complete removal of the intended dose.
  • the vial comprises an overfill of 5 to 35%, 10 to 30%, 15 to 25%, or 10 to 20%.
  • the vial comprises an overfill of about 20%.
  • the formulation may be a liquid formulation.
  • the amount of IL-13 antibody in the container is suitable for administration as a single dose.
  • the amount of IL-13 antibody in the container is suitable for administration in multiple doses.
  • the pharmaceutical formulation comprises the IL-13 antibody in an amount of 0.1 to 200 mg.
  • the pharmaceutical formulation comprises the IL-13 antibody in an amount of 1 to 200 mg, 10 to 200 mg, 20 to 200 mg, 50 to 200 mg, 100 to 200 mg, 200 to 500 mg, 500 to 2000 mg, 1000 to 2000 mg, 0.1 to 1000 mg, 1 to 1000 mg, 10 to 1000 mg, 20 to 1000 mg, 50 to 1000 mg, 100 to 1000 mg, 200 to 1000 mg, 500 to 1000 mg, 0.1 to 500 mg, 1 to 500 mg, 10 to 500 mg, 20 to 500 mg, 50 to 500 mg, 100 to 500 mg, 200 to 500 mg, 0.1 to 200 mg, 1 to 200 mg, 10 to 200 mg, 20 153 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR to 200 mg, 50 to 200 mg, 100 to 200 mg, 0.1 to 100
  • the pharmaceutical formulation comprises the IL-13 antibody in an amount of about 0.1 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 450 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1500 mg, or about 2000 mg.
  • Methods of Use [00320] The present application provides compositions comprising a formulation or vial described herein for use in the treatment of an inflammatory disorder or disease.
  • the present application also provides compositions comprising a formulation or vial (e.g., pre-filled syringe) described herein for use in methods of treating inflammatory, allergic, and immunologic diseases, such as atopic dermatitis, in a patient in need thereof.
  • a formulation or vial e.g., pre-filled syringe
  • the patient has been diagnosed with moderate-to-severe atopic dermatitis.
  • the patient has had moderate-to-severe atopic dermatitis for at least one year.
  • the patient is a pediatric patient.
  • the patient has one or more of: (a) an Eczema Area and Severity Index Score (EASI) of ⁇ 10 (e.g., an EASI of ⁇ 16 or an EASI ⁇ 10 and ⁇ 16), (b) an Investigator Global Assessment (IGA) score of ⁇ 3 and (c) a body surface area (BSA) of ⁇ 10%.
  • EASI Eczema Area and Severity Index Score
  • ASI Eczema Area and Severity Index Score
  • the patient has an Eczema Area and Severity Index Score (EASI) of ⁇ 16.
  • the patient has an Eczema Area and Severity Index Score (EASI) of ⁇ 10 and less than 16.
  • EASI Eczema Area and Severity Index Score
  • the patient has an Investigator Global Assessment (IGA) score of ⁇ 3.
  • the patient has a body surface area (BSA) of ⁇ 10%.
  • the “Investigator Global Assessment” or “IGA” is an assessment measure used globally to rate the severity of the patient’s AD (Simpson E, et al. J Am Acad Dermatol. 2020;83(3):839-846).
  • AOE-003PR score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. It is not necessary that all characteristics under Morphological Description be present.
  • the IGA can be conducted prior to conducting the EASI and BSA assessments.
  • the “Eczema Area and Severity Index” or “EASE is a measure used in clinical settings to assess the severity and extent of AD (Hanifin et al., Exp Dermatol. 2001; 10: 11-18).
  • EASI is a composite index with scores ranging from 0 to 72, with the higher values indicating more severe and or extensive disease.
  • the severity of erythema, induration/papulation, excoriation, and lichenification can be assessed by a clinician or other medical professional on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head and neck, trunk, upper limbs, and lower limbs, with half points allowed.
  • the extent of AD involvement in each of the 4 body areas can be assessed as a percentage by body surface area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6.
  • a total score (0 – 72) is assigned based on the sum of total scores for each of the four body region scores.
  • the “Scoring of Atopic Dermatitis” or “SCORAD” is a validated clinical tool for assessing the extent and intensity of AD developed by the European Task Force on Atopic Dermatitis (Consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993; 186(l):23-31).
  • AD extent of AD is assessed as a percentage of each defined body area and reported as the sum of all areas, with a score ranging from 0 to 100 (assigned as “A” in the overall SCORAD calculation);
  • A the severity of 6 symptoms of AD: redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness.
  • Each item is graded as follows: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points, assigned as “B” in the overall SCORAD calculation); (iii) subjective assessment of itch and of sleeplessness is recorded for each symptom using a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum possible score of 20 (assigned as “C” in the overall SCORAD calculation).
  • VAS visual analogue scale
  • the SCORAD Index formula is: A/5 + 7B/2 + C.
  • the maximal score of the SCORAD Index is 103.
  • Pruritus Numerical Rating Scale is an 11 -point scale used by patients (and if applicable, with help of parents/ caregiver if required) to rate their worst itch severity over the past 24 hours with 0 indicating “No itch” and 10 indicating “Worst itch imaginable” (Phan NQ, et al. Acta Derm Venereol 2012; 92: 502-507). Assessments are recorded by the patient daily 155 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR using an electronic diary.
  • the baseline pruritus NRS is determined based on the average of daily Pruritus NRS during the 7 days immediately preceding baseline. A minimum of 4 daily scores out of the 7 days immediately preceding baseline is required for this calculation.
  • Sleep loss scale rates patient’s sleep loss due to pruritus on a 5-point Likert scale (with scores ranging from 0 [not at all], 1 [a little], 2 [moderately], 3 [quite a bit], to 4 [unable to sleep at all]). Assessments will be recorded daily by the patient using an electronic diary.
  • the Patient-Oriented Eczema Measure is a 7-item, validated, questionnaire completed by the patient (and if applicable, with help of parents/ caregiver if required) to assess disease symptoms over the last week (Centre of Evidence Based Dermatology. POEM – Patient Oriented Eczema Measure. Available at www.nottingham.ac.uk/research/groups/cebd/resources/poem.aspx). Patients are asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping.
  • DLQI Dermatology Life Quality Index
  • the 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week.
  • Each question is scored from 0 to 3 (“not at all,” “a little,” “a lot,” and “very much”), giving a total score ranging from 0 to 30. A high score is indicative of a poor quality of life.
  • methods described herein comprise determining one or more of the following characteristics of the patient at baseline and during and after the induction period: Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Body Surface Area (BSA), Pruritus Numerical Rating Scale (NRS), Sleep loss scale, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI).
  • EASI Eczema Area and Severity Index
  • IGA Investigator Global Assessment
  • BSA Body Surface Area
  • NRS Pruritus Numerical Rating Scale
  • SCORing Atopic Dermatitis SCORAD
  • POEM Patient Oriented Eczema Measure
  • DLQI Dermatology Life Quality Index
  • methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: 156 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Eczema Area and Severity Index (EASI).
  • methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Investigator Global Assessment (IGA).
  • methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Body Surface Area (BSA).
  • BSA Body Surface Area
  • methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Pruritus Numerical Rating Scale (NRS). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Sleep loss scale, SCORing Atopic Dermatitis (SCORAD). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Patient Oriented Eczema Measure (POEM). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Dermatology Life Quality Index (DLQI).
  • DLQI Dermatology Life Quality Index
  • a patient described herein is determined to have one or more of the following characteristics of the patient at baseline and during and after the induction period: Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Body Surface Area (BSA), Pruritus Numerical Rating Scale (NRS), Sleep loss scale, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI).
  • EASI Eczema Area and Severity Index
  • IGA Investigator Global Assessment
  • BSA Body Surface Area
  • NRS Pruritus Numerical Rating Scale
  • PES Patient Oriented Eczema Measure
  • DLQI Dermatology Life Quality Index
  • a patient herein is determined to have a characteristic Eczema Area and Severity Index (EASI) at baseline and during and after the induction period.
  • a patient herein is determined to have a characteristic Investigator Global Assessment (IGA) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Body Surface Area (BSA) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Pruritus Numerical Rating Scale (NRS) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Sleep loss scale, SCORing Atopic Dermatitis (SCORAD) at baseline and during and after the induction period.
  • IGA Investigator Global Assessment
  • BSA Body Surface Area
  • NRS Pruritus Numerical Rating Scale
  • a patient herein is determined to have a characteristic Sleep loss scale, SCORing Atopic Dermatitis (SCORAD) at baseline and during and after the induction period.
  • a patient herein is determined to have a characteristic Patient Oriented Eczema Measure (POEM) at baseline and during and after the induction period. 157 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR
  • a patient herein is determined to have a characteristic Dermatology Life Quality Index (DLQI) at baseline and during and after the induction period.
  • DLQI Dermatology Life Quality Index
  • the present application provides methods of contacting IL-13 with an IL- 13 antibody, such as a human, humanized, or chimeric antibody, which results in inhibition of IL-13 binding to an IL-13 receptor expressed on a cell.
  • compositions comprising a formulation or vial described herein for use in the treatment of an inflammatory disorder or disease selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of an inflammatory disorder or disease selected from the group consisting
  • the present application provides methods for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein.
  • the inflammatory disorder or disease is atopic dermatitis.
  • the inflammatory disorder or disease is selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold In
  • the inflammatory disorder or disease is asthma. In some embodiments, the inflammatory disorder or disease is idiopathic pulmonary fibrosis. In some embodiments, the inflammatory disorder or disease is alopecia areata. In some embodiments, the inflammatory disorder or disease is chronic sinusitis with nasal polyps. In some embodiments, the inflammatory disorder or disease is Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In some embodiments, the inflammatory disorder or disease is eosinophilic esophagitis (EoE).
  • EoE eosinophilic esophagitis
  • the inflammatory disorder or disease is an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG).
  • EoG Eosinophilic Gastritis
  • the inflammatory disorder or disease is Eosinophilic Enteritis (EoN).
  • EoC Eosinophilic Colitis
  • the inflammatory disorder or disease is and Eosinophilic Gastroenteritis (EGE).
  • the inflammatory disorder or disease is Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA).
  • the inflammatory disorder or disease is Prurigo Nodularis (PN).
  • the inflammatory disorder or disease is of Chronic Spontaneous Urticaria (CSU).
  • the inflammatory disorder or disease is Chronic Pruritis of Unknown Origin (CPUO).
  • the inflammatory disorder or disease is Bullous Pemphigoid (BP).
  • the inflammatory disorder or disease is Cold Inducible Urticaria (ColdU).
  • the inflammatory disorder or disease is Allergic Fungal Rhinosinusitis (AFRS).
  • the inflammatory disorder or disease is Allergic Bronchopulmonary Aspergillosis (ABPA).
  • the inflammatory disorder or disease is Chronic Obstructive Pulmonary Disease (COPD).
  • COPD Chronic Obstructive Pulmonary Disease
  • the present application provides methods for treating a pathology associated with elevated levels of IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein.
  • the present application provides methods of reducing biological activity of IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein.
  • the present application provides methods of inhibiting the TH2 type allergic response in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein.
  • the present application provides methods of reducing levels of Thymus and Activation Regulated Chemokine (TARC)/CCL17 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein.
  • the present application provides methods of preventing an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein.
  • the formulation is administered subcutaneously or intravenously.
  • Example 1 Formulation of an Anti-Interleukin 13 Antibody: pH and Buffer Studies [00344] This Example describes formulation studies of an interleukin 13 (IL-13) antibody, Construct 133. In formulating the antibody, twelve pH/buffers were investigated under stress conditions (40 °C for up to 4 weeks) to select pH and buffer system that stabilize the antibody.
  • IL-13 interleukin 13
  • a panel of analytical methods were used to characterize the pH and buffer studies, including appearance, pH, protein concentration, size exclusion-ultra performance liquid chromatography (SE-UPLC), imaged capillary isoelectric focusing (iCIEF), chip method of sodium dodecyl sulfate-polyacrylamide capillary electrophoresis (non-reduced and reduced, Caliper-SDS-NR & R, respectively), and differential scanning calorimetry (DSC), described below.
  • SE-UPLC size exclusion-ultra performance liquid chromatography
  • iCIEF imaged capillary isoelectric focusing
  • chip method of sodium dodecyl sulfate-polyacrylamide capillary electrophoresis non-reduced and reduced, Caliper-SDS-NR & R, respectively
  • DSC differential scanning calorimetry
  • Buffers tested included a histidine buffer (i.e., combination L-histidine and L-histidine HCl buffer), an acetate buffer, a succinate buffer, and a phosphate buffer (PB). The histidine, acetate, and succinate buffers stabilized the antibody well.
  • a histidine buffer i.e., combination L-histidine and L-histidine HCl buffer
  • PB phosphate buffer
  • the spectrometer was used to measure the absorbance in two cuvettes in parallel, and the concentration value was calculated.
  • SE-UPLC The pH meter was calibrated with three different standards (pH 4.01, 7.00, and 9.21) prior to usage. The slope of calibration was between 95.0% to 105.0%. Each sample was measured twice, and an average result was reported.
  • SE-UPLC [00350] SE-UPLC was used as a purity analysis method to separate proteins based on their sizes. Size exclusion chromatography was performed on an Agilent UPLC system with a size 161 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR exclusion chromatography (SEC) column (Waters Acquity BEH 150 ⁇ 4.6 mm, 1.7 ⁇ m).
  • the sampler temperature was set to 5 ⁇ 3 °C and the column oven temperature was set as 25 ⁇ 3 °C.
  • the mobile phase was 50 mM PB, 300 mM NaCl, pH 6.8 ⁇ 0.1; and the flow rate was set as 0.4 mL/min. 10 ⁇ g of each sample was injected. Detection wavelength was set at 280 nm and the run time was 8 min. Data was analyzed by Agilent CDS Software.
  • iCIEF [00351] iCIEF was used to monitor the distribution of charged variants.
  • the isoelectric point (pI) which is an intrinsic property of a given protein, is the pH at which the protein molecule did not carry net electrical charge.
  • Antibody samples were mixed with master mixture to generate loading mixture, which contained 4.0 ⁇ L Pharmalyte 3-10, 35 ⁇ L 1% MC, 0.5 ⁇ L pI marker 4.65, 0.5 ⁇ L pI marker 9.22, 37.5 ⁇ L 8 M urea solution, and 2.5 ⁇ L ultrapure water at a final protein concentration of 1.0 mg/mL.
  • the loading mixture was loaded into a Maurice iCIEF cartridge and analyzed with Maurice Capillary Isoelectric Focusing Analyzer with whole-column detection camera. After the analysis, the raw data were processed with Empower 3.
  • Reduced Caliper SDS (Caliper-SDS-R) was performed based on a PerkinElmer Caliper automated electrophoresis that allowed protein separation by size after reduction of 162 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR sample.
  • samples were diluted to 1 mg/mL with pure water. 2 ⁇ L of diluted samples were mixed with 7 ⁇ L of the sample denaturing solution (the mixture of sample buffer, 10% SDS solution, and 1 M dithiothreitol as a reduction agent, with the volume ratio of 100:10:4).
  • Measurements were performed on MicroCalTM VP Capillary DSC for thermal transition midpoint (Tm) and onset of unfolding (T Onset ) testing. Samples were diluted to 1 mg/mL with the reference buffer. 400 ⁇ L of respective reference buffers were added into the odd-numbered wells of a 96-well plate, and 400 ⁇ L of samples were added into the even-numbered wells of the same plate. Experimental parameters were set such that the scan temperature ramped from 10 °C to 95 °C at a scan rate of 200 °C/hour. Data analysis was performed in MicroCal VP Capillary DSC automated data analysis software.
  • a total of 12 pH/buffer systems covering the pH range from 4.5 to 7.5 were designed, including 20 mM acetate buffer (pH 4.5, pH 5.0, and pH 5.5), 20 mM succinate buffer (pH 5.0, pH 5.5, and pH 6.0), 20 mM histidine buffer (pH 5.5, pH 6.0, and pH 6.5; histidine buffers refers throughout Examples to a combination of L-histidine and L-histidine HCl), and 20 mM phosphate buffer (PB) (pH 6.5, pH 7.0, and pH 7.5).
  • the antibody was buffer-exchanged into 12 buffers, then concentrated to target protein concentration (150 mg/mL), respectively.
  • Each of the 12 solutions was filtered with a 0.22 ⁇ m polyvinylidene fluoride (PVDF) filter and filled into 2 mL glass vials (1 mL per vial), then stoppered, capped, and labeled.
  • PVDF polyvinylidene fluoride
  • Each of the twelve samples was tested for appearance, protein concentration, SE-UPLC, iCIEF, Caliper-SDS-NR & R, DSC, 163 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR and pH at Day 0. Additionally, at Day 0, after testing, the twelve samples were stored at 40 °C for up to 4 weeks.
  • Caliper-SDS-NR & R For Caliper-SDS-NR, the purity of all samples decreased with the increase of incubation time at 40 °C for up to 4 weeks (up to 22.0%). Acetate at pH 4.5 (B1), PB at pH 7.0 and 7.5 (B11 and B12, respectively) showed a faster and greater decline (> 8% by 4 weeks) than the samples in the other pH/buffer systems. Samples in the succinate and histidine buffer systems, particularly succinate at pH 6.0 (B6) and histidine at pH 5.5, 6.0, and 6.5 (B7, B8 and B9, respectively) performed relatively better.
  • T Onset values were higher than 55.0 °C in all formulations except acetate buffer at pH 4.5 (B1) and succinate buffer at pH 5.0 (B4), indicating good conformational thermal stability overall.
  • the pH/buffer studies investigated twelve pH/buffer types under stress conditions (40 °C for up to 4 weeks), and the results showed that stability of the antibody was dependent upon both the pH and buffer. Taken together, the studies herein demonstrated relatively poor protein stability in acetate at pH 4.5 and 5.0 (B1 and B2, respectively), succinate at pH 5.0 and 5.5 (B4 and B5, respectively) and all PB buffer systems (pH 6.5-7.5, B10-B12, respectively).
  • Example 2 Formulation of an Anti-IL-13 Antibody: Excipients and Surfactant Strength Studies [00365] This Example describes formulation studies of an IL-13 antibody.
  • excipients e.g., sucrose, ⁇ / ⁇ -trehalose dihydrate, and L-arginine hydrochloride (Arg-HCl), L-methionine, etc.
  • concentration of a polysorbate e.g., polysorbate 80 (PS80) at 0.02% w/v, 0.04% w/v, and 0.06% w/v
  • a poloxamer e.g., poloxamer 188 (P188) at 0.05% w/v, 0.08% w/v, and 0.10% w/v
  • stress conditions 40 °C for up to 4 weeks, agitation at 300 rpm for up to 3 days, and freeze and thaw for up to 5 cycles
  • a panel of analytical methods were used to characterize the excipients and surfactant strengths, including appearance, pH, protein concentration, SE-UPLC, Caliper-SDS-NR & R, and iCIEF (the Methods of which are described in Example 1), as well as osmolality, viscosity, and amount of sub-visible particles by micro-flow imaging (MFI), described below.
  • MFI micro-flow imaging
  • Excipient L-arginine was selected for further testing based upon data that demonstrated that it improved (decreased) viscosity.
  • Table 11 Excipients Name Vendor Cat. No. 166 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Name Vendor Cat. No. Sodium acetate trihydrate Avantor 3461-01 0 0 0 0 0 0 C 0 0 2 0 , , , , , , [00368] See Example 1.
  • Osmolality was measured using an Advanced 2020 Multi-Sample Osmometer. Before and after the tests, the testing accuracy of the osmometer was confirmed with a Clinitrol 290 mOsm/kg reference solution. The sample volume for testing was 20 ⁇ L, and only one test was performed for each sample. Viscosity [00370] A viscosity test was used to characterize the fluid properties of liquid sample. Measurements were performed by a VROC® initium one plus viscometer (Rheosense).
  • Osmolality, viscosity, and pH As shown in Table 14, the pH of all the tested formulations was reported at their target value at T0. The osmolality, which is not a stability- indicative parameter, of all samples was approximately 285 mOsm/kg to 320 mOsm/kg, which demonstrated suitability for subcutaneous administration. The viscosity of all samples was between 5.9 mPa-s to 9.3 mPa-s, where the addition of Arg-HCl (E4 and E5) reduced the viscosity compared to those of other formulations.
  • Table 14 Osmolality, pH, and Viscosity Results Osmolality H Viscosity ) 170 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR E1 (Sucrose, 0.02% PS80) 302 6.0 8.4 E2 (Sucrose Methionine 002% PS80) 295 60 82 remained relatively stable during the study.
  • Sub-visible particle Compared with T0, no substantial changes were observed in the amount of sub-visible particles ( ⁇ 2 ⁇ m, ⁇ 10 ⁇ m, or ⁇ 25 ⁇ m) after FT for 5 cycles, agitation for 3 days, or 40 °C incubation for 4 weeks in all tested formulations. By comparing samples within the same buffer system but different excipients (E1-E7), no differences of the amount of sub-visible particles were observed. Additionally, there were no obvious differences in the amount of the sub-visible particles in E1 (0.02% PS80), E8 (0.04% PS80), E9 (0.06% PS80), E10 (0.10% P188), E11 (0.08% P188), and E12 (0.05% P188).
  • SE-UPLC The data summary from the SE-UPLC testing for excipients and surfactants strength study is provided in Table 15. After freeze and thaw for 5 cycles or agitation for 3 days, the main peak % of all the test formulations remained at approximately 99.0% indicating consistent antibody freeze and thaw stability and agitation stability under the studied parameter in all studied formulations. [00381] After incubation at 40 °C for 4 weeks, the main peak % in all formulations declined by up to 2.9% compared to T0, although the differences were small. E8 and E9 (Sucrose, 0.04% and 0.06% PS80) showed slightly lower main peak levels.
  • E2 (Sucrose, Methionine, 171 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 0.02% PS80) showed the smallest changes in main peak purity and HMW species, indicating that L-methionine helped control HMW formation.
  • Table 15 SE-UPLC Results Formulation No. Stress SE-UPLC (Main peak % 3 6 3 6 3 6 172 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Formulation No. Stress SE-UPLC (Main peak % 3 6 3 6 .
  • Caliper-SDS-NR & R The data summary from the Caliper-SDS-NR & R testing for excipients and surfactants strength study is provided in Table A.
  • E1 Sudrose
  • E3 Sudrose, EDTA-2Na
  • E6 Tehalose dihydrate
  • E7 Sorbitol
  • Example 3 Formulation of an Anti-IL-13 Antibody: Viscosity and Osmolality Studies
  • This Example describes formulation studies of an IL-13 antibody.
  • a key parameter was viscosity.
  • Different excipients e.g., Arg-HCl, glycine, and proline
  • a panel of analytical methods were used to characterize the viscosity excipient studies, including appearance, MFI, protein concentration, SE-UPLC, pH, osmolality, and viscosity (the Methods of which are described in Example 1 and Example 2).
  • the formulations selected for this stage of testing included a pH of about 5.8 due to its favorable results in SE-UPLC experiments (see Example 1), a histidine buffer (or comparable acetate or succinate buffer, respectively) and L-methionine, which was demonstrated to help control HMW formation and antibody purity (see Example 2).
  • the excipient L-arginine was identified as useful for reducing viscosity.
  • Methods [00388] In brief, the IL-13 antibody was in a histidine buffer system at pH 6.0 with protein concentration at 257 mg/mL.
  • Arg-HCl was selected as a viscosity modulator, and further experiments were conducted to identify a suitable Arg-HCl concentration to enable a high protein concentration, yet reduce viscosity.
  • Arg-HCl and antibody protein concentrations that minimize viscosity and achieve osmolality in an acceptable range.
  • Analytical testing included measurement of protein concentration, pH, osmolality, and viscosity at 20 °C and 25 °C. The results are shown in Table 19 and Table 20, with Table 19 outlining the formulations used in the experiments of Table 20.
  • Formulation A 10 mM His buffer, 10 mM Met, 150 mM Arg-HCl, 0.05% PS80, pH 5.8
  • Formulation B 10 mM His buffer, 10 mM Met, 80 mM Arg-HCl, 3%(w/v) sucrose, 0.05% PS80, pH 5.8
  • Formulation C 10 mM His buffer, 10 mM Met, 120 mM Arg-HCl, 0.05% PS80, pH 5.8.
  • Table 21 Additional osmolality and viscosity experiments of the three formulations are shown in Table 21, which were used to characterize the formulations over a range of antibody protein concentration.
  • Arg-HCl was selected for inclusion in the final formulation as a viscosity modifier and L-Methionine was included in the formulation based on experiments described in Example 2, particularly the finding that L-methionine helped control HMW formation and antibody purity.
  • sucrose may be advantageous as a cryoprotectant, however it increased viscosity and osmolality. Based upon this, the inclusion of sucrose was further tested with a reduced concentration of L- arginine to compensate for the impact to osmolality in long term storage and stability studies described in Example 6 and Example 7.
  • Table 19 Formulations Tested in Further Viscosity Studies Target concentration (mg/mL) Final formulation 220 0, 0, Table 20: Further Viscosity Study Results [Arg- Target Measured pH Osmolality Viscosity Viscosity 186 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [Arg- Target Measured pH Osmolality Viscosity Viscosity HCl] conc.
  • the experiment consisted of: Run 1: 904.4 g/m 2 , Run 2: 965.8 g/m 2 , and Run 3: 971.9 g/m 2 using a Millipore, PES Type D Screen, 30 kDa membrane with 2 ⁇ 0.11 m 2 for Run 1 and 3 ⁇ 88 cm 2 for Runs 2 and 3.
  • the DF buffers tested were 15 mM His-HCl, 120 mM Arg-HCl with a pH of 5.7, 5.5, and 5.9 for Runs 1-3, respectively. The results are provided in Table 23.
  • Example 5 Formulation of an Anti-IL-13 Antibody: Injectability Study [00401]
  • This Example describes injectability studies to evaluate whether the forces required for injection would be acceptable for the formulation, as described and developed in Examples 1-4, of an IL-13 antibody.
  • the formulations selected for this stage of testing included a pH of about 5.8 due to its favorable results in SE-UPLC experiments (see Example 1), a histidine buffer (or comparable acetate or succinate buffer, respectively), L-methionine, which was demonstrated to help control HMW formation and antibody purity (see Example 2), and the excipient Arg-HCl, based on its ability to reduce viscosity (see Example 3).
  • the break-loose force and glide force method quantitatively measured the forces required to complete a prefilled syringe (PFS) injection (i.e., expel the content of the PFS).
  • PFS prefilled syringe
  • Break-loose force was defined as the force required to cause a change (from a rested position) in the plunger stopper position.
  • Glide force maximum glide force was defined as the maximum force measured on the glide force profile during the course of expelling the contents of a PFS.
  • the test was conducted with an Instron materials testing machine-34TM-5 equipped with a 2000N load cell. The load cell was selected based on the sample property (the maximum force is within the 70% of the load cell range).
  • the crosshead moved at a 140 mm/min speed to apply compressive force to the PFS plunger rod.
  • the measured compression force was recorded at 60 Hz as the content of the PFS being extruded (expelled).
  • the measurement stopped when the force reached end of test criteria where the plunger stopper hits the end of syringe barrel. Data are reported numerically in 2 decimal places (N). [00403]
  • the required amounts of material, excipient stock solutions, and surfactant stock solution were calculated, weighed, and well-mixed to prepare formulations with the target protein concentration at 220 mg/mL according to the formulation recipes listed in Table 24.
  • a panel of analytical methods were used to evaluate long-term storage conditions, the Methods of which are described in Example 1 and Example 2 and in the Potency section, below.
  • formulated antibody was used to fill either a 2R glass vial and stopper (e.g.. Schott cat no 1626151 and West cat no 1970-0173) to represent a drug product configuration or a Sartorius Celsius FFT bag to represent a drug substance configuration.
  • the vial configuration was tested at 5 °C (the intended storage temperature), 25 °C, or 40 °C, as well as for photostability under dark versus light conditions.
  • the higher temperatures and photostability conditions were intended to evaluate more stressful conditions to provide an early indication of potential degradation pathways that may occur during long term storage at the intended storage 194 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR temperature and/or manufacturing procedures.
  • the bag configuration was tested at -70 °C and for freeze thaw cycles to evaluate stability during long term storage and/or manufacturing procedures. Potency [00408]
  • the binding assay used was an enzyme-linked immunosorbent assay (ELISA).
  • IL-13 is an immunoregulatory cytokine, which regulates the function of human B cells and monocytes. In this assay, IL-13 was immobilized onto a 96-well plate.
  • WBP2546 was added and bound to the captured human IL-13.
  • the bound WBP2546 was detected by anti-human IgG (F(ab’)2 specific)-peroxidase secondary antibody.
  • 3,3',5,5' tetramethylbenzidine (TMB) substrate solution was loaded into the wells subsequently.
  • a blue color developed in proportion to the amount of bound secondary antibody. Blue color development was stopped by adding stop solution and the color changed to yellow.
  • the measured absorbance at 450 nm was subtracted from absorbance at 650 nm, producing a signal that was proportional to the concentration of the analyte in the well.
  • the vial configuration was tested at 5 °C (the intended storage temperature), 25 °C, or 40 °C as well as for photostability under dark versus light conditions, The higher temperatures and photostability conditions were intended to evaluate more stressful conditions to provide an early indication of potential degradation pathways that may occur during long term storage at the intended storage temperature and/or manufacturing procedures.
  • the bag configuration was tested at -70 °C and for freeze thaw cycles to evaluate stability during long term storage and/or manufacturing procedures. [00411] Using a fill volume of 2.7 mL per vial or bag, three formulations (F1, F2, and F3), outlined in Table 26, were tested under the various conditions.
  • the formulations selected this stage of testing included a pH of about 5.8 due to its favorable results in SE-UPLC experiments (see Example 1), a histidine buffer (or comparable acetate or succinate buffer, respectively), L-methionine, which was demonstrated to help control HMW formation and antibody purity (see Example 2), and the excipient Arg-HCl, based on its ability to reduce viscosity (see Example 3).
  • Table 26 Formulations Tested for Long-Term Storage and Stability No. Protein pH Buffer and Excipient Excipient Excipient conc.
  • surfactant 1 2 3 pH, appearance, sub-visible particles (MFI), protein concentration, SE-UPLC, iCIEF, and CE-SDS, were evaluated for the vial configuration using the Materials and Methods described throughout Examples 1-2 after 1 month of storage at 5 °C, 25 °C, or 40 °C, photostability under dark and light conditions. Storage at -70 °C and free/thaw stability was evaluated for the bag configuration. [00413] The T0 antibody, histidine, and L-arginine concentrations, osmolality, and viscosity data are presented in Table 27. Table 27: Concentrations, Osmolality, and Viscosity Results No.
  • the decreased purity may be caused by aggregates instead of fragments.
  • No substantial decreases were observed for dark control samples stored at 25°C for 7 days and 14 days (two weeks). No substantial difference between F1, F2, and F3 were observed after 1000 lux light exposure for 7 days (1 week) and 14 days (2 weeks).
  • F2, stored at -70 °C for 1 month (1M) a substantial increase in ⁇ 2 ⁇ m was observed in sub-visible particles results (Table 30).
  • F1, F2, and F3, stored at -70 °C for 1 month no substantial changes were observed in SEC/Caliper/iCIEF/PS80 test results (Table 30).
  • Example 7 12-Month Stability Study of Three Formulations
  • three formulations were tested for stability under various conditions over a 12-month period.
  • the tested formulations are shown in Table 32, referred to as F1, F2 and F3, with the control formulation referred to as F4.
  • the anti-IL-13 antibody (protein) used in this example was Construct 133.
  • Table 32 Formulations Tested Protein pH Buffer and Excipient Excipient Excipient Formulation Conc.
  • Surfactant 1 2 3 - Samples were prepared to a fill-volume of 2.7 ml/vial or 4 ml/bag. The study plan for the various conditions tested, and the sampling schedule, are shown in Table 33.
  • the quality aspects set forth in Table 33 were tested as described in previous examples. The results for the stability data at 5°C, 25°C, 40°C and -70°C storage conditions are shown in Table 34, Table 35, Table 36 and Table 37, respectively.
  • Example 8 Investigation of PS80 Degradation In the stability studies described in Example 7, degradation of PS80 was observed in certain samples under certain conditions. Accordingly, studies were performed to identify the mechanism(s) of PS80 degradation. In one study, formulation buffers were formulated with different lots of raw materials and a metal ion chelator (EDTA-2Na) was added to certain formulations, along with increasing the concentration of PS80 in certain formulations. The formulations tested in the study are shown in Table 40.
  • EDTA-2Na metal ion chelator
  • Table 40 Formulations Tested in Metal Ion Chelator Study , Attorney Docket No.: AOE-003PR 10 mM L-His/L-His-HCl, 120 mM L-Arg-HCl, 10 mM L-Met, F03 , y p p p y levels of iron (Fe), cobalt (Co), nickel (Ni), copper (Cu) and zinc (Zn) in the formulations.
  • the concentration of PS80 was also measured in the formulations at T0 and after storage at 25°C for defined periods of time (1 week, 2 weeks, 1 month). The results of the metal ion chelator study are summarized in Table 41.
  • Table 41 Metal Ion Chelator Study Results Comment Analysis Result Fe C ( /L) Ni ( /L) C ( /L) Zn ( /L) (PS80 # Attorney Docket No.: AOE-003PR 25C-1M: 0.021% Additional investigational studies were performed to evaluate the impact on PS80 degradation of clone material, formulation buffers, water, PS80 lots and the material of construction of vials (glass vs. polymer). Representative results are shown in Table 42.
  • Example 9 Formulations to Counteract PS80 Degradation
  • a panel of formulations was prepared that included either PS80 or P188 as surfactant. Additionally, a metal ion chelator was included in some formulations and omitted from others. The formulations were tested for various quality parameters, as described in previous examples. Table 43 shows results for surfactant stability (%) over time at the indicated temperatures. Table 44 and Table 45 show the SE-UPLC results over time at 25°C and 5°C, respectively. Table 46 and Table 47 show the iCIEF results over time at 25°C and 5°C, respectively.
  • Example 10 Determination of Minimum Effective Amount of PS80 to Protect Against Mechanical Shear Stress This example describes a study to establish a minimum PS80 concentration that can protect the formulation against mechanical stress induced by agitation (e.g., during shipping).
  • Formulations having PS80 concentrations of 0, 0.0005, 0.003, 0.005, 0.01, 0.03, 0.05 % (w/v) were evaluated for their resistance against agitation at 300 rpm for 3 days. Tested formulations are shown in Table 51. Table 51: Formulations with Varying PS80 Concentrations Attorney Docket No.: AOE-003PR No. Protein conc. pH/buffer Excipients Surfactant The study plan is summarized in Table 52. The formulations were tested for various quality parameters, as described in previous examples. Table 52: Study Plan Attorney Docket No.: AOE-003PR The results for sub-visible particles (MFI), SE-UPLC, iCIEF and CE-SDS are shown in Table 53, Table 54, Table 55 and Table 56, respectively.
  • MFI sub-visible particles
  • Example 11 Compatibility Studies with Glass Pre-Filled Syringes and Rubber Plunger Stoppers
  • PFS pre-filled syringe
  • C and D the syringes and plunger stoppers.
  • a and B two different plunger stoppers from two different manufacturers
  • FIG. 8 Table 57 Attorney Docket No.: AOE-003PR summarizes the overall assessment of visual appearance, turbidity, concentration, subvisible particles, pH, PS80, SEC, iCIEF, CE-SDS-NR/R, and ELISA for the samples.
  • the formulations tested were: (1) 180 mg/mL IL-13 antibody, L-10 mM His/L-His-HCl, 120 mM L-Arg-HCl, 10 mM L-Met, 0.05 mM EDTA, 0.05% PS80, pH 6.0; and (2) 180 mg/mL IL-13 antibody, 10 mM L-His/L-His-HCl, 120 mM L-Arg-HCl, 10 mM L-Met, 0.5 mg/mL P188, pH 6.0
  • Formulations were tested for various quality parameters over time and at various temperatures as described in the previous examples according to the study plan set forth in Table 58.
  • Tg viscosity, pH, osmolality and excipient concentration at time zero (T0) are shown in Table 59.
  • the 5°C data is summarized in Table 60.
  • the 25°C data is summarized in Table 61.
  • the 40°C data is summarized in Table 62.
  • the data for agitation is summarized in Table 63.
  • the -70°C data is summarized in Table 64.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

Described herein are pharmaceutical formulations of interleukin (IL)- 13 antibodies. Also provided are pharmaceutical formulations for use in the treatment of an inflammatory disorder or disease.

Description

Attorney Docket No.: AOJ-017PC AOE-003WO PHARMACEUTICAL FORMULATIONS OF ANTIBODIES THAT BIND INTERLEUKIN 13 Related Applications [0001] This application claims priority to, and the benefit to U.S. Provisional Application Patent No.63/612,892, filed December 20, 2023, the entire disclosure of which is hereby incorporated by reference in its entirety for all purposes. Background [0002] The interleukin (IL)-13 is a T helper cell subclass 2 (Th2) cytokine, and belongs to the family of type I cytokines. However, IL-13 is involved in the differentiation of naïve T cells into Th2 cells. IL-13 promotes B-cell proliferation and induces class switching to IgG4 and IgE in combination with CD40/CD40L co-stimulation (IL-13 up-regulates FcεRI and thus helps in IgE priming of mast cells). In monocytes/macrophages, IL-13 up-regulates expression of CD23 and MHC class I and class II antigens; down-regulates the expression of CD14; inhibits antibody-dependent cytotoxicity IL-13; and promotes eosinophil survival, activation, and recruitment. IL-13 also manifests important functions on nonhematopoietic cells, such as smooth muscle cells, epithelial cells, endothelial cells, and fibroblast cells. IL- 13 enhances proliferation and cholinergic-induced contractions of smooth muscles. In epithelial cells, IL-13 potently induces chemokine production, alters mucociliary differentiation, decreases ciliary beat frequency of ciliated epithelial cells, and results in goblet cell metaplasia. In endothelial cells, IL-13 is a potent inducer of vascular cell adhesion molecule 1 (VCAM-1), which is important for recruitment of eosinophils. In human dermal fibroblasts, IL-13 induces type 1 collagen synthesis in human dermal fibroblasts. [0003] The inhibition of IL-13 may be used to treat or prevent inflammatory diseases and conditions, such as those related to elevated levels of IgE, including but not limited to: asthma, allergic rhinitis, urticaria, asthma, allergic rhinitis, urticaria, and allergic or atopic dermatitis. Thus, the development of potent and specific inhibitors of IL-13, for example, inhibitors that remain active for longer terms when administered to subjects, are needed for the prevention and/or treatment of IL-13 and IgE-mediated diseases or conditions. Furthermore, formulations comprising IL-13 antibodies sufficiently stable and suitable for administration to patients remains an unmet need. Attorney Docket No.: AOJ-017PC AOE-003WO Summary [0004] In certain aspects, described herein is a formulation comprising: (a) an interleukin 13 (IL-13) antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0. In embodiments, the formulation further comprises a metal ion chelator, such as EDTA or a salt thereof (e.g., EDTA-2Na). [0005] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0, and wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [0006] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID Attorney Docket No.: AOJ-017PC AOE-003WO NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and (f) CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. [0007] In other embodiments, the formulation comprises: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises the sequence set forth in SEQ ID NO: 58 or 67; b. CDR-H2 comprises the sequence set forth in SEQ ID NO: 100 or 104; c. CDR-H3 comprises the sequence set forth in SEQ ID NO: 112; d. CDR-L1 comprises the sequence set forth in SEQ ID NO: 141 or 149; e. CDR-L2 comprises the sequence set forth in SEQ ID NO: 153 or 596; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. [0008] In embodiments, the formulation further comprises a metal ion chelator. In embodiments, the metal ion chelator is EDTA or salt thereof. Other metal ion chelators are described herein. Attorney Docket No.: AOJ-017PC AOE-003WO [0009] In embodiments, the IL-13 antibody comprises a means for extending the half-life of the IL-13 antibody. In embodiments, the means comprises at least one amino acid modification in the IL-13 antibody, as described further herein. [0010] In certain embodiments, the formulation further comprises: (e) a sugar or sugar alcohol. [0011] In certain embodiments, the IL-13 antibody is at a concentration between 160 mg/mL and 250 mg/mL. In certain embodiments, the IL-13 antibody is at a concentration of about 180 mg/mL. In certain embodiments, the IL-13 antibody is at a concentration of about 200 mg/mL. In certain embodiments, the antibody is at a concentration of about 160-200 mg/mL. [0012] In certain embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 5 mM and 20 mM. In certain embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 10 mM. [0013] In certain embodiments, the histidine buffer comprises a histidine and a histidine salt. In certain embodiments, the histidine is L-histidine. In certain embodiments, the histidine salt is L-histidine HCl monohydrate. [0014] In certain embodiments, the formulation comprises methionine, and wherein the methionine is L-methionine. In certain embodiments, the L-methionine is at a concentration between 1 mM and 20 mM. In certain embodiments, the L-methionine is at a concentration of about 10 mM. [0015] In certain embodiments, the formulation comprises arginine, and wherein the arginine is L-arginine. In certain embodiments, the formulation comprises an L-arginine salt solution. In certain embodiments, the L-arginine salt solution salt solution comprises HCl monohydrate. In certain embodiments, wherein the L-arginine salt solution is at a concentration between 40 mM and 250 mM. In certain embodiments, the L-arginine salt solution is at a concentration of about 80 mM. In certain embodiments, the L-arginine salt solution is at a concentration of about 120 mM. [0016] In certain embodiments, the formulation further comprises a surfactant. [0017] In certain embodiments, the formulation comprises a polysorbate. In certain embodiments the polysorbate is at a concentration between 0.005% w/v and 0.15% w/v, e.g., 0.01% w/v-0.10% w/v. In certain embodiments, the polysorbate is at a concentration of about 0.05% w/v. In certain embodiments, the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In certain embodiments, the polysorbate is polysorbate 80. Attorney Docket No.: AOJ-017PC AOE-003WO In certain embodiments, polysorbate 80 is at a concentration of about 0.05% w/v or at 0.05% w/v. [0018] In certain embodiments, the formulation comprises a poloxamer. In certain embodiments, the poloxamer is poloxamer 188. In certain embodiments, poloxamer 188 is at a concentration between 0.5-1.0 mg/ml. [0019] In certain embodiments, the pH is between 5.5 and 7.0. In certain embodiments, the pH is between 5.6 and 5.9. In certain embodiments, the pH is about 5.8. In certain embodiments, the pH is between 5.5 and 6.5, such as at about 6.0. In certain embodiments, the pH is 5.8. In certain embodiments, the pH is 6.0. [0020] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [0021] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L- histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 80 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [0022] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody present at a concentration of about 200 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L- histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [0023] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody at a concentration of about 180-200 mg/mL (e.g., at 180 mg/mL or 200 mg/mL); (b) a histidine buffer at a concentration of about 10 mM (e.g., at 10 mM), wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); (e) polysorbate 80 at a concentration of about 0.05% w/v Attorney Docket No.: AOJ-017PC AOE-003WO (e.g., at 0.05% polysorbate 80), (f) EDTA or a salt thereof (e.g., EDTA-2Na) at a concentration of about 0.05 mM (e.g., at 0.05 mM), at pH of about 5.8-6.0 (e.g., at a pH of 5.8 or a pH of 6.0). [0024] In certain aspects, described herein is a formulation comprising: (a) an IL-13 antibody at a concentration of about 180-200 mg/mL (e.g., at 180 mg/mL or 200 mg/mL); (b) a histidine buffer at a concentration of about 10 mM (e.g., at 10 mM), wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); and (e) poloxamer 188 at a concentration of about 0.5 mg/ml (e.g., at 0.5 mg/ml), at pH of about 5.8-6.0 (e.g., at a pH of 5.8 or a pH of 6.0). [0025] In certain embodiments, the formulation further comprises: (f) a sugar or sugar alcohol. In certain embodiments, the sugar or sugar alcohol is at a concentration between 1% w/v and 8% w/v. In certain embodiments, the sugar or sugar alcohol is at a concentration of about 3% w/v. In certain embodiments, the sugar or sugar alcohol is a disaccharide. In certain embodiments, the disaccharide is sucrose. [0026] In certain embodiments, the IL-13 antibody comprises: (a) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR- H3; and (b) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (i) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (ii) CDR- H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; (iii) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (iv) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, (v) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and (vi) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [0027] In certain embodiments, the (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ Attorney Docket No.: AOJ-017PC AOE-003WO ID NO: 141 and SEQ ID NO: 149, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and (f) CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. [0028] In certain embodiments, the IL-13 antibody comprises: (a) CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-66; (b) CDR- H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-103; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [0029] In certain embodiments, the IL-13 antibody comprises: (a) CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 67-83; (b) CDR- H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 104-107; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [0030] In certain embodiments, the IL-13 antibody comprises: (a) CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 84-99 and 121; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 108-111; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 130-140, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 149-152, (e) CDR-L2 comprises the amino acid sequence LAS; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [0031] In certain embodiments, the IL-13 antibody does not comprise: (a) CDR-H1 set forth in SEQ ID NO: 58; CDR-H2 set forth in SEQ ID NO: 100; CDR-H3 set forth in SEQ ID NO: 112; CDR-L1 set forth in SEQ ID NO: 141; CDR-L2 set forth in SEQ ID NO: 153; and CDR-L3 set forth in SEQ ID NO: 165; or (b) CDR-H1 set forth in SEQ ID NO: 67; CDR-H2 set forth in SEQ ID NO: 104; CDR-H3 set forth in SEQ ID NO: 112; CDR-L1 set forth in SEQ ID NO: 141; CDR-L2 set forth in SEQ ID NO: 153; and CDR-L3 set forth in Attorney Docket No.: AOJ-017PC AOE-003WO SEQ ID NO: 165; or (c) CDR-H1 set forth in SEQ ID NO: 84; CDR-H2 set forth in SEQ ID NO: 108; CDR-H3 set forth in SEQ ID NO: 130; CDR-L1 set forth in SEQ ID NO: 149; CDR-L2 set forth in the amino acid sequence LAS; and CDR-L3 set forth in SEQ ID NO: 165. [0032] In certain embodiments, the IL-13 antibody does not comprise any combination of: (a) a CDR-H1 set forth in any of SEQ ID NOs: 58, 67, or 84; (b) a CDR-H2 set forth in any of SEQ ID NOs: 100, 104, or 108; (c) a CDR-H3 set forth in any of SEQ ID NOs: 112 or 130; (d) a CDR-L1 set forth in any of SEQ ID NOs: 141 or 149; (e) a CDR-L2 set forth in any of SEQ ID NOs: 153 or 154; and (f) a CDR-L3 set forth in SEQ ID NO: 165. [0033] In certain embodiments, the IL-13 antibody comprises a VH sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NOs: 1-32. [0034] In certain embodiments, the IL-13 antibody comprises a VL sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NOs: 33-57. [0035] In certain embodiments, the IL-13 antibody comprises a VH sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NOs: 1-32 and a VL sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in of SEQ ID NOs: 33-57. [0036] The formulation of any one of the above claims, wherein the IL-13 antibody comprises a VH comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NO: 39. [0037] In certain embodiments, the IL-13 antibody comprises a VH sequence selected from the sequences set forth in any one of SEQ ID NOs: 1-32. [0038] In certain embodiments, the IL-13 antibody comprises a VL sequence selected from the sequences set forth in any one of SEQ ID NOs: 33-57. [0039] In certain embodiments, the IL-13 antibody comprises a VH sequence selected from the sequences set forth in any one of SEQ ID NOs: 1-32 and a VL sequence selected from the sequences set forth in any one of SEQ ID NOs: 33-57. Attorney Docket No.: AOJ-017PC AOE-003WO [0040] In certain embodiments, the IL-13 antibody comprises a VH comprising an amino acid sequence as set forth in SEQ ID NO: 3 and a VL comprising an amino acid sequence as set forth in SEQ ID NO: 39. [0041] In certain embodiments, the isolated antibody comprises a HCDR1 comprising SEQ ID NO: 58, a HCDR2 comprising SEQ ID NO: 100, a HCDR3 comprising SEQ ID NO: 112, a LCDR1 comprising SEQ ID NO: 141, a LCDR2 comprising SEQ ID NO: 153, and a LCDR3 comprising SEQ ID NO: 165. In certain embodiments, the isolated antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO:3. In certain embodiments, the isolated antibody comprises a VL comprising an amino acid sequence set forth in SEQ ID NO:39. In certain embodiments, the isolated antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO:3 and a VL comprising an amino acid sequence set forth in SEQ ID NO:39. In certain embodiments, the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439. In certain embodiments, the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 624. In certain embodiments, the isolated antibody comprises a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. In certain embodiments, the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. [0042] In certain embodiments, the isolated antibody comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of Construct 133. In certain embodiments, the isolated antibody comprises the VH of Construct 133. In certain embodiments, the isolated antibody comprises the VL of Construct 133. In certain embodiments, the isolated antibody comprises the VH and VL of Construct 133. In certain embodiments, the isolated antibody comprises the heavy chain constant (HC) region of Construct 133. In certain embodiments, the isolated antibody comprises the constant light chain (LC) region of Construct 133. In certain embodiments, the isolated antibody comprises the heavy chain constant (HC) region and constant light chain (LC) region of Construct 133. [0043] In certain embodiments, the isolated antibody comprises Construct 133, i.e., comprising a HCDR1 comprising SEQ ID NO: 58, a HCDR2 comprising SEQ ID NO: 100, a HCDR3 comprising SEQ ID NO: 112, a LCDR1 comprising SEQ ID NO: 141, a LCDR2 comprising SEQ ID NO: 153, a LCDR3 comprising SEQ ID NO: 165, a VH comprising SEQ Attorney Docket No.: AOJ-017PC AOE-003WO ID NO:3, a VL comprising SEQ ID NO:39, a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. [0044] In certain embodiments, the IL-13 antibody is a humanized, human, or chimeric antibody. In certain embodiments, the IL-13 antibody is a humanized antibody. [0045] In certain embodiments, the IL-13 antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. In certain embodiments, the IL-13 antibody comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. [0046] In certain embodiments, the human Fc region comprises a human IgG1 Fc. In certain embodiments, the human Fc region comprises a human IgG4 Fc. In certain embodiments, the human Fc region comprises a human IgG2 Fc. [0047] In certain embodiments, the IL-13 antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the sequences set forth in any one of SEQ ID NOs: 425-468, 484-539, and 610-709. In certain embodiments, the IL-13 antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the sequences set forth in any one of SEQ ID NOs: 610, 615-641, and 654-709 [0048] In certain embodiments, the IL-13 antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a change in antibody half-life, ADCC activity, ADCP activity, or CDC activity as compared to an otherwise equivalent antibody comprising an Fc without the one or more substitutions. [0049] In certain embodiments, the IL-13 antibody comprises an Fc region, and wherein the Fc region binds to Neonatal Fc receptor (FcRn). [0050] In certain embodiments, the IL-13 antibody is a monoclonal antibody. [0051] In certain embodiments, the IL-13 antibody binds an IL-13 sequence selected from a sequence set forth in any one of SEQ ID NOs: 472-475. [0052] In certain embodiments, the IL-13 antibody does not have a heavy chain variable region sequence set forth in SEQ ID NO: 470. [0053] In certain embodiments, a formulation of the disclosure can be filtered, such as by Ultrafiltration and Diafiltration (UFDF). [0054] In certain aspects, described herein is a vial, bag, bottle or on-body delivery device comprising the formulation of any one of the above-described aspects and Attorney Docket No.: AOJ-017PC AOE-003WO embodiments. In certain embodiments, the vial is a prefilled syringe. In certain embodiments, the vial is a glass syringe. In certain embodiments, the vial is a prefilled glass syringe. In certain embodiments, the vial is an autoinjector. In certain embodiments, the vial is an injector cartridge. In certain embodiments, the vial is a pre-filled autoinjector cartridge. In certain embodiments, an extractable volume of the vial is between 1.0 mL and 3.0 mL. In certain embodiments, the extractable volume of the vial is about 2.0 mL. In certain embodiments, an extractable volume of the vial is between 3.0 mL and 10.0 mL, e.g., 5.0 mL. In certain embodiments, the vial has an extractable volume between 1.0 mL and 10.0 mL, such as about 3.0-5.0 mL. [0055] In certain aspects, described herein is a composition comprising the formulation, vial of any one of the above-described aspects and embodiments for use in the treatment of an inflammatory disorder or disease. [0056] In certain embodiments, any one of the above-described aspects and embodiments are for use in the treatment of atopic dermatitis. In certain embodiments, the treatment reduces disease severity in a subject, and wherein disease severity is assessed by an Atopic Dermatitis Disease Severity Outcome Measure. [0057] In certain embodiments, any one of the above described aspects and embodiments are for use in the treatment of an inflammatory disorder or disease selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic Bronchopulmonary Aspergillosis (ABPA), and Chronic Obstructive Pulmonary Disease (COPD). [0058] In certain aspects, described herein is a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation vial of any one of the above-described aspects and embodiments. Attorney Docket No.: AOJ-017PC AOE-003WO [0059] In certain embodiments, the inflammatory disorder or disease is atopic dermatitis. In certain embodiments, the inflammatory disorder or disease is selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic Bronchopulmonary Aspergillosis (ABPA), and Chronic Obstructive Pulmonary Disease (COPD). [0060] In certain aspects, described herein is a method for treating a pathology associated with elevated levels of IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation or vial of any one of the above-described aspects and embodiments. [0061] In certain aspects, described herein is a diafiltration buffer comprising: (a) a histidine buffer; and (b) arginine or a salt solution thereof, at pH of from 5.4 to 7.0., e.g., from 5.5 to 6.5 or from 5.8 to 6.8. [0062] In certain embodiments, the histidine buffer comprises a histidine and a histidine salt. In certain embodiments, the histidine is L-histidine. In certain embodiments, the histidine salt is L-histidine HCl monohydrate. [0063] In certain embodiments, the formulation comprises arginine, and wherein the arginine is L-arginine. In certain embodiments, the formulation comprises an L-arginine salt solution. In certain embodiments, the L-arginine salt solution salt solution comprises HCl monohydrate. In certain embodiments, the L-arginine salt solution is at a concentration between 40 mM and 200 mM. In certain embodiments, the L-arginine salt solution is at a concentration of about 50 mM. In certain embodiments, the L-arginine salt solution is at a concentration of about 100 mM. In certain embodiments, the L-arginine salt solution is at a concentration of about 120 mM. [0064] In certain embodiments, the pH is from about 5.7 to about 7.0., such as from about 5.5 to about 6.5. In certain embodiments, the pH is about 5.8. In certain embodiments, the Attorney Docket No.: AOJ-017PC AOE-003WO pH is 5.8. In certain embodiments, the pH is about 6.0. In certain embodiments, the pH is 6.0. [0065] In certain aspects, described herein is a method of manufacturing an intermediate preparation of an interleukin 13 (IL-13) antibody comprising: (a) obtaining a purified preparation of the IL-13 antibody; and (b) adjusting the matrix of the purified preparation of step (a), wherein adjusting the matrix of the purified preparation comprises performing Ultrafiltration and Diafiltration (UFDF) with the diafiltration buffer of the above described aspect or any one of the embodiments thereof, thereby obtaining the intermediate preparation of the IL-13 antibody. [0066] In certain embodiments, the intermediate preparation of the IL-13 antibody has a higher concentration of the IL-13 antibody relative to the purified preparation. [0067] In certain embodiments, the method of manufacturing further comprises: (c) formulating the intermediate preparation to obtain a formulation of the IL-13 antibody. In certain embodiments, the formulation of the IL-13 antibody comprises the formulation of any one of the above-described aspects or embodiments. [0068] In certain other embodiments, the formulation comprises: (a) an interleukin 13 (IL-13) antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; (d) a polysorbate or a poloxamer; and (e) a metal ion chelator, wherein the formulation is at pH 5.0 to 7.0. [0069] In certain other embodiments, the formulation comprises: (a) an interleukin 13 (IL-13) antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; (e) polysorbate 80 at a concentration of about 0.05% w/v; and (f) EDTA or salt thereof at a concentration of about 0.05 mM, wherein the formulation is at a pH of about 6.0 Attorney Docket No.: AOJ-017PC AOE-003WO [0070] In certain other embodiments, the formulation comprises: (a) an interleukin 13 (IL-13) antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a poloxamer; wherein the formulation is at pH 5.0 to 7.0. [0071] In certain other embodiments, the formulation comprises: (a) an interleukin 13 (IL-13) antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) poloxamer 188 at a concentration of about 0.5 mg/ml; wherein the formulation is at a pH of about 6.0. In certain embodiments of the formulations, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. Attorney Docket No.: AOJ-017PC AOE-003WO In certain embodiments of the formulations, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. In other embodiments of the formulation, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a.CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. Attorney Docket No.: AOJ-017PC AOE-003WO In other embodiments of the formulation, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises the sequence set forth in SEQ ID NO: 58 or 67; b. CDR-H2 comprises the sequence set forth in SEQ ID NO: 100 or 104; c. CDR-H3 comprises the sequence set forth in SEQ ID NO: 112; d. CDR-L1 comprises the sequence set forth in SEQ ID NO: 141 or 149; e. CDR-L2 comprises the sequence set forth in SEQ ID NO: 153 or 596; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. In embodiments, the IL-13 antibody comprises a means for extending the half-life of the IL-13 antibody. In embodiments, the means comprises at least one amino acid modification in the IL-13 antibody, as described further herein. In embodiments, the formulation further comprises a sugar or sugar alcohol. Brief Description of the Drawings [0072] These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, and accompanying drawings, where: [0073] FIG.1 is a graph depicting the viscosity in centipoise (cP) of a formulation of an interleukin 13 (IL-13) antibody (200 mg/mL, except where indicated), when stored at 20 °C (light grey) or 25 °C (dark gray). Abbreviations: His, histidine buffer (i.e., combination L- histidine and L-histidine HCl buffer); Su, sucrose; Met, L-Methionine; R. HCl, L-Arginine- HCl (Arg-HCl); Pro, L-proline; Gly, glycine. [0074] FIG.2 is a graph depicting the average gliding force in Newtons (N) (y-axis) at room temperature of a formulation with varied concentrations of an IL-13 antibody (x-axis) and including 150 mM Arg-HCl, 80 mM Arg-HCl and 3% w/v sucrose, or 120 mM Arg-HCl injected through a pre-filled syringe (PFS). All three formulations had 10 mM histidine buffer (i.e., combination L-histidine and L-histidine HCl buffer), 10 mM L-methionine, 0.05% polysorbate 80, at a pH of 5.8. Attorney Docket No.: AOJ-017PC AOE-003WO [0075] FIG.3A-3B show bar graphs of the levels of subvisible particles equal to or greater than 2µm (FIG.3A) or 10 µm (FIG.3B) in samples tested with different syringes and plungers. [0076] FIG.4A-4B show bar graphs of pH (FIG.4A) and PS80 stability (FIG. 4B) in samples tested with different combinations of syringes (C and D) and plungers (A and B). [0077] FIG.5 shows bar graphs of SEC results for samples tested with different combinations of syringes (C and D) and plungers (A and B), wherein the data has been normalized to 100% at T=0. [0078] FIG.6 shows bar graphs of iCIEF results for samples tested with different combinations of syringes (C and D) and plungers (A and B), wherein the data has been normalized to 100% at T=0. [0079] FIG.7A-7B show bar graphs of CE-SDS-NR (FIG.7A) and CE-SDS-R (FIG.7B) results in samples tested with different combinations of syringes (C and D) and plungers (A and B). [0080] FIG.8 shows a bar graph of ELISA results for container closure compatibility for samples tested with different combinations of syringes (C and D) and plungers (A and B). Detailed Description Definitions [0081] Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodologies by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 4th ed. (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer-defined protocols and conditions unless otherwise noted. Attorney Docket No.: AOJ-017PC AOE-003WO [0082] As used herein, the singular form “a,” “an,” and “the” includes plural references unless indicated otherwise. [0083] It is understood that aspects and embodiments of the invention described herein include “comprising,” “consisting,” and “consisting essentially of” aspects and embodiments. [0084] For all compositions described herein, and all methods using a composition described herein, the compositions can either comprise the listed components or steps, or can “consist essentially of” the listed components or steps. When a composition is described as “consisting essentially of” the listed components, the composition contains the components listed, and may contain other components which do not substantially affect the condition being treated, but do not contain any other components which substantially affect the condition being treated other than those components expressly listed; or, if the composition does contain extra components other than those listed which substantially affect the condition being treated, the composition does not contain a sufficient concentration or amount of the extra components to substantially affect the condition being treated. When a method is described as “consisting essentially of” the listed steps, the method contains the steps listed, and may contain other steps that do not substantially affect the condition being treated, but the method does not contain any other steps which substantially affect the condition being treated other than those steps expressly listed. As a non-limiting specific example, when a composition is described as ‘consisting essentially of’ a component, the composition may additionally contain any amount of pharmaceutically acceptable carriers, vehicles, or diluents and other such components which do not substantially affect the condition being treated. [0085] An “effective amount” or “therapeutically effective amount” as used herein refers to an amount of therapeutic compound, such as an IL-13 antibody, administered to an individual, either as a single dose or as part of a series of doses, which is effective to produce or contribute to a desired therapeutic effect, either alone or in combination with another therapeutic modality. Examples of a desired therapeutic effect is enhancing an immune response, slowing or delaying tumor development; stabilization of disease; amelioration of one or more symptoms. An effective amount may be given in one or more dosages. [0086] The term “treating” (and variations thereof such as “treat” or “treatment”) refers to clinical intervention in an attempt to alter the natural course of a disease or condition in a subject in need thereof. Treatment can be performed during the course of clinical pathology. Desirable effects of treatment include preventing recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, Attorney Docket No.: AOJ-017PC AOE-003WO preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. [0087] The term “sufficient amount” means an amount sufficient to produce a desired effect, e.g., an amount sufficient to modulate an immune response in a subject. [0088] As used herein, the terms “subject”, “patient”, and “individual” are used interchangeably herein. The term “subject”, “patient”, or “individual” means a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, and sheep. In certain embodiments, the subject is a human. In certain embodiments the subject has a disease or condition that can be treated with an antibody provided herein. [0089] The term “pharmaceutical composition” refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective in treating a subject, and which contains no additional components which are unacceptably toxic to the subject in the amounts provided in the pharmaceutical composition. [0090] The terms “modulate” and “modulation” refer to reducing or inhibiting or, alternatively, activating or increasing, a recited variable. [0091] The terms “increase” and “activate” refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable. [0092] The terms “reduce” and “inhibit” refer to a decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable. [0093] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, where applicable, the term “about” indicates the designated value(s) ± one standard deviation of that value(s). [0094] For any of the structural and functional characteristics described herein, methods of determining these characteristics are known in the art. [0095] The term “optionally” is meant, when used sequentially, to include from one to all of the enumerated combinations and contemplates all sub-combinations. [0096] The term “amino acid” refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), Attorney Docket No.: AOJ-017PC AOE-003WO glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V). As used herein, an amino acid described herein may refer to its L-isomer form. For example, methionine may refer to L-methionine, proline may refer to L-proline, and arginine may refer to L-arginine. [0097] The term “affinity” refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or epitope). Unless indicated otherwise, as used herein, “affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen or epitope). [0098] The term “kd” (sec-1), as used herein, refers to the dissociation rate constant of a particular antibody - antigen interaction. This value is also referred to as the koff value. [0099] The term “ka” (M-1×sec-1), as used herein, refers to the association rate constant of a particular antibody -antigen interaction. This value is also referred to as the kon value. [00100] The term “KD” (M), as used herein, refers to the dissociation equilibrium constant of a particular antibody -antigen interaction. KD = kd/ka. In certain embodiments, the affinity of an antibody is described in terms of the KD for an interaction between such antibody and its antigen. For clarity, as known in the art, a smaller KD value indicates a higher affinity interaction, while a larger KD value indicates a lower affinity interaction. [00101] The term “KA” (M-1), as used herein, refers to the association equilibrium constant of a particular antibody-antigen interaction. KA = ka/kd. [00102] The term “antibody” is used herein in its broadest sense and includes certain types of immunoglobulin molecules comprising one or more antigen-binding domains that specifically bind to an antigen or epitope. An antibody specifically includes intact antibodies (e.g., intact immunoglobulins), antibody fragments, and multi-specific antibodies. [00103] A “anti-IL-13 antibody,” “IL-13 antibody,” or “IL-13 specific antibody” is an antibody, as provided herein, which specifically binds to the antigen IL-13. [00104] The term “epitope” means a portion of an antigen that specifically binds to an antibody. [00105] The term “hypervariable region” or “HVR,” as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and/or form structurally defined loops (“hypervariable loops”). Attorney Docket No.: AOJ-017PC AOE-003WO [00106] The term “antigen-binding domain” means the portion of an antibody that is capable of specifically binding to an antigen or epitope. [00107] The term “chimeric antibody” refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species. [00108] The term “human antibody” refers to an antibody which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies. [00109] The term “humanized antibody” refers to a protein having a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject. [00110] The term “multispecific antibody” refers to an antibody that comprises two or more different antigen-binding domains that collectively specifically bind two or more different epitopes. [00111] A “monospecific antibody” is an antibody that comprises one or more binding sites that specifically bind to a single epitope. An example of a monospecific antibody is a naturally occurring IgG molecule which, while divalent (i.e., having two antigen-binding domains), recognizes the same epitope at each of the two antigen-binding domains. The binding specificity may be present in any suitable valency. [00112] The term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for Attorney Docket No.: AOJ-017PC AOE-003WO example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject. [00113] The term “single-chain” refers to a molecule comprising amino acid monomers linearly linked by peptide bonds. In a particular such embodiment, the C-terminus of the Fab light chain is connected to the N-terminus of the Fab heavy chain in the single-chain Fab molecule. As described in more detail herein, an scFv has a variable domain of light chain (VL) connected from its C-terminus to the N-terminal end of a variable domain of heavy chain (VH) by a polypeptide chain. Alternately the scFv comprises of polypeptide chain where in the C-terminal end of the VH is connected to the N-terminal end of VL by a polypeptide chain. [00114] The “Fab fragment” (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CH1) of the heavy chain along with the variable domains VL and VH on the light and heavy chains respectively. The variable domains comprise the complementarity determining loops (CDR, also referred to as hypervariable region) that are involved in antigen-binding. Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. [00115] “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds. F(ab’)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab’) fragments can be dissociated, for example, by treatment with ß-mercaptoethanol. [00116] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain. [00117] “Single-chain Fv” or “sFv” or “scFv” includes the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. In one embodiment, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding. For a review of scFv see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenburg and Moore eds., Springer-Verlag, New York, pp.269-315 (1994). HER2 antibody scFv fragments are described in WO93/16185; U.S. Pat. No.5,571,894; and U.S. Pat. No. 5,587,458. [00118] “scFv-Fc” fragments comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminal of the scFv. The Fc domain may follow the VH Attorney Docket No.: AOJ-017PC AOE-003WO or VL, depending on the orientation of the variable domains in the scFv (i.e., VH -VL or VL - VH). Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain comprises an IgG4 Fc domain. [00119] The term “single domain antibody” or “sdAb” refers to a molecule in which one variable domain of an antibody specifically binds to an antigen without the presence of the other variable domain. Single domain antibodies, and fragments thereof, are described in Arabi Ghahroudi et al., FEBS Letters, 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sci., 2001, 26:230-245, each of which is incorporated by reference in its entirety. Single domain antibodies are also known as sdAbs or nanobodies. Sdabs are fairly stable and easy to express as fusion partner with the Fc chain of an antibody (Harmsen MM, De Haard HJ (2007). “Properties, production, and applications of camelid single-domain antibody fragments”. Appl. Microbiol Biotechnol.77(1): 13-22). [00120] The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a naturally occurring antibody structure and having heavy chains that comprise an Fc region. For example, when used to refer to an IgG molecule, a “full length antibody” is an antibody that comprises two heavy chains and two light chains. [00121] The term “antibody fragment” refers to an antibody that comprises a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, and scFv-Fc fragments. [00122] The term “Fc domain” or “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. [00123] The term “purified” or “substantially purified” refers to a construct described herein, or variant thereof that may be substantially or essentially free of components that normally accompany or interact with the protein as found in its naturally occurring environment, i.e., a native cell, or host cell in the case of recombinantly produced antibody that in certain embodiments, is substantially free of cellular material includes preparations of protein having 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 1% (by dry weight or by relative concentration) of contaminating protein. Attorney Docket No.: AOJ-017PC AOE-003WO [00124] The term percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill) or by visual inspection. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. Depending on the application, the percent “identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared. [00125] For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. [00126] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math.2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra). [00127] Ranges recited herein are understood to be shorthand for all of the values within the range, inclusive of the recited endpoints. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50. Attorney Docket No.: AOJ-017PC AOE-003WO [00128] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. [00129] The term “stable formulation” refers to a formulation in which the protein of interest (here an antibody or an antigen binding fragment thereof) essentially retains its physical, chemical and/or biological properties upon storage. In order to measure the protein stability in a formulation, various analytical methods are well within the knowledge of the skilled person (see some examples in the Example section). Stability is typically assessed at a selected temperature (for instance −70 °C, -40° C, -20° C, 2-8 °C, 25 °C, 35 °C, or more) for a selected time period (e.g., 3 months, 6 months, 12 months, or more). As an antibody, once formulated, it may be stored frozen (-20 °C to -70 °C) , under refrigerated conditions (typically 2-8° C), or at room temperature (typically 20-26° C) before being prepared for administration to a patient. It is important that the formulated antibody is stable over time at least at 2-25° C or under frozen conditions (-20 to -70° C), as shown for example at 2-8° C, 25° C, -20° C, -40° C, and -70° C. Various values can be used to conclude about stability over a given time period (in comparison of the initial data), such as (and not limited to): 1) no more than 10% of alteration of the monomeric form of the antibody, 2) no more than 10% of increase in High Molecular Weight Species (HMW; also herein referred to as aggregates), 3) no more than 10% of increase in Low Molecular Weight species (LMW), 4) no more than +1-0.3 unit variation of the pH, 5) changes in charge variation, 6) changes in potency, or 7) changes in particulates, the relevant changed ranges of which one of skill in the art could determine. [00130] In all the embodiments of the invention, “formulation,” “pharmaceutical formulation,” and “pharmaceutical composition” can also be referred to as “stable formulation” without any differentiation. [00131] As used herein, the term “vial” refers to a container that holds the drug product. In some embodiments, the vial may be a vial, a pen, an autoinjector, a cartridge or a syringe. In some embodiments, the vial may be a vial, e.g., a glass vial or a pre-filled syringe or pre- filled autoinjector, e.g., an autoinjector cartridge. Anti-IL-13 Antibodies [00132] In some embodiments, the present disclosure provides formulations comprising (a) an IL-13 antibody present at a concentration between, e.g., about 140 mg/mL and about Attorney Docket No.: AOJ-017PC AOE-003WO 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0. [00133] In some embodiments, the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration of, e.g., about 180 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [00134] In some embodiments, the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration of, e.g., about 180 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 80 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [00135] In some embodiments, the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration of, e.g., about 160-250 mg/mL (e.g., 180 mg/mL or 200 mg/mL); (b) a histidine buffer (e.g., combination L-histidine and L- histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.5 to 7.0, e.g., 5.8 or 6.0. [00136] In some embodiments, the formulation comprises a sugar, for example, sucrose. [00137] In some embodiments, the IL-13 antibody is a humanized, human, or chimeric antibody. In some embodiments, the IL-13 antibody is a humanized antibody. Anti-IL-13 Antibody Structure [00138] The present application provides antibodies and formulations comprising an IL-13 antibody. [00139] The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. The “class” of an Attorney Docket No.: AOJ-017PC AOE-003WO antibody or immunoglobulin refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. [00140] An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD). The N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains respectively. The IgG1 heavy chain comprises of the VH, CH1, CH2, and CH3 domains respectively from the N- to C-terminus. The light chain comprises of the VL and CL domains from N- to C-terminus. The IgG1 heavy chain comprises a hinge between the CH1 and CH2 domains. In certain embodiments, the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide. In some embodiments, the immunoglobulin domain found in an antibody provided herein, is from or derived from an immunoglobulin based construct such as a diabody or a nanobody. In certain embodiments, the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody. In certain embodiments, the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody, or any chimeric antibody. [00141] In some embodiments, the antibodies provided herein comprise a heavy chain. In one embodiment, the heavy chain is an IgA. In one embodiment, the heavy chain is an IgD. In one embodiment, the heavy chain is an IgE. In one embodiment, the heavy chain is an IgG. In one embodiment, the heavy chain is an IgM. In one embodiment, the heavy chain is an IgG1. In one embodiment, the heavy chain is an IgG2. In one embodiment, the heavy chain is an IgG3. In one embodiment, the heavy chain is an IgG4. In one embodiment, the heavy chain is an IgA1. In one embodiment, the heavy chain is an IgA2. [00142] In some embodiments, an antibody is an IgG1 antibody. In some embodiments, an antibody is an IgG3 antibody. In some embodiments, an antibody is an IgG2 antibody. In some embodiments, an antibody is an IgG4 antibody. Attorney Docket No.: AOJ-017PC AOE-003WO [00143] Generally, native four-chain antibodies comprise six hypervariable regions (HVRs); three in the VH (H1, H2, and H3), and three in the VL (L1, L2, and L3). HVRs generally comprise amino acid residues from the hypervariable loops and/or from the complementarity determining regions (CDRs), the latter being of highest sequence variability and/or involved in antigen recognition. With the exception of CDR1 in VH, CDRs generally comprise the amino acid residues that form the hypervariable loops. HVRs are also referred to as CDRs, and these terms are used herein interchangeably in reference to portions of the variable region that form the antigen-binding regions. This particular region has been described by Kabat et al., U.S. Dept. of Health and Human Services, Sequences of Proteins of Immunological Interest (1983) and by Chothia et al., J Mol Biol 196:901-917 (1987), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or variants thereof is intended to be within the scope of the term as defined and used herein. The exact residue numbers which encompass a particular CDR will vary depending on the sequence and size of the CDR. Those skilled in the art can routinely determine which residues comprise a particular CDR given the variable region amino acid sequence of the antibody. [00144] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol.262:732- 745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol. Biol., 2001, 309:657-70 (“AHo” numbering scheme); each of which is incorporated by reference in its entirety. [00145] Table 1 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR- H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes. [00146] CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available at www.bioinf.org.uk/abs/abnum/, and described in Abhinandan and Martin, Immunology, 2008, 45:3832-3839, incorporated by reference in its entirety. Table 1. Residues in CDRs according to Kabat and Chothia numbering schemes CDR Kabat Chothia
Figure imgf000029_0001
Attorney Docket No.: AOJ-017PC AOE-003WO L1 L24-L34 L24-L34 L2 L50-L56 L50-L56 * Th n, varies betw
Figure imgf000030_0001
, [00147] The “EU numbering scheme” is generally used when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein. [00148] One example of an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer of an antibody. Another example of an antigen-binding domain is an antigen-binding domain formed by diversification of certain loops from the tenth fibronectin type III domain of an Adnectin. An antigen-binding domain can include CDRs 1, 2, and 3 from a heavy chain in that order; and CDRs 1, 2, and 3 from a light chain in that order. [00149] Epitopes frequently consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter may be lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to IL-13 variants with different point-mutations or to chimeric IL-13 variants. [00150] To screen for antibodies which bind to an epitope on a target antigen bound by an antibody of interest (e.g., IL-13), a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. Alternatively, or additionally, epitope mapping can be performed by methods known in the art. Attorney Docket No.: AOJ-017PC AOE-003WO [00151] Chimeric antibodies are antibodies in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species. [00152] Human antibodies are antibodies which possess an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies. [00153] A humanized antibody has a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non- human species antibody, when it is administered to a human subject. In one embodiment, certain amino acids in the framework and constant domains of the heavy and/or light chains of the non-human species antibody are mutated to produce the humanized antibody. In another embodiment, the constant domain(s) from a human antibody are fused to the variable domain(s) of a non-human species. In another embodiment, one or more amino acid residues in one or more CDR sequences of a non-human antibody are changed to reduce the likely immunogenicity of the non-human antibody when it is administered to a human subject, wherein the changed amino acid residues either are not critical for immunospecific binding of the antibody to its antigen, or the changes to the amino acid sequence that are made are conservative changes, such that the binding of the humanized antibody to the antigen is not significantly worse than the binding of the non-human antibody to the antigen. Examples of how to make humanized antibodies can be found in U.S. Pat. Nos.6,054,297, 5,886,152 and 5,877,293. For further details, see Jones et al., Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated by reference in its entirety. [00154] The two or more different epitopes may be epitopes on the same antigen (e.g., a single IL-13) or on different antigens (e.g., different IL-13 molecules, or a IL-13 molecule and a non- IL-13 molecule). In some embodiments, a multi-specific antibody binds two different epitopes (i.e., a “bispecific antibody”). In some embodiments, a multi-specific antibody binds three different epitopes (i.e., a “trispecific antibody”). Attorney Docket No.: AOJ-017PC AOE-003WO [00155] Anti-IL-13 antibodies can include those described herein such as the clones set forth in the drawings and/or tables. In some embodiments, the antibody comprises an alternative scaffold. In some embodiments, the antibody consists of an alternative scaffold. In some embodiments, the antibody consists essentially of an alternative scaffold. In some embodiments, the antibody comprises an antibody fragment. In some embodiments, the antibody consists of an antibody fragment. In some embodiments, the antibody consists essentially of an antibody fragment. [00156] In some embodiments the antibodies are monoclonal antibodies. [00157] In some embodiments the antibodies are polyclonal antibodies. [00158] In some embodiments the antibodies are produced by hybridomas. In other embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains. [00159] In some embodiments the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof. [00160] In some embodiments the antibodies may be polyfunctional antibodies, recombinant antibodies, human antibodies, humanized antibodies, fragments or variants thereof. In particular embodiments, the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab′2 fragment, a CDR, and ScFv. [00161] In some embodiments, the antibodies are capable of forming an immune complex. For example, an immune complex can be a tumor cell covered by antibodies. Sequences of IL-13 Antibodies VH Domains [00162] In some embodiments, the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0. In some embodiments, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence Attorney Docket No.: AOJ-017PC AOE-003WO comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [00163] In some embodiments, the present disclosure further provides formulations comprising: (a) an IL-13 antibody present at a concentration, e.g., between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0. In some embodiments, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and (f) CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. [00164] In some embodiments, an antibody provided herein comprises a VH sequence selected from SEQ ID NOs: 1-32. [00165] In some embodiments, an antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VH sequence provided in SEQ ID NOs: 1-32. In some embodiments, an antibody provided herein comprises a VH sequence provided in SEQ ID NOs: 1-32, with up Attorney Docket No.: AOJ-017PC AOE-003WO to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. VL Domains [00166] In some embodiments, an antibody provided herein comprises a VL sequence selected from SEQ ID NOs: 33-57. [00167] In some embodiments, an antibody provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VL sequence provided in SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises a VL sequence provided in SEQ ID NOs: 33-57 with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. VH-VL Combinations [00168] In some embodiments, an antibody provided herein comprises a VH sequence selected from SEQ ID NOs: 1-32; and a VL sequence selected from SEQ ID NOs: 33-57, such as any of the VH-VL combinations set forth for Constructs 3-127 and 132-144 in Table 2, below. [00169] In certain aspects, any of SEQ ID NOs: 1-32 can be combined with any of SEQ ID NOs: 33-57. [00170] In certain embodiments, the antibody comprises a VH sequence selected from the sequences set forth in SEQ ID NOs: 1-32 and a VL sequence set forth in SEQ ID NO: 39. Attorney Docket No.: AOJ-017PC AOE-003WO [00171] In certain embodiments, the antibody comprises the VH sequence set forth in SEQ ID NO: 3 and the VL sequence set forth in SEQ ID NO: 39. [00172] In certain embodiments, the antibody comprises a VH sequence selected from the sequences set forth in SEQ ID NOs: 1-32 and a VL sequence set forth in SEQ ID NO: 51. [00173] In some embodiments, an antibody provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VH sequence provided in SEQ ID NOs: 1-32; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an VL sequence provided in SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises a VH sequence provided in SEQ ID NOs: 1-32, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions; and a VL sequence provided in SEQ ID NOs: 33-57, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00174] In some embodiments, an antibody provided herein comprises a VH sequence and a VL sequence selected from combinations set forth for Constructs 3-127 and 132-144 in Table 2, below. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 1 and a VL sequence set forth in SEQ ID NO: 33. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 2 and a VL sequence set forth in SEQ ID NO: 33. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 35. In certain embodiments, the Attorney Docket No.: AOJ-017PC AOE-003WO antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 4 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 5 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 40. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 8 and a VL sequence set forth in SEQ ID NO: 42. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 9 and a VL sequence set forth in SEQ ID NO: 43. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 44. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 45. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 47. In certain embodiments, the Attorney Docket No.: AOJ-017PC AOE-003WO antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 48. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 49. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 50. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 51. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 52. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 53. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 54. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 55. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 56. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 57. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 10 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 11 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 12 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 13 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 14 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 15 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 16 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 17 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 18 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 19 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 20 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 21 and a VL sequence set forth in SEQ ID NO: 39. In Attorney Docket No.: AOJ-017PC AOE-003WO certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 22 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 23 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 24 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 25 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 26 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 27 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 28 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 28 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 29 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 30 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 31 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 32 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 8 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 8 and a VL sequence set forth in SEQ ID NO: 51. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 51. [00175] In certain embodiments, the IL-13 antibody comprises a heavy chain variable domain comprising a framework region sequence selected from a sequence set forth in SEQ ID NOs: 198-229, 255-256, 258-259, 261-285, 311-315, 317-342, 368-369, 371-399, and 540-580. In certain embodiments, the IL-13 antibody comprises a heavy chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 198-229, 255-256, 258-259, 261-285, 311-315, 317-342, 368-369, 371-399, and 540-580. [00176] In certain embodiments, the IL-13 antibody comprises a light chain variable domain comprising a framework region sequence selected from a sequence set forth in SEQ ID NOs: 230-231, 233-235, 239, 241-254, 286, 288, 290-291, 293, 296-310, 343-345, 347, Attorney Docket No.: AOJ-017PC AOE-003WO 400-424, and 581-609. In certain embodiments, the IL-13 antibody comprises a light chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 230-231, 233-235, 239, 241-254, 286, 288, 290-291, 293, 296-310, 343-345, 347, 400-424, and 581-609. [00177] In certain embodiments, the IL-13 antibody comprises a heavy chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 198-229, 255-256, 258-259, 261-285, 311-315, 317-342, 368-369, 371-399, and 540-580, and comprises a light chain variable domain comprising 1, 2, 3, or 4 framework region sequences selected from a sequence set forth in SEQ ID NOs: 230-231, 233-235, 239, 241-254, 286, 288, 290-291, 293, 296-310, 343-345, 347, 400-424, and 581- 609. Table 2. Anti-interleukin (IL)-13 antibody VH-VL sequences Construc VH; VL; HC VH sequence VL sequence t ID t t R F Y S T R F Y S
Figure imgf000039_0001
Attorney Docket No.: AOJ-017PC AOE-003WO Human kappa CAGDGYYPYAMDNW YYCQQNNEDPRTFGGGT LC GQGSLVTVSS (SEQ ID KVEIK (SEQ ID NO: 471) R F Y S S T R F Y S S T F Y Y K F Y
Figure imgf000040_0001
Attorney Docket No.: AOJ-017PC AOE-003WO YTE; Human WLGMIWGDGKIVYNS LASNLESGVPSRFSGSGS kappa LC ALKSRLTITKDSSTSTV RTDFTLTISSLQPEDFATY K F Y Y K F Y Y K F Y Y K
Figure imgf000041_0001
Attorney Docket No.: AOJ-017PC AOE-003WO HC1; LC3; EVQLQESGPGLVKPSE EIVLTQSPATLSVSPGERA hIgG1-LAGA TLSLTCTVSGFSLNAYS TLSCRASKSVDSYGNSF Y R Y V A Y R Y V A Y R Y V A Y R Y
Figure imgf000042_0001
Attorney Docket No.: AOJ-017PC AOE-003WO YCAGDGYYPYAMDN CQQNNEDPRTFGGGTKV WGQGTTVTVSS (SEQ EIK (SEQ ID NO: 36) A Y R Y V F Y Y K F Y Y K F Y
Figure imgf000043_0001
Attorney Docket No.: AOJ-017PC AOE-003WO YTE; Human LGMIWGDGKIVYNSA LASNLESGVPSRFSGSGS kappa LC LKSRLTITKDSSTSTVY GTDFTLTISSLQPEDFATY K F Y Y K F Y Y K A Y G Y V
Figure imgf000044_0001
Attorney Docket No.: AOJ-017PC AOE-003WO HC2; LC7; EVQLVQSGAEVKKPGS EIVLTQSPATLSVSPGERA hIgG1-LAGA SVKVSCKASGFSLNAY TLSCRASKSVDSYGNSF Y G Y V A Y G Y V A Y G Y V A Y G Y
Figure imgf000045_0001
Attorney Docket No.: AOJ-017PC AOE-003WO LQMNSLRAEDTAVYY CQQNNEDPRTFGGGTKV CAGDGYYPYAMDNW EIK (SEQ ID NO: 40) F Y S V T F S V T F Y Y K R
Figure imgf000046_0001
Attorney Docket No.: AOJ-017PC AOE-003WO hIgG1-LAGA SVNWVRQAPGKGLEW MHWYQQKPGKAPKLLIY YTE; Human LGMIWGDGKIVYNSA LASNLESGVPSRFSGSGS Y K S Y Y K F R Y K F F Y K
Figure imgf000047_0001
Attorney Docket No.: AOJ-017PC AOE-003WO GQGTTVTVSS (SEQ ID NO: 7) F Y Y K F Y Y K F Y Y K F Y
Figure imgf000048_0001
Attorney Docket No.: AOJ-017PC AOE-003WO YTE; Human LKSRLTISKDSSKNTVY GTDFTLTISSLQPEDFATY kappa LC LQMNSLRAEDTAVYY YCQQNNEDPRTFGGGTK F Y Y K F Y Y K F Y Y
Figure imgf000049_0001
Attorney Docket No.: AOJ-017PC AOE-003WO HC5; EVQLLESGGGLVQPGG DIQLTQSPSSLSASVGDR LC6 m12; SLRLSCAASGFSLNAY VTITCRASKSVDSYGNSF Y Y K F Y Y K F Y Y K F Y Y
Figure imgf000050_0001
Attorney Docket No.: AOJ-017PC AOE-003WO CAGDGYYPYAMDNW YCQQNNEDPRTFGGGTK GQGTTVTVSS (SEQ ID VEIK (SEQ ID NO: 39) F Y Y K F Y Y K F Y Y K F Y
Figure imgf000051_0001
Attorney Docket No.: AOJ-017PC AOE-003WO Human kappa LGMIWGDGKIVYNSA LASNLESGVPSRFSGSGS LC LKSRLTISKDSSKNTVY GTDFTLTISSLQPEDFATY K F Y Y K F Y Y K F Y Y K
Figure imgf000052_0001
Attorney Docket No.: AOJ-017PC AOE-003WO HC5_m9; EVQLLESGGGLVQPGG DIQLTQSPSSLSASVGDR LC6; hIgG1- SLRLSCAASGFSLNHY VTITCRASKSVDSYGNSF Y Y K F Y Y K F Y Y K F Y Y
Figure imgf000053_0001
Attorney Docket No.: AOJ-017PC AOE-003WO AGDGYYPYAMDNWG YCQQNNEDPRTFGGGTK QGTTVTVSS (SEQ ID VEIK (SEQ ID NO: 39) F Y Y K F Y Y K F Y Y K F Y
Figure imgf000054_0001
Attorney Docket No.: AOJ-017PC AOE-003WO Human kappa LGMIWADGKIVYNSA LASNLESGVPSRFSGSGS LC LKSRLTISKDSSKNTVY GTDFTLTISSLQPEDFATY K F Y Y K F Y Y K F Y Y K
Figure imgf000055_0001
Attorney Docket No.: AOJ-017PC AOE-003WO HC5_m20; EVQLLESGGGLVQPGG DIQLTQSPSSLSASVGDR LC6; hIgG1- SLRLSCAASGFSLNAY VTITCRASKSVDSYGNSF Y Y K F Y Y K F Y Y K F Y Y
Figure imgf000056_0001
Attorney Docket No.: AOJ-017PC AOE-003WO CAGDGYYTYAMDNW YCQQNNEDPRTFGGGTK GQGTTVTVSS (SEQ ID VEIK (SEQ ID NO: 39) F Y S T F Y S T F Y S T F Y
Figure imgf000057_0001
Attorney Docket No.: AOJ-017PC AOE-003WO – LC; hIgG1- AMIWGDGKIVYNSAL LASNLESGVPDRFSGSGS LALA-LS; KSRLTISKDTSKNQVV GTDFTLTISSLQAEDVAV T F Y Y K F Y Y K F Y Y K
Figure imgf000058_0001
Attorney Docket No.: AOJ-017PC AOE-003WO HC1; LC6; EVQLQESGPGLVKPSE DIQLTQSPSSLSASVGDR hIgG4-LS; TLSLTCTVSGFSLNAYS VTITCRASKSVDSYGNSF Y Y K F Y Y K F Y Y K F Y Y
Figure imgf000059_0001
Attorney Docket No.: AOJ-017PC AOE-003WO CAGDGYYPYAMDNW YCQQNNEDPRTFGGGTK GQGTTVTVSS (SEQ ID VEIK (SEQ ID NO: 51) F Y Y K F Y Y K F Y Y K F Y
Figure imgf000060_0001
Attorney Docket No.: AOJ-017PC AOE-003WO Human kappa GMIWGDGKIVYNSAL LASELESGVPSRFSGSGS LC KSRLTISKDSSKNQVSL GTDFTLTISSLQPEDFATY K F Y Y K F Y Y K *
Figure imgf000061_0001
[00178] In some embodiments, a VH domain listed for any one of Constructs 3-127 and 132-144 in Table 2 can be combined with a heavy chain constant (HC) domain provided herein. In certain embodiments, an IL-13 antibody comprises a VH domain selected from any one the VH domains of Constructs 3-127 and 132-144 in Table 2 or a VH domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and a HC domain comprising a sequence selected from any one of SEQ ID NOs: 425-468, 484-539, and 610-709 or an HC domain having at least about 80%, 90%, 91%, 92%, 93%, Attorney Docket No.: AOJ-017PC AOE-003WO 94%, 95%, 96%, 97%, 98% or 99% identity thereto. In some embodiments, a VH domain listed for any one of Constructs 3-127 and 132-144 in Table 2 can be combined with a heavy chain constant (HC) domain provided herein. In certain embodiments, an IL-13 antibody comprises a VH domain selected from any one the VH domains of Constructs 3-127 and 132- 144 in Table 2 or a VH domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity thereto, and a HC domain comprising a sequence selected from any one of SEQ ID NOs: 610, 615-641, and 654-709 or an HC domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto. Each and every combination of (1) VH/VL listed for Constructs 3-127 and 132-144 in Table 2 and (2) HC domain is contemplated herein. In certain embodiments, the HC domain is an IgG1 HC domain. [00179] In certain embodiments, the HC domain includes IgG4-SP, hIgG1-LALA-YTE, hIgG1-LAGA YTE, hIgG1-LALA-LS, IgG4-YTE HC, and IgG4-LS. [00180] In some embodiments, such an IgG4-SP HC constant domain has the sequence: ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 427). [00181] In some embodiments, such a hIgG1-LALA-YTE HC constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP EAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 439). [00182] In some embodiments, such a hIgG1-LAGA YTE HC constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELAGAPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT Attorney Docket No.: AOJ-017PC AOE-003WO KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 440). [00183] In some embodiments, such a hIgG1-LALA-LS HC constant domain has the sequence: [00184] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPG (SEQ ID NO: 446). [00185] In some embodiments, such an IgG4-YTE HC constant domain has the sequence: ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLG GPSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 457). [00186] In some embodiments, such an IgG4-LS HC constant domain has the sequence: ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS RLTVDKSRWQEGNVFSCSVLHEALHSYTQKSLSLSLGK (SEQ ID NO: 460). [00187] In some embodiments, such a hIgG1-LALA-YTE HC C-terminal lysine variant constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP EAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG Attorney Docket No.: AOJ-017PC AOE-003WO SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 624). [00188] In some embodiments, such a hIgG1-LAGA YTE HC C-terminal lysine variant constant domain has the sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELAGAPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 625). [00189] In some embodiments, such a hIgG1-LALA-LS HC C-terminal lysine variant constant domain has the sequence: [00190] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK (SEQ ID NO: 631). [00191] In some embodiments, a VL domain listed for Constructs 3-127 and 132-144 in Table 2 can be combined with a light chain constant (LC) domain provided herein. In some embodiments, the LC domain is a human kappa LC constant domain. In some embodiments, such a human kappa LC constant domain has the sequence: RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 469). CDRs [00192] In some embodiments, an antibody provided herein comprises one to three CDRs of a VH domain selected from SEQ ID NOs: 1-32, such as any of the CDRs listed in Table 3, Table 4, or Table 5, below. In some embodiments, an antibody provided herein comprises two to three CDRs of a VH domain selected from SEQ ID NOs: 1-32. In some embodiments, an antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1-32. In some embodiments, the CDRs are Exemplary CDRs. In some embodiments, Attorney Docket No.: AOJ-017PC AOE-003WO the CDRs are Kabat CDRs. In some embodiments, the CDRs are Chothia CDRs. In some embodiments, the CDRs are IMGT CDRs. In some embodiments, the CDRs are AbM CDRs. In some embodiments, the CDRs are Contact CDRs. [00193] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with a CDR-H1, CDR-H2, or CDR-H3 of SEQ ID NOs: 58-140. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from SEQ ID NOs: 1-32, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain of SEQ ID NO: 1-32, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from SEQ ID NOs: 1-32, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00194] In some embodiments, an antibody provided herein comprises one to three CDRs of a VL domain of SEQ ID NOs: 33-57, such as any of the CDRs listed in Table 6, Table 7, or Table 8, below. In some embodiments, an antibody provided herein comprises two to three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, the CDRs are Exemplary CDRs. In some embodiments, the CDRs are Kabat CDRs. In some embodiments, the CDRs are Chothia CDRs. In some embodiments, the CDRs are IMGT CDRs. In some embodiments, the CDRs are AbM CDRs. In some embodiments, the CDRs are Contact CDRs. [00195] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with a CDR-L1, CDR-L2, or CDR-L3 of SEQ ID NOs: 141-188. In some embodiments, the CDR-L1 is a CDR-L1 of a VL domain of SEQ ID NOs: 33-57, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain of SEQ ID NOs: 33-57 , with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR- Attorney Docket No.: AOJ-017PC AOE-003WO L3 of a VL domain of SEQ ID NOs: 33-57, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00196] In some embodiments, an antibody provided herein comprises one to three CDRs of a VH domain selected from SEQ ID NOs: 1-32 and one to three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises two to three CDRs of a VH domain selected from SEQ ID NOs: 1-32 and two to three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, an antibody provided herein comprises three CDRs of a VH domain selected from SEQ ID NOs: 1-32 and three CDRs of a VL domain of SEQ ID NOs: 33-57. In some embodiments, the CDRs are Exemplary CDRs. In some embodiments, the CDRs are Kabat CDRs. In some embodiments, the CDRs are Chothia CDRs. In some embodiments, the CDRs are IMGT CDRs. In some embodiments, the CDRs are AbM CDRs. In some embodiments, the CDRs are Contact CDRs. [00197] In some embodiments, an antibody provided herein comprises a CDR-H3 selected of SEQ ID NOs: 112-120 and 130-40. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112-120 or 130-40. In some embodiments, the CDR-H3 is a CDR-H3 selected of SEQ ID NOs: 112-120 and 130-40, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. Attorney Docket No.: AOJ-017PC AOE-003WO [00198] In some embodiments, an antibody provided herein comprises a CDR-H1 of SEQ ID NOs: 58-99 and 121. In some embodiments, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58-99 or 121. In some embodiments, the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58-99 or 121, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00199] In some embodiments, an antibody provided herein comprises a CDR-H2 of any one of SEQ ID NOs: 100-111. In some embodiments, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of any one of SEQ ID NOs: 100-111. In some embodiments, the CDR-H2 is a CDR-H2 of any one of SEQ ID NOs: 100-111, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00200] In some embodiments, an antibody provided herein comprises a CDR-L3 selected from SEQ ID NOs: 165-172. In some embodiments, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NOs: 165-172. In some embodiments, the CDR-L3 is a CDR-L3 of SEQ ID NOs: 165- 172, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method Attorney Docket No.: AOJ-017PC AOE-003WO known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00201] In some embodiments, an antibody provided herein comprises a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS. In some embodiments, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS. In some embodiments, the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00202] In some embodiments, an antibody provided herein comprises a CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152. In some embodiments, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR- L1 selected from SEQ ID NOs: 141-144 and 149-152. In some embodiments, the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00203] In some embodiments, an antibody provided herein comprises a CDR-H3 selected from SEQ ID NOs: 112-120 and 130-140, a CDR-H2 of SEQ ID NOs: 100-111, a CDR-H1 selected from SEQ ID NOs: 58-99 and 121, a CDR-L3 selected from SEQ ID NOs: 165-172, a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, and a Attorney Docket No.: AOJ-017PC AOE-003WO CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152. In some embodiments, the CDR- H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 selected from SEQ ID NOs: 112-120 and 130-140, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100-111, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 selected from SEQ ID NOs: 58-99 and 121, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 selected from SEQ ID NOs: 165-172, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L1 selected from SEQ ID NOs: 141-144 and 149-152. In some embodiments, the CDR-H3 is a CDR-H3 selected from SEQ ID NOs: 112-120 and 130-140, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR- H2 of SEQ ID NOs: 100-111, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from SEQ ID NOs: 58-99 and 121, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 selected from SEQ ID NOs: 165-172, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 selected from SEQ ID NOs: 153-158 and the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from SEQ ID NOs: 141-144 and 149- 152, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions. [00204] In some embodiments, an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112, 121, and 130, a CDR-H2 of SEQ ID NOs: 100, 104, and 108, a CDR-H1 of SEQ ID NOs: 58, 68, and 85, a CDR-L3 of SEQ ID NOs: 168, 173, and 181, a CDR-L2 of SEQ ID NOs: 153 and the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 and 149. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104 or 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 68 or 85, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 168, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a Attorney Docket No.: AOJ-017PC AOE-003WO CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR- L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104 or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 68 or 85, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 168 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions. [00205] In some embodiments, an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112, 121 or 130, a CDR-H2 of SEQ ID NOs: 100, 104 or 108, a CDR-H1 of SEQ ID NOs: 58, 68, or 85, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104 or 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 68 or 85, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 165, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104 or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 68 or 85, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of SEQ ID NO: 153 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions. Attorney Docket No.: AOJ-017PC AOE-003WO [00206] In some embodiments, an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112 or 130, a CDR-H2 of SEQ ID NOs: 100, 104, or 108, a CDR-H1 of SEQ ID NOs: 58, 68, or 85, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104, or108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 68 or 85, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 165, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104, or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 68, or 85, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR- L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions. [00207] In some embodiments, an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112, 121 or 130, a CDR-H2 of SEQ ID NOs: 100, 104 or 108, a CDR-H1 of SEQ ID NOs: 58, 67, or 84, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104 or 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 67 or 84, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 165, the CDR-L2 has at least about Attorney Docket No.: AOJ-017PC AOE-003WO 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 of SEQ ID NOs: 153 or the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104 or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 67 or 84, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of SEQ ID NO: 153 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions. [00208] In some embodiments, an antibody provided herein comprises a CDR-H3 of SEQ ID NOs: 112 or 130, a CDR-H2 of SEQ ID NOs: 100, 104, or 108, a CDR-H1 of SEQ ID NOs: 58, 67, or 84, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H3 of SEQ ID NOs: 112 or 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H2 of SEQ ID NOs: 100, 104, or108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-H1 of SEQ ID NOs: 58, 67 or 84, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L3 of SEQ ID NO: 165, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with a CDR-L1 of SEQ ID NOs: 141 or 149. In some embodiments, the CDR-H3 is a CDR-H3 of SEQ ID NOs: 112 or 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of SEQ ID NOs: 100, 104, or 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of SEQ ID NOs: 58, 67, or 84, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 165, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR- L1 of SEQ ID NOs: 141 or 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions. Attorney Docket No.: AOJ-017PC AOE-003WO [00209] In some embodiments, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or cones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies. [00210] In certain aspects, the antibodies disclosed herein do not include antibodies disclosed in US Patent number 9,067,994.
Attorney Docket No.: AOE-003PR Table 3. Anti-interleukin (IL)-13 antibody Heavy Chain Kabat CDRs Construc * ID 1 (lebrikizu mab), 2, and 128- 131
Figure imgf000074_0001
73 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 3 4 5, 10, 15, 20, 133- 136, and 141-144 6, 11, 16, and 21
Figure imgf000075_0001
SCKAS EDTAV GFSLN YYCAG 74 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 7, 12, 17, and 22 8, 13, 18, and 23 9, 14, 19, 24, 90- 104, 132, and 137- 140 25
Figure imgf000076_0001
GGSLN VYYCA R 75 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 26 105 106 107
Figure imgf000077_0001
GFSLH VYYCA G 76 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 108 109 110 111
Figure imgf000078_0001
GFSLN VYYCA G 77 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 112 113 114 115
Figure imgf000079_0001
GFSLN VYYCA G 78 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 116 117 118 119
Figure imgf000080_0001
GFSLN VYYCA G 79 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 120 121 122 123
Figure imgf000081_0001
GFSLN VYYCA G 80 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 124 125 126 127
Figure imgf000082_0001
GFSLN VYYCA G *Names correspond with name in informal sequence listing. 81 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Table 4. Anti-interleukin (IL)-13 antibody Heavy Chain Chothia CDRs Construc VH N * FR1 E DR1 E FR2 E DR2 E FR E DR E FR4 E t ID 1 (lebrikizu mab), 2, and 128- 131 3
Figure imgf000083_0001
G 82 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 4 5, 10, 15, 20, 133- 136, and 141-144 6, 11, 16, and 21
Figure imgf000084_0001
YYCAG 83 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 7, 12, 17, and 22 8, 13, 18, and 23 9, 14, 19, 24, 90- 104, 132, and 137- 140
Figure imgf000085_0001
G 84 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 25 26 105
Figure imgf000086_0001
G 85 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 106 107 108
Figure imgf000087_0001
VYYCA G 86 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 109 110 111
Figure imgf000088_0001
VYYCA G 87 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 112 113 114
Figure imgf000089_0001
VYYCA G 88 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 115 116 117
Figure imgf000090_0001
VYYCA G 89 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 118 119 120
Figure imgf000091_0001
VYYCA G 90 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 121 122 123
Figure imgf000092_0001
VYYCA G 91 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 124 125 126
Figure imgf000093_0001
VYYCA G 92 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construc VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ t ID 127
Figure imgf000094_0001
*Names correspond with name in informal sequence listing. Table 5. Anti-interleukin (IL)-13 antibody Heavy Chain IMGT CDRs Construc ID 1 (lebrikizu mab), 2, and 128- 131
Figure imgf000094_0002
YYC 93 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 3 4 5, 10, 15, 20, and 133-136
Figure imgf000095_0001
YC 94 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 6, 11, 16, and 21 7, 12, 17, and 22 8, 13, 18, and 23
Figure imgf000096_0001
YYC 95 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 9, 14, 19, 24, 90- 104, 132, and 137- 140 25 26
Figure imgf000097_0001
YC 96 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 105 106 107
Figure imgf000098_0001
YYC 97 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 108 109 110
Figure imgf000099_0001
YYC 98 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 111 112 113
Figure imgf000100_0001
YYC 99 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 114 115 116
Figure imgf000101_0001
YYC 100 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 117 118 119
Figure imgf000102_0001
YYC 101 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 120 121 122
Figure imgf000103_0001
YYC 102 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 123 124 125
Figure imgf000104_0001
YYC 103 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VH N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 126 127
Figure imgf000105_0001
YYC *Names correspond with name in informal sequence listing. 104 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Table 6. Anti-interleukin (IL)-13 antibody Light Chain Kabat CDRs Construc * ID 1 (lebrikizu mab), 2, and 128- 131 3 and 4 - 5-9
Figure imgf000106_0001
FATYY C 105 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 10-14 - - 15-19, 90, 105-127, and 132- 136
Figure imgf000107_0001
FATYY C 106 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 20-24 - 25 26
Figure imgf000108_0001
VAVY YC 107 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 91 92 93 94
Figure imgf000109_0001
FATYY C 108 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 95 96 97 98 and 137-140
Figure imgf000110_0001
FATYY C 109 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 99 100 101 102
Figure imgf000111_0001
FATYY C 110 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 103 104
Figure imgf000112_0001
C *Names correspond with name in informal sequence listing. Table 7. Anti-interleukin (IL)-13 antibody Light Chain Chothia CDRs Construc ID 1 (lebrikizu mab), 2, and 128- 131
Figure imgf000112_0002
VAVY YC 111 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 3 and 4 - 5-9 10-14
Figure imgf000113_0001
LSC QSEDF AVYYC 112 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID - - 15-19, 90, 105-127, and 132- 136 20-24
Figure imgf000114_0001
LSC QSEDF AVYYC 113 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID - 25 26 91
Figure imgf000115_0001
FATYY C 114 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 92 93 94 95
Figure imgf000116_0001
FATYY C 115 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 96 97 98 and 137-144 99
Figure imgf000117_0001
FATYY C 116 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 100 101 102 103
Figure imgf000118_0001
FATYY C 117 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 SEQ FR3 SEQ CDR3 SEQ FR4 SEQ ID 104
Figure imgf000119_0001
*Names correspond with name in informal sequence listing. Table 8. Anti-interleukin (IL)-13 antibody Light Chain IMGT CDRs Construc ID 1 (lebrikizu mab), 2, and 128- 131 3 and 4
Figure imgf000119_0002
EADDA ASYYC 118 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 FR3 SEQ CDR3 SEQ FR4 SEQ ID - 5-9 10-14 -
Figure imgf000120_0001
VGVY YC 119 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 FR3 SEQ CDR3 SEQ FR4 SEQ ID - 15-19, 90 105-127, and 132- 136 20-24 -
Figure imgf000121_0001
VGVY YC 120 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 FR3 SEQ CDR3 SEQ FR4 SEQ ID 25 26 91 92
Figure imgf000122_0001
QPEDF ATYYC 121 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 FR3 SEQ CDR3 SEQ FR4 SEQ ID 93 94 95 96
Figure imgf000123_0001
QPEDF ATYYC 122 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL N m * FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 FR3 SEQ CDR3 SEQ FR4 SEQ ID 97 98 and 137-144 99 100
Figure imgf000124_0001
QPEDF ATYYC 123 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Construct VL Name* FR1 SEQ CDR1 SEQ FR2 SEQ CDR2 FR3 SEQ CDR3 SEQ FR4 SEQ ID 101 102 103 104
Figure imgf000125_0001
QPEDF ATYYC *Names correspond with name in informal sequence listing. 124 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR [00211] In some embodiments, IL-13 antibody does not comprise: (a) CDR-H1 set forth in SEQ ID NO: 58; CDR-H2 set forth in SEQ ID NO: 100; CDR-H3 set forth in SEQ ID NO: 112; CDR-L1 set forth in SEQ ID NO: 141; CDR-L2 set forth in SEQ ID NO: 153; and CDR-L3 set forth in SEQ ID NO: 165; or (b) CDR-H1 set forth in SEQ ID NO: 67; CDR-H2 set forth in SEQ ID NO: 104; CDR-H3 set forth in SEQ ID NO: 112; CDR-L1 set forth in SEQ ID NO: 141; CDR-L2 set forth in SEQ ID NO: 153; and CDR-L3 set forth in SEQ ID NO: 165; or (c) CDR- H1 set forth in SEQ ID NO: 84; CDR-H2 set forth in SEQ ID NO: 108; CDR-H3 set forth in SEQ ID NO: 130; CDR-L1 set forth in SEQ ID NO: 149; CDR-L2 set forth in the amino acid sequence LAS; and CDR-L3 set forth in SEQ ID NO: 165. [00212] In some embodiments, IL-13 antibody does not comprise any combination of: (a) a CDR-H1 set forth in any of SEQ ID NOs: 58, 67, or 84; (b) a CDR-H2 set forth in any of SEQ ID NOs: 100, 104, or 108; (c) a CDR-H3 set forth in any of SEQ ID NOs: 112 or 130; (d) a CDR-L1 set forth in any of SEQ ID NOs: 141 or 149; (e) a CDR-L2 set forth in any of SEQ ID NOs: 153 or 154; and (f) a CDR-L3 set forth in SEQ ID NO: 165. Fc Region [00213] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder and Cavacini, J. Allergy Clin. Immunol., 2010, 125:S41-52, incorporated by reference in its entirety. The Fc region may be a naturally occurring Fc region, or an Fc region modified as described in the art or elsewhere in this disclosure. [00214] Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al, Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. An “Fc polypeptide” of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e., a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association. For example, an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence. An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. 125 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00215] The terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody. For example, an FcR can be a native sequence human FcR. Generally, an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcγRII receptors include FcγRIIA (an “activating receptor”) and FcγRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)). Activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. Inhibiting receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Daëron, Annu. Rev. Immunol. 15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term “FcR” herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol. 117:587 (1976); and Kim et al., J. Immunol. 24:249 (1994)). [00216] Modifications in the CH2 domain can affect the binding of FcRs to the Fc. A number of amino acid modifications in the Fc region are known in the art for selectively altering the affinity of the Fc for different Fcgamma receptors. In some aspects, the Fc comprises one or more modifications to promote selective binding of Fc-gamma receptors. [00217] Exemplary mutations that alter the binding of FcRs to the Fc are listed below: [00218] S298A/E333A/K334A, S298A/E333A/K334A/K326A (Lu Y, Vernes JM, Chiang N, et al. J Immunol Methods. 2011 Feb 28;365(1-2):132-41); [00219] F243L/R292P/Y300L/V305I/P396L, F243L/R292P/Y300L/L235V/P396L (Stavenhagen JB, Gorlatov S, Tuaillon N, et al. Cancer Res. 2007 Sep 15;67(18):8882- 90; Nordstrom JL, Gorlatov S, Zhang W, et al. Breast Cancer Res. 2011 Nov 30;13(6):R123); [00220] F243L (Stewart R, Thom G, Levens M, et al. Protein Eng Des Sel. 2011 Sep;24(9):671-8.), S298A/E333A/K334A (Shields RL, Namenuk AK, Hong K, et al. J Biol Chem. 2001 Mar 2;276(9):6591-604); 126 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00221] S239D/I332E/A330L, S239D/I332E (Lazar GA, Dang W, Karki S, et al. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4005-10); [00222] S239D/S267E, S267E/L328F (Chu SY, Vostiar I, Karki S, et al. Mol Immunol. 2008 Sep;45(15):3926-33); [00223] S239D/D265S/S298A/I332E, S239E/S298A/K326A/A327H, G237F/S298A/A330L/I 332E, S239D/I332E/S298A, S239D/K326E/A330L/I332E/S298A, G236A/S239D/D270L/I332E , S239E/S267E/H268D, L234F/S267E/N325L, G237F/V266L/S267D and other mutations listed in WO2011/120134 and WO2011/120135, herein incorporated by reference. Therapeutic Antibody Engineering (by William R. Strohl and Lila M. Strohl, Woodhead Publishing series in Biomedicine No 11, ISBN 1907568379, Oct 2012) lists mutations on page 283. [00224] In certain embodiments an antibody described herein includes modifications designed to improve its ability to mediate effector function. Such modifications are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards C1q for CDC. The following Table 9 summarizes various designs reported in the literature for effector function engineering. [00225] Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art. The GlymaX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody production. This prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody-producing cells. (von Horsten et al. (2010) Glycobiology. 2010 Dec; 20 (12):1607-18. Another approach to obtaining antibodies with lowered levels of fucosylation can be found in U.S. Patent No. 8,409,572, which teaches selecting cell lines for antibody production for their ability to yield lower levels of fucosylation on antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the isolated antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system. [00226] Thus, in one embodiment, an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in Table 9 that confer improved 127 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR effector function. In another embodiment, the antibody can be afucosylated to improve effector function. Table 9. CH2 domains and effector function engineering Reference Mutations Effect C C C C C C C C C C C
Figure imgf000129_0001
[00227] Fc modifications designed to reduce FcgR and/or complement binding and/or effector function are known in the art. Recent publications describe strategies that have been used to engineer antibodies with reduced or silenced effector activity (see Strohl, WR (2009), Curr Opin Biotech 20:685-691, and Strohl, WR and Strohl LM, “Antibody Fc engineering for optimal antibody performance” In Therapeutic Antibody Engineering, Cambridge: Woodhead Publishing (2012), pp 225-249). These strategies include reduction of effector function through modification of glycosylation, use of IgG2/IgG4 scaffolds, or the introduction of mutations in the hinge or CH2 regions of the Fc. For example, U.S. Patent Publication No. 2011/0212087 (Strohl), International Patent Publication No. WO 2006/105338 (Xencor), U.S. Patent Publication No. 2012/0225058 (Xencor), U.S. Patent Publication No. 2012/0251531 (Genentech), and Strop et al 128 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR ((2012) J. Mol. Biol. 420: 204-219) describe specific modifications to reduce FcgR or complement binding to the Fc. [00228] Specific, non-limiting examples of known amino acid modifications designed to reduce FcgR or complement binding to the Fc include those identified in the following Table 10: Table 10. Modifications to reduce FcgR or complement binding to the Fc Company Modifications A
Figure imgf000130_0001
[00229] Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art. The GlymaxX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody 129 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR production. This prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody-producing cells. (von Horsten et al. (2010) Glycobiology. 2010 Dec; 20 (12):1607-18.) Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D- lyxo-4-hexylose reductase (RMD) (see Henning von Horsten et al., Glycobiol 2010, 20:1607- 1618) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al., Arch. Biochem. Biophys., 1986, 249:533-545; U.S. Pat. Pub. No. 2003/0157108; WO 2004/056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha- 1,6-fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane-Ohnuki et al., Biotech. Bioeng., 2004, 87: 614-622; Kanda et al., Biotechnol. Bioeng., 2006, 94:680-688; and WO 2003/085107; each of which is incorporated by reference in its entirety). Another approach to obtaining antibodies with lowered levels of fucosylation can be found in U.S. Patent No. 8,409,572, which teaches selecting cell lines for antibody production for their ability to yield lower levels of fucosylation on antibodies. [00230] Examples of cell lines capable of producing defucosylated antibody include CHO- DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D-lyxo-4- hexylose reductase (RMD) (see Henning von Horsten et al., Glycobiol 2010, 20:1607-1618) or Lec13 CHO cells, which are deficient in protein fucosylation (see Ripka et al., Arch. Biochem. Biophys., 1986, 249:533-545; U.S. Pat. Pub. No. 2003/0157108; WO 2004/056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha-1,6- fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane-Ohnuki et al., Biotech. Bioeng., 2004, 87: 614-622; Kanda et al., Biotechnol. Bioeng., 2006, 94:680-688; and WO 2003/085107; each of which is incorporated by reference in its entirety). [00231] Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system. [00232] In some aspects, an antibody provided herein comprises an IgG1 domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgG1 domain. Such Fc domains are known to have improved ADCC. See Shields et al., J. Biol. Chem., 2002, 130 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 277:26733-26740, incorporated by reference in its entirety. In some aspects, such antibodies do not comprise any fucose at position Asn 297. The amount of fucose may be determined using any suitable method, for example as described in WO 2008/077546, incorporated by reference in its entirety. [00233] In certain embodiments, an antibody provided herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region. In certain embodiments, an antibody provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al., Proc. Natl. Acad. Sci. USA, 2006,103:4005-4010, incorporated by reference in its entirety. [00234] Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub. Nos. 2003/0157108, 2004/0093621, 2003/0157108, 2003/0115614, 2002/0164328, 2004/0093621, 2004/0132140, 2004/0110704, 2004/0110282, 2004/0109865; International Pat. Pub. Nos. 2000/61739, 2001/29246, 2003/085119, 2003/084570, 2005/035586, 2005/035778; 2005/053742, 2002/031140; Okazaki et al., J. Mol. Biol., 2004, 336:1239-1249; and Yamane-Ohnuki et al., Biotech. Bioeng., 2004, 87: 614-622; each of which is incorporated by reference in its entirety. [00235] In certain embodiments, an antibody provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764; each of which his incorporated by reference in its entirety. [00236] In certain embodiments, an antibody provided herein comprises one or more alterations that improves or diminishes C1q binding and/or CDC. See U.S. Pat. No. 6,194,551; WO 99/51642; and Idusogie et al., J. Immunol., 2000, 164:4178-4184; each of which is incorporated by reference in its entirety. [00237] In certain embodiments, an antibody provided herein comprises a heavy chain comprising a constant heavy chain (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or SEQ ID NO: 624. [00238] In certain embodiments, an antibody provided herein comprises a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. 131 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00239] In certain embodiments, an antibody provided herein comprises (1) a constant heavy chain (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or SEQ ID NO: 624 or a HC region comprising sequence comprising an amino acid sequence having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 439 or SEQ ID NO: 624 (2) a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469, or a LC region comprising sequence comprising an amino acid sequence having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 469 (3) a VH comprising an amino acid sequence set forth in SEQ ID NO: 3 or a VH having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 3 and (4) a VL comprising an amino acid sequence set forth in SEQ ID NO: 39 or a VL comprising an amino acid sequence at least 95% 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 39. [00240] In certain embodiments, the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a light chain constant (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469, wherein the antibody further comprises a VH comprising an amino acid sequence having at least 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 3 and a VL comprising an amino acid sequence at least 95% 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 39, wherein the VH comprises a HCDR1 comprising SEQ ID NO: 58, SEQ ID NO: 68, or SEQ ID NO: 85; a HCDR2 comprising SEQ ID NO: 100, SEQ ID NO: 104, or SEQ ID NO: 108; and a HCDR3 comprising SEQ ID NO: 112 or SEQ ID NO: 130; and the VL comprises a LCDR1 comprising SEQ ID NO: 141 or SEQ ID NO: 149; a LCDR2 comprising SEQ ID NO: 153 or SEQ ID NO: 164, and a LCDR3 comprising SEQ ID NO: 165. [00241] In certain embodiments, the isolated antibody comprises a HCDR1 comprising SEQ ID NO: 58, a HCDR2 comprising SEQ ID NO: 100, a HCDR3 comprising SEQ ID NO: 112, a LCDR1 comprising SEQ ID NO: 141, a LCDR2 comprising SEQ ID NO: 153, and a LCDR3 comprising SEQ ID NO: 165. In certain embodiments, the isolated antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO:3. In certain embodiments, the isolated antibody comprises a VL comprising an amino acid sequence set forth in SEQ ID NO:39. In certain embodiments, the isolated antibody comprises a VH comprising an amino acid sequence set forth in SEQ ID NO:3 and a VL comprising an amino acid sequence set forth in SEQ ID NO:39. In certain embodiments, the isolated antibody comprises a heavy chain 132 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439. In certain embodiments, the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 624. In certain embodiments, the isolated antibody comprises a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. In certain embodiments, the isolated antibody comprises a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. [00242] In certain embodiments, the isolated antibody comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of Construct 133. In certain embodiments, the isolated antibody comprises the VH of Construct 133. In certain embodiments, the isolated antibody comprises the VL of Construct 133. In certain embodiments, the isolated antibody comprises the VH and VL of Construct 133. In certain embodiments, the isolated antibody comprises the heavy chain constant (HC) region of Construct 133. In certain embodiments, the isolated antibody comprises the constant light chain (LC) region of Construct 133. In certain embodiments, the isolated antibody comprises the heavy chain constant (HC) region and constant light chain (LC) region of Construct 133. [00243] In certain embodiments, the isolated antibody comprises Construct 133, i.e., comprising a HCDR1 comprising SEQ ID NO: 58, a HCDR2 comprising SEQ ID NO: 100, a HCDR3 comprising SEQ ID NO: 112, a LCDR1 comprising SEQ ID NO: 141, a LCDR2 comprising SEQ ID NO: 153, a LCDR3 comprising SEQ ID NO: 165, a VH comprising SEQ ID NO:3, a VL comprising SEQ ID NO:39, a heavy chain constant (HC) region comprising an amino acid sequence set forth in SEQ ID NO: 439 or 624 and a constant light chain (LC) region comprising an amino acid sequence set forth in SEQ ID NO: 469. [00244] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more substitutions result in increased antibody half-life, increased ADCC activity, increased ADCP activity, or increased CDC activity compared with the Fc without the one or more substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region. 133 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00245] In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P (SP); M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W. In certain embodiments, the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L/N434S (LS); M252Y/S254T/T256E (YTE); T250Q/M428L; T307A/E380A/N434A; T256D/T307Q (DQ); T256D/T307W (DW); M252Y/T256D (YD); T307Q/Q311V/A378V (QVV); T256D/H285D/T307R/Q311V/A378V (DDRVV); L309D/Q311H/N434S (DHS); S228P/L235E (SPLE); L234A/L235A (LA), M428L/N434A L234A/G237A (LALA), L234A/L235A/G237A, L234A/L235A/P329G, N297A, D265A/YTE, LALA/YTE, LAGA/YTE, LALAGA/YTE, LALAPG/YTE, N297A/LS; D265A/LS; LALA/LS; LALAGA/LS; LALAPG/LS; N297A/DHS; D265A/DHS; LALA/DHS; LAGA/DHS; LALAGA/DHS; LALAPG/DHS; SP/YTE; SPLE/YTE; SP/LS; SPLE/LS, SP/DHS; SPLE/DHS; N297A/LA; D265A/LA, LALA/LA, LAGA/LA, LALAGA/LA, LALAPG/LA, N297A/N434A; D265A/N434A; LALA/N434A, LAGA/N434A, LALAGA/N434A, LALAPG/N434A, N297A/N434W, D265A/N434W, LALA/N434W, LAGA/N434W, LALAGA/N434W, LALAPG/N434W, N297A/DQ, D265A/DQ, LALA/DQ, LAGA/DQ, LALAGA/DQ, LALAPG/DQ, N297A/DW, D265A/DW, LALA/DW, LAGA/DW, LALAGA/DW, LALAPG/DW N297A/YD, D265A/YD, LALA/YD, LAGA/YD, LALAGA/YD, LALAPG/YD, T307Q/Q311V/A378V (QVV), N297A/QVV, D265A/QVV, LALA/QVV, LAGA/QVV, LALAGA/QVV, LALAPG/QVV, DDRVV, N297A/DDRVV, D265A/DDRVV, LALA/DDRVV, LAGA/DDRVV, LALAGA/DDRVV, and LALAPG/DDRVV. [00246] In certain embodiments, the antibodies described herein comprise an Fc region with YTE mutations at positions 253, 255, and 257. In certain embodiments, the antibodies described herein comprise an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, the antibodies described herein comprise an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236. In certain embodiments, the antibodies described herein comprise the heavy and light chain variable regions (VH and VL) as set forth in SEQ ID NOs: 3 and 39, respectively, and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively. 134 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00247] In certain embodiments, the antibodies described herein comprise a human IgG1 Fc with LALA mutations. In certain embodiments, the antibodies described herein comprise a human IgG1 Fc with YTE mutations. In certain embodiments, the antibodies described herein comprise a human IgG1 Fc with LALA and YTE mutations. In certain embodiments, when direct numbering is used these “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, in one embodiment, the human Fc region comprises a human IgG1 Fc with LALA mutations at L235A/L236A and/or YTE mutations at M253Y/S255T/T257E. [00248] In certain embodiments, the Fc region binds an Fcγ Receptor selected from the group consisting of: FcγRI, FcγRIIa, FcγRIIb, FcγRIIc, FcγRIIIa, and FcγRIIIb. In certain embodiments, the Fc region binds an Fcγ Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region. Modifications YTE Modifications [00249] In certain embodiments, the fragment crystallizable region (Fc region) of the IL-13 antibody described herein carries a triple substitution M252Y/S254T/T256E (YTE) designed to increase the half-life of the IgG. In certain embodiments, the Fc region of the anti-IL-13 antibody described herein carries a triple substitution M253Y/S255T/T257E (YTE) designed to increase the half-life of the IgG. YTE substitutions increase the binding of the modified IgG to the human neonatal Fc receptor (FcRn). FcRn-bound IgG is recycled via lysosomal salvage, resulting in the IgG returning to the circulation. Thus, the YTE substitutions confer greater FcRn-IgG binding, prolonging the IgG serum half-life compared to an unmodified IgG. LALA Modification [00250] In certain embodiments, the IL-13 antibodies described herein additionally carries Fc region amino acid modifications L234A/L235A or L235A/L236A in the IgG1 heavy chain, commonly called LALA mutations. These changes can impair Fc receptor binding to IgG and prevent undesired effector cell activation. 135 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Binding [00251] In certain embodiments, an IL-13 antibody described herein is a high-affinity IgG1 humanized monoclonal antibody (mAb) that binds IL-13. In certain embodiments, the IL-13 antibody described herein contains YTE and LALA modifications and is built on an IgG1 backbone. [00252] Without wishing to be bound by theory, the binding of the IL-13 antibodies described herein to IL-13 prevent the formation of the IL-13Rα1/IL-4Rα active receptor heterodimer and subsequent IL-13-mediated signaling. The direct consequences of IL-13 signaling in atopic dermatitis (AD) pathology include dermal thickening, increased CD4+ T cell infiltration, and dermal barrier disruption. Consequently, preventing receptor heterodimer formation is believed to decrease the clinical severity of AD. [00253] The affinity of a molecule X for its partner Y can be represented by the dissociation equilibrium constant (KD). The kinetic components that contribute to the dissociation equilibrium constant are described in more detail below. Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). [00254] With regard to the binding of an antibody to a target molecule, the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non- target molecule). Specific binding can be measured, for example, by measuring binding to a target molecule (i.e., IL-13) and comparing it to binding to a non-target molecule. Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule. In certain embodiments, the affinity of an IL-13 antibody for a non-target molecule is less than about 50% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non- target molecule is less than about 40% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non-target molecule is less than about 30% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non-target molecule is less than about 20% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 136 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR antibody for a non-target molecule is less than about 10% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non-target molecule is less than about 1% of the affinity for IL-13. In certain embodiments, the affinity of an IL-13 antibody for a non- target molecule is less than about 0.1% of the affinity for IL-13. [00255] When used herein in the context of two or more antibodies, the term “competes with” or “cross-competes with” indicates that the two or more antibodies compete for binding to an antigen (e.g., IL-13). In one exemplary assay, IL-13 is coated on a surface and contacted with a first IL-13 antibody, after which a second IL-13 antibody is added. In another exemplary assay, a first IL-13 antibody is coated on a surface and contacted with IL-13, and then a second IL-13 antibody is added. If the presence of the first IL-13 antibody reduces binding of the second IL-13 antibody, in either assay, then the antibodies compete with each other. The term “competes with” also includes combinations of antibodies where one antibody reduces binding of another antibody, but where no competition is observed when the antibodies are added in the reverse order. However, in certain embodiments, the first and second antibodies inhibit binding of each other, regardless of the order in which they are added. In certain embodiments, one antibody reduces binding of another antibody to its antigen by at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% as measured in a competitive binding assay. A skilled artisan can select the concentrations of the antibodies used in the competition assays based on the affinities of the antibodies for IL-13 and the valency of the antibodies. The assays described in this definition are illustrative, and a skilled artisan can utilize any suitable assay to determine if antibodies compete with each other. Suitable assays are described, for example, in Cox et al., “Immunoassay Methods,” in Assay Guidance Manual [Internet], Updated December 24, 2014 (ncbi.nlm.nih.gov/books/NBK92434/; accessed September 29, 2015); Silman et al., Cytometry, 2001, 44:30-37; and Finco et al., J. Pharm. Biomed. Anal., 2011, 54:351-358; each of which is incorporated by reference in its entirety. [00256] A test antibody competes with a reference antibody if an excess of a test antibody (e.g., at least 2x, 5x, 10x, 20x, or 100x) inhibits or blocks binding of the reference antibody by, e.g., at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% as measured in a competitive binding assay. Antibodies identified by competition assay (competing antibody) include antibodies binding to the same epitope as the reference antibody and antibodies binding to an adjacent epitope sufficiently proximal to the epitope bound by the reference antibody for steric 137 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR hindrance to occur. For example, a second, competing antibody can be identified that competes for binding to IL-13 with a first antibody described herein. In certain instances, the second antibody can block or inhibit binding of the first antibody by, e.g., at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% as measured in a competitive binding assay. In certain instances, the second antibody can displace the first antibody by greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%. [00257] In certain embodiments, the antibody binds an IL-13 sequence set forth in SEQ ID NOs: 472-475. [00258] In certain embodiments, the antibody binds to an IL-13 sequence set forth in SEQ ID NOs: 472-475 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10-9 M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody binds to an IL-13 sequence set forth in SEQ ID NOs: 472-475 with a KD of less than or equal to about 1 x 10-10 M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody binds to human IL-13 with a KD of less than or equal to about 1 x 10-9 M, as measured by surface plasmon resonance (SPR). [00259] In certain embodiments, an antibody provided herein binds IL-13 with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10-8 M, as measured by ELISA or any other suitable method known in the art. In certain embodiments, an antibody provided herein binds IL-13 with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10-9 M, as measured by ELISA or any other suitable method known in the art. [00260] In certain embodiments, the KD of an antibody provided herein for the binding of IL- 13 is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2-1.3, 1.3-1.4, 1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10-8 M, as measured by ELISA or any other suitable method known in the art. In certain embodiments, an antibody provided herein binds IL-13 with a KD of less than or equal to about 1 x 10-8 M, or less than or equal to above 1 x 10-9 M as measured by ELISA or any other suitable method known in the art. 138 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00261] In certain embodiments, an antibody provided herein binds IL-13 with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10-8 M, or less, as measured by ELISA or any other suitable method known in the art . In certain embodiments, an antibody provided herein binds IL-13 with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8-1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10-8 M as measured by ELISA or any other suitable method known in the art. Pharmaceutical Formulations and Methods of Manufacture Thereof [00262] In some embodiments, the present disclosure provides pharmaceutical formulations that comprise a therapeutically effective amount of an IL-13 antibody disclosed herein. The pharmaceutical formulation comprises one or more excipients and/or surfactants and is maintained at a certain pH. Non-limiting examples of an “excipient,” as used herein, include any non-therapeutic agent added to the formulation to provide a desired physical or chemical property, for example, pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption, or penetration. [00263] Methods of manufacturing pharmaceutical formulations of the disclosure are also contemplated. The method can include adjusting the matrix of an intermediate preparation of the disclosure (e.g., changing the buffer composition and/or the concentration of a purified preparation of an IL-13 antibody), such as by Ultrafiltration and Diafiltration (UFDF), to increase a concentration of an IL-13 antibody. [00264] In certain aspects, described herein is a method of manufacturing an intermediate preparation of an interleukin 13 (IL-13) antibody comprising: (a) obtaining a purified preparation of the IL-13 antibody; and (b) adjusting the matrix of the purified preparation of step (a), wherein adjusting the matrix of comprises performing Ultrafiltration and Diafiltration (UFDF) with the diafiltration buffer of the above described aspect or any one of the embodiments thereof, thereby obtaining the intermediate preparation of the IL-13 antibody. In some embodiments, the intermediate preparation (e.g., a UFDF intermediate preparation) can be used to prepare a final preparation through the addition of excipients and/or dilution. 139 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00265] In certain embodiments, the intermediate preparation of the IL-13 antibody has a higher concentration of the IL-13 antibody relative to the purified preparation. [00266] In certain embodiments, the method of manufacturing further comprises: (c) formulating the intermediate preparation to obtain a formulation of the IL-13 antibody. In certain embodiments, the formulation of the IL-13 antibody comprises a formulation described herein. [00267] In some embodiments, described herein is a diafiltration buffer comprising: (a) a histidine buffer; and (b) arginine or a salt solution thereof, at pH of from 5.4 to 7.0, e.g., from 5.5-6.5. In some embodiments, the pH is from about 5.7 to about 6.5. In some embodiments, the pH is about 5.8 or about 6.0. [00268] In some embodiments, the histidine buffer comprises a histidine and a histidine salt. In some embodiments, the histidine is L-histidine. In some embodiments, the histidine salt is L- histidine HCl monohydrate. Histidine buffer can be present in an amount of about 15-20 mM, for example, at about 18 mM. [00269] In some embodiments, the diafiltration buffer comprises arginine, and wherein the arginine is L-arginine. In some embodiments, the diafiltration buffer comprises an L-arginine salt solution. In some embodiments, the L-arginine salt solution salt solution comprises HCl monohydrate. In some embodiments, the L-arginine salt solution is at a concentration between 40 mM and 200 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 50 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 100 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 120 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 170 mM. [00270] Additional methods for the manufacture of pharmaceutical formulations of the disclosure are known in the art. Excipients, Surfactants, and pH [00271] Excipients may be selected for their suitability for intravenous or subcutaneous administration, providing the necessary stabilizing, buffering capacity, viscosity, and tonicity. The formulation can improve the stability of the IL-13 antibody and can provide a sterile solution suitable for subcutaneous or intravenous administration. In some embodiments the excipients and/or surfactants contained in the formulation are pharmacopoeial grade excipients. In some embodiments, the excipients in the formulation comprise a histidine buffer (also referred 140 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR to as a His buffer) (e.g., a combination L-histidine and L-histidine HCl buffer, also referred to as L-His and L-His HCl), an acetate buffer, or a succinate buffer; arginine (Arg) and/or methionine (Met) (e.g., L-arginine (L-Arg) and/or L-methionine (L-Met)) or a salt solution thereof; and a polysorbate or a poloxamer. In some embodiments, the formulation further comprises a sugar or sugar alcohol. [00272] The one or more excipients in the pharmaceutical formulation of the present invention can comprise a buffering agent. The term “buffering agent,” as used herein, refers to one or more components that when added to an aqueous solution is able to protect the solution against variations in pH when adding acid or alkali, or upon dilution with a solvent. In addition to histidine buffers, acetate buffers, and succinate buffers, in certain embodiments, phosphate buffers, glycinate buffers, carbonate buffers, citrate buffers and the like can be used. In some embodiments, sodium, potassium or ammonium ions can serve as counterion. [00273] In certain embodiments, the buffer or buffer system, such as a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer), acetate buffer, or succinate buffer, comprises at least one buffer that has a buffering range that overlaps fully or in part with the range of between 5.5 and 7.0 (e.g., between 5.6 and 6.5, and 5.7 and 6.2). In some embodiments, the pH is between 5.6 and 6.5. In some embodiments, the pH is between 5.8 and 6.0. [00274] In some embodiments, the buffer has a pH of about 5.5. In some embodiments, the buffer has a pH of about 5.6. In some embodiments, the buffer has a pH of about 5.7. In some embodiments, the buffer has a pH of about 5.8. In some embodiments, the buffer has a pH of about 5.9. In some embodiments, the buffer has a pH of about 6.0. In some embodiments, the buffer has a pH of about 6.1. In some embodiments, the buffer has a pH of about 6.2. In some embodiments, the buffer has a pH of about 6.3. In some embodiments, the buffer has a pH of about 6.4. In some embodiments, the buffer has a pH of about 6.5. In some embodiments, the buffer has a pH of about 5.9-6.3. In some embodiments, the buffer has a pH of about 6.0. Under the rules of scientific rounding, a pH greater than or equal to 5.45 and smaller than or equal to 5.55 is rounded as 5.5. [00275] In some embodiments, the histidine buffer (e.g., a combination L-histidine and L- histidine HCl buffer), acetate buffer, or succinate buffer is at a concentration between 5 mM and 20 mM (e.g., between 6 mM and 19 mM, 7 mM and 18 mM, 8 mM and 17 mM, 9 mM and 16 mM, and 10 mM and 15 mM). In some embodiments, the histidine buffer, acetate buffer, or 141 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR succinate buffer is at a concentration between 6 mM and 19 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 7 mM and 18 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 8 mM and 17 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 9 mM and 16 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 10 mM and 15 mM. [00276] In some embodiments, the histidine buffer (e.g., a combination L-histidine and L- histidine HCl buffer), acetate buffer, or succinate buffer is at a concentration of about 1 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 2 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 3 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 4 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 5 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 6 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 7 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 8 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 9 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 10 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 11 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 12 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 13 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 14 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 15 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 16 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 17 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 18 mM. In some embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 19 mM. In some 142 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR embodiments, the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 20 mM. [00277] In some embodiments the formulation comprises a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer), acetate buffer, or succinate buffer. In some embodiments the formulation comprises a histidine buffer. In some embodiments, the histidine buffer comprises L-histidine and L-histidine HCl. In some embodiments the formulation comprises an acetate buffer. In some embodiments, the formulation comprises a succinate buffer. [00278] In some embodiments, a histidine buffer (e.g., L-histidine and L-histidine HCl monohydrate) acts as a buffering agent. In some embodiments, the histidine buffer comprises a histidine and a histidine salt. In some embodiments, the histidine is L-histidine. In some embodiments, the histidine salt is L-histidine HCl monohydrate. [00279] In some embodiments, the formulation comprises methionine. In some embodiments, the methionine is L-methionine. [00280] In some embodiments, the methionine (e.g., L-methionine) is at a concentration between 1 mM and 20 mM (e.g., between 2 mM and 19 mM, 3 mM and 18 mM, 4 mM and 17 mM, 5 mM and 16 mM, and 5 mM and 15 mM). In some embodiments, the L-methionine is at a concentration between 1 mM and 19 mM. In some embodiments, the L-methionine is at a concentration between 2 mM and 18 mM. In some embodiments, the L-methionine is at a concentration between 3 mM and 17 mM. In some embodiments, the L-methionine is at a concentration between 4 mM and 16 mM. In some embodiments, the L-methionine is at a concentration between 5 mM and 15 mM. [00281] In some embodiments, the methionine (e.g., L-methionine) is at a concentration of about 1 mM. In some embodiments, the L-methionine is at a concentration of about 2 mM. In some embodiments, the L-methionine is at a concentration of about 3 mM. In some embodiments, the L-methionine is at a concentration of about 4 mM. In some embodiments, the L-methionine is at a concentration of about 5 mM. In some embodiments, the L-methionine is at a concentration of about 6 mM. In some embodiments, the L-methionine is at a concentration of about 7 mM. In some embodiments, the L-methionine is at a concentration of about 8 mM. In some embodiments, the L-methionine is at a concentration of about 9 mM. In some embodiments, the L-methionine is at a concentration of about 10 mM. In some embodiments, the L-methionine is at a concentration of about 11 mM. In some embodiments, the L-methionine is 143 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR at a concentration of about 12 mM. In some embodiments, the L-methionine is at a concentration of about 13 mM. In some embodiments, the L-methionine is at a concentration of about 14 mM. In some embodiments, the L-methionine is at a concentration of about 15 mM. In some embodiments, the L-methionine is at a concentration of about 16 mM. In some embodiments, the L-methionine is at a concentration of about 17 mM. In some embodiments, the L-methionine is at a concentration of about 18 mM. In some embodiments, the L-methionine is at a concentration of about 19 mM. In some embodiments, the L-methionine is at a concentration of about 20 mM. [00282] In some embodiments, the formulation comprises arginine. In some embodiments, the arginine is L-arginine. In some embodiments, the formulation comprises an L-arginine salt solution. In some embodiments, the L-arginine or L-arginine salt solution acts as a viscosity modulator. In some embodiments, the L-arginine salt solution salt solution comprises HCl monohydrate. [00283] In some embodiments, the arginine (e.g., L-arginine) salt solution is at a concentration between 40 mM and 250 mM (e.g., between 50 mM and 200 mM, 60 mM and 150 mM, 70 mM and 125 mM, 80 mM and 100 mM, and about 90 mM). For example, in some embodiments, the arginine (e.g., L-arginine) salt solution is at a concentration between 70 mM and 130 mM. [00284] In some embodiments, the L-arginine salt solution is at a concentration of about 40 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 50 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 60 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 70 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 80 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 90 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 100 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 120 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 125 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 150 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 170 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 200 mM. In some embodiments, the L-arginine salt solution is at a concentration of about 250 mM. 144 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00285] The one or more excipients in the pharmaceutical formulation disclosed herein further comprises a surfactant. The term “surfactant,” as used herein, refers to a surface active molecule containing both a hydrophobic portion (e.g., alkyl chain) and a hydrophilic portion (e.g., carboxyl and carboxylate groups). Surfactants are useful in pharmaceutical formulations for reducing aggregation of a therapeutic protein. Surfactants suitable for use in the pharmaceutical formulations are generally non-ionic surfactants and include, but are not limited to, polysorbates (e.g., polysorbates 20 or 80); poloxamers (e.g., poloxamer 188); sorbitan esters and derivatives; Triton; sodium laurel sulfate; sodium octyl glycoside; lauryl-, myristyl-, linoleyl-, or stearyl- sulfobetadine; lauryl-, myristyl-, linoleyl- or stearyl-sarcosine; linoleyl-, myristyl-, or cetyl- betaine; lauramidopropyl-cocamidopropyl-, linoleamidopropyl-, myristamidopropyl-, palmidopropyl-, or isostearamidopropylbetaine (e.g., lauroamidopropyl); myristamidopropyl-, palmidopropyl-, or isostearamidopropyl-dimethylamine; sodium methyl cocoyl-, or disodium methyl oleyl-taurate; and the MONAQUATTM series (Mona Industries, Inc., Paterson, N.J.), polyethylene glycol, polypropyl glycol, and copolymers of ethylene and propylene glycol (e.g., Pluronics, PF68, etc.). In certain embodiments, the surfactant is a polysorbate. In certain embodiments, the surfactant is polysorbate 80. In certain embodiments, the surfactant is a poloxamer. In certain embodiments, the surfactant is poloxamer 188. [00286] In some embodiments, a polysorbate or poloxamer acts as a stabilizer. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.005% w/v and 0.15% w/v or between 0.01% w/v and 0.15% w/v (e.g., between 0.02% and 0.14%, 0.03% and 0.13%, 0.04% and 0.12%, 0.05% and 0.11%, or about 0.1%). In some embodiments, the polysorbate or poloxamer is at a concentration between 0.02% and 0.14%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.03% and 0.13%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.04% and 0.12%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.05% and 0.11%. In some embodiments, the polysorbate or poloxamer is at a concentration between 0.005% w/v and 0.10% w/v, or between 0.005% w/v and 0.05% w/v or between 0.05% w/v and 0.10 w/v, or at about 0.05% w/v or at 0.05% w/v. [00287] In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.005% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.01% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 145 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 0.02% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.03% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.04% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.05% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.06% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.07% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.08% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.09% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.1% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.11% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.12% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.13% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.14% w/v. In some embodiments, the polysorbate or poloxamer is at a concentration of about 0.15% w/v. [00288] In some embodiments, the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In some embodiments, the polysorbate is polysorbate 20. In some embodiments, the polysorbate is polysorbate 40. In some embodiments, the polysorbate is polysorbate 60. In some embodiments, the polysorbate is polysorbate 80. [00289] In some embodiments, the poloxamer is poloxamer 188, also referred to herein as P188. In some embodiments, P188 is included in the formulation at a concentration in a range of, for example 0.1-2.0 mg/ml, 0.25-1.5 mg/ml or 0.5-1.0 mg/ml, or at a concentration of 0.25 mg/ml, 0.5 mg/ml, 0.75 mg/ml or 1.0 mg/ml. In some embodiments, the formulation comprises P188 at a concentration of 0.5 mg/ml. [00290] The one or more excipients in the pharmaceutical formulation of the present invention can further comprise a metal ion chelator. Metal ion chelators, also known as chelating agents, bind metal ions to form water soluble complexes and thus can be used to remove metal ions from a formulation. In embodiments, the metal ion chelator is ethylenediaminetetraacetic acid (EDTA), or a salt thereof (e.g., disodium EDTA, sodium calcium edetate, tetrasodium EDTA). In embodiments, the metal ion chelator is EDTA disodium salt (EDTA-2Na). In embodiments, the metal ion chelator is EDTA-2Na, which is included in the formulation at a concentration in a range of, for example, 0.001-1 mM or 0.01-1mM or 0.001-0.5 mM or 0.01-0.5 mM or at a 146 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR concentration of 0.01 mM, 0.02 mM, 0.03 mM, 0.04 mM, 0.05 mM, 0.06 mM, 0.07 mM, 0.08 mM, 0.09 mM, 0.1 mM, 0.2 mM, 0.3 mM, 0.4 mM, 0.5 mM, 0.6 mM, 0.7 mM, 0.8 mM, 0.9 mM or 1 mM. In embodiments, the formulation comprises EDTA (e.g., EDTA-2Na) at a concentration of 0.05 mM. [00291] Other metal ion chelators are known in the art, non-limiting examples of which include ethylenediamine (1,2-diaminoethane), diethylenetriaminepentaacetic acid (DTPA), ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), succimer (dimercaptonol), dimercaprol (BAL), nitrilotriacetic acid (NTA), iminodisuccinic acid (IDS), polyaspartic acid, S,S-ethylenediamine-N,N′-disuccinic acid (EDDS), methylglycinediacetic acid (MGDA), L-Glutamic acid N,N-diacetic acid, tetrasodium salt (GLDA), metachelate and citric acid. [00292] The one or more excipients in the pharmaceutical formulation of the present invention can further comprise a sugar or sugar alcohol. Sugars and sugar alcohols are useful in pharmaceutical formulations as a thermal stabilizer. In certain embodiments, the pharmaceutical formulation comprises a sugar, for example, a monosaccharide (glucose, xylose, or erythritol), a disaccharide (e.g., sucrose, trehalose, maltose, or galactose), or an oligosaccharide (e.g., stachyose). In specific embodiments, the pharmaceutical formulation comprises sucrose. In certain embodiments, the pharmaceutical composition comprises a sugar alcohol, for example, a sugar alcohol derived from a monosaccharide (e.g., mannitol, sorbitol, or xylitol), a sugar alcohol derived from a disaccharide (e.g., lactitol or maltitol), or a sugar alcohol derived from an oligosaccharide. In specific embodiments, the pharmaceutical formulation comprises sucrose. [00293] In some embodiments, a sugar or sugar alcohol (e.g., sucrose) acts as a stabilizer. In some embodiments, the sugar or sugar alcohol is at a concentration between 1% w/v and 5% w/v (e.g., between 2% w/v and 4% w/v, or about 3% w/v). In some embodiments, the sugar or sugar alcohol is at a concentration between 2% w/v and 4% w/v. [00294] In some embodiments, the sugar or sugar alcohol is at a concentration of about 1% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 2% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 3% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 4% w/v. In some embodiments, the sugar or sugar alcohol is at a concentration of about 5% w/v. 147 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00295] In some embodiments, the sugar or sugar alcohol is a disaccharide. In some embodiments, the disaccharide is sucrose. [00296] In some embodiments, the formulation is adjusted to final volume in water for injection (WFI). [00297] In certain embodiments, the drug product is diluted in an aqueous carrier suitable for the route of administration, e.g., intravenous administration. Exemplary carriers include sterile water for injection (SWFI), bacteriostatic water for injection (BWFI), a pH buffered solution (e.g., phosphate-buffered saline), sterile saline solution, Ringer's solution, or dextrose solution. In one embodiment, when the pharmaceutical formulation is prepared for intravenous administration, the pharmaceutical formulation can be diluted in a 5% dextrose solution (D5W). Exemplary Formulations [00298] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0. [00299] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., combination L-histidine and L-histidine HCl buffer), an acetate buffer (e.g., combination acetic acid and sodium acetate trihydrate), or a succinate buffer (e.g., combination succinic acid and sodium succinate hexahydrate); (c) arginine and/or methionine (e.g., L-arginine and/or L-methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0. In some embodiments, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; 148 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and (f) CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. [00300] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody at a concentration, e.g., between 140 mg/mL and 290 mg/mL; (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer), an acetate buffer, or a succinate buffer; (c) arginine and/or methionine (e.g., L-arginine and/or L- methionine) or a salt solution thereof; and (d) a polysorbate or a poloxamer, at pH 5.0 to 7.0. In some embodiments, the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR- L2, and CDR-L3; wherein: (a) CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; (b) CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; (c) CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, (d) CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, (e) CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and (f) CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. [00301] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) an IL-13 present at a concentration of, e.g., about 180 mg/mL; (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [00302] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) IL-13 antibody present at a concentration of, e.g., about 180 mg/mL; (b) a 149 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR histidine buffer (e.g.,, a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 80 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [00303] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) IL-13 antibody present at a concentration of, e.g., about 200 mg/mL; (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L- methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, at pH of about 5.8. [00304] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody present at a concentration of, e.g., about 180 mg/mL (e.g., at 180 mg/ml); (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM (e.g., at 10 mM); (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); (e) polysorbate 80 at a concentration of about 0.05% w/v (e.g., at 0.05% w/v); and (f) EDTA or a salt thereof (e.g., EDTA-2Na) at a concentration of about 0.05 mM (e.g., at 0.05 mM), at pH of about 5.8-6.0 (e.g., at pH 5.8 or pH 6.0). [00305] In some embodiments, the pharmaceutical formulation of the present invention comprises: (a) an IL-13 antibody present at a concentration of, e.g., about 180 mg/mL (e.g., at 180 mg/ml); (b) a histidine buffer (e.g., a combination L-histidine and L-histidine HCl buffer) at a concentration of about 10 mM (e.g., at 10 mM); (c) an L-arginine salt solution at a concentration of about 120 mM (e.g., at 120 mM); (d) L-methionine at a concentration of about 10 mM (e.g., at 10 mM); (e) poloxamer 188 at a concentration of about 0.5 mg/ml (e.g., at 0.5 mg/ml), at pH of about 5.8-6.0 (e.g., at pH 5.8 or pH 6.0). [00306] In some embodiments, the formulation comprises a sugar, for example, sucrose at a concentration between about 2% w/v and 8% w/v, such as a concentration of about 3% w/v or about 5% w/v. 150 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Stability of the Anti-IL-13 Antibody [00307] The pharmaceutical formulations of the present invention exhibit high levels of stability. A pharmaceutical formulation is stable when the IL-13 antibody within the formulation retains an acceptable degree of physical property, chemical structure, and/or biological function after storage under defined conditions. [00308] Exemplary methods to determine stability of the IL-13 antibody in the pharmaceutical formulation are described in the Examples of the present disclosure. Additionally, stability of the protein can be assessed by measuring the binding affinity of the IL-13 antibody to its targets or the biological activity of the IL-13 antibody in certain in vitro assays. [00309] The pharmaceutical formulation can be prepared and stored as a liquid formulation. In certain embodiments, the pharmaceutical formulation is a liquid formulation for storage frozen (-20 to -70° C), under refrigerated conditions (typically 2-8° C), or at room temperature (typically 20-26° C) before preparation for administration. In certain embodiments, the pharmaceutical formulation is a liquid formulation for storage at a suitable temperature and protected from light. [00310] Stability studies have found an antibody concentration for solution of 180 mg/mL or 200 mg/mL for injection to be compatible with its excipients and primary packaging materials. Antibody 180 mg/mL or 200 mg/mL concentrate for injection is suitable for subcutaneous administration with disposable syringes, without dilution or with dilution in a carrier buffer. Materials found to be compatible with an antibody herein comprise injection syringes composed of polypropylene or polycarbonate, and needles for injection composed of stainless steel. Compatibility of antibody concentrate for solution for injection has been demonstrated with pre- filled syringes for an antibody concentration of from 160 mg/mL and 250 mg/mL. Dosage Forms [00311] Prior to pharmaceutical use, the pharmaceutical formulation can be diluted in an aqueous carrier if suitable for the route of administration. In some embodiments, a IL-13 antibody is fully formulated for subcutaneous administration (i.e., no diluents are added), and thus is identical in composition to the formulation described herein. Alternatively, if suitable for the route of administration, e.g., for intravenous administration, the IL-13 antibody may be further diluted in an appropriate carrier prior to pharmaceutical use. 151 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00312] For intravenous administration, suitable carriers include sterile water for injection (SWFI), bacteriostatic water for injection (BWFI), a pH buffered solution (e.g., phosphate- buffered saline), sterile saline solution, Ringer’s solution, or dextrose solution. For example, when the pharmaceutical formulation is prepared for intravenous administration, the pharmaceutical formulation may comprises a dextrose solution, such as a 5% dextrose solution (D5W). In certain embodiments, the diluted pharmaceutical formulation is isotonic and suitable for administration by intravenous infusion, e.g., D5W. In certain embodiments, the formulation is diluted in about 50 mL D5W, 100 mL D5W, 150 mL D5W, 200 mL D5W, 250 mL D5W, 300 mL D5W, 350 mL D5W, 400 mL D5W, 450 mL D5W, 500 mL D5W, or 1 L D5W. [00313] The pharmaceutical formulation comprises the IL-13 antibody at a concentration suitable for storage. In certain embodiments, the pharmaceutical formulation comprises the IL-13 antibody at a concentration between 160 mg/mL and 250 mg/mL (e.g., between 170 mg/mL and 210 mg/mL, 180 mg/mL and 200 mg/mL, or about 190 mg/mL). In some embodiments, the IL- 13 antibody is at a concentration between 170 mg/mL and 210 mg/mL. In some embodiments, the IL-13 antibody is at a concentration between 180 mg/mL and 200 mg/mL. [00314] In some embodiments, the IL-13 antibody is at a concentration of about 160 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 170 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 180 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 190 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 200 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 210 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 220 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 230 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 240 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of about 250 mg/mL. [00315] In some embodiments, the IL-13 antibody is at a concentration of 160 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 170 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 180 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 190 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 200 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 210 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 220 mg/mL. In 152 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR some embodiments, the IL-13 antibody is at a concentration of 230 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 240 mg/mL. In some embodiments, the IL-13 antibody is at a concentration of 250 mg/mL. [00316] Formulations described herein may be included in e.g., a vial, bag, bottle or on-body device. In some embodiments, the vial is a syringe. In some embodiments, the vial is a glass syringe. In some embodiments, the syringe is a prefilled syringe. In some embodiments, the prefilled syringe is a prefilled glass syringe. Additionally, formulations herein may be included in and administered by pens, autoinjectors, including autoinjector syringes and cartridges, and on-body devices. In some embodiments, when an on-body device is used for administration, up to 5 mL of the formulation may be present in the device. [00317] In some embodiments, an extractable volume of the vial (e.g., prefilled syringe) is between 1.0 mL and 10.0 mL, e.g., between 1.0 mL and 3.0 mL or between 3.0 mL and 10.0 mL. In some embodiments, the extractable volume of the vial is about 1.0, 2.0 mL, 3.0 mL, 4.0 mL, 5.0 mL, 6.0 mL, 7.0 mL, 8.0 mL, 9.0 mL or 10.0 mL. As used herein, the “extractable volume” of the vial is the amount that can be withdrawn from the receptacle. The fill volume is greater than the extractable volume to ensure that the extractable volume can be obtained. [00318] In certain embodiments, the pharmaceutical formulation is packaged in a vial (e.g., a pen or syringe). In certain embodiments, the vial comprises an overfill to allow for complete removal of the intended dose. In certain embodiments, the vial comprises an overfill of 5 to 35%, 10 to 30%, 15 to 25%, or 10 to 20%. In a particular embodiment, the vial comprises an overfill of about 20%. [00319] In certain embodiments, the formulation may be a liquid formulation. In certain embodiments, the amount of IL-13 antibody in the container is suitable for administration as a single dose. In certain embodiments, the amount of IL-13 antibody in the container is suitable for administration in multiple doses. In certain embodiments, the pharmaceutical formulation comprises the IL-13 antibody in an amount of 0.1 to 200 mg. In certain embodiments, the pharmaceutical formulation comprises the IL-13 antibody in an amount of 1 to 200 mg, 10 to 200 mg, 20 to 200 mg, 50 to 200 mg, 100 to 200 mg, 200 to 500 mg, 500 to 2000 mg, 1000 to 2000 mg, 0.1 to 1000 mg, 1 to 1000 mg, 10 to 1000 mg, 20 to 1000 mg, 50 to 1000 mg, 100 to 1000 mg, 200 to 1000 mg, 500 to 1000 mg, 0.1 to 500 mg, 1 to 500 mg, 10 to 500 mg, 20 to 500 mg, 50 to 500 mg, 100 to 500 mg, 200 to 500 mg, 0.1 to 200 mg, 1 to 200 mg, 10 to 200 mg, 20 153 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR to 200 mg, 50 to 200 mg, 100 to 200 mg, 0.1 to 100 mg, 1 to 100 mg, 10 to 100 mg, 20 to 100 mg, 50 to 100 mg, 0.1 to 50 mg, 1 to 50 mg, 10 to 50 mg, 20 to 50 mg, 0.1 to 20 mg, 1 to 20 mg, 10 to 20 mg, 0.1 to 10 mg, 1 to 10 mg, or 0.1 to 1 mg. In certain embodiments, the pharmaceutical formulation comprises the IL-13 antibody in an amount of about 0.1 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 450 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1500 mg, or about 2000 mg. Methods of Use [00320] The present application provides compositions comprising a formulation or vial described herein for use in the treatment of an inflammatory disorder or disease. In some embodiments, the present application also provides compositions comprising a formulation or vial (e.g., pre-filled syringe) described herein for use in methods of treating inflammatory, allergic, and immunologic diseases, such as atopic dermatitis, in a patient in need thereof. In certain embodiments, the patient has been diagnosed with moderate-to-severe atopic dermatitis. In certain embodiments, the patient has had moderate-to-severe atopic dermatitis for at least one year. In certain embodiments, the patient is a pediatric patient. [00321] In certain embodiments, the patient has one or more of: (a) an Eczema Area and Severity Index Score (EASI) of ≥10 (e.g., an EASI of ≥16 or an EASI ≥10 and <16), (b) an Investigator Global Assessment (IGA) score of ≥3 and (c) a body surface area (BSA) of ≥10%. In certain embodiments, the patient has an Eczema Area and Severity Index Score (EASI) of ≥10. In certain embodiments, the patient has an Eczema Area and Severity Index Score (EASI) of ≥16. In certain embodiments, the patient has an Eczema Area and Severity Index Score (EASI) of ≥10 and less than 16. In certain embodiments, the patient has an Investigator Global Assessment (IGA) score of ≥3. In certain embodiments, the patient has a body surface area (BSA) of ≥10%. [00322] The “Investigator Global Assessment” or “IGA” is an assessment measure used globally to rate the severity of the patient’s AD (Simpson E, et al. J Am Acad Dermatol. 2020;83(3):839-846). It is based on a 5-point scale ranging from 0 (clear) to 4 (severe) and a 154 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. It is not necessary that all characteristics under Morphological Description be present. The IGA can be conducted prior to conducting the EASI and BSA assessments. [00323] The “Eczema Area and Severity Index” or “EASE is a measure used in clinical settings to assess the severity and extent of AD (Hanifin et al., Exp Dermatol. 2001; 10: 11-18). EASI is a composite index with scores ranging from 0 to 72, with the higher values indicating more severe and or extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification can be assessed by a clinician or other medical professional on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head and neck, trunk, upper limbs, and lower limbs, with half points allowed. In addition, the extent of AD involvement in each of the 4 body areas can be assessed as a percentage by body surface area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. A total score (0 – 72) is assigned based on the sum of total scores for each of the four body region scores. [00324] The “Scoring of Atopic Dermatitis” or “SCORAD” is a validated clinical tool for assessing the extent and intensity of AD developed by the European Task Force on Atopic Dermatitis (Consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993; 186(l):23-31). There are 3 components to the assessment: (i) the extent of AD is assessed as a percentage of each defined body area and reported as the sum of all areas, with a score ranging from 0 to 100 (assigned as “A” in the overall SCORAD calculation); (ii) the severity of 6 symptoms of AD: redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness. Each item is graded as follows: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points, assigned as “B” in the overall SCORAD calculation); (iii) subjective assessment of itch and of sleeplessness is recorded for each symptom using a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum possible score of 20 (assigned as “C” in the overall SCORAD calculation). The SCORAD Index formula is: A/5 + 7B/2 + C. The maximal score of the SCORAD Index is 103. [00325] Pruritus Numerical Rating Scale (NRS) is an 11 -point scale used by patients (and if applicable, with help of parents/ caregiver if required) to rate their worst itch severity over the past 24 hours with 0 indicating “No itch” and 10 indicating “Worst itch imaginable” (Phan NQ, et al. Acta Derm Venereol 2012; 92: 502-507). Assessments are recorded by the patient daily 155 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR using an electronic diary. The baseline pruritus NRS is determined based on the average of daily Pruritus NRS during the 7 days immediately preceding baseline. A minimum of 4 daily scores out of the 7 days immediately preceding baseline is required for this calculation. [00326] Sleep loss scale rates patient’s sleep loss due to pruritus on a 5-point Likert scale (with scores ranging from 0 [not at all], 1 [a little], 2 [moderately], 3 [quite a bit], to 4 [unable to sleep at all]). Assessments will be recorded daily by the patient using an electronic diary. [00327] The Patient-Oriented Eczema Measure (POEM) is a 7-item, validated, questionnaire completed by the patient (and if applicable, with help of parents/ caregiver if required) to assess disease symptoms over the last week (Centre of Evidence Based Dermatology. POEM – Patient Oriented Eczema Measure. Available at www.nottingham.ac.uk/research/groups/cebd/resources/poem.aspx). Patients are asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1- 2 days = 1; 3-4 days = 2; 5-6 days = 3; everyday = 4). A high score is Indicative of a poor quality of life. POEM responses are captured weekly using an electronic diary. [00328] The Dermatology Life Quality Index (DLQI) is a 10-item, validated questionnaire completed by the patient or caregiver, used to assess the impact of skin disease on the quality of life of the patient (Finlay, A. Y. and Khan, G. K. 1994. Clinical and Experimental Dermatology 1993 Sep 23; 19:210-216). The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Each question is scored from 0 to 3 (“not at all,” “a little,” “a lot,” and “very much”), giving a total score ranging from 0 to 30. A high score is indicative of a poor quality of life. [00329] In certain embodiments, methods described herein comprise determining one or more of the following characteristics of the patient at baseline and during and after the induction period: Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Body Surface Area (BSA), Pruritus Numerical Rating Scale (NRS), Sleep loss scale, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: 156 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Eczema Area and Severity Index (EASI). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Investigator Global Assessment (IGA). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Body Surface Area (BSA). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Pruritus Numerical Rating Scale (NRS). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Sleep loss scale, SCORing Atopic Dermatitis (SCORAD). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Patient Oriented Eczema Measure (POEM). In certain embodiments, methods described herein comprise determining the following characteristic of the patient at baseline and during and after the induction period: Dermatology Life Quality Index (DLQI). [00330] In certain embodiments, a patient described herein is determined to have one or more of the following characteristics of the patient at baseline and during and after the induction period: Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Body Surface Area (BSA), Pruritus Numerical Rating Scale (NRS), Sleep loss scale, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI). In certain embodiments, a patient herein is determined to have a characteristic Eczema Area and Severity Index (EASI) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Investigator Global Assessment (IGA) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Body Surface Area (BSA) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Pruritus Numerical Rating Scale (NRS) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Sleep loss scale, SCORing Atopic Dermatitis (SCORAD) at baseline and during and after the induction period. In certain embodiments, a patient herein is determined to have a characteristic Patient Oriented Eczema Measure (POEM) at baseline and during and after the induction period. 157 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR In certain embodiments, a patient herein is determined to have a characteristic Dermatology Life Quality Index (DLQI) at baseline and during and after the induction period. [00331] In an aspect, the present application provides methods of contacting IL-13 with an IL- 13 antibody, such as a human, humanized, or chimeric antibody, which results in inhibition of IL-13 binding to an IL-13 receptor expressed on a cell. [00332] In an aspect, the present application provides compositions comprising a formulation or vial described herein for use in the treatment of an inflammatory disorder or disease selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic Bronchopulmonary Aspergillosis (ABPA), and Chronic Obstructive Pulmonary Disease (COPD). [00333] In an aspect, the present application provides methods for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein. [00334] In some embodiments, the inflammatory disorder or disease is atopic dermatitis. [00335] In some embodiments, the inflammatory disorder or disease is selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic 158 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Bronchopulmonary Aspergillosis (ABPA), and Chronic Obstructive Pulmonary Disease (COPD). [00336] In some embodiments, the inflammatory disorder or disease is asthma. In some embodiments, the inflammatory disorder or disease is idiopathic pulmonary fibrosis. In some embodiments, the inflammatory disorder or disease is alopecia areata. In some embodiments, the inflammatory disorder or disease is chronic sinusitis with nasal polyps. In some embodiments, the inflammatory disorder or disease is Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). In some embodiments, the inflammatory disorder or disease is eosinophilic esophagitis (EoE). In some embodiments, the inflammatory disorder or disease is an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG). In some embodiments, the inflammatory disorder or disease is Eosinophilic Enteritis (EoN). In some embodiments, the inflammatory disorder or disease is Eosinophilic Colitis (EoC). In some embodiments, the inflammatory disorder or disease is and Eosinophilic Gastroenteritis (EGE). In some embodiments, the inflammatory disorder or disease is Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA). In some embodiments, the inflammatory disorder or disease is Prurigo Nodularis (PN). In some embodiments, the inflammatory disorder or disease is of Chronic Spontaneous Urticaria (CSU). In some embodiments, the inflammatory disorder or disease is Chronic Pruritis of Unknown Origin (CPUO). In some embodiments, the inflammatory disorder or disease is Bullous Pemphigoid (BP). In some embodiments, the inflammatory disorder or disease is Cold Inducible Urticaria (ColdU). In some embodiments, the inflammatory disorder or disease is Allergic Fungal Rhinosinusitis (AFRS). In some embodiments, the inflammatory disorder or disease is Allergic Bronchopulmonary Aspergillosis (ABPA). In some embodiments, the inflammatory disorder or disease is Chronic Obstructive Pulmonary Disease (COPD). [00337] In an aspect, the present application provides methods for treating a pathology associated with elevated levels of IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein. [00338] In an aspect, the present application provides methods of reducing biological activity of IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein. 159 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00339] In an aspect, the present application provides methods of inhibiting the TH2 type allergic response in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein. [00340] In an aspect, the present application provides methods of reducing levels of Thymus and Activation Regulated Chemokine (TARC)/CCL17 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein. [00341] In an aspect, the present application provides methods of preventing an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation described herein. [00342] In some embodiments, the formulation is administered subcutaneously or intravenously. EXAMPLES [00343] The disclosure now being generally described, will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present disclosure, and are not intended to limit the scope of the disclosure in any way. Example 1: Formulation of an Anti-Interleukin 13 Antibody: pH and Buffer Studies [00344] This Example describes formulation studies of an interleukin 13 (IL-13) antibody, Construct 133. In formulating the antibody, twelve pH/buffers were investigated under stress conditions (40 °C for up to 4 weeks) to select pH and buffer system that stabilize the antibody. [00345] A panel of analytical methods were used to characterize the pH and buffer studies, including appearance, pH, protein concentration, size exclusion-ultra performance liquid chromatography (SE-UPLC), imaged capillary isoelectric focusing (iCIEF), chip method of sodium dodecyl sulfate-polyacrylamide capillary electrophoresis (non-reduced and reduced, Caliper-SDS-NR & R, respectively), and differential scanning calorimetry (DSC), described below. [00346] The pH studies evaluated pH from about 4.5 to about 7.5, such as pH 5.5, 6.0, and 6.5. It was determined that the range of 5.5 to 6.5 was suitable for a formulation described 160 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR herein, and a pH of 5.8 was selected due to its favorable results in SE-UPLC experiments. Buffers tested included a histidine buffer (i.e., combination L-histidine and L-histidine HCl buffer), an acetate buffer, a succinate buffer, and a phosphate buffer (PB). The histidine, acetate, and succinate buffers stabilized the antibody well. Materials and Methods Appearance [00347] The appearance of samples, including color, clarity, and visible particles, was examined against black and white background using YB-2 lightbox. Light intensity of lightbox was set as 2000~3750 lx. Protein Concentration (A280) [00348] Protein concentration was measured using a UV/visual light absorbance spectrometer (Lunatic, Unchained Labs or SoloVPE). According to the Lambert-Beer law, the concentration of a protein solution was calculated based on its absorbance at a given wavelength, the cuvette cell path length, and extinction coefficient value. The absorbance at 280 nm relied on the absorption properties of the aromatic amino acid residues in a respective protein. After loading a 2 μL sample volume, the spectrometer was used to measure the absorbance in two cuvettes in parallel, and the concentration value was calculated. The SoloVPE system was dependent on the variable pathlength Spectroscopy Technology. Slope m= A/L was obtained by measuring the absorbance at multiple different path lengths (>5 data points). Through the curve of path length and absorbance, the slope m was calculated. As C=m/ε, with ε and m known, the concentration was calculated. The extinction coefficient used in this evaluation was 1.45 (mg/mL)-1-cm-1. pH [00349] The pH of samples was measured using a pH meter with a glass electrode at 25 ℃. The pH meter was calibrated with three different standards (pH 4.01, 7.00, and 9.21) prior to usage. The slope of calibration was between 95.0% to 105.0%. Each sample was measured twice, and an average result was reported. SE-UPLC [00350] SE-UPLC was used as a purity analysis method to separate proteins based on their sizes. Size exclusion chromatography was performed on an Agilent UPLC system with a size 161 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR exclusion chromatography (SEC) column (Waters Acquity BEH 150×4.6 mm, 1.7 μm). The sampler temperature was set to 5 ± 3 °C and the column oven temperature was set as 25 ± 3 °C. The mobile phase was 50 mM PB, 300 mM NaCl, pH 6.8 ± 0.1; and the flow rate was set as 0.4 mL/min. 10 μg of each sample was injected. Detection wavelength was set at 280 nm and the run time was 8 min. Data was analyzed by Agilent CDS Software. iCIEF [00351] iCIEF was used to monitor the distribution of charged variants. The isoelectric point (pI), which is an intrinsic property of a given protein, is the pH at which the protein molecule did not carry net electrical charge. Under an external electric field, the charge variants moved along a continuous pH gradient formed by carrier ampholytes and stopped where the pH equaled its pI. [00352] Antibody samples were mixed with master mixture to generate loading mixture, which contained 4.0 μL Pharmalyte 3-10, 35 μL 1% MC, 0.5 μL pI marker 4.65, 0.5 μL pI marker 9.22, 37.5 μL 8 M urea solution, and 2.5 μL ultrapure water at a final protein concentration of 1.0 mg/mL. The loading mixture was loaded into a Maurice iCIEF cartridge and analyzed with Maurice Capillary Isoelectric Focusing Analyzer with whole-column detection camera. After the analysis, the raw data were processed with Empower 3. Caliper-SDS-NR & R [00353] Non-reduced Caliper Sodium Dodecyl Sulfate (SDS, Caliper-SDS-NR) was performed based on a PerkinElmer Caliper automated electrophoresis that allowed protein separation by size. In the non-reduced microchip capillary electrophoresis (CE) SDS (CE-SDS) analysis, samples were diluted to 1 mg/mL with pure water. 2 μL of diluted samples were mixed with 7 μL of the sample denaturing solution (the mixture of sample buffer, 10% SDS solution, and 100 mM N- Ethylmaleimide (NEM), with the volume ratio of 100:10:4). The well-mixed samples were incubated at 70 ℃ for 10 min. 35 μL of water was added to each sample, vortexed for 10 seconds, and centrifuged at 14000 rpm for 1 min. 42 μL of the prepared samples were transferred to a 96-well plate, centrifuged at 4000 rpm for 15 min, placed onto a Labchip GXII’s plate holder, separated, and detected in the HT Protein Express LabChip filled with destain-gel, gel-dye, and lower marker. Results were analyzed with LabChip GX Reviewer software. [00354] Reduced Caliper SDS (Caliper-SDS-R) was performed based on a PerkinElmer Caliper automated electrophoresis that allowed protein separation by size after reduction of 162 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR sample. In the reduced microchip CE-SDS analysis, samples were diluted to 1 mg/mL with pure water. 2 μL of diluted samples were mixed with 7 μL of the sample denaturing solution (the mixture of sample buffer, 10% SDS solution, and 1 M dithiothreitol as a reduction agent, with the volume ratio of 100:10:4). The well-mixed samples were incubated at 70 ℃ for 10 min. 35 μL of water was added to each sample, vortexed for 10 seconds, and centrifuged at 14000 rpm for 1 min. 42 μL of the prepared samples were transferred to a 96-well plate, centrifuged at 4000 rpm for 15 min, placed onto a Labchip GXII’s plate holder, separated, and detected in the HT Protein Express LabChip filled with destain-gel, gel-dye, and lower marker. Results were analyzed with LabChip GX Reviewer software. DSC [00355] The DSC thermos-analytical technique was used to characterize the thermal stability of protein samples and assess conformational differences between them. Measurements were performed on MicroCalTM VP Capillary DSC for thermal transition midpoint (Tm) and onset of unfolding (TOnset) testing. Samples were diluted to 1 mg/mL with the reference buffer. 400 μL of respective reference buffers were added into the odd-numbered wells of a 96-well plate, and 400 μL of samples were added into the even-numbered wells of the same plate. Experimental parameters were set such that the scan temperature ramped from 10 °C to 95 °C at a scan rate of 200 °C/hour. Data analysis was performed in MicroCal VP Capillary DSC automated data analysis software. Results [00356] A total of 12 pH/buffer systems covering the pH range from 4.5 to 7.5 were designed, including 20 mM acetate buffer (pH 4.5, pH 5.0, and pH 5.5), 20 mM succinate buffer (pH 5.0, pH 5.5, and pH 6.0), 20 mM histidine buffer (pH 5.5, pH 6.0, and pH 6.5; histidine buffers refers throughout Examples to a combination of L-histidine and L-histidine HCl), and 20 mM phosphate buffer (PB) (pH 6.5, pH 7.0, and pH 7.5). The antibody was buffer-exchanged into 12 buffers, then concentrated to target protein concentration (150 mg/mL), respectively. Each of the 12 solutions was filtered with a 0.22 μm polyvinylidene fluoride (PVDF) filter and filled into 2 mL glass vials (1 mL per vial), then stoppered, capped, and labeled. Each of the twelve samples was tested for appearance, protein concentration, SE-UPLC, iCIEF, Caliper-SDS-NR & R, DSC, 163 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR and pH at Day 0. Additionally, at Day 0, after testing, the twelve samples were stored at 40 °C for up to 4 weeks. At Week 2 and Week 4, the samples were further tested for appearance, protein concentration, SE-UPLC, iCIEF, and Caliper-SDS-NR & R. [00357] Appearance: all samples remained slightly yellow, slightly opalescent, liquid, and free of visible particles after incubation at 40 °C for 4 weeks. The sample opalescent strength varied across formulations with different buffer type, with opalescent strength greatest in the PB group, followed in-order by, succinate, histidine, and acetate. With an increase of pH, the opalescent intensity increased gradually in succinate and PB buffer groups. [00358] pH and protein concentration: the pH and protein concentration of the formulations were assessed over 4 weeks. The pH was observed near the target value at T0, and protein concentration (approximately 150.0 mg/mL) of all candidates remained relatively consistent after 4 weeks of incubation at 40 °C compared to those at T0, indicating that these parameters were stable under the tested thermal stress condition. [00359] SE-UPLC: All candidates showed a decline in the main peak % (2.4% to 16.8%) after 4 weeks of incubation at 40 °C. This change was the most pronounced in the acetate buffer at pH 4.5 (B1) and PB buffer at pH 7.5 (B12), while the acetate buffer at pH 5.5 (B3) and histidine buffer at pH 5.5, 6.0, and 6.5 (B7, B8, and B9, respectively) showed the smallest changes in main peak purity and high molecular weight species (HMW). Taken together, the results of the SE-UPLC experiments demonstrated that the antibody was the least stable in the acetate buffer at pH 4.5 (B1) and PB buffer at pH 7.5 (B12), and most stable in the acetate buffer at pH 5.5 (B3) and histidine buffer at pH 5.5, 6.0, and 6.5 (B7, B8, and B9, respectively). [00360] Caliper-SDS-NR & R: For Caliper-SDS-NR, the purity of all samples decreased with the increase of incubation time at 40 °C for up to 4 weeks (up to 22.0%). Acetate at pH 4.5 (B1), PB at pH 7.0 and 7.5 (B11 and B12, respectively) showed a faster and greater decline (> 8% by 4 weeks) than the samples in the other pH/buffer systems. Samples in the succinate and histidine buffer systems, particularly succinate at pH 6.0 (B6) and histidine at pH 5.5, 6.0, and 6.5 (B7, B8 and B9, respectively) performed relatively better. For Caliper-SDS-R, less changes were seen in all the samples (up to 10.8%) compared with Caliper-SDS-NR results, indicating that the fragmentation of the protein may, without being bound by theory, be primarily caused by inter- chain disulfide bonds breakage during incubation at 40 °C. There was a decline in the purity after 4 weeks of incubation at 40 °C in the samples formulated in acetate at pH 4.5 (B1), succinate at 164 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR pH 5.0 (B4), and PB at pH 7.0 and 7.5 (B11, and B12, respectively). Aside from the change in these four samples, no substantial difference in purity was observed among the other samples. Taken together, the results of the Caliper-SDS-NR & R experiments demonstrated that the succinate buffer at pH 6.0 (B) and histidine buffer at pH 5.5, 6.0, and 6.5 (B7, B8, and B9, respectively) performed relatively better in improving the stability of the antibody protein compared with other buffers. [00361] iCIEF: The measured pI value of all samples was 8.0. A decline in the main peak % (more than 26.2% for acetate at pH 4.5 and 5.0 (B1 and B2, respectively), succinate at pH 5.0 and 5.5 (B4 and B5, respectively), and PB buffer) was seen in all buffers after incubation at 40 °C for 4 weeks. Taken together, the results of the iCIEF studies demonstrated that the histidine buffer system performed better than the succinate and acetate buffer systems, followed by the PB buffer. Specifically, histidine at pH 5.5, 6.0, and 6.5 (B7, B8, and B9, respectively) showed the best performance, followed by succinate at pH 6.0 (B6) and acetate at pH 5.5 (B3). Further, the data from the iCIEF study indicated that the antibody protein was most stable in buffer systems with pH from 6.5 to 5.5 (except for PB buffer at pH 6.5 (B10) and succinate buffer at pH 5.5 (B5)), among which, the histidine at pH 5.5, 6.0, and 6.5 (B7, B8, and B9, respectively) buffer performed the best. [00362] DSC: the TOnset (°C) and Tm values (Tm1, Tm2, and Tm3 at °C) increased with the increase of pH for the same buffer (except for histidine buffer at pH 6.5 (B9)). Additionally, TOnset values were higher than 55.0 °C in all formulations except acetate buffer at pH 4.5 (B1) and succinate buffer at pH 5.0 (B4), indicating good conformational thermal stability overall. [00363] In summary, the pH/buffer studies investigated twelve pH/buffer types under stress conditions (40 °C for up to 4 weeks), and the results showed that stability of the antibody was dependent upon both the pH and buffer. Taken together, the studies herein demonstrated relatively poor protein stability in acetate at pH 4.5 and 5.0 (B1 and B2, respectively), succinate at pH 5.0 and 5.5 (B4 and B5, respectively) and all PB buffer systems (pH 6.5-7.5, B10-B12, respectively). Good protein stability was observed in acetate at pH 5.5 (B3), succinate at pH 5.5 (B6), and histidine buffer systems overall (pH 5.5-6.5, B7-B9, respectively). Given these results, it was identified that a histidine buffer, an acetate buffer, or a succinate buffer can be used to formulate an IL-13 antibody. Among the twelve total formulations tested, histidine at pH 5.5, 165 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 6.0, and 6.5 (B7, B8, and B9, respectively) showed the best performance, followed by acetate at pH 5.5 (B3) and succinate at pH 6.0 (B6). [00364] A formulation including an IL-13 antibody and a histidine buffer at pH 6.0 (B8) was further investigated for optimal excipient and surfactant strength (see Example 2). Example 2: Formulation of an Anti-IL-13 Antibody: Excipients and Surfactant Strength Studies [00365] This Example describes formulation studies of an IL-13 antibody. In formulating the antibody, different types of excipients (e.g., sucrose, α/α-trehalose dihydrate, and L-arginine hydrochloride (Arg-HCl), L-methionine, etc.), as well as various concentration of a polysorbate (e.g., polysorbate 80 (PS80) at 0.02% w/v, 0.04% w/v, and 0.06% w/v) and a poloxamer (e.g., poloxamer 188 (P188) at 0.05% w/v, 0.08% w/v, and 0.10% w/v) were evaluated under stress conditions (40 °C for up to 4 weeks, agitation at 300 rpm for up to 3 days, and freeze and thaw for up to 5 cycles) to select suitable excipients and surfactant strengths to improve protein stability. A panel of analytical methods were used to characterize the excipients and surfactant strengths, including appearance, pH, protein concentration, SE-UPLC, Caliper-SDS-NR & R, and iCIEF (the Methods of which are described in Example 1), as well as osmolality, viscosity, and amount of sub-visible particles by micro-flow imaging (MFI), described below. [00366] Among the different excipients tested, L-methionine was selected for further testing based upon the Caliper-SDS-NR & R data showing well-preserved purity as well as the SE- UPLC data that demonstrated that it helped maintain high molecular weight species (HMW). Additionally, the excipient L-arginine was selected for further testing based upon data that demonstrated that it improved (decreased) viscosity. Materials and Methods Excipients [00367] Excipients used in the Examples are outlined in Table 11. Table 11: Excipients Name Vendor Cat. No.
Figure imgf000167_0001
166 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Name Vendor Cat. No. Sodium acetate trihydrate Avantor 3461-01 0 0 0 0 0 C 0 0 2 0
Figure imgf000168_0001
, , , , , [00368] See Example 1. Osmolality [00369] Osmolality was measured using an Advanced 2020 Multi-Sample Osmometer. Before and after the tests, the testing accuracy of the osmometer was confirmed with a Clinitrol 290 mOsm/kg reference solution. The sample volume for testing was 20 μL, and only one test was performed for each sample. Viscosity [00370] A viscosity test was used to characterize the fluid properties of liquid sample. Measurements were performed by a VROC® initium one plus viscometer (Rheosense). When the sample fluid flowed through the VROC® chip with controlled flow rates, the pressure drop 167 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR of the fluid was detected by the sensors and the viscosity at a certain shear rate was determined using the Hagen-Poiseuille Principle. 35 µL of samples were loaded on A05 chip and the set chip temperature was 25 ± 0.1°C. The viscosity of the sample was measured at 3 different shear rates, and the testing at each shear rate was repeated 3 times. The mean value was reported as the final viscosity. MFI [00371] Sub-visible particles were monitored by a Micro Flow Imaging (MFI) system. 1.5 mL of each sample was transferred into the MFI 96-well plate for analysis. The results were analyzed by the vendor’s MVSS software. The sub-visible particle amount in the equivalent circular diameter over 2 μm, 5 μm, 10 μm, and 25 μm was reported. Stress Conditions [00372] For freeze and thaw (FT), samples were completely frozen at -70 °C and thawed at room temperature (RT). For thermal stress, samples were stored at 40 °C for up to 4 weeks. For agitation stress, samples were agitated at 300 rpm at 25 °C, for up to 3 days. Study Design [00373] The study design is outlined in Table 12. Table 12: Study Design Attributes Condition Sampling points and assay ) 5
Figure imgf000169_0001
Y = Caliper-SDS-NR & R, and iCIEF Z= Osmolality, pH, and viscosity 168 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR S= MFI Results [00374] An IL-13 antibody described herein was in 20 mM histidine buffer at pH 6.0. Stock solutions of 40% (w/w) sucrose, 22.5% (w/w) sorbitol, 44% (w/w) α/α- trehalose dihydrate, 700 mM Arg-HCl, 100 mM L-methionine (Met), 5 mM ethylene dinitrilo tetraacetic acid disodium salt dihydrate (EDTA-2Na), 5% (w/w) PS80, and 5% (w/w) P188 were prepared. The required amounts of antibody, excipient stock solutions, and surfactant stock solutions were calculated, weighed, and well-mixed based on the formulation recipes listed in Table 13. The proportion of excipients was adjusted based on the requirements for an isotonic solution. [00375] Each of the formulation solutions were filtered with a 0.22 μm PVDF filter and filled into 2 mL glass vials (1 mL per vial), then stoppered, capped, and labeled. Table 13: Formulation Candidates with Various Excipients and Surfactants Formulation No. Protein Excipients and Comments n ntr ti n rf t nt nt o
Figure imgf000170_0001
169 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Formulation No. Protein Excipients and Comments (notable ingredients) concentration, surfactants nt s
Figure imgf000171_0001
[00376] Appearance: All formulations remained slightly yellow, slightly opalescent, liquid, and free of visible particles. Formulations E4 (4% sucrose, 50 mM Arg-HCl, 0.02% PS80) and E5 (135 mM Arg-HCl, 0.02% PS80), both of which contain Arg-HCl, showed relatively stronger opalescence than other formulations. However, no substantial changes of opalescence were observed in E4 and E5 with the increase of incubation time for up to 4 weeks at 40 ℃. [00377] Osmolality, viscosity, and pH: As shown in Table 14, the pH of all the tested formulations was reported at their target value at T0. The osmolality, which is not a stability- indicative parameter, of all samples was approximately 285 mOsm/kg to 320 mOsm/kg, which demonstrated suitability for subcutaneous administration. The viscosity of all samples was between 5.9 mPa-s to 9.3 mPa-s, where the addition of Arg-HCl (E4 and E5) reduced the viscosity compared to those of other formulations. Table 14: Osmolality, pH, and Viscosity Results Osmolality H Viscosity )
Figure imgf000171_0002
170 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR E1 (Sucrose, 0.02% PS80) 302 6.0 8.4 E2 (Sucrose Methionine 002% PS80) 295 60 82
Figure imgf000172_0001
remained relatively stable during the study. [00379] Sub-visible particle (MFI): Compared with T0, no substantial changes were observed in the amount of sub-visible particles (≥ 2 μm, ≥10 μm, or ≥ 25 μm) after FT for 5 cycles, agitation for 3 days, or 40 °C incubation for 4 weeks in all tested formulations. By comparing samples within the same buffer system but different excipients (E1-E7), no differences of the amount of sub-visible particles were observed. Additionally, there were no obvious differences in the amount of the sub-visible particles in E1 (0.02% PS80), E8 (0.04% PS80), E9 (0.06% PS80), E10 (0.10% P188), E11 (0.08% P188), and E12 (0.05% P188). [00380] SE-UPLC: The data summary from the SE-UPLC testing for excipients and surfactants strength study is provided in Table 15. After freeze and thaw for 5 cycles or agitation for 3 days, the main peak % of all the test formulations remained at approximately 99.0% indicating consistent antibody freeze and thaw stability and agitation stability under the studied parameter in all studied formulations. [00381] After incubation at 40 °C for 4 weeks, the main peak % in all formulations declined by up to 2.9% compared to T0, although the differences were small. E8 and E9 (Sucrose, 0.04% and 0.06% PS80) showed slightly lower main peak levels. In addition, E2 (Sucrose, Methionine, 171 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 0.02% PS80) showed the smallest changes in main peak purity and HMW species, indicating that L-methionine helped control HMW formation. Table 15: SE-UPLC Results Formulation No. Stress SE-UPLC (Main peak % 3 6 3 6 3 6
Figure imgf000173_0001
172 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Formulation No. Stress SE-UPLC (Main peak % 3 6 3 6 . 6 3 6
Figure imgf000174_0001
173 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Formulation No. Stress SE-UPLC (Main peak % 3 7 3 7 3 6
Figure imgf000175_0001
174 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Formulation No. Stress SE-UPLC (Main peak % 3 6 3 6
Figure imgf000176_0001
thaw; CYS, cycles; D, day (s); W, weeks. [00382] Caliper-SDS-NR & R: The data summary from the Caliper-SDS-NR & R testing for excipients and surfactants strength study is provided in Table A. Table A: Caliper-SDS-NR & R Results Caliper-SDS-NR (Purity Caliper-SDS-R Formulation No. Stress
Figure imgf000176_0002
175 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Caliper-SDS-NR (Purity Caliper-SDS-R Formulation No. Stress % (Δ Purity %)) (Purity) %
Figure imgf000177_0001
176 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Caliper-SDS-NR (Purity Caliper-SDS-R Formulation No. Stress % (Δ Purity %)) (Purity) %
Figure imgf000178_0001
[00383] After freeze and thaw for 5 cycles or agitation for 3 days, both Caliper-SDS-NR & R testing data indicated that purity remained stable. After incubation at 40 °C for 4 weeks, the purity for all formulations remained stable in the Caliper-SDS-R testing. Slight 2.6% to 4.1% declines of Caliper-SDS-NR purity were observed in all formulations except E2 (Sucrose, Methionine, 0.02% PS80), which showed the lowest change of 2.0% decline in the main peak. 177 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Together, this data indicated that under thermal condition (40 ℃ incubation for 4 weeks) slight declines in Caliper-SDS-NR purity and Caliper-SDS-R were observed in all formulations. [00384] iCIEF: The measured pI value of all samples was 8.3. After freeze and thaw for 5 cycles or agitation for 3 days, no substantial changes of main peak % were observed in all samples. After incubation at 40 °C for 4 weeks, 19.5% to 24.4% iCIEF main peak % declines were observed in all formulations compared to T0, where E4 and E5 (both containing Arg-HCl) showed the lowest changes of main peak % (< 20%). Overall, all samples degraded similarly. [00385] The results of the studies undertaken to select one or more excipients and identify optimal surfactant strength to maximize the antibody protein stability are summarized qualitatively in Table 16. By comparing formulations with different excipients (E1-E7), E2 (Sucrose, Methionine), E4 (Sucrose, Arg-HCl), and E5 (Arg-HCl) showed relatively better performance compared to other formulations. E1 (Sucrose), E3 (Sucrose, EDTA-2Na), E6 (Trehalose dihydrate), and E7 (Sorbitol) showed acceptable performance. By comparing formulations with different surfactant types and strength, E1, E8, E9 (0.02%, 0.04% and 0.06% PS80, respectively), E10, E11, and E12 (0.10%, 0.08% and 0.05% P188, respectively) showed comparable and good performance. 178 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Table 16: Stability Performance Comparison of Formulations F E2 E3 h E5 ( E E E E
Figure imgf000180_0001
12 (Sucrose, 0.05% P188) Good Good Medium Medium Good Good Appearance: good performance, FP throughout the study. SE-UPLC: good performance, decrease of main peak % no more than 3.0%. iCIEF: 179 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR medium performance, decrease of main peak % > 20%; good performance, decrease of main peak % no more than 20.0%. Caliper-SDS-NR: medium performance, decrease of purity > 2.0%; good performance, no substantial changes. Caliper-SDS-R: good performance, no substantial changes. MFI: good performance, no substantial changes. 180 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR [00386] Methionine and sucrose were selected as the leading excipients and the three excipients Arg-HCl, glycine, and proline underwent further testing (See Example 3). Also, considering the large volume, antibody freeze-thaw stability, and antibody long-term storage stability, 0.04% PS80 was selected for further studies. Therefore, variations of a formulation including 20 mM histidine buffer, 10 mM Methionine, and 0.04% (w/v) PS80 at pH 6.0 were further tested with or without sucrose and Arg-HCl (or other excipients e.g., glycine and proline), as described in Example 3. Example 3: Formulation of an Anti-IL-13 Antibody: Viscosity and Osmolality Studies [00387] This Example describes formulation studies of an IL-13 antibody. In formulating the antibody, a key parameter was viscosity. Different excipients (e.g., Arg-HCl, glycine, and proline) were evaluated for their ability to improve formulation viscosity, while maximizing protein stability. A panel of analytical methods were used to characterize the viscosity excipient studies, including appearance, MFI, protein concentration, SE-UPLC, pH, osmolality, and viscosity (the Methods of which are described in Example 1 and Example 2). As described throughout Examples 1-2, the formulations selected for this stage of testing included a pH of about 5.8 due to its favorable results in SE-UPLC experiments (see Example 1), a histidine buffer (or comparable acetate or succinate buffer, respectively) and L-methionine, which was demonstrated to help control HMW formation and antibody purity (see Example 2). In the experiments herein, the excipient L-arginine was identified as useful for reducing viscosity. Methods [00388] In brief, the IL-13 antibody was in a histidine buffer system at pH 6.0 with protein concentration at 257 mg/mL. Stock solutions of 50% (w/w) sucrose, 1400 mM Arg.HCl, 200 mM L-Methionine, 2400 mM Glycine, 2400 mM L-Proline and 5% (w/w) PS80 were prepared. The required amounts of antibody, excipient stock solutions and surfactant stock solutions were calculated, weighed and well-mixed based on the formulation recipes listed in Table 17. Each of the formulation solutions were filtered with a 0.22 μm PVDF filter and filled into 2 mL (2R) glass vials (2.4 mL per vial), then stoppered, capped and labeled immediately. All samples filtration and aliquoting were carried out with aseptic procedures in a biosafety cabinet. 181 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Analytical tests including appearance (visual inspection), pH, protein concentration, osmolality, viscosity, SE-UPLC and sub-visible particles were performed in this study. Results [00389] Formulation candidates with various excipients, outlined in Table 17, were tested. 182 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Table 17: Formulations with Various Excipients Tested For
Figure imgf000184_0001
F13 200 / 240 mM Proline 10 mM Methionine 183 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Table 18: Sub-Visible Particles Protein Concentration SEC-ULPC Data pH Osmolality and Viscosity Results No. F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 F13 F14 F15
Figure imgf000185_0001
/ Arg-HCl / 58 9 2 198.6 1.1 98.9 6.0 323 21.7 17.7 184 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR [00390] All formulations remained slightly yellow, slightly opalescent, liquid, and free of visible particles. Formulations F4, F5, F9, F10 and F15 (containing Arg.HCl) showed slightly stronger turbidity than other formulations, and the opalescence of all formulations was in the range from 3 NTU to 18 NTU. The sub-visible particles, protein concentration, SEC-ULPC data, pH, osmolality, and viscosity data of the above-described 15 formulations is shown in Table 18, and the viscosity data is further depicted in FIG. 1. The data in Table 18 and FIG. 1 show that inclusion of the excipient Arg-HCl reduced viscosity compared to corresponding glycine and proline groups. [00391] Arg-HCl was selected as a viscosity modulator, and further experiments were conducted to identify a suitable Arg-HCl concentration to enable a high protein concentration, yet reduce viscosity. [00392] To assess Arg-HCl and antibody protein concentrations that minimize viscosity and achieve osmolality in an acceptable range, further analytical testing was conducted. Analytical testing included measurement of protein concentration, pH, osmolality, and viscosity at 20 ℃ and 25 ℃. The results are shown in Table 19 and Table 20, with Table 19 outlining the formulations used in the experiments of Table 20. [00393] It was observed that both Arg-HCl concentration and product concentration impacted viscosity. Protein concentration was the main contributor to viscosity in the range of Arg-HCl tested. The 190 mM Arg formulations had a osmolality higher than desired for a subcutaneous formulation. The feasibility of manufacturing both a 200 mg/mL formulation and a 180 mg/mL formulation was demonstrated. Based upon the results of these studies, three formulations were identified for further testing: Formulation A: 10 mM His buffer, 10 mM Met, 150 mM Arg-HCl, 0.05% PS80, pH 5.8; Formulation B: 10 mM His buffer, 10 mM Met, 80 mM Arg-HCl, 3%(w/v) sucrose, 0.05% PS80, pH 5.8; and Formulation C: 10 mM His buffer, 10 mM Met, 120 mM Arg-HCl, 0.05% PS80, pH 5.8. [00394] Additional osmolality and viscosity experiments of the three formulations are shown in Table 21, which were used to characterize the formulations over a range of antibody protein concentration. [00395] No major stability issues were observed for the selected formulations, and the results demonstrated that there was no impact to product quality as assayed by the analytical testing 185 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR panel. pH and protein concentration were close to the target, and the osmolality ranged from approximately 280 mOsm/kg to 390 mOsm/kg. [00396] Taken together, based on the experiments described in this Example, Arg-HCl was selected for inclusion in the final formulation as a viscosity modifier and L-Methionine was included in the formulation based on experiments described in Example 2, particularly the finding that L-methionine helped control HMW formation and antibody purity. Additionally, sucrose may be advantageous as a cryoprotectant, however it increased viscosity and osmolality. Based upon this, the inclusion of sucrose was further tested with a reduced concentration of L- arginine to compensate for the impact to osmolality in long term storage and stability studies described in Example 6 and Example 7. Table 19: Formulations Tested in Further Viscosity Studies Target concentration (mg/mL) Final formulation 220 0, 0,
Figure imgf000187_0001
Table 20: Further Viscosity Study Results [Arg- Target Measured pH Osmolality Viscosity Viscosity
Figure imgf000187_0002
186 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [Arg- Target Measured pH Osmolality Viscosity Viscosity HCl] conc. protein (mOsmol/kg) (mPa•S, (mPa•S, ° °
Figure imgf000188_0001
Measured Viscosity Protein C 9 6 6 7 1 9 5 9 4 7 3 5 8 6 0 7
Figure imgf000188_0002
187 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Example 4: Formulation of an Anti-IL-13 Antibody: UFDF Studies [00397] Because ultrafiltration/diafiltration (UFDF) enables material to be prepared as a concentrated solution in a buffer of choice, ensuring that a formulation was compatible with a UFDF step was desirable, particularly as this step often presents challenges when the protein solution has a high viscosity. High viscosity can present challenges for the UFDF step due to increased back-pressure in the system as the protein gets more concentrated. As the pressure builds, the processing time gets longer and exposes the product to more shear stress. In these experiments, different diafiltration (DF) buffers were evaluated to see what impact Arg-HCl had on viscosity and manufacturing feasibility. Diafiltration was performed using a Millipore, PES Type D Screen, 30 kDa membrane, as well as the DF buffers listed in Table 22, below. An overconcentrated (OC) pool was analyzed, and the pH, osmolality, viscosity, and protein percent yield data was determined, as shown in Table 22. [00398] In conclusion, it was observed that the addition of Arg-HCl to the DF buffer reduced the viscosity of the UFDF pool. The protein concentration also impacted the viscosity, and the increase in pH and reduction in the histidine concentration from the Donnan effect was reduced as the Arg-HCl concentration was increased in the DF buffer. [00399] To identify how to prepare the formulation by UFDF to identify suitable formulations, the DF buffer was evaluated for its impact on pH from the Donnan effect during UFDF (3 runs at different pH). Further, the excipient concentrations following UFDF due to the Donnan effect were evaluated. The experiment consisted of: Run 1: 904.4 g/m2, Run 2: 965.8 g/m2, and Run 3: 971.9 g/m2 using a Millipore, PES Type D Screen, 30 kDa membrane with 2 × 0.11 m2 for Run 1 and 3 × 88 cm2 for Runs 2 and 3. The DF buffers tested were 15 mM His-HCl, 120 mM Arg-HCl with a pH of 5.7, 5.5, and 5.9 for Runs 1-3, respectively. The results are provided in Table 23. [00400] In comparison to the load sample, all overconcentrated pool (OC) samples showed a minimal (less than 0.3%) SEC-UPLC purity loss, and the yields with chase sample consistently exceed 95%. This ensured the maintenance of sample quality and yield throughout the process. The excipient concentrations shifted due to the Donnan effect, while the pH shift remained minimal (less than 0.1), consistent with the experiments described in Table 22. The viscosity of 188 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR the OC pool was previously reduced by the addition of Arg-HCl. These runs were pooled for subsequent experiments described and to demonstrate the manufacturing feasibility for this step. 189 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR 18 m 18 m 5 18 m 1
Figure imgf000191_0001
p 5. Abbreviations: OC, overconcentrated pool; cP, centipoise. * determined via High-performance liquid chromatography; method not provided. Run 1 2
Figure imgf000191_0002
OC-2 260.6 5.55 99.3/0.7/ND 10.449 82.533 95.1 299 104.9 78.8 190 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR 3
Figure imgf000192_0001
OC: overconcentrated pool, HMW: high molecular weight, LMW: low molecular weight, ND: not detected: cP: centipoise. 191 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Example 5: Formulation of an Anti-IL-13 Antibody: Injectability Study [00401] This Example describes injectability studies to evaluate whether the forces required for injection would be acceptable for the formulation, as described and developed in Examples 1-4, of an IL-13 antibody. As described throughout Examples 1-3, the formulations selected for this stage of testing included a pH of about 5.8 due to its favorable results in SE-UPLC experiments (see Example 1), a histidine buffer (or comparable acetate or succinate buffer, respectively), L-methionine, which was demonstrated to help control HMW formation and antibody purity (see Example 2), and the excipient Arg-HCl, based on its ability to reduce viscosity (see Example 3). Materials and Methods [00402] The break-loose force and glide force method quantitatively measured the forces required to complete a prefilled syringe (PFS) injection (i.e., expel the content of the PFS). Break-loose force was defined as the force required to cause a change (from a rested position) in the plunger stopper position. Glide force (maximum glide force) was defined as the maximum force measured on the glide force profile during the course of expelling the contents of a PFS. The test was conducted with an Instron materials testing machine-34TM-5 equipped with a 2000N load cell. The load cell was selected based on the sample property (the maximum force is within the 70% of the load cell range). The crosshead moved at a 140 mm/min speed to apply compressive force to the PFS plunger rod. The measured compression force was recorded at 60 Hz as the content of the PFS being extruded (expelled). The measurement stopped when the force reached end of test criteria where the plunger stopper hits the end of syringe barrel. Data are reported numerically in 2 decimal places (N). [00403] The required amounts of material, excipient stock solutions, and surfactant stock solution were calculated, weighed, and well-mixed to prepare formulations with the target protein concentration at 220 mg/mL according to the formulation recipes listed in Table 24. Then, a stepwise gravimetric dilution on protein concentration from 220 mg/mL to 170 mg/mL in 10 mg/mL increments was performed with the respective formulation buffers. Each of the formulation solution were filtered with a 0.22 μm PES filter. All sample filtration and aliquoting was carried out with aseptic procedures in a bio-safety cabinet. 192 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Results [00404] The study was conducted in triplicate. Pre-filled syringes with plunger stoppers and standard syringes were evaluated. The formulations tested in the injectability studies are outlined in Table 24. It was observed that the increase of Arg-HCl concentration from 120 mM to 150 mM led to an increasing osmolality, but no substantial difference in viscosity were observed between these two formulations. The formulation with 3% sucrose had a higher viscosity than the other two formulations, and with the protein concentration increase, the osmolality and viscosity showed a substantial increase. [00405] Based upon the force data, provided in Table 25 and FIG. 2, it was observed that as the protein concentration increased, the Max/Average gliding force increased, and it was determined that a pre-filled syringe was suitable for administration of a formulation described herein. For the standard syringe with the 25 gauge needle, clogging of the needle was observed for many of the samples. The clogging may have been due to differences between the two formats in syringe barrel cross-sectional area, needle wall thickness, silicone distribution, and/or needle length. Table 24: Formulations Tested in Injectability Study Protein conc. (mg/mL) Formulation 170 10 mM His buffer 10 mM Met 150 mM Arg-HCl 005% ) )
Figure imgf000194_0001
ab e 5: njec ab y S udy esu s PFS e g
Figure imgf000194_0002
193 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Arg-HCl, 0.05% PS80, 200 140 22.2 15.90 17.36 4.84 pH 5.8 210 140 28.3 18.74 20.79 4.50
Figure imgf000195_0001
[00406] This Example describes long term stability studies, under different conditions, of the IL-13 antibody formulation described and developed in Examples 1-5. Materials and Methods [00407] A panel of analytical methods were used to evaluate long-term storage conditions, the Methods of which are described in Example 1 and Example 2 and in the Potency section, below. In brief, formulated antibody was used to fill either a 2R glass vial and stopper (e.g.. Schott cat no 1626151 and West cat no 1970-0173) to represent a drug product configuration or a Sartorius Celsius FFT bag to represent a drug substance configuration. The vial configuration was tested at 5 ℃ (the intended storage temperature), 25 ℃, or 40 ℃, as well as for photostability under dark versus light conditions. The higher temperatures and photostability conditions were intended to evaluate more stressful conditions to provide an early indication of potential degradation pathways that may occur during long term storage at the intended storage 194 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR temperature and/or manufacturing procedures. The bag configuration was tested at -70 ℃ and for freeze thaw cycles to evaluate stability during long term storage and/or manufacturing procedures. Potency [00408] The binding assay used was an enzyme-linked immunosorbent assay (ELISA). IL-13 is an immunoregulatory cytokine, which regulates the function of human B cells and monocytes. In this assay, IL-13 was immobilized onto a 96-well plate. WBP2546 was added and bound to the captured human IL-13. The bound WBP2546 was detected by anti-human IgG (F(ab’)₂ specific)-peroxidase secondary antibody. 3,3',5,5' tetramethylbenzidine (TMB) substrate solution was loaded into the wells subsequently. A blue color developed in proportion to the amount of bound secondary antibody. Blue color development was stopped by adding stop solution and the color changed to yellow. The measured absorbance at 450 nm was subtracted from absorbance at 650 nm, producing a signal that was proportional to the concentration of the analyte in the well. [00409] Dose response curves were plotted according to a 4-parameter logistic (Auto- Estimate) regression model using the Softmax Pro Software for samples, as well as control and reference standards. Relative binding potency of the sample was calculated using the EC50 of reference to samples on the same plate derived from 4-parameter logistic fit. Results [00410] Formulated antibody was used to fill either a 2R glass vial to represent a drug product configuration or a Sartorius Celsius FFT bag to represent a drug substance configuration. The vial configuration was tested at 5 ℃ (the intended storage temperature), 25 ℃, or 40 ℃ as well as for photostability under dark versus light conditions, The higher temperatures and photostability conditions were intended to evaluate more stressful conditions to provide an early indication of potential degradation pathways that may occur during long term storage at the intended storage temperature and/or manufacturing procedures. The bag configuration was tested at -70 ℃ and for freeze thaw cycles to evaluate stability during long term storage and/or manufacturing procedures. [00411] Using a fill volume of 2.7 mL per vial or bag, three formulations (F1, F2, and F3), outlined in Table 26, were tested under the various conditions. As described throughout 195 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR Examples 1-4, the formulations selected this stage of testing included a pH of about 5.8 due to its favorable results in SE-UPLC experiments (see Example 1), a histidine buffer (or comparable acetate or succinate buffer, respectively), L-methionine, which was demonstrated to help control HMW formation and antibody purity (see Example 2), and the excipient Arg-HCl, based on its ability to reduce viscosity (see Example 3). Table 26: Formulations Tested for Long-Term Storage and Stability No. Protein pH Buffer and Excipient Excipient Excipient conc. surfactant 1 2 3
Figure imgf000197_0001
[00412] pH, appearance, sub-visible particles (MFI), protein concentration, SE-UPLC, iCIEF, and CE-SDS, were evaluated for the vial configuration using the Materials and Methods described throughout Examples 1-2 after 1 month of storage at 5 ℃, 25 ℃, or 40 ℃, photostability under dark and light conditions. Storage at -70 ℃ and free/thaw stability was evaluated for the bag configuration. [00413] The T0 antibody, histidine, and L-arginine concentrations, osmolality, and viscosity data are presented in Table 27. Table 27: Concentrations, Osmolality, and Viscosity Results No. Measured Osmolality Viscosity (mPa·s) Measured Measured n
Figure imgf000197_0002
196 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR [00414] As shown in Table 28, no substantial changes in F1, F2, and F3, were observed after storage at 5 ℃ for 1 month for any of the tested attributes. [00415] After incubation at 25 ℃ for 1 month, small (0.5% - 0.6%) SEC monomer decreases were observed for F1, F2, and F3 groups, with no substantial differences between F1, F2 and F3. After incubation at 25 ℃ for 1 month, decreases (about 50%) in PS80 concentration were observed in F1, F2, and F3, compared to T0. The formulation buffer control (F4; not shown) had even lower levels of PS80 after 2 weeks at 25 ℃ and 40 ℃ (< 0.010%), indicating that the degradation was slowed in the presence of antibody (Table 28). These results suggested that the PS80 may have undergone oxidative degradation which is a known degradation pathway that may be accelerated at higher temperatures and/or light exposure. [00416] After incubation at 40 ℃ for 1 month, for F1, F2 and F3, the color deepened slightly compared to the T0 samples, and substantial decreases were observed in SEC, CE-NR and iCIEF results demonstrating these methods as stability indicating. No substantial differences were observed between F1, F2, and F3 in all test results. After incubation at 40 ℃ for 1 month, decreases (about 50%) in in PS80 concentration were observed in which F1, F2, and F3, compared with T0 (Table 28). [00417] After 1000 lux light exposure at 25 ℃ for 14 days, substantial decreases in purity as assessed by SEC, CE-NR, and iCIEF were observed for F1, F2, and F3 (Table 29). In the CE- NR assay, without being bound by theory, the decreased purity may be caused by aggregates instead of fragments. No substantial decreases were observed for dark control samples stored at 25℃ for 7 days and 14 days (two weeks). No substantial difference between F1, F2, and F3 were observed after 1000 lux light exposure for 7 days (1 week) and 14 days (2 weeks). For F2, stored at -70 ℃ for 1 month (1M), a substantial increase in ≥ 2 µm was observed in sub-visible particles results (Table 30). For F1, F2, and F3, stored at -70 ℃ for 1 month, no substantial changes were observed in SEC/Caliper/iCIEF/PS80 test results (Table 30). [00418] For F3, after 5 freeze/thaw (F/T) cycles (F/T-5 Cycles), substantial increases (≥ 2 µm) were observed in sub-visible particles results (Table 31). For F1, F2, and F3, after 5 freeze/thaw cycles, no substantial changes were observed in SEC/Caliper/iCIEF/PS80 test results Table 31). 197 4925-0461-2873 v.1 4925-0461-2873 v.1 Attorney Docket No.: AOE-003PR T em p . 5C F F F
Figure imgf000199_0001
. SOL, 198 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR 25C F F F
Figure imgf000200_0001
FP 199 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR 40C F F F
Figure imgf000201_0001
. 1W SOL, 200 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR
Figure imgf000202_0001
Abbreviations: W, Weeks; M, Months; SY, Slightly yellow; SOL, Slightly opalescent liquid; C, Colorless; CL, Clear liquid; FP, Free of visible particles. HMW, High molecular weight; LMW, Low molecular weight; Mono., monomer; NT, not tested. F o rm u la tio n F1
Figure imgf000202_0002
g . . . . FP (-1.5) (+1.3) (-1.1) (-3.9) 201 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR F2 F3
Figure imgf000203_0001
(- .5) (+ .3) (- . ) (- .0) Abbreviations: W, Week(s); SY, Slightly yellow; SOL, Slightly opalescent liquid; C, Colorless; CL, Clear liquid; FP, Free of visible particles. HMW, High molecular weight; LMW, Low molecular weight; Mono., monomer. 202 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Table 30: -70 ℃ Results F o rm . N o . F1 T - 1 F2 T - 1 F3 T -
Figure imgf000204_0001
1M SOL, FP Abbreviations: M, Month(s); SY, Slightly yellow; SOL, Slightly opalescent liquid; C, Colorless; CL, Clear liquid; FP, Free of visible particles. HMW, High molecular weight; LMW, Low molecular weight; Mono., monomer. Table F o rm u la tio n F1
Figure imgf000204_0002
. . . . . . . . FP 203 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR F2 F3
Figure imgf000205_0001
y Abbreviations: F/T, freeze/thaw; SY, Slightly yellow; SOL, Slightly opalescent liquid; FP, Free of visible particles. HMW, High molecular weight; LMW, Low molecular weight; Mono., monomer. 204 4925-0461-2873 v.1 4925-0461-2873 v.1
Attorney Docket No.: AOE-003PR Example 7: 12-Month Stability Study of Three Formulations In this example, three formulations were tested for stability under various conditions over a 12-month period. The tested formulations are shown in Table 32, referred to as F1, F2 and F3, with the control formulation referred to as F4. The anti-IL-13 antibody (protein) used in this example was Construct 133. Table 32: Formulations Tested Protein pH Buffer and Excipient Excipient Excipient Formulation Conc. Surfactant 1 2 3 -
Figure imgf000206_0001
Samples were prepared to a fill-volume of 2.7 ml/vial or 4 ml/bag. The study plan for the various conditions tested, and the sampling schedule, are shown in Table 33. Table 33: Stability Study Plan Sampling points n
Figure imgf000206_0002
Attorney Docket No.: AOE-003PR X, X X, X, X, X, Z, X, Z, 2-8 ℃ / X Z, ， Z, W Z,W W W n
Figure imgf000207_0001
iCIEF, CE-SDS Z= Potency W= PS80 X’= pH, Appearance, Sub-visible particles (MFI), PS80 Y’= Viscosity, Osmolarity The quality aspects set forth in Table 33 were tested as described in previous examples. The results for the stability data at 5°C, 25°C, 40°C and -70°C storage conditions are shown in Table 34, Table 35, Table 36 and Table 37, respectively. The results of the freeze- Attorney Docket No.: AOE-003PR thaw study are shown in Table 38. The results of the photostability study are shown in Table 39. Analysis of SE-UPLC is presented as monomer peak normalized to T0 and high molecular weight species (HMW) are presented as a fold-change over T0. Values for low molecular weight (LMW) species for all tested samples at all conditions < 1.0%. Analysis of iCIEF is presented as main peak (MP) normalized to T0 and acidic peaks (AP) and basic peaks (BP) are presented as a fold-change over T0. Abbreviations used in the tables are as follows: SY: Slightly yellow; SOL: Slightly opalescent liquid; FP: Free of visible particles; C: Clear; CL: Clear liquid.
Attorney Docket No.: AOE-003PR Table 34: Formulation Stability Data at 5°C Storage Conditions F# F1 F2
Figure imgf000209_0001
- . FP 99.5 1.3 . . 1.1 1.0 98.7 015)
Attorney Docket No.: AOE-003PR F3
Figure imgf000210_0001
. . . . . ° FB No. F01
Figure imgf000210_0002
1M . SOL, FP 8 99.5 1.4 . . 1.3 1.0 98.0 21)
Attorney Docket No.: AOE-003PR F02 F03 F04
Figure imgf000211_0001
.
Attorney Docket No.: AOE-003PR Table 36: Formulation Stability Data at 40°C Storage Conditions FB No. F01 F02 F03
Figure imgf000212_0001
1M . FP 5 98.0 2.9 (↓1.7) .3) 2.7 2.0 65.6 21)
Attorney Docket No.: AOE-003PR F04
Figure imgf000213_0001
T l 7 F l i ili D 7° ii FB No. F01 F02
Figure imgf000213_0002
-70C-6M 5.8 SY, SO, FP 3147 322 27 99.9 1.2 98.5 97.7 1.1 1.0 99.3 0.039 93
Attorney Docket No.: AOE-003PR F03 F04
Figure imgf000214_0001
FB No. F01 F02
Figure imgf000214_0002
, , 100.0 1.0 1.0 1.0 100.0
Attorney Docket No.: AOE-003PR F03
Figure imgf000215_0001
FB No. F01
Figure imgf000215_0002
99.7 1.1 1.1 1.0 98.7
Attorney Docket No.: AOE-003PR F02 F03
Figure imgf000216_0001
99.2 2.0 1.2 1.1 96.8
Attorney Docket No.: AOE-003PR
Figure imgf000217_0001
Attorney Docket No.: AOE-003PR Regarding storage at 5° C, there were no substantial changes in formulations F1 through F3 observed after storage at 5° C for 9 months in all tested quality aspects except PS80 exhibited a 0.017-0.022% decrease over that time. Regarding storage at 25° C, after incubation for 3 months, SEC monomer slight decreases were observed, 1.2%-1.3% CE-SDS-NR purity decreases were observed and slight iCIEF main peak decreases were observed for the F1, F2 and F3 formulations. There were no substantial differences observed between F1, F2 and F3. Regarding PS80 concentrations over time, after incubation at 25°C for one month there were substantial decreases in PS80 concentration observed in formulations F1 through F3 as compared to time zero (T0). For formulation F4, after incubation at 25°C for two weeks, the PS80 concentration was less than 0.010%. Regarding storage at 40° C, after incubation for one month, the color of formulations F1 through F3 deepened slightly compared as compared to the time zero (T0) samples. In addition, substantial decreases in monomer, purity and main peak were observed in formulations F1 through F3 via SEC, CE-NR and iCIEF results, respectively. No substantial differences between formulations F1 through F3 were observed in any of the test results. Regarding PS80 concentrations over time, after incubation at 40℃ for one month there were substantial decreases in PS80 concentration observed in formulations F1 through F3 as compared to time zero (T0). For formulation F4, after incubation at 40°C for one week the PS80 concentration was less than 0.010%. Regarding storage at -70° C, for formulations F1 through F4, after storage at -70℃ for six months, there were substantial increases in sub-visible particles observed. These samples were filled in bags, whereby the samples stuck to the inlet of the bag and as a result may have impacted the sub-visible particle testing. For formulations F1 through F3, no substantial changes were observed in monomer, purity and main peak via SEC, CE-NR and iCIEF, respectively, after storage at -70°C for six months. In addition, no substantial PS80 concentration changes were observed in formulations F1 through F3 after storage at -70℃ for 6 months. Regarding the freeze/thaw studies, F3 exhibited substantial increases (≥2 µm) in sub- visible particle testing results after five freeze/thaw cycles. For all three formulations tested, after five freeze/thaw cycles there were no substantial changes observed in monomer, purity or Attorney Docket No.: AOE-003PR main peak (tested via SEC/CE-NR and iCIEF, respectively) and there were also no substantial changes observed in PS80 concentration. Regarding the photostability study, there were no substantial differences between formulations F1 through F3 observed after 1000 lux light exposure for 7 days and 14 days. However, after 1000 lux light exposure for 14 days, substantial decreases in monomer, purity and main peak were observed for all three formulations via SEC, CE-NR and iCIEF, respectively. There were no substantial changes observed in dark control samples stored at 25℃ for 7 days and 14 days. F1, F2, and F3 were designed so that osmolality was approximately 300 mOsm/kg, which is a range that is suitable for injectable parenteral formulations. The osmolality and viscosity results were consistent with previous data for these formulations. For formulations F1 through F3 the histidine, arginine and chloride concentrations were close to the target values. Example 8: Investigation of PS80 Degradation In the stability studies described in Example 7, degradation of PS80 was observed in certain samples under certain conditions. Accordingly, studies were performed to identify the mechanism(s) of PS80 degradation. In one study, formulation buffers were formulated with different lots of raw materials and a metal ion chelator (EDTA-2Na) was added to certain formulations, along with increasing the concentration of PS80 in certain formulations. The formulations tested in the study are shown in Table 40. Table 40: Formulations Tested in Metal Ion Chelator Study ,
Figure imgf000219_0001
Attorney Docket No.: AOE-003PR 10 mM L-His/L-His-HCl, 120 mM L-Arg-HCl, 10 mM L-Met, F03 ,
Figure imgf000220_0001
y p p p y levels of iron (Fe), cobalt (Co), nickel (Ni), copper (Cu) and zinc (Zn) in the formulations. The concentration of PS80 was also measured in the formulations at T0 and after storage at 25°C for defined periods of time (1 week, 2 weeks, 1 month). The results of the metal ion chelator study are summarized in Table 41. Table 41: Metal Ion Chelator Study Results Comment Analysis Result Fe C ( /L) Ni ( /L) C ( /L) Zn ( /L) (PS80 #
Figure imgf000220_0002
Attorney Docket No.: AOE-003PR 25C-1M: 0.021%
Figure imgf000221_0001
Additional investigational studies were performed to evaluate the impact on PS80 degradation of clone material, formulation buffers, water, PS80 lots and the material of construction of vials (glass vs. polymer). Representative results are shown in Table 42.
Attorney Docket No.: AOE-003PR Table 42: Results of PS80 Degradation Study Run
Figure imgf000222_0001
HPW 1A polymer vials w/o 0.04 0.032 0.031 0.030 0.030
Attorney Docket No.: AOE-003PR
Attorney Docket No.: AOE-003PR Regarding the results shown in Table 42, samples with added EDTA showed no significant degradation, while some samples with 1% PS80 added but without EDTA were observed to possibly undergo degradation. The protein-free formulation buffer did not undergo significant degradation under any conditions. Overall, the results of the PS80 degradation studies determined that PS80 degradation was mediated by oxidation (major) and hydrolysis (minor). From a formulation perspective, PS80 degradation can be addressed by, for example, inclusion of a metal ion chelator in the formulation or by use of an alternate surfactant, as described further in Example 9. Example 9: Formulations to Counteract PS80 Degradation To evaluate formulations to counteract PS80 degradation, a panel of formulations was prepared that included either PS80 or P188 as surfactant. Additionally, a metal ion chelator was included in some formulations and omitted from others. The formulations were tested for various quality parameters, as described in previous examples. Table 43 shows results for surfactant stability (%) over time at the indicated temperatures. Table 44 and Table 45 show the SE-UPLC results over time at 25°C and 5°C, respectively. Table 46 and Table 47 show the iCIEF results over time at 25°C and 5°C, respectively. Analysis of SE-UPLC is presented as monomer peak normalized to T0 and high molecular weight species (HMW) are presented as a fold-change over T0. Values for low molecular weight (LMW) species for all tested samples at all conditions < 1.0%. Analysis of iCIEF is presented as main peak (MP) normalized to T0 and acidic peaks (AP) and basic peaks (BP) are presented as a fold-change over T0. Table 48 and Table 49 show the CD-SDS-NR and CD-SDS-R results, respectively, over time at the indicated temperatures. Table 50 shows the PS80-CAD results. In Tables 43, 48 and 49, values in parentheses denote a significant change and indicate the associated change in the value. Attorney Docket No.: AOE-003PR Table 43: Surfactant Stability of PS80 and P188 Formulations No. F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11
Figure imgf000225_0001
120mM L-Arg-HCl, 10 mM L-Met, 0.5 mg/mL P188 0.058 0.057 0.06 0.058 0.06 0.058 0.06
Attorney Docket No.: AOE-003PR 80mM F12
Figure imgf000226_0003
mg/mL
Figure imgf000226_0001
Table 44: SE-UPLC Data for PS80 and P188 Formulations at 25°C No. F1 F2 F3 F4 F5 F6 F7
Figure imgf000226_0002
, . 100.0 1.0 99.7 1.3 99.6 1.3
Attorney Docket No.: AOE-003PR F8 F9 F10 F11 F12
Figure imgf000227_0001
° No. F1 F2 F3 F4
Figure imgf000227_0002
L-Met, 3% sucrose, 0.01 100.0 1.0 100.0 1.1 100.0 1.1
Attorney Docket No.: AOE-003PR F5 F6 F7 F8 F9 F10 F11 F12
Figure imgf000228_0001
mg/mL P188 100.0 1.0 99.9 1.1 99.9 1.1 No.
Figure imgf000228_0002
xcpents & suractants (w/v) 0 5℃- 5℃-
Attorney Docket No.: AOE-003PR
Figure imgf000229_0001
P188 1.0 100.0 1.0 1.0 99.3 1.0 1.1 97.4 1.2 Table 47: iCIEF Data for PS80 and P188 Formulations at 5°C
Attorney Docket No.: AOE-003PR No. F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11
Figure imgf000230_0001
0.5 mg/mL P188 1.0 100.0 1.0 1.0 99.5 1.0 1.0 98.8 1.1
Attorney Docket No.: AOE-003PR F12
Figure imgf000231_0001
Table 48: CE-SDS-NR Data for PS80 and P188 Formulations at 5°C and 25°C No. F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Figure imgf000231_0002
F11 120mM L-Arg-HCl, 10 mM L-Met, 0.5 mg/mL P188 97.6 96.2(↓1.4) 94.3 (↓3.3) 97.4 97.3 97.5 97.6
Attorney Docket No.: AOE-003PR 80mM F12
Figure imgf000232_0003
mg/mL
Figure imgf000232_0001
Table 49: CE-SDS-R Data for PS80 and P188 Formulations at 5°C and 25°C No. F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Figure imgf000232_0002
.
Attorney Docket No.: AOE-003PR F11 F12
Figure imgf000233_0001
Table 50: PS80-CAD Results No. F01 F02 F03 F04 F05 F06 F07 F08
Figure imgf000233_0002
Attorney Docket No.: AOE-003PR Regarding the surfactant stability data in Table 43, for F1-F8, PS80 content decrease was observed after 40 ℃ -4W and 25 ℃ -4W. In F01/F02 (no EDTA.2Na), adding EDTA.2Na (F3- F8) improved the PS80 stability. For F9-F12, no P188 content changes were observed after incubation at 40 ℃, 25 ℃ and 5℃ for 4 weeks. Regarding the SE-UPLC data in Table 44 and Table 45, no substantial changes of SEC monomer % were observed after 4 weeks incubation at either 25℃ or 5℃ for all formulations. No substantial differences were observed among all formulations. Regarding the iCIEF data in Table 46, a slight decrease in main peak% was observed after 4 weeks incubation at 25℃ compared with T0, whereas no substantial change of main peak% were observed after 4 weeks incubation at 5℃ for all formulations compared with T0 (Table 47). No substantial differences were observed among all formulations. Regarding the CE-SDS-NR data in Table 48, no substantial change of CE-NR purity was observed after 4W incubation at 5 ℃ or 25℃ compared with T0. 3.1-3.4% CE-NR purity was observed in all formulations after 4W incubation at 40℃. Regarding the CE-SDS-NR data in Table 49, no substantial change of CE-R purity was observed after 4W incubation at 5 ℃ or 25℃ compared with T0. 1.3-1.8% CE-R purity was observed in all formulations after 4W incubation at 40℃. No substantial differences were observed among all formulations. Overall, the studies demonstrated that addition of a metal ion chelator (EDTA) to the formulations mitigated PS80 degradation and formulations that used P188 instead of PS80 exhibited no degradation over time at various temperatures. Example 10: Determination of Minimum Effective Amount of PS80 to Protect Against Mechanical Shear Stress This example describes a study to establish a minimum PS80 concentration that can protect the formulation against mechanical stress induced by agitation (e.g., during shipping). Formulations having PS80 concentrations of 0, 0.0005, 0.003, 0.005, 0.01, 0.03, 0.05 % (w/v) were evaluated for their resistance against agitation at 300 rpm for 3 days. Tested formulations are shown in Table 51. Table 51: Formulations with Varying PS80 Concentrations Attorney Docket No.: AOE-003PR No. Protein conc. pH/buffer Excipients Surfactant
Figure imgf000235_0001
The study plan is summarized in Table 52. The formulations were tested for various quality parameters, as described in previous examples. Table 52: Study Plan
Figure imgf000235_0002
Attorney Docket No.: AOE-003PR The results for sub-visible particles (MFI), SE-UPLC, iCIEF and CE-SDS are shown in Table 53, Table 54, Table 55 and Table 56, respectively.
Attorney Docket No.: AOE-003PR Table 53: Sub-Visible Particle (MFI) Results No. F8 F9 F10 F11 F12 F13 F14
Figure imgf000237_0001
T bl 54: SE-UPLC R lt No.
Figure imgf000237_0002
Attorney Docket No.: AOE-003PR F8 F9 F10 F11 F12 F13 F14
Figure imgf000238_0001
. . . . . . Table 55: iCIEF Results No. F8 F9 F10
Figure imgf000238_0002
, . 100.0 1.0 1.0 98.8 1.0 1.0 98.3 1.0 1.0
Attorney Docket No.: AOE-003PR F11 F12 F13 F14
Figure imgf000239_0001
Table 56: CE-R/NR Results No. F8 F9 F10 F11 F12 F13
Figure imgf000239_0002
Attorney Docket No.: AOE-003PR F14
Figure imgf000240_0001
Attorney Docket No.: AOE-003PR Regarding the sub-visible particle data in Table 53, except for F07/F13/F14, no substantial changes of sub-visible particles were observed after 3 days of agitation. Analysis of SE-UPLC is presented as monomer peak normalized to T0 and high molecular weight species (HMW) are presented as a fold-change over T0. Values for low molecular weight (LMW) species for all tested samples at all conditions < 1.0%. Analysis of iCIEF is presented as main peak (MP) normalized to T0 and acidic peaks (AP) and basic peaks (BP) are presented as a fold-change over T0. Regarding the SE-UPLC data in Table 54, no substantial changes in SEC monomer % were observed after 3 days of agitation. Regarding the iCIEF data in Table 55, no substantial changes in the iCIEF main peak % were observed after 3 days of agitation. Regarding the CE-SDS-R/NR data in Table 56, no substantial changes in CE-R or NR purity % were observed after 3 days of agitation. Overall, no substantial changes were observed in all the tested quality items after 3 days of agitation except the visible particles and sub-visible particles in F13/F14. A PS80 concentration higher than 0.0005% was shown to efficiently protect against particle formation from agitation in the formulation. Samples with PS80 > 0.003% showed good resistance against mechanical stress induced by agitation. Example 11: Compatibility Studies with Glass Pre-Filled Syringes and Rubber Plunger Stoppers The IL-13 antibody formulation was evaluated for compatibility with additional pre-filled syringe (PFS) components: the syringes and plunger stoppers. Compatibility with two different syringe types from two different manufacturers (C and D) and two different plunger stoppers from two different manufacturers (A and B) were evaluated. The results for subvisible particles over time and at increasing temperatures are shown in FIG. 3A and FIG. 3B, which show results for particles equal to or greater than 2 µm or 10 µm, respectively. The results for pH and PS80 stability are shown in FIG. 4A and FIG. 4B, respectively. The SEC data results are shown in FIG. 5, wherein the data has been normalized to 100% at T=0. The iCIEF data results are shown in FIG. 6, wherein the data has been normalized to 100% at T=0. The CE-SDS results are shown in FIG. 7A (non-reduced) and FIG. 7B (reduced). ELISA data for container closure compatibility are shown in FIG. 8. Table 57 Attorney Docket No.: AOE-003PR summarizes the overall assessment of visual appearance, turbidity, concentration, subvisible particles, pH, PS80, SEC, iCIEF, CE-SDS-NR/R, and ELISA for the samples.
Attorney Docket No.: AOE-003PR Table 57: Overall Scorecard for Tested Quality Parameters of Syringes and Plungers PPM Vial Contro C+A C+B D+A D+B
Figure imgf000243_0001
Attorney Docket No.: AOE-003PR In summary, all biochemical assays and physicochemical assays showed a similar performance for the syringes and plunger combinations tested except for sub-visible particles, wherein certain syringes demonstrated a lower total particle load than others and thus are recommended for selection. The results of the studies demonstrated that the IL-13 antibody formulation is compatible with glass pre-filled syringes and rubber plunger stoppers and support a pre-filled syringe product presentation. Example 12: Two Lead Formulation Candidates Confirmed through 3 Months Stability Data Two lead formulation candidates from non-GMP development lots were tested for 3- month stability after storage at various conditions. The anti-IL-13 antibody (protein) used in this example was Construct 133. The formulations tested were: (1) 180 mg/mL IL-13 antibody, L-10 mM His/L-His-HCl, 120 mM L-Arg-HCl, 10 mM L-Met, 0.05 mM EDTA, 0.05% PS80, pH 6.0; and (2) 180 mg/mL IL-13 antibody, 10 mM L-His/L-His-HCl, 120 mM L-Arg-HCl, 10 mM L-Met, 0.5 mg/mL P188, pH 6.0 Formulations were tested for various quality parameters over time and at various temperatures as described in the previous examples according to the study plan set forth in Table 58. The Tg’, viscosity, pH, osmolality and excipient concentration at time zero (T0) are shown in Table 59. The 5°C data is summarized in Table 60. The 25°C data is summarized in Table 61. The 40°C data is summarized in Table 62. The data for agitation is summarized in Table 63. The -70°C data is summarized in Table 64. Abbreviations used in the tables are as follows: SY=slightly yellow, SO=slightly opalescent, FP = free of visible particles, ND = not detected, LMW= low molecular weight, HMW= high molecular weight, LC=light chain, HC= heavy chain, MP= main peak, AP=acidic peak, BP= basic peak, C= colorless, CL= clear. Attorney Docket No.: AOE-003PR Table 58: Study Plan Formul F01: 18 APG77 His/L-H mM L- mM L- EDTA, PS80, p F02: 18 APG77 His/L-H mg/mL L-Arg-H Met, pH
Figure imgf000245_0001
X = Ap Y = Sub Z = Pote W = Tg
Figure imgf000245_0003
, Viscosity, protein concentration, pH, Osmolality, His & Arg con., Cl conc. No. F01
Figure imgf000245_0002
Attorney Docket No.: AOE-003PR F02 F03 F04
Figure imgf000246_0001
T bl 60 5°C D t S No. Appeara SVP by HIAC, particles/ SE-UPL CE-NR CE-R
Figure imgf000246_0002
iCIEF Main peak % 100.0 97.0 100.1 97.0 98.1 100.0 99.6 102.2 101.6 101.0
Attorney Docket No.: AOE-003PR PS80/P1 Potency
Figure imgf000247_0001
Tbl 61: 25°C Dt S mmr No. Appeara Sub-visi particles HIAC, particles/ SE-UPL CE-NR CE-R iCIEF
Figure imgf000247_0002
peak 1.0 1.0 1.1 1.2 1.3 1.0 1.0 1.1 1.1 1.2
Attorney Docket No.: AOE-003PR PS80/P1
Figure imgf000248_0001
Table 62: 40°C Data Summar Testing Appeara Sub-visi by HIAC particles/ SE-UPL CE-NR CE-R iCIEF PS80%
Figure imgf000248_0002
Potency% 99 / 90 96 / 91 Table 63: 1D/3D Agitation Data Summary
Attorney Docket No.: AOE-003PR No. F01 (0.05 mM EDTA, 0.05% (w/v) PS80) F02 (0.5 mg/mL P188)
Figure imgf000249_0001
99.9 1.1 102.4 0.9 1.0 Testing
Figure imgf000249_0002
Attorney Docket No.: AOE-003PR Appeara Sub-vis by HIA particles PS80/P1
Figure imgf000250_0001
Attorney Docket No.: AOE-003PR Analysis of SE-UPLC is presented as monomer peak normalized to T0 and high molecular weight species (HMW) are presented as a fold-change over T0. Values for low molecular weight (LMW) species for all tested samples at all conditions < 1.0%. Analysis of iCIEF is presented as main peak (MP) normalized to T0 and acidic peaks (AP) and basic peaks (BP) are presented as a fold-change over T0. Regarding the data in Table 60, after three months of incubation at 5°C, all samples were slightly yellow and slightly opalescent but free of visible particles, similar to their appearance at time zero (T0). No substantial changes were observed in either tested formulation after three months of incubation at 5°C as compared to time zero (T0). Regarding the data in Table 61, after three months of incubation at 25°C, all samples were slightly yellow and slightly opalescent but free of visible particles, similar to how they appeared at time zero (T0). No substantial changes were observed in either formulation in terms of sub-visible particles, SEC, CE-R purity, PS80/P188 content or potency after three months of incubation at 25°C. Slight decreases of CE-NR purity (1.1-1.2%) and iCIEF main peak percentages were observed in both formulations after three months incubation at 25°C as compared to time zero (T0). Regarding the data in Table 62, after three months of incubation at 40°C, all samples were slightly yellow and slightly opalescent. Samples were free of visible particles at time zero (T0) and after four weeks of incubation at 40°C. There were no substantial changes in sub- visible particles, PS80 content or percent potency in either formulation after four weeks of incubation at 40°C. Slight decreases of SEC percent monomer, CE-NR percent purity (2.7- 3.0%), and CE-R percent purity (1.2-1.4%), and substantial decreases of iCIEF main peak percentages were observed in both formulations after one month incubation at 40°C as compared with time zero (T0). Regarding the data in Table 63, after three days of agitation all samples were slightly yellow, slightly opalescent and free of visible particles, just as they appeared at time zero (T0). There were no substantial changes observed in any test results after one day or three days of agitation as compared to at time zero (T0). Regarding the data in Table 64, after storage for three months at -70°C, all samples were colorless, clear, and free of visible particles, just as they appeared at time zero (T0). No Attorney Docket No.: AOE-003PR substantial changes were observed in any test results after three months storage at -70°C as compared to at time zero (T0).
Attorney Docket No.: AOE-003PR Informal sequence listing Description Sequence SEQ ID NO
Figure imgf000253_0001
Attorney Docket No.: AOE-003PR Heavy EVQLVESGGGLVKPGGSLRLSCAASGFSLNAYSVNWVRQ SEQ ID Chain APGKGLEWLGMIWGDGKIVYNSALKSRLTISKDSSKNTVY NO: 6
Figure imgf000254_0001
Attorney Docket No.: AOE-003PR Heavy EVQLLESGGGLVQPGGSLRLSCAASGFSLHAYSVNWVRQ SEQ ID Chain APGKGLEWLGMIWGDGKIVYNSALKSRLTISKDSSKNTVY NO: 12
Figure imgf000255_0001
Attorney Docket No.: AOE-003PR Heavy EVQLLESGGGLVQPGGSLRLSCAASGFSLNHYSVNWVRQ SEQ ID Chain APGKGLEWLGMIWGDGKIVYNSALKSRLTISKDSSKNTVY NO: 18
Figure imgf000256_0001
Attorney Docket No.: AOE-003PR Heavy EVQLLESGGGLVQPGGSLRLSCAASGFSLNAYSVNWVRQ SEQ ID Chain APGKGLEWLGMIWSDGKIVYNSALKSRLTISKDSSKNTVY NO: 24
Figure imgf000257_0001
Attorney Docket No.: AOE-003PR Heavy EVQLLESGGGLVQPGGSLRLSCAASGFSLNAYSVNWVRQ SEQ ID Chain APGKGLEWLGMIWGDGKIVYNSALKSRLTISKDSSKNTVY NO: 30
Figure imgf000258_0001
Attorney Docket No.: AOE-003PR Light Chain DIVLTQSPLSLPVTPGEPASISCRASKSVDSYGNSFMHWYL SEQ ID Variable QKPGQSPQLLIYLASNLESGVPDRFSGSGSRTDFTLKISRVE NO: 37
Figure imgf000259_0001
Attorney Docket No.: AOE-003PR LC6_m1 Light Chain DIQLTQSPSSLSASVGDRVTITCRASKSVDSYGNSSMHWY SEQ ID
Figure imgf000260_0001
Attorney Docket No.: AOE-003PR Light Chain DIQLTQSPSSLSASVGDRVTITCRASKSVDSYGNSFMHWY SEQ ID Variable QQKPGKAPKLLIYLASNLESGVPSRFSGSGSGTDFTLTISSL NO: 52
Figure imgf000261_0001
Attorney Docket No.: AOE-003PR HC5_m8 KYSVN SEQ ID Kabat NO: 60
Figure imgf000262_0001
Attorney Docket No.: AOE-003PR HC7 GGSLNAY SEQ ID Chothia NO: 70
Figure imgf000263_0001
Attorney Docket No.: AOE-003PR HC5_m11 GFSLNEY SEQ ID Chothia NO: 80
Figure imgf000264_0001
Attorney Docket No.: AOE-003PR HC5_m4 GFSLDAYS SEQ ID IMGT NO: 90
Figure imgf000265_0001
Attorney Docket No.: AOE-003PR Parental MIWGDGKIVYNSALKS SEQ ID Kabat NO: 100 1 2 3 4 5 6 7 8 9
Figure imgf000266_0001
Attorney Docket No.: AOE-003PR HC5_m15 IWSDGKI SEQ ID IMGT NO: 110 1 2 3 4 5 6 7
Figure imgf000267_0001
Attorney Docket No.: AOE-003PR HC5_m21 DGYYAYAMDN SEQ ID Kabat and NO: 118 9 0 1 2 3 4 5 6 7 8
Figure imgf000268_0001
Attorney Docket No.: AOE-003PR SEQ ID NO: 129 0 1 2 3 4 5 6 7 8 9
Figure imgf000269_0001
Attorney Docket No.: AOE-003PR HCDR3 HC1 m6 AGDGYYPYAMDN SEQ ID 0 1 2 3 4 5 6 7 8 9
Figure imgf000270_0001
Attorney Docket No.: AOE-003PR LC10 QSVDSNGNNF SEQ ID IMGT NO: 150 1 2 3 4 5 6 7 8
Figure imgf000271_0001
Attorney Docket No.: AOE-003PR Kabat and Chothia 9 0 1 2 3 4 5 6 7
Figure imgf000272_0001
Attorney Docket No.: AOE-003PR LC6_m10 QQNYEDPRT SEQ ID Kabat, NO: 168 9 0 1 2 3 4 5
Figure imgf000273_0001
Attorney Docket No.: AOE-003PR SEQ ID NO: 176 7 8 9 0 1 2 3 4 5 6 7 8 8
Figure imgf000274_0001
Attorney Docket No.: AOE-003PR HC QVQLQESGPGLVAPSQSLSITCTVSGFSLN SEQ ID Framework NO: 198 0 1 2 3 4 5
Figure imgf000275_0001
Attorney Docket No.: AOE-003PR HC QVQLQESGPGLVKPSETLSLTCTVSGGSLN SEQ ID Framework NO: 206 7 8 9 0 1
Figure imgf000276_0001
Attorney Docket No.: AOE-003PR HC EVQLLESGGGLVQPGGSLRLSCAASGFSLS SEQ ID Framework NO: 212 4 4 4 4 4
Figure imgf000277_0001
Attorney Docket No.: AOE-003PR HC EVQLLESGGGLVQPGGSLRLSCAASGFSLN SEQ ID Framework NO: 204 4 4 4 4 4
Figure imgf000278_0001
Attorney Docket No.: AOE-003PR HC EVQLLESGGGLVQPGGSLRLSCAASGFSLN SEQ ID Framework NO: 204 4 4 4 4 4
Figure imgf000279_0001
Attorney Docket No.: AOE-003PR LC NIVLTQSPASLAVSLGQRATISC SEQ ID Framework NO: 230 1 1 3 4 5 1 3
Figure imgf000280_0001
Attorney Docket No.: AOE-003PR LC7 Kabat LC DIVLTQSPLSLPVTPGEPASISC SEQ ID 4 9 9 1 1 1 1
Figure imgf000281_0001
Attorney Docket No.: AOE-003PR LC6_m4 Kabat 1 1 1 1 1 1
Figure imgf000282_0001
Attorney Docket No.: AOE-003PR LC6_m10 Kabat 1 1 1 1 5 6
Figure imgf000283_0001
Attorney Docket No.: AOE-003PR HC WVRQPPGKGLEWLG SEQ ID Framework NO: 256 8 9 9 2 2 3
Figure imgf000284_0001
Attorney Docket No.: AOE-003PR HC WVRQPPGKGLEWLG SEQ ID Framework NO: 263 2 2 2 2 2
Figure imgf000285_0001
Attorney Docket No.: AOE-003PR HC WVRQAPGKGLEWLG SEQ ID Framework NO: 262 2 2 2 2 2
Figure imgf000286_0001
Attorney Docket No.: AOE-003PR HC WVRQAPGKGLEWLG SEQ ID Framework NO: 262 2 2 2 2 2
Figure imgf000287_0001
Attorney Docket No.: AOE-003PR HC WVRQAPGKGLEWLG SEQ ID Framework NO: 262 2 2 2 2 2
Figure imgf000288_0001
Attorney Docket No.: AOE-003PR Lebrikizuma WYQQKPGQPPKLLIY SEQ ID b - LC NO: 286 6 8 8 0 1 6 8
Figure imgf000289_0001
Attorney Docket No.: AOE-003PR LC WYQQKPGQAPRLLIY SEQ ID Framework NO: 290 1 2 6 8 8 0
Figure imgf000290_0001
Attorney Docket No.: AOE-003PR LC WYQQKPGKAPKLLIF SEQ ID Framework NO: 301 8 8 8 8 8
Figure imgf000291_0001
Attorney Docket No.: AOE-003PR LC WYQQKPGKAPKLLIY SEQ ID Framework NO: 288 8 8 8 8 1 2
Figure imgf000292_0001
Attorney Docket No.: AOE-003PR HC RLTISKDSSKSQVFLKMSSLQSDDTARYYCAG SEQ ID Framework NO: 313 4 5 5 7 8 9
Figure imgf000293_0001
Attorney Docket No.: AOE-003PR HC RLTISLDTSKSQVFLKMSSLTAADTAVYYCAR SEQ ID Framework NO: 319 8 8 8 8 8
Figure imgf000294_0001
Attorney Docket No.: AOE-003PR HC RLTISKDSSKNTVYLQMNSLRAEDTAVYYCAG SEQ ID Framework NO: 318 8 8 8 8 8
Figure imgf000295_0001
Attorney Docket No.: AOE-003PR HC RLTISKDSSKNTVYLQMNSLRAEDTAVYYCAG SEQ ID Framework NO: 318 8 8 8 8 8
Figure imgf000296_0001
Attorney Docket No.: AOE-003PR HC RLTISKDSSKNTVYLQMNSLRAEDTAVYYCAG SEQ ID Framework NO: 318 8 8 8 8 8
Figure imgf000297_0001
Attorney Docket No.: AOE-003PR Lebrikizuma GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC SEQ ID b - LC NO: 343 4 5 5 7 8 3 1
Figure imgf000298_0001
Attorney Docket No.: AOE-003PR LC GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC SEQ ID Framework NO: 352 3 3 9 9 9 9
Figure imgf000299_0001
Attorney Docket No.: AOE-003PR LC6_m4 Kabat 9 9 9 9 9 9
Figure imgf000300_0001
Attorney Docket No.: AOE-003PR LC6_m10 Kabat 9 9 9 9 8 9 9
Figure imgf000301_0001
Attorney Docket No.: AOE-003PR HC0_M Kabat 1 1 1 1 1 1 1
Figure imgf000302_0001
Attorney Docket No.: AOE-003PR HC WGQGTTVTVSS SEQ ID Framework NO: 371 1 1 1 1 1
Figure imgf000303_0001
Attorney Docket No.: AOE-003PR HC WGQGTTVTVSS SEQ ID Framework NO: 371 1 1 1 1 1
Figure imgf000304_0001
Attorney Docket No.: AOE-003PR HC WGQGTTVTVSS SEQ ID Framework NO: 371 1 1 1 1 1
Figure imgf000305_0001
Attorney Docket No.: AOE-003PR HC WGQGTTVTVSS SEQ ID Framework NO: 371 1 1 1 1 0 1
Figure imgf000306_0001
Attorney Docket No.: AOE-003PR LC FGGGTKVEIK SEQ ID Framework NO: 400 0 0 0 0 0 0 0
Figure imgf000307_0001
Attorney Docket No.: AOE-003PR LC8 Kabat LC FGGGTKLEIK SEQ ID 1 1 0 0 0 0 0
Figure imgf000308_0001
Attorney Docket No.: AOE-003PR Region 4 LC6 m5 0 0 0 0 0 0
Figure imgf000309_0001
Attorney Docket No.: AOE-003PR LC6_m11 Kabat 0 0 0 5 6
Figure imgf000310_0001
Attorney Docket No.: AOE-003PR CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD 7 8 9
Figure imgf000311_0001
Attorney Docket No.: AOE-003PR Heavy ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID Chain WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT NO: 430 1 2 3
Figure imgf000312_0001
Attorney Docket No.: AOE-003PR YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 4 5 6
Figure imgf000313_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG 7 8 9 0
Figure imgf000314_0001
Attorney Docket No.: AOE-003PR hIgG1- YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAGA LAGA/YTE PSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNW 1 2 3
Figure imgf000315_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSH 4 5 6
Figure imgf000316_0001
Attorney Docket No.: AOE-003PR Heavy ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID Chain WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT NO: 447 8 9 0
Figure imgf000317_0001
Attorney Docket No.: AOE-003PR YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVDHHDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 1 2 3
Figure imgf000318_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHSH YTQKSLSLSP 4 5 6 7
Figure imgf000319_0001
Attorney Docket No.: AOE-003PR IgG4-YTE CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL FPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGV 8 9 0
Figure imgf000320_0001
Attorney Docket No.: AOE-003PR QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSRLTVDKSRWQEGNVFSCSVLHEALHSYTQKSLS 1 2 3
Figure imgf000321_0001
Attorney Docket No.: AOE-003PR Heavy ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW SEQ ID Chain NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT NO: 464 5 6 7
Figure imgf000322_0001
Attorney Docket No.: AOE-003PR EVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKC KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ 8 9 0 1 2
Figure imgf000323_0001
Attorney Docket No.: AOE-003PR Full ESLINVSGCSAIEKTQRMLSGFCPHKVSAGQFSSLHVRDTK sequence IEVAQFVKDLLLHLKKLFREGRFN 3 4 5 6 7 8 9
Figure imgf000324_0001
Attorney Docket No.: AOE-003PR Human IL- LTCLGGFASPGPVPPSTALRELIEELVNITQNQKAPLCNGS SEQ ID 13 MVWSINLTAGMYCAALESLINVSGCSAIEKTQRMLSGFCP NO: 480 1 2 3 4 5
Figure imgf000325_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHAH 6 7 8
Figure imgf000326_0001
Attorney Docket No.: AOE-003PR hIgG1- ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID LALAGA/L NO: 489 WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 0 1 2
Figure imgf000327_0001
Attorney Docket No.: AOE-003PR YVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 3 4 5
Figure imgf000328_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHAH YTQKSLSLSPG 6 7 8 9
Figure imgf000329_0001
Attorney Docket No.: AOE-003PR YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW 0 1 2
Figure imgf000330_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHW 3 4 5
Figure imgf000331_0001
Attorney Docket No.: AOE-003PR hIgG1- ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID N297A/DQ NO: 506 WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 7 8 9
Figure imgf000332_0001
Attorney Docket No.: AOE-003PR YVDGVEVHNAKTKPREEQYNSTYRVVSVLQVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 0 1 2
Figure imgf000333_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG 3 4 5 6
Figure imgf000334_0001
Attorney Docket No.: AOE-003PR YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAGA PSVFLFPPKPKDTLMISRDPEVTCVVVDVSHEDPEVKFNW 7 8 9
Figure imgf000335_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 0 1 2
Figure imgf000336_0001
Attorney Docket No.: AOE-003PR hIgG1- ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID LAGA/YD NO: 523 WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 4 5 6
Figure imgf000337_0001
Attorney Docket No.: AOE-003PR YVDGVEVHNAKTKPREEQYNSTYRVVSVLQVLHVDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 7 8 9
Figure imgf000338_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG 0 1 2 3
Figure imgf000339_0001
Attorney Docket No.: AOE-003PR YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRDPEVTCVVVDVSHEDPEVKFNW 4 5 6
Figure imgf000340_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIVVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 7 8 9
Figure imgf000341_0001
Attorney Docket No.: AOE-003PR Heavy ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID NO: 610 Chain WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 1 2 3
Figure imgf000342_0001
Attorney Docket No.: AOE-003PR lysine VEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK variant CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN 4 5 6
Figure imgf000343_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK 7 8 9 0
Figure imgf000344_0001
Attorney Docket No.: AOE-003PR hIgG1- YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG LALAPG c- PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW 1 2 3
Figure imgf000345_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 4 5 6
Figure imgf000346_0001
Attorney Docket No.: AOE-003PR Heavy ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID NO: 627 Chain WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 8 9 0
Figure imgf000347_0001
Attorney Docket No.: AOE-003PR lysine YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN variant GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 1 2 3
Figure imgf000348_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK 4 5 6 7
Figure imgf000349_0001
Attorney Docket No.: AOE-003PR hIgG1- YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG D265A/DH PSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNW 8 9 0
Figure imgf000350_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHSH 1 2 3
Figure imgf000351_0001
Attorney Docket No.: AOE-003PR Heavy ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW SEQ ID NO: 644 Chain NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT 5 6 7
Figure imgf000352_0001
Attorney Docket No.: AOE-003PR terminal VEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK lysine CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN 8 9 0
Figure imgf000353_0001
Attorney Docket No.: AOE-003PR DGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHSHYTQK SLSLSLGKK 1 2 3 4
Figure imgf000354_0001
Attorney Docket No.: AOE-003PR lysine YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG variant PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW 5 6 7
Figure imgf000355_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHAH 8 9 0
Figure imgf000356_0001
Attorney Docket No.: AOE-003PR hIgG1- ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID NO: 661 N434A c- WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 2 3 4
Figure imgf000357_0001
Attorney Docket No.: AOE-003PR lysine YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN variant GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 5 6 7
Figure imgf000358_0001
Attorney Docket No.: AOE-003PR PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHA HYTQKSLSLSPGK 8 9 0 1
Figure imgf000359_0001
Attorney Docket No.: AOE-003PR N434W c- YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG terminal PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW 2 3 4
Figure imgf000360_0001
Attorney Docket No.: AOE-003PR DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHW 5 6 7
Figure imgf000361_0001
Attorney Docket No.: AOE-003PR hIgG1- ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID NO: 678 LALA/DQ WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 9 0 1
Figure imgf000362_0001
Attorney Docket No.: AOE-003PR lysine YVDGVEVHNAKTKPREEQYNSTYRVVSVLQVLHQDWLN variant GKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSR 2 3 4
Figure imgf000363_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK 5 6 7 8
Figure imgf000364_0001
Attorney Docket No.: AOE-003PR W c- YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG terminal PSVFLFPPKPKDTLMISRDPEVTCVVVDVSHEDPEVKFNW 9 0 1
Figure imgf000365_0001
Attorney Docket No.: AOE-003PR GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP 2 3 4
Figure imgf000366_0001
Attorney Docket No.: AOE-003PR hIgG1- ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS SEQ ID NO: 695 LALAPG/Y WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 6 7 8
Figure imgf000367_0001
Attorney Docket No.: AOE-003PR lysine YVDGVEVHNAKTKPREEQYNSTYRVVSVLQVLHVDWLN variant GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 9 0 1
Figure imgf000368_0001
Attorney Docket No.: AOE-003PR VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK 2 3 4 5
Figure imgf000369_0001
Attorney Docket No.: AOE-003PR RVV c- YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG terminal PSVFLFPPKPKDTLMISRDPEVTCVVVAVSHEDPEVKFNW 6 7 8
Figure imgf000370_0001
Attorney Docket No.: AOE-003PR ELTKNQVSLTCLVKGFYPSDIVVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 9
Figure imgf000371_0001

Claims

Attorney Docket No.: AOE-003PR WHAT IS CLAIMED IS: 1. A formulation comprising: (a) an interleukin 13 (IL-13) antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0. 2. A formulation comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0, and wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, Attorney Docket No.: AOE-003PR e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. 3. A formulation comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. Attorney Docket No.: AOE-003PR 4. A formulation comprising: (a) an IL-13 antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a polysorbate or a poloxamer, wherein the formulation is at pH 5.0 to 7.0, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises the sequence set forth in SEQ ID NO: 58 or 67; b. CDR-H2 comprises the sequence set forth in SEQ ID NO: 100 or 104; c. CDR-H3 comprises the sequence set forth in SEQ ID NO: 112; d. CDR-L1 comprises the sequence set forth in SEQ ID NO: 141 or 149; e. CDR-L2 comprises the sequence set forth in SEQ ID NO: 153 or 596; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. 5. The formulation of any one of the above claims, wherein the IL-13 antibody has a means for extending the half-life of the IL-13 antibody. 6. The formulation of claim 5, wherein the means comprises at least one amino acid modification in the IL-13 antibody. 7. The formulation of any one of the above claims, wherein the formulation further comprises a metal ion chelator. Attorney Docket No.: AOE-003PR 8. The formulation of claim 7, wherein the metal ion chelator is EDTA or salt thereof. 9. The formulation of any one of the above claims, wherein the formulation further comprises a sugar or sugar alcohol. 10. The formulation of any one of the above claims, wherein the IL-13 antibody is present at a concentration between 160 mg/mL and 250 mg/mL. 11. The formulation of claim 10, wherein the IL-13 antibody is present at a concentration of about 180 mg/mL. 12. The formulation of claim 10, wherein the IL-13 antibody is present at a concentration of about 200 mg/mL. 13. The formulation of any one of the above claims, wherein the histidine buffer, acetate buffer, or succinate buffer is at a concentration between 5 mM and 20 mM. 14. The formulation of any one of the above claims, wherein the histidine buffer, acetate buffer, or succinate buffer is at a concentration of about 10 mM. 15. The formulation of any one of the above claims, wherein the histidine buffer comprises a histidine and a histidine salt. 16. The formulation of claim 15, wherein the histidine is L-histidine. 17. The formulation of claim 15 or 16, wherein the histidine salt is L-histidine HCl monohydrate. 18. The formulation of any one of the above claims, wherein the formulation comprises methionine, and wherein the methionine is L-methionine. Attorney Docket No.: AOE-003PR 19. The formulation of claim 18, wherein the L-methionine is at a concentration between 1 mM and 15 mM. 20. The formulation of claim 19, wherein the L-methionine is at a concentration of about 10 mM. 21. The formulation of any one of the above claims, wherein the formulation comprises arginine, and wherein the arginine is L-arginine. 22. The formulation of claim 21, wherein the formulation comprises an L-arginine salt solution. 23. The formulation of claim 22, wherein the L-arginine salt solution salt solution comprises HCl monohydrate. 24. The formulation of claim 22 or 23, wherein the L-arginine salt solution is at a concentration between 40 mM and 250 mM. 25. The formulation of claim 24, wherein the L-arginine salt solution is at a concentration of about 80 mM. 26. The formulation of claim 24, wherein the L-arginine salt solution is at a concentration of about 120 mM. 27. The formulation of any one of the above claims, wherein the formulation comprises a polysorbate, and wherein the polysorbate is at a concentration between 0.005% w/v and 0.15% w/v. 28. The formulation of any one of the above claims, wherein the polysorbate is at a concentration of about 0.05% w/v. Attorney Docket No.: AOE-003PR 29. The formulation of any one of the above claims, wherein the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. 30. The formulation of claim 29, wherein the polysorbate is polysorbate 80. 31. The formulation of any one of the above claims, wherein the formulation comprises a poloxamer, and wherein the poloxamer is poloxamer 188. 32. The formulation of any one of the above claims, wherein the pH is between 5.5 and 7.0. 33. The formulation of any one of the above claims, wherein the pH is between 5.5 and 6.5. 34. The formulation of claim 33, wherein the pH is about 5.8 or about 6.0. 35. A formulation comprising: (a) an IL-13 antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, wherein the formulation is at a pH of about 5.8. 36. A formulation comprising: (a) an IL-13 antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 80 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, wherein the formulation is at a pH of about 5.8. Attorney Docket No.: AOE-003PR 37. A formulation comprising: (a) an IL-13 antibody present at a concentration of about 200 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) polysorbate 80 at a concentration of about 0.05% w/v, wherein the formulation is at a pH of about 5.8. 38. The formulation of claim 0, wherein the formulation further comprises: (f) a sugar or sugar alcohol. 39. The formulation of any one of claims 9-38, wherein the sugar or sugar alcohol is at a concentration between 1% w/v and 8% w/v. 40. The formulation of claim 39, wherein the sugar or sugar alcohol is at a concentration of about 3% w/v. 41. The formulation of any one of claims 9-40, wherein the sugar or sugar alcohol is a disaccharide. 42. The formulation of claim 41, wherein the disaccharide is sucrose. 43. The formulation of any one of claims 1 and 5-42 wherein the IL-13 antibody comprises: (a) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (b) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; Attorney Docket No.: AOE-003PR b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. 44. The formulation of claim 43, wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. 45. The formulation of claim 43, wherein the IL-13 antibody comprises: a. CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-66; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-103; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120, Attorney Docket No.: AOE-003PR d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. 46. The formulation of claim 43, wherein the IL-13 antibody comprises: a. CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 67-83; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 104-107; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. 47. The formulation of claim 43, wherein the IL-13 antibody comprises: a. CDR-H1 comprising a sequence selected from the sequences set forth in any one of SEQ ID NOs: 84-99 and 121; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 108-111; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 130-140, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 149-152, e. CDR-L2 comprises the amino acid sequence LAS; and Attorney Docket No.: AOE-003PR f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. 48. The formulation of claim 43, wherein the IL-13 antibody does not comprise: (a) CDR-H1 set forth in SEQ ID NO: 58; CDR-H2 set forth in SEQ ID NO: 100; CDR- H3 set forth in SEQ ID NO: 112; CDR-L1 set forth in SEQ ID NO: 141; CDR-L2 set forth in SEQ ID NO: 153; and CDR-L3 set forth in SEQ ID NO: 165; or (b) CDR-H1 set forth in SEQ ID NO: 67; CDR-H2 set forth in SEQ ID NO: 104; CDR- H3 set forth in SEQ ID NO: 112; CDR-L1 set forth in SEQ ID NO: 141; CDR-L2 set forth in SEQ ID NO: 153; and CDR-L3 set forth in SEQ ID NO: 165; or (c) CDR-H1 set forth in SEQ ID NO: 84; CDR-H2 set forth in SEQ ID NO: 108; CDR- H3 set forth in SEQ ID NO: 130; CDR-L1 set forth in SEQ ID NO: 149; CDR-L2 set forth in the amino acid sequence LAS; and CDR-L3 set forth in SEQ ID NO: 165. 49. The formulation of claim 43, wherein the IL-13 antibody present does not comprise any combination of: (a) a CDR-H1 set forth in any of SEQ ID NOs: 58, 67, or 84; (b) a CDR-H2 set forth in any of SEQ ID NOs: 100, 104, or 108; (c) a CDR-H3 set forth in any of SEQ ID NOs: 112 or 130; (d) a CDR-L1 set forth in any of SEQ ID NOs: 141 or 149; (e) a CDR-L2 set forth in any of SEQ ID NOs: 153 or 154; and (f) a CDR-L3 set forth in SEQ ID NO: 165. 50. The formulation of claim 43, wherein the IL-13 antibody comprises a VH sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NOs: 1-32. 51. The formulation of claim 43, wherein the IL-13 antibody comprises a VL sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NOs: 33-57. Attorney Docket No.: AOE-003PR 52. The formulation of claim 43, wherein the IL-13 antibody comprises a VH sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NOs: 1-32 and a VL sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in of SEQ ID NOs: 33-57. 53. The formulation of any one of the above claims, wherein the IL-13 antibody comprises a VH comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence set forth in SEQ ID NO: 39. 54. The formulation of any one of the above claims, wherein the IL-13 antibody is a humanized, human, or chimeric antibody. 55. The formulation of claim 54, wherein the IL-13 antibody is a humanized antibody. 56. The formulation of any one of the above claims, wherein the IL-13 antibody comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM. 57. The formulation of any one of the above claims, wherein the IL-13 antibody comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4. 58. The formulation of claim 57, wherein the human Fc region comprises a human IgG1 Fc. 59. The formulation of claim 57, wherein the human Fc region comprises a human IgG4 Fc. 60. The formulation of claim 57, wherein the human Fc region comprises a human IgG2 Fc. 61. The formulation of any one of the above claims, wherein the IL-13 antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the sequences set forth in Attorney Docket No.: AOE-003PR any one of SEQ ID NOs: 425-468, 484-539, and 610-709, optionally wherein the IL-13 antibody comprises a heavy chain comprising a constant heavy chain sequence selected from the sequences set forth in any one of SEQ ID NOs: 610, 615-641, and 654-709. 62. The formulation of any one of the above claims, wherein the IL-13 antibody comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more substitutions result in a change in antibody half-life, ADCC activity, ADCP activity, or CDC activity as compared to an otherwise equivalent antibody comprising an Fc without the one or more substitutions. 63. The formulation of any one of the above claims, wherein the IL-13 antibody comprises an Fc region, and wherein the Fc region binds to Neonatal Fc receptor (FcRn). 64. The formulation of any one of the above claims, wherein the IL-13 antibody is a monoclonal antibody. 65. The formulation of any one of the above claims, wherein the IL-13 antibody binds an IL-13 sequence selected from a sequence set forth in any one of SEQ ID NOs: 472-475. 66. The formulation of any one of the above claims, wherein the IL-13 antibody does not have a heavy chain variable region sequence set forth in SEQ ID NO: 470. 67. A vial, bag, or bottle comprising the formulation of any one of claims 1-66. 68. The vial of claim 67, wherein the vial is a prefilled syringe or injector cartridge. 69. The vial of claim 67 or 68, wherein an extractable volume of the vial is between 1.0 mL and 10.0 mL. 70. The vial of claim 69, wherein the extractable volume of the vial is about 3.0-5.5 mL. Attorney Docket No.: AOE-003PR 71. A composition comprising the formulation or vial of any one of the above claims for use in the treatment of an inflammatory disorder or disease. 72. The composition of claim 71, for use in the treatment of atopic dermatitis. 73. The composition of claim 72, wherein the treatment reduces disease severity in a subject, and wherein disease severity is assessed by an Atopic Dermatitis Disease Severity Outcome Measure. 74. The composition of claim 71, for use in the treatment of an inflammatory disorder or disease selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic Bronchopulmonary Aspergillosis (ABPA), and Chronic Obstructive Pulmonary Disease (COPD). 75. A method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation of any one of claims 1-66 or the vial of any one of claims 67-70. 76. The method of claim 75, wherein the inflammatory disorder or disease is atopic dermatitis. 77. The method of claim 75, wherein the inflammatory disorder or disease is selected from the group consisting of asthma, idiopathic pulmonary fibrosis, alopecia areata, chronic sinusitis with nasal polyps, Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), eosinophilic esophagitis Attorney Docket No.: AOE-003PR (EoE), an Eosinophilic gastrointestinal disorder or disease (ENID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE), Churg-Strauss syndrome/Eosinophilic granulomatosis with polyangiitis (EGPA), Prurigo Nodularis (PN), of Chronic Spontaneous Urticaria (CSU), Chronic Pruritis of Unknown Origin (CPUO), Bullous Pemphigoid (BP), Cold Inducible Urticaria (ColdU), Allergic Fungal Rhinosinusitis (AFRS), Allergic Bronchopulmonary Aspergillosis (ABPA), and Chronic Obstructive Pulmonary Disease (COPD). 78. A method for treating a pathology associated with elevated levels of IL-13 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the formulation of any one of claims 1-66 or the vial of any one of claims 67-70. 79. A diafiltration buffer comprising: (a) a histidine buffer; and (b) arginine or a salt solution thereof, wherein the diafiltration buffer is at pH of from 5.2 to 6.1. 80. The diafiltration buffer of claim 79, wherein the histidine buffer comprises a histidine and a histidine salt. 81. The diafiltration buffer of claim 80, wherein the histidine is L-histidine. 82. The diafiltration buffer of claim 80 or 81, wherein the histidine salt is L-histidine HCl monohydrate. 83. The diafiltration buffer of any one of claims 79-82, wherein the formulation comprises arginine, and wherein the arginine is L-arginine. Attorney Docket No.: AOE-003PR 84. The diafiltration buffer of claim 83, wherein the formulation comprises an L-arginine salt solution. 85. The diafiltration buffer of claim 84, wherein the L-arginine salt solution salt solution comprises HCl monohydrate. 86. The diafiltration buffer of claim 84 or 85, wherein the L-arginine salt solution is at a concentration between 40 mM and 200 mM. 87. The diafiltration buffer of 86, wherein the L-arginine salt solution is at a concentration of about 50 mM. 88. The diafiltration buffer of 86, wherein the L-arginine salt solution is at a concentration of about 100 mM. 89. The diafiltration buffer of 86, wherein the L-arginine salt solution is at a concentration of about 120 mM. 90. The diafiltration buffer of any one of claims 79-89, wherein the pH is from about 5.5 to about 7.0. 91. The diafiltration buffer of claim 90, wherein the pH is about 5.8 or 6.0. 92. A method of manufacturing an intermediate preparation of an interleukin 13 (IL-13) antibody comprising: (a) obtaining a purified preparation of the IL-13 antibody; and (b) adjusting the matrix of the purified preparation of step (a), wherein adjusting the matrix comprises performing Ultrafiltration and Diafiltration (UFDF) with the diafiltration buffer of any one of claims 80-92, thereby obtaining the intermediate preparation of the IL-13 antibody. Attorney Docket No.: AOE-003PR 93. The method of manufacturing of claim 92, wherein the intermediate preparation of the IL-13 antibody has a higher concentration of the IL-13 antibody relative to the purified preparation. 94. The method of manufacturing of claim 92 or 93, wherein the method of manufacturing further comprises: (c) formulating the intermediate preparation to obtain a formulation of the IL-13 antibody. 95. The method of manufacturing of claim 94, wherein the formulation of the IL-13 antibody comprises the formulation of any one of claims 1-66. 96. A formulation comprising: (a) an interleukin 13 (IL-13) antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; (d) a polysorbate or a poloxamer; and (e) a metal ion chelator, wherein the formulation is at pH 5.0 to 7.0. 97. The formulation of claim 96, which comprises: (a) an interleukin 13 (IL-13) antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; (e) polysorbate 80 at a concentration of about 0.05% w/v; and (f) EDTA or salt thereof at a concentration of about 0.05 mM, wherein the formulation is at a pH of about 6.0 Attorney Docket No.: AOE-003PR 98. A formulation comprising: (a) an interleukin 13 (IL-13) antibody present at a concentration between 140 mg/mL and 290 mg/mL; (b) a histidine buffer, an acetate buffer, or a succinate buffer; (c) arginine and/or methionine or a salt solution thereof; and (d) a poloxamer; wherein the formulation is at pH 5.0 to 7.0. 99. The formulation of claim 98, which comprises: (a) an interleukin 13 (IL-13) antibody present at a concentration of about 180 mg/mL; (b) a histidine buffer at a concentration of about 10 mM, wherein the histidine buffer comprises L-histidine and L-histidine HCl monohydrate; (c) an L-arginine salt solution at a concentration of about 120 mM; (d) L-methionine at a concentration of about 10 mM; and (e) poloxamer 188 at a concentration of about 0.5 mg/ml; wherein the formulation is at a pH of about 6.0. 100. The formulation of any one of claims 96-99, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 58-99 and 121; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 100-111; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 112-120 and 130-140, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 141-144 and 149-152, Attorney Docket No.: AOE-003PR e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS; and f. CDR-L3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NOs: 165-172. 101. The formulation of any one of claims 96-99, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 58, SEQ ID NO: 68, and SEQ ID NO: 85; b. CDR-H2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 100, SEQ ID NO: 104, and SEQ ID NO: 108; c. CDR-H3 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 112 and SEQ ID NO: 130, d. CDR-L1 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 141 and SEQ ID NO: 149, e. CDR-L2 comprises a sequence selected from the sequences set forth in any one of SEQ ID NO: 153 and SEQ ID NO: 164; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. 102. The formulation of any one of claims 96-99, wherein the IL-13 antibody comprises: (i) a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and (ii) a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein: a. CDR-H1 comprises the sequence set forth in SEQ ID NO: 58 or 67; Attorney Docket No.: AOE-003PR b. CDR-H2 comprises the sequence set forth in SEQ ID NO: 100 or 104; c. CDR-H3 comprises the sequence set forth in SEQ ID NO: 112; d. CDR-L1 comprises the sequence set forth in SEQ ID NO: 141 or 149; e. CDR-L2 comprises the sequence set forth in SEQ ID NO: 153 or 596; and f. CDR-L3 comprises the sequence set forth in SEQ ID NO: 165. 103. The formulation of claim 102, wherein the IL-13 antibody comprises a means for extending the half-life of the IL-13 antibody. 104. The formulation of claim 103, wherein the means comprises at least one amino acid modification in the IL-13 antibody. 105. The formulation of any one of claims 96-104, wherein the formulation further comprises a sugar or sugar alcohol.
PCT/US2024/061395 2023-12-20 2024-12-20 Pharmaceutical formulations of antibodies that bind interleukin 13 Pending WO2025137523A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363612892P 2023-12-20 2023-12-20
US63/612,892 2023-12-20

Publications (2)

Publication Number Publication Date
WO2025137523A2 true WO2025137523A2 (en) 2025-06-26
WO2025137523A3 WO2025137523A3 (en) 2025-07-24

Family

ID=94384399

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/061395 Pending WO2025137523A2 (en) 2023-12-20 2024-12-20 Pharmaceutical formulations of antibodies that bind interleukin 13

Country Status (1)

Country Link
WO (1) WO2025137523A2 (en)

Citations (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993016185A2 (en) 1992-02-06 1993-08-19 Creative Biomolecules, Inc. Biosynthetic binding protein for cancer marker
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
US5587458A (en) 1991-10-07 1996-12-24 Aronex Pharmaceuticals, Inc. Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
WO1997030087A1 (en) 1996-02-16 1997-08-21 Glaxo Group Limited Preparation of glycosylated antibodies
WO1998058964A1 (en) 1997-06-24 1998-12-30 Genentech, Inc. Methods and compositions for galactosylated glycoproteins
US5877293A (en) 1990-07-05 1999-03-02 Celltech Therapeutics Limited CDR grafted anti-CEA antibodies and their production
US5886152A (en) 1991-12-06 1999-03-23 Sumitomo Pharmaceuticals Company, Limited Humanized B-B10
WO1999022764A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
WO1999051642A1 (en) 1998-04-02 1999-10-14 Genentech, Inc. Antibody variants and fragments thereof
US6054297A (en) 1991-06-14 2000-04-25 Genentech, Inc. Humanized antibodies and methods for making them
WO2000061739A1 (en) 1999-04-09 2000-10-19 Kyowa Hakko Kogyo Co., Ltd. Method for controlling the activity of immunologically functional molecule
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
WO2001029246A1 (en) 1999-10-19 2001-04-26 Kyowa Hakko Kogyo Co., Ltd. Process for producing polypeptide
WO2002031140A1 (en) 2000-10-06 2002-04-18 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions
US20020164328A1 (en) 2000-10-06 2002-11-07 Toyohide Shinkawa Process for purifying antibody
US20030115614A1 (en) 2000-10-06 2003-06-19 Yutaka Kanda Antibody composition-producing cell
US20030157108A1 (en) 2001-10-25 2003-08-21 Genentech, Inc. Glycoprotein compositions
WO2003085107A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Cells with modified genome
WO2003084570A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. DRUG CONTAINING ANTIBODY COMPOSITION APPROPRIATE FOR PATIENT SUFFERING FROM FcϜRIIIa POLYMORPHISM
WO2003085119A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. METHOD OF ENHANCING ACTIVITY OF ANTIBODY COMPOSITION OF BINDING TO FcϜ RECEPTOR IIIa
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
US20040110282A1 (en) 2002-04-09 2004-06-10 Kyowa Hakko Kogyo Co., Ltd. Cells in which activity of the protein involved in transportation of GDP-fucose is reduced or lost
US20040109865A1 (en) 2002-04-09 2004-06-10 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
WO2004056312A2 (en) 2002-12-16 2004-07-08 Genentech, Inc. Immunoglobulin variants and uses thereof
US20040132140A1 (en) 2002-04-09 2004-07-08 Kyowa Hakko Kogyo Co., Ltd. Production process for antibody composition
WO2005035778A1 (en) 2003-10-09 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. PROCESS FOR PRODUCING ANTIBODY COMPOSITION BY USING RNA INHIBITING THE FUNCTION OF α1,6-FUCOSYLTRANSFERASE
WO2005035586A1 (en) 2003-10-08 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Fused protein composition
WO2005053742A1 (en) 2003-12-04 2005-06-16 Kyowa Hakko Kogyo Co., Ltd. Medicine containing antibody composition
WO2006105338A2 (en) 2005-03-31 2006-10-05 Xencor, Inc. Fc VARIANTS WITH OPTIMIZED PROPERTIES
WO2008077546A1 (en) 2006-12-22 2008-07-03 F. Hoffmann-La Roche Ag Antibodies against insulin-like growth factor i receptor and uses thereof
US20110212087A1 (en) 2009-11-30 2011-09-01 William Strohl Antibody Fc Mutants with Ablated Effector Functions
WO2011120134A1 (en) 2010-03-29 2011-10-06 Zymeworks, Inc. Antibodies with enhanced or suppressed effector function
US20120225058A1 (en) 2004-10-21 2012-09-06 Xencor, Inc. Novel immunoglobulin insertions, deletions, and substitutions
US20120251531A1 (en) 2011-03-29 2012-10-04 Genentech, Inc. ANTIBODY Fc VARIANTS
US8409572B2 (en) 2000-04-12 2013-04-02 Laboratoire Francais Du Fractionnement Et Des Biotechnologies Monoclonal antibodies with enhanced ADCC function
US9067994B2 (en) 2003-12-23 2015-06-30 Genentech, Inc. Anti-IL13 antibodies and uses thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102259829B1 (en) * 2011-10-31 2021-06-03 제넨테크, 인크. Antibody formulations

Patent Citations (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5877293A (en) 1990-07-05 1999-03-02 Celltech Therapeutics Limited CDR grafted anti-CEA antibodies and their production
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
US6054297A (en) 1991-06-14 2000-04-25 Genentech, Inc. Humanized antibodies and methods for making them
US5587458A (en) 1991-10-07 1996-12-24 Aronex Pharmaceuticals, Inc. Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
US5886152A (en) 1991-12-06 1999-03-23 Sumitomo Pharmaceuticals Company, Limited Humanized B-B10
WO1993016185A2 (en) 1992-02-06 1993-08-19 Creative Biomolecules, Inc. Biosynthetic binding protein for cancer marker
WO1997030087A1 (en) 1996-02-16 1997-08-21 Glaxo Group Limited Preparation of glycosylated antibodies
WO1998058964A1 (en) 1997-06-24 1998-12-30 Genentech, Inc. Methods and compositions for galactosylated glycoproteins
WO1999022764A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
WO1999051642A1 (en) 1998-04-02 1999-10-14 Genentech, Inc. Antibody variants and fragments thereof
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
WO2000061739A1 (en) 1999-04-09 2000-10-19 Kyowa Hakko Kogyo Co., Ltd. Method for controlling the activity of immunologically functional molecule
WO2001029246A1 (en) 1999-10-19 2001-04-26 Kyowa Hakko Kogyo Co., Ltd. Process for producing polypeptide
US8409572B2 (en) 2000-04-12 2013-04-02 Laboratoire Francais Du Fractionnement Et Des Biotechnologies Monoclonal antibodies with enhanced ADCC function
WO2002031140A1 (en) 2000-10-06 2002-04-18 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions
US20020164328A1 (en) 2000-10-06 2002-11-07 Toyohide Shinkawa Process for purifying antibody
US20030115614A1 (en) 2000-10-06 2003-06-19 Yutaka Kanda Antibody composition-producing cell
US20030157108A1 (en) 2001-10-25 2003-08-21 Genentech, Inc. Glycoprotein compositions
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
WO2003084570A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. DRUG CONTAINING ANTIBODY COMPOSITION APPROPRIATE FOR PATIENT SUFFERING FROM FcϜRIIIa POLYMORPHISM
WO2003085107A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Cells with modified genome
US20040110704A1 (en) 2002-04-09 2004-06-10 Kyowa Hakko Kogyo Co., Ltd. Cells of which genome is modified
US20040110282A1 (en) 2002-04-09 2004-06-10 Kyowa Hakko Kogyo Co., Ltd. Cells in which activity of the protein involved in transportation of GDP-fucose is reduced or lost
US20040109865A1 (en) 2002-04-09 2004-06-10 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
US20040132140A1 (en) 2002-04-09 2004-07-08 Kyowa Hakko Kogyo Co., Ltd. Production process for antibody composition
WO2003085119A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. METHOD OF ENHANCING ACTIVITY OF ANTIBODY COMPOSITION OF BINDING TO FcϜ RECEPTOR IIIa
WO2004056312A2 (en) 2002-12-16 2004-07-08 Genentech, Inc. Immunoglobulin variants and uses thereof
WO2005035586A1 (en) 2003-10-08 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Fused protein composition
WO2005035778A1 (en) 2003-10-09 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. PROCESS FOR PRODUCING ANTIBODY COMPOSITION BY USING RNA INHIBITING THE FUNCTION OF α1,6-FUCOSYLTRANSFERASE
WO2005053742A1 (en) 2003-12-04 2005-06-16 Kyowa Hakko Kogyo Co., Ltd. Medicine containing antibody composition
US9067994B2 (en) 2003-12-23 2015-06-30 Genentech, Inc. Anti-IL13 antibodies and uses thereof
US20120225058A1 (en) 2004-10-21 2012-09-06 Xencor, Inc. Novel immunoglobulin insertions, deletions, and substitutions
WO2006105338A2 (en) 2005-03-31 2006-10-05 Xencor, Inc. Fc VARIANTS WITH OPTIMIZED PROPERTIES
WO2008077546A1 (en) 2006-12-22 2008-07-03 F. Hoffmann-La Roche Ag Antibodies against insulin-like growth factor i receptor and uses thereof
US20110212087A1 (en) 2009-11-30 2011-09-01 William Strohl Antibody Fc Mutants with Ablated Effector Functions
WO2011120134A1 (en) 2010-03-29 2011-10-06 Zymeworks, Inc. Antibodies with enhanced or suppressed effector function
WO2011120135A1 (en) 2010-03-29 2011-10-06 Zymeworks, Inc. Antibodies with enhanced or suppressed effector function
US20120251531A1 (en) 2011-03-29 2012-10-04 Genentech, Inc. ANTIBODY Fc VARIANTS

Non-Patent Citations (52)

* Cited by examiner, † Cited by third party
Title
"Antibodies, A Laboratory Manual", 1988, COLD SPRING HARBOR LABORATORY
"Centre of Evidence Based Dermatology", POEM - PATIENT ORIENTED ECZEMA MEASURE, Retrieved from the Internet <URL:www.nottingham.ac.uk/research/groups/cebd/resources/poem.aspx>
"Consensus report of the European Task Force on Atopic Dermatitis", DERMATOLOGY, vol. 186, no. 1, 1993, pages 23 - 31
ABHINANDANMARTIN, IMMUNOLOGY, vol. 2008, no. 45, pages 3832 - 3839
ABNUM, Retrieved from the Internet <URL:www.bioinf.org.uk/abs/abnum>
AL-LAZIKANI ET AL., J. MOL. BIOL., vol. 273, 1997, pages 927 - 948
ARABI GHAHROUDI ET AL., FEBS LETTERS, vol. 1998, no. 414, pages 521 - 526
CAPEL ET AL., IMMUNOMETHODS, vol. 113, 1994, pages 269 - 315
CHOTHIA ET AL., J MOL BIOL, vol. 196, 1987, pages 901 - 917
CHU SYVOSTIAR IKARKI S ET AL., MOL IMMUNOL., vol. 45, no. 15, September 2008 (2008-09-01), pages 3926 - 33
COX ET AL.: "Assay Guidance Manual", 24 December 2014, article "Immunoassay Methods"
DAËRON, ANNU. REV. IMMUNOL., vol. 15, 1997, pages 203 - 234
DE HAAS ET AL., J. LAB. CLIN. MED., vol. 126, 1995, pages 330 - 41
FINCO ET AL., J. PHARM. BIOMED. ANAL., vol. 2011, no. 54, pages 351 - 358
FINLAY, A. Y.KHAN, G. K., CLINICAL AND EXPERIMENTAL DERMATOLOGY, vol. 19, 23 September 1993 (1993-09-23), pages 210 - 216
GUYER ET AL., J. IMMUNOL., vol. 117, 1976, pages 587
HANIFIN ET AL., EXP DERMATOL., vol. 2001, no. 10, pages 11 - 18
HARMSEN MMDE HAARD HJ: "Properties, production, and applications of camelid single-domain antibody fragments", APPL. MICROBIOL BIOTECHNOL., vol. 77, no. 1, 2007, pages 13 - 22
HENNING VON HORSTEN ET AL., GLYCOBIOL, vol. 2010, no. 20, pages 1607 - 1618
HONEGGEPLUCKTHUN, J. MOL. BIOL., vol. 2001, no. 309, 2012, pages 204 - 219
IDUSOGIE ET AL., J. IMMUNOL., vol. 2000, no. 164, pages 4178 - 4184
JANEWAY ET AL.: "Immuno Biology: the immune system in health and disease", 1999, ELSEVIER SCIENCE LTD.
KANDA ET AL., BIOTECHNOL. BIOENG., vol. 2006, no. 94, pages 680 - 688
KIM ET AL., J. IMMUNOL., vol. 24, 1994, pages 249
LAZAR ET AL., PROC. NATL. ACAD. SCI. USA, vol. 2006, no. 103, pages 4005 - 4010
LAZAR GADANG WKARKI S ET AL., PROC NATL ACAD SCI U S A, vol. 103, no. 11, 14 March 2006 (2006-03-14), pages 4005 - 10
LEFRANC ET AL., DEV. COMP. IMMUNOL., vol. 2003, no. 27, pages 55 - 77
LU YVERNES JMCHIANG N ET AL., J IMMUNOL METHODS, vol. 365, no. 1-2, 28 February 2011 (2011-02-28), pages 132 - 41
MACCALLUM ET AL., J. MOL. BIOL., vol. 262, 1996, pages 732 - 745
MUYLDERMANS ET AL., TRENDS IN BIOCHEM. SCI., vol. 2001, no. 26, pages 230 - 245
NEEDLEMANWUNSCH, J. MOL. BIOL., vol. 48, 1970, pages 443
NORDSTROM JLGORLATOV SZHANG W ET AL., BREAST CANCER RES., vol. 13, no. 6, 30 November 2011 (2011-11-30), pages R123
OKAZAKI ET AL., J. MOL. BIOL., vol. 2004, no. 336, pages 1239 - 1249
PEARSONLIPMAN, PROC. NAT'L. ACAD. SCI. USA, vol. 85, 1988, pages 2444
PHAN NQ ET AL., ACTA DERM VENEREAL, vol. 2012, no. 92, pages 502 - 507
PRESTA, CURR. OP. STRUCT. BIOL., vol. 1992, no. 2, pages 593 - 596
RAVETCHKINET, ANNU. REV. IMMUNOL, vol. 9, 1991, pages 457 - 92
RIECHMANN ET AL., NATURE, vol. 1988, no. 332, pages 323 - 329
RIPKA ET AL., ARCH. BIOCHEM. BIOPHYS., vol. 1986, no. 249, pages 533 - 545
SCHROEDERCAVACINI, J. ALLERGY CLIN. IMMUNOL., vol. 2010, no. 125, pages 41 - 52
SHIELDS ET AL., J. BIOL. CHEM., vol. 2002, no. 277, pages 26733 - 26740
SHIELDS RLNAMENUK AKHONG K ET AL., J BIOL CHEM., vol. 276, no. 9, 2 March 2001 (2001-03-02), pages 6591 - 604
SILMAN ET AL., CYTOMETRY, vol. 2001, no. 44, pages 30 - 37
SIMPSON E ET AL., JAM ACAD DERMATOL., vol. 83, no. 3, 2020, pages 839 - 846
SMITHWATERMAN, ADV. APPL. MATH., vol. 2, 1981, pages 482
STAVENHAGEN JBGORLATOV STUAILLON N ET AL., CANCER RES., vol. 67, no. 18, 15 September 2007 (2007-09-15), pages 8882 - 90
STEWART RTHOM GLEVENS M ET AL., PROTEIN ENG DES SEL., vol. 24, no. 9, September 2011 (2011-09-01), pages 671 - 8
STROHL, WR, CURR OPIN BIOTECH, vol. 20, 2009, pages 685 - 691
STROHL, WRSTROHL LM: "Molecular Cloning: A Laboratory Manual", 2012, COLD SPRING HARBOR LABORATORY PRESS, article "Antibody Fc engineering for optimal antibody performance", pages: 225 - 249
VON HORSTEN ET AL., GLYCOBIOLOGY, vol. 20, no. 12, December 2010 (2010-12-01), pages 1607 - 18
WILLIAM R. STROHLLILA M. STROHL: "Biomedicine", 9 October 2012, WOODHEAD PUBLISHING, article "Therapeutic Antibody Engineering", pages: 283
YAMANE-OHNUKI ET AL., BIOTECH. BIOENG., vol. 2004, no. 87, pages 614 - 622

Also Published As

Publication number Publication date
WO2025137523A3 (en) 2025-07-24

Similar Documents

Publication Publication Date Title
US11787860B2 (en) Anti-CD47 antibodies and uses thereof
CN102301235B (en) Stabilized antibody compositions and methods for stabilizing the same
US20240228615A1 (en) Anti-trem-1 antibodies and uses thereof
AU2022229993A1 (en) Pharmaceutical composition containing anti-tslp antibody
JP2022084782A (en) Pharmaceutical composition and administration regimen for clinical use of anti-blood dendritic cell antigen 2 antibody
US12358979B2 (en) Antibodies that bind interleukin 13 and methods of use
KR20220143882A (en) Pharmaceutical compositions containing anti-IL-4R antibodies and uses thereof
AU2024262173A1 (en) Methods of administering antibodies that bind interleukin 13
CN106687133A (en) Methods of treating autoimmune disease using a domain antibody directed against CD40L
RS66193B1 (en) Anti-pd-1 antibodies
IL310427A (en) Pharmaceutical preparation of anti-R4IL antibody and use thereof
US20250059285A1 (en) Galectin-10 antibodies
TW202509068A (en) Antibodies that bind ox40l and methods of use
WO2025137523A2 (en) Pharmaceutical formulations of antibodies that bind interleukin 13
KR20250150541A (en) Antibodies that bind to interleukin 4 receptor alpha and methods of use
CN119768431A (en) IGF1R antibodies
WO2025137410A1 (en) Pharmaceutical compositions of anti-il-13 antibodies with and without c-terminal lysine
RU2841944C1 (en) Pharmaceutical composition comprising anti-il-4r antibody and use thereof
CN121241066A (en) Administration method of antibodies against interleukin-13
WO2025166234A1 (en) Methods of administering antibodies that bind interleukin 4 receptor alpha
JP2025539796A (en) LAG-3 and PD-1/LAG-3 antibodies

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24846987

Country of ref document: EP

Kind code of ref document: A2