Methods of administering antibodies that bind interleukin 13

Abstract

Described herein are methods of administration of antibodies that bind interleukin 13 (IL-13) and methods of use thereof. In certain aspects, described herein are methods of inhibiting IL-13 biological activity. In certain aspects, the antibodies and methods described herein are used for treatment of an inflammatory disorder or disease, such as atopic dermatitis.

Description

AOJ-008PCAOE-OIOIWOMETHODS OF ADMINISTERING ANTIBODIES THAT BIND INTERLEUKIN 13CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 705,714 (filed October 10, 2024), U.S. Provisional Application No. 63 / 720,543 (filed November 14, 2024), U.S. Provisional Application No. 63 / 735,494 (filed December 18, 2024), U.S. Provisional Application No. 63 / 838,294 (filed July 3, 2025), U.S. Provisional Application No. 63 / 846,567 (filed July 18, 2025), and U.S. Provisional Application No. USSN 63 / 880,678 (filed September 12, 2025), each of which is incorporated by reference herein in its entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on October 10, 2025, is named AOJ-008PC_SL.vml and is 549,219 bytes in size.BACKGROUND

[0003] Atopic dermatitis (AD), the most common form of eczema, is a common chronic inflammatory skin disorder that affects individuals of all ages, races, and geographic regions worldwide (Stander S, N Engl J Med. 384(12): 1136- 1143, 2021; Bieber T, N Engl J Med. 358(14): 1483- 1494, 2008). The pathogenesis of AD involves both genetic and environmental factors that interact to produce a complex inflammatory response in the skin. Multiple studies have demonstrated interleukin (IL)-13 as a key driver of inflammation in AD (Tsoi et al., J Invest Dermatol. 139(7): 1480-1489, 2019; Tazawa et al., Arch Dermatol Res. 295(11):459- 464, 2004) that has been shown to be elevated in the skin of AD inflammation.

[0004] IL- 13 is a T helper cell subclass 2 (Th2) cytokine, and belongs to the family of type I cytokines. IL- 13 is involved in the differentiation of naive T cells into Th2 cells, promotes B-cell proliferation, and induces class switching to IgG4 and IgE in combination with CD40 / CD40L co-stimulation (IL- 13 up-regulates FcsRI 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-AOJ-008PCAOE-OIOIWO dependent cytotoxicity, 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.

[0005] The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved monoclonal antibodies (mAbs) targeting IL- 13 (tralokinumab and lebrikizumab). Both regulatory agencies have approved mAbs targeting IL-4Ra (dupilumab) for patients with moderate- to- severe AD. Although these mAbs have shown a positive benefit-risk profile, injections are required every 2 to 4 weeks to achieve this positive clinical benefit, representing a high injection burden over time for patients with this chronic disease.

[0006] Accordingly, there is a need in the art for improved therapeutic approaches for treating AD that allow for less frequent dosing. It is an object of the present invention to provide improved methods for treating patients with AD.SUMMARY

[0007] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) one to five or more induction doses, each selected from 100 mg, 125 mg, 150 mg, 180 mg, 200 mg, 250 mg, 300 mg, 360 mg, 400 mg, 450 mg, 600 mg, 720 mg, 800 mg, 900 mg, 1080 mg, or 1200 mg or a dose listed in any one of Tables 11-13 of an anti-IL-13 antibody, or antigen binding fragment thereof; and b) one or more maintenance doses administered about 4-17 weeks or 20-24 weeks or more after the first induction dose; wherein the maintenance dose is 150 mg, 180 mg, 200 mg, 250 mg, 300 mg, 360 mg, 400 mg, 450 mg, 600 mg, 800 mg, 1080 mg, or 1200 mg or a dose listed in Table 14 of the anti-IL-13 antibody, or antigen binding fragment thereof; andAOJ-008PCAOE-OIOIWO wherein the anti-IL-13 antibody, or antigen binding fragment thereof comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0008] In certain embodiments, the method further comprises administering a loading dose prior to the one to five or more induction doses, wherein the loading dose is 2 times the induction dose.

[0009] In certain embodiments, the method further comprises administering two loading doses prior to the one to five or more induction doses, wherein the loading dose is 2 times the induction dose.

[0010] In certain embodiments, the one or more maintenance doses are administered about 4-16 weeks or 12-16 weeks after the first induction dose.

[0011] In certain embodiments, the one or more maintenance doses are administered about 20-24 weeks after the first induction dose. In certain embodiments, the one or more maintenance doses are administered about 20 weeks after the first induction dose. In certain embodiments, the one or more maintenance doses are administered about 24 weeks after the first induction dose.

[0012] In certain embodiments, the first induction dose is 150 mg, 180 mg, 300 mg, 360 mg, 600 mg, or 720 mg. In certain embodiments, the first induction dose is 360 mg. In certain embodiments, the first induction dose is 180 mg. In certain embodiments, the first induction dose is 720 mg.

[0013] In certain embodiments, the method further comprises administering a second, third, fourth, and / or fifth induction dose of 180 mg, 300 mg, 360 mg, or 720 mg of the anti- IL-13 antibody, or antigen binding fragment thereof. In certain embodiments, the method further comprises administering a second, third, fourth, and / or fifth induction dose of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof. In certain embodiments, the method further comprises administering a second induction dose of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof. In certain embodiments, the method further comprises administering a second, third, and fourth induction dose of 360 mg of the anti-IL- 13 antibody, or antigen binding fragment thereof. In certain embodiments, the method furtherAOJ-008PCAOE-OIOIWO comprises administering a second induction dose of 180 mg of the anti-IL-13 antibody, or antigen binding fragment thereof. In certain embodiments, the method further comprises administering a second, third, fourth, and fifth induction dose of 720 mg of the anti-IL-13 antibody, or antigen binding fragment thereof.

[0014] In certain embodiments, the second induction dose is administered about 2 to about 16 weeks after the first induction dose.

[0015] In certain embodiments, the second induction dose is administered about two or about eight weeks after the first induction dose. In certain embodiments, the second induction dose is administered about two weeks after the first induction dose. In certain embodiments, the second induction dose is administered about eight weeks after the first induction dose.

[0016] In certain embodiments, the second induction dose is administered about four weeks after the first induction dose.

[0017] In certain embodiments, the method further comprises administering a second, third, fourth, and / or fifth induction dose of 600 mg of the anti-IL-13 antibody, or antigen binding fragment thereof.

[0018] In certain embodiments, the second induction dose is administered about 2 to about 16 weeks after the first induction dose.

[0019] In certain embodiments, the method comprises administering two loading doses of 720 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, two induction doses of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, and one or more maintenance doses administered starting at about 20 weeks after the first induction dose, wherein the second loading dose is administered two weeks after the first loading dose, wherein the first induction dose is administered two weeks after the second loading dose, and wherein the second induction dose is administered eight weeks after the first induction dose.

[0020] In certain embodiments, the method comprises administering five induction doses of 720 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, and one or more maintenance doses administered starting at about 24 weeks after the first induction dose, wherein the second induction dose is administered two weeks after the first induction dose, the third induction dose is administered two weeks after the second induction dose, the fourth induction dose is administered four weeks after the third induction dose, and the fifth induction dose is administered four weeks after the fourth induction dose.AOJ-008PCAOE-OIOIWO

[0021] In certain embodiments, the method comprises administering one loading dose of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, two induction doses of 180 mg of the anti-IL- 13 antibody, or antigen binding fragment thereof, and one or more maintenance doses administered starting at about 20 weeks after the first induction dose, wherein the first induction dose is administered four weeks after the loading dose, and wherein the second induction dose is administered eight weeks after the first induction dose.

[0022] In certain embodiments, the maintenance dose is 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 600 mg, 720 mg, 800 mg, or 1200 mg and is administered every 3 months, every 12 weeks, or 4 times a year.

[0023] In certain embodiments, the maintenance dose is 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 600 mg, 720 mg, 800 mg, or 1200 mg and is administered every 2 months or every 8 weeks.

[0024] In certain embodiments, the maintenance dose is 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 600 mg, 720 mg, 800 mg, or 1200 mg and is administered every 16 weeks or three times a year.

[0025] In certain embodiments, the maintenance dose is 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 600 mg, 720 mg, 800 mg, or 1200 mg and is administered every 20 weeks.

[0026] In certain embodiments, the maintenance dose is 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 600 mg, 720 mg, 800 mg or 1200 mg, and is administered every 24 weeks, every 26 weeks, every 6 months, or twice a year.

[0027] In certain embodiments, the maintenance dose is 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 600 mg, 720 mg, 800 mg, or 1200 mg and is administered once a year.

[0028] In certain embodiments, the maintenance dose is 180 mg, 300 mg, 360 mg, 600 mg, 720 mg or 1200 mg and is administered every 3 months, 12 weeks, or 4 times a year.

[0029] In certain embodiments, the maintenance dose is 180 mg, 300 mg, 360 mg, 600 mg, 720 mg, or 1200 mg and is administered every 2 months or 8 weeks.

[0030] In certain embodiments, the maintenance dose is 180 mg, 300 mg, 360 mg, 600 mg, 720 mg, or 1200 mg and is administered every 16 weeks or three times a year.

[0031] In certain embodiments, the maintenance dose is 180 mg, 300 mg, 360 mg, 600 mg, 720 mg, or 1200 mg and is administered every 20 weeks.AOJ-008PCAOE-OIOIWO

[0032] In certain embodiments, the maintenance dose is 180 mg, 300 mg, 360 mg, 600 mg, 720 mg, or 1200 mg and is administered every 6 months or twice a year.

[0033] In certain embodiments, the maintenance dose is 180 mg, 300 mg, 360 mg, 600 mg, 720 mg, or 1200 mg and is administered once a year.

[0034] In certain embodiments, each unit dose is administered as composition comprising 150 mg / mL, 180 mg / mL, or 200 mg / mL of the anti-IL-13 antibody, or antigen binding fragment thereof.

[0035] In certain embodiments, the unit dose has an extractable volume of about 1 mL, about 2 mL, about 2.25 mL, about 2.7 mL, about 3 mL, about 4 mL or about 5 mL.

[0036] In certain embodiments, the anti-IL-13 antibody, or antigen binding fragment thereof is administered by an autoinjector or a prefilled syringe.

[0037] In certain embodiments, the patient has been diagnosed with moderate-to-severe atopic dermatitis.

[0038] In certain embodiments, the patient has or has been diagnosed with moderate-to- severe atopic dermatitis and comorbid asthma.

[0039] In certain embodiments, the patient has or has been diagnosed with moderate-to- severe atopic dermatitis and a comorbid sinonasal condition.

[0040] In certain embodiments, the patient has had moderate-to-severe atopic dermatitis for at least one year.

[0041] 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 score of >16),(b) an Investigator Global Assessment (IGA) score (i.e., a validated Investigator Global Assessment for AD (vIGA-AD score)) of >3 and(c) a body surface area (BSA) of >10% (AD affecting >10% BSA).

[0042] In certain embodiments of any of the foregoing aspects, the patient has an EASI score of >16, a vIGA-AD score of >3, and AD affecting >10% BSA.

[0043] In certain embodiments of any of the foregoing aspects, the patient has or has been diagnosed with moderate atopic dermatitis.

[0044] In certain embodiments of any of the foregoing aspects, the patient has or has been diagnosed with severe atopic dermatitis.AOJ-008PCAOE-OIOIWO

[0045] In certain embodiments, the method further comprises 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), Validated Investigator Global Assessment (vIGA or vIGA-AD), Body Surface Area (BSA), Itch Numeric Rating Scale (I-NRS), Skin Pain Numerical Rating Scale (SP-NRS), Atopic Dermatitis Sleep Scale (ADSS), SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Asthma Control Questionnaire 5-item version (ACQ-5), and Sino-nasal Outcome Test 22-item version (SNOT-22). In certain embodiments, the method further comprises determining one or more of EASI, vIGA-AD, BSA, I-NRS, SP-NRS, ADSS, SCORAD, POEM, DLQI, ACQ-5, and SNOT-22 during or after the maintenance period.

[0046] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising: subcutaneously administering to the patient an anti-IL-13 antibody, or antigen binding fragment thereof for an induction period of 4 to 17 weeks, wherein, during the induction period, the anti-IL-13 antibody, or antigen binding fragment thereof is administered once or twice at a loading dose of from about 100 mg to about 1200 mg or a dose listed in any one of Tables 11-13, and, optionally, at least once at a dose that is at one-half or one-quarter of the loading dose; and subcutaneously administering to the patient the anti-IL-13 antibody, or antigen binding fragment thereof at a dose of from about 100 mg to about 1200 mg or a dose listed in Table 14 for a maintenance period; wherein the anti-IL-13 antibody, or antigen binding fragment thereof comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90% ( g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence at least 90% (eg., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 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 LCDR1AOJ-008PCAOE-OIOIWO comprising SEQ ID NO: 141 or SEQ ID NO: 149; a LCDR2 comprising SEQ ID NO: 153, and a LCDR3 comprising SEQ ID NO: 165.

[0047] In certain embodiments, during the induction period, the loading dose is about 100 mg, 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 450 mg, 600 mg, 720 mg, 800 mg, 900 mg, 1080 mg, or 1200 mg.

[0048] In certain embodiments, during the induction period, the loading dose is administered at week 0 and week 2.

[0049] In certain embodiments, during the induction period, the loading dose is administered at week 0 and week 4.

[0050] In certain embodiments, during the induction period, the loading dose is administered at week 0 and week 8.

[0051] In certain embodiments, during the induction period, the loading dose is administered at week 0 and week 12.

[0052] In certain embodiments, during the induction period, the loading dose is administered at week 0.

[0053] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 8, 12, and 16.

[0054] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 4, 8, 12, and 16.

[0055] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 4 and 12.

[0056] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 4 and 8.

[0057] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 2, 4, and 12.

[0058] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 2 and 12.

[0059] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at week 12.

[0060] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 8 and 16.AOJ-008PCAOE-OIOIWO

[0061] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at week 16.

[0062] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 4 and 14.

[0063] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at week 14.

[0064] In certain embodiments, during the induction period, the one-half or one-quarter dose is administered at weeks 2, 4, and 14.

[0065] In certain embodiments, the maintenance dose is 100 mg, 150 mg, 180 mg, 200 mg, 300 mg, 360 mg, 400 mg, 450 mg, 600 mg, 720 mg, 800 mg, 900 mg, or 1200 mg.

[0066] In certain embodiments, during the maintenance period, the anti-IL-13 antibody, or antigen binding fragment thereof, is administered every 3 months, 12 weeks, or 4 times a year.

[0067] In certain embodiments, during the maintenance period, the anti-IL-13 antibody, or antigen binding fragment thereof, is administered every 2 months or 8 weeks.

[0068] In certain embodiments, during the maintenance period, the anti-IL-13 antibody, or antigen binding fragment thereof, is administered every 16 weeks or three times a year.

[0069] In certain embodiments, during the maintenance period, the anti-IL-13 antibody, or antigen binding fragment thereof, is administered every 20 weeks.

[0070] In certain embodiments, during the maintenance period, the anti-IL-13 antibody, or antigen binding fragment thereof, is administered every 6 months or twice a year.

[0071] In certain embodiments, during the maintenance period, the anti-IL-13 antibody, or antigen binding fragment thereof, is administered once a year.

[0072] In certain embodiments, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0073] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient:AOJ-008PCAOE-OIOIWO a) five induction doses of 720 mg of the anti-IL-13 antibody, or antigen binding fragment thereof; and c) one or more maintenance doses of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, administered starting at about 24 weeks or more after the first induction dose; wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0074] In certain embodiments, the second induction dose is administered about 2 weeks after the first induction dose.

[0075] In certain embodiments, the third induction dose is administered about 2 weeks after the second induction dose.

[0076] In certain embodiments, the fourth induction dose is administered about 4 weeks after the third induction dose.

[0077] In certain embodiments, the fifth induction dose is administered about 4 weeks after the fourth induction dose.

[0078] In certain embodiments, the first maintenance dose is administered 24 weeks after the first induction dose.

[0079] In certain embodiments, the first maintenance dose is administered 12 weeks after the fifth induction dose.

[0080] In certain embodiments, the maintenance dose is administered every 12 weeks.

[0081] In certain embodiments, the maintenance dose is administered every 24 weeks.

[0082] In certain embodiments, the maintenance dose is administered every 3 months.

[0083] In certain embodiments, the maintenance dose is administered every 6 months.

[0084] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) two loading doses of 720 mg of an anti-IL-13 antibody, or antigen binding fragment thereof, prior to two induction doses;AOJ-008PCAOE-OIOIWO b) two induction doses of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof; and c) one or more maintenance doses of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, administered starting at about 12 weeks or 20 weeks or more after the first induction dose; wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0085] In certain embodiments, the second loading dose is administered about 2 weeks after the first loading dose.

[0086] In certain embodiments, the first induction dose is administered about 2 weeks after the second loading dose.

[0087] In certain embodiments, the second induction dose is administered about 8 weeks after the first induction dose.

[0088] In certain embodiments, the first maintenance dose is administered 24 weeks after the first loading dose.

[0089] In certain embodiments, the first maintenance dose is administered 12 weeks after the second induction dose.

[0090] In certain embodiments, the first maintenance dose is administered 20 weeks after the first induction dose.

[0091] In certain embodiments, the maintenance dose is administered every 12 weeks.

[0092] In certain embodiments, the maintenance dose is administered every 24 weeks.

[0093] In certain embodiments, the maintenance dose is administered every 3 months.

[0094] In certain embodiments, the maintenance dose is administered every 6 months.

[0095] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) a loading dose of 360 mg of an anti-IL-13 antibody, or antigen binding fragment thereof, prior to two induction doses;AOJ-008PCAOE-OIOIWO b) two induction doses of 180 mg of the anti-IL-13 antibody, or antigen binding fragment thereof; and c) one or more maintenance doses of 180 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, administered starting at about 12 weeks or 20 weeks or more after the first induction dose; and wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0096] In certain embodiments, the first induction dose is administered about 4 weeks after the loading dose.

[0097] In certain embodiments, the second induction dose is administered about 8 weeks after the first induction dose.

[0098] In certain embodiments, the first maintenance dose is administered 12 weeks after the second induction dose.

[0099] In certain embodiments, the first maintenance dose is administered 24 weeks after the loading dose.

[0100] In certain embodiments, the first maintenance dose is administered 20 weeks after the first induction dose.

[0101] In certain embodiments, the maintenance dose is administered every 12 weeks.

[0102] In certain embodiments, the maintenance dose is administered every 24 weeks.

[0103] In certain embodiments, the maintenance dose is administered every 3 months.

[0104] In certain embodiments, the maintenance dose is administered every 6 months.

[0105] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) one loading dose of 720 mg of an anti-IL-13 antibody, or antigen binding fragment thereof, prior to two induction doses; b) two induction doses of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof; andAOJ-008PCAOE-OIOIWO c) one or more maintenance doses of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, administered starting at about 16 weeks after the first induction dose, wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0106] In certain embodiments, the first induction dose is administered about 4 weeks after the loading dose.

[0107] In certain embodiments, the second induction dose is administered about 8 weeks after the first induction dose.

[0108] In certain embodiments, the maintenance dose is administered every 3 months or 12 weeks.

[0109] In certain aspects, described herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: an initial dose of 720 mg of an anti-IL-13 antibody, or antigen binding fragment thereof, a dose of 360 mg of the anti-IL-13 antibody, or antigen binding fragment thereof, administered at 4 weeks and 8 weeks after the initial dose of 720 mg, and a dose of 360 mg administered every 3 months or 12 weeks starting 20 weeks after the initial dose of 720 mg, wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0110] In certain embodiments of any of the foregoing aspects, the maintenance dose is 720 mg and is administered every 24 weeks.

[0111] In certain embodiments of any of the foregoing aspects, the maintenance dose is 720 mg and is administered every 6 months.AOJ-008PCAOE-OIOIWO

[0112] In certain embodiments of any of the foregoing aspects, the maintenance dose is 1200 mg and is administered every 24 weeks.

[0113] In certain embodiments of any of the foregoing aspects, the maintenance dose is 1200 mg and is administered every 6 months.

[0114] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 39.

[0115] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a constant heavy chain sequence set forth in any one of SEQ ID NOs: 425-468, 484-539, and 610-709. In certain embodiments, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain constant region of SEQ ID NO: 439 and / or SEQ ID NO: 624.

[0116] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 610-709), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 425-468 and 484-539). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 610-709), a human IgG sequence lacking a C-terminal lysine e.g., any one of SEQ ID NOs: 425-468 and 484-539), or a mixture thereof (e.g., a mixture of the same heavy chain constant region sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 624 and SEQ ID NO: 439).

[0117] In certain embodiments of any of the foregoing aspects, the anti-IL 13 antibody, or antigen binding fragment thereof, comprises a light chain comprising a human kappa light chain constant region. In some embodiments, the light chain comprises a constant light chain sequence set forth in SEQ ID NO: 469.

[0118] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a human Fc region comprising a human heavy chain constant region of the class IgG and a subclass selected from IgGl, IgG2, IgG3, and IgG4.AOJ-008PCAOE-OIOIWO

[0119] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a constant heavy chain region having a means for extending the half-life of the antibody.

[0120] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a human Fc region comprising one or more amino acid substitutions, wherein the one or more amino acid substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more substitutions.

[0121] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a human Fc region comprising one or more amino acid substitutions, wherein the one or more amino acid substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region.

[0122] 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 (LALA), M428L / N434A (LA), L235A / G237A (LAGA), L234A / L235A / G237A (LALAGA), L234A / L235A / P329G (LALAPG), 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,AOJ-008PCAOE-OIOIWON297A / 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. In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q / M428L, T307A / E380A / N434A, DQ, DW, YD, QVV, DHS, LA, 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 / 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, N297A / QVV, D265A / QVV, LALA / QVV, LAGA / QVV, LALAGA / QVV, and LALAPG / QVV.

[0123] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257, respectively. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, an antibody described herein comprises an Fc region (e.g., an IgGl Fc region) with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236, respectively. In certain embodiments, an antibody described herein comprises the VH sequence and VL sequence of Construct 133 and an Fc region with YTE mutations at positions 253, 255 and 257 and with LALA mutations at positions 235 and 236, respectively.

[0124] In certain embodiments the human Fc region comprises a human IgGl Fc region with LALA mutations. In certain embodiments, the human Fc region comprises a human IgGl Fc region with YTE mutations. In certain embodiments, the human Fc region comprises a human IgGl Fc region with LALA and YTE mutations. In certain embodiments, the human Fc region comprises a human IgGl Fc region with LALA mutations atAOJ-008PCAOE-OIOIWOL235A / L236A by direct numbering and / or YTE mutations at M253Y / S255T / T257E by direct numbering.

[0125] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 240 mg to about 480 mg (e.g., about 240 mg to about 480 mg, about 240 mg to about 460 mg, about 240 mg to about 440 mg, about 240 mg to about 420 mg, about 240 mg to about 400 mg, about 240 mg to about 395 mg, about 240 mg to about 380 mg, about 240 mg to about 360 mg, about 240 mg to about 340 mg, about 240 mg to about 320 mg, about 240 mg to about 300 mg, about 240 mg to about 280 mg, about 240 mg to about 260 mg, about 260 mg to about 480 mg, about 280 mg to about 480 mg, about 300 mg to about 480 mg, about 320 mg to about 480 mg, about 340 mg to about 480 mg, about 360 mg to about 480 mg, about 380 mg to about 480 mg, about 395 mg to about 480 mg, about 400 mg to about 480 mg, about 420 mg to about 480 mg, about 440 mg to about 480 mg, about 460 mg to about 480 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 395 mg, about 410 mg, about 430 mg, about 450 mg, about 460 mg, about 470 mg, or about 480 mg) of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0126] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 240 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO

[0127] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 260 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0128] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 280 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0129] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 300 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0130] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 320 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO

[0131] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 340 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0132] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 360 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0133] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 380 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0134] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 395 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO

[0135] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0136] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 240 mg to about 480 mg (e.g., about 240 mg to about 480 mg, about 240 mg to about 460 mg, about 240 mg to about 440 mg, about 240 mg to about 420 mg, about 240 mg to about 400 mg, about 240 mg to about 395 mg, about 240 mg to about 380 mg, about 240 mg to about 360 mg, about 240 mg to about 340 mg, about 240 mg to about 320 mg, about 240 mg to about 300 mg, about 240 mg to about 280 mg, about 240 mg to about 260 mg, about 260 mg to about 480 mg, about 280 mg to about 480 mg, about 300 mg to about 480 mg, about 320 mg to about 480 mg, about 340 mg to about 480 mg, about 360 mg to about 480 mg, about 380 mg to about 480 mg, about 395 mg to about 480 mg, about 400 mg to about 480 mg, about 420 mg to about 480 mg, about 440 mg to about 480 mg, about 460 mg to about 480 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 395 mg, about 410 mg, about 430 mg, about 450 mg, about 460 mg, about 470 mg, or about 480 mg) of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting atWeek 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0137] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; andAOJ-008PCAOE-OIOIWO b) about 240 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0138] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 260 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0139] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 280 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0140] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 300 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0141] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; andAOJ-008PCAOE-OIOIWO b) about 320 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0142] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 340 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0143] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 360 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0144] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 380 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0145] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; andAOJ-008PCAOE-OIOIWO b) about 395 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0146] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0147] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 240 mg to about 480 mg (e.g., about 240 mg to about 480 mg, about 240 mg to about 460 mg, about 240 mg to about 440 mg, about 240 mg to about 420 mg, about 240 mg to about 400 mg, about 240 mg to about 395 mg, about 240 mg to about 380 mg, about 240 mg to about 360 mg, about 240 mg to about 340 mg, about 240 mg to about 320 mg, about 240 mg to about 300 mg, about 240 mg to about 280 mg, about 240 mg to about 260 mg, about 260 mg to about 480 mg, about 280 mg to about 480 mg, about 300 mg to about 480 mg, about 320 mg to about 480 mg, about 340 mg to about 480 mg, about 360 mg to about 480 mg, about 380 mg to about 480 mg, about 395 mg to about 480 mg, about 400 mg to about 480 mg, about 420 mg to about 480 mg, about 440 mg to about 480 mg, about 460 mg to about 480 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 395 mg, about 410 mg, about 430 mg, about 450 mg, about 460 mg, about 470 mg, or about 480 mg) of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chainAOJ-008PCAOE-OIOIWO sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0148] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 240 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0149] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 260 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0150] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 280 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0151] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 300 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, aAOJ-008PCAOE-OIOIWO constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0152] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 320 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0153] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 340 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0154] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 360 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0155] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 380 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, aAOJ-008PCAOE-OIOIWO constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0156] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 395 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0157] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) or every three months (Q3M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0158] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg to about 960 mg (e.g., about 480 mg to about 960 mg, about 480 mg to about 900 mg, about 480 mg to about 850 mg, about 480 mg to about 790 mg, about 480 mg to about 780 mg, about 480 mg to about 760 mg, about 480 mg to about 740 mg, about 480 mg to about 720 mg, about 480 mg to about 700 mg, about 480 mg to about 680 mg, about 480 mg to about 660 mg, about 480 mg to about 640 mg, about 480 mg to about 620 mg, about 480 mg to about 600 mg, about 480 mg to about 580 mg, about 480 mg to about 560 mg, about 480 mg to about 540 mg, about 480 mg to about 520 mg, about 480 mg to about 500 mg, about 500 mg to about 960 mg, about 520 mg to about 960 mg, about 540 mg to about 960 mg, about 560 mg to about 960 mg, about 580 mg to about 960 mg, about 600 mg to about 960 mg, about 620 mg to about 960 mg, about 640 mg to about 960 mg, about 660 mg to about 960 mg, about 680 mg to about 960 mg,AOJ-008PCAOE-OIOIWO about 700 mg to about 960 mg, about 720 mg to about 960 mg, about 740 mg to about 960 mg, about 760 mg to about 960 mg, about 780 mg to about 960 mg, about 790 mg to about 960 mg, about 850 mg to about 960 mg, about 900 mg to about 960 mg, about 500 mg to about 640 mg, about 520 mg to about 640 mg, about 540 mg to about 640 mg, about 560 mg to about 640 mg, about 580 mg to about 640 mg, about 600 mg to about 640 mg, about 620 mg to about 640 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 850 mg, about 900 mg, or about 960 mg) of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0159] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0160] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 520 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO

[0161] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 560 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0162] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 600 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0163] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 640 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0164] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 680 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO

[0165] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 720 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0166] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 760 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0167] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 790 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0168] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO

[0169] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 480 mg to about 960 mg (e.g., about 480 mg to about 960 mg, about 480 mg to about 900 mg, about 480 mg to about 850 mg, about 480 mg to about 790 mg, about 480 mg to about 780 mg, about 480 mg to about 760 mg, about 480 mg to about 740 mg, about 480 mg to about 720 mg, about 480 mg to about 700 mg, about 480 mg to about 680 mg, about 480 mg to about 660 mg, about 480 mg to about 640 mg, about 480 mg to about 620 mg, about 480 mg to about 600 mg, about 480 mg to about 580 mg, about 480 mg to about 560 mg, about 480 mg to about 540 mg, about 480 mg to about 520 mg, about 480 mg to about 500 mg, about 500 mg to about 960 mg, about 520 mg to about 960 mg, about 540 mg to about 960 mg, about 560 mg to about 960 mg, about 580 mg to about 960 mg, about 600 mg to about 960 mg, about 620 mg to about 960 mg, about 640 mg to about 960 mg, about 660 mg to about 960 mg, about 680 mg to about 960 mg, about 700 mg to about 960 mg, about 720 mg to about 960 mg, about 740 mg to about 960 mg, about 760 mg to about 960 mg, about 780 mg to about 960 mg, about 790 mg to about 960 mg, about 850 mg to about 960 mg, about 900 mg to about 960 mg, about 500 mg to about 640 mg, about 520 mg to about 640 mg, about 540 mg to about 640 mg, about 560 mg to about 640 mg, about 580 mg to about 640 mg, about 600 mg to about 640 mg, about 620 mg to about 640 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 850 mg, about 900 mg, or about 960 mg) of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0170] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; andAOJ-008PCAOE-OIOIWO b) about 480 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0171] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL- 13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 520 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0172] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 560 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0173] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL- 13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 600 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0174] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; andAOJ-008PCAOE-OIOIWO b) about 640 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0175] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL- 13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 680 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0176] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 720 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0177] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL- 13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 760 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0178] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; andAOJ-008PCAOE-OIOIWO b) about 790 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0179] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0180] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg to about 960 mg (e.g., about 480 mg to about 960 mg, about 480 mg to about 900 mg, about 480 mg to about 850 mg, about 480 mg to about 790 mg, about 480 mg to about 780 mg, about 480 mg to about 760 mg, about 480 mg to about 740 mg, about 480 mg to about 720 mg, about 480 mg to about 700 mg, about 480 mg to about 680 mg, about 480 mg to about 660 mg, about 480 mg to about 640 mg, about 480 mg to about 620 mg, about 480 mg to about 600 mg, about 480 mg to about 580 mg, about 480 mg to about 560 mg, about 480 mg to about 540 mg, about 480 mg to about 520 mg, about 480 mg to about 500 mg, about 500 mg to about 960 mg, about 520 mg to about 960 mg, about 540 mg to about 960 mg, about 560 mg to about 960 mg, about 580 mg to about 960 mg, about 600 mg to about 960 mg, about 620 mg to about 960 mg, about 640 mg to about 960 mg, about 660 mg to about 960 mg, about 680 mg to about 960 mg, about 700 mg to about 960 mg, about 720 mg to about 960 mg, about 740 mg to about 960 mg, about 760 mg to about 960 mg, about 780 mg to about 960 mg, about 790 mg to about 960 mg, about 850 mg to about 960 mg, about 900 mg to about 960 mg, about 500 mg to about 640 mg, about 520 mg to about 640 mg, about 540 mg to about 640 mg, about 560 mg to about 640 mg, about 580 mg to about 640 mg, about 600 mg to about 640 mg, about 620 mg to about 640AOJ-008PCAOE-OIOIWO mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 850 mg, about 900 mg, or about 960 mg) of the anti -IL- 13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0181] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0182] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 520 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0183] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 560 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises aAOJ-008PCAOE-OIOIWOVH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0184] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL- 13 antibody at Week 4 and Week 12; and c) about 600 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0185] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 640 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0186] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 680 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0187] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 720 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises aAOJ-008PCAOE-OIOIWOVH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0188] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-1 antibody at Week 0; b) 180 mg of the anti-IL- 13 antibody at Week 4 and Week 12; and c) about 760 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0189] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 790 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0190] In another aspect, provided herein is a method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) or every six months (Q6M) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624 and / or SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0191] In certain embodiments of any of the foregoing aspects, the anti-IL 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, and a human IgGl Fc region comprising LALA and YTE mutations. In certain embodiments, the anti-IL- 13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQAOJ-008PCAOE-OIOIWOID NO: 439 and / or a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469. In certain embodiments, the anti- IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 439, and a constant light chain sequence set forth in SEQ ID NO: 469. In certain embodiments, the anti- IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469. A C-terminal lysine is present in SEQ ID NO: 624, which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 439. Accordingly, a composition comprising an antibody comprising the constant heavy chain sequence set forth in SEQ ID NO: 624 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 624 or SEQ ID NO: 439, or a mixture thereof (e.g., a composition comprising anti-IL-13 antibodies may contain a mixture of antibodies having either a constant heavy chain sequence set forth in SEQ ID NO: 624 or a constant heavy chain sequence set forth in SEQ ID NO: 439 and / or antibodies containing both constant heavy chain sequences (e.g., in an antibody containing two constant heavy chain sequences)).

[0192] In certain embodiments of any of the foregoing aspects, the anti-IL 13 antibody comprises a heavy chain sequence set forth in SEQ ID NO: 710 and / or SEQ ID NO: 711 and a light chain sequence set forth in SEQ ID NO: 712. In certain embodiments, anti-IL 13 antibody comprises a heavy chain sequence set forth in SEQ ID NO: 710 and a light chain sequence set forth in SEQ ID NO: 712. In certain embodiments, anti-IL 13 antibody comprises a heavy chain sequence set forth in SEQ ID NO: 711 and a light chain sequence set forth in SEQ ID NO: 712. The heavy chain sequence of SEQ ID NO: 710 contains a C- terminal lysine, which may be cleaved off during manufacture or after administration, resulting in an antibody containing the heavy chain sequence of SEQ ID NO: 711.

[0193] In certain embodiments of any of the foregoing aspects, each dose is administered as composition comprising 150 mg / mL, 180 mg / mL, or 200 mg / mL of the anti-IL- 13 antibody.

[0194] In certain embodiments of any of the foregoing aspects, the composition is a unit dose with an extractable volume of 1 mL, 2 mL, 2.25 mL, 2.7 mL, 3 mL, 4 mL or 5 mL.AOJ-008PCAOE-OIOIWO

[0195] In certain embodiments, the composition is a unit dose with an extractable volume of 2 mL.

[0196] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody is administered using an autoinjector.

[0197] In certain embodiments of any of the foregoing aspects, the anti-IL-13 antibody is administered using a pre-filled syringe.

[0198] In certain embodiments of any of the foregoing aspects, the patient has been diagnosed with moderate-to-severe atopic dermatitis.

[0199] In certain embodiments of any of the foregoing aspects, the patient has or has been diagnosed with moderate-to-severe atopic dermatitis and comorbid asthma.

[0200] In certain embodiments of any of the foregoing aspects, the patient has or has been diagnosed with moderate-to-severe atopic dermatitis and a comorbid sinonasal condition.

[0201] In certain embodiments of any of the foregoing aspects, the patient has had moderate-to-severe atopic dermatitis for at least one year.

[0202] In certain embodiments of any of the foregoing aspects, the patient has one or more of:(a) an Eczema Area and Severity Index Score (EASI) of >10 (e.g., an EASI score of >16),(b) an Investigator Global Assessment (IGA) score (i.e., a validated Investigator Global Assessment for AD (vIGA-AD score)) of >3 and(c) a body surface area (BSA) of >10% (AD affecting >10% BSA).

[0203] In certain embodiments of any of the foregoing aspects, the patient has an EASI score of >16, a vIGA-AD score of >3, and AD affecting >10% BSA.

[0204] In certain embodiments of any of the foregoing aspects, the patient has or has been diagnosed with moderate atopic dermatitis.

[0205] In certain embodiments of any of the foregoing aspects, the patient has or has been diagnosed with severe atopic dermatitis.

[0206] In certain embodiments of any of the foregoing aspects, the patient has a vIGA- AD score of 3 at Baseline.AOJ-008PCAOE-OIOIWO

[0207] In certain embodiments of any of the foregoing aspects, the patient has a vIGA- AD score of 4 at Baseline.

[0208] In certain embodiments of any of the foregoing aspects, the patient has an EASI score of >16 at Baseline. In certain embodiments, the patient has an EASI score of <21 at Baseline. In certain embodiments, the patient has an EASI score of >21 at Baseline. In certain embodiments, the patient has an EASI score of <48 at Baseline.

[0209] In certain embodiments, the method further comprises determining one or more of the following characteristics of the patient at baseline and during and after the induction period (z.<?., before treatment initiation, from Weeks 0-16, and after Week 16): Eczema Area and Severity Index (EASI), Validated Investigator Global Assessment (vIGA or vIGA-AD), Body Surface Area (BSA), Itch Numeric Rating Scale (I-NRS), Skin Pain Numerical Rating Scale (SP-NRS), Atopic Dermatitis Sleep Scale (ADSS), SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Asthma Control Questionnaire 5-item version (ACQ-5), and Sino-nasal Outcome Test 22-item version (SNOT-22). In certain embodiments, the method further comprises determining one or more of EASI, vIGA-AD, BSA, I-NRS, SP-NRS, ADSS, SCORAD, POEM, DLQI, ACQ-5, and SNOT-22 during or after the maintenance period (e.g., from Week 16 to Week 52 or after Week 52).

[0210] In certain embodiments, the treatment methods described herein result in inhibition of pSTAT6. In certain embodiments, the treatment results in sustained inhibition of pSTAT6. In certain embodiments, the treatment results in sustained inhibition of pSTAT6 for at least 6 months (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 months) after administration of one of more doses of the anti-lL- 13 antibody, or antigen binding fragment thereof.

[0211] In certain embodiments, the treatment methods described herein result in inhibition of thymus and activation-regulated chemokine (TARC). In certain embodiments, the treatment results in sustained inhibition of TARC. In certain embodiments, the treatment results in sustained inhibition of TARC for at least 6 months e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 months) after administration of one of more doses of the anti-IL-13 antibody, or antigen binding fragment thereof.

[0212] In certain embodiments, the treatment methods described herein result in a one or more point reduction (e.g., one, two, three, or four point reduction) in vIGA-AD scoreAOJ-008PCAOE-OIOIWO compared to Baseline. In certain embodiments, the treatment methods described herein result in a vIGA-AD score of 3 (e.g., for a subject with an initial vIGA-AD score of 4). In certain embodiments, the treatment methods described herein result in a vIGA-AD score of 2. In certain embodiments, the treatment methods described herein result in a vIGA-AD score of 1. In certain embodiments, the treatment methods described herein result in a vIGA-AD score of 0. In certain embodiments, the treatment methods described herein result in a > 2-point reduction from Baseline in vIGA-AD score (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in a vIGA-AD score of 0 (clear) or 1 (almost clear) and a > 2-point reduction from Baseline (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in at least 20%, at least 30%, at least 40%, or at least 50% of patients achieving a vIGA-AD score of 0 or 1 with a reduction of at least 2 points from Baseline (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 30% of patients achieving a vIGA- AD score of 0 or 1 with a reduction of at least 2 points from Baseline (e.g., after 16 weeks of treatment).

[0213] In certain embodiments, the treatment methods described herein result in a decrease in EASI score compared to Baseline (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in an at least about 20% decrease in EASI score compared to Baseline (e.g., at least about 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%, 45%, 47%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%,58%, 59%, 60%, 61%, , 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% decrease in EASI score compared to Baseline, e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or through Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in a decrease in EASI from Baseline of at least 70% (e.g., by Week 16). In certain embodiments, the treatment methods described hereinAOJ-008PCAOE-OIOIWO result in achievement of EASI-50, EASI-75, EASI-90, or EASI-100 (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in achievement EASI-75 e.g., at Week 16). In certain embodiments, the treatment methods described herein result in achievement EASI-90 (e.g., at Week 16). In certain embodiments, the treatment methods described herein result in at least 20%, at least 30%, at least 40%, at least 50%, or at least 60% of patients achieving EASI-75 (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 60% of patients achieving EASI-75 (e.g., after 16 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 10%, at least 20%, at least 30%, or at least 40% of patients achieving EASI- 90 (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 30% of patients achieving EASI-90 (e.g., after 16 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease in EASI from Baseline across all body regions (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease in EASI from Baseline of at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% across all body regions (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease in EASI from Baseline of at least 70% across all body regions (e.g., by 16 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease from Baseline EASI by clinical signs (e.g., erythema, edema / papulation, excoriation, and / or lichenification) across all body regions (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease from Baseline EASI by clinical signs of at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% across all body regions (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment).

[0214] In certain embodiments, the treatment methods described herein result in a decrease in BSA involvement compared to Baseline (e.g., at least about 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%,AOJ-008PCAOE-OIOIWO40%, 41%, 42%, 43%, 44%, 45%, 45%, 47%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, , 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% decrease in BSA involvement compared to Baseline) (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or through Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in a reduction in Body Surface Area (BSA) involvement from Baseline by at least 20%, at least 30%, at least 40%, at least 50%, or at least 60% (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in Body Surface Area (BSA) involvement from Baseline by at least 60% (e.g., after 16 weeks of treatment).

[0215] In certain embodiments, the treatment methods described herein result in an improvement in AD-related pruritis. In certain embodiments, the treatment methods described herein result in an improvement as assessed by the daily Itch Numeric Rating Scale (I-NRS) compared to Baseline. In certain embodiments, the treatment methods described herein result in a one or more point reduction (e.g., one, two, three, four, five, six, seven, eight, nine, ten, or eleven point reduction) in I-NRS score compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction (e.g., a one or more point reduction, such as a one, two, three, four, five, six, seven, eight, nine, ten, or eleven point reduction) in the weekly mean of the daily I-NRS from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease in Itch NRS from Baseline of at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a decrease in Itch NRS from Baseline of at least 50% (e.g., after 16 weeks of 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a > 4-point improvement (e.g., an improvement of 4, 5, 6, 7, 8, 9, or more points) in the weekly mean of the daily I-NRS from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, theAOJ-008PCAOE-OIOIWO treatment methods described herein result in at least 20%, at least 30%, at least 40%, or at least 50% of patients achieving at least a 4-point improvement in Itch NRS from Baseline. In certain embodiments, the treatment methods described herein result in at least 40% of patients achieving at least a 4-point improvement in Itch NRS from Baseline (e.g., after 16 weeks of treatment). In certain embodiments, the treatment methods described herein result in an at least about 10% decrease in the weekly mean of the daily I-NRS score from Baseline (e.g., at least about 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%, 45%, 47%, 49%, 50%, 51%, 52%, 53%, 54%, 55%,56%, 57%, 58%, 59%, 60%, 61%, , 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% decrease in the weekly mean of the daily I-NRS score from Baseline) e.g., at or through Week 16 or Week 52).

[0216] In certain embodiments, the treatment methods described herein result in an improvement in sleep disturbance. In certain embodiments, the treatment methods described herein result in an improvement as assessed by the daily ADSS compared to Baseline. In certain embodiments, the treatment methods described herein result in a one or more point reduction (e.g., one, two, three, four, or more point reduction) in ADSS score compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction (e.g., a one or more point reduction) in the weekly mean of the daily ADSS (e.g., for Item 1 and / or Item 2) from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a > 2-point improvement (e.g., an improvement of 2, 3, 4, or more points) in the weekly mean of the daily ADSS Item 2 from Baseline (e.g., at or though Week 16 or Week 52).

[0217] In certain embodiments, the treatment methods described herein result in an improvement in AD-related skin pain. In certain embodiments, the treatment methods described herein result in an improvement as assessed by the daily skin pain numerical rating scale (SP-NRS) compared to Baseline. In certain embodiments, the treatment methods described herein result in a one or more point reduction (e.g., one, two, three, four, five, six,AOJ-008PCAOE-OIOIWO seven, eight, nine, ten, or eleven point reduction) in SP-NRS score compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction (e.g., a one or more point reduction, such as a one, two, three, four, five, six, seven, eight, nine, ten, or eleven point reduction) in the weekly mean of the daily SP-NRS from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a > 4-point improvement e.g. , an improvement of 4, 5, 6, 7, 8, 9, or more points) in the weekly mean of the daily SP-NRS from Baseline e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in at least 20%, at least 30%, at least 40%, or at least 50% of patients achieving a > 4-point improvement in the weekly mean of the daily SP-NRS from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 50% of patients achieving a > 4-point improvement in the weekly mean of the daily SP-NRS from Baseline (e.g., after 16 weeks of treatment). In certain embodiments, the treatment methods described herein result in an at least about 10% decrease in the weekly mean of the daily SP-NRS score from Baseline (e.g., at least about 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%, 45%, 47%, 49%, 50%, 51%, 52%, 53%,54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, , 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%,86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% decrease in the weekly mean of the daily SP-NRS score from Baseline) (e.g., at or through Week 16 or Week 52).

[0218] In certain embodiments, the treatment methods described herein result in an improvement as assessed by the Patient-oriented Eczema Measure (POEM) compared to Baseline. In certain embodiments, the treatment methods described herein result in a three or more point reduction (e.g., three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty one, twenty two, twenty three, twenty four, twenty five, twenty six, twenty seven, or twenty eight pointAOJ-008PCAOE-OIOIWO reduction) in POEM score compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment, such as at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in a > 3-point improvement (e.g., an improvement of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more points) in POEM total score from Baseline e.g., at or through Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% of patients achieving a > 3-point improvement in POEM total score from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 70% of patients achieving a > 3-point improvement in POEM total score from Baseline (e.g., after 16 weeks of treatment).

[0219] In certain embodiments, the treatment methods described herein result in an improvement as assessed by the DLQ1 compared to Baseline. In certain embodiments, the treatment methods described herein result in a one or more point reduction (e.g., one, two, three, four, five, six, seven, or more point reduction) in DLQI total score compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a > 4-point improvement (e.g., an improvement of 4, 5, 6, 7, 8, 9, 10 or more points) in DLQI total score from Baseline (e.g., at or though Week 16 or Week 52). In certain embodiments, the treatment methods described herein result in at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% of patients achieving a > 4-point improvement in DLQI from Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in at least 70% of patients achieving a > 4-point improvement in DLQI from Baseline (e.g., after 16 weeks of treatment). In certain embodiments, the treatment methods described herein result in a value of 0 or 1 for at least one DLQI item (e.g. , at or though Week 16 or Week 52).

[0220] In certain embodiments, the treatment methods described herein result in an improvement in quality of life (e.g., as assessed by POEM and / or DLQI).

[0221] In certain embodiments, the treatment methods described herein result in an improvement in asthma control in patients with moderate-to-severe AD and comorbid asthma.AOJ-008PCAOE-OIOIWOIn certain embodiments, the treatment methods described herein result in an improvement as assessed by the ACQ-5 compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in an ACQ-5 improvement of > 0.5 (e.g., an improvement of 0.5, I, 1.5, 2, 2.5, or more) compared to Baseline (e.g., at or though Week 16 or Week 52).

[0222] In certain embodiments, the treatment methods described herein result in an improvement sinonasal symptoms in patients with moderate-to-severe AD and a comorbid sinonasal condition. In certain embodiments, the treatment methods described herein result in an improvement as assessed by the SNOT-22 compared to Baseline (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a SNOT-22 improvement of > 8.9 (e.g., an improvement of 8.9, 9.0, 9.5, 10.0 or more) compared to Baseline (e.g., at or though Week 16 or Week 52).

[0223] In certain embodiments, the treatment methods described herein result in a reduction in serum TARC levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum IL-13 levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum IL-17C levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum IL-19 levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum eotaxin-3 levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum periostin levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum PARC levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methods described herein result in a reduction in serum IgE levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In certain embodiments, the treatment methodsAOJ-008PCAOE-OIOIWO described herein result in a reduction in serum LDH levels (e.g., after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment).

[0224] In certain embodiments, the treatment methods described herein result in an EASI score of < 7 (e.g., an EASI score of 7, 6, 5, 4, 3, 2, 1, or less) or an I-NRS score of < 4 (e.g., an I-NRS score of 4, 3, 2, I, or less).

[0225] In certain embodiments, the treatment methods described herein result in an EASI score of < 7 (e.g., an EASI score of 7, 6, 5, 4, 3, 2, 1, or less) and an I-NRS score of < 4 (e.g., an I-NRS score of 4, 3, 2, 1, or less).

[0226] In certain embodiments, the patient has an exposure level of the anti-IL-13 antibody of at least 100 pg / mL or greater (e.g., at least 102.4 g / mL or greater) as determined by Cavg. In certain embodiments, the patient has an exposure level of the anti-IL-13 antibody of at least 120 pg / mL or greater (e.g., at least 123.5 pg / mL or greater) as determined by Cav - In certain embodiments, the patient has an exposure level of the anti-IL-13 antibody of at least 150 pg / mL or greater (e.g., at least 153 pg / mL or greater) as determined by Cavg.

[0227] In certain embodiments, the treatment methods described herein do not result in conjunctivitis.

[0228] In certain embodiments, the patient develops conjunctivitis that resolves in less than one month (e.g., the conjunctivitis resolves in 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 6, 7, 5, 4, 3 days or less).

[0229] In certain embodiments, the treatment methods described herein do not result in injection site reactions (i.e., injection site reactions related to treatment).

[0230] In certain embodiments, the treatment methods described herein result in itch relief within the first week of treatment (i.e., a reduction in I-NRS in Week 1).

[0231] In certain embodiments, the treatment methods described herein result in itch relief within 48 hours of the first dose of the anti-IL-13 antibody (i.e., a reduction in LNRS as early as Day 3 of treatment).

[0232] In certain embodiments, the patient is female.

[0233] In certain embodiments, the patient is male.

[0234] In certain embodiments, the patient is 18 to < 65 years of age.

[0235] In certain embodiments, the patient is 65 years of age or older.

[0236] In certain embodiments, the patient weighs less than 60 kg.

[0237] In certain embodiments, the patient weighs > 60 kg and less than 100 kg.AOJ-008PCAOE-OIOIWO

[0238] In certain embodiments, the patient weighs 100 kg or more.

[0239] In certain embodiments, the patient has not received prior systemic treatment.

[0240] In certain embodiments, the patient has received prior systemic treatment.

[0241] In certain embodiments, the patient has a history of inadequate response to treatment with topical medications or a medical determination that topical therapies are inadvisable.

[0242] In certain aspects, described herein is a composition comprising 150 mg / mL, 180 mg / mL, or 200 mg / mL of an anti-IL-13 antibody, or antigen binding fragment thereof, wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0243] In certain embodiments, the composition is a unit dose with an extractable volume of about 1 mL, about 2 mL, about 2.25 mL, about 2.7 mL, about 3 mL, about 4 mL or about 5 mL.

[0244] In certain aspects, described herein is an autoinjector configured to deliver a composition comprising 150 mg / mL, 180 mg / mL, or 200 mg / mL of an anti-IL-13 antibody, or antigen binding fragment thereof, wherein the anti-IL-13 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid set forth in SEQ ID NO: 39.

[0245] In certain embodiments, the composition is a unit dose with an extractable volume of 1 mL, 2 mL, 2.25 mL, 2.7 mL, 3 mL, 4 mL or 5 mL.

[0246] In certain embodiments, the method, composition, or autoinjector described herein further comprises a heavy chain constant region of SEQ ID NO: 439 or SEQ ID NO: 624 or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity thereto.AOJ-008PCAOE-OIOIWO

[0247] In certain embodiments, the method, composition, or autoinjector described herein further comprises a light chain constant region of SEQ ID NO: 469 or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity thereto.BRIEF DESCRIPTION OF THE DRAWINGS

[0248] 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:

[0249] Figure 1 is a schematic depicting the design of a single- and multiple-ascending dose (SAD and MAD, respectively) study, respectively, using an anti-IL-13 antibody described herein. Bold arrows indicate equivalent dosages between the SAD and MAD dosing schemes. Abbreviations: Q4wk every 4 weeks; SRC, safety review committee; SC, SQ, subcutaneous.

[0250] Figure 2 is a graph depicting the serum concentration (ng / mL) of Construct 133 and lebrikizumab over time (days post injection) in non-human primates (NHPs). The halflife of Construct 133 was 27.6 days, as compared to 17 to 18 days for lebrikizumab.

[0251] Figure 3 is a graph depicting normalized AUCo- / (CnOrm*day), or area under the curve (AUC) from dosing to infinity, among antibodies with the YTE substitution.

[0252] Figure 4 is a schematic depicting the design of a single- and multiple- ascending dose (SAD and MAD, respectively) study, respectively, using Construct 133 described herein. Abbreviations: PK, pharmacokinetics, ADA, anti-drug antibodies, pSTAT6, phosphorylated signal transducer and activator or transcription 6, TARC, thymus- and activation-regulated chemokine, SQ, subcutaneous.

[0253] Figure 5 is a set of graphs depicting the serum concentration (pg / mL) of Construct 133 over time (weeks post injection) in humans enrolled in the SAD (left panel) and MAD (right panel) studies described in Figure 4. Abbreviations: DI, day 1, 29, day 29.

[0254] Figure 6 is a graph depicting the median percent change from baseline of inhibition of IL-13-induced phosphorylation of STAT6 (pSTAT6) in humans enrolled in the SAD study described in Figure 4. At about three months (Week 12, up arrow), which was the latest follow-up, pSTAT6 remained suppressed after a single-dose of Construct 133.AOJ-008PCAOE-OIOIWO

[0255] Figure 7 is a set of graphs depicting the median percent change from baseline of inhibition of IL-13-induced release of thymus-and activation-regulated chemokine (TARC) in humans enrolled the SAD study described in Figure 4 (right panel) as compared to subjects receiving Dupixent (right panel).

[0256] Figure 8 is a graph depicting the median percent pSTAT6 over time for Construct 133 at varying doses (i.e., placebo, 300mg, 600mg, and 1200mg).

[0257] Figure 9 is a graph depicting the median percent pSTAT6 over time for Construct 133 at varying doses (i.e., placebo and 300mg).

[0258] Figure 10 is a graph depicting the single dose concentration-time PK profile for Construct 133.

[0259] Figure 11 is a graph depicting the multiple dose concentration-time PK profile for Construct 133.

[0260] Figures 12A-12B are graphs depicting the median percent pSTAT6 over time for Construct 133 in MD Cohort 1 (FIG. 12A) and MD Cohort 2 (FIG. 12B).

[0261] Figure 13 is a schematic depicting the design of a Phase 2 clinical trial, using Construct 133 described herein.

[0262] Figure 14 is a graph depicting the median percent pSTAT6 over time (up to day 337) for Construct 133 at varying doses (i.e., placebo, 300 mg, 600 mg, and 1200 mg).

[0263] Figures 15A-15C are graphs depicting both the median percent pSTAT6 and serum concentration of Construct 133 over time at doses of 300 mg, 600 mg, and 1200 mg, respectively.

[0264] Figure 16 is a graph depicting the single dose concentration-time PK profile for Construct 133 up to 48 weeks at varying doses (i.e., 300 mg, 600 mg, and 1200 mg).

[0265] Figure 17 is a graph depicting percent change in absolute blood eosinophil counts relative to baseline over time (up to day 337) in the SAD study for Construct 133 at varying doses (i.e., placebo, 300 mg, 600 mg, and 1200 mg).

[0266] Figure 18 is a graph depicting the multiple dose concentration-time PK profile for Construct 133 up to 36 weeks for Cohort 1 and 24 weeks for Cohort 2.

[0267] Figures 19A and 19B are graphs depicting the median percent pSTAT6 over time for Construct 133 and placebo in Cohort 1 (up to day 253) and Cohort 2 (up to day 169), respectively.AOJ-008PCAOE-OIOIWO

[0268] Figures 20A and 20B are graphs depicting both the median percent pSTAT6 and serum concentration of Construct 133 over time in Cohort 1 (up to day 253) and Cohort 2 (up to day 169), respectively.

[0269] Figures 21A and 21B are graphs depicting percent change in absolute blood eosinophil counts relative to baseline over time in the MAD study for Construct 133 in Cohort 1 (up to day 253) and Cohort 2 (up to day 169), respectively.

[0270] Figure 22 is a graph depicting median percent change from baseline of inhibition of IL-13-induced release of TARC over time in the SAD study for Construct 133 at varying doses (i.e., placebo, 300 mg, 600 mg, and 1200 mg).

[0271] Figures 23A and 23B are graphs depicting median percent change from baseline of inhibition of IL- 13 -induced release of TARC over time in the MAD study for Construct 133 in Cohort 1 (up to day 253) and Cohort 2 (up to day 169), respectively.

[0272] Figure 24 is a schematic of the long-term extension study.

[0273] Figures 25A and 25B are graphs depicting Construct 133 serum concentration over time (semi-logarithmic scale) for SAD and MD cohorts. Figure 25A shows single-dose concentration-time profile; and Figure 25B shows multiple-dose concentration-time profile. Graphs show mean ± SD. D, day; MD, multiple dose; SAD, single ascending dose; SD, standard deviation.

[0274] Figures 26A-26C are graphs depicting inhibition of the biomarkers pSTAT6 (Figure 26A), TARC (Figure 26B), and IgE (Figure 26C) after single-dose subcutaneous administration of Construct 133. Graphs represent individual data points with a median line. Placebo data are pooled across SAD cohorts. Note: n = 1 in the Construct 133 300 mg SAD group because the pSTAT6 assay was not available when the first participants reached the prespecified study visits. IgE, immunoglobulin E; pSTAT6, phosphorylated signal transducer and activator of transcription 6; SAD, single ascending dose; TARC, thymus and activation- regulated chemokine.

[0275] Figures 27A-27C are graphs depicting inhibition of the biomarkers pSTAT6 (Figure 27A), TARC (Figure 27B), and IgE (Figure 27C) after multiple-dose subcutaneous administration of Construct 133. Graphs represent individual data points with a median line. Placebo data are pooled across MD cohorts. D, day; IgE, immunoglobulin E; MD, multiple dose; pSTAT6, phosphorylated signal transducer and activator of transcription 6; TARC, thymus and activation-regulated chemokine.AOJ-008PCAOE-OIOIWO

[0276] Figure 28 is a graph depicting median percent change from baseline over time of pSTAT6 in IL-13 stimulated monocytes (CD14+) across all Construct 133 dose groups (linear scale). MD, multiple dose; SAD, single ascending dose.

[0277] Figure 29 is a graph depicting the least-squares (LS) mean percent change from Baseline in Eczema Area and Severity Index (EASI) score as percent change from Baseline from Week 0 to Week 16 in participants administered placebo or Construct 133.

[0278] Figure 30 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved EASI-50 (> 50% reduction in Eczema Area and Severity Index score from Baseline) from Week 0 to Week 16.

[0279] Figure 31 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved EASI-75 (> 75% reduction in Eczema Area and Severity Index score from Baseline) from Week 0 to Week 16.

[0280] Figure 32 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved EASI-90 (> 90% reduction in Eczema Area and Severity Index score from Baseline) from Week 0 to Week 16.

[0281] Figure 33 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved a validated Investigator Global Assessment (vIGA or vIGA- AD) score of 0 or 1 with a reduction of > 2 points from Baseline from Week 0 to Week 16.

[0282] Figure 34 is a graph depicting the LS mean percent change from Baseline in Itch Numerical Rating Scale (Itch NRS) as percent change from Baseline from Week 0 to Week 16 in participants administered placebo or Construct 133.

[0283] Figure 35 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved an improvement of > 4 points in Itch NRS score from Week 0 to Week 16.

[0284] Figure 36 is a graph depicting Week 16 results across several secondary endpoints of the Phase 2 study described in Examples 2 and 5: the proportion of participants administered placebo or Construct 133 who achieved EASI-75; EASI-90; EASI-100; a vIGA- AD score of 0 or 1 with > 2 point reduction from Baseline; and > 4 points improvement in Itch NRS.

[0285] Figure 37 is a graph depicting the change in Body Surface Area (BSA) involvement from Week 0 to Week 16 in participants administered placebo or Construct 133.AOJ-008PCAOE-OIOIWO

[0286] Figure 38 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved EASI-75 at Week 16 using different analytical methods: MCMC-MI with rescue as NRI, NRI and As Observed.

[0287] Figure 39 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved EASI-90 at Week 16 using different analytical methods: MCMC-MI with rescue as NRI, NRI and As Observed.

[0288] Figure 40 is a graph depicting the proportion of participants administered placebo or Construct 133 who achieved EASI-100 (100% reduction in Eczema Area and Severity Index score from Baseline) at Week 16 using different analytical methods: MCMC-MI with rescue as NRI, NRI and As Observed.

[0289] Figures 41A and 4 IB are graphs depicting the proportion of participants analyzed by age (FIG. 41A) and sex (FIG. 41B) who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed using the NRI method.

[0290] Figures 42A and 42B are graphs depicting the proportion of participants analyzed by country of enrollment (FIG. 42A) and race (FIG. 42B) who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed using the NRI method.

[0291] Figures 43A and 43B are graphs depicting the proportion of participants analyzed by weight (FIG. 43A) and EASI Baseline (FIG. 43B) who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed using the NRI method.

[0292] Figures 44A and 44B are graphs depicting the proportion of participants analyzed by Baseline vIGA-AD score (FIG. 44A) and whether they had received prior systemic treatment (FIG. 44B) who were administered placebo or Construct 133 who achieved EASI- 75 at Week 16, as analyzed by the NRI method.

[0293] Figure 45 is a graph depicting the proportion of participants analyzed by ethnicity who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed by the NRI method.

[0294] Figures 46A and 46B are graphs depicting the proportion of participants analyzed by age (FIG. 46A) and sex (FIG. 46B) who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed using the As Observed method.

[0295] Figures 47A and 47B are graphs depicting the proportion of participants analyzed by country of enrollment (FIG. 47A) and race (FIG. 47B) who were administered placebo orAOJ-008PCAOE-OIOIWOConstruct 133 who achieved EASI-75 at Week 16, as analyzed using the As Observed method.

[0296] Figures 48A and 48B are graphs depicting the proportion of participants analyzed by weight (FIG. 48A) and EASI Baseline (FIG. 48B) who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed using the As Observed method.

[0297] Figures 49A and 49B are graphs depicting the proportion of participants analyzed by Baseline vIGA-AD score (FIG. 49A) and whether they had received prior systemic treatment (FIG. 49B) who were administered placebo or Construct 133 who achieved EASI- 75 at Week 16, as analyzed by the As Observed method.

[0298] Figure 50 is a graph depicting the proportion of participants analyzed by ethnicity who were administered placebo or Construct 133 who achieved EASI-75 at Week 16, as analyzed by the As Observed method.

[0299] Figures 51A, 51B and 51C are graphs depicting the proportion of Construct 133- treated participants that achieved EASI-75 at Week 16 based on the exposure quartile of the participants, with exposure quartiles determined by post-hoc Cavg of Construct 133 from Week 0 to 16 (FIG. 51A), post-hoc Cmax of Construct 133 from Week 0 to 16 (FIG. 51B) and Ctrough of Construct 133 from Week 0 to 16 (FIG. 51C), respectively.

[0300] Figures 52A, 52B and 52C are graphs depicting the proportion of Construct 133- treated participants that achieved EASI-90 at Week 16 based on the exposure quartile of the participants, with exposure quartiles determined by post-hoc Cavgof Construct 133 from Week 0 to 16 (FIG. 52A), post-hoc Cmax of Construct 133 from Week 0 to 16 (FIG. 52B) and observed Ctrough of Construct 133 from Week 0 to 16 (FIG. 52C), respectively.

[0301] Figures 53A, 53B and 53C are graphs depicting the mean EASI percent change from Baseline at Week 16 in Construct 133-treated participants based on the exposure quartile of the participants, with exposure quartiles determined by post-hoc Cavg of Construct 133 from Week 0 to 16 (FIG. 53A), post-hoc Cmax of Construct 133 from Week 0 to 16 (FIG. 53B) and observed Ctrough of Construct 133 from Week 0 to 16 (FIG. 53C), respectively.

[0302] Figures 54A, 54B and 54C are graphs depicting the median EASI percent change from Baseline at Week 16 in Construct 133-treated participants based on the exposure quartile of the participants, with exposure quartiles determined by post-hoc Cavg of ConstructAOJ-008PCAOE-OIOIWO133 from Week 0 to 16 (FIG. 54A), post-hoc Cmax of Construct 133 from Week 0 to 16 (FIG. 54B) and observed Ctrough of Construct 133 from Week 0 to 16 (FIG. 54C), respectively.

[0303] Figures 55A, 55B and 55C are graphs depicting the proportion of Construct 133- treated participants that achieved a vIGA-AD score of 0 or 1 with > 2-point reduction from Baseline at Week 16 based on the exposure quartile of the participants, with exposure quartiles determined by post-hoc Cavgof Construct 133 from Week 0 to 16 (FIG. 55A), post- hoc Cmax of Construct 133 from Week 0 to 16 (FIG. 55B) and observed Ctrough of Construct 133 from Week 0 to 16 (FIG. 55C), respectively.

[0304] Figure 56 is a graph depicting the percent change in EASI from Baseline for Construct 133-treated participants from Week 0 to Week 16, shown by exposure quartile (as determined by post-hoc Cavg), as observed.

[0305] Figure 57 is a graph depicting the proportion of Construct 133-administered participants that achieved EASI-75 from Week 0 to Week 16, shown by exposure quartile (as determined by post-hoc Cavg), as observed.

[0306] Figure 58 is a graph depicting the absolute change from Baseline in EASI score from Week 0 to Week 16 in participants administered placebo or Construct 133. Error bars represent standard error.

[0307] Figure 59 is a graph depicting the percent change from Baseline (CFBL) in daily Itch Numeric Rating Scale (I-NRS) in Week 1, evaluated as observed without imputation for missing data. *p<0.05, **p<0.01, ***p<0.001 vs placebo. Arrow indicates dosing day.Baseline is defined as the weekly average of the I-NRS score on the 7 days prior to the first dose. Error bars represent standard error.

[0308] Figure 60 is a graph depicting the change from Baseline in daily I-NRS in Week 1, as observed. *p<0.05, **p<0.01, ***p<0.001. Day 0: Baseline is defined as the weekly average of the I-NRS score on the 7 days prior to the first dose. Day 1 : Day of first drug administration.

[0309] Figure 61 is a graph depicting the change from Baseline in SP-NRS. *p<0.05, **p<0.01, ***p<0.001.

[0310] Figure 62 is a graph depicting the proportion of patients achieving > 4 improvement in SP-NRS. N=28 for Placebo group; N=63 for Construct 133 group;AOJ-008PCAOE-OIOIWON=number of patients in mITT for Induction Period who have at least 4 points of the Weekly mean of the daily SP-NRS at Baseline. *p<0.05, **p<0.01, ***p<0.001.

[0311] Figure 63 is a graph depicting the change from Baseline in ADSS Item 1 :Difficulty Falling Asleep. *p<0.05, **p<0.01, ***p<0.001.

[0312] Figure 64 is a graph depicting the change from Baseline in ADSS Item 2: WakeUp from Itch. *p<0.05, **p<0.0I, ***p<0.001.

[0313] Figure 65 is a schematic depicting the EASI and percent change from Baseline EASI by body region for Construct 133 and Placebo.

[0314] Figure 66 is a schematic depicting the mean (SE) percentage change from Baseline in EASI by clinical signs by body region for Construct 133 vs. placebo.

[0315] Figure 67 is a graph depicting Baseline serum TARC levels for the Construct 133 and placebo treatment groups.

[0316] Figure 68 is a graph depicting the median percent change from Baseline in serum TARC levels in the Construct 133 and placebo treatment groups. W=week.

[0317] Figure 69 is a graph depicting median serum TARC levels in the in the Construct 133 and placebo treatment groups.

[0318] Figure 70 is a graph depicting percent change from Baseline in serum TARC levels by exposure quartile at Week 16.

[0319] Figure 71 is a graph depicting change from Baseline in POEM score at Week 16 for Construct 133 and Placebo treatment groups. ***p<0.001.

[0320] Figure 72 is a graph depicting the proportion of patients achie ving > 3 improvement in POEM score at Week 16 for Construct 133 and Placebo treatment groups.

[0321] Figure 73 is a graph depicting the proportion of patients achieving > 4 improvement in DLQI score at Week 16 for Construct 133 and Placebo treatment groups.***p<0.001.

[0322] Figure 74 is a graph depicting the percent change from Baseline mean for BSA at Week 16 for Construct 133 and Placebo treatment groups. *p<0.05.

[0323] Figure 75 is a graph depicting the percent change from Baseline mean for BSA for Construct 133 and Placebo treatment groups.

[0324] Figure 76 is a graph depicting the proportion of patients achieving EASI < 7 or I- NRS < 4 evaluated as observed for Construct 133 and Placebo treatment groups. *p<0.05;AOJ-008PC AOE-OIOIWO**p<0.01; ***p<0.001. Analysis did not exclude patients with baseline EASI < 7 or I-NRS < 4.

[0325] Figure 77 is a graph depicting the proportion of patients achieving EASI < 7 and I-NRS < 4 evaluated as observed for Construct 133 and Placebo treatment groups. *p<0.05;**p<0.01; ***p<0.001.

[0326] Figure 78 is a graph depicting the median percent change from Baseline in serum eotaxin-3 levels in the Construct 133 and placebo treatment groups. W=week.

[0327] Figure 79 is a graph depicting the median percent change from Baseline in serum periostin levels in the Construct 133 and placebo treatment groups. W=week.

[0328] Figure 80 is a graph depicting the median percent change from Baseline in serum Pulmonary and Activation-Regulated Chemokine (PARC) levels in the Construct 133 and placebo treatment groups. W=week.

[0329] Figure 81 is a graph depicting the Log2 fold change from Baseline in serum IL- 13 levels in the Construct 133 and placebo treatment groups. W=week.

[0330] Figure 82 is a graph depicting the Log2 fold change from Baseline in serum IL- 19 levels in the Construct 133 and placebo treatment groups. W=week.

[0331] Figure 83 is a graph depicting the Log2 fold change from Baseline in serum IL- 17C levels in the Construct 133 and placebo treatment groups. W=week.

[0332] Figure 84 is a graph depicting the median percent change from Baseline in serum IgE levels in the Construct 133 and placebo treatment groups. W=week.

[0333] Figure 85 is a graph depicting the median percent change from Baseline in serum LDH levels in the Construct 133 and placebo treatment groups. W=week.DETAILED DESCRIPTIONDefinitions

[0334] 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, suchAOJ-008PCAOE-OIOIWO 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.

[0335] As used herein, the singular forms “a,” “an,” and “the” include plural references unless indicated otherwise.

[0336] It is understood that aspects and embodiments of the invention described herein include “comprising,” “consisting,” and “consisting essentially of” aspects and embodiments.

[0337] 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.

[0338] The term “vector,” as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a selfreplicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors.”AOJ-008PCAOE-OIOIWO

[0339] The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably herein and refer to cells into which an exogenous nucleic acid has been introduced, and the progeny of such cells. Host cells include “transformants” (or “transformed cells”) and “transfectants” (or “transfected cells”), which each include the primary transformed or transfected cell and progeny derived therefrom. Such progeny may not be completely identical in nucleic acid content to a parent cell, and may contain mutations. A “recombinant host cell” or “host cell” refers to a cell that includes an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells.

[0340] As used herein, the term “eukaryote” refers to organisms belonging to the phylogenetic domain Eukarya such as animals (including but not limited to, mammals, insects, reptiles, birds, etc.), ciliates, plants (including but not limited to, monocots, dicots, algae, etc.), fungi, yeasts, flagellates, microsporidia, protists, etc.

[0341] As used herein, the term “prokaryote” refers to prokaryotic organisms. For example, a non-eukaryotic organism can belong to the Eubacteria (including but not limited to, Escherichia coli, Thermits thermophilus, Bacillus stearothermophilus , Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas putida, etc.) phylogenetic domain, or the Archaea (including but not limited to, Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Halobacterium such as Haloferax volcanii and Halobacterium species NRC-1 , Archaeo globus fulgidus, Pyrococcus furiosus, Pyrococcus horikoshii, Aeuropyrum pernix, etc.) phylogenetic domain.

[0342] An “effective amount” or “therapeutically effective amount” as used herein refers to an amount of therapeutic compound, such as an anti-IL-13 antibody, or antigen binding fragment thereof, 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 are reducing an aberrant immune response, slowing or delaying disease development or progression; stabilization of disease; and amelioration of one or more symptoms. An effective amount may be given in one or more dosages.

[0343] 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.AOJ-008PCAOE-OIOIWODesirable effects of treatment include preventing recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.

[0344] 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.

[0345] 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, or antigen binding fragment thereof, provided herein. In some aspects, the disease or condition is atopic dermatitis. In some aspects, the disease or condition is asthma (e.g., in patients with AD and co-morbid asthma).

[0346] The term “in vitro” refers to processes that occur in a living cell growing separate from a living organism, e.g., growing in tissue culture.

[0347] The term “in vivo” refers to processes that occur in a living organism.

[0348] The term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic or diagnostic products (e.g., kits) that contain information about the indications, usage, dosage, administration, combination therapy, contraindications and / or warnings concerning the use of such therapeutic or diagnostic products.

[0349] 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.

[0350] As used herein, the term “pharmaceutically acceptable” refers to those compounds, materials, compositions and / or dosage forms, which are suitable for contact with the tissues of a subject, such as a mammal (e.g., a human) without excessive toxicity, irritation, allergic response and other problem complications commensurate with a reasonable benefit / risk ratio. Preferably, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia orAOJ-008PCAOE-OIOIWO other generally recognized pharmacopeia for use in mammals, and more particularly in humans.

[0351] The terms “co-administration,” “co-administer,” and “in combination with” include the administration of two or more therapeutic agents either simultaneously, concurrently or sequentially within no specific time limits. In one embodiment, the agents are present in the cell or in the subject's body at the same time or exert their biological or therapeutic effect at the same time. In one embodiment, the therapeutic agents are in the same composition or unit dosage form. In other embodiments, the therapeutic agents are in separate compositions or unit dosage forms. In certain embodiments, a first agent can be administered prior to the administration of a second therapeutic agent.

[0352] The terms “modulate” and “modulation” refer to reducing or inhibiting or, alternatively, activating or increasing, a recited variable.

[0353] 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.

[0354] 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.

[0355] 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).

[0356] The term “agonize” refers to the activation of receptor signaling to induce a biological response associated with activation of the receptor. An “agonist” is an entity that binds to and agonizes a receptor.

[0357] The term “antagonize” refers to the inhibition of receptor signaling to inhibit a biological response associated with activation of the receptor. An “antagonist” is an entity that binds to and antagonizes a receptor.

[0358] For any of the structural and functional characteristics described herein, methods of determining these characteristics are known in the art.

[0359] The term “optionally” is meant, when used sequentially, to include from one to all of the enumerated combinations and contemplates all sub-combinations.AOJ-008PCAOE-OIOIWO

[0360] 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), glutamine (Gin; Q), Glycine (Gly; G), histidine (His; H), isoleucine (He; 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 (Vai; V).

[0361] 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).

[0362] 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.

[0363] The term “ka” (M-lxsec-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.

[0364] 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.

[0365] The term “KA” (M-l), as used herein, refers to the association equilibrium constant of a particular antibody-antigen interaction. KA = ka / kd.

[0366] As used herein, “administration” refers to providing or giving a subject a therapeutic agent (e.g., an anti-IL-13 antibody described herein) by any effective route. Exemplary routes of administration are described herein below.

[0367] As used herein, the term “polypeptide” describes a single polymer in which the monomers are amino acid residues which are covalently conjugated together through amide bonds. A polypeptide is intended to encompass any amino acid sequence, either naturally occurring, recombinant, or synthetically produced.

[0368] As used herein, the terms “nucleic acid” and “polynucleotide,” used interchangeably herein, refer to a polymeric form of nucleosides in any length. Typically, a polynucleotide is composed of nucleosides that are naturally found in DNA or RNA (e.g.,AOJ-008PCAOE-OIOIWO adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine) joined by phosphodiester bonds. The term encompasses molecules comprising nucleosides or nucleoside analogs containing chemically or biologically modified bases, modified backbones, etc., whether or not found in naturally occurring nucleic acids, and such molecules may be preferred for certain applications. Where this application refers to a polynucleotide it is understood that both DNA, RNA, and in each case both single- and double-stranded forms (and complements of each single-stranded molecule) are provided.

[0369] As used herein, the terms “conservative mutation,’- “conservative substitution,” and “conservative amino acid substitution” refer to a substitution of one or more amino acids for one or more different amino acids that exhibit similar physicochemical properties, such as polarity, electrostatic charge, and steric volume. These properties are summarized for each of the twenty naturally occurring amino acids in Table A below.Table A. Representative physicochemical properties of naturally occurring amino acidsAOJ-008PCAOE-OIOIWOFrom this table it is appreciated that the conservative amino acid families include (i) G, A, V, L and I; (ii) D and E; (iii) C, S and T; (iv) H, K and R; (v) N and Q; and (vi) F, Y and W. A conservative mutation or substitution is therefore one that substitutes one amino acid for a member of the same amino acid family (e.g., a substitution of Ser for Thr or Lys for Arg).

[0370] 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.

[0371] An “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.

[0372] The term “epitope” means a portion of an antigen that specifically binds to an antibody.

[0373] 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”).AOJ-008PCAOE-OIOIWO

[0374] The term “antigen-binding domain” means the portion of an antibody that is capable of specifically binding to an antigen or epitope.

[0375] 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.

[0376] 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.

[0377] 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.

[0378] 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.

[0379] 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.

[0380] 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, forAOJ-008PCAOE-OIOIWO 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.

[0381] 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.

[0382] The “Fab fragment” (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CHI) 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 CHI domain including one or more cysteines from the antibody hinge region.

[0383] “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 B-mercaptoethanol.

[0384] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.

[0385] “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).

[0386] “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 or VL, depending on the orientation of the variable domains in the scFv (i.e., VH-VL or VL-AOJ-008PCAOE-OIOIWOVH). 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.

[0387] 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).

[0388] 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.

[0389] 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.

[0390] 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.

[0391] The term “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) of contaminating protein.AOJ-008PCAOE-OIOIWO

[0392] 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.

[0393] 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.

[0394] 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. Sei. 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).

[0395] 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.AOJ-008PCAOE-OIOIWO

[0396] 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.Anti-IL-13 AntibodiesAntibody Structure

[0397] The present application provides antibodies, or antigen binding fragments thereof, and compositions comprising an antibody, or antigen binding fragment thereof, which binds IL- 13 as well as methods of use thereof. Exemplary anti-IL-13 antibodies are described in PCT Publication No. WO2023245187 and U.S. Patent Application Publication No. US20250129150, each of which is incorporated herein by reference in its entirety. In some embodiments, an anti-IL-13 antibody, or an antigen binding fragment thereof, described herein is selected from an anti-IL-13 antibody, or antigen binding fragment thereof, described in either of the foregoing patent applications.

[0398] 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 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., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, 5, s, y, and p, respectively.

[0399] 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 IgGl heavy chain comprises of the VH, CHI , 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 IgGl heavy chain comprises a hinge between the CHI 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 antibodyAOJ-008PCAOE-OIOIWO 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.

[0400] 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 IgGl. 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 IgAl. In one embodiment, the heavy chain is an IgA2.

[0401] In some embodiments, an antibody is an IgGl 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.

[0402] Generally, native four-chain antibodies comprise six hypervariable regions (HVRs); three in the VH (Hl, H2, and H3), and three in the VL (LI, 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 whichAOJ-008PCAOE-OIOIWO residues comprise a particular CDR given the variable region amino acid sequence of the antibody.

[0403] 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-.73'2- 745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Pliickthun, J. Mol. Biol., 2001, 309:657-70 (“AHo” numbering scheme); each of which is incorporated by reference in its entirety.

[0404] Table 1 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CORED, 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.

[0405] 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.* The C-terminus of CDR-H1, when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR.

[0406] 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.AOJ-008PCAOE-OIOIWO

[0407] 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.

[0408] 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.

[0409] 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.

[0410] 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.

[0411] Human antibodies are antibodies 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.

[0412] 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,AOJ-008PCAOE-OIOIWO 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.

[0413] In some embodiments, an antibody can bind to two or more different epitopes. 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 an 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”).

[0414] 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.

[0415] In some embodiments the antibodies are monoclonal antibodies.

[0416] In some embodiments the antibodies are polyclonal antibodies.

[0417] 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.AOJ-008PCAOE-OIOIWO

[0418] 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.

[0419] 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.

[0420] In some embodiments, the antibodies are capable of forming an immune complex.

[0421] 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.

[0422] 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).

[0423] One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al., J. Mol. Biol. 215:403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (www. ncbi. nlm. nih. gov / ) .Sequences of IL- 13 Antibodies VH Domains

[0424] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1-32.AOJ-008PCAOE-OIOIWO

[0425] In some embodiments, an antibody, or antigen binding fragment thereof, 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 illustrative VH sequence provided in any one of SEQ ID NOs: 1-32. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence provided in any one of SEQ ID NOs: 1-32, with up to 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 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

[0426] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 33-57.

[0427] In some embodiments, an antibody, or antigen binding fragment thereof, 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 illustrative VL sequence provided in any one of SEQ ID NOs: 33-57. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence provided in any one of 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.AOJ-008PCAOE-OIOIWOVH-VL Combinations

[0428] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 1-32; and a VL sequence selected from any one of SEQ ID NOs: 33-57, such as the VH-VL combinations set forth for Constructs 3-127 and 1 2-144 in Table 2, below.

[0429] In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in PCT Publication No. WO2023245187 and U.S. Patent Application Publication No.US20250129150, each of which is incorporated by reference herein in their entirety. In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Publication No. WO2023245187 and U.S. Patent Application Publication No. US20250129150 (e.g., a VH sequence and a VL sequence from the same row of Table 2).

[0430] In certain aspects, any one of SEQ ID NOs: 1-32 can be combined with any one of SEQ ID NOs: 33-57.

[0431] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence selected from the sequences set forth in any one of SEQ ID NOs: 1-32 and a VL sequence set forth in SEQ ID NO: 49.

[0432] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence selected from the sequences set forth in any one of SEQ ID NOs: 1-32 and a VL sequence set forth in SEQ ID NO: 51.

[0433] In some embodiments, an antibody, or antigen binding fragment thereof, 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 any one of 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 any one of SEQ ID NOs: 33- 57. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence provided in any one of 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 any one of 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, theAOJ-008PCAOE-OIOIWO 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.

[0434] In some embodiments, an antibody, or antigen binding fragment thereof, 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, or a VH sequence or VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In certain embodiments, the antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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 antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, comprises a VHAOJ-008PCAOE-OIOIWO sequence set forth in SEQ ID NO: 6 and a VL sequence set forth in SEQ ID NO: 36. In certain embodiments, the antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, comprises a VHAOJ-008PCAOE-OIOIWO sequence set forth in SEQ ID NO: 7 and a VL sequence set forth in SEQ ID NO: 45. In certain embodiments, the antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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 antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, comprises a VHAOJ-008PCAOE-OIOIWO sequence set forth in SEQ ID NO: 13 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 21 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, comprises a VHAOJ-008PCAOE-OIOIWO sequence set forth in SEQ ID NO: 28 and a VL sequence set forth in SEQ ID NO: 39. In certain embodiments, the antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 3 and a VL sequence set forth in SEQ ID NO: 51.

[0435] In certain embodiments, the isolated antibody, or antigen binding fragment thereof, comprises a heavy chain variable domain comprising a framework region sequence selected from a sequence set forth in any one of 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 isolated antibody, or antigen binding fragment thereof, 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.

[0436] In certain embodiments, the isolated antibody, or antigen binding fragment thereof, comprises a light chain variable domain comprising a framework region sequence selected from a sequence set forth in any one of 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. In certain embodiments, the isolated antibody, or antigen binding fragment thereof, 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.AOJ-008PC AOE-OIOIWO

[0437] In certain embodiments, the isolated antibody, or antigen binding fragment thereof, 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 sequencesAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO*Names correspond with name in informal sequence listing

[0438] 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 anti-IL-13 antibody, or antigen binding fragment thereof, 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 heavy chain constant (HC) domain comprisingAOJ-008PCAOE-OIOIWO 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%, 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 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 anti- IL-13 antibody, or antigen binding fragment thereof, 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. In certain embodiments, the HC domain is an IgGl HC domain. In certain embodiments, the VL domain of any one of Constructs 3- 127 and 132-144 in Table 2 is combined with an IgGl light chain constant (LC) domain. In certain embodiments, the VL domain of any one of Constructs 3-127 and 132-144 in Table 2 is combined with a LC domain comprising SEQ ID NO: 469 or an LC domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0439] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 610-709) it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 425-468 and 484-539). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 610-709), a human IgG sequence lacking a C-terminal lysine e.g., any one of SEQ ID NOs: 425-468 and 484-539), or a mixture thereof (e.g., a mixture of the same heavy chain constant region sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 691 and SEQ ID NO: 439).

[0440] In certain embodiments, the HC domain includes IgG4-SP, hlgGl-LALA-YTE, hlgGl-LAGA-YTE, hlgGl-LALA-LS, IgG4-YTE HC, or IgG4-LS.

[0441] In some embodiments, such an IgG4-SP HC constant domain has the sequence: ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGAOJ-008PCAOE-OIOIWOGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY TLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 427).

[0442] In some embodiments, such a hlgGI-LALA-YTE HC constant domain has the sequence:ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP EAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:439).

[0443] In some embodiments, such a hlgGl-LAGA YTE HC constant domain has the sequence:ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELAGAPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:440).

[0444] In some embodiments, such a hlgGl-LALA-LS HC constant domain has the sequence:

[0445] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPG (SEQ ID NO: 446).

[0446] In some embodiments, such an IgG4-YTE HC constant domain has the sequence:AOJ-008PCAOE-OIOIWOASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLG GPSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ TD NO: 457).

[0447] In some embodiments, such an IgG4-LS HC constant domain has the sequence:ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY TLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVLHEALHSYTQKSLSLSLG (SEQ ID NO: 460).

[0448] In some embodiments, the heavy chain constant domain includes a C -terminal lysine. In some embodiments, such a hlgGl-LALA-YTE HC C-terminal lysine variant constant domain has the sequence:ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR EPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:624).

[0449] In some embodiments, such a hlgGl-LAGA YTE HC C-terminal lysine variant constant domain has the sequence:ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAGAPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR EPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:625).AOJ-008PCAOE-OIOIWO

[0450] In some embodiments, such a hlgGl-LALA-LS HC C-terminal lysine variant constant domain has the sequence:

[0451] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK (SEQ ID NO: 631).

[0452] In some embodiments, such an IgG4-SP HC terminal lysine variant constant domain has the sequence:ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY TLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 612).

[0453] In some embodiments, such a IgG4-YTE HC terminal lysine variant constant domain has the sequence:ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLG GPSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYT LPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 642).

[0454] In some embodiments, such an IgG4-LS HC C-terminal lysine variant constant domain has the sequence:ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYAOJ-008PCAOE-OIOIWOTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSRLTVDKSRWQEGNVFSCSVLHEALHSYTQKSLSLSLGK (SEQ ID NO: 645).

[0455] In some embodiments, a VL domain listed for Constructs 3-127 and 132-144 in Table 2 or a VL domain having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto 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

[0456] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from any one of 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, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VH domain selected from any one of SEQ ID NOs: 1-32. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from any one of SEQ ID NOs: 1-32. 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.

[0457] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Publication No. WO2023245187 and U.S. Patent Application Publication No. US20250129150, each incorporated by reference herein in its entirety. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody provided in PCT Publication No. WO2023245187. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody provided in PCT Publication No. WO2023245187. In some embodiments, disclosed herein is an antibody, orAOJ-008PCAOE-OIOIWO an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IM GT CDRs of an antibody provided in PCT Publication No. WO2023245187. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single antibody described in Tables 3-8 of PCT Publication No. WO2023245187 and U.S. Patent Application Publication No. US20250129150.

[0458] 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 to 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 any one of 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 any one 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 any one of 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.

[0459] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VL domain of any one 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, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VL domain of any one of SEQ ID NOs: 33-57. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain of any one 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.AOJ-008PCAOE-OIOIWO

[0460] 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 to a CDR-L1, CDR-L2, or CDR-L3 of SEQ ID NOs: 141-144, 149-158, and 165-172. In some embodiments, the CDR- L1 is a CDR-L1 of a VL domain of any one 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 any one 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-L3 of a VL domain of any one 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.

[0461] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from any one of SEQ ID NOs: 1-32 and one to three CDRs of a VL domain selected from any one of SEQ ID NOs: 33-57. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VH domain selected from any one of SEQ ID NOs: 1-32 and two to three CDRs of a VL domain selected from any one of SEQ ID NOs: 33-57. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from any one of SEQ ID NOs: 1-32 and three CDRs of a VL domain selected from any one 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.

[0462] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112-120 and 130-140. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 112-AOJ-008PCAOE-OIOIWO120 or 130-140. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 112-120 and 130-140, 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.

[0463] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from any one 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 to a CDR-H1 selected from any one of SEQ ID NOs: 58-99 and 121. In some embodiments, the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 58-99 and 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.

[0464] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from 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 to a CDR-H2 selected from any one of SEQ ID NOs: 100-111. In some embodiments, the CDR-H2 is a CDR-H2 selected from 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, byAOJ-008PCAOE-OIOIWO 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.

[0465] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L3 selected from any one of 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 to a CDR-L3 selected from any one of SEQ ID NOs: 165-172. In some embodiments, the CDR-L3 is a CDR-L3 selected from any one 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 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.

[0466] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from any one of 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 to a CDR-L2 selected from any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS. In some embodiments, the CDR-L2 is a CDR-L2 selected from any one of 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.AOJ-008PCAOE-OIOIWO

[0467] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from any one of 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 to a CDR-L1 selected from any one of SEQ ID NOs: 141- 144 and 149-152. In some embodiments, the CDR-L1 is a CDR-L1 selected from any one of 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.

[0468] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112-120 and 130-140, a CDR-H2 selected from any one of SEQ ID NOs: 100-111 , a CDR-H1 selected from any one of SEQ ID NOs: 58-99 and 121, a CDR-L3 selected from any one of SEQ ID NOs: 165-172, a CDR-L2 selected from any one of SEQ ID NOs: 153-158 and the amino acid sequence LAS, and a CDR-L1 selected from any one of 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 to a CDR-H3 selected from any one of 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 to a CDR-H2 selected from any one 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 to a CDR-H1 selected from any one of 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 to a CDR-L3 selected from any one of 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 to a CDR-L2 selected from any one of 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 to a CDR-L1 selected from any one of SEQ ID NOs: 141-144 and 149-152. In someAOJ-008PCAOE-OIOIWO embodiments, the CDR-H3 is a CDR-H3 selected from any one of 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 selected from any one 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 any one of 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 any one of 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 any one of 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 any one of SEQ ID NOs: 141-144 and 149-152, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0469] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112, 121, and 130, a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, a CDR-H1 selected from any one of SEQ ID NOs: 58, 68, and 85, a CDR-L3 selected from any one of SEQ ID NOs: 168, 173, and 181, a CDR-L2 selected from SEQ ID NO: 153 and the amino acid sequence LAS, and a CDR-L1 selected from 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 to a CDR-H3 selected from SEQ ID NOs: 112 and 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 100, 104 and 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 58, 68 and 85, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to 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 to a CDR-L2 of SEQ ID NO: 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 to a CDR-L1 selected from SEQ ID NOs: 141 and 149. In some embodiments, the CDR-H3 is a CDR-H3 of SEQ ID NO: 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 NO: 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 NO: 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-AOJ-008PCAOE-OIOIWOL2 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 NO: 141 or 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0470] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112, 121 and 130, a CDR-H2 selected from any one of SEQ ID NOs: 100, 104 and 108, a CDR-H1 selected from any one of SEQ ID NOs: 58, 68, and 85, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NO: 153 or the amino acid sequence LAS, and a CDR-L1 selected from any one 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 to a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 100, 104 and 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 58, 68, and 85, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to 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 to a CDR-L2 of SEQ ID NO: 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 to a CDR-L1 selected from any one of SEQ ID NOs: 141 and 149. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 100, 104 and 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 58, 68, and 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 selected from any one of SEQ ID NOs: 141 and 149, with up to 1 , 2, 3, 4, 5, or 6 amino acid substitutions.

[0471] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, a CDR-H1 selected from any oneAOJ-008PCAOE-OIOIWO of SEQ ID NOs: 58, 68, and 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 selected from any one 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 to a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 58, 68, and 85, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to 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 to 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 to a CDR-L1 selected from any one of SEQ ID NOs: 141 and 149. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR- H1 selected from any one of SEQ ID NOs: 58, 68, and 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 selected from any one of SEQ ID NOs: 141 and 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0472] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112, 121 and 130, a CDR-H2 selected from any one of SEQ ID NOs: 100, 104 and 108, a CDR-H1 selected from any one of SEQ ID NOs: 58, 67, and 84, a CDR-L3 of SEQ ID NO: 165, a CDR-L2 of SEQ ID NO: 153 or the amino acid sequence LAS, and a CDR-L1 selected from any one 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 to a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from any one ofAOJ-008PCAOE-OIOIWOSEQ ID NOs: 100, 104 and 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 58, 67 and 84, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to 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 to a CDR-L2 of SEQ ID NO: 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 to a CDR-L1 selected from any one of SEQ ID NOs: 141 and 149. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 100, 104 and 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 58, 67, and 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 selected from any one of SEQ ID NOs: 141 and 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0473] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, a CDR-H1 selected from any one 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 selected from any one 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 to a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 58, 67 and 84, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to 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 to a CDR-L2 of SEQ ID NO: 158 or the amino acid sequence LAS, and the CDR-L1 has at least about 80%, 90%,AOJ-008PCAOE-OIOIWO91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 141 and 149. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 112 and 130, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 100, 104, and 108, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR- H1 selected from any one of SEQ ID NOs: 58, 67, and 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 selected from any one of SEQ ID NOs: 141 and 149, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0474] 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.

[0475] In certain aspects, the antibodies disclosed herein do not include antibodies disclosed in US Patent number 9,067,994.AOJ-008PCAOE-OIOIWOTable 3. Anti-interleukin (IL)-13 antibody Heavy Chain Kabat CDRsAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO* Names correspond with name in informal sequence listing.AOJ-008PCAOE-OIOIWOTable 4. Anti -interleukin (IL)-13 antibody Heavy Chain Chothia CDRsAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO'"Names correspond with name in informal sequence listing.AOJ-008PCAOE-OIOIWOTable 5. Anti-interleukin (IL)-13 antibody Heavy Chain IMGT CDRsAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO'"Names correspond with name in informal sequence listing.AOJ-008PCAOE-OIOIWOTable 6. Anti-interleukin (IL)- 13 antibody Light Chain Kabat CDRsAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO*Names correspond with name in informal sequence listing.AOJ-008PCAOE-OIOIWOTable 7. Anti-interleukin (IL)-13 antibody Light Chain Chothia CDRsAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO*Names correspond with name in informal sequence listing.AOJ-008PCAOE-OIOIWOTable 8. Anti-interleukin (IL)-13 antibody Light Chain IMGT CDRsAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWOAOJ-008PCAOE-OIOIWO*Names correspond with name in informal sequence listing.AOJ-008PCAOE-OIOIWOFc Region

[0476] 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.

[0477] 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., IgGi, IgGz, IgGs, IgG4, IgAi, and IgA2.

[0478] 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 FcyRI, FcyRII, and FcyRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcyRII receptors include FcyRIIA (an “activating receptor”) and FcyRIIB (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 FcyRIIA contains an immunoreceptor tyrosine-based activation motif (IT AM) in its cytoplasmic domain. Inhibiting receptor FcyRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Daeron, 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 neonatalAOJ-008PCAOE-OIOIWO 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)).

[0479] 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 designed to promote selective binding of Fc-gamma receptors.

[0480] Exemplary mutations that may alter the binding of FcRs to the Fc are listed below (in EU numbering format):• S298A / E333A / K334A, S298A / E333A / K334A / K326A (Lu Y, Vernes JM, Chiang N, et al., J Immunol Methods. 2011 Feb 28;365(l-2): 132-41);• F243L / R292P / Y300L / V305I / P396L, F243L / R292P / Y300L / L235V / P396L (Stavenhagen JB, Gorlatov S, Tuaillon N, et al., Cancer Res. 2007 Sep15 ;67(18) : 8882-90; Nordstrom JL, Gorlatov S, Zhang W, et al., Breast Cancer Res. 2011 Nov 30;13(6):R123);• F243L (Stewart R, Thom G, Levens M, et al., Protein Eng Des Sei. 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);• S239D / I332E / A330L, S239D / I332E (Lazar et al., (2006) Proc Natl Acad Sci U SA. 103(11):4005-10);• S239D / S267E, S267E / L328F (Chu et al., (2008) Mol Immunol. 45(15):3926-33);• S239D / D265S / S298A / I332E, S239E / S298A / K326A / A327H, G237F / S298A / A330L / I 332E, S239D / I332E / S298A, S239D / K326E / A330L / I332E / S298A, G236A / S239D / D2 70L / 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 1 907568 37 9, Oct 2012) lists mutations on page 283.

[0481] In certain embodiments an antibody, or antigen binding fragment thereof, described herein includes modifications to improve its ability to mediate effector function. Such modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a forAOJ-008PCAOE-OIOIWOADCC, and towards Clq for CDC. The following Table 9 summarizes various designs reported in the literature for effector function engineering.

[0482] 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.) 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 von Horsten et al. (2010) supra) or Lecl3 CHO cells, which are deficient in protein fucosylation (see Ripka et al. (1986) Arch. Biochem. Biophys. 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. (2004) Biotech. Bioeng. 87: 614-622; Kanda et al. (2006) Biotechnol. Bioeng. 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.

[0483] 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.

[0484] In some aspects, an antibody provided herein comprises an IgGl domain with reduced fucose content at position Asn 297 compared to a naturally occurring IgGl domain. Such Fc domains can have improved ADCC. See Shields et al. (2002) J. Biol. Chem. 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.AOJ-008PCAOE-OIOIWO

[0485] 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 some embodiments, an antibody, or an antigen binding fragment thereof, 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. (2006) Proc. Natl. Acad. Sci. USA 103:4005-4010, incorporated by reference in its entirety.

[0486] 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. (2004) supra', each of which is incorporated by reference in its entirety.

[0487] In some 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 is incorporated by reference in its entirety.

[0488] 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 may confer improved effector function. In another embodiment, the antibody can be afucosylated to improve effector function.Table 9. CH2 domains and effector function engineeringAOJ-008PCAOE-OIOIWO

[0489] Fc modifications reducing 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), Cure 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. ((2012) J. Mol. Biol. 420: 204- 219), each of which is incorporated by reference in its entirety, describe specific modifications designed to reduce FcgR or complement binding to the Fc.

[0490] Specific, non-limiting examples of amino acid modifications intended to reduce FcgR or complement binding to the Fc include those identified in the following Table 10:Table 10. Modifications designed to reduce FcgR or complement binding to the FcAOJ-008PCAOE-OIOIWO

[0491] In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one or more alterations that is designed to improve or diminish Clq 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.

[0492] In certain embodiments, an antibody, or antigen binding fragment thereof, 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.

[0493] In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a constant light chain (EC) region comprising an amino acid sequence set forth in SEQ ID NO: 469.

[0494] In certain embodiments, an antibody, or antigen binding fragment thereof, 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%,AOJ-008PCAOE-OIOIWO98%, 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.

[0495] In certain embodiments, the isolated antibody, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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 the amino acid sequence LAS, and a LCDR3 comprising SEQ ID NO: 165.

[0496] 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 amino acid 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.

[0497] In certain embodiments, the Fc region comprises one or more amino acid substitutions, wherein the one or more amino acid substitutions result in increased antibody half-life, and a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared with the Fc region without the one or more amino acid 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.

[0498] 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,AOJ-008PCAOE-OIOIWON434S, 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 (LALA), M428L / N434A (LA), L235A / G237A (LAGA), L234A / L235A / G237A (LALAGA), L234A / L235A / P329G (LALAPG), 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.

[0499] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 253, 255 and 257. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 235 and 236, respectively. In certain embodiments, an antibody described herein comprises 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 anti-IL-13 antibody described herein comprises the heavy and light chain variable regions of Construct 133 and an Fc region comprising YTE mutations at positions 253, 255 and 257, respectively and with LALA mutations at positions 235 and 236, respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 710 and 711).

[0500] In certain embodiments the human Fc region comprises a human IgGl Fc region with LALA mutations. In certain embodiments, the human Fc region comprises a humanAOJ-008PCAOE-OIOIWOIgGl Fc region with YTE mutations. In certain embodiments, the human Fc region comprises a human IgGl Fc region with LALA and YTE mutations. In certain embodiments, when direct numbering is used, “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, a human Fc region can comprise a human IgGl Fc with LALA mutations at L235A / L236A and / or YTE mutations at M253Y / S255T / T257E.

[0501] In certain embodiments, the IL- 13 antibody comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 3, a constant heavy chain sequence set forth in SEQ ID NO: 439 and / or a constant heavy chain sequence set forth in SEQ ID NO: 624, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 39, and a constant light chain sequence set forth in SEQ ID NO: 469. In certain embodiments, the IL- 13 antibody comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 3, a constant heavy chain sequence set forth in SEQ ID NO: 624, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 39, and a constant light chain sequence set forth in SEQ ID NO: 469. In certain embodiments, the IL- 13 antibody comprises a heavy chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 3, a constant heavy chain sequence set forth in SEQ ID NO: 439, a light chain variable region sequence comprising an amino acid sequence set forth in SEQ ID NO: 39, and a constant light chain sequence set forth in SEQ ID NO: 469.

[0502] The C-terminal Lys330 of the constant heavy chain sequence of SEQ ID NO: 624 may or may not be present. The disclosure specifically contemplates SEQ ID NO: 624 that does not include the C-terminal Lys corresponding to Lys330 (as set forth in SEQ ID NO: 439). A polypeptide comprising SEQ ID NO: 624 (e.g., the polypeptide of SEQ ID NO: 710) may be expressed including a C-terminal Lys330 which then may be proteolytically cleaved upon expression of the polypeptide (e.g., a polypeptide comprising SEQ ID NO: 624 is expressed using a nucleic acid construct encoding the polypeptide including a C-terminal lysine residue, which may then be removed via cleavage to produce a polypeptide in which the constant heavy chain has the sequence of SEQ ID NO: 439, such as the polypeptide of SEQ ID NO: 711). Accordingly, the IL- 13 antibody that is administered can have the constant heavy chain sequence of SEQ ID NO: 624, SEQ ID NO: 439, or a mixture thereof.

[0503] In some embodiments, the IL- 13 antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 712. In some embodiments, the IL- 13 antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 710 or SEQ ID NO: 711. InAOJ-008PCAOE-OIOIWO some embodiments, the IL- 13 antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 710. In some embodiments, the IL-13 antibody comprises a heavy chain comprising the sequence set forth in SEQ ID NO: 711. The heavy chain sequence of SEQ ID NO: 710 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in an antibody containing the heavy chain sequence of SEQ ID NO: 711.

[0504] In some embodiments, the IL- 13 antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 712 and a heavy chain comprising the sequence set forth in SEQ ID NO: 710. In some embodiments, the IL-13 antibody comprises a light chain comprising the sequence set forth in SEQ ID NO: 712 and a heavy chain comprising the sequence set forth in SEQ ID NO: 711.

[0505] In certain embodiments, the Fc region binds an Fey Receptor selected from the group consisting of: FcyRI, FcyRIIa, FcyRIIb, FcyRIIc, FcyRIIIa, and FcyRIIIb. In certain embodiments, the Fc region binds an Fey Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.ModificationsYTE Substitutions

[0506] In certain embodiments, the fragment crystallizable region (Fc region) of the anti- 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 YTE substitutions may be at positions M253Y / S255T / T257E by direct numbering. YTE substitutions (also referred to herein as YTE mutations) 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 mutations confer greater FcRn-IgG binding, prolonging the IgG serum half-life compared to an unmodified IgG.LALA Substitutions

[0507] In certain embodiments, the anti-IL-13 antibodies described herein additionally carry Fc region amino acid substitutions L234A / L235A in the IgGl heavy chain, commonly called LALA substitutions or LALA mutations. In certain embodiments, the LALA substitutions may be at positions L235A / L236A by direct numbering. These changes impair Fc receptor binding to IgG and prevent undesired effector cell activation.AOJ-008PCAOE-OIOIWOBinding

[0508] In certain embodiments, an anti-IL-13 antibody, or antigen binding fragment thereof, described herein is a high-affinity IgGl humanized monoclonal antibody (mAb) that binds IL-13. In certain embodiments, the anti-IL-13 antibody, or antigen binding fragment thereof, described herein comprises an IgGl constant region comprising YTE substitutions and LALA substitutions.

[0509] Without wishing to be bound by theory, the binding of the anti-IL-13 antibodies described herein to IL-13 is believed to prevent the formation of the IL-13Ral / IL-4Ra 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.

[0510] 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®).

[0511] 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 anti-IL-13 antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for IL-13. In certain embodiments, the affinity of an anti-IL-13 antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for IL-13. In certain embodiments, the affinity of an anti-IL-13 antibody, or antigen bindingAOJ-008PCAOE-OIOIWO fragment thereof, for a non-target molecule is less than about 30% of the affinity for IL- 13. In certain embodiments, the affinity of an anti-IL-13 antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity for IL-13. In certain embodiments, the affinity of an anti-IL-13 antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for IL- 13. In certain embodiments, the affinity of an anti-IL-13 antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for IL- 13. In certain embodiments, the affinity of an anti-IL- 13 antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for IL- 13.

[0512] 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 anti-IL- 13 antibody, after which a second anti-IL- 13 antibody is added. In another exemplary assay, a first anti-IL- 13 antibody is coated on a surface and contacted with IL-13, and then a second anti-IL- 13 antibody is added. If the presence of the first anti- IL- 13 antibody reduces binding of the second anti-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.AOJ-008PCAOE-OIOIWO

[0513] A test antibody competes with a reference antibody if an excess of a test antibody (e.g., at least 2x, 5x, lOx, 20x, or lOOx) 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 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%.

[0514] In certain embodiments, the antibody, or antigen binding fragment thereof, binds an IL-13 sequence set forth in SEQ ID NO: 472 or SEQ ID NO: 473.

[0515] In certain embodiments, the antibody, or antigen binding fragment thereof, binds to an IL-13 sequence set forth in SEQ ID NO: 472 or SEQ ID NO: 473 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9 x 10'9M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or antigen binding fragment thereof, binds to an IL-13 sequence set forth in SEQ ID NO: 472 or SEQ ID NO: 473 with a KD of less than or equal to about 1 x 10-1° M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or antigen binding fragment thereof, binds to human IL- 13 with a KD of less than or equal to about 1 x 10'9M, as measured by surface plasmon resonance (SPR).

[0516] In certain embodiments, an antibody, or antigen binding fragment thereof, 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 10’8M, as measured by ELISA or any other suitable method known in the art. In certain embodiments, an antibody, or antigen binding fragment thereof, 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‘9M, as measured by ELISA or any other suitable method known in the art.AOJ-008PCAOE-OIOIWO

[0517] In certain embodiments, the KD of an antibody, or antigen binding fragment thereof, 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 108M, as measured by ELISA or any other suitable method known in the art. In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein binds IL-13 with a KD of less than or equal to about 1 x 10'8M, or less than or equal to about 1 x 10"9M as measured by ELISA or any other suitable method known in the art.

[0518] In certain embodiments, an antibody, or antigen binding fragment thereof, 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 10'8M, or less, as measured by ELISA or any other suitable method known in the art . In certain embodiments, an antibody, or antigen binding fragment thereof, 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"8M as measured by ELISA or any other suitable method known in the art.

[0519] In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein results in inhibition of pSTAT6 with an IC50 of at least about 60 days, at least about 65 days, at least about 70 days, at least about 75 days, at least about 80 days, at least about 85 days, at least about 90 days, at least about 95 days, at least about 100 days, or at least about 105 days. In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein results in inhibition of pSTAT6 with an IC50 of between about 85 and about 100 days, between about 90 and about 95 days, or between about 91 and about 93 days. In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein results in inhibition of pSTAT6 with an IC50 of at least about 100 days, at least about 120 days, at least about 140 days, at least about 160 days, at least about 180 days, at least about 200 days, at least about 220 days, at least about 240 days, at least about 260 days, at least about 280 days, at least about 300 days, at least about 320 days, or at least about 340 days. In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein results in inhibition of pSTAT6 with an IC50 of at least about 200 days, at least about 210 days, at least about 220 days, at least about 230 days, at least about 240 days, at leastAOJ-008PCAOE-OIOIWO about 250 days, at least about 260 days, at least about 270 days, at least about 280 days, at least about 290 days, at least about 300 days, at least about 310 days, at least about 320 days, at least about 330 days, at least about 340 days, or at least about 350 days. In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein results in inhibition of pSTAT6 with an IC50 of at least about 24 weeks, at least about 36 weeks, or at least about 48 weeks. In certain embodiments, an antibody, or antigen binding fragment thereof, provided herein results in inhibition of pSTAT6 with an IC50 of between about 24 weeks and about 60 weeks, between about 24 weeks and about 48 weeks, between about 24 weeks and about 36 weeks, between about 36 weeks and about 60 weeks, between about 36 weeks and about 48 weeks, or between about 48 weeks and about 60 weeks. In certain embodiments, inhibition of pSTAT6 is determined by administering an antibody provided herein to a mammal, collecting whole blood, staining with a fluorescent anti-pSTAT6 antibody, and using FACS to determine the concentration of antibody, or antigen binding fragment thereof, needed to inhibit 50% of the maximum MFI of pSTAT6. In certain embodiments, inhibition of pSTAT6 is determined by contacting cells with IL- 13 or IL-4 and an antibody, or antigen binding fragment thereof, provided herein, staining the cell with a fluorescent anti-pSTAT6 antibody, and using FACS to determine the concentration of antibody, or antigen binding fragment thereof, needed to inhibit 50% of the maximum MFI of pSTAT6.Pharmaceutical compositions

[0520] The present application provides compositions comprising the antibodies including pharmaceutical compositions comprising any one or more of the antibodies, or antigen binding fragments thereof, described herein with one or more pharmaceutically acceptable excipients. In certain embodiments the composition is sterile. The pharmaceutical compositions generally comprise an effective amount of an antibody, or antigen binding fragment thereof.

[0521] In certain aspects, a composition comprises 150 mg / mL, 180 mg / mL, or 200 mg / mL of an anti-IL- 13 antibody, or antigen binding fragment thereof, described herein. In certain embodiments, the anti-IL- 13 antibody, or antigen binding fragment thereof, 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. In certain embodiments, the anti-IL- 13 antibody, or antigen binding fragment thereof, comprises a heavy chain constant regionAOJ-008PCAOE-OIOIWO comprising a sequence set forth in SEQ ID NO: 439 or 624 and a light chain constant region comprising a sequence set forth in SEQ ID NO: 469, wherein the antibody further comprises a VH comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 3 and a VL comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 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 the amino acid sequence LAS, and a LCDR3 comprising SEQ ID NO: 165.

[0522] These compositions can comprise, in addition to one or more of the antibodies, or antigen binding fragments thereof, disclosed herein, a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material can depend on the route of administration, e.g., oral, intravenous, cutaneous or subcutaneous, nasal, intramuscular, intraperitoneal routes.

[0523] In certain embodiments, the composition comprises a histidine buffer, arginine and / or methionine and optionally a surfactant and / or sucrose. In certain embodiments, the surfactant is polysorbate (e.g., polysorbate 80) or a poloxamer (e.g. , poloxamer 188).

[0524] Pharmaceutical compositions for oral administration can be in tablet, capsule, powder or liquid form. A tablet can include a solid carrier such as gelatin or an adjuvant. Liquid pharmaceutical compositions generally include a liquid carrier such as water, petroleum, animal or vegetable oils, mineral oil or synthetic oil. Physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol can be included.

[0525] For intravenous, cutaneous or subcutaneous injection, or injection at the site of affliction, the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer’s Injection, Lactated Ringer’s Injection.AOJ-008PCAOE-OIOIWOPreservatives, stabilizers, buffers, antioxidants and / or other additives can be included, as required.

[0526] The anti-IL-13 antibody, or antigen binding fragment thereof, that is to be given to an individual, administration is preferably in a “therapeutically effective amount” or “prophylactically effective amount” (as the case can be, although prophylaxis can be considered therapy), this being sufficient to show benefit to the individual. The actual amount administered, and rate and time-course of administration, will depend on the nature and severity of protein aggregation disease being treated. Prescription of treatment, e.g., decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors, and typically takes account of the disorder to be treated, the condition of the individual patient, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington’s Pharmaceutical Sciences, 16thedition, Osol, A. (ed), 1980.

[0527] A composition can be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated.MethodsMethods of Preparation

[0528] Antibodies, or antigen binding fragments thereof, described herein can be produced using recombinant methods and compositions, e.g., as described in U.S. Pat. No. 4,816,567. In one embodiment, isolated nucleic acid encoding an antibody, or antigen binding fragment thereof, described herein is provided. Such nucleic acid may encode an amino acid sequence comprising the VL and / or an amino acid sequence comprising the VH of the antibody e.g., the light and / or heavy chains of the antibody) or an amino acid sequence comprising the VH of a single domain antibody. In a further embodiment, one or more vectors e.g., expression vectors) comprising such nucleic acid are provided. In one embodiment, the nucleic acid is provided in a multicistronic vector. In a further embodiment, a host cell comprising such nucleic acid is provided. In one such embodiment, a host cell comprises (e.g., has been transformed with): (1) a vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and an amino acid sequence comprising the VH of the antigen-binding polypeptide construct, or (2) a first vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL ofAOJ-008PCAOE-OIOIWO the antigen-binding polypeptide construct and a second vector comprising a nucleic acid that encodes an amino acid sequence comprising the VH of the antigen-binding polypeptide construct. In one embodiment, the host cell is eukaryotic, e.g., a Chinese Hamster Ovary (CHO) cell, or human embryonic kidney (HEK) cell, or lymphoid cell (e.g., YO, NSO, Sp20 cell). In one embodiment, a method of making an antibody is provided, wherein the method comprises culturing a host cell comprising nucleic acid encoding the antibody, as provided above, under conditions suitable for expression of the antibody, and optionally recovering the antibody from the host cell (or host cell culture medium).

[0529] For recombinant production of the antibody, a nucleic acid encoding an antibody, e.g., as described above, is isolated and inserted into one or more vectors for further cloning and / or expression in a host cell. Such nucleic acid may be readily isolated and sequenced using conventional procedures e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the antibody).

[0530] When an antibody or variant thereof is recombinantly produced by the host cells, the protein in certain embodiments is present at about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, about 2%, or about 1% or less of the dry weight of the cells. When the antibody or variant thereof is recombinantly produced by the host cells, the protein, in certain embodiments, is present in the culture medium at about 5 g / L, about 4 g / L, about 3 g / L, about 2 g / L, about 1 g / L, about 750 mg / L, about 500 mg / L, about 250 mg / L, about 100 mg / L, about 50 mg / L, about 10 mg / L, or about 1 mg / L or less of the dry weight of the cells. In certain embodiments, “substantially purified” antibody produced by the methods described herein, has a purity level of at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, specifically, a purity level of at least about 75%, 80%, 85%, and more specifically, a purity level of at least about 90%, a purity level of at least about 95%, a purity level of at least about 99% or greater as determined by appropriate methods such as SDS / PAGE analysis, RP-HPLC, SEC, and capillary electrophoresis.

[0531] Suitable host cells for cloning or expression of antibody-encoding vectors include prokaryotic or eukaryotic cells described herein.

[0532] Recombinant host cells or host cells are cells that include an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells.AOJ-008PCAOE-OIOIWOThe exogenous polynucleotide may be maintained as a nonintegrated vector, for example, a plasmid, or alternatively, may be integrated into the host genome. Host cells can include CHO, derivatives of CHO, NSO, Sp2O, CV-1, VERO-76, HeLa, HepG2, Per.C6, or BHK.

[0533] For example, an antibody may be produced in bacteria, in particular when glycosylation and Fc effector function are not needed. For expression of antibody fragments and polypeptides in bacteria, see, e.g., U.S. Pat. Nos. 5,648,237, 5,789,199, and 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol. 248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J., 2003), pp. 245-254, describing expression of antibody fragments in E. coli.) After expression, the antibody may be isolated from the bacterial cell paste in a soluble fraction and can be further purified.

[0534] In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for antibody-encoding vectors, including fungi and yeast strains whose glycosylation pathways have been “humanized,” resulting in the production of an antibody with a partially or fully human glycosylation pattern. See Gerngross, Nat. Biotech. 22: 1409-1414 (2004), and Li et al., Nat. Biotech. 24:210-215 (2006).

[0535] Suitable host cells for the expression of glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains have been identified which may be used in conjunction with insect cells, particularly for transfection of Spodoptera frugiperda cells.

[0536] Plant cell cultures can also be utilized as hosts. See, e.g., U.S. Pat. Nos. 5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (describing PLANTIBODIES™ technology for producing antibodies in transgenic plants).

[0537] Vertebrate cells may also be used as hosts. For example, mammalian cell lines that are adapted to grow in suspension may be useful. Other examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7); human embryonic kidney line (293 or 293 cells as described, e.g., in Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK); mouse sertoli cells (TM4 cells as described, e.g., in Mather, Biol. Reprod. 23:243-251 (1980)); monkey kidney cells (CV1); African green monkey kidney cells (VERO-76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK; buffalo rat liver cells (BRL 3A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, e.g., in Mather etAOJ-008PCAOE-OIOIWO al. , Annals N.Y. Acad. Sci. 383:44-68 (1982); MRC 5 cells; and FS4 cells. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR- CHO cells (Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); and myeloma cell lines such as Y0, NSO and Sp2 / 0. For a review of certain mammalian host cell lines suitable for antibody production, see, e.g., Yazaki and Wu, Methods in Molecular Biology, Vol. 248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J.), pp. 255-268 (2003).

[0538] In one embodiment, the antibodies described herein are produced in stable mammalian cells, by a method comprising: transfecting at least one stable mammalian cell with: nucleic acid encoding the antibody, in a predetermined ratio; and expressing the nucleic acid in the at least one mammalian cell. In certain embodiments, the predetermined ratio of nucleic acid is determined in transient transfection experiments to determine the relative ratio of input nucleic acids that results in the highest percentage of the antibody in the expressed product.

[0539] In some embodiments, the method of producing an antibody in stable mammalian cells as described herein results in an expression product of the at least one stable mammalian cell comprising a larger percentage of the desired glycosylated antibody as compared to the monomeric heavy or light chain polypeptides, or other antibodies.

[0540] In some embodiments, the method of producing a glycosylated antibody in stable mammalian cells described herein comprises identifying and purifying the desired glycosylated antibody. In some embodiments, the said identification is by one or both of liquid chromatography and mass spectrometry.

[0541] If required, the antibodies can be purified or isolated after expression. Proteins may be isolated or purified in a variety of ways known to those skilled in the art. Standard purification methods include chromatographic techniques, including ion exchange, hydrophobic interaction, affinity, sizing or gel filtration, and reversed-phase, carried out at atmospheric pressure or at high pressure using systems such as FPLC and HPLC. Purification methods also include electrophoretic, immunological, precipitation, dialysis, and chromato focusing techniques. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. As is well known in the art, a variety of natural proteins bind Fc and antibodies, and these proteins can find use in the present invention for purification of antibodies. For example, the bacterial proteins A and G bind to the Fc region. Likewise, the bacterial protein L binds to the Fab region of some antibodies. Purification can often be enabled by a particular fusion partner. For example, antibodies may be purified usingAOJ-008PCAOE-OIOIWO glutathione resin if a GST fusion is employed, Ni+2affinity chromatography if a His-tag is employed or immobilized anti-flag antibody if a flag-tag is used. For general guidance in suitable purification techniques, see, e.g., incorporated entirely by reference Protein Purification: Principles and Practice, 3rdEd., Scopes, Springer- Verlag, NY, 1994, incorporated entirely by reference. The degree of purification necessary will vary depending on the use of the antibodies. In some instances, no purification is necessary.

[0542] In certain embodiments, the antibodies are purified using Anion Exchange Chromatography including, but not limited to, chromatography on Q-sepharose, DEAE sepharose, poros HQ, poros DEAF, Toyopearl Q, Toyopearl QAE, Toyopearl DEAE, Resource / Source Q and DEAE, Fractogel Q and DEAE columns.

[0543] In specific embodiments, the proteins described herein are purified using Cation Exchange Chromatography including, but not limited to, SP-sepharose, CM sepharose, poros HS, poros CM, Toyopearl SP, Toyopearl CM, Resource / Source S and CM, Fractogel S and CM columns and their equivalents and comparables.

[0544] In addition, antibodies described herein can be chemically synthesized using techniques known in the art (e.g., see Creighton, 1983, Proteins: Structures and Molecular Principles, W. H. Freeman & Co., N.Y and Hunkapiller et al. , Nature, 310:105-111 (1984)). For example, a polypeptide corresponding to a fragment of a polypeptide can be synthesized by use of a peptide synthesizer. Furthermore, if desired, nonclassical amino acids or chemical amino acid analogs can be introduced as a substitution or addition into the polypeptide sequence. Non-classical amino acids include, but are not limited to, to the D-isomers of the common amino acids, 2,4diaminobutyric acid, alpha-amino isobutyric acid, 4aminobutyric acid, Abu, 2-amino butyric acid, g-Abu, e-Ahx, 6amino hexanoic acid, Aib, 2-amino isobutyric acid, 3-amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, alanine, fluoro-amino acids, designer amino acids such as methyl amino acids, C -methyl amino acids, N-methyl amino acids, and amino acid analogs in general. Furthermore, the amino acid can be D (dextrorotary) or L (levorotary).Methods of Use

[0545] The present application provides methods of treating an inflammatory disorder or disease, 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 certainAOJ-008PCAOE-OIOIWO embodiments, the patient has had moderate-to-severe atopic dermatitis for at least one year. In certain embodiments, the patient has been diagnosed with moderate-to-severe atopic dermatitis and comorbid asthma. In certain embodiments, the patient has been diagnosed with moderate-to-severe atopic dermatitis and a comorbid sinonasal condition. In certain embodiments, the patient is a pediatric patient. In certain embodiments, the patient has a history of inadequate response to treatment with topical medications, or has received a medical determination that topical therapies are inadvisable.

[0546] 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 (also referred to as a vIGA-AD score) of >3 and (c) AD affecting 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 EASI score of >16 and <21. In certain embodiments, the patient has an EASI score of >21 and <48. 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%. In certain embodiments, moderate-to-severe AD is defined as an EASI score of >16, a vIGA-AD score of >3, and AD affecting a body surface area (BSA) of >10%. In certain embodiments, the patient has or has been diagnosed as having moderate AD. In certain embodiments, the patient has or has been diagnosed as having severe AD. In certain embodiments, the patient has a vIGA-AD score of 3. In certain embodiments, the patient has a vIGA-AD score of 4 at Baseline.

[0547] The “Investigator Global Assessment” or “IGA” is an assessment measure used globally to rate the severity of the patient’s AD (Simpson E, el al. J Am Acad Dermatol. 2020;83(3): 839-846). This assessment measure may also be referred to as the Validated Investigator Global Assessment-AD (vIGA-AD). It is based on a 5-point scale ranging from 0 (clear) to 4 (severe) and a 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.

[0548] In one embodiment, the treatment results in a one or more point reduction (e.g., one, two, three, or four point reduction) in vIGA-AD score compared to Baseline. In oneAOJ-008PCAOE-OIOIWO embodiment, the treatment results in a vIGA-AD score of 3 (e.g., for a subject with an initial vIGA-AD score of 4). In one embodiment, the treatment results in a vIGA-AD score of 2. In one embodiment, the treatment results in a vIGA-AD score of 1. In one embodiment, the treatment results in a vIGA-AD score of 0. In one embodiment, the treatment results in a > 2-point reduction from Baseline in vIGA-AD score (e.g., at or though Week 16 or Week 52). In one embodiment, the treatment results in a vIGA-AD score of 0 (clear) or 1 (almost clear) and a > 2-point reduction from Baseline (e.g. , at or though Week 16 or Week 52). In one embodiment, the treatment results in a vIGA-AD score of 0 or 1 with a reduction of at least 2 points from Baseline by Week 4. In one embodiment, the treatment results in a vIGA- AD score of 0 or 1 with a reduction of at least 2 points from Baseline by Week 8. In one embodiment, the treatment results in a vIGA-AD score of 0 or 1 with a reduction of at least 2 points from Baseline by Week 12. In one embodiment, the treatment results in a vIGA-AD score of 0 or 1 with a reduction of at least 2 points from Baseline by Week 16. In one embodiment, treatment results in at least 20%, at least 30%, at least 40%, or at least 50%, of patients achieving a vIGA-AD score of 0 or 1 with a reduction of at least 2 points from Baseline (e.g., after 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and / or 52 weeks of treatment). In one embodiment, treatment results in at least 30% of patients achieving a vIGA-AD score of 0 or 1 with a reduction of at least 2 points from Baseline (e.g., by Week 16).

[0549] The “Eczema Area and Severity Index” or “EASI i...

Claims

1. AOJ-008PCAOE-OIOIWOClaims1. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) five induction doses of 720 mg of the anti-IL-13 antibody; and b) one or more maintenance doses of 360 mg of the anti-IL-13 antibody administered starting at about 24 weeks or more after the first induction dose, wherein the anti-IL-13 antibody comprises a heavy chain variable region (VH) comprising an amino acid sequence as set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence as set forth in SEQ ID NO: 39.

2. The method of claim 1 , wherein the second induction dose is administered about 2 weeks after the first induction dose.

3. The method of claim 1 or 2, wherein the third induction dose is administered about 2 weeks after the second induction dose.

4. The method of any one of claims 1-3, wherein the fourth induction dose is administered about 4 weeks after the third induction dose.

5. The method of any one of claims 1-4, wherein the fifth induction dose is administered about 4 weeks after the fourth induction dose.

6. The method of any one of claims 1-5, wherein the maintenance dose is administered every 3 months or every 12 weeks.

7. The method of any one of claims 1-5, wherein the maintenance dose is administered every 6 months or every 24 weeks.

8. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) two loading doses of 720 mg of an anti-IL-13 antibody prior to two induction doses; b) two induction doses of 360 mg of the anti-IL-13 antibody; andAOJ-008PCAOE-OIOIWO c) one or more maintenance doses of 360 mg of the anti-IL-13 antibody administered starting at about 12 weeks or 20 weeks or more after the first induction dose, wherein the anti-IL-13 antibody comprises a heavy chain variable region (VH) comprising an amino acid sequence as set forth in SEQ ID NO: 3 and a light chain variable region (VL) comprising an amino acid sequence as set forth in SEQ ID NO: 39.

9. The method of claim 8, wherein the second loading dose is administered about 2 weeks after the first loading dose.

10. The method of claim 8 or 9, wherein the first induction dose is administered about 2 weeks after the second loading dose.

11. The method of any one of claims 8-10, wherein the second induction dose is administered about 8 weeks after the first induction dose.

12. The method of any one of claims 8-11, wherein the maintenance dose is administered every 3 months or every 12 weeks.

13. The method of any one of claims 8-11, wherein the maintenance dose is administered every 6 months or every 24 weeks.

14. The method of any one of claims 8-13, wherein the maintenance dose is administered starting at about 20 weeks after the first induction dose.

15. The method of any one of claims 1-14, wherein each dose is administered as a composition comprising 150 mg / mL, 180 mg / mL, or 200 mg / mL of the anti-IL-13 antibody.

16. The method of claim 15, wherein the composition is a unit dose with an extractable volume of 1 mL, 2 mL, 2.25 mL, 2.7 mb, 3 mL, 4 mL or 5 mL.

17. The method of claim 16, wherein the composition is a unit dose with an extractable volume of 2 mL.AOJ-008PCAOE-OIOIWO18. The method of any one of claims 1-17, wherein the patient has been diagnosed with moderate-to-severe atopic dermatitis.

19. The method of any one of claims 1-18, wherein the patient has had moderate-to-severe atopic dermatitis for at least one year.

20. The method of any one of claims 1-18, wherein the patient has one or more of:(a) an Eczema Area and Severity Index Score (EASI) of >10,(b) an Investigator Global Assessment (IGA) score of >3 and(c) a body surface area (BSA) of >10%.

21. The method of any one of claims 1-20, further comprising 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), validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), Itch Numerical Rating Scale (I-NRS), Skin Pain Numerical Rating Scale (SP-NRS), Atopic Dermatitis Sleep Scale (ADSS), Sleep loss scale, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Asthma Control Questionnaire 5-item version (ACQ-5), and Sino-nasal Outcome Test 22-item version (SNOT-22).

22. The method of any one of claims 1-21, wherein the anti-IL-13 antibody further comprises a heavy chain constant region of SEQ ID NO: 439 or SEQ ID NO: 624 or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity thereto.

23. The method of any one of claims 1-22, wherein the anti-IL-13 antibody further comprises a light chain constant region of SEQ ID NO: 469 or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity thereto.

24. The method of any one of claims 1-23, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO25. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 240 mg to about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.

26. The method of claim 25, wherein the method comprises administering about 240 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

27. The method of claim 25, wherein the method comprises administering about 260 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

28. The method of claim 25, wherein the method comprises administering about 280 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

29. The method of claim 25, wherein the method comprises administering about 300 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

30. The method of claim 25, wherein the method comprises administering about 320 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

31. The method of claim 25, wherein the method comprises administering about 340 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

32. The method of claim 25, wherein the method comprises administering about 360 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.AOJ-008PCAOE-OIOIWO33. The method of claim 25, wherein the method comprises administering about 380 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

34. The method of claim 25, wherein the method comprises administering about 395 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

35. The method of claim 25, wherein the method comprises administering about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

36. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 240 mg to about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.

37. The method of claim 36, wherein the method comprises administering about 240 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

38. The method of claim 36, wherein the method comprises administering about 260 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

39. The method of claim 36, wherein the method comprises administering about 280 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

40. The method of claim 36, wherein the method comprises administering about 300 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

41. The method of claim 36, wherein the method comprises administering about 320 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.AOJ-008PCAOE-OIOIWO42. The method of claim 36, wherein the method comprises administering about 340 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

43. The method of claim 36, wherein the method comprises administering about 360 mg of the anti-IL- 13 antibody every 12 weeks (Q12W) starting at Week 24.

44. The method of claim 36, wherein the method comprises administering about 380 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

45. The method of claim 36, wherein the method comprises administering about 395 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

46. The method of claim 36, wherein the method comprises administering about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

47. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 240 mg to about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.

48. The method of claim 47, wherein the method comprises administering about 240 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

49. The method of claim 47, wherein the method comprises administering about 260 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.AOJ-008PCAOE-OIOIWO50. The method of claim 47, wherein the method comprises administering about 280 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

51. The method of claim 47, wherein the method comprises administering about 300 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

52. The method of claim 47, wherein the method comprises administering about 320 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

53. The method of claim 47, wherein the method comprises administering about 340 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

54. The method of claim 47, wherein the method comprises administering about 360 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

55. The method of claim 47, wherein the method comprises administering about 380 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

56. The method of claim 47, wherein the method comprises administering about 395 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

57. The method of claim 47, wherein the method comprises administering about 480 mg of the anti-IL-13 antibody every 12 weeks (Q12W) starting at Week 24.

58. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 720 mg of an anti-IL-13 antibody at Week 0 and Week 2; b) 360 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg to about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.AOJ-008PCAOE-OIOIWO59. The method of claim 58, wherein the method comprises administering about 480 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

60. The method of claim 58, wherein the method comprises administering about 520 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) starting at Week 24.

61. The method of claim 58, wherein the method comprises administering about 560 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

62. The method of claim 58, wherein the method comprises administering about 600 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

63. The method of claim 58, wherein the method comprises administering about 640 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

64. The method of claim 58, wherein the method comprises administering about 680 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

65. The method of claim 58, wherein the method comprises administering about 720 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

66. The method of claim 58, wherein the method comprises administering about 760 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

67. The method of claim 58, wherein the method comprises administering about 790 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

68. The method of claim 58, wherein the method comprises administering about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

69. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient:AOJ-008PCAOE-OIOIWO a) 720 mg of an anti-IL-13 antibody at Week 0, Week 2, Week 4, Week 8, and Week 12; and b) about 480 mg to about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.

70. The method of claim 69, wherein the method comprises administering about 480 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

71. The method of claim 69, wherein the method comprises administering about 520 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

72. The method of claim 69, wherein the method comprises administering about 560 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

73. The method of claim 69, wherein the method comprises administering about 600 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

74. The method of claim 69, wherein the method comprises administering about 640 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

75. The method of claim 69, wherein the method comprises administering about 680 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

76. The method of claim 69, wherein the method comprises administering about 720 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

77. The method of claim 69, wherein the method comprises administering about 760 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.AOJ-008PCAOE-OIOIWO78. The method of claim 69, wherein the method comprises administering about 790 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

79. The method of claim 69, wherein the method comprises administering about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

80. A method of treating atopic dermatitis in a patient in need thereof, the method comprising subcutaneously administering to the patient: a) 360 mg of an anti-IL-13 antibody at Week 0; b) 180 mg of the anti-IL-13 antibody at Week 4 and Week 12; and c) about 480 mg to about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24, wherein the anti-IL-13 antibody comprises a VH sequence set forth in SEQ ID NO: 3, a VL sequence set forth in SEQ ID NO: 39, a constant heavy chain sequence set forth in SEQ ID NO: 624, and a constant light chain sequence set forth in SEQ ID NO: 469.

81. The method of claim 80, wherein the method comprises administering about 480 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

82. The method of claim 80, wherein the method comprises administering about 520 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

83. The method of claim 80, wherein the method comprises administering about 560 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

84. The method of claim 80, wherein the method comprises administering about 600 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

85. The method of claim 80, wherein the method comprises administering about 640 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

86. The method of claim 80, wherein the method comprises administering about 680 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.AOJ-008PCAOE-OIOIWO87. The method of claim 80, wherein the method comprises administering about 720 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

88. The method of claim 80, wherein the method comprises administering about 760 mg of the anti-IL- 13 antibody every 24 weeks (Q24W) starting at Week 24.

89. The method of claim 80, wherein the method comprises administering about 790 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

90. The method of claim 80, wherein the method comprises administering about 960 mg of the anti-IL-13 antibody every 24 weeks (Q24W) starting at Week 24.

91. The method of any one of claims 25-90, wherein the patient has been diagnosed with moderate-to-severe atopic dermatitis.

92. The method of any one of claims 25-91, wherein the patient has had moderate-to-severe atopic dermatitis for at least one year.

93. The method of any one of claims 25-92, wherein the patient has one or more of:(a) an Eczema Area and Severity Index Score (EASI) of >16,(b) an Investigator Global Assessment (IGA) score of >3 and(c) a body surface area (BSA) of >10%.

94. The method of any one of claims 25-93, further comprising determining one or more of the following characteristics of the patient at baseline and during and after Weeks 0-16 of treatment: Eczema Area and Severity Index (EASI), validated Investigator Global Assessment (vIGA or vIGA-AD), Body Surface Area (BSA), Itch Numerical Rating Scale (I- NRS), Skin Pain Numerical Rating Scale (SP-NRS), Atopic Dermatitis Sleep Scale (ADSS), Sleep loss scale, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Asthma Control Questionnaire 5-item version (ACQ-5), and Sino-nasal Outcome Test 22-item version (SNOT-22).AOJ-008PCAOE-OIOIWO95. The method of any one of claims 25-94, wherein the anti-IL-13 antibody is administered in a composition comprising 150 mg / mL, 180 mg / mL, or 200 mg / mL of the anti-IL-13 antibody.

96. The method of claim 95, wherein the composition is a unit dose with an extractable volume of 1 mL, 2 mL, 2.25 mL, 2.7 mL, 3 mL, 4 mL or 5 mL.

97. The method of claim 96, wherein the composition is a unit dose with an extractable volume of 2 mL.

98. The method of any one of claims 1-97, wherein the anti-IL-13 antibody is administered using an autoinjector.

99. The method of any one of claims 1-97, wherein the anti-IL-13 antibody is administered using a pre-filled syringe.

100. The method of any one of claims 1-99, wherein the patient has been diagnosed with moderate-to-severe atopic dermatitis and comorbid asthma.

101. The method of any one of claims 1-100, wherein the patient has been diagnosed with moderate-to-severe atopic dermatitis and a comorbid sinonasal condition.

102. The method of any one of claims 1-101, wherein the patient has an EASI score of >16, a vIGA-AD score of >3, and AD affecting >10% BSA.

103. The method of any one of claims 1-102, wherein the anti-IL-13 antibody comprises a heavy chain sequence set forth in SEQ ID NO: 710 and a light chain sequence set forth in SEQ ID NO: 712.

104. The method of any one of claims 1-103, wherein the treatment inhibits phosphorylated Signal Transducer and Activator of Transcription 6 (pSTAT6).AOJ-008PCAOE-OIOIWO105. The method of claim 104, wherein the treatment results in sustained inhibition of pSTAT6 for at least 6 months after administration of one or more doses of the anti-IL-13 antibody.

106. The method of claim 105, wherein the treatment results in sustained inhibition of pSTAT6 for at least 9 months after administration of one or more doses of the anti-IL-13 antibody.

107. The method of claim 106, wherein the treatment results in sustained inhibition of pSTAT6 for at least 11 months after administration of one or more doses of the anti-IL-13 antibody.

108. The method of any one of claims 1-107, wherein the treatment inhibits thymus and activation-regulated chemokine (TARC).

109. The method of claim 108, wherein the treatment results in sustained inhibition of TARC for at least 6 months after administration of one or more doses of the anti-IL-13 antibody.

110. The method of claim 109, wherein the treatment results in sustained inhibition of TARC for at least 9 months after administration of one or more doses of the anti-IL-13 antibody.

111. The method of claim 110, wherein the treatment results in sustained inhibition of TARC for at least 11 months after administration of one or more doses of the anti-IL-13 antibody.

112. The method of any one of claims 1-111, wherein the treatment results in a decrease in EASI from Baseline of at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% after 16 weeks of treatment.

113. The method of claim 112, wherein the treatment results in a decrease in EASI from Baseline of at least 70%.

114. The method of any one claims 1-113, wherein the treatment results in achievement of EASI-75 after 2 weeks, 4 weeks, 8 weeks, 12 weeks, and / or 16 weeks of treatment.AOJ-008PCAOE-OIOIWO115. The method of any one of claims 1-1 14, wherein the treatment results in a vIGA-AD of 0 or 1 with a reduction of at least 2 points from Baseline after 2 weeks, 4 weeks, 8 weeks, 12 weeks, and / or 16 weeks of treatment.

116. The method of any one of claims 1-1 15, wherein the treatment results in a decrease in Itch NRS from Baseline after 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and / or 16 weeks of treatment.

117. The method of any one of claims 1-116, wherein the treatment results in a decrease in Itch NRS from Baseline of at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%.

118. The method of claim 117, wherein the treatment results in a decrease in Itch NRS from Baseline of at least 50%.

119. The method of any one of claims 1-118, wherein the treatment results in an Itch NRS reduction of at least 4 points from Baseline after 2 weeks, 4 weeks, 8 weeks, 12 weeks and / or 16 weeks of treatment.

120. The method of any one of claims 1-119, wherein the treatment results in a reduction in Body Surface Area (BSA) involvement from Baseline.

121. The method of any one of claims 1-120, wherein the treatment results in a reduction in the weekly mean of the daily ADSS for Item 1 and / or Item 2 from Baseline.

122. The method of any one of claims 1-121, wherein the treatment results in a reduction in the weekly mean of the daily SP-NRS from Baseline.

123. The method of any one of claims 1-122, wherein the treatment results in a reduction in POEM score compared to Baseline.AOJ-008PCAOE-OIOIWO124. The method of any one of claims 1-123, wherein the treatment results in an at least 3- point improvement in POEM total score from Baseline.

125. The method of any one of claims 1-124, wherein the treatment results in a reduction in DLQI compared to Baseline.

126. The method of any one of claims 1-125, wherein the treatment results in an at least 4-point improvement in DLQI from Baseline.

127. The method of any one of claims 1-126, wherein the treatment results in a reduction in serum IL- 13 levels.

128. The method of any one of claims 1-127, wherein the treatment results in a reduction in serum IgE levels.

129. The method of any one of claims 1-128, wherein the treatment results in a reduction in serum eotaxin-3 levels.

130. The method of any one of claims 1-129, wherein the treatment results in a reduction in serum IL-17C levels.

131. The method of any one of claims 1-130, wherein the treatment results in a reduction in serum IL- 19 levels.

132. The method of any one of claims 1-131, wherein the treatment results in a reduction in serum periostin levels.

133. The method of any one of claims 1-132, wherein the treatment results in a reduction in serum PARC levels.

134. The method of any one of claims 1-133, wherein the treatment results in a reduction in serum LDH levels.AOJ-008PCAOE-OIOIWO135. The method of any one of claims 1-134, wherein the treatment results in an EASI score of 7 or less or an I-NRS score of 4 or less.

136. The method of any one of claims 1-135, wherein the treatment results in an EASI score of 7 or less and an I-NRS score of 4 or less.

137. The method of any one of claims 1-136, wherein the treatment results in itch relief within the first week of treatment.

138. The method of any one of claims 1-137, wherein the treatment results in itch relief within 48 hours of the first dose of the anti-IL- 13 antibody.

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