Anti-tl1a antibody compositions and methods of treatment for sarcoidosis

Abstract

Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of sarcoidosis.

Description

25746 ANTI-TL1A ANTIBODY COMPOSITIONS AND METHODS OF TREATMENT FOR SARCOIDOSIS CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S Provisional Application No. 63 / 489,411 filed March 9, 2023. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML file, created on January 24, 2024 is named 25746-WO-PCT_SL.xml and is 387,830 bytes in size. BACKGROUND

[0003] Sarcoidosis is a disease characterized by the growth of aggregations of inflammatory cells in parts of patients’ body, most commonly in the lungs, lymph nodes and skin, and presents itself as small patches of swollen tissue, called granulomas, in these affected organs of the body. Sarcoidosis in the lung is known as pulmonary sarcoidosis. Sarcoidosis in the skin is known as cutaneous sarcoidosis. In some estimates, 9 out of 10 sarcoidosis patients develop pulmonary sarcoidosis, the symptoms of which include shortness of breath and a persistent dry cough and may also include pain and discomfort in their chest. The cutaneous sarcoidosis further includes lupus pernio, papular sarcoidosis, nodular sarcoidosis, subcutaneous sarcoidosis (also known and referred to herein as Darier-Roussy sarcoidosis), maculopapular sarcoidosis, plaque sarcoidosis, hypopigmented sarcoidosis, and atrophic and ulcerative sarcoidosis. Plaque sarcoidosis further includes angiolupoid sarcoidosis, psoriasiform sarcoidosis, and verrucous sarcoidosis. Other sarcoidosis includes neurologic sarcoidosis, cardiac sarcoidosis, gastrointestinal sarcoidosis, hepatic sarcoidosis, pancreatic sarcoidosis, peritoneal sarcoidosis, sarcoidosis of bone, sarcoid arthropathy, ichthyosiform sarcoidosis, erythrodermic sarcoidosis, and perforating sarcoidosis.

[0004] Sarcoidosis, including pulmonary sarcoidosis and cutaneous sarcoidosis, among others, is currently treated with over the counter painkillers, and in some instances, with steroids. However, steroids can cause side effects such as weight gain and mood swings if taken in high doses, and osteoporosis, if taken for a prolonged periods of time.

[0005] Therefore, there is an unmet need for novel treatment for sarcoidosis, including pulmonary sarcoidosis. SUMMARY

[0006] The disclosure provides that an anti-TL1A antagonistic monoclonal antibody provided herein can treat sarcoidosis, including pulmonary sarcoidosis and / or cutaneous sarcoidosis.

[0007] The present disclosure provides tumor necrosis factor ligand 1A (TL1A) binding antibodies and compositions thereof for the treatment of sarcoidosis, including pulmonary sarcoidosis and / or cutaneous sarcoidosis. In various aspects, antibodies described herein possess features useful for therapeutic application such as low immunogenicity, and / or features that facilitate antibody manufacture, such as high percentage of monomeric fraction as measured by size-exclusion chromatography, and / or high expression. In further aspects, antibodies described herein possess features useful for subcutaneous administration, such as low viscosity at high antibody concentration. Further aspects of the antibodies and antibody formulations may include high solubility, low subvisible particles, low opalescence, no visible particulates, and any combination thereof.

[0008] In one aspect, provided herein is a method of treating sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen- binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen binding fragment).

[0009] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is pulmonary sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is cutaneous sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the cutaneous sarcoidosis is lupus pernio, papular sarcoidosis, nodular sarcoidosis, Darier-Roussy sarcoidosis, maculopapular sarcoidosis, plaque sarcoidosis, hypopigmented sarcoidosis, or atrophic and ulcerative sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is neurologic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is cardiac sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is gastrointestinal sarcoidosis. In some embodiments of the various methods provided herein,including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is hepatic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is pancreatic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is peritoneal sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is sarcoidosis of bones. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is sarcoid arthropathy. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is plaque sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the plaque sarcoidosis is angiolupoid sarcoidosis, psoriasiform sarcoidosis, or verrucous sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is ichthyosiform sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is erythrodermic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is perforating sarcoidosis.

[0010] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody or antigen binding fragment is administered in a pharmaceutical composition.

[0011] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration greater than about 150 mg / mL.

[0012] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration greater than about 160 mg / ml, about 165 mg / ml, about 170 mg / ml, about 175 mg / ml, about 180 mg / ml, about 185 mg / ml, about 190 mg / ml, about 195 mg / ml, about 200 mg / ml, about 205 mg / ml, about 210 mg / ml, about 215 mg / ml, about 220 mg / ml, about 225 mg / ml, about 230 mg / ml, about 235 mg / ml, about 240 mg / ml, about 245 mg / ml, or about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration about 125 mg / mL to about 175 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 225 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 225 mg / mL, about 150 mg / mL to about 250 mg / mL, about 175mg / mL to about 225 mg / mL, about 175 mg / mL to about 250 mg / mL, about 175 mg / mL to about 275 mg / mL, about 200 mg / mL to about 250 mg / mL, or about 200 mg / mL to about 275 mg / mL.

[0013] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition is administered subcutaneously.

[0014] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition is administered intravenously.

[0015] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition comprises about 150 mg to about 1000 mg of the anti-TL1A antibody or antigen binding fragment. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition has a total volume of less than or equal to about 2 mL, about 1.9 ml, about 1.8 ml, about 1.7 ml, about 1.6 ml, about 1.5 ml, about 1.4 ml, about 1.3 ml, about 1.2 ml, about 1.1 ml, about 1.0 ml, about 0.9 ml, or about 0.8 mL.

[0016] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition comprises a therapeutically effective dose of the anti-TL1A antibody or antigen binding fragment.

[0017] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition has a viscosity of less than about 20cP, less than about 19cP, less than about 18cP, less than about 17cP, less than about 16cP, less than about 15cP, less than about 14cP, less than about 13cP, less than about 12cP, less than about 11cP, less than about 10cP, less than about 9cP, less than about 8cP, less than about 7cP, less than about 6cP, or less than about 5 cP.

[0018] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the pharmaceutical composition comprises a surfactant, a salt, a stabilizer, and / or a buffering agent. In some embodiments, the surfactant comprises polysorbate-20, and wherein optionally the surfactant is present at a concentration of about 0.02% in the pharmaceutical composition. In some embodiments, the salt comprises NaCl, and wherein optionally the NaCl is at a concentration of about 40 mM in the pharmaceutical composition. In some embodiments, the stabilizer comprises sucrose, wherein optionally the sucrose is at a concentration of about 220 mM in the pharmaceutical composition. In some embodiments, the buffering agent comprises sodium acetate, wherein optionally the sodiumacetate is at a concentration of about 20 mM in the pharmaceutical composition. In some embodiments, the pharmaceutical composition has a pH of about 5.3.

[0019] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody or antigen binding fragment is administered to the subject at a first dose up to about 1000 mg. In some embodiments, the anti-TL1A antibody or antigen binding fragment is administered to the subject at a first dose of about 500 mg.

[0020] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody or antigen binding fragment is administered to the subject at a second dose up to about 1000 mg. In some embodiments, the anti-TL1A antibody or antigen binding fragment is administered to the subject at a second dose of about 500 mg.

[0021] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the first dose is administered to the subject at a first time point, and the second dose is administered to the subject at a second time point. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the first dose and the second dose is different or wherein the first dose and the second dose is identical. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the second time point is about 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, or 31 days after the first time point.

[0022] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody or antigen binding fragment is administered to the subject at an induction regimen. In some embodiments, the induction regimen comprises 500 mg / dose once every 4 weeks.

[0023] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody or antigen binding fragment is administered to the subject at a maintenance regimen. In some embodiments, the maintenance regimen comprises 500 mg / dose once every 4 weeks.

[0024] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen and the maintenance regimen are identical. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen and the maintenance regimen are different.

[0025] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen is about 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, or 31 days after the induction regimen.

[0026] In one aspect, provided herein is a method of neutralizing monomeric TL1A and trimeric TL1A in a subject having sarcoidosis comprising (a) administering an effective dose of anti-TL1A antibody or antigen binding fragment to the subject, wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A, wherein the antibody or antigen binding fragment blocks interaction of TL1A to DR3, wherein the concentration of TL1A in a diseased tissue in the subject is reduced below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, and wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

[0027] In one aspect, provided herein is a method of reducing the concentration of TL1A in a diseased tissue in a subject with sarcoidosis comprising (a) administering an effective dose of anti-TL1A antibody or antigen binding fragment to the subject, thereby reducing the concentration of TL1A in the diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other and tissues afflicted by sarcoidosis.

[0028] In one aspect, provided herein is a method of treating sarcoidosis in a subject in need thereof comprising (a) administering an anti-TL1A antibody or antigen binding fragment to the subject, wherein the anti-TL1A antibody or antigen binding fragment is administered at an effective dose such that the concentration of TL1A in a diseased tissue in the subject after step (a) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, and wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

[0029] In one aspect, provided herein is a method of treating sarcoidosis in a subject in need thereof comprising (a) administering an anti-TL1A antibody or antigen binding fragment to the subject at an effective dose, and (b) reducing the concentration of TL1A in a diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in acontrol subject without sarcoidosis, wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

[0030] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is pulmonary sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is cutaneous sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the cutaneous sarcoidosis is lupus pernio, papular sarcoidosis, nodular sarcoidosis, Darier-Roussy sarcoidosis, maculopapular sarcoidosis, plaque sarcoidosis, hypopigmented sarcoidosis, or atrophic and ulcerative sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is neurologic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is cardiac sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is gastrointestinal sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is hepatic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is pancreatic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is peritoneal sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is sarcoidosis of bones. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is sarcoid arthropathy. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is plaque sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the plaque sarcoidosis is angiolupoid sarcoidosis, psoriasiform sarcoidosis, or verrucous sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is ichthyosiform sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is erythrodermic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is perforating sarcoidosis.

[0031] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the effective dose comprises an induction regimen.

[0032] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the method further comprises (c) maintaining TL1A in the diseased tissue in the subject at a concentration below the concentration of TL1A in the corresponding tissue in the control subject. In some embodiments, the TL1A in the diseased tissue in the subject is maintained with a maintenance regimen of the anti-TL1A antibody or antigen binding fragment.

[0033] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen and the maintenance regimen are identical.

[0034] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen and the maintenance regimen are different.

[0035] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen is administered after the induction regimen.

[0036] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject during the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject.

[0037] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises a one-time administration of the anti-TL1A antibody or antigen binding fragment. In some embodiments, the one-time administration of the anti-TL1A antibody or antigen binding fragment comprises an administration at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 120025746 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

[0038] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

[0039] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or (v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

[0040] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

[0041] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administration once every 2, 4, 6, or 8 weeks. In some embodiments, the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

[0042] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.25746

[0043] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

[0044] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0045] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

[0046] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

[0047] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

[0048] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

[0049] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.25746

[0050] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A and wherein the antibody or antigen binding fragment blocks binding of TL1A to DR3. In some embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment. In some embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment.

[0051] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the binding affinity of the antibody or antigen binding fragment to monomeric TL1A as measured by dissociation equilibrium constant (KD- monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1A as measured by dissociation equilibrium constant (KD-trimer).

[0052] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the KD-monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD-trimer. In some embodiments, the KD-monomer is no more than 0.06 nM. In some embodiments, the KD-trimer is no more than 0.06 nM.

[0053] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the effective dose or the induction regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the effective dose or the induction regimen such that the concentration of TL1A in diseased tissue in the subject after step (a) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis

[0054] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold over-production comparing to TL1A production in the normal reference tissue.25746

[0055] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (ii) integrating the parameter received in (i) to an integrated whole- body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the maintenance regimen such that the concentration of TL1A in diseased tissue in the subject after step (c) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis.

[0056] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more fold over-production comparing to TL1A production in the normal reference tissue.

[0057] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the step (i) in the dose determination method further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1A in normal tissue (ksyn-normal), synthesis rate of TL1A in diseased tissue (ksyn-disease), and / or degradation rate of TL1A (kdeg-total-TL1A).

[0058] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the association rate of the antibody to TL1A (kon-mAb) comprises the association rate of the antibody to monomeric TL1A (kon-monomer) and association rate of the antibody to trimeric TL1A (kon-trimer), wherein the dissociation rate of the antibody from TL1A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff-monomer) and dissociation rate of the antibody from trimeric TL1A (koff-trimer), and / or wherein the degradation rate of TL1A (kdeg-total-TL1A) comprises degradation rate of monomeric TL1A (kdeg-TL1A-monomer) and degradation rate of trimeric TL1A (kdeg-TL1A-trimer).

[0059] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the step (i) in the dose determination method further comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn), and / or dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn).25746

[0060] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] ,, the association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn) comprises association rate of the antibody-monomeric-TL1A complex to FcRn receptor (kon-(mAb-monoTL1A)-FcRn) and association rate of the antibody- trimeric-TL1A complex to FcRn receptor (kon-(mAb-triTL1A)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn) comprises dissociation rate of the antibody-monomeric-TL1A complex from FcRn (koff-(mAb-monoTL1A)-FcRn) and dissociation rate of the antibody-trimeric-TL1A complex from FcRn (koff-(mAb-triTL1A)-FcRn).

[0061] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the step (i) in the dose determination method further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn).

[0062] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) comprises clearance rate of the antibody to FcRn bound by the antibody- monomeric-TL1A complex (kdeg-(mAb-monoTL1A)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TL1A complex (kdeg-(mAb-triTL1A)-FcRn).

[0063] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , in the dose determination method: (1) kon-monomerand kon-trimerare identical or different; (2) koff-monomer and koff-trimer are identical or different; (3) kdeg-monomer and kdeg-trimerare identical or different; (4) kon-(mAb-monoTL1A)-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (5) kon-mAb-FcRn and kon-(mAb-monoTL1A)-FcRn are identical or different; (6) kon-mAb-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (7) koff-(mAb-monoTL1A)-FcRnand koff-(mAb-triTL1A)-FcRn are identical or different; (8) koff- mAb-FcRn and koff-(mAb-monoTL1A)-FcRn are identical or different; (9) koff- mAb-FcRnand koff-(mAb-triTL1A)-FcRnare identical or different; (10) kdeg-(mAb-monoTL1A)-FcRn and kdeg-(mAb-triTL1A)-FcRn are identical or different; (11) kdeg-mAb-FcRn and kdeg-(mAb-triTL1A)-FcRnare identical or different; (12) kdeg-mAb-FcRnand kdeg-(mAb-monoTL1A)-FcRnare identical or different; or (13) any combination of (1) to (12).

[0064] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , in the dose determination method: ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn-normal.

[0065] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the step (i) in the dose determination method further25746 comprises receiving rate of TL1A trimerization (kon-TL1A-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TL1A-trimer-to-monomer).

[0066] In one aspect, provided herein is a method of determining an effective dose regimen for administering an anti-TL1A antibody to a subject having sarcoidosis, wherein the method comprises: (a) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (b) integrating the parameter received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model; and (c) determining the effective dose regimen of the anti-TL1A antibody with the PBPK model from (b) such that after administration of the effective dose regimen the concentration of TL1A in a diseased tissue in the subject having sarcoidosis is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other tissues with sarcoidosis, and other tissues of pathogenesis for the sarcoidosis.

[0067] In one aspect, provided herein is a method of determining an effective dose regimen for administering an anti-TL1A antibody to a subject having sarcoidosis, wherein the method comprises: (a) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (b) integrating the parameter received in (a) to a population pharmacokinetic (popPK) model; and (c) determining the effective dose regimen of the anti-TL1A antibody with the popPK model from (b) such that after administration of the effective dose regimen the concentration of TL1A in a diseased tissue in the subject having sarcoidosis is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other tissues with sarcoidosis, and other tissues of pathogenesis for the sarcoidosis.

[0068] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is pulmonary sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is cutaneous sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the cutaneous sarcoidosis is lupus pernio, papular sarcoidosis, nodular sarcoidosis, Darier-Roussy sarcoidosis, maculopapular sarcoidosis, plaque sarcoidosis, hypopigmented sarcoidosis, or atrophic and ulcerative sarcoidosis. In some embodiments of the various methods provided25746 herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is neurologic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is cardiac sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is gastrointestinal sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is hepatic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is pancreatic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is peritoneal sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is sarcoidosis of bones. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is sarcoid arthropathy. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is plaque sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the plaque sarcoidosis is angiolupoid sarcoidosis, psoriasiform sarcoidosis, or verrucous sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is ichthyosiform sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is erythrodermic sarcoidosis. In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the sarcoidosis is perforating sarcoidosis.

[0069] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more fold over-production comparing to TL1A production in the normal reference tissue.

[0070] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the step (a) further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1A in normal tissue (ksyn-normal), synthesis rate of TL1A in diseased tissue (ksyn-disease), and / or degradation rate of TL1A (kdeg-total-TL1A).25746

[0071] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the association rate of the antibody to TL1A (kon-mAb) comprises the association rate of the antibody to monomeric TL1A (kon-monomer) and association rate of the antibody to trimeric TL1A (kon-trimer), wherein the dissociation rate of the antibody from TL1A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff-monomer) and dissociation rate of the antibody from trimeric TL1A (koff-trimer), and / or wherein the degradation rate of TL1A (kdeg-total-TL1A) comprises degradation rate of monomeric TL1A (kdeg-TL1A-monomer) and degradation rate of trimeric TL1A (kdeg-TL1A-trimer).

[0072] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the step (a) comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody-TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn), and / or dissociation rate of the antibody-TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn).

[0073] In some embodiments of the various methods provided herein, including in Sections2,

[0456] , and

[0551] , the association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn) comprises association rate of the antibody-monomeric-TL1A complex to FcRn receptor (kon-(mAb-monoTL1A)-FcRn) and association rate of the antibody- trimeric-TL1A complex to FcRn receptor (kon-(mAb-triTL1A)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn) comprises dissociation rate of the antibody-monomeric-TL1A complex from FcRn (koff-(mAb-monoTL1A)-FcRn) and dissociation rate of the antibody-trimeric-TL1A complex from FcRn (koff-(mAb-triTL1A)-FcRn).

[0074] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the step (a) further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn).

[0075] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) further comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TL1A complex (kdeg-(mAb-monoTL1A)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TL1A complex (kdeg-(mAb-triTL1A)-FcRn).

[0076] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , (1) kon-monomer and kon-25746 trimer are identical or different; (2) koff-monomer and koff-trimer are identical or different; (3) kdeg-monomerand kdeg-trimerare identical or different; (4) kon-(mAb-monoTL1A)-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (5) kon-mAb-FcRn and kon-(mAb-monoTL1A)-FcRn are identical or different; (6) kon-mAb-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (7) koff-(mAb-monoTL1A)-FcRnand koff-(mAb-triTL1A)-FcRn are identical or different; (8) koff- mAb-FcRn and koff-(mAb-monoTL1A)-FcRn are identical or different; (9) koff- mAb-FcRnand koff-(mAb-triTL1A)-FcRnare identical or different; (10) kdeg-(mAb-monoTL1A)-FcRn and kdeg-(mAb-triTL1A)-FcRn are identical or different; (11) kdeg-mAb-FcRn and kdeg-(mAb-triTL1A)-FcRnare identical or different; (12) kdeg-mAb-FcRnand kdeg-(mAb-monoTL1A)-FcRnare identical or different; or (13) any combination of (1) to (12).

[0077] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn-normal.

[0078] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the effective dose regimen comprises an induction regimen of the anti-TL1A antibody or antigen binding fragment.

[0079] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the effective dose regimen comprises a maintenance regimen of the anti-TL1A antibody or antigen binding fragment.

[0080] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen and the maintenance regimen are identical.

[0081] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen and the maintenance regimen are different.

[0082] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen is administered after the induction regimen.

[0083] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject during the induction regimen. In some25746 embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

[0084] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject.

[0085] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises a one-time administration of the anti-TL1A antibody or antigen binding fragment. In some embodiments, the one-time administration of the anti-TL1A antibody or antigen binding fragment comprises an administration at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

[0086] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

[0087] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or (v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

[0088] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.25746

[0089] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

[0090] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

[0091] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

[0092] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

[0093] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

[0094] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 15025746 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0095] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

[0096] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

[0097] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

[0098] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] . the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

[0099] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

[0100] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the effective dose regimen maintains the concentration of TL1A in diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis for at least 4 weeks, 8 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 2 years, and longer.

[0101] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , at least 91%, at least25746 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment during the effective dose regimen. In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment during the effective dose regimen.

[0102] In some embodiments of the various methods of determining an effective dose regimen provided herein, including in Sections 2,

[0456] , and

[0551] , the step (a) further comprises receiving the rate of TL1A trimerization (kon-TL1A-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TL1A-trimer-to-monomer).

[0103] In some methods of determining an effective doseregimen provided 2,

[0456] , and

[0551] , the concentration of TL1A is the concentration of free TL1A.

[0104] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6- 9; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10, an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15. In some cases, the anti-TL1A antibody comprises the CDRs of antibody J of Table 10. In some cases, the anti-TL1A antibody comprises the CDRs of antibody J2 of Table 10. In some cases, the anti-TL1A antibody comprises the CDRs of antibody K of Table 10.

[0105] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody comprises, a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively25746 comprise no or fewer than nine amino acid modification(s) from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

[0106] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 201-220. In some cases, the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 420, and a light chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 430. In some cases, the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 421, and a light chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 431. In some cases, the anti-TL1A antibody comprises a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 423, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 433. In some cases, the anti-TL1A antibody comprises a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 424, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434.

[0107] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody comprises a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDR FSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein HCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 1, HCDR2 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, HCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 6-9, LCDR125746 comprises an amino acid sequence set forth by SEQ ID NO: 10, LCDR2 comprises an amino acid sequence set forth by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 12 or 13. In some cases, the anti-TL1A antibody comprises the CDRs of antibody J of Table 10. In some cases, the anti-TL1A antibody comprises the CDRs of antibody J2 of Table 10. In some cases, the anti-TL1A antibody comprises the CDRs of antibody K of Table 10.

[0108] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 401, 407, 413, or 450, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 402, 408, 414, or 451, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 403, 409, 415, or 452; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 404, 410, 416, or 453, an LCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 405, 411, 417, or 454, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 406, 412, 418, or 455.

[0109] In some embodiments of the various methods provided herein, including in Sections 2,

[0456] , and

[0551] , the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 420-427, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 430-437.

[0110] Additional numbered embodiments are provided in the below paragraphs of this section.

[0111] Embodiment 1. An antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment) for use in the treatment of sarcoidosis in a subject in need thereof.

[0112] Embodiment 2. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is cutaneous sarcoidosis.

[0113] Embodiment 3. The anti-TL1A antibody or antigen-binding fragment of embodiment 2, wherein the cutaneous sarcoidosis is lupus pernio, papular sarcoidosis, nodular sarcoidosis, Darier-Roussy sarcoidosis, maculopapular sarcoidosis, plaque sarcoidosis, hypopigmented sarcoidosis, or atrophic and ulcerative sarcoidosis.

[0114] Embodiment 4. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is neurologic sarcoidosis.25746

[0115] Embodiment 5. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is cardiac sarcoidosis.

[0116] Embodiment 6. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is gastrointestinal sarcoidosis.

[0117] Embodiment 7. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is hepatic sarcoidosis.

[0118] Embodiment 8. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is pancreatic sarcoidosis.

[0119] Embodiment 9. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is peritoneal sarcoidosis.

[0120] Embodiment 10. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is sarcoidosis of bones.

[0121] Embodiment 11. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is sarcoid arthropathy.

[0122] Embodiment 12. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is plaque sarcoidosis.

[0123] Embodiment 13. The anti-TL1A antibody or antigen-binding fragment of embodiment 12, wherein the plaque sarcoidosis is angiolupoid sarcoidosis, psoriasiform sarcoidosis, or verrucous sarcoidosis.

[0124] Embodiment 14. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is ichthyosiform sarcoidosis.

[0125] Embodiment 15. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is erythrodermic sarcoidosis.

[0126] Embodiment 16. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is perforating sarcoidosis.

[0127] Embodiment 17. The anti-TL1A antibody or antigen-binding fragment of embodiment 1, wherein the sarcoidosis is pulmonary sarcoidosis.

[0128] Embodiment 18. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 17, wherein the anti-TL1A antibody or antigen binding fragment is administered in a pharmaceutical composition.

[0129] Embodiment 19. The anti-TL1A antibody or antigen-binding fragment of embodiment 18, wherein the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration greater than about 150 mg / mL.

[0130] Embodiment 20. The anti-TL1A antibody or antigen-binding fragment of embodiment 18 or 19, wherein the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration greater than about 160 mg / ml, about 165 mg / ml, about 170 mg / ml, about 175 mg / ml, about 180 mg / ml, about 185 mg / ml, about 190 mg / ml, about 195 mg / ml, about 200 mg / ml, about 205 mg / ml, about 210 mg / ml, about 215 mg / ml, about 220 mg / ml, about 225 mg / ml, about 230 mg / ml, about 235 mg / ml, about 240 mg / ml, about 245 mg / ml, or about 250 mg / mL.

[0131] Embodiment 21. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 20, wherein the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration about 125 mg / mL to about 175 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 225 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 225 mg / mL, about 150 mg / mL to about 250 mg / mL, about 175 mg / mL to about 225 mg / mL, about 175 mg / mL to about 250 mg / mL, about 175 mg / mL to about 275 mg / mL, about 200 mg / mL to about 250 mg / mL, or about 200 mg / mL to about 275 mg / mL.

[0132] Embodiment 22. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 21, wherein the pharmaceutical composition is administered subcutaneously.

[0133] Embodiment 23. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 21, wherein the pharmaceutical composition is administered intravenously.

[0134] Embodiment 24. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 23, wherein the pharmaceutical composition comprises about 150 mg to about 1000 mg of the anti-TL1A antibody or antigen binding fragment.

[0135] Embodiment 25. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 24, wherein the pharmaceutical composition has a total volume of less than or equal to about 2 mL, about 1.9 ml, about 1.8 ml, about 1.7 ml, about 1.6 ml, about 1.5 ml, about 1.4 ml, about 1.3 ml, about 1.2 ml, about 1.1 ml, about 1.0 ml, about 0.9 ml, or about 0.8 mL.

[0136] Embodiment 26. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 25, wherein the pharmaceutical composition comprises a therapeutically effective dose of the anti-TL1A antibody or antigen binding fragment.

[0137] Embodiment 27. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 26, wherein the pharmaceutical composition has a viscosity of lessthan about 20cP, less than about 19cP, less than about 18cP, less than about 17cP, less than about 16cP, less than about 15cP, less than about 14cP, less than about 13cP, less than about 12cP, less than about 11cP, less than about 10cP, less than about 9cP, less than about 8cP, less than about 7cP, less than about 6cP, or less than about 5 cP.

[0138] Embodiment 28. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 18 to 27, wherein the pharmaceutical composition comprises a surfactant, a salt, a stabilizer, and / or a buffering agent.

[0139] Embodiment 29. The anti-TL1A antibody or antigen-binding fragment of embodiment 28, wherein the surfactant comprises polysorbate-20, and wherein optionally the surfactant is present at a concentration of about 0.02% in the pharmaceutical composition.

[0140] Embodiment 30. The anti-TL1A antibody or antigen-binding fragment of embodiment 28 or 29, wherein the salt comprises NaCl, and wherein optionally the NaCl is at a concentration of about 40 mM in the pharmaceutical composition.

[0141] Embodiment 31. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 28 to 30, wherein the stabilizer comprises sucrose, wherein optionally the sucrose is at a concentration of about 220 mM in the pharmaceutical composition.

[0142] Embodiment 32. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 28 to 31, wherein the buffering agent comprises sodium acetate, wherein optionally the sodium acetate is at a concentration of about 20 mM in the pharmaceutical composition.

[0143] Embodiment 33. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 28 to 32, wherein the pharmaceutical composition has a pH of about 5.3.

[0144] Embodiment 34. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 33, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a first dose up to about 1000 mg.

[0145] Embodiment 35. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 34, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a first dose of about 500 mg.

[0146] Embodiment 36. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 35, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a second dose up to about 1000 mg.

[0147] Embodiment 37. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 36, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a second dose of about 500 mg.25746

[0148] Embodiment 38. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 37, wherein the first dose is administered to the subject at a first time point, and the second dose is administered to the subject at a second time point.

[0149] Embodiment 39. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 38, wherein the first dose and the second dose is different or wherein the first dose and the second dose is identical.

[0150] Embodiment 40. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 38, wherein the second time point is about 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, or 31 days after the first time point.

[0151] Embodiment 41. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 33, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at an induction regimen.

[0152] Embodiment 42. The anti-TL1A antibody or antigen-binding fragment of embodiment 41, wherein the induction regimen comprises 500 mg / dose once every 4 weeks.

[0153] Embodiment 43. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 33 and 41 to 42, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a maintenance regimen.

[0154] Embodiment 44. The anti-TL1A antibody or antigen-binding fragment of embodiment 43, wherein the maintenance regimen comprises 500 mg / dose once every 4 weeks.

[0155] Embodiment 45. The anti-TL1A antibody or antigen-binding fragment of embodiment 43 or 44, wherein the induction regimen and the maintenance regimen are identical.

[0156] Embodiment 46. The anti-TL1A antibody or antigen-binding fragment of embodiment 43, wherein the induction regimen and the maintenance regimen are different.

[0157] Embodiment 47. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 43 to 46,wherein the maintenance regimen is about 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, or 31 days after the induction regimen.

[0158] Embodiment 48. An anti-TL1A antibody or antigen-binding fragment for use in neutralizing monomeric TL1A and trimeric TL1A in a subject having sarcoidosis, wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A,25746 wherein the antibody or antigen binding fragment blocks interaction of TL1A to DR3, wherein the concentration of TL1A in a diseased tissue in the subject is reduced below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, and wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

[0159] Embodiment 49. An anti-TL1A antibody or antigen-binding fragment for use in reducing the concentration of TL1A in a diseased tissue in a subject with sarcoidosis, wherein the anti-TL1A antibody or antigen binding fragment is formulated in an effective dose for administration to the subject to reduce the concentration of TL1A in the diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other and tissues afflicted by sarcoidosis.

[0160] Embodiment 50. An anti-TL1A antibody or antigen-binding fragment for use in the treatment of sarcoidosis in a subject in need thereof, wherein the anti-TL1A antibody or antigen binding fragment is administered at an effective dose such that the concentration of TL1A in a diseased tissue in the subject after the administration is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, and wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

[0161] Embodiment 51. An anti-TL1A antibody or antigen-binding fragment for use in the treatment of sarcoidosis in a subject in need thereof, wherein the anti-TL1A antibody or antigen binding fragment is administered in the method of: (a) administering an anti-TL1A antibody or antigen binding fragment to the subject at an effective dose, and (b) reducing the concentration of TL1A in a diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein diseased tissue comprises any one or more selected from the group25746 consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

[0162] Embodiment 52. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 51, wherein the sarcoidosis is cutaneous sarcoidosis.

[0163] Embodiment 53. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 51, wherein the sarcoidosis is pulmonary sarcoidosis.

[0164] Embodiment 54. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 53, wherein the effective dose comprises an induction regimen.

[0165] Embodiment 55. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 54, wherein anti-TL1A antibody or antigen-binding fragment is also for use in the maintenance of TL1A in the diseased tissue in the subject at a concentration below the concentration of TL1A in the corresponding tissue in the control subject.

[0166] Embodiment 56. The anti-TL1A antibody or antigen-binding fragment of embodiment 55, wherein the TL1A in the diseased tissue in the subject is maintained with a maintenance regimen of the anti-TL1A antibody or antigen binding fragment.

[0167] Embodiment 57. The anti-TL1A antibody or antigen-binding fragment of embodiment 56, wherein the induction regimen and the maintenance regimen are identical.

[0168] Embodiment 58. The anti-TL1A antibody or antigen-binding fragment of embodiment 56, wherein the induction regimen and the maintenance regimen are different.

[0169] Embodiment 59. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 58, wherein the maintenance regimen is administered after the induction regimen.

[0170] Embodiment 60. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 59, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject during the induction regimen.

[0171] Embodiment 61. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 59, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

[0172] Embodiment 62. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 59, wherein the diseased tissue in the subject produces up to 50,25746 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject.

[0173] Embodiment 63. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 54 to 62, wherein the induction regimen comprises a one-time administration of the anti-TL1A antibody or antigen binding fragment.

[0174] Embodiment 64. The anti-TL1A antibody or antigen-binding fragment of embodiment 63, wherein one-time administration of the anti-TL1A antibody or antigen binding fragment comprises an administration at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

[0175] Embodiment 65. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 54 to 62, wherein the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

[0176] Embodiment 66. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 54 to 62 and 65, wherein the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or(v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

[0177] Embodiment 67. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 54 to 62 or 65, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

[0178] Embodiment 68. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 54 to 62, 65, or 67, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.25746

[0179] Embodiment 69. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 54 to 62, 65, or 67, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

[0180] Embodiment 70. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 55 to 69, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject.

[0181] Embodiment 71. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 55 to 66, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

[0182] Embodiment 72. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 55 to 66, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

[0183] Embodiment 73. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 72, wherein the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

[0184] Embodiment 74. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 73, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every25746 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0185] Embodiment 75. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 73, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

[0186] Embodiment 76. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 73 or 75, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

[0187] Embodiment 77. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 76, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

[0188] Embodiment 78. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 76, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

[0189] Embodiment 79. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 78, wherein the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

[0190] Embodiment 80. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 49 to 79, wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A and wherein the antibody or antigen binding fragment blocks binding of TL1A to DR3.

[0191] Embodiment 81. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 80, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment.

[0192] Embodiment 82. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 81, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment.25746

[0193] Embodiment 83. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 82, wherein binding affinity of the antibody or antigen binding fragment to monomeric TL1A as measured by dissociation equilibrium constant (KD- monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1A as measured by dissociation equilibrium constant (KD-trimer).

[0194] Embodiment 84. The anti-TL1A antibody or antigen-binding fragment of embodiment 83, wherein the KD-monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD-trimer.

[0195] Embodiment 85. The anti-TL1A antibody or antigen-binding fragment of embodiment 83 or 84, wherein the KD-monomer is no more than 0.06 nM.

[0196] Embodiment 86. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 83 to 85, wherein the KD-trimer is no more than 0.06 nM.

[0197] Embodiment 87. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 48 to 86, wherein the effective dose or the induction regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the effective dose or the induction regimen such that the concentration of TL1A in diseased tissue in the subject after step (a) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis

[0198] Embodiment 88. The anti-TL1A antibody or antigen-binding fragment of embodiment 87, wherein the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold over-production comparing to TL1A production in the normal reference tissue.

[0199] Embodiment 89. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 56 to 88, wherein the maintenance regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue;25746 (ii) integrating the parameter received in (i) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the maintenance regimen such that the concentration of TL1A in diseased tissue in the subject after step (c) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis.

[0200] Embodiment 90. The anti-TL1A antibody or antigen-binding fragment of embodiment 89, wherein the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more fold over-production comparing to TL1A production in the normal reference tissue.

[0201] Embodiment 91. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 87 to 90, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1A in normal tissue (ksyn-normal), synthesis rate of TL1A in diseased tissue (ksyn-disease), and / or degradation rate of TL1A (kdeg- total-TL1A).

[0202] Embodiment 92. The anti-TL1A antibody or antigen-binding fragment of embodiment to 91, wherein the association rate of the antibody to TL1A (kon-mAb) comprises the association rate of the antibody to monomeric TL1A (kon-monomer) and association rate of the antibody to trimeric TL1A (kon-trimer), wherein the dissociation rate of the antibody from TL1A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff-monomer) and dissociation rate of the antibody from trimeric TL1A (koff-trimer), and / or wherein the degradation rate of TL1A (kdeg-total-TL1A) comprises degradation rate of monomeric TL1A (kdeg-TL1A-monomer) and degradation rate of trimeric TL1A (kdeg-TL1A-trimer).

[0203] Embodiment 93. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 87 to 92, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn), and / or dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn).

[0204] Embodiment 94. The anti-TL1A antibody or antigen-binding fragment of embodiment 93, wherein the association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn) comprises association rate of the antibody-monomeric-TL1A complex to FcRn receptor (kon-(mAb-monoTL1A)-FcRn) and association rate of the antibody-25746 trimeric-TL1A complex to FcRn receptor (kon-(mAb-triTL1A)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn) comprises dissociation rate of the antibody-monomeric-TL1A complex from FcRn (koff-(mAb-monoTL1A)-FcRn) and dissociation rate of the antibody-trimeric-TL1A complex from FcRn (koff-(mAb-triTL1A)-FcRn).

[0205] Embodiment 95. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 87 to 94, wherein the step (i) in the dose determination method further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn).

[0206] Embodiment 96. The anti-TL1A antibody or antigen-binding fragment of embodiment 95, wherein the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric- TL1A complex (kdeg-(mAb-monoTL1A)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TL1A complex (kdeg-(mAb-triTL1A)-FcRn).

[0207] Embodiment 97. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 91 to 96, wherein in the dose determination method: (1) kon-monomer and kon-trimer are identical or different; (2) koff-monomer and koff-trimer are identical or different; (3) kdeg- monomer and kdeg-trimer are identical or different; (4) kon-(mAb-monoTL1A)-FcRn and kon-(mAb-triTL1A)-FcRn are identical or different; (5) kon-mAb-FcRn and kon-(mAb-monoTL1A)-FcRn are identical or different; (6) kon-mAb-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (7) koff-(mAb-monoTL1A)-FcRnand koff-(mAb-triTL1A)-FcRn are identical or different; (8) koff- mAb-FcRn and koff-(mAb-monoTL1A)-FcRn are identical or different; (9) koff- mAb-FcRnand koff-(mAb-triTL1A)-FcRnare identical or different; (10) kdeg-(mAb-monoTL1A)-FcRn and kdeg-(mAb-triTL1A)-FcRn are identical or different; (11) kdeg-mAb-FcRn and kdeg-(mAb-triTL1A)-FcRnare identical or different; (12) kdeg-mAb-FcRnand kdeg-(mAb-monoTL1A)-FcRnare identical or different; or (13) any combination of (1) to (12).

[0208] Embodiment 98. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 87 to 97, wherein in the dose determination method: ksyn-diseaseis up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn-normal.

[0209] Embodiment 99. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 87 to 98, wherein step (i) in the dose determination method further comprises receiving rate of TL1A trimerization (kon-TL1A-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TL1A-trimer-to-monomer).

[0210] Embodiment 100. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 99, wherein the anti-TL1A antibody comprises a heavy chain25746 variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10, an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15.

[0211] Embodiment 101. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 100, wherein the anti-TL1A antibody comprises, a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

[0212] Embodiment 102. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 101, wherein the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 201-220.

[0213] Embodiment 103. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 102, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDR FSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein HCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 1, HCDR2 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, HCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 6-9, LCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 10, LCDR2 comprises an amino25746 acid sequence set forth by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 12 or 13.

[0214] Embodiment 104. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 99, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 401, 407, 413, or 450, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 402, 408, 414, or 451, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 403, 409, 415, or 452; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 404, 410, 416, or 453, an LCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 405, 411, 417, or 454, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 406, 412, 418, or 455.

[0215] Embodiment 105. The anti-TL1A antibody or antigen-binding fragment of any one of embodiments 1 to 99 or embodiment 104, wherein the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 420-427, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 430-437. BRIEF DESCRIPTION OF THE FIGURES

[0216] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0217] Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.

[0218] FIGS.1A-1C show chromatograms for analytical size exclusion chromatography of anti-TL1A antibodies. The large peaks (main peak) correspond to monomeric fraction. The percentage of monomeric sample is indicated for each antibody. FIG.1A shows chromatographs for antibodies A193, A194, and A195. FIG.1B shows chromatographs for antibodies A196, A197, and A198. FIG.1C shows chromatographs for antibodies A199, A200, and A201.

[0219] FIG.2 depicts inhibition of interferon gamma in human blood with anti-TL1A antibodies.25746

[0220] FIG.3A depicts the comparison between the predicted and measured viscosity. FIGS.3B-3D depict a PLS model demonstrating effect of pH and protein concentration on viscosity. FIG.3B shows a PLS graph (x-axis is pH, y-axis is protein concentration (mg / ml), z-axis is viscosity (mPa-s) for the PLS graphs), FIG.3C shows a model of the predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration (x- axis) in mg / mL, and FIG.3D shows a model of the estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). FIG.3E depicts the effects of pH versus acetate concentration on viscosity. FIG.3F shows the effect of sucrose versus NaCl on viscosity. FIG.3G depicts the effect of Arg-HCl versus Lys-HCl on viscosity. Viscosity units are in mPa-s. The arrow points to the region of highest viscosity. The star corresponds to the region of lowest viscosity.

[0221] FIG.4A depicts the PLS1 model for the effect on high molecular weight (HMW) aggregates. FIG.4B depicts the effect of pH versus acetate on aggregation. FIG. 4C depicts the effect of sucrose versus NaCl concentration. FIG.4D depicts the effect of Arg-HCl versus Lys-HCl on aggregation. FIG.4E depicts the effect of sucrose concentration versus Lys-HCl concentration.

[0222] FIG.5A depicts the predicted versus measured loss of main peak at 2 weeks and 25°C. FIG.5B depicts the effect of pH and protein concentration on the loss of main peak in the CEX profile. FIG.5C depicts the effect of pH and acetate concentration on the loss of main peak in the CEX profile. FIG.5D depicts the effect of sucrose and NaCl concentration on the loss of main peak in the CEX profile. FIG.5E depicts the effect of Lys- HCl and sucrose concentration on the loss of main peak in the CEX profile.

[0223] FIG.6A depicts the loss of monomer by SEC with agitation. FIG.6B depicts the loss of monomer by SEC with freeze-thaw.

[0224] FIG.7A depicts the binding of an anti-TL1A antibody to cynomolgus and human TL1A, but not to mouse or rat TL1A. ELISA for each protein was performed at least three times. The data from a representative experiment are shown and are mean ± SD. Abbreviations: A=absorbance, Ab=antibody, Cyno=cynomolgus, nm=nanometer, nM=nanomolar. FIG.7B depicts mean levels of sTL1A increased with increasing IV doses of anti-TL1A to cynomolgus monkeys, as measured in an ELISA. Samples were assayed in triplicate, on two separate occasions. Data presented are the mean TL1A concentrations of three animals per group ± SD. Samples collected from animals administered isotype control antibody are shown in circles, samples collected from animals administered anti-TL1A are25746 shown in the triangles and square. Abbreviations: hr=hour, kg=kilogram, mg=milligram, mL=milliliter, ng=nanogram; TL1A=tumor necrosis factor-like cytokine 1A.

[0225] FIG.8 demonstrates that TL1A drives inflammation and fibrosis through binding to DR3.

[0226] FIGS.9A-9C demonstrates size-exclusion chromatography (SEC) profiles of recombinant human TL1A (rhTL1A). Briefly, rhTL1A was labeled with Alexa fluor 488 (AF488) and spiked into normal human serum (NHS). In FIG.9A, when injected alone, rhTL1A SEC profile shows two peaks on SEC, representing trimeric and monomeric forms of TL1A. In FIG.9B, when rhTL1A is pre-incubated with a control reference antibody, the trimeric peak was shifted leftward, indicating a larger complex formation of the reference antibody and trimeric rhTL1A. There was no shift in the monomeric peak, indicating that the reference antibody only binds to the trimeric rhTL1A. In FIG.9C, when rhTL1A is pre- incubated with A219, both the trimeric and the monomeric rhTL1A peaks were shifted, thus indicating that A219 binds both trimeric and monomeric forms of TL1A.

[0227] FIG.10A depicts a whole-body physiologically based pharmacokinetic (PBPK) model. FIG.10B depicts a tissue-level diagram of the integrated whole-body PBPK model used to characterize the PK of the monoclonal antibody (mAb), ligand, and complex between mAb and ligand.

[0228] FIG.11A depicts the comparison of the pharmacokinetics of the mAb as predicted by the integrated whole-body PBPK (solid curve) with the pharmacokinetics of the mAb as observed in normal healthy volunteers (various points with points from the same subject shown by the same format), in each case after injection of A219 at the indicated dose. FIG.11B depicts the comparison of the TL1A concentration as predicted by the integrated whole-body PBPK with the TL1A concentration as observed in normal healthy volunteers, in each case after injection of A219 at the indicated dose.

[0229] FIG.12A depicts the observed concentration of TL1A in serum after injecting (i) an anti-TL1A antibody A219 that binds to both TL1A monomer and trimer (shown in red, top of the 2 curves, and the observed data points accompanying such curve) and (ii) a control reference anti-TL1A antibody that binds to only TL1A trimer (shown in blue, bottom of the 2 curves, and the observed data points accompanying such curve). In FIG.12A, solid curves depict the prediction from the model and various dots depict the observations from subjects injected with the indicated antibodies. FIG.12B depicts the predicted total TL1A concentration (monomer and trimer, solid curve and the observed data points accompanying such curve), the monomer TL1A concentration (fine dotted line), and the trimer TL1A25746 concentration (coarse dotted line), in each case at the basal level (no injection of any anti- TL1A antibodies). FIG.12C depicts the serum TL1A concentration in normal healthy volunteers (NHV) and UC patients, as predicted by the whole-body PBPK model (solid lines, upper line for UC patient and lower line for NHV) and as observed (various points).

[0230] FIGS.13A-13B demonstrate the fitness of the model. FIG.13A depicts the observed concentration of TL1A in serum of NHVs after injecting an anti-TL1A antibody that binds to only TL1A trimer (dots) and the prediction of the model (solid curve) that fits the observations at the indicated dose. Q2WX3= every 2 weeks for three times. FIG.13B depicts the observed concentration of TL1A in serum of UC patients after injecting an anti- TL1A antibody that binds to only TL1A trimer (dots) and the prediction of the model (solid curve) that fits the observations at the indicated dose. Q2WX7= every 2 weeks for seven times. FIG.13C depicts the concentration of TL1A in intestine of NHV (black, solid, lower line of the two lines as predicted from the model and the observed data points accompanying such line) and the concentration of TL1A in the intestine of UC patient (red, solid, upper line of the two lines).

[0231] FIGS.14A-14B depict the baseline concentration of TL1A based on various parameters of TL1A production in intestine (14A) and in serum (14B). In FIGS.14A-14B, 1× would be the baseline in NHV; 25×, 50×, 75×, and 100× indicate various parameters of TL1A over-production in intestine.

[0232] FIGS 15A-15V depict the concentration of free soluble TL1A in tissue as determined by the whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimen of anti-TL1A antibody A219 as indicated. FIG. 15W depicts the free soluble TL1A in tissue as determined by the whole-body PBPK model according to various parameters of TL1A overproduction under the dose regimen of a reference anti-TL1A antibody as indicated. FIGS.15X-15Z depict the comparison of the modeled free soluble TL1A concentration in subjects treated with a reference anti-TL1A antibody (red, the upper curve of the two curves) or A219 (green, the lower curve of the two curves). In FIG.15W-15Z, reference antibody light chain sequence is SEQ ID NO: 382, heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses a rapid equilibrium between the monomeric and trimeric form of TL1A with a continuous 60:40 ratio of monomer and trimer as observed. The black solid lines in FIGS.15A-15Z indicate the TL1A concentration in the tissue of NHV. Q2W=every 2 weeks. Q4W=every 4 weeks. SC=subcutaneous. LD=loading dose (the first dose). 4W=week 4. D1=day 1. W 2, 6, 10=week 2, week 6, and week 10. W 2, 4, 6, 10=week 2, week 4, week 6, and week 10.25746 EOW=every other week. W 4, 8, 12=week 4, week 8, and week 12. W 2, 4, 8, 12=week 2, week 4, week 8, and week 12. sTL1A=soluble TL1A.

[0233] FIGS 16A-16H depict the goodness of fit plots for A219 with the population PK model.

[0234] FIG.17A depicts the visual predictive check for the A219 concentration predicted from the popPK model against the observed A219 concentration. FIG.17B depicts an induction dose selected in the popPK model to rapidly achieve steady state concentration.

[0235] FIG.18 depicts osmotic pressures at 5°C measured for the stability of A219 samples of various formulations at T0, 3 and 6 months.

[0236] FIG.19 depicts A219 protein concentration at 5°C measured for evaluating the stability of A219 samples of various formulations at T0, 3 and 6 months.

[0237] FIG.20 depicts pH at 5°C measured for the evaluating the stability A219 samples of various formulations at T0, 3 and 6 months.

[0238] FIG.21A depicts viscosity data for T0 and 3M for Formulations 1 to 5 at 25°C; FIG.21B depicts viscosity data for T0 and 3M for Formulations 6 to 8 at 25°C.

[0239] FIG.22A depicts monomer contents for formulations at 5°C as measured by SEC; FIG.22B depicts loss of monomer (main peak) per month for the formulations at 5°C as determined by SEC; FIG.22C depicts monomer contents for formulations at 25°C as measured by SEC; FIG.22D depicts loss of monomer (main peak) per month for the formulations at 5°C as determined by SEC.

[0240] FIG.23A depicts the relative area (%) of the main peak for formulations at 5°C as characterized by cation exchange chromatography; FIG.23B depicts the loss of main peak (Rel. Area (%) per month) for the formulations at 5°C as determined by cation exchange chromatography; FIG.23C depicts the relative area (%) of the main peak for formulations at 25°C as characterized by cation exchange chromatography; FIG.23D depicts the loss of main peak (Rel. Area (%) per month) for the formulations at 25°C as determined by cation exchange chromatography.

[0241] FIG.24A depicts predicted vs. measured values according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25°C as the endpoint; FIG. 24B depicts effect of pH and protein according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25°C as the endpoint. In FIG.24B, the sucrose concentration was fixed at 200 mM. FIG.24C depicts effect of pH and acetate according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25°C as the25746 endpoint. In FIG.24C, the sucrose concentration was fixed at 200 mM. FIG.24D depicts effect of sucrose and lysine according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25°C as the endpoint. In FIG.24D, the protein concentration was fixed at 150 mg / mL, pH at 5.5 and acetate at 20 mM. FIG.24E depicts effect of glycine and NaCl according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25°C as the endpoint. In FIG.24E, the protein concentration was fixed at 150 mg / mL, pH at 5.5 and acetate at 20 mM.

[0242] In FIGS.18, 19, 20, 21A-21B, 22A-22D, 23A-23D, and 24A-24E, the formulations 1-8 (F01-F08, Form.1-8, or simply 1-8) referenced therein are the formulations 1-8 as described in Table 31 of Example 22.

[0243] FIG.25 shows the scheme of double blind, randomized, placebo-controlled clinical study to evaluate the efficacy and safety of A219 in subjects with pulmonary sarcoidosis.

[0244] FIG.26A shows geometric mean serum A219 concentration-time profiles following single doses of A219 administered as IV infusion (Linear Scale) (SAD study). FIG.26B shows geometric mean serum A219 concentration-time profiles following multiple doses of A219 Q2W administered as IV infusion - day 29 (linear scale) (MAD study). Q2W=every 2 weeks.

[0245] FIG.27A shows geometric mean serum sTL1A concentration versus nominal time following single dose of A219 administered as IV Infusion (semi-log scale) (SAD study). FIG.27B geometric mean serum sTL1A concentration versus nominal time following multiple doses of A219 Q2W administered as IV infusion (semi-log scale) (MAD study).

[0246] FIG.28A shows total A219 concentration in the central compartment (in circulation) in SAD as predicted by the model (curves) and as determined in the phase I trial (dots). FIG.28B shows total soluble TL1A in the central compartment (circulation) in SAD as predicted by the model (curves) and as determined in the phase I trial. FIG.28C shows total A219 concentration in the central compartment (in circulation) in MAD as predicted by the model (curves) and as determined in the phase I trial (dots). FIG.28D shows total soluble TL1A in the central compartment (circulation) in MAD as predicted by the model (curves) and as determined in the phase I trial (dots). The predicted curves fitted with the measured data points. FIGS.28E-28K show model prediction for and the data of a control reference antibody that binds only to TL1A trimer (light chain SEQ ID NO: 382 and heavy25746 chain SEQ ID NO: 383) with regard to (1) phase I single ascending dose data (FIGS.28E and 28F), (2) phase I multiple ascending dose data (FIGS.28G and 28H), and (3) phase II data on PK & total sTL1A levels (FIGS.28I and 28J). The IBD specific parameters were then calibrated to capture free tissue TL1A levels in the gut (FIG.28K) as observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383). NR=non-responder and R=responder.

[0247] FIG.29A shows doses of A219 determined from the validated model that can bring the free TL1A concentration in the patient’s diseased tissue to below the TL1A concentration of a healthy subject. FIG.29B shows the percent reduction of the free TL1A in the diseased tissue after administering doses of A219 as determined from the model. IV_4×= 1000 mg loading dose, 3 × 500 mg on days 14, 42, 70. SC dosing 240 mg Q1W or Q2W. FIG.29C shows that, in a head-to-head comparison in the validated model, anti- TL1A antibodies that bind to both TL1A monomer and trimer engaged more (3.5 fold more) TL1A in circulation than anti-TL1A antibodies that only bind to TL1A trimer. FIG.29D shows that, in a head-to-head comparison in the validated model, anti-TL1A antibodies that bind to both TL1A monomer and trimer also resulted in higher percentage of TL1A reduction of TL1A in diseased tissue (about 100%) when compared to anti-TL1A antibodies that only bind to TL1A trimer.

[0248] FIG.30A shows the diagram of a popPK model. FIG.30B shows the comparison of the A219 concentration predicted from the popPK model and the A219 concentration observed in the population of subjects in phase I clinical trial via a linear regression plot. FIG.30C shows the comparison of the TL1A concentration predicted from the popPK model and the TL1A concentration observed in the population of subjects in phase I clinical trial via a linear regression plot. FIG.30D shows the comparison of the A219 concentration predicted from the popPK model and the A219 concentration observed in the population of subjects in phase I clinical trial via a time series plot. FIG.30E shows the comparison of the TL1A concentration predicted from the popPK model and the TL1A concentration observed in the population of subjects in phase I clinical trial via a time series plot.

[0249] FIGS.31A-31H show the A219 and TL1A engagement (TL1A concentration in serum) predicted from the validated popPK model under various A219 doses. FIGS.31A and 31B show A219 concentration (31A) and TL1A concentration (31B) in circulation with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 500 mg Q2W from week 12 to week 52 (20 doses). FIGS.31C and 31D show A21925746 concentration (31C) and TL1A concentration (31D) in circulation with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 500 mg Q4W from week 12 to week 52 (10 doses). FIGS.31E and 31F show A219 concentration (31E) and TL1A concentration (31F) in circulation with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 100 mg Q2W from week 12 to week 52 (20 doses). FIGS.31G and 31H show A219 concentration (31G) and TL1A concentration (31H) with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 250 mg Q4W from week 12 to week 52 (10 doses).

[0250] FIGS.32A-32B depict TL1A (TNFSF15) and DR3 (TNFRSF25) gene expression in sarcoidosis afflicted tissues. FIG.32A shows TL1A (TNFSF15) gene expression and upregulation of DR3 (TNFRSF25) gene expression in BAL cells from sarcoidosis patients compared to BAL cells from healthy volunteers. Fig 32B shows that TNFSF15 is upregulated and TNFRSF25 is downregulated in lesional skin samples compared to non-lesional in skin from cutaneous sarcoidosis patients and healthy control skin.

[0251] FIGS.33A-33B depict various pathway gene expression signatures evaluated by GSVA score. Th1, Th2, and Th17 (FIG.33A) pathways were elevated in BAL cells from sarcoidosis patients compared to BAL cells from healthy volunteer (FIGS.33A) and in lesional skin samples compared to non-lesional skin from cutaneous sarcoidosis patients or skin samples from healthy control subjects (FIG.33B).

[0252] FIGS.34A-34B depict fibrosis pathway gene expression signatures evaluated by GSVA score. Fibrosis pathway was elevated in BAL cells from sarcoidosis patients compared to BAL cells from healthy volunteer (FIGS.34A) and in lesional skin samples compared to non-lesional skin from cutaneous sarcoidosis patients or skin samples from healthy control subjects (FIG.34B).

[0253] FIGS.35A-35B depict TL1A induced genes in Th17 cells and TL1A induced genes in IFNg producing cells as evaluated by GSVA score. TL1A induced genes in Th17 cells (FIG.35A, left panel) and TL1A induced genes in IFNg producing cells (FIG.35A, right panel) were elevated in BAL cells from sarcoidosis patients compared to BAL cells from healthy volunteer. TL1A induced genes in Th17 cells (FIG.35B, left panel) and TL1A induced genes in IFNg producing cells (FIG.35B, right panel) were also elevated in lesional skin samples compared to non-lesional skin from cutaneous sarcoidosis patients or skin samples from healthy control subjects.

[0254] FIGS.36A-36B depict TL1A expression profiles of sarcoidosis pathway genes as evaluated by modified GSVA score. TL1A target genes identified from sarcoidosis25746 disease network (FIG.36A) was upregulated in BAL cells from sarcoidosis patients compared to BAL cells from healthy volunteer. TL1A target genes identified from sarcoidosis disease network (FIG.36B) was also elevated in lesional skin samples compared to non-lesional skin from cutaneous sarcoidosis patients or skin samples from healthy control subjects

[0255] FIGS.37A-37D depict TL1A and DR3 expression in various cell types in the lung. In FIG.37A, each dot represents one cell where the expression of TNFSF15 gene (top panel) or TNFRSF25 (bottom panel) was detected. The y-axis in FIG.37A indicates gene expression level as normalized to the overall RNA sequencing read. FIG.37A shows that, among the various lung tissues, TL1A (TNFSF15) was expressed by epithelial cells (AT1, AT2, Basal, KRT5-KRT17+, transitional AT2), secretory (SCGB3A2) and immune cells (macrophages and monocytes), and DR3 (TNFRSF25) was highly expressed by T cells and expressed by a lower percentage of other immune cells including macrophages, and NK cells. In FIGS.37B-37D, dot plots show increased level of protein expression of TL1A ligand in epithelial (FIG.37B) and secretory cells (FIG.37C) and increased level of protein expression of DR3 receptor in T and NK cells (FIG.37D) pulmonary sarcoidosis lung. In FIGS.37B-37D, the color scale represents the expression levels and the diameter represents the percentage, as indicated in the legend at the top.

[0256] FIGS.38A-38B depict TL1A gene expression as detected by fluorescence in- situ hybridization (FISH) in lung tissues from pulmonary sarcoidosis patients. TL1A was detected throughout the tissue and in granuloma regions (fluorescence staining for TL1A in FIG.38B compared with autofluorescence in FIG.38A). FIG.38B shows a zoom-in view of the boxed region indicated in FIG.38A, with TL1A stained in red, autofluorescence in green, and nuclei in blue. The scale bar in FIG.38B is 20 µm.

[0257] FIGS.39A-39B depict TL1A and DR3 protein expression as detected in skin tissues from sarcoidosis patients. The immunohistochemistry staining of sarcoidosis afflicted skin samples reveals TL1A (FIG.39A with anti-TL1A staining shown in brown) and DR3 (FIG.39B with anti-DR3 staining shown in brown) are highly expressed in granuloma cells (FIGS.39A-39B). In FIGS.39A-39B, blue indicates cell nuclei staining by hematoxylin. The scale bar in FIGS.39A-39B is 100 µm. FIGS.39C-39D depict TL1A (39C) and DR3 (39D) protein expression as detected in healthy control skin tissues.DESCRIPTION OF THE INVENTION

[0258] TL1A is a cytokine that is secreted by antigen-presenting cells, T cells, epithelial and endothelial cells. TL1A signals through death receptor 3 (DR3), a TNF-family receptor that is found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphoid cells (ILC), fibroblasts, and epithelial cells and potently drives Th1, Th2, Th9, and Th17 responses. In addition, it is induced in antigen-presenting cells by toll like receptor (TLR) ligands and FcR cross-linking and in T cells by T cell receptor (TCR) stimulation.

[0259] FIG.8 demonstrates how TL1A binding to DR3 independently drives inflammation and fibrosis. TL1A is a pleiotropic cytokine that can promote secretion of several downstream cytokines including IFNγ, IL1, IL6, IL11, IL17 and TGFβ that are produced by macrophages and T cells. TL1A-DR3 pathway activation on Teffector cells is potentiated by IL12, IL18 cytokines and enhances IFNγ and IL17 production, driving granuloma formation in sarcoidosis. The inventors recognize that several of these cytokines downstream of TL1A are also pro-fibrotic and persistent granuloma inflammation promotes localized fibrosis. For example, IL1 mediated lung fibrosis is dependent on IL17A, can activate human lung fibroblasts and induces elevated IL6 from sarcoidosis fibroblasts relative to controls. IL6 can also be produced from macrophages and blockade of this pathway attenuates pulmonary fibrosis. IL-11 is a pro-fibrotic cytokine that can be secreted by immune cells, epithelial cells and human primary fibroblasts. IL11 can promote fibroblast activation in an autocrine manner and blockade of this pathway attenuates lung fibrosis in mice. Similarly, TGFβ can promote fibrosis through activation of fibroblasts. While levels of circulating TL1A are low in healthy subjects, the inventors recognize that they are elevated in patients suffering from sarcoidosis, including pulmonary sarcoidosis and / or cutaneous sarcoidosis.

[0260] In one aspect, provided herein are methods of treating sarcoidosis with an anti- TL1A antibody or an antigen binding fragment. In another aspect, provided herein are methods of treating pulmonary sarcoidosis with an anti-TL1A antibody or an antigen binding fragment. In another aspect, provided herein are methods of treating cutaneous sarcoidosis with an anti-TL1A antibody or an antigen binding fragment. In one aspect, provided herein are methods of treating lupus pernio with an anti-TL1A antibody or an antigen binding fragment. In one aspect, provided herein are methods of treating papular sarcoidosis with an anti-TL1A antibody or an antigen binding fragment. In one aspect, provided herein are methods of treating nodular sarcoidosis with an anti-TL1A antibody or an antigen binding fragment. In one aspect, provided herein are methods of treating Darier-Roussy sarcoidosiswith an anti-TL1A antibody or an antigen binding fragment. In one aspect, provided herein are methods of treating maculopapular sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating hypopigmented sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating atrophic and ulcerative sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating neurologic sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating cardiac sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating gastrointestinal sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating hepatic sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating pancreatic sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating peritoneal sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating sarcoidosis of bones with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating sarcoid arthropathy with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating plaque sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating angiolupoid sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating psoriasiform sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating verrucous sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating ichthyosiform sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating erythrodermic sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In one aspect, provided herein are methods of treating perforating sarcoidosis with an anti-TL1A antibody or antigen binding fragment. In certain embodiments, the anti-TL1A antibodies bind to membrane-bound and soluble forms of TL1A with high affinity and specificity and block the binding of TL1A to its functional receptor DR3.

[0261] The term “and / or” as used in a phrase with a list of members is intended to include all members individually and all combination of full or partial list of members. For example, a phrase such as “A and / or B” herein is intended to include both A and B; A or B;25746 A (alone); and B (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone). General Techniques

[0262] Techniques and procedures described or referenced herein include those that are generally well understood and / or commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual (3d ed.2001); Current Protocols in Molecular Biology (Ausubel et al. eds., 2003); Therapeutic Monoclonal Antibodies: From Bench to Clinic (An ed.2009); Monoclonal Antibodies: Methods and Protocols (Albitar ed.2010); and Antibody Engineering Vols 1 and 2 (Kontermann and Dübel eds., 2d ed.2010). Anti-TL1A Antibodies

[0263] TL1A exists in both monomeric and trimeric form in vivo and in vitro. The disclosure provides that although the trimeric form is the biologically active form that can bind to the physiological receptor, death receptor 3 (“DR3”) and trigger TL1A mediated signaling (e.g. Zhan, C et al., Structure 19: 162-171 (2011)), monomeric TL1A accounts for a large fraction of the TL1A pool in a subject. By one of the inventors’ estimates, the monomeric TL1A can be 60% of the total TL1A in the circulating blood. The term “total TL1A” refers to both monomeric and trimeric TL1A. The disclosure further provides that, despite monomeric TL1A being biologically inactive, anti-TL1A antibodies binding to both monomeric and trimeric TL1A provide advantages over antibodies binding to only trimeric TL1A. As provided herein and further demonstrated in Section

[0551] , such advantages include more efficient reduction of the TL1A concentration in a diseased tissue in a subject including the concentration trimeric TL1A in the diseased tissue, more efficient reduction of the TL1A concentration in the blood in a subject including the concentration trimeric TL1A in the blood, more sustained reduction of TL1A concentration (including trimeric TL1A concentration) in a diseased tissue in a subject, and / or more sustained reduction of TL1A concentration (including trimeric TL1A concentration) in the blood in a subject.

[0264] In one aspect, provided herein are antibodies or antigen binding fragments thereof that bind to tumor necrosis factor-like protein 1A (“TL1A,” and such antibody or antigen binding fragment thereof, “anti-TL1A antibody or antigen binding fragment” or “anti-TL1A antibody(ies)” in the specification for simplicity), wherein the antibodies or25746 antigen binding fragments bind to both monomeric TL1A and trimeric TL1A. Further embodiments of the anti-TL1A antibodies, including embodiments with exemplary CDRs, framework sequences, constant region sequences, Fc mutations, variable regions, Fc regions, and other properties are further provided in this Section (Section

[0256] ). Assays for screening, testing, and validating the anti-TL1A antibodies are provided in Section

[0379] . Methods for generating, improving, mutating, cloning, expressing, and isolating the anti- TL1A antibodies are provided in Section

[0385] . Pharmaceutical compositions for the anti- TL1A antibodies are described and provided in Section

[0416] . Methods of using the anti- TL1A antibodies are provided in Section

[0456] . Further specific and validated embodiments for the anti-TL1A antibodies and the methods of using the same are provided in Section

[0551] . As such, the disclosure provides the various combinations of the anti-TL1A antibodies, the pharmaceutical compositions of such anti-TL1A antibodies, the methods of generating the anti-TL1A antibodies, the methods of assaying the anti-TL1A antibodies, and the methods of using the anti-TL1A antibodies for treatment.

[0265] In one embodiment of the various anti-TL1A antibodies or antigen binding fragments thereof provided herein, the antibody or antigen binding fragment blocks binding of TL1A to Death Receptor 3 (“DR3”). In another embodiment, the antibody or antigen binding fragment blocks the binding of trimeric TL1A to DR3. In a further embodiment, the antibody or antigen binding fragment blocks the signaling DR3 signaling mediated by TL1A. In yet another embodiment, the antibody or antigen binding fragment blocks the increase of IFNγ secretion by various immune cells. In a specific embodiment, the antibody or antigen binding fragment blocks the increase of IFNγ secretion by peripheral blood mononuclear cells, including various B cells, T cells, natural killer cells, and / or macrophages.

[0266] As described herein, the disclosure provides anti-TL1A antibodies or antigen binding fragments for binding both monomeric and trimeric TL1A. Therefore, in one embodiment of the various anti-TL1A antibodies or antigen binding fragments thereof provided herein, binding affinity of the antibody or antigen binding fragment to monomeric TL1A as measured by dissociation equilibrium constant (KD-monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1A as measured by dissociation equilibrium constant (KD-trimer). Such KD-monomer and / or KD-trimer can be determined via any of theand practice by ain the field and via any of the applicable assays and methods described herein, including in this Section (Section

[0265] ) and Section

[0551] .25746

[0267] The terms “binds” or “binding” refer to an interaction between molecules including, for example, to form a complex. Interactions can be, for example, non-covalent interactions including hydrogen bonds, ionic bonds, hydrophobic interactions, and / or van der Waals interactions. A complex can also include the binding of two or more molecules held together by covalent or non-covalent bonds, interactions, or forces. The strength of the total non-covalent interactions between a single antigen-binding site on an antibody and a single epitope of a target molecule, such as TL1A, is the affinity of the antibody or functional fragment for that epitope. The ratio of dissociation rate (koff) to association rate (kon) of an antibody to a monovalent antigen (koff / kon) is the dissociation constant KD, which is inversely related to affinity. The lower the KDvalue, the higher the affinity of the antibody. The value of KD varies for different complexes of antibody and antigen and depends on both kon and koff. The dissociation constant KDfor an antibody provided herein can be determined using any method provided herein or any other method well known to those skilled in the art. The affinity at one binding site does not always reflect the true strength of the interaction between an antibody and an antigen. When complex antigens containing multiple, repeating antigenic determinants, such as a polyvalent TL1A trimer, come in contact with antibodies containing multiple binding sites, the interaction of antibody with antigen at one site will increase the probability of a reaction at a second site. The strength of such multiple interactions between a multivalent antibody and antigen is called the avidity. The avidity of an antibody can be a better measure of its binding capacity than is the affinity of its individual binding sites.

[0268] “Binding affinity” generally refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., a binding protein such as an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). As described above, the affinity of a binding molecule X for its binding partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein. Low-affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend to remain bound longer. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present disclosure. Specific illustrative embodiments include the following. In one embodiment, the “KD” or “KDvalue” can be measured by assays known in the art, for example by a binding assay. The KD can be measured in a RIA, for example, performed with the Fab version of an antibody of25746 interest and its antigen (Chen et al., 1999, J. Mol Biol 293:865-81). The KD or KD value can also be measured by using surface plasmon resonance assays by Biacore®, using, for example, a Biacore®TM-2000 or a Biacore®TM-3000, or by biolayer interferometry using, for example, the Octet®QK384 system. An “on-rate” or “rate of association” or “association rate” or “kon” can also be determined with the same surface plasmon resonance or biolayer interferometry techniques described above using, for example, a Biacore®TM-2000 or a Biacore®TM-3000, or the Octet®QK384 system.

[0269] Accordingly, the relative binding affinity of the anti-TL1A antibody or antigen binding fragment for the TL1A monomer and TL1A trimer can be described and provided by KD-monomerand KD-trimer. In one embodiment of the various anti-TL1A antibodies or antigen binding fragments provided herein, the KD-monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD-trimer. In another embodiment of the various anti-TL1A antibodies or antigen binding fragments provided herein, the KD-monomer is within 10%, 20%, 30%, 40%, or 50% of the KD-trimer. In a further embodiment of the various anti-TL1A antibodies or antigen binding fragments provided herein, the KD-trimer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD- monomer. In another embodiment of the various anti-TL1A antibodies or antigen binding fragments provided herein, the KD-trimer is within 10%, 20%, 30%, 40%, or 50% of the KD- monomer.

[0270] More specifically, in one embodiment of the various anti-TL1A antibodies or antigen binding fragments provided herein, KD-monomer is at most 5×10-12M, at most 6×10-12M, at most 7×10-12M, at most 8×10-12M, at most 9×10-12M, at most 1×10-11M, at most 2×10-11M, at most 3×10-11M, at most 4×10-11M, at most 5×10-11M, at most 6×10-11M, at most 7×10-11M, at most 8×10-11M, at most 9×10-11M, at most 1×10-10M, at most 2×10-10M, at most 3×10-10M, at most 4×10-10M, at most 5×10-10M, at most 6×10-10M, at most 7×10-10M, at most 8×10-10M, at most 9×10-10M, or at most 1×10-9M. In another embodiment, KD-monomer is about 5×10-12M, about 6×10-12M, about 7×10-12M, about 8×10-12M, about 9×10-12M, about 1×10-11M, about 2×10-11M, about 3×10-11M, about 4×10-11M, about 5×10-11M, about 6×10-11M, about 7×10-11M, about 8×10-11M, about 9×10-11M, about 1×10-10M, about 2×10-10M, about 3×10-10M, about 4×10-10M, about 5×10-10M, about 6×10-10M, about 7×10-10M, about 8×10-10M, about 9×10-10M, or about 1×10-9M. In a further embodiment of the various anti-TL1A antibodies or antigen binding fragments provided herein, KD-trimeris at most 5×10-12M, at most 6×10-12M, at most 7×10-12M, at most 8×10-12M, at most 9×10-12M, at most 1×10-11M, at most 2×10-11M, at most 3×10-11M, at most 4×10-11M, at most 5×10-11M, at most 6×10-11M, at most 7×10-11M, at most 8×10-11M, at most 9×10-11M, at most25746 1×10-10M, at most 2×10-10M, at most 3×10-10M, at most 4×10-10M, at most 5×10-10M, at most 6×10-10M, at most 7×10-10M, at most 8×10-10M, at most 9×10-10M, or at most 1×10-9M. In yet another embodiment, KD-trimer is about 5×10-12M, about 6×10-12M, about 7×10-12M, about 8×10-12M, about 9×10-12M, about 1×10-11M, about 2×10-11M, about 3×10-11M, about 4×10-11M, about 5×10-11M, about 6×10-11M, about 7×10-11M, about 8×10-11M, about 9×10-11M, about 1×10-10M, about 2×10-10M, about 3×10-10M, about 4×10-10M, about 5×10-10M, about 6×10-10M, about 7×10-10M, about 8×10-10M, about 9×10-10M, or about 1×10-9M. The disclosure further provides that the KD-monomerand KD-trimercan be any combination of the KD-monomer and KD-trimer value or range as provided herein, including in this Section (Section

[0265] ) and this paragraph.

[0271] In a further specific embodiment, the KD-monomer is about 59 pM. In another specific embodiment, the KD-trimeris about 59 pM. In a further embodiment, the KD-monomeris about 59 pM and the KD-trimer is about 59 pM. In one specific embodiment, the KD-monomer is about 60 pM. In another specific embodiment, the KD-trimeris about 60 pM. In a further embodiment, the KD-monomer is about 60 pM and the KD-trimer is about 60 pM. In one specific embodiment, the KD-monomer is at most 60 pM. In another specific embodiment, the KD-trimer is at most 60 pM. In a further embodiment, the KD-monomer is at most 60 pM and the KD-trimer is at most 60 pM.

[0272] In one aspect, provided herein are antibodies that bind to TL1A. As used herein, the term “antibody” refers to any form of antibody that exhibits the desired biological or binding activity. Thus, it is used in the broadest sense and specifically covers, but is not limited to, monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized, fully human antibodies, chimeric antibodies and camelized single domain antibodies.

[0273] In general, the basic antibody structural unit comprises a tetramer. Each tetramer includes two identical pairs of polypeptide chains, each pair having one “light” (about 25 kDa) and one “heavy” chain (about 50-70 kDa). The amino-terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The carboxy-terminal portion of the heavy chain may define a constant region primarily responsible for effector function. Typically, human light chains are classified as kappa and lambda light chains. Furthermore, human heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon, and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Within light and heavy chains, the variable and constant regions are joined by a “J” region of about 12 or more amino acids, with the heavy25746 chain also including a “D” region of about 10 more amino acids. See generally, Fundamental Immunology Ch.7 (Paul, W., ed., 2nd ed. Raven Press, N.Y. (1989).

[0274] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, in general, an intact antibody has two binding sites. Except in bifunctional or bispecific antibodies, the two binding sites are, in general, the same.

[0275] Typically, the variable domains of both the heavy and light chains comprise three hypervariable regions, also called complementarity determining regions (CDRs), which are located within relatively conserved framework regions (FR). The CDRs are usually aligned by the framework regions, enabling binding to a specific epitope. In general, from N- terminal to C-terminal, both light and heavy chains variable domains comprise FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain is, generally, in accordance with the definitions of Sequences of Proteins of Immunological Interest, Kabat, et al.; National Institutes of Health, Bethesda, Md.; 5thed.; NIH Publ. No.91- 3242 (1991); Kabat (1978) Adv. Prot. Chem.32:1-75; Kabat, et al., (1977) J. Biol. Chem. 252:6609-6616; Chothia, et al., (1987) J Mol. Biol.196:901-917 or Chothia, et al., (1989) Nature 342:878-883.

[0276] As used herein, unless otherwise indicated, “antibody fragment,” “antigen- binding fragment,” and “antigen binding fragment” are used interchangeably to refer to antigen binding fragments of antibodies, i.e., antibody fragments that retain the ability to bind specifically to the antigen bound by the full-length antibody, e.g., fragments that retain one or more CDR regions. Examples of antibody binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules, e.g., sc-Fv; nanobodies and multispecific antibodies formed from antibody fragments.

[0277] In some embodiments, an antibody comprises an antigen-binding fragment that refers to a portion of an antibody having antigenic determining variable regions of an antibody. Examples of antigen-binding fragments include, but are not limited to Fab, Fab’, F(ab’)2, and Fv fragments, linear antibodies, single chain antibodies, and multispecific antibodies formed from antibody fragments. In some embodiments, an antibody refers to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule. In some embodiments, an antibody includes intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab’, F(ab’)2, and Fv fragments),25746 single chain Fv (scFv) mutants, a CDR-grafted antibody, multispecific antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins comprising an antigen determination portion of an antibody, and any other modified immunoglobulin molecule comprising an antigen recognition site so long as the antibodies exhibit the desired biological activity. An antibody can be of any the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well-known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated to other molecules such as toxins, radioisotopes, etc.

[0278] In some embodiments, a humanized antibody refers to forms of non-human (e.g., murine) antibodies having specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. In a non- limiting example, a humanized antibody comprises less than about 40% non-human sequence in the variable region. In some cases, a humanized antibody comprises less than about 20% non-human sequence in a full-length antibody sequence. In a further non-limiting example, a humanized antibody comprises less than about 20% non-human sequence in the framework region of each of the heavy chain and light chain variable regions. For instance, the humanized antibody comprises less than about 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% non-human sequence in the framework region of each of the heavy chain and light chain variable regions. As another example, the humanized antibody comprises about or less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequences in the framework region of each of the heavy chain and light chain variable regions. In some cases, humanized antibodies are human immunoglobulins in which residues from the complementarity determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and capability. These humanized antibodies may contain one or more non-human species mutations, e.g., the heavy chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework region, and the light chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework region. The humanized heavy chain variable domain may comprise IGHV1-46*02 framework with no or fewer than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations. The humanized light chain variable domain may comprise25746 IGKV3-20 framework with no or fewer than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations.

[0279] In some embodiments, chimeric antibodies refer to antibodies wherein the sequence of the immunoglobulin molecule is derived from two or more species. As a non- limiting example, the variable region of both light and heavy chains corresponds to the variable region of antibodies derived from one species of mammals (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies derived from another (usually human) to avoid eliciting an immune response in that species.

[0280] The terms “complementarity determining region,” and “CDR,” which are synonymous with “hypervariable region” or “HVR,” are known in the art to refer to non- contiguous sequences of amino acids within antibody variable regions, which confer antigen specificity and / or binding affinity. In general, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3). “Framework regions” and “FR” are known in the art to refer to the non-CDR portions of the variable regions of the heavy and light chains. In general, there are four FRs in each full-length heavy chain variable region (FR-H1, FR-H2, FR-H3, and FR-H4), and four FRs in each full-length light chain variable region (FR-L1, FR- L2, FR-L3, and FR-L4). The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme), Al-Lazikani et al., (1997) JMB 273,927-948 (“Chothia” numbering scheme); MacCallum et al., J. Mol. Biol.262:732-745 (1996), “Antibody-antigen interactions: Contact analysis and binding site topography,” J. Mol. Biol.262, 732-745.” (“Contact” numbering scheme); Lefranc MP et al.,“IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol, 2003 Jan;27(1):55-77 (“IMGT” numbering scheme); Honegger A and Plückthun A, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J Mol Biol, 2001 Jun 8;309(3):657-70, (“Aho” numbering scheme); and Whitelegg NR and Rees AR, “WAM: an improved algorithm for modelling antibodies on the WEB,” Protein Eng.2000 Dec;13(12):819-24 (“AbM” numbering scheme. In certain embodiments, the CDRs of the antibodies described herein can be defined by a method selected from Kabat, Chothia, IMGT, Aho, AbM, or combinations thereof.25746

[0281] In some embodiments, an antibody that specifically binds to a protein indicates that the antibody reacts or associates more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of the above to the protein than with alternative substances, including unrelated proteins.

[0282] In some embodiments, the terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as fusion with another polypeptide and / or conjugation, e.g., with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (for example, unnatural amino acids, etc.), as well as other modifications known in the art.

[0283] In some embodiments, a protein such as an antibody described herein comprises a hydrophobic amino acid. Non-limiting exemplary hydrophobic amino acids include glycine (Gly), proline (Pro), phenylalanine (Phe), alanine (Ala), isoleucine (Ile), leucine (Leu), and valine (Val). In some embodiments, a protein such as an antibody described herein comprises a hydrophilic amino acid. Non-limiting exemplary hydrophilic amino acids include serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), cysteine (Cys), asparagine (Asn), glutamine (Gln), arginine (Arg), and histidine (His). In some embodiments, a protein such as an antibody described herein comprises an amphipathic amino acid. Non-limiting exemplary amphipathic amino acids include lysine (Lys), tryptophan (Trp), tyrosine (Tyr), and methionine (Met). In some embodiments, a protein such as an antibody described herein comprises an aliphatic amino acid. Non-limiting exemplary aliphatic amino acids include alanine (Ala), isoleucine (Ile), leucine (Leu) and valine (Val). In some embodiments, a protein such as an antibody described herein comprises an aromatic amino acid. Non-limiting exemplary aromatic amino acids include phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). In some embodiments, a protein such as an antibody described herein comprises an acidic amino acid. Non-limiting exemplary acidic amino acids include aspartic acid (Asp) and glutamic acid (Glu). In some embodiments, a protein such as an antibody described herein comprises a basic amino acid. Non-limiting exemplary basic amino acids include arginine (Arg), histidine (His), and lysine (Lys). In some embodiments, a protein such as an antibody described herein comprises a hydroxylic amino acid. Non-limiting exemplary hydroxylic amino acids include serine (Ser) and threonine (Thr). In some embodiments, a protein such as an antibody described herein comprises a sulfur-containing amino acid. Non-limiting exemplary sulfur-containing amino acids include cysteine (Cys) and methionine (Met). In some embodiments, a protein such as an antibody described herein comprises an amidic amino acid. Non-limiting exemplary amidic amino acids include asparagine (Asn) and glutamine (Gln).

[0284] In some embodiments, “polynucleotide,” or “nucleic acid,” as used interchangeably herein, refer to polymers of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. A polynucleotide may comprise modified nucleotides, such as, but not limited to methylated nucleotides and their analogs or non-nucleotide components. Modifications to the nucleotide structure may be imparted before or after assembly of the polymer. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component.

[0285] Percent (%) sequence identity with respect to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are known for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences are able to be determined, including algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or may be compiled from the source code. The ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

[0286] In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0287] In some embodiments, the term “about” means within 10% of the stated amount. For instance, an antibody variable region comprising about 80% identity to a reference variable region may comprise 72% to 88% identity to the reference variable region.

[0288] In certain aspects, antibodies are described herein that specifically bind to TL1A (Entrez Gene: 9966; UniProtKB: O95150). In some embodiments, the antibodies specifically bind to soluble TL1A. In some embodiments, the antibodies specifically bind to membrane bound TL1A. In some embodiments, an anti-TL1A antibody is provided having a heavy chain comprising four heavy chain framework regions (HCFR) and three heavy chain complementarity-determining regions (HCDR): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3, and HCFR4; and a light chain comprising four light chain framework regions (LCFR) and three light chain complementarity-determining regions (LCDR): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3, and LCFR4. An anti-TL1A antibody may comprise any region provided herein, for example, as provided in the tables, the examples, and the sequences. Exemplary anti-TL1A CDRs

[0289] In certain embodiments, an anti-TL1A antibody comprises a HCDR1 as set forth by SEQ ID NO: 1. In certain embodiments, an anti-TL1A antibody comprises a HCDR2 as set forth by any one of SEQ ID NOS: 2-5. In certain embodiments, an anti-TL1A antibody comprises a HCDR3 as set forth by any one of SEQ ID NOS: 6-9. In certain embodiments, an anti-TL1A antibody comprises a LCDR1 as set forth by SEQ ID NO: 10. In certain embodiments, an anti-TL1A antibody comprises a LCDR2 as set forth by SEQ ID NO: 11. In25746 certain embodiments, an anti-TL1A antibody comprises a LCDR3 as set forth by any one of SEQ ID NOS: 12-15. In a non-limiting example, an anti-TL1A antibody comprises a HCDR1 as set forth by SEQ ID NO: 1, a HCDR2 as set forth by SEQ ID NO: 2, a HCDR3 as set forth by SEQ ID NO: 6, a LCDR1 as set forth by SEQ ID NO: 10, a LCDR2 as set forth by SEQ ID NO: 11, and a LCDR3 as set forth by SEQ ID NO: 12. In some cases, the anti-TL1A antibody comprises the CDRs of antibody J of Table 10. In some cases, the anti-TL1A antibody comprises the CDRs of antibody J2 of Table 10. In some cases, the anti-TL1A antibody comprises the CDRs of antibody K of Table 10.

[0290] In certain embodiments, an anti-TL1A antibody comprises a HCDR1 as set forth by SEQ ID NOS: 401, 407, 413, or 450. In certain embodiments, an anti-TL1A antibody comprises a HCDR2 as set forth by SEQ ID NOS: 402, 408, 414, or 451. In certain embodiments, an anti-TL1A antibody comprises a HCDR3 as set forth by SEQ ID NOS: 403, 409, 415, or 452. In certain embodiments, an anti-TL1A antibody comprises a LCDR1 as set forth by SEQ ID NOS: 404, 410, 416, or 453. In certain embodiments, an anti-TL1A antibody comprises a LCDR2 as set forth by SEQ ID NOS: 405, 411, 417, or 454. In certain embodiments, an anti-TL1A antibody comprises a LCDR3 as set forth by SEQ ID NOS: 406, 412, 418, or 455.

[0291] In certain embodiments, an anti-TL1A antibody comprises a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 selected from Table 6. Table 6. Example CDR amino acid sequences SEQ ID NO Description Sequence 1 HCDR1 GFDIQDTYMH25746 404 LCDR1j RASQSVSSYLA 405 LCDR2j DASNRAT 4 L DR R P T 1 sth in antibody A, B, C, D, E, F, G, H, I, A2, B2, C2, D2, E2, F2, G2, H2, I2, J, J2, K, M, or N of Table 10. Table 10. CDR sequences from example anti-TL1A antibodies Antibody Heavy Chain CDR SEQ ID NOS Light Chain CDR SEQ ID NOS CDR1 CDR2 CDR3 CDR1 CDR2 CDR325746 D2 1, 2, 7 10, 11, 13 E2 1, 2, 7 10, 11, 14 F2 1 1 11 12CDRs set forth in an antibody selected from Table 7. Table 7. Example heavy chain variable region sequences25746 SEQ Description Sequence ID NO L A L A L L V L V L L L L L V L V L L L V L25746 116 203 VH, 197 EVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQAPGQGL VH, 209 VH, EWMGRIEPASGHIKYDPKFQGRVTMTRDTSTSTVYMELSSLRSEDTA 224 VH VYYCARSGGLPDWWGQGTTVTVSS L A L V L A L L A L A L V L V L A L A L A L A L A L A L V L A25746 133 109 VH, 91 VH, QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVRQAPGQGL 135 VH, 145 EWMGRIEPASGHIKYDPKFQGRVTMTRDTSTSTAYMELSSLRSEDTA VH, 153 VH VYYCARSGGLPDWWGQGTTVTVSS L A L A L A L A L L L V L L V L V L V L L V L V L V L25746 150 57 VH, 111 VH QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVRQRPGQGL EWMGRIEPASGHIKYDPKFQGRVTMTRDTSTSTVYMELSSLRSEDTA VYYCARSGGLPDWWGQGTTVTVSS L A L V L V L L V L A L A L V L A L V L L L V L L V L L A25746 168 171 VH, 177 VH QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVRQAPGQGL EWMGRIDPASGHIKYDPKFQGRATITTDTSTSTVYMELSSLRSEDTAV YYCARSGGLPDWWGQGTTVTVSS L V E T E T G F E T A S P G T E T S S K K W E T E T E Tn ceran emo mens, an an - an oy comprses e g can CDRs set forth in an antibody selected from Table 8. Table 8. Example light chain variable region sequences25746 SEQ Description Sequence ID NO Q Q S Q S Q S Q S25746 196 VL, 172 VL, 75 VL, 174 VL, 109 VL, 198 VL, Q Q S Q L Q S L Q T Q T Q L Q T Q T Q S Q S25746 218 88 VL EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQ KPGQAPRLLIYATSNLASGIPDRFSGSGSGTDYTLTIS RVEPEDFAVYYCQQWEGNPRTFGGGTKLEIK I I Q TI W S L Y T EI Q TI A W W S L A L I I W Sce a e o e s, a a - a o y co p ses e s se orth in any one of the antibodies of Table 1. For instance, an anti-TL1A antibody comprises the CDRs of antibody A15, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A107, A108, A109,25746 A110, A111, A112, A113, A114, A115, A116, A117, A118, A119, A120, A121, A122, A123, A124, A125, A126, A127, A128, A129, A130, A132, A133, A134, A135, A136, A137, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A148, A149, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A160, A161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A184, A185, A186, A187, A188, A189, A190, A191, A192, A193, A194, A195, A196, A197, A198, A199, A200, A201, A202, A203, A204, A205, A206, A207, A208, A209, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN. In a non-limiting example, an anti-TL1A antibody comprises the CDRs of antibody A219. Antibody CDRs may be defined by the Aho, Kabat, Chothia, or IMGT methods. Exemplary anti-TL1A Framework Regions

[0296] In certain embodiments, an anti-TL1A antibody comprises a heavy chain (HC) framework 1 (FR1) as set forth by SEQ ID NO: 304. In certain embodiments, an anti-TL1A antibody comprises a HC FR2 as set forth by any one of SEQ ID NOS: 305 or 313. In certain embodiments, an anti-TL1A antibody comprises a HC FR3 as set forth by any one of SEQ ID NOS: 306-307, 314-315. In certain embodiments, an anti-TL1A antibody comprises a HC FR4 as set forth by SEQ ID NO: 308. In certain embodiments, an anti-TL1A antibody comprises a LC FR1 as set forth by SEQ ID NO: 309. In certain embodiments, an anti-TL1A antibody comprises a LC FR2 as set forth by SEQ ID NO: 310. In certain embodiments, an anti-TL1A antibody comprises a LC FR3 as set forth by SEQ ID NO: 311. In certain embodiments, an anti-TL1A antibody comprises a LC FR4 as set forth by SEQ ID NO: 312. In a non-limiting example, an anti-TL1A antibody comprises a HC FR1 as set forth by SEQ ID NO: 304, a HC FR2 as set forth by SEQ ID NO: 305, a HC FR3 as set forth by SEQ ID NO: 306, a HC FR4 as set forth by SEQ ID NO: 308, a LC FR1 as set forth by SEQ ID NO: 309, a LC FR2 as set forth by SEQ ID NO: 310, a LC FR3 as set forth by SEQ ID NO: 311, and a LC FR4 as set forth by SEQ ID NO: 312. In a non-limiting example, an anti-TL1A antibody comprises a HC FR1 as set forth by SEQ ID NO: 304, a HC FR2 as set forth by SEQ ID NO: 305, a HC FR3 as set forth by SEQ ID NO: 307, a HC FR4 as set forth by SEQ ID NO: 308, a LC FR1 as set forth by SEQ ID NO: 309, a LC FR2 as set forth by SEQ ID NO: 310, a LC FR3 as set forth by SEQ ID NO: 311, and a LC FR4 as set forth by SEQ ID NO: 312.25746

[0297] In certain embodiments, an anti-TL1A antibody comprises the heavy chain framework regions set forth in an antibody selected from Table 7. In certain embodiments, an anti-TL1A antibody comprises the light chain framework regions set forth in an antibody selected from Table 8. In certain embodiments, an anti-TL1A antibody comprises the framework regions set forth in any one of the antibodies of Table 1. For instance, an anti- TL1A antibody comprises the framework regions of antibody A15, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A107, A108, A109, A110, A111, A112, A113, A114, A115, A116, A117, A118, A119, A120, A121, A122, A123, A124, A125, A126, A127, A128, A129, A130, A132, A133, A134, A135, A136, A137, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A148, A149, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A160, A161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A184, A185, A186, A187, A188, A189, A190, A191, A192, A193, A194, A195, A196, A197, A198, A199, A200, A201, A202, A203, A204, A205, A206, A207, A208, A209, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN. In a non-limiting example, an anti-TL1A antibody comprises the framework region of antibody A219. In another non- limiting example, the anti-TL1A antibody comprises the framework region of an antibody comprising SESQ ID NOS: 420 and 430. In another non-limiting example, the anti-TL1A antibody comprises the framework region of an antibody comprising SESQ ID NOS: 421 and 431. In another non-limiting example, the anti-TL1A antibody comprises the framework region of an antibody comprising SESQ ID NOS: 424 and 434. Antibody CDR and framework regions may be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0298] In some embodiments, an anti-TL1A antibody comprises a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human25746 IGHV1-46*02 framework and the human IGKV3-20 framework. In some embodiments, the amino acid modification(s) comprise: (a) a modification at amino acid position 45 in the heavy chain variable region; (b) a modification at amino acid position 47 in the heavy chain variable region; (c) a modification at amino acid position 55 in the heavy chain variable region; (d) a modification at amino acid position 78 in the heavy chain variable region; (e) a modification at amino acid position 80 in the heavy chain variable region; (f) a modification at amino acid position 82 in the heavy chain variable region; (g) a modification at amino acid position 89 in the heavy chain variable region; or (h) a modification at amino acid position 91 in the heavy chain variable region, per Aho or Kabat numbering; or a combination of two or more modifications selected from (a) to (h). In some embodiments, the amino acid modification(s) comprise (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L in the heavy chain variable region, per Aho or Kabat numbering; or a combination of two or more modifications selected from (a) to (h). In some embodiments, the amino acid modification(s) comprise: A47R. In some embodiments, the amino acid modification(s) comprise: A47R, M55I, V78A, M80I, R82T, V89A, and M91L; A47R, M80I, and R82T; A47R, M80I, R82T, V89A, and M91L; or A47R, M55I, V78A, M80I, V89A, and M91L. In some embodiments, the amino acid modification(s) comprise: R45K and A47R. In some embodiments, the amino acid modification(s) comprise: R45K, A47R, V89A, and M91L. In some embodiments, the amino acid modification(s) comprise: R45K and A47R, and M80I. In some embodiments, the amino acid modification(s) comprise: R45K, A47R, M80I, and M91L; R45K, A47R, V78A, M80I, V89A, and M91L; R45K, A47R, M55I, V78A, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, V89A, and M91L; R45K, A47R, M55I, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, and V89A; R45K, A47R, M80I, R82T, V89A, M91L; or R45K, A47R, M55I, M80I, V89A, and M91L. In some embodiments, the amino acid modification(s) comprise: R45K. In some embodiments, the amino acid modification(s) comprise: R45K and V78A. In some embodiments, the amino acid modification(s) comprise: V78A. In some embodiments, the amino acid modification(s) comprise: V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. In some embodiments, the amino acid modification(s) comprise: V89A. In some embodiments, the amino acid modification(s) comprise: M80I. In some embodiments, the amino acid modification(s) comprises: (a) a modification at amino acid position 54 in the light chain variable region; and / or (b) a modification at amino acid position 55 in the light chain variable region, per Aho or Kabat numbering. In some embodiments, the amino acid modification(s) comprises L54P in the light chain variable region, per Aho or Kabat25746 numbering. In some embodiments, the amino acid modification(s) comprises L55W in the light chain variable region, per Aho or Kabat numbering.

[0299] In some embodiments, an anti-TL1A antibody comprises a heavy chain framework comprising SEQ ID NO: 301 (X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS) or SEQ ID NO: 302 (X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC[HCDR3]WGQGTTVTVSS). In some cases, X1 is Q. In some cases, X1 = E. In some cases, X2 = R. In some cases, X2 = K. In some cases, X3 = A. In some cases, X3 = R. In some cases, X4 = M. In some cases, X4 = I. In some cases, X5 = V. In some cases, X5 = A. In some cases, X6 = M. In some cases, X6 = I. In some cases, X7 = R. In some cases, X7 = T. In some cases, X8 = V. In some cases, X8 = A. In some cases, X9 = M. In some cases, X9 = L. In some embodiments, X1 is at position 1 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X2 is at position 45 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X3 is at position 47 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X4 is at position 55 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X5 is at position 78 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X6 is at position 80 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X7 is at position 82 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X8 is at position 89 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X9 is at position 91 of IGHV1-46*02 as determined by Aho or Kabat numbering.

[0300] In one aspect, provided herein is a first embodiment of an anti-TL1A antibody comprising a heavy chain framework comprising IGHV1-46*02, or a variant thereof, wherein the variant comprises between about 1 and about 9 amino acid substitutions, or between about 1 and about 20 amino acid substitutions, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from IGHV1-46*02 framework. Additional embodiments include: (2) The anti-TL1A of embodiment (1), wherein the heavy chain framework comprises SEQ ID NO: 301. (3) The anti-TL1A of embodiment 2, wherein X1 = Q. (4) The anti-TL1A of embodiment 2, wherein X1 = E. (5) The anti-TL1A of any one of embodiments 2-4, wherein X2 = R. (6) The anti-TL1A of any one of embodiments 2-4,wherein X2 = K. (7) The anti-TL1A of any one of embodiments 2-6, wherein X3 = A. (8) The anti-TL1A of any one of embodiments 2-6, wherein X3 = R. (9) The anti-TL1A of any one of embodiments 2-8, wherein X4 = M. (10) The anti-TL1A of any one of embodiments 2-8, wherein X4 = I. (11) The anti-TL1A of any one of embodiments 2-10, wherein X5 = V. (12) The anti-TL1A of any one of embodiments 2-10, wherein X5 = A. (13) The anti-TL1A of any one of embodiments 2-12, wherein X6 = M. (14) The anti-TL1A of any one of embodiments 2-12, wherein X6 = I. (15) The anti-TL1A of any one of embodiments 2-14, wherein X7 = R. (16) The anti-TL1A of any one of embodiments 2-14, wherein X7 = T. (17) The anti-TL1A of any one of embodiments 2-16, wherein X8 = V. (18) The anti-TL1A of any one of embodiments 2-16, wherein X8 = A. (19) The anti-TL1A of any one of embodiments 2-18, wherein X9 = M. (20) The anti-TL1A of any one of embodiments 2-4, wherein X9 = L. (21) The anti-TL1A of any one of embodiments 1-20, comprising antibody A. (22) The anti- TL1A of any one of embodiments 1-20, comprising antibody B. (23) The anti-TL1A of any one of embodiments 1-20, comprising antibody C. (24) The anti-TL1A of any one of embodiments 1-20, comprising antibody D. (25) The anti-TL1A of any one of embodiments 1-20, comprising antibody E. (26) The anti-TL1A of any one of embodiments 1-20, comprising antibody F. (27) The anti-TL1A of any one of embodiments 1-20, comprising antibody G or I. (28) The anti-TL1A of any one of embodiments 1-20, comprising antibody H. (34) The anti-TL1A of any one of embodiments 1-33, comprising a light chain comprising a light chain framework comprising IGKV3-20*01, or a variant thereof, wherein the variant comprises between about 1 and about 2 substitutions, or between about 1 and about 20 amino acid substitutions, or about 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 the framework. (35) The anti-TL1A antibody of embodiment 34, wherein X10 is L. (36) The anti-TL1A antibody of embodiment 34, wherein X10 is P. (37) The anti-TL1A antibody of any one of embodiments 34-36, wherein X11 is L. (38) The anti-TL1A antibody of any one of embodiments 34-36, wherein X11 is W.

[0301] In some embodiments, an anti-TL1A antibody comprises a light chain framework comprising SEQ ID NO: 303 (EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDR FSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK). In some cases, X10 is L. In some cases, X10 is P. In some cases, X11 is L. In some cases, X11 is W. In some embodiments, X10 is at position 54 of IGKV3-20*01 as determined by Aho or Kabat numbering. In some embodiments, X11 is at position 55 of IGKV3-20*01 as determined by Aho or Kabat numbering.

[0302] In some embodiments, an anti-TL1A antibody comprises a heavy chain framework comprising IGHV1-46*02. In some embodiments, an anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising between about 1 and about 20 amino acid substitutions from SEQ ID NO: 316. In some embodiments, an anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising between about 1 and about 9 amino acid substitutions from SEQ ID NO: 316. In some embodiments, an anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from SEQ ID NO: 316 in the framework. In some cases, the heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises R45K, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises A47R, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises M55I, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises V78A, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises M80I, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises R82T, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises V89A, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises M91L, as determined by Aho or Kabat numbering.

[0303] In some embodiments, an anti-TL1A antibody comprises a light chain framework comprising IGKV3-20*01. In some embodiments, an anti-TL1A antibody comprises a variant of IGKV3-20*01 comprising between about 1 and about 20 amino acid substitutions from SEQ ID NO: 317. In some embodiments, an anti-TL1A antibody comprises a variant of IGKV3-20*01 comprising about 1 amino acid substitution from SEQ ID NO: 317. In some embodiments, an anti-TL1A antibody comprises a light chain framework comprising a variant of IGKV3-20*01 comprising about 2 amino acid substitutions from SEQ ID NO: 317. In some embodiments, an anti-TL1A antibody comprises a light chain framework comprising a variant of IGKV3-20*01 comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from SEQ ID NO: 317 in the framework. In some cases, the light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some cases, the25746 light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

[0304] In some embodiments, an anti-TL1A antibody comprises a heavy chain FR1 as set forth by SEQ ID NO: 304. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR2 as set forth by SEQ ID NO: 305. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR2 as set forth by SEQ ID NO: 313. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 306. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 307. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 314. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 315. In some embodiments, an anti-TL1A antibody comprises a heavy chain FR4 as set forth by SEQ ID NO: 308. In some embodiments, an anti-TL1A antibody comprises a light chain FR1 as set forth by SEQ ID NO: 309. In some embodiments, an anti-TL1A antibody comprises a light chain FR2 as set forth by SEQ ID NO: 310. In some embodiments, an anti-TL1A antibody comprises a light chain FR3 as set forth by SEQ ID NO: 311. In some embodiments, an anti-TL1A antibody comprises a light chain FR4 as set forth by SEQ ID NO: 312. In some embodiments, an anti-TL1A antibody comprises a framework region of Table 9A. Table 9A. Example framework sequences25746 SEQ Description Sequence ID R,25746 304 219 HC FR1, QVQLVQSGAEVKKPGASVKVSCKAS 212 HC FR1 305 219 HC FR2 WVK RPG GLEWMG G A

[0305] In one aspect, provided herein is an anti-TL1A antibody comprising a heavy chain variable region comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 101-169 or 420-427; and a light chain variable region at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 201-220 or 430-437.

[0306] Further provided herein is a first embodiment of an anti-TL1A antibody comprising a heavy chain variable region and a light chain variable region. Non-limiting additional embodiments include: (Embodiment 2) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101 or a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 101. (Embodiment 3) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,25746 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 102. (Embodiment 4) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 103. (Embodiment 5) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 104. (Embodiment 6) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 105. (Embodiment 7) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 106 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 106. (Embodiment 8) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 107. (Embodiment 9) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 108. (Embodiment 10) The anti-TL1A antibody of embodiment 1, wherein the heavy chain25746 variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 109. (Embodiment 11) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 110 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 110. (Embodiment 12) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 111 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 111. (Embodiment 13) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 112 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 112. (Embodiment 14) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 113 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 113. (Embodiment 15) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 114. (Embodiment 16) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 115 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:25746 115. (Embodiment 17) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 116. (Embodiment 18) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 117. (Embodiment 19) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 118 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 118. (Embodiment 20) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 119. (Embodiment 21) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 120 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 120. (Embodiment 22) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 121. (Embodiment 23) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122 or the heavy chain variable region comprises a sequence having about 1,25746 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 122. (Embodiment 24) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 123 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 123. (Embodiment 25) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 124. (Embodiment 26) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 125 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 125. (Embodiment 27) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 126. (Embodiment 28) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 127. (Embodiment 29) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 128. (Embodiment 30) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical25746 to SEQ ID NO: 129 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 129. (Embodiment 31) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 130. (Embodiment 32) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 131 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 131. (Embodiment 33) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 132. (Embodiment 34) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 133 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 133. (Embodiment 35) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 134 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 134. (Embodiment 36) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 135 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 135. (Embodiment 37) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%,25746 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 136 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 136. (Embodiment 38) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 137 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 137. (Embodiment 39) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 138 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 138. (Embodiment 40) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 139 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 139. (Embodiment 41) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 140 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 140. (Embodiment 42) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 141 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 141. (Embodiment 43) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 142 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 142. (Embodiment 44) The anti-TL1A antibody of embodiment 1, wherein the heavy chain25746 variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 143 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 143. (Embodiment 45) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 144 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 144. (Embodiment 46) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 145 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 145. (Embodiment 47) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 146 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 146. (Embodiment 48) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 147 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 147. (Embodiment 49) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 148 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 148. (Embodiment 50) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 149 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:25746 149. (Embodiment 51) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 150 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 150. (Embodiment 52) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 151 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 151. (Embodiment 53) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 152 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 152. (Embodiment 54) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 153 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 153. (Embodiment 55) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 154 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 154. (Embodiment 56) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 155 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 155. (Embodiment 57) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 156 or the heavy chain variable region comprises a sequence having about 1,25746 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 156. (Embodiment 58) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 157 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 157. (Embodiment 59) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 158 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 158. (Embodiment 60) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 159 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 159. (Embodiment 61) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 160 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 160. (Embodiment 62) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 161 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 161. (Embodiment 63) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 162 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 162. (Embodiment 64) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical25746 to SEQ ID NO: 163 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 163. (Embodiment 65) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 164 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 164. (Embodiment 66) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 165 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 165. (Embodiment 67) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 166 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 166. (Embodiment 68) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 167 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 167. (Embodiment 70) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 168 or 169, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 168 or 169. (Embodiment 70) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, 421, 422 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 430, 431, or 432.25746

[0307] (Embodiment 71) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 201. (Embodiment 72) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 202. (Embodiment 73) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 203 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 203. (Embodiment 74) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 204. (Embodiment 75) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 205. (Embodiment 76) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 206. (Embodiment 77) The anti-TL1A antibody of any one of embodiments 1- 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,25746 98%, 99%, or 100% identical to SEQ ID NO: 207 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 207. (Embodiment 78) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 208 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 208. (Embodiment 79) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 209 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 209. (Embodiment 80) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 210 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 210. (Embodiment 81) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 211 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 211. (Embodiment 82) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 212 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 212. (Embodiment 83) The anti-TL1A antibody of any one of embodiments 1- 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 213 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 213. (Embodiment 84) The anti-TL1A antibody of any one of25746 embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 214 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 214. (Embodiment 85) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 215 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 215. (Embodiment 86) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 216 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 216. (Embodiment 87) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 217 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 217. (Embodiment 88) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 218 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 218. (Embodiment 89) The anti-TL1A antibody of any one of embodiments 1- 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 219 or 220, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 219 or 220. (Embodiment 90) The anti-TL1A antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430, 431, or25746 432 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 430, 431, or 432.

[0308] (Embodiment 91) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 92) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 93) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 94) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 95) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0309] (Embodiment 96) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or25746 100% identical to SEQ ID NO: 103, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 97) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 106, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 98) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 99) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 100) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.

[0310] (Embodiment 101) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 102) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%,25746 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 103) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 203. (Embodiment 104) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 105) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0311] (Embodiment 106) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 107) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 110, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 108) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a25746 sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 111, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 109) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 112, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 110) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 113, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0312] (Embodiment 111) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 112) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 115, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 113) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 114) The anti-TL1A antibody of25746 embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 115) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 118, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0313] (Embodiment 116) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 117) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 118) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 119) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to25746 SEQ ID NO: 204. (Embodiment 120) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0314] (Embodiment 121) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 122) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 123) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 120, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 124) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 125) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence25746 at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.

[0315] (Embodiment 126) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 207. (Embodiment 127) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 123, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 128) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 129) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 125, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 130) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.

[0316] (Embodiment 131) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or25746 100% identical to SEQ ID NO: 117, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 132) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 133) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 134) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 135) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0317] (Embodiment 136) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 137) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%,25746 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 138) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206. (Embodiment 139) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 140) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0318] (Embodiment 141) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 142) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206. (Embodiment 143) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a25746 sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 129, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 144) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 145) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 131, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.

[0319] (Embodiment 146) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 147) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 133, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 148) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 134, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 149) The anti-TL1A antibody of25746 embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 135, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 150) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 151) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 152) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 153) The anti-TL1A antibody of embodiment 1, comprising A500. (Embodiment 154) The anti-TL1A antibody of embodiment 1, comprising A501. (Embodiment 155) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430. (Embodiment 156) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 421, and the light chain variable region comprises a sequence25746 at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 431. (Embodiment 157) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 422, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 432. (Embodiment 158) The anti- TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 427, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 437. Exemplary anti-TL1A Constant Regions

[0320] In some embodiments, one or more amino acid modifications may be introduced into the Fragment crystallizable (Fc) region of a human or humanized antibody, thereby generating an Fc region variant. An Fc region may comprise a C-terminal region of an immunoglobulin heavy chain that comprises a hinge region, CH2 domain, CH3 domain, or any combination thereof. As used herein, an Fc region includes native sequence Fc regions and variant Fc regions. The Fc region variant may comprise a human Fc region sequence (e.g., a human IgG1, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g., a substitution, addition, or deletion) at one or more amino acid positions. In an exemplary embodiment, the Fc region comprises any one of SEQ ID NOS: 320-367. In some embodiments, the anti-TL1A antibody comprises a constant region comprising any one of SEQ ID NOS: 319, 368-381.

[0321] In some embodiments, antibodies of this disclosure have a reduced effector function as compared to a human IgG. Effector function refers to a biological event resulting from the interaction of an antibody Fc region with an Fc receptor or ligand. Non-limiting effector functions include C1q binding, complement dependent cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody- dependent cellular phagocytosis (ADCP), cytokine secretion, immune complex-mediated antigen uptake by antigen presenting cells, down regulation of cell surface receptors (e.g., B cell receptor), and B cell activation. In some cases, antibody-dependent cell-mediated25746 cytotoxicity (ADCC) refers to a cell-mediated reaction in which nonspecific cytotoxic cells expressing Fc receptors (e.g., natural killer cells, neutrophils, macrophages) recognize bound antibody on a target cell, subsequently causing lysis of the target cell. In some cases, complement dependent cytotoxicity (CDC) refers to lysing of a target cells in the presence of complement, where the complement action pathway is initiated by the binding of C1q to antibody bound with the target.

[0322] Some Fc regions have a natural lack of effector function, and some Fc regions can comprise mutations that reduce effector functions. For instance, IgG4 has low ADCC and CDC activities and IgG2 has low ADCC activity.

[0323] The disclosure provides antibodies comprising Fc regions characterized by exhibiting ADCC that is reduced by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70% or more as compared to an antibody comprising a non-variant Fc region, i.e., an antibody with the same sequence identity but for the substitution(s) that decrease ADCC (such as human IgG1, SEQ ID NO: 320). The disclosure provides antibodies comprising Fc regions characterized by exhibiting CDC that is reduced by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70% or more as compared to an antibody comprising a non-variant Fc region, i.e., an antibody with the same sequence identity but for the substitution(s) that decrease CDC (such as human IgG1, SEQ ID NO: 320). In certain embodiments, the antibodies of this disclosure have reduced effector function as compared with human IgG1. In certain embodiments, antibodies herein have no detectable ADCC activity. In certain embodiments, the reduction and / or abatement of ADCC activity may be attributed to the reduced affinity antibodies of the invention exhibit for Fc ligands and / or receptors. In certain embodiments, antibodies herein exhibit no detectable CDC activities. In some embodiments, the reduction and / or abatement of CDC activity may be attributed to the reduced affinity antibodies of the invention exhibit for Fc ligands and / or receptors. Measurement of effector function may be performed as described in Example 3.

[0324] In some embodiments, antibodies comprising Fc regions described herein exhibit decreased affinities to C1q relative to an unmodified antibody (e.g., human IgG1 having SEQ ID NO: 320). In some embodiments, antibodies herein exhibit affinities for C1q receptor that are at least 2 fold, or at least 3 fold, or at least 5 fold, or at least 7 fold, or at least 10 fold, or at least 20 fold, or at least 30 fold, or at least 40 fold, or at least 50 fold, or at least 60 fold, or at least 70 fold, or at least 80 fold, or at least 90 fold, or at least 100 fold, or at least 200 fold less than an unmodified antibody. In some embodiments, antibodies herein25746 exhibit affinities for C1q that are at least 90%, at least 80%, at least 70%, at least 60%, at least 50%, at least 40%, at least 30%, at least 20%, at least 10%, or at least 5% less than an unmodified antibody.

[0325] In some embodiments, the antibodies of this disclosure are variants that possess some but not all effector functions, which make it a desirable candidate for applications in which the half-life of the antibody in vivo is important yet certain effector functions (such as complement and ADCC) are unnecessary or deleterious.

[0326] In vitro and / or in vivo cytotoxicity assays can be conducted to confirm the reduction / depletion of CDC and / or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks FcγR binding (hence likely lacking ADCC activity) but retains FcRn binding ability. Measurement of effector function may be performed as described in Example 3.

[0327] In some embodiments, antibodies are tested for binding to Fcγ receptors and complement C1q by ELISA. In some embodiments, antibodies are tested for the ability to activate primary human immune cells in vitro, for example, by assessing their ability to induce expression of activation markers.

[0328] In some embodiments, assessment of ADCC activity of an anti-TL1A antibody comprises adding the antibody to target cells in combination with immune effector cells, which may be activated by the antigen antibody complexes resulting in cytolysis of the target cell. Cytolysis may be detected by the release of label (e.g. radioactive substrates, fluorescent dyes or natural intracellular proteins) from the lysed cells. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Specific examples of in vitro ADCC assays are described in Wisecarver et al., 1985 79:277-282; Bruggemann et al., 1987, J Exp Med 166:1351-1361; Wilkinson et al., 2001, J Immunol Methods 258:183-191; Patel et al., 1995 J Immunol Methods 184:29-38. Alternatively, or additionally, ADCC activity of the antibody of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al., 1998, PNAS USA 95:652-656.

[0329] In some embodiments, an assessment of complement activation, a CDC assay, may be performed as described in Gazzano-Santoro et al., 1996, J. Immunol. Methods, 202:163.

[0330] Non-limiting examples of Fc mutations in IgG1 that may reduce ADCC and / or CDC include substitutions at one or more of positions: 231, 232, 234, 235, 236, 237, 238, 239, 264, 265, 267, 269, 270, 297, 299, 318, 320, 322, 325, 327, 328, 329, 330, and 331 in25746 IgG1, where the numbering system of the constant region is that of the EU index as set forth by Kabat. In certain embodiments, the antibodies of this disclosure have reduced effector function as compared with human IgG1.

[0331] In some embodiments, an antibody comprises an IgG1 Fc region comprising one or more of the following substitutions according to the Kabat numbering system: N297A, N297Q, N297D, D265A, S228P, L235A, L237A, L234A, E233P, L234V, C236 deletion, P238A, A327Q, P329A, P329G, L235E, P331S, L234F, 235G, 235Q, 235R, 235S, 236F, 236R, 237E, 237K, 237N, 237R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, 254V, 255N, 256H, 256K, 256R, 256V, 264S, 265H, 265K, 265S, 265Y, 267G, 267H, 267I, 267K, 268K, 269N, 269Q, 270A, 270G, 270M, 270N, 271T, 272N, 279F, 279K, 279L, 292E, 292F, 292G, 292I, 293S, 301W, 304E, 311E, 311G, 311S, 316F, 327T, 328V, 329Y, 330R, 339E, 339L, 343I, 343V, 373A, 373G, 373S, 376E, 376W, 376Y, 380D, 382D, 382P, 385P, 424H, 424M, 424V, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, 440V.

[0332] In some embodiments, an antibody comprises a Fc region selected from the representative sequences disclosed in Table 3, Table 13, and Table 9B. In some embodiments, an antibody comprises an IgG1 Fc region comprising E233P, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising S228P and L235E. In some embodiments, an antibody comprises an IgG1 Fc region comprising L235E, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A and L235A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A, L235A, and G237A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A, L235A, P329G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234F, L235E, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A, L235E, and G237A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A, L235E, G237A, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A, L235A, G237A, P238S, H268A, A330S, and P331S (IgG1σ), according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising L234A, L235A, and P329A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region25746 comprising G236R and L328R, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising G237A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising F241A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising V264A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising D265A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising D265A and N297A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising D265A and N297G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising D270A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising N297A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising N297G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising N297D, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising N297Q, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising P329A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising P329G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising P329R, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising A330L, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising P331A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG1 Fc region comprising P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region. In some embodiments, an antibody comprises an IgG4 Fc region. In some embodiments, an antibody comprises an IgG4 Fc region comprising S228P, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising S228P, F234A, and L235A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2-IgG4 cross-subclass (IgG2 / G4) Fc region. In some embodiments, an antibody comprises an IgG2-IgG3 cross-subclass Fc region. In some embodiments, an antibody comprises an IgG2 Fc region comprising H268Q, V309L, A330S, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an25746 IgG2 Fc region comprising V234A, G237A, P238S, H268A, V309L, A330S, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises a Fc region comprising high mannose glycosylation.

[0333] In some embodiments, an antibody comprises an IgG4 Fc region comprising a S228P substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising an A330S substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising a P331S substitution, according to the Kabat numbering system.

[0334] In some embodiments, an antibody comprises an IgG2 Fc region comprising an A330S substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising an P331S substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising an 234A substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising an 237A substitution, according to the Kabat numbering system.

[0335] In certain embodiments, an anti-TL1A described herein comprises a Fc region as shown in Table 13. Table 13. Exemplary Fc Mutations MutationsConstant Region (SEQ ID NO)KDL R EM K EMmprises a Fc region comprising a sequence from Table 9B. In certain embodiments, an anti-TL1A25746 antibody described herein comprises a Fc region comprising any one of SEQ ID NOS: 320- 367 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 320-367

[0337] In some embodiments, anti-TL1A described herein comprise a light chain constant region comprising SEQ ID NO: 319 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 319. Additional Non-limiting Example anti-TL1A Antibody Embodiments CDR Embodiments

[0338] In one aspect, provided herein is a first embodiment of an anti-TL1A antibody. As used herein, an anti-TL1A antibody includes an anti-TL1A antigen binding fragment. Non-limiting additional embodiments include: (Embodiment 2) The anti-TL1A antibody of embodiment 1, comprising a heavy chain comprising a HCDR1 comprising SEQ ID NO: 1, 401, 407, 413, or 450, a HCDR2 comprising SEQ ID NO: 2, 3, 4, 5, 402, 408, 414, or 451, and a HCDR3 comprising SEQ ID NO: 6, 7, 8, 9, 403, 409, 415, or 452, and a light chain comprising a LCDR1 comprising SEQ ID NO: 10, 404, 410, 416, or 453, a LCDR2 comprising SEQ ID NO: 11, 405, 411, 417, or 454, and a LCDR3 comprising SEQ ID NO: 12, 13, 14, 15, 406, 412, 418, or 455. (Embodiment 3) The anti-TL1A antibody of embodiment 1, comprising a HCDR1 comprising SEQ ID NO: 1. (Embodiment 4) The anti- TL1A antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 2. (Embodiment 5) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 3. (Embodiment 6) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 4. (Embodiment 7) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 5. (Embodiment 8) The anti-TL1A antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 6. (Embodiment 9) The anti-TL1A antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 7. (Embodiment 10) The anti-TL1A antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 8. (Embodiment 11) The anti-TL1A antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 9. (Embodiment 12) The anti-TL1A antibody of any one of embodiments 1-10, comprising a LCDR1 comprising SEQ ID NO: 10. (Embodiment 13) The anti-TL1A antibody of any one of embodiments 1-11, comprising a LCDR2 comprising SEQ ID NO: 11. (Embodiment 14) The anti-TL1A antibody of any one of embodiments 1-12, comprising a LCDR3 comprising SEQ ID NO: 12. (Embodiment 15) The anti-TL1A antibody of any one of embodiments 1-12,25746 comprising a LCDR3 comprising SEQ ID NO: 13. (Embodiment 16) The anti-TL1A antibody of any one of embodiments 1-12, comprising a LCDR3 comprising SEQ ID NO: 14 or 15. (Embodiment 17) the anti-TL1A antibody of embodiment 1, comprising the CDRs of antibody A, B, C, D, E, F, G, H, I, A2, B2, C2, D2, E2, F2, G2, H2, I2, J, K, M, or N (Table 10). (Embodiment 18) The anti-TL1A antibody of embodiment 1, comprising a heavy chain variable region comprising: (a) an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1; (b) an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5; and (c) an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and the light chain variable region comprises: (d) an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10; (e) an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11; and (f) an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15. (Embodiment 19) The anti-TL1A antibody of embodiment 1, comprising a HCDR1 as set forth by SEQ ID NO: 1, a HCDR2 as set forth by SEQ ID NO: 2, a HCDR3 as set forth by SEQ ID NO: 6, a LCDR1 as set forth by SEQ ID NO: 10, a LCDR2 as set forth by SEQ ID NO: 11, and a LCDR3 as set forth by SEQ ID NO: 12 Framework Embodiments

[0339] (Embodiment 20) The anti-TL1A antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising IGHV1-46*02. (Embodiment 21) The anti- TL1A antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising a variant of IGHV1-46*02 comprising between about 1 and about 20 amino acid substitutions from SEQ ID NO: 316. (Embodiment 22) The anti-TL1A antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising a variant of IGHV1- 46*02 comprising between about 1 and about 9 amino acid substitutions from SEQ ID NO: 316. (Embodiment 23) The anti-TL1A antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising a variant of IGHV1-46*02 comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from SEQ ID NO: 316 in the framework. (Embodiment 24) The anti-TL1A antibody of any one of embodiments 21-23, wherein the heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. (Embodiment 25) The anti-TL1A antibody of any one of embodiments 21-24, wherein the heavy chain framework substitution comprises R45K, as determined by Aho or Kabat numbering. (Embodiment 26) The anti-TL1A antibody of any one of embodiments 21-25, wherein the heavy chain framework substitution comprises A47R, as determined by Aho or Kabat numbering. (Embodiment 27) The anti-25746 TL1A antibody of any one of embodiments 21-26, wherein the heavy chain framework substitution comprises M55I, as determined by Aho or Kabat numbering. (Embodiment 28) The anti-TL1A antibody of any one of embodiments 21-27, wherein the heavy chain framework substitution comprises V78A, as determined by Aho or Kabat numbering. (Embodiment 29) The anti-TL1A antibody of any one of embodiments 21-28, wherein the heavy chain framework substitution comprises M80I, as determined by Aho or Kabat numbering. (Embodiment 30) The anti-TL1A antibody of any one of embodiments 21-29, wherein the heavy chain framework substitution comprises R82T, as determined by Aho or Kabat numbering. (Embodiment 31) The anti-TL1A antibody of any one of embodiments 21- 30, wherein the heavy chain framework substitution comprises V89A, as determined by Aho or Kabat numbering. (Embodiment 32) The anti-TL1A antibody of any one of embodiments 21-31, wherein the heavy chain framework substitution comprises M91L, as determined by Aho or Kabat numbering.

[0340] (Embodiment 33) The anti-TL1A antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising SEQ ID NO: 301. (Embodiment 34) The anti-TL1A antibody of embodiment 33, wherein X1 is Q. (Embodiment 35) The anti-TL1A of embodiment 33, wherein X1 = E. (Embodiment 36) The anti-TL1A of any one of embodiments 33-35, wherein X2 = R. (Embodiment 37) The anti-TL1A of any one of embodiments 33-35, wherein X2 = K. (Embodiment 38) The anti-TL1A of any one of embodiments 33-37, wherein X3 = A. (Embodiment 39) The anti-TL1A of any one of embodiments 33-37, wherein X3 = R. (Embodiment 40) The anti-TL1A of any one of embodiments 33-39, wherein X4 = M. (Embodiment 41) The anti-TL1A of any one of embodiments 33-39, wherein X4 = I. (Embodiment 42) The anti-TL1A of any one of embodiments 33-41, wherein X5 = V. (Embodiment 43) The anti-TL1A of any one of embodiments 33-41, wherein X5 = A. (Embodiment 44) The anti-TL1A of any one of embodiments 33-43, wherein X6 = M. (Embodiment 45) The anti-TL1A of any one of embodiments 33-43, wherein X6 = I. (Embodiment 46) The anti-TL1A of any one of embodiments 33-45, wherein X7 = R. (Embodiment 47) The anti-TL1A of any one of embodiments 33-45, wherein X7 = T. (Embodiment 48) The anti-TL1A of any one of embodiments 33-47, wherein X8 = V. (Embodiment 49) The anti-TL1A of any one of embodiments 33-47, wherein X8 = A. (Embodiment 50) The anti-TL1A of any one of embodiments 33-49, wherein X9 = M. (Embodiment 51) The anti-TL1A of any one of embodiments 33-49, wherein X9 = L.25746

[0341] (Embodiment 52) The anti-TL1A antibody of any one of embodiments 1-51, comprising a light chain framework comprising IGKV3-20*01. (Embodiment 53) The anti- TL1A antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3-20*01 comprising between about 1 and about 20 amino acid substitutions from SEQ ID NO: 317. (Embodiment 54) The anti-TL1A antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3- 20*01 comprising about 1 amino acid substitution from SEQ ID NO: 317. (Embodiment 55) The anti-TL1A antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3-20*01 comprising about 2 amino acid substitutions from SEQ ID NO: 317. (Embodiment 56) The anti-TL1A antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3- 20*01 comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from SEQ ID NO: 317 in the framework. (Embodiment 57) The anti-TL1A antibody of any one of embodiments 53-56, wherein the light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. (Embodiment 58) The anti-TL1A antibody of any one of embodiments 53-57, wherein the light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

[0342] (Embodiment 59) The anti-TL1A antibody of any one of embodiments 1-51, comprising a light chain comprising a light chain framework comprising SEQ ID NO: 303. (Embodiment 60) The anti-TL1A antibody of embodiment 59, wherein X10 is L. (Embodiment 61) The anti-TL1A antibody of embodiment 59, wherein X10 is P. (Embodiment 62) The anti-TL1A antibody of any one of embodiments 59-61, wherein X11 is L. (Embodiment 63) The anti-TL1A antibody of any one of embodiments 59-61, wherein X11 is W.

[0343] (Embodiment 64) The anti-TL1A antibody of any one of embodiments 1-19, comprising a heavy chain variable framework region comprising a modified human IGHV1- 46*02 framework, and a light chain variable framework region comprising a human IGKV3- 20 framework or a modified human IGKV3-20 framework, wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise at least one amino acid modification(s) as compared to the human IGHV1-46*02 framework and the human IGKV3-20 framework. (Embodiment 65) The antibody of embodiment 64, wherein the at least one amino acid modification(s) is no more than about 13, 12, 11, 10, 9, or 8 amino acid modifications. (Embodiment 66) The antibody of embodiment 64 or embodiment 65, wherein the amino acid modification(s) comprise: a modification at amino25746 acid position 45 in the heavy chain variable region. (Embodiment 67) The antibody of any one of embodiments 64-66, wherein the amino acid modification(s) comprise a modification at amino acid position 47 in the heavy chain variable region. (Embodiment 68) The antibody of any one of embodiments 64-67, wherein the amino acid modification(s) comprise a modification at amino acid position 55 in the heavy chain variable region. (Embodiment 69) The antibody of any one of embodiments 64-68, wherein the amino acid modification(s) comprise a modification at amino acid position 78 in the heavy chain variable region. (Embodiment 70) The antibody of any one of embodiments 64-69, wherein the amino acid modification(s) comprise a modification at amino acid position 80 in the heavy chain variable region. (Embodiment 71) The antibody of any one of embodiments 64-70, wherein the amino acid modification(s) comprise a modification at amino acid position 82 in the heavy chain variable region. (Embodiment 72) The antibody of any one of embodiments 64-71, wherein the amino acid modification(s) comprise a modification at amino acid position 89 in the heavy chain variable region. (Embodiment 73) The antibody of any one of embodiments 64- 72, wherein the amino acid modification(s) comprise a modification at amino acid position 91 in the heavy chain variable region, per Aho or Kabat numbering. (Embodiment 74) The antibody of any one of embodiments 64-65, wherein the amino acid modification(s) comprise (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L in the heavy chain variable region, per Aho or Kabat numbering; or a combination of two or more modifications selected from (a) to (h). (Embodiment 75) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: A47R. (Embodiment 76) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: A47R, M55I, V78A, M80I, R82T, V89A, and M91L; A47R, M80I, and R82T; A47R, M80I, R82T, V89A, and M91L; or A47R, M55I, V78A, M80I, V89A, and M91L. (Embodiment 77) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K and A47R. (Embodiment 78) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K, A47R, V89A, and M91L. (Embodiment 79) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K and A47R, and M80I. (Embodiment 80) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K, A47R, M80I, and M91L; R45K, A47R, V78A, M80I, V89A, and M91L; R45K, A47R, M55I, V78A, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, V89A, and M91L; R45K, A47R, M55I, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, and V89A; R45K, A47R, M80I, R82T, V89A, M91L; or R45K, A47R, M55I, M80I, V89A, and M91L. (Embodiment 81) The antibody of embodiment 74, wherein the amino acid modification(s)25746 comprise: R45K. (Embodiment 82) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K and V78A. (Embodiment 83) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: V78A. (Embodiment 84) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. (Embodiment 85) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: V89A. (Embodiment 86) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: M80I. (Embodiment 87) The antibody of any one of embodiments 64-86, wherein the amino acid modification(s) comprises: (a) a modification at amino acid position 54 in the light chain variable region; and / or (b) a modification at amino acid position 55 in the light chain variable region, per Aho or Kabat numbering. (Embodiment 88) The antibody of embodiment 87, wherein the amino acid modification(s) comprises L54P in the light chain variable region, per Aho or Kabat numbering. (Embodiment 89) The antibody of embodiment 87 or 88, wherein the amino acid modification(s) comprises L55W in the light chain variable region, per Aho or Kabat numbering.

[0344] (Embodiment 90) The antibody of any one of embodiments 1-19, comprising a heavy chain FR1 as set forth by SEQ ID NO: 304. (Embodiment 91) The antibody of any one of embodiments 1-19 or 90, comprising a heavy chain FR2 as set forth by SEQ ID NO: 305. (Embodiment 92) The antibody of any one of embodiments 1-19 or 90, comprising a heavy chain FR2 as set forth by SEQ ID NO: 313. (Embodiment 93) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 306. (Embodiment 94) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 307. (Embodiment 95) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 314. (Embodiment 96) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 315. (Embodiment 97) The antibody of any one of embodiments 1-19 or 90-96, comprising a heavy chain FR4 as set forth by SEQ ID NO: 308. (Embodiment 98) The antibody of any one of embodiments 1-19 or 90-97, comprising a light chain FR1 as set forth by SEQ ID NO: 309. (Embodiment 99) The antibody of any one of embodiments 1-19 or 90-98, comprising a light chain FR2 as set forth by SEQ ID NO: 310. (Embodiment 100) The antibody of any one of embodiments 1-19 or 90-99, comprising a light chain FR3 as set forth by SEQ ID NO: 311. (Embodiment 101) The antibody of any one of embodiments 1-19 or 90-100, comprising a light chain FR4 as set forth by SEQ ID NO: 312. (Embodiment 102) The antibody of any one of embodiments 1-19, comprising a25746 HC FR1 as set forth by SEQ ID NO: 304, a HC FR2 as set forth by SEQ ID NO: 305, a HC FR3 as set forth by SEQ ID NO: 307, a HC FR4 as set forth by SEQ ID NO: 308, a LC FR1 as set forth by SEQ ID NO: 309, a LC FR2 as set forth by SEQ ID NO: 310, a LC FR3 as set forth by SEQ ID NO: 311, and a LC FR4 as set forth by SEQ ID NO: 312. Variable Region Embodiments

[0345] (Embodiment 103) The antibody of embodiment 1, comprising a heavy chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 101-169 or 420-427, and a light chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 201-220 or 430-437. (Embodiment 104) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104, and a light chain variable domain comprising an amino acid sequence at least 97% identical to SEQ ID NO: 201. (Embodiment 105) The antibody of embodiment 103, comprising an amino acid sequence at least 97% identical to SEQ ID NO: 104. (Embodiment 106) The antibody of embodiment 103, comprising an amino acid sequence at least 98% identical to SEQ ID NO: 104. (Embodiment 107) The antibody of embodiment 103, comprising an amino acid sequence at least 99% identical to SEQ ID NO: 104. (Embodiment 108) The antibody of embodiment 103, comprising SEQ ID NO: 104. (Embodiment 109) The antibody of any one of embodiments 103-108, comprising an amino acid sequence at least 98% identical to SEQ ID NO: 201. (Embodiment 110) The antibody of embodiment 109, comprising an amino acid sequence at least about 99% identical to SEQ ID NO: 201. (Embodiment 111) The antibody of embodiment 109, comprising SEQ ID NO: 201.

[0346] (Embodiment 112) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least about 97% identical to SEQ ID NO: 104, and a light chain variable domain comprising an amino acid sequence at least about 97% identical to SEQ ID NO: 201. (Embodiment 113) The antibody of embodiment 112, wherein the heavy chain variable domain comprises an amino acid sequence at least about 98% identical to SEQ ID NO: 104. (Embodiment 114) The antibody of embodiment 112, wherein the heavy chain variable domain comprises an amino acid sequence at least about 99% identical to SEQ ID NO: 104. (Embodiment 115) The antibody of embodiment 112, wherein the heavy chain variable domain comprises SEQ ID NO: 104.25746 (Embodiment 116) The antibody of any one of embodiments 112-115, wherein the light chain variable domain comprises an amino acid sequence at least about 98% identical to SEQ ID NO: 201. (Embodiment 117) The antibody of any one of embodiments 112-116, wherein the light chain variable domain comprises an amino acid sequence at least about 99% identical to SEQ ID NO: 201. (Embodiment 118) The antibody of any one of embodiments 112-117, wherein the light chain variable domain comprises SEQ ID NO: 201. (Embodiment 119) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, and a light chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430. (Embodiment 120) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 421, and a light chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 431. Fc region Embodiments

[0347] (Embodiment 121) The antibody of any one of embodiments 1-120, comprising a fragment crystallizable (Fc) region. (Embodiment 122) The antibody of embodiment 121, comprising reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and / or reduced complement-dependent cytotoxicity (CDC) as compared to human IgG1. (Embodiment 123) The antibody of embodiment 122, wherein the human IgG1 comprises SEQ ID NO: 320. (Embodiment 124) The antibody of embodiment 120 or embodiment 123, wherein the ADCC function of the Fc region comprising reduced ADCC is at least about 50% reduced as compared to human IgG1. (Embodiment 125) The antibody of any one of embodiments 122-124, wherein the CDC function of the Fc region comprising reduced ADCC is at least about 50% reduced as compared to human IgG1. (Embodiment 126) The anti-TL1A antibody of any one of embodiments 121-125, comprising a human IgG1 Fc region comprising (a) 297A, 297Q, 297G, or 297D, (b) 279F, 279K, or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R, or 235S, (e) 237A, 237E, 237K, 237N, or 237R, (f) 234A, 234V, or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R (k) 331S, (l) 236F or 236R, (m) 238A,25746 238E, 238G, 238H, 238I, 238V, 238W, or 238Y, (n) 248A, (o) 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, or 254V, (p) 255N, (q) 256H, 256K, 256R, or 256V, (r) 264S, (s) 265H, 265K, 265S, 265Y, or 265A, (t) 267G, 267H, 267I, or 267K, (u) 268K, (v) 269N or 269Q, (w) 270A, 270G, 270M, or 270N, (x) 271T, (y) 272N, (z) 292E, 292F, 292G, or 292I, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 311E, 311G, or 311S, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii) 343I or 343V, (jj) 373A, 373G, or 373S, (kk) 376E, 376W, or 376Y, (ll) 380D, (mm) 382D or 382P, (nn) 385P, (oo) 424H, 424M, or 424V, (pp) 434I, (qq) 438G, (rr) 439E, 439H, or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T, or 440V, (tt) E233P, (uu) L235E, (vv) L234A and L235A, (ww) L234A, L235A, and G237A, (xx) L234A, L235A, and P329G, (yy) L234F, L235E, and P331S, (zz) L234A, L235E, and G237A, (aaa), L234A, L235E, G237A, and P331S (bbb) L234A, L235A, G237A, P238S, H268A, A330S, and P331S (IgG1σ), (ccc) L234A, L235A, and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) any combination of (a) – (uu), per Kabat numbering. (Embodiment 127) The anti-TL1A of any one of embodiments 121-125, comprising a (i) human IgG4 Fc region or (ii) a human IgG4 Fc region comprising (a) S228P, (b) S228P and L235E, or (c) S228P, F234A, and L235A, per Kabat numbering. (Embodiment 128) The anti-TL1A of any one of embodiments 121-125, comprising a human IgG2 Fc region; IgG2-IgG4 cross-subclass Fc region; IgG2-IgG3 cross- subclass Fc region; IgG2 comprising H268Q, V309L, A330S, P331S (IgG2m4); or IgG2 comprising V234A, G237A, P238S, H268A, V309L, A330S, P331S (IgG2 ^ ^ ^ ^(Embodiment 129) The antibody of any one of embodiments 121-125, comprising a human IgG1 comprising one or more substitutions selected from the group comprising 329A, 329G, 329Y, 331S, 236F, 236R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, and 440V, per Kabat numbering. (Embodiment 130) The anti-TL1A of any one of embodiments 121-125, comprising a heavy chain Fc region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 320-362. (Embodiment 131) The anti-TL1A of any one of embodiments 121-125, comprising a heavy chain Fc region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical25746 to any one of SEQ ID NOS: 368-380. (Embodiment 132) The anti-TL1A of any one of embodiments 121-125, comprising a constant region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 381. Additional antibody features

[0348] (Embodiment 133) The anti-TL1A antibody of any one of embodiments 1- 132, comprising a light chain constant region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 319.

[0349] (Embodiment 134) The anti-TL1A antibody of any one of embodiments 1- 133, comprising at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% monomeric fraction as determined by size exclusion chromatography. (Embodiment 135) The antibody of embodiment 134, wherein the size exclusion chromatography comprises injecting purified antibody onto a size exclusion column, wherein the antibody is purified by protein A. (Embodiment 136) The antibody of embodiment 134 or 135, wherein the antibody is purified as described in Example 2. (Embodiment 137) The antibody of any one of embodiments 134- 136, wherein the antibody is expressed under conditions described in Example 2. (Embodiment 138) The antibody of any one of embodiments 134-137, wherein the size exclusion chromatography column has an inner diameter of 4.6 mm. (Embodiment 139) The antibody of any one of embodiments 134-138, wherein the size exclusion chromatography column has a length of 150 mm. (Embodiment 140) The antibody of any one of embodiments 134-139, wherein the size exclusion chromatography column has a pore size of 200 Å. (Embodiment 141) The antibody of any one of embodiments 134-140, wherein the size exclusion chromatography column has a particle size of 1.7 micrometer. (Embodiment 142) The antibody of any one of embodiments 134-141, wherein the size exclusion chromatography column is ACQUITY UPLC BEH200 SEC column. (Embodiment 143) The antibody of any one of embodiments 134-142, wherein the antibody or antigen binding fragment is injected at a total volume of 15 µL. (Embodiment 144) The antibody of any one of embodiments 134-143, wherein the antibody is injected at a concentration of about 0.1 μg / μL to about 1.0 μg / μL. (Embodiment 145) The antibody of any one of embodiments 134- 144, wherein the size exclusion chromatography is performed on a Shimadzu UPLC instrument. (Embodiment 146) The antibody of any one of embodiments 134-145, wherein the size exclusion chromatography is performed at a flow rate of 0.2 mL / min. (Embodiment25746 147) The antibody of any one of embodiments 134-146, wherein the size exclusion chromatography is performed at a column oven temperature of 30°C. (Embodiment 148) The antibody of any one of embodiments 134-147, wherein the percentage of monomer is calculated using Shimadzu software. (Embodiment 149) The antibody of any one of embodiments 134-148, wherein the size exclusion chromatography is performed as described in Example 2.

[0350] (Embodiment 150) The anti-TL1A antibody of any one of embodiments 1- 149, wherein the anti-TL1A is expressed at a concentration of at least about 2 µg / mL, between about 2 µg / mL and about 60 µg / mL, between about 5 µg / mL and about 60 µg / mL, between about 10 µg / mL and about 60 µg / mL, at least about 5 µg / mL, at least about 10 µg / mL, at least about 15 µg / mL, at least about 20 µg / mL, between about 2 µg / mL and about 50 µg / mL, between about 2 µg / mL and about 40 µg / mL, between about 2 µg / mL and about 30 µg / mL, between about 2 µg / mL and about 20 µg / mL, between about 5 µg / mL and about 50 µg / mL, between about 5 µg / mL and about 40 µg / mL, between about 5 µg / mL and about 30 µg / mL, between about 10 µg / mL and about 50 µg / mL, between about 10 µg / mL and about 40 µg / mL, or between about 10 µg / mL and about 30 µg / mL, as determined by a method disclosed herein. (Embodiment 151) The anti-TL1A antibody of any one of embodiments 1-149, wherein the expression level is at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 µg / mL as determined by a method disclosed herein. (Embodiment 152) The antibody of embodiment 150 or embodiment 151, wherein the antibody is expressed in FreeStyle 293-F cells. (Embodiment 153) The antibody of any one of embodiments 150-152, wherein the antibody is expressed as described in Example 2. (Embodiment 154) The antibody of any one of embodiments 150-153, wherein the antibody expression level is quantified using Enzyme- Linked Immunosorbent assay (ELISA). (Embodiment 155) The antibody of embodiment 154, wherein the ELISA comprises coating a surface of a substrate with a capture antibody that binds to a human or humanized antibody, applying the anti-TL1A antibody to the substrate, and applying to the substrate a second antibody that binds to a human or humanized antibody. (Embodiment 156) The antibody of embodiment 155, where the capture antibody comprises an anti-kappa antibody. (Embodiment 157) The antibody of embodiment 155 or embodiment 156, where the second antibody comprises an anti-Fc antibody. (Embodiment 158) The antibody of any one of embodiments 154-157, where the ELISA is performed as described in Example 2.25746

[0351] (Embodiment 159) A method of treating sarcoidosis (such as pulmonary sarcoidosis and / or cutaneous sarcoidosis) in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158. (Embodiment 160) A method of treating pulmonary sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158. (Embodiment 161) A method of treating cutaneous sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating lupus pernio in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating papular sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating nodular sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating Darier- Roussy sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating maculopapular sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating plaque sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating hypopigmented sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating atrophic and ulcerative sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating neurologic sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating cardiac sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating gastrointestinal sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating hepatic sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody25746 or antigen binding fragment of any one of embodiments 1-158; a method of treating pancreatic sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating peritoneal sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating sarcoidosis of bones in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating sarcoid arthropathy in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating plaque sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating angiolupoid sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating psoriasiform sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating verrucous sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating ichthyosiform sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-158; a method of treating erythrodermic sarcoidosi...

Claims

25746 CLAIMS WHAT IS CLAIMED IS:

1. A method of treating sarcoidosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen binding fragment).

2. The method of claim 1, wherein the sarcoidosis is cutaneous sarcoidosis.

3. The method of claim 2, wherein the cutaneous sarcoidosis is lupus pernio, papular sarcoidosis, nodular sarcoidosis, Darier-Roussy sarcoidosis, maculopapular sarcoidosis, plaque sarcoidosis, hypopigmented sarcoidosis, or atrophic and ulcerative sarcoidosis.

4. The method of claim 1, wherein the sarcoidosis is neurologic sarcoidosis.

5. The method of claim 1, wherein the sarcoidosis is cardiac sarcoidosis.

6. The method of claim 1, wherein the sarcoidosis is gastrointestinal sarcoidosis.

7. The method of claim 1, wherein the sarcoidosis is hepatic sarcoidosis.

8. The method of claim 1, wherein the sarcoidosis is pancreatic sarcoidosis.

9. The method of claim 1, wherein the sarcoidosis is peritoneal sarcoidosis.

10. The method of claim 1, wherein the sarcoidosis is sarcoidosis of bones.

11. The method of claim 1, wherein the sarcoidosis is sarcoid arthropathy.

12. The method of claim 1, wherein the sarcoidosis is plaque sarcoidosis.

13. The method of claim 12, wherein the plaque sarcoidosis is angiolupoid sarcoidosis, psoriasiform sarcoidosis, or verrucous sarcoidosis.25746 14. The method of claim 1, wherein the sarcoidosis is ichthyosiform sarcoidosis.

15. The method of claim 1, wherein the sarcoidosis is erythrodermic sarcoidosis.

16. The method of claim 1, wherein the sarcoidosis is perforating sarcoidosis.

17. The method of claim 1, wherein the sarcoidosis is pulmonary sarcoidosis.

18. The method of any one of claims 1 to 17, wherein the anti-TL1A antibody or antigen binding fragment is administered in a pharmaceutical composition.

19. The method of claim 18, wherein the pharmaceutical composition comprises anti- TL1A antibody or antigen binding fragment at a concentration greater than about 150 mg / mL.

20. The method of claim 18 or 19, wherein the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration greater than about 160 mg / ml, about 165 mg / ml, about 170 mg / ml, about 175 mg / ml, about 180 mg / ml, about 185 mg / ml, about 190 mg / ml, about 195 mg / ml, about 200 mg / ml, about 205 mg / ml, about 210 mg / ml, about 215 mg / ml, about 220 mg / ml, about 225 mg / ml, about 230 mg / ml, about 235 mg / ml, about 240 mg / ml, about 245 mg / ml, or about 250 mg / mL.

21. The method of any one of claims 18 to 20, wherein the pharmaceutical composition comprises anti-TL1A antibody or antigen binding fragment at a concentration about 125 mg / mL to about 175 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 225 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 225 mg / mL, about 150 mg / mL to about 250 mg / mL, about 175 mg / mL to about 225 mg / mL, about 175 mg / mL to about 250 mg / mL, about 175 mg / mL to about 275 mg / mL, about 200 mg / mL to about 250 mg / mL, or about 200 mg / mL to about 275 mg / mL.

22. The method of any one of claims 18 to 21, wherein the pharmaceutical composition is administered subcutaneously.25746 23. The method of any one of claims 18 to 21, wherein the pharmaceutical composition is administered intravenously.

24. The method of any one of claims 18 to 23, wherein the pharmaceutical composition comprises about 150 mg to about 1000 mg of the anti-TL1A antibody or antigen binding fragment.

25. The method of any one of claims 18 to 24, wherein the pharmaceutical composition has a total volume of less than or equal to about 2 mL, about 1.9 ml, about 1.8 ml, about 1.7 ml, about 1.6 ml, about 1.5 ml, about 1.4 ml, about 1.3 ml, about 1.2 ml, about 1.1 ml, about 1.0 ml, about 0.9 ml, or about 0.8 mL.

26. The method of any one of claims 18 to 25, wherein the pharmaceutical composition comprises a therapeutically effective dose of the anti-TL1A antibody or antigen binding fragment.

27. The method of any one of claims 18 to 26, wherein the pharmaceutical composition has a viscosity of less than about 20cP, less than about 19cP, less than about 18cP, less than about 17cP, less than about 16cP, less than about 15cP, less than about 14cP, less than about 13cP, less than about 12cP, less than about 11cP, less than about 10cP, less than about 9cP, less than about 8cP, less than about 7cP, less than about 6cP, or less than about 5 cP.

28. The method of any one of claims 18 to 27, wherein the pharmaceutical composition comprises a surfactant, a salt, a stabilizer, and / or a buffering agent.

29. The method of claim 28, wherein the surfactant comprises polysorbate-20, and wherein optionally the surfactant is present at a concentration of about 0.02% in the pharmaceutical composition.

30. The method of claim 28 or 29, wherein the salt comprises NaCl, and wherein optionally the NaCl is at a concentration of about 40 mM in the pharmaceutical composition.25746 31. The method of any one of claims 28 to 30, wherein the stabilizer comprises sucrose, wherein optionally the sucrose is at a concentration of about 220 mM in the pharmaceutical composition.

32. The method of any one of claims 28 to 31, wherein the buffering agent comprises sodium acetate, wherein optionally the sodium acetate is at a concentration of about 20 mM in the pharmaceutical composition.

33. The method of any one of claims 28 to 32, wherein the pharmaceutical composition has a pH of about 5.

3.

34. The method of any one of claims 1 to 33, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a first dose up to about 1000 mg.

35. The method of any one of claims 1 to 34, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a first dose of about 500 mg.

36. The method of any one of claims 1 to 35, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a second dose up to about 1000 mg.

37. The method of any one of claims 1 to 36, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a second dose of about 500 mg.

38. The method of any one of claims 1 to 37, wherein the first dose is administered to the subject at a first time point, and the second dose is administered to the subject at a second time point.

39. The method of any one of claims 1 to 38, wherein the first dose and the second dose is different or wherein the first dose and the second dose is identical.

40. The method of any one of claims 1 to 38, wherein the second time point is about 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, or 31 days after the first time point.25746 41. The method of any one of claims 1 to 33, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at an induction regimen.

42. The method of claim 41, wherein the induction regimen comprises 500 mg / dose once every 4 weeks.

43. The method of any one of claims 1 to 33 and 41 to 42, wherein the anti-TL1A antibody or antigen binding fragment is administered to the subject at a maintenance regimen.

44. The method of claim 43, wherein the maintenance regimen comprises 500 mg / dose once every 4 weeks.

45. The method of claim 43 or 44, wherein the induction regimen and the maintenance regimen are identical.

46. The method of claim 43, wherein the induction regimen and the maintenance regimen are different.

47. The method of any one of claims 43 to 46, wherein the maintenance regimen is about 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, or 31 days after the induction regimen.

48. A method of neutralizing monomeric TL1A and trimeric TL1A in a subject having sarcoidosis comprising (a) administering an effective dose of anti-TL1A antibody or antigen binding fragment to the subject, wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A, wherein the antibody or antigen binding fragment blocks interaction of TL1A to DR3, wherein the concentration of TL1A in a diseased tissue in the subject is reduced below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, and wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.25746 49. A method of reducing the concentration of TL1A in a diseased tissue in a subject with sarcoidosis comprising (a) administering an effective dose of anti-TL1A antibody or antigen binding fragment to the subject, thereby reducing the concentration of TL1A in the diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other and tissues afflicted by sarcoidosis.

50. A method of treating sarcoidosis in a subject in need thereof comprising (a) administering an anti-TL1A antibody or antigen binding fragment to the subject, wherein the anti-TL1A antibody or antigen binding fragment is administered at an effective dose such that the concentration of TL1A in a diseased tissue in the subject after step (a) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, and wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

51. A method of treating sarcoidosis in a subject in need thereof comprising (a) administering an anti-TL1A antibody or antigen binding fragment to the subject at an effective dose, and (b) reducing the concentration of TL1A in a diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis, wherein diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, and other tissues afflicted by sarcoidosis.

52. The method of any one of claims 48 to 51, wherein the sarcoidosis is cutaneous sarcoidosis.25746 53. The method of any one of claims 48 to 51, wherein the sarcoidosis is pulmonary sarcoidosis.

54. The method of any one of claims 48 to 53, wherein the effective dose comprises an induction regimen.

55. The method of any one of claims 48 to 54, further comprising (c) maintaining TL1A in the diseased tissue in the subject at a concentration below the concentration of TL1A in the corresponding tissue in the control subject.

56. The method of claim 55, wherein the TL1A in the diseased tissue in the subject is maintained with a maintenance regimen of the anti-TL1A antibody or antigen binding fragment.

57. The method of claim 56, wherein the induction regimen and the maintenance regimen are identical.

58. The method of claim 56, wherein the induction regimen and the maintenance regimen are different.

59. The method of any one of claims 56 to 58, wherein the maintenance regimen is administered after the induction regimen.

60. The method of any one of claims 48 to 59, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject during the induction regimen.

61. The method of any one of claims 48 to 59, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

62. The method of any one of claims 48 to 59, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject.25746 63. The method of any one of claims 54 to 62, wherein the induction regimen comprises a one-time administration of the anti-TL1A antibody or antigen binding fragment.

64. The method of claim 63, wherein one-time administration of the anti-TL1A antibody or antigen binding fragment comprises an administration at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

65. The method of any one of claims 54 to 62, wherein the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

66. The method of any one of claims 54 to 62 and 65, wherein the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or (v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

67. The method of any one of claims 54 to 62 or 65, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.25746 68. The method of any one of claims 54 to 62, 65, or 67, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

69. The method of any one of claims 54 to 62, 65, or 67, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

70. The method of any one of claims 55 to 69, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject.

71. The method of any one of claims 55 to 66, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

72. The method of any one of claims 55 to 66, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

73. The method of any one of claims 56 to 72, wherein the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

74. The method of any one of claims 56 to 73, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks,25746 (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

75. The method of any one of claims 56 to 73, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

76. The method of any one of claims 56 to 73 or 75, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.25746 77. The method of any one of claims 56 to 76, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

78. The method of any one of claims 56 to 76, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

79. The method of any one of claims 56 to 78, wherein the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

80. The method of any one of claims 49 to 79, wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A and wherein the antibody or antigen binding fragment blocks binding of TL1A to DR3.

81. The method of any one of claims 48 to 80, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment.

82. The method of any one of claims 48 to 81, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment.

83. The method of any one of claims 48 to 82, wherein binding affinity of the antibody or antigen binding fragment to monomeric TL1A as measured by dissociation equilibrium constant (KD-monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1A as measured by dissociation equilibrium constant (KD-trimer).

84. The method of claim 83, wherein the KD-monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD-trimer.25746 85. The method of claim 83 or 84, wherein the KD-monomer is no more than 0.06 nM.

86. The method of any one of claims 83 to 85, wherein the KD-trimer is no more than 0.06 nM.

87. The method of any one of claims 48 to 86, wherein the effective dose or the induction regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the effective dose or the induction regimen such that the concentration of TL1A in diseased tissue in the subject after step (a) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis.

88. The method of claim 87, wherein the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold over-production comparing to TL1A production in the normal reference tissue.

89. The method of any one of claims 56 to 88, wherein the maintenance regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (ii) integrating the parameter received in (i) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the maintenance regimen such that the concentration of TL1A in diseased tissue in the subject after step (c) is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis.25746 90. The method of claim 89, wherein the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more fold over- production comparing to TL1A production in the normal reference tissue.

91. The method of any one of claims 87 to 90, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1A in normal tissue(ksyn-normal),synthesis rate of TL1A in diseased tissue (ksyn-disease), and / or degradation rate of TL1A (kdeg-total-TL1A).

92. The method of claim to 91, wherein the association rate of the antibody to TL1A (kon-mAb) comprises the association rate of the antibody to monomeric TL1A (kon-monomer) and association rate of the antibody to trimeric TL1A (kon-trimer), wherein the dissociation rate of the antibody from TL1A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff-monomer) and dissociation rate of the antibody from trimeric TL1A (koff- trimer), and / or wherein the degradation rate of TL1A (kdeg-total-TL1A) comprises degradation rate of monomeric TL1A (kdeg-TL1A-monomer) and degradation rate of trimeric TL1A (kdeg-TL1A-trimer).

93. The method of any one of claims 87 to 92, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn),dissociation rate of the antibody from FcRn (koff- mAb-FcRn),association rate of the antibody-TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn), and / or dissociation rate of the antibody-TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn).

94. The method of claim 93, wherein the association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn) comprises association rate of the antibody-monomeric- TL1A complex to FcRn receptor (kon-(mAb-monoTL1A)-FcRn) and association rate of the antibody- trimeric-TL1A complex to FcRn receptor (kon-(mAb-triTL1A)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn)comprises dissociation rate of the antibody-monomeric-TL1A complex from FcRn (koff-(mAb-monoTL1A)-FcRn) and dissociation rate of the antibody-trimeric-TL1A complex from FcRn (koff-(mAb-triTL1A)-FcRn).25746 95. The method of any one of claims 87 to 94, wherein the step (i) in the dose determination method further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn).

96. The method of claim 95, wherein the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TL1A complex (kdeg-(mAb-monoTL1A)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TL1A complex (kdeg-(mAb-triTL1A)-FcRn).

97. The method of any one of claims 91 to 96, wherein in the dose determination method: (1) kon-monomer and kon-trimer are identical or different; (2) koff-monomerand koff-trimerare identical or different; (3) kdeg-monomer and kdeg-trimer are identical or different; (4) kon-(mAb-monoTL1A)-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (5) kon-mAb-FcRn and kon-(mAb-monoTL1A)-FcRn are identical or different; (6) kon-mAb-FcRn and kon-(mAb-triTL1A)-FcRn are identical or different; (7) koff-(mAb-monoTL1A)-FcRn and koff-(mAb-triTL1A)-FcRn are identical or different; (8) koff- mAb-FcRn and koff-(mAb-monoTL1A)-FcRn are identical or different; (9) koff- mAb-FcRnand koff-(mAb-triTL1A)-FcRnare identical or different; (10) kdeg-(mAb-monoTL1A)-FcRn and kdeg-(mAb-triTL1A)-FcRn are identical or different; (11) kdeg-mAb-FcRnand kdeg-(mAb-triTL1A)-FcRnare identical or different; (12) kdeg-mAb-FcRn and kdeg-(mAb-monoTL1A)-FcRn are identical or different; or (13) any combination of (1) to (12).

98. The method of any one of claims 87 to 97, wherein in the dose determination method: ksyn-diseaseis up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn-normal.

99. The method of any one of claims 87 to 98, wherein step (i) in the dose determination method further comprises receiving rate of TL1A trimerization (kon-TL1A-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TL1A-trimer-to-monomer).25746 100. A method of determining an effective dose regimen for administering an anti-TL1A antibody to a subject having sarcoidosis, wherein the method comprises: (a) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (b) integrating the parameter received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model; and (c) determining the effective dose regimen of the anti-TL1A antibody with the PBPK model from (b) such that after administration of the effective dose regimen the concentration of TL1A in a diseased tissue in the subject having sarcoidosis is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other tissues with sarcoidosis, and other tissues of pathogenesis for the sarcoidosis.

101. A method of determining an effective dose regimen for administering an anti-TL1A antibody to a subject having sarcoidosis, wherein the method comprises: (a) receiving a parameter of TL1A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (b) integrating the parameter received in (a) to a population pharmacokinetic (popPK) model; and (c) determining the effective dose regimen of the anti-TL1A antibody with the popPK model from (b) such that after administration of the effective dose regimen the concentration of TL1A in a diseased tissue in the subject having sarcoidosis is below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar duct, alveoli, pleura, a fibrotic tissue in the lung, other tissues with sarcoidosis, and other tissues of pathogenesis for the sarcoidosis.

102. The method of claim 100 or 101, wherein the sarcoidosis is cutaneous sarcoidosis.

103. The method of claim 100 or 101, wherein the sarcoidosis is pulmonary sarcoidosis.

104. The method of any one of claims 100 to 103, wherein the parameter of TL1A over- production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110,25746 120, 130, 140, 150, 160, 170, 180, 190, 200 or more fold over-production comparing to TL1A production in the normal reference tissue.

105. The method of any one of claims 100 to 104, wherein the step (a) further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1A in normal tissue (ksyn-normal), synthesis rate of TL1A in diseased tissue (ksyn-disease), and / or degradation rate of TL1A (kdeg-total-TL1A).

106. The method of claim 105, wherein the association rate of the antibody to TL1A (kon-mAb) comprises the association rate of the antibody to monomeric TL1A (kon-monomer) and association rate of the antibody to trimeric TL1A (kon-trimer), wherein the dissociation rate of the antibody from TL1A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff-monomer) and dissociation rate of the antibody from trimeric TL1A (koff-trimer), and / or wherein the degradation rate of TL1A (kdeg-total-TL1A) comprises degradation rate of monomeric TL1A (kdeg-TL1A-monomer) and degradation rate of trimeric TL1A (kdeg-TL1A-trimer).

107. The method of any one of claims 100 to 106, wherein the step (a) comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody-TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn), and / or dissociation rate of the antibody-TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn).

108. The method of claim 107, wherein the association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TL1A)-FcRn) comprises association rate of the antibody- monomeric-TL1A complex to FcRn receptor (kon-(mAb-monoTL1A)-FcRn) and association rate of the antibody-trimeric-TL1A complex to FcRn receptor (kon-(mAb-triTL1A)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TL1A)-FcRn) comprises dissociation rate of the antibody-monomeric-TL1A complex from FcRn (koff-(mAb-monoTL1A)-FcRn) and dissociation rate of the antibody-trimeric-TL1A complex from FcRn (koff-(mAb-triTL1A)-FcRn).

109. The method of any one of claims 100 to 108, wherein the step (a) further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn).25746 110. The method of claim 109, wherein the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) further comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TL1A complex (kdeg-(mAb-monoTL1A)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TL1A complex (kdeg-(mAb-triTL1A)-FcRn).

111. The method of any one of claims 100 to 110, wherein: (1) kon-monomer and kon-trimer are identical or different; (2) koff-monomerand koff-trimerare identical or different; (3) kdeg-monomer and kdeg-trimer are identical or different; (4) kon-(mAb-monoTL1A)-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (5) kon-mAb-FcRn and kon-(mAb-monoTL1A)-FcRn are identical or different; (6) kon-mAb-FcRnand kon-(mAb-triTL1A)-FcRnare identical or different; (7) koff-(mAb-monoTL1A)-FcRn and koff-(mAb-triTL1A)-FcRn are identical or different; (8) koff- mAb-FcRnand koff-(mAb-monoTL1A)-FcRnare identical or different; (9) koff- mAb-FcRn and koff-(mAb-triTL1A)-FcRn are identical or different; (10) kdeg-(mAb-monoTL1A)-FcRn and kdeg-(mAb-triTL1A)-FcRn are identical or different; (11) kdeg-mAb-FcRn and kdeg-(mAb-triTL1A)-FcRn are identical or different; (12) kdeg-mAb-FcRn and kdeg-(mAb-monoTL1A)-FcRn are identical or different; or (13) any combination of (1) to (12).

112. The method of any one of claims 100 to 111, wherein: ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold ofksyn-normal.

113. The method of any one of claims 100 to 112, wherein the effective dose regimen comprises an induction regimen of the anti-TL1A antibody or antigen binding fragment.

114. The method of any one of claims 100 to 113, wherein the effective dose regimen comprises a maintenance regimen of the anti-TL1A antibody or antigen binding fragment.

115. The method of claim 114, wherein the induction regimen and the maintenance regimen are identical.25746 116. The method of claim 114, wherein the induction regimen and the maintenance regimen are different.

117. The method of any one of claims 114 to 116, wherein the maintenance regimen is administered after the induction regimen.

118. The method of any one of claims 113 to 117, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject during the induction regimen.

119. The method of any one of claims 113 to 118, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

120. The method of any one of claims 100 to 117, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1A compared to the corresponding tissue in the control subject.

121. The method of any one of claims 113 to 120, wherein the induction regimen comprises a one-time administration of the anti-TL1A antibody or antigen binding fragment.

122. The method of claim 121, wherein the one-time administration of the anti-TL1A antibody or antigen binding fragment comprises an administration at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

123. The method of any one of claims 113 to 120, wherein the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.25746 124. The method of any one of claims 113 to 120 or 123, wherein the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or (v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

125. The method of any one of claims 113 to 120 or 123, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

126. The method of any one of claims 113 to 120, 123, or 125, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

127. The method of any one of claims 113 to 120, 123, or 125, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

128. The method of any one of claims 100 to 117 or 121 to 127, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject.

129. The method of any one of claims 114 to 128, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.25746 130. The method of any one of claims 114 to 129, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

131. The method of any one of claims 114 to 130, wherein the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen binding fragment.

132. The method of any one of claims 114 to 131, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks,25746 (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

133. The method of any one of claims 114 to 131, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

134. The method of any one of claims 114 to 131 or 133, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

135. The method of any one of claims 114 to 134, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

136. The method of any one of claims 114 to 135, wherein the maintenance regimen comprises administrations of the anti-TL1A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

137. The method of any one of claims 114 to 136, wherein the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

138. The method of any one of claims 100 to 137, wherein the effective dose regimen maintains the concentration of TL1A in diseased tissue in the subject below the concentration of TL1A in a corresponding tissue in a control subject without sarcoidosis for at least 425746 weeks, 8 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 2 years, and longer.

139. The method of any one of claims 100 to 138, wherein at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment during the effective dose regimen.

140. The method of any one of claims 100 to 139, wherein at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen binding fragment during the effective dose regimen.

141. The method of any one of claims 100 to 140, wherein step (a) further comprises receiving the rate of TL1A trimerization (kon-TL1A-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TL1A-trimer-to-monomer).

142. The method of any one of claims 100 to 141, wherein the concentration of TL1A is the concentration of free TL1A.

143. The method of any one of claims 1 to 142, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10, an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15.

144. The method of any one of claims 1 to 143, wherein the anti-TL1A antibody comprises, a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3- 20 framework; wherein the heavy chain variable framework region and the light chain25746 variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

145. The method of any one of claims 1 to 144, wherein the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 201-220.

146. The method of any one of claims 1 to 145, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDR FSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein HCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 1, HCDR2 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, HCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 6-9, LCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 10, LCDR2 comprises an amino acid sequence set forth by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 12 or 13.

147. The method of any one of claims 1 to 142, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 401, 407, 413, or 450, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 402, 408, 414, or 451, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 403, 409, 415, or 452; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 404, 410, 416, or 453, an LCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 405, 411, 417, or 454, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 406, 412, 418, or 455.25746 148. The method of any one of claims 1 to 142 or claim 147, wherein the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 420-427, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 430- 437.

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