Anti-TL1A antibody compositions and methods of treatment in the lungs

Abstract

Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of pulmonary diseases and / or conditions.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent No. 63 / 285,785, filed December 3, 2021, U.S. Provisional Patent No. 63 / 226,041, filed July 27, 2021, U.S. Provisional Patent No. 63 / 180,896, filed April 28, 2021, and U.S. Provisional Patent No. 63 / 150,832, filed February 18, 2021. The entire contents of each of the four priority applications are expressly incorporated herein by reference.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in ASCII format, which is incorporated herein by reference in its entirety. The ASCII copy, created on February 14, 2022, is named 56884-788_601_SL.txt and is 356,830 bytes in size. [Background technology]

[0003] TL1A is a cytokine secreted by antigen-presenting cells, T cells, and endothelial cells. TL1A signals through death receptor 3 (DR3), a TNF family receptor found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphoid cells (ILCs), fibroblasts, and epithelial cells, and potently drives Th1, Th2, Th9, and Th17 responses. Furthermore, it is induced in antigen-presenting cells by toll-like receptor (TLR) ligands and FcR crosslinking, and in T cells by T cell receptor (TCR) stimulation. TL1A has been shown to be upregulated in the mucosa and serum of patients with inflammatory bowel disease. In dextran sulfate sodium (DSS) and adoptive transfer mouse models, antibodies against TL1A reduced inflammation and reversed fibrosis, even when treatment was administered late in the disease course, after inflammation and fibrosis had been established. Summary of the Invention

[0004] The present disclosure provides tumor necrosis factor ligand 1A (TL1A)-binding antibodies and compositions thereof for the treatment of inflammation and / or fibrosis, including diseases or conditions present in the lungs of a subject. In various aspects, the antibodies described herein possess characteristics useful for therapeutic applications, such as low immunogenicity, and / or characteristics that facilitate antibody manufacturing, such as a high percentage of monomeric fraction as measured by size exclusion chromatography and / or high expression. In further aspects, the antibodies described herein possess characteristics useful for subcutaneous administration, such as low viscosity at high antibody concentrations. Further aspects of the antibodies and antibody formulations may include high solubility, low sub-visible particles, low opalescence, no visible particles, and any combination thereof.

[0005] In one aspect, provided herein is a method of treating inflammation in a subject in need thereof, comprising administering to the subject an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody). In some embodiments, the subject has inflammation in the lung. Further provided is a method of treating fibrosis in a subject in need thereof, comprising administering to the subject an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody). In some embodiments, the subject has fibrosis in the lung. Further provided is a method of treating a pulmonary disease and / or condition in a subject in need thereof, comprising administering to the subject an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody).

[0006] In some embodiments, the subject has a chronic lung disorder. In some embodiments, the subject has idiopathic pulmonary fibrosis. In some embodiments, the subject has viral-induced pulmonary fibrosis. In some embodiments, the subject has asthma. In some embodiments, the subject has COPD. In some embodiments, the subject has pneumonia. In some embodiments, the subject has idiopathic interstitial pneumonia, pulmonary sarcoidosis, interstitial lung disease, bronchiolitis, alveolitis, vasculitis, interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, idiopathic organizing pneumonia, acute interstitial pneumonia, allergic rhinitis, emphysema, chronic bronchitis, primary biliary cholangitis, primary biliary cholangitis, Behcet's disease, systemic sclerosis-related interstitial lung disease, or cystic fibrosis, or a combination thereof.

[0007] In some embodiments, the anti-TL1A antibody is administered in a pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises an anti-TL1A antibody at a concentration greater than about 150 mg / mL. In some embodiments, the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, or 200 mg / mL. In some embodiments, the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, or 225 mg / mL. In some embodiments, the concentration is between about 150 mg / mL and about 250 mg / mL. In some embodiments, the concentration is between about 175 mg / mL and about 225 mg / mL. In one aspect, provided herein is a pharmaceutical composition comprising an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody) at a concentration greater than about 50 mg / mL. In some embodiments, the concentration is greater than about 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, or 145 mg / mL. In certain embodiments, the concentration is about 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, or 145 mg / mL. In some embodiments, the pharmaceutical composition is administered subcutaneously. In some embodiments, about 150 mg to about 500 mg of anti-TL1A antibody is present in the composition. In some embodiments, the composition has a total volume of about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 mL or less. In some embodiments, the pharmaceutical composition comprises a therapeutically effective dose of an anti-TL1A antibody.In some embodiments, the composition comprises about 9.0, 8.9, 8.8, 8.7, 8.6, 8.5, 8.4, 8.3, 8.2, 8.1, 8.0, 7.9, 7.8, 7.7, 7.6, 7.5, 7.4, 7.3, 7.2, 7.1, 7.0, 6.9, 6.8, 6.7, 6.6, 6.5, 6.4, 6.3, 6.2, 6.1, 6.0, 5.9, 5.8, 5.7, 5.6, 5.5, 5.4, 5.3, 5.2, 5.1, 5.0, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 ...1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4. In some embodiments, the compositions have a total volume of about 0.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, or 0.8 mL or less. In some embodiments, the compositions have a total volume of about 0.5 mL to about 1.5 mL. In some embodiments, the compositions herein have a total volume of about 0.5 mL to about 2.5 mL. In some embodiments, the compositions herein have a total volume of about 0.5 mL to about 3.5 mL. In some embodiments, the compositions herein have a total volume of about 0.5 mL to about 4.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 1.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 2.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 3.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 4.5 mL. In some embodiments, the compositions herein have a viscosity of less than about 20 cP. In some embodiments, the compositions have a viscosity of less than about 15 cP. In some embodiments, the compositions have a viscosity of less than about 10 cP. In some embodiments, the compositions have a viscosity of less than about 9, 8, 7, 6, or 5 cP. In some embodiments, the compositions have a viscosity of about 1 cP to about 7 cP, about 1 cP to about 2 cP, or about 10 cP to about 20 cP. In some embodiments, the compositions have a viscosity of about 1 cP to about 10 cP. In some embodiments, the compositions have a viscosity of about 1 cP to about 15 cP. In some embodiments, the composition has a viscosity of about 1 cP to about 20 cP.In some embodiments, the pharmaceutical composition has an anti-TL1A antibody aggregation rate of less than about 5% of the total anti-TL1A antibody in the composition, as measured by size exclusion chromatography. In some embodiments, the aggregation is less than about 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5%. In some embodiments, the composition comprises a surfactant. In some embodiments, the surfactant comprises a non-ionic surfactant. In some embodiments, the non-ionic surfactant comprises polysorbate-20. In some embodiments, the surfactant is present at a concentration of about 0.005% to about 0.05% of the composition. In some embodiments, the surfactant is present at a concentration of about 0.01% to about 0.02% of the composition. In some embodiments, the surfactant is present at a concentration of about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, about 0.015%, about 0.016%, about 0.017%, about 0.018%, about 0.019%, about 0.02%, about 0.021%, about 0.022%, about 0.023%, about 0.024%, about 0.025%, about 0.026%, about 0.027%, about 0.028%, about 0.029%, or about 0.03% (v / v) of the composition. In some embodiments, the composition comprises a salt. In some embodiments, the salt comprises sodium chloride, glycine, lysine hydrochloride, arginine hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof. In some embodiments, the salt comprises sodium chloride. In some embodiments, the salt comprises lysine-HCl. In some embodiments, the salt is present in the composition at a concentration of about 10 mM to about 100 mM. In some embodiments, the salt is present in the composition at a concentration of about 25 mM. In some embodiments, the salt is present in the composition at a concentration of about 40 mM. In some embodiments, the composition comprises a stabilizer. In some embodiments, the stabilizer comprises a sugar, a polyol, an amino acid, or a polymer, a cyclodextrin (e.g., HP-b-CD), or a combination thereof. In some embodiments, the stabilizer comprises a sugar. In some embodiments, the sugar comprises sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof.In some embodiments, the sugar comprises sucrose. In some embodiments, the amino acid comprises glycine. In some embodiments, the stabilizer is present in the composition at a concentration of about 50 mM to about 300 mM. In some embodiments, the stabilizer is present at a concentration of about 200 mM to about 280 mM. In some embodiments, the stabilizer is present at a concentration of about 220 to about 240 mM. In certain embodiments, the stabilizer is present at a concentration of about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 210 mM, about 220 mM, about 230 mM, about 240 mM, or about 250 mM. In some embodiments, the stabilizer comprises sucrose and glycine. In certain embodiments, sucrose is present at a concentration of about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 210 mM, about 220 mM, about 230 mM, about 240 mM, or about 250 mM. In some embodiments, glycine is present at a concentration of about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 105 mM, about 110 mM, about 115 mM, or about 120 mM. In some embodiments, the composition comprises a buffering agent. In some embodiments, the buffering agent comprises acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, tris(tris(hydroxymethyl)aminomethane), or diethanolamine, or a combination thereof. In some embodiments, the buffering agent comprises acetate. In some embodiments, the buffering agent comprises phosphate. In some embodiments, the buffering agent is present in the composition at a concentration of about 10 mM to about 50 mM. In some embodiments, the composition comprises about 20 mM buffer. In some embodiments, the composition has a pH of about 4.5 to about 8.0. In some embodiments, the composition has a pH of about 4.5 to about 7.5. In some embodiments, the composition has a pH of about 6 to about 7. In some embodiments, the composition has a pH of about 6.5. In some embodiments, the composition has a pH of about 5 to about 5.5.In some embodiments, the composition has a pH of about 5.3.

[0008] In some embodiments, the anti-TL1A antibody is administered to the subject at a first dose of up to about 1000 mg. In some embodiments, the anti-TL1A antibody is administered to the subject at a first dose of about 150 mg to about 1000 mg. In some embodiments, the first dose is about 500 mg to about 1000 mg. In some embodiments, the first dose is about 500 mg or about 800 mg. In some embodiments, 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, 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. In some embodiments, the second time point is about 1, 2, 3, or 4 weeks after the first time point. In some embodiments, the second dose comprises up to about 1000 mg of anti-TL1A. In some embodiments, the second dose comprises about 150 mg to about 1000 mg. In some embodiments, the second dose comprises about 150 mg to about 600 mg. In some embodiments, a third dose of anti-TL1A is administered to the subject at a third time point. In some embodiments, the third 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 second time point. In some embodiments, the third time point is about 1, 2, 3, or 4 weeks after the second time point. In some embodiments, the third dose comprises up to about 1000 mg of anti-TL1A. In some embodiments, the third dose comprises about 150 mg to about 1000 mg. In some embodiments, the third dose comprises about 150 mg to about 600 mg. In some embodiments, a fourth dose of anti-TL1A is administered to the subject at the fourth time point. In some embodiments, the fourth 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 third time point. In some embodiments, the fourth time point is about 1, 2, 3, or 4 weeks after the third time point.In some embodiments, the fourth dose comprises up to about 1000 mg of anti-TL1A. In some embodiments, the fourth dose comprises about 150 mg to about 1000 mg. In some embodiments, the fourth dose comprises about 150 mg to about 600 mg. In some embodiments, a fifth dose of anti-TL1A is administered to a subject at a fifth time point. In some embodiments, the fifth 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 fourth time point. In some embodiments, the fifth time point is about 1, 2, 3, or 4 weeks after the fourth time point. In some embodiments, the fifth dose comprises up to about 1000 mg of anti-TL1A. In some embodiments, the fifth dose comprises about 150 mg to about 1000 mg. In some embodiments, the fifth dose comprises about 150 mg to about 600 mg. In some embodiments, a sixth dose of anti-TL1A is administered to a subject at a sixth time point. In some embodiments, the sixth 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 fifth time point. In some embodiments, the sixth time point is about 1, 2, 3, or 4 weeks after the fifth time point. In some embodiments, the sixth dose comprises up to about 1000 mg of anti-TL1A. In some embodiments, the sixth dose comprises about 150 mg to about 1000 mg. In some embodiments, the sixth dose comprises from about 150 mg to about 600 mg.

[0009] In some embodiments, additional doses of anti-TL1A antibody are administered to the subject at one or more additional time points. In some embodiments, the one or more additional time points include about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 additional time points. In some embodiments, the composition is administered to the subject at about 12 additional time points. In some embodiments, each additional time point is independently 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 previous time point. In some embodiments, each additional time point is independently about 1, 2, 3, or 4 weeks after the previous time point. In some embodiments, at least one of the additional time points is about 2 weeks after the previous time point. In some embodiments, the additional dose comprises up to about 1000 mg of anti-TL1A. In some embodiments, the additional dose comprises about 150 mg to about 1000 mg of anti-TL1A. In some embodiments, the additional dose is about 175 mg to about 300 mg of anti-TL1A.

[0010] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A ("TL1A", and such an antibody or antigen-binding fragment, "anti-TL1A antibody or antigen-binding fragment"), wherein the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A.

[0011] In some embodiments, the antibody or antigen-binding fragment blocks the interaction of TL1A with death receptor 3 ("DR3"). In some embodiments, the dissociation equilibrium constant (K D-monomer The binding affinity of an antibody or antigen-binding fragment to monomeric TL1A, as measured by the dissociation equilibrium constant (K D-trimer ) corresponds to the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A. In some embodiments, K D-monomer But, K D-trimerIn some embodiments, K is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times of D-monomer is 0.06 nM or less. D-trimer is less than 0.06 nM.

[0012] In one aspect, provided herein is a method for neutralizing monomeric and trimeric TL1A in a subject with pulmonary inflammation and / or pulmonary fibrosis, the method comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A, and wherein the antibody or antigen-binding fragment blocks the interaction of TL1A with DR3, such that the concentration of TL1A in diseased tissue of the subject is reduced to below the concentration of TL1A in the corresponding tissue of a control subject not having pulmonary inflammation and / or pulmonary fibrosis, and the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar ducts, alveoli, pleura, fibrotic tissue in the lung, other tissues with pulmonary inflammation and / or pulmonary fibrosis, and other tissues involved in the pathogenesis of pulmonary inflammation and / or pulmonary fibrosis. In some embodiments, the subject has one or more inflammatory conditions selected from the group consisting of systemic sclerosis-associated interstitial lung disease, idiopathic pulmonary fibrosis, viral-induced pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. In some embodiments, the subject has chronic lung disorder, idiopathic interstitial pneumonia, pulmonary sarcoidosis, interstitial lung disease, bronchiolitis, alveolitis, vasculitis, interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, idiopathic organizing pneumonia, acute interstitial pneumonia, allergic rhinitis, emphysema, chronic bronchitis, primary biliary cholangitis, primary biliary cholangitis, Behcet's disease, systemic sclerosis-associated interstitial lung disease, or cystic fibrosis, or a combination thereof.

[0013] In one aspect, provided herein is a method for reducing the concentration of TL1A in diseased tissue of a subject with pulmonary inflammation and / or pulmonary fibrosis, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment, thereby reducing the concentration of TL1A in the subject's diseased tissue to below the concentration of TL1A in the corresponding tissue of a control subject not having pulmonary inflammation and / or pulmonary fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar ducts, alveoli, pleura, fibrotic tissue in the lung, other tissues with pulmonary inflammation and / or pulmonary fibrosis, and other tissues involved in the pathogenesis of pulmonary inflammation and / or pulmonary fibrosis.

[0014] In one aspect, provided herein is a method of treating pulmonary inflammation and / or pulmonary fibrosis in a subject in need thereof, comprising: (a) administering to the subject an anti-TL1A antibody or antigen-binding fragment, wherein the anti-TL1A antibody or antigen-binding fragment is administered at an effective dose such that the concentration of TL1A in the subject's diseased tissue after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject not having pulmonary inflammation and / or pulmonary fibrosis, and the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar ducts, alveoli, pleura, fibrotic tissue in the lung, other tissues having pulmonary inflammation and / or pulmonary fibrosis, and other tissues involved in the pathogenesis of pulmonary inflammation and / or pulmonary fibrosis.

[0015] In one aspect, provided herein is a method of treating pulmonary inflammation and / or pulmonary fibrosis in a subject in need thereof, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment; and (b) reducing the concentration of TL1A in the subject's diseased tissue to below the concentration of TL1A in the corresponding tissue of a control subject not having pulmonary inflammation and / or pulmonary fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar ducts, alveoli, pleura, fibrotic tissue in the lung, other tissues having pulmonary inflammation and / or pulmonary fibrosis, and other tissues involved in the pathogenesis of pulmonary inflammation and / or pulmonary fibrosis.

[0016] In some embodiments, the effective dose includes an induction regimen.

[0017] In some embodiments, the method further comprises (c) maintaining TL1A in the diseased tissue of the subject at a concentration that is less than the concentration of TL1A in the corresponding tissue of the control subject.

[0018] In some embodiments, TL1A in the subject's diseased tissue is maintained with a maintenance regimen of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the induction regimen and the maintenance regimen are the same. In some embodiments, the induction regimen and the maintenance regimen are different. In some embodiments, the maintenance regimen is administered after the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A during the induction regimen compared to corresponding tissue in a control subject. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to corresponding tissue in a control subject within 1, 2, 3, 4, 5, or 6 weeks of starting the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to corresponding tissue in a control subject.

[0019] In some embodiments, the induction regimen comprises a single administration of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody or antigen-binding fragment is administered 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.

[0020] In some embodiments, the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the induction regimen comprises: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 100 mg / dose at week 2, 100 mg / dose at week 6, and 100 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; or (v) 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10.

[0021] In some embodiments, 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. In some embodiments, the induction regimen comprises administration once every 2, 4, 6, or 8 weeks. In some embodiments, the induction regimen involves administration once every 2 or 4 weeks for the first two doses, then once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

[0022] In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than corresponding tissue in a control subject. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than corresponding tissue in a control subject during a maintenance regimen. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than corresponding tissue in a 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 more of the start of a maintenance regimen.

[0023] In some embodiments, the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the maintenance regimen includes (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. g / dose, (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.

[0024] In some embodiments, the maintenance regimen comprises administration of an 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. In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks. In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every 4 weeks. In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every 4 weeks. In some embodiments, 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.

[0025] In some embodiments, the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A, and the antibody or antigen-binding fragment blocks TL1A binding 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 subject's blood 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 subject's blood is occupied by anti-TL1A antibodies or antigen-binding fragments.

[0026] In some embodiments, the dissociation equilibrium constant (K D-monomer The binding affinity of an antibody or antigen-binding fragment to monomeric TL1A, as measured by the dissociation equilibrium constant (K D-trimer ) corresponds to the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A. In some embodiments, K D-monomer But, K D-trimerIn some embodiments, K is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times of D-monomer is 0.06 nM or less. D-trimer is less than 0.06 nM.

[0027] In some embodiments, the subject has one or more inflammatory conditions selected from the group consisting of systemic sclerosis-related interstitial lung disease, idiopathic pulmonary fibrosis, viral-induced pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), and pneumonia.

[0028] In some embodiments, the subject has a chronic lung disorder, idiopathic interstitial pneumonia, pulmonary sarcoidosis, interstitial lung disease, bronchiolitis, alveolitis, vasculitis, interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, idiopathic organizing pneumonia, acute interstitial pneumonia, allergic rhinitis, emphysema, chronic bronchitis, primary biliary cholangitis, primary biliary cholangitis, Behcet's disease, systemic sclerosis-related interstitial lung disease, or cystic fibrosis, or a combination thereof.

[0029] In some embodiments, the effective dose or induction regimen is determined by a dose determination method, which includes: (i) receiving parameters of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (ii) integrating the parameters received in (i) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or population pharmacokinetic (popPK) model; and (iii) determining an effective dose or induction regimen such that the concentration of TL1A in the subject's diseased tissue after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject not having pulmonary inflammation and / or pulmonary fibrosis. In some embodiments, the parameter for TL1A overproduction 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-fold or more overproduction compared to TL1A production in normal reference tissue.

[0030] In some embodiments, the maintenance regimen is determined by a dose-determination method, the dose-determination method comprising: (i) receiving a parameter of TL1A overproduction in the diseased tissue compared to TL1A production in a normal reference tissue; (ii) integrating the parameter received in (i) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic (popPK) model; and (iii) determining a maintenance regimen such that the concentration of TL1A in the diseased tissue of the subject after step (c) is less than the concentration of TL1A in the corresponding tissue of a control subject without pulmonary inflammation and / or pulmonary fibrosis. In some embodiments, the parameter of TL1A overproduction is 10-, 15-, 20-, 25-, 30-, 35-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-, 80-, 85-, 90-, 95-, 100-, or more-fold overproduction compared to TL1A production in the normal reference tissue.

[0031] In some embodiments, step (i) of the dose determination method comprises measuring the association rate of the antibody to TL1A (k on-mAb ), the dissociation rate of the antibody from TL1A (k off-mAb ), the synthesis rate of TL1A in normal tissues (k syn-normal ), the synthesis rate of TL1A in diseased tissue (k syn-disease ), and / or the degradation rate of TL1A (k deg-total-TL1A In some embodiments, the association rate of the antibody to TL1A (k on-mAb ) is the association rate of the antibody to monomeric TL1A (k on-monomer ) and the association rate of the antibody to trimeric TL1A (k on-trimer ), and the dissociation rate of the antibody from TL1A (k off-mAb ) is the dissociation rate of the antibody from monomeric TL1A (k off-monomer ) and the dissociation rate of the antibody from trimeric TL1A (k off-trimer ) and / or the degradation rate of TL1A (k deg-total-TL1A ) is the degradation rate of monomeric TL1A (k deg-TL1A-monomer ) and the degradation rate of trimeric TL1A (k deg-TL1A-trimer ) is included.

[0032] In some embodiments, step (i) of the dose determination method comprises measuring the association rate of the antibody to the FcRn receptor (k on-mAb-FcRn ), the dissociation rate of the antibody from FcRn (k off-mAb-FcRn ), and the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn In some embodiments, the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ) is the association rate (k on-(mAb-monoTL1A)-FcRn ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k on-(mAb-triTL1A)-FcRn ) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is the dissociation rate of the antibody-monomer-TL1A complex from FcRn (k off-(mAb-monoTL1A)-FcRn ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k off-(mAb-triTL1A)-FcRn ) is included.

[0033] In some embodiments, step (i) of the dose determination method comprises measuring the clearance rate of antibody-bound FcRn receptor (k deg-mAb-FcRn In some embodiments, the clearance rate (k) of the antibody-bound FcRn receptor is measured. deg-mAb-FcRn ) is the clearance rate (k deg-(mAb-monoTL1A)-FcRn ) and the clearance rate (k deg-(mAb-triTL1A)-FcRn In some embodiments, the method for determining the dose comprises: (1) k on-monomer and k on-trimer are the same or different, (2)k off-monomer and k off-trimer are the same or different, (3)k deg-monomer and k deg-trimer are the same or different, (4)k on-(mAb-monoTL1A)-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (5)k on-mAb-FcRn and k on-(mAb-monoTL1A)-FcRnare the same or different, (6)k on-mAb-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (7)k off-(mAb-monoTL1A)-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (8)k off-mAb-FcRn and k off-(mAb-monoTL1A)-FcRn are the same or different, (9)k off-mAb-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (10)k deg-(mAb-monoTL1A)-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (11)k deg-mAb-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (12)k deg-mAb-FcRn and k deg-(mAb-monoTL1A)-FcRn are the same or different, and are any combination of (13)(1) to (12). In some embodiments, in the dosage determination method, k syn-disease But, k syn-normal In some embodiments, step (i) of the dose determination method comprises measuring the rate of TL1A trimerization (k on-TL1A-monomer-to-trimer ) and / or the rate of TL1A monomerization (k off-TL1A-trimer-to-monomer ).

[0034] In one aspect, provided herein is a method for determining an effective dose regimen for administering an anti-TL1A antibody to a subject with pulmonary inflammation and / or pulmonary fibrosis, the method comprising: (a) receiving parameters of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (b) integrating the parameters received in (a) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model; and (c) determining an effective dose regimen of the anti-TL1A antibody in the PBPK model from (b), such that after administration of the effective dose regimen, the concentration of TL1A in the diseased tissue of the subject with pulmonary inflammation and / or pulmonary fibrosis is less than the concentration of TL1A in the corresponding tissue of a control subject without pulmonary inflammation and / or pulmonary fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar ducts, alveoli, pleura, fibrotic tissue in the lung, other tissues with pulmonary inflammation and / or pulmonary fibrosis, and other tissues involved in the pathogenesis of pulmonary inflammation and / or pulmonary fibrosis.

[0035] In one aspect, provided herein is a method for determining an effective dose regimen for administering an anti-TL1A antibody to a subject with pulmonary inflammation and / or pulmonary fibrosis, the method comprising: (a) receiving parameters of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (b) integrating the parameters received in (a) into a population pharmacokinetic (popPK) model; and (c) determining an effective dose regimen of the anti-TL1A antibody in the popPK model from (b) such that after administration of the effective dose regimen, the concentration of TL1A in the diseased tissue of the subject with pulmonary inflammation and / or pulmonary fibrosis is less than the concentration of TL1A in the corresponding tissue of a control subject without pulmonary inflammation and / or pulmonary fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of bronchi, bronchioles, alveolar ducts, alveoli, pleura, fibrotic tissue in the lung, other tissues with pulmonary inflammation and / or pulmonary fibrosis, and other tissues involved in the pathogenesis of pulmonary inflammation and / or pulmonary fibrosis.

[0036] In some embodiments of the dose-determining method, the parameter of TL1A overproduction 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-fold or more overproduction compared to TL1A production in a normal reference tissue. In some embodiments of the dose-determining method, step (a) comprises measuring the association rate of the antibody to TL1A (k on-mAb ), the dissociation rate of the antibody from TL1A (k off-mAb ), the synthesis rate of TL1A in normal tissues (k syn-normal ), the synthesis rate of TL1A in diseased tissue (k syn-disease ), and / or the degradation rate of TL1A (k deg-total-TL1A ).

[0037] In some embodiments of the dose determination method, the association rate of the antibody to TL1A (k on-mAb ) is the association rate of the antibody to monomeric TL1A (k on-monomer ) and the association rate of the antibody to trimeric TL1A (k on-trimer ), and the dissociation rate of the antibody from TL1A (k off-mAb ) is the dissociation rate of the antibody from monomeric TL1A (k off-monomer ) and the dissociation rate of the antibody from trimeric TL1A (k off-trimer ) and / or the degradation rate of TL1A (k deg-total-TL1A ) is the degradation rate of monomeric TL1A (k deg-TL1A-monomer ) and the degradation rate of trimeric TL1A (k deg-TL1A-trimer In some embodiments of the dose determination method, step (a) comprises determining the association rate of the antibody to the FcRn receptor (k on-mAb-FcRn ), the dissociation rate of the antibody from FcRn (k off-mAb-FcRn ), and the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is received.

[0038] In some embodiments of the dose determination method, the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn) is the association rate (k on-(mAb-monoTL1A)-FcRn ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k on-(mAb-triTL1A)-FcRn ) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is the dissociation rate of the antibody-monomer-TL1A complex from FcRn (k off-(mAb-monoTL1A)-FcRn ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k off-(mAb-triTL1A)-FcRn ) is included.

[0039] In some embodiments of the dose determination method, step (a) comprises determining the clearance rate of antibody-bound FcRn receptor (k deg-mAb-FcRn In some embodiments of the method for determining the dose, the clearance rate (k deg-mAb-FcRn ) is the clearance rate (k deg-(mAb-monoTL1A)-FcRn ) and the clearance rate (k deg-(mAb-triTL1A)-FcRn ) further included.

[0040] In some embodiments of the dose-determining method, the subject has one or more inflammatory conditions selected from the group consisting of systemic sclerosis-associated interstitial lung disease, idiopathic pulmonary fibrosis, viral-induced pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. In some embodiments of the dose-determining method, the subject has chronic lung disorder, idiopathic interstitial pneumonia, pulmonary sarcoidosis, interstitial lung disease, bronchiolitis, alveolitis, vasculitis, interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, idiopathic organizing pneumonia, acute interstitial pneumonia, allergic rhinitis, emphysema, chronic bronchitis, primary biliary cholangitis, primary biliary cholangitis, Behcet's disease, systemic sclerosis-associated interstitial lung disease, or cystic fibrosis, or a combination thereof.

[0041] In some embodiments of the dosage determination method, the dosage determination method comprises: (1) k on-monomer and k on-trimer are the same or different, (2)k off-monomer and koff-trimer are the same or different, (3)k deg-monomer and k deg-trimer are the same or different, (4)k on-(mAb-monoTL1A)-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (5)k on-mAb-FcRn and k on-(mAb-monoTL1A)-FcRn are the same or different, (6)k on-mAb-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (7)k off-(mAb-monoTL1A)-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (8)k off-mAb-FcRn and k off-(mAb-monoTL1A)-FcRn are the same or different, (9)k off-mAb-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (10)k deg-(mAb-monoTL1A)-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (11)k deg-mAb-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (12)k deg-mAb-FcRn and k deg-(mAb-monoTL1A)-FcRn are the same or different, or any combination of (13)(1) to (12).

[0042] In some embodiments of the dosage method, the dosage method further comprises: syn-disease But, k syn-normal 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 times or more.

[0043] In some embodiments of the dose-determining method, the effective dose regimen comprises an induction regimen of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose-determining method, the effective dose regimen comprises a maintenance regimen of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose-determining method, the induction regimen and the maintenance regimen are the same. In some embodiments of the dose-determining method, the induction regimen and the maintenance regimen are different. In some embodiments of the dose-determining method, the maintenance regimen is administered after the induction regimen.

[0044] In some embodiments of the dose-determining method, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A during the induction regimen compared to corresponding tissue in a control subject. In some embodiments of the dose-determining method, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A within 1, 2, 3, 4, 5, or 6 weeks of the start of the induction regimen compared to corresponding tissue in a control subject. In some embodiments of the dose-determining method, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to corresponding tissue in a control subject. In some embodiments of the dose-determining method, the induction regimen comprises a single administration of an anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dosing method, the anti-TL1A antibody or antigen-binding fragment is administered 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.

[0045] In some embodiments of the dose-determining method, the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose-determining method, the induction regimen comprises: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; or (v) 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10.

[0046] In some embodiments of the dosage method, 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. In some embodiments of the dosage method, the induction regimen comprises administration once every 2, 4, 6, or 8 weeks. In some embodiments of the dosing method, the induction regimen includes administration once every 2 or 4 weeks for the first two doses, then once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

[0047] In some embodiments of the dosage-determining method, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than the corresponding tissue in the control subject. In some embodiments of the dosage-determining method, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than the corresponding tissue in the control subject during the maintenance regimen. In some embodiments of the dose determination method, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times or more TL1A compared to the corresponding tissue in a 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 more of the initiation of the maintenance regimen.

[0048] In some embodiments of the dosing method, the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose determination method, the maintenance regimen is (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) 50 mg / dose every 6 ... (xxiii) 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.

[0049] In some embodiments of the dose-determining method, the maintenance regimen comprises administering 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. In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks. In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every 4 weeks. In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every 4 weeks. In some embodiments of the dosing method, 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.

[0050] In some embodiments of the dose determination method, an effective dose regimen maintains the concentration of TL1A in the subject's diseased tissues below the concentration of TL1A in the corresponding tissues of a control subject without pulmonary inflammation and / or pulmonary fibrosis 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.

[0051] In some embodiments of the dose determination method, step (a) comprises measuring the rate of TL1A trimerization (k on-TL1A-monomer-to-trimer ) and / or the rate of TL1A monomerization (k off-TL1A-trimer-to-monomer ).

[0052] In some embodiments of the methods provided herein, including the methods of use / treatment and dosing methods provided herein, the concentration of TL1A is the concentration of free TL1A.

[0053] In some embodiments, an anti-TL1A antibody comprises a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-5, and an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 6-9; and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 10, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 11, and an LCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-15. In certain embodiments, an anti-TL1A antibody comprises an HCDR1 set forth in SEQ ID NO: 401, 407, 413, or 450. In certain embodiments, an anti-TL1A antibody comprises an HCDR2 set forth in SEQ ID NO: 402, 408, 414, or 451. In certain embodiments, an anti-TL1A antibody comprises an HCDR3 set forth in SEQ ID NO: 403, 409, 415, or 452. In certain embodiments, an anti-TL1A antibody comprises an LCDR1 described by SEQ ID NO: 404, 410, 416, or 453. In certain embodiments, an anti-TL1A antibody comprises an LCDR2 described by SEQ ID NO: 405, 411, 417, or 454. In certain embodiments, an anti-TL1A antibody comprises an LCDR3 described by SEQ ID NO: 406, 412, 418, or 455.

[0054] In some embodiments, 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 fewer than nine amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

[0055] In some embodiments, 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 or 420-427, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220 or 430-437.

[0056] In some embodiments, the anti-TL1A antibody is SEQ ID NO: 301 a heavy chain variable region comprising: X1VQLVQSGAEVKKPGASVKVSCKAS [HCDR1] WVX2QX3PGQGLEWX4G [HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [HCDR3] WGQGTTVTVSS; and and a light chain variable region comprising: EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1 to 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; HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 1; HCDR2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 2 to 5; HCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 6 to 9; LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 10; LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 11; and LCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 12 or 13. [Brief explanation of the drawings]

[0057] 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.

[0058] Exemplary embodiments are illustrated in the referenced drawings. It is intended that the embodiments and figures disclosed herein be considered illustrative and not restrictive.

[0059] [Figure 1A] Figure 1 shows chromatograms of analytical size exclusion chromatography of anti-TL1A antibodies. The large peak (main peak) corresponds to the monomer fraction. The percentage of the monomer sample is indicated for each antibody. Figure 1A shows chromatograms of antibodies A193, A194, and A195. Figure 1B shows chromatograms of antibodies A196, A197, and A198. Figure 1C shows chromatograms of antibodies A199, A200, and A201. [Figure 1B] Figure 1 shows chromatograms of analytical size exclusion chromatography of anti-TL1A antibodies. The large peak (main peak) corresponds to the monomer fraction. The percentage of the monomer sample is indicated for each antibody. Figure 1A shows chromatograms of antibodies A193, A194, and A195. Figure 1B shows chromatograms of antibodies A196, A197, and A198. Figure 1C shows chromatograms of antibodies A199, A200, and A201. [Figure 1C] Figure 1 shows chromatograms of analytical size exclusion chromatography of anti-TL1A antibodies. The large peak (main peak) corresponds to the monomer fraction. The percentage of the monomer sample is indicated for each antibody. Figure 1A shows chromatograms of antibodies A193, A194, and A195. Figure 1B shows chromatograms of antibodies A196, A197, and A198. Figure 1C shows chromatograms of antibodies A199, A200, and A201. [Figure 2] 1 shows the inhibition of interferon gamma in human blood by anti-TL1A antibody. [Figure 3A] 1 shows a comparison between predicted and measured viscosity. [Figure 3B]Figure 3B shows a PLS model demonstrating the effect of pH and protein concentration on viscosity. Figure 3B shows a PLS graph (the x-axis of the PLS graph is pH, the y-axis is protein concentration (mg / ml), and the z-axis is viscosity (mPa-s)), Figure 3C shows a model of predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration in mg / mL (x-axis), and Figure 3D shows a model of estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). [Figure 3C] Figure 3B shows a PLS model demonstrating the effect of pH and protein concentration on viscosity. Figure 3B shows a PLS graph (the x-axis of the PLS graph is pH, the y-axis is protein concentration (mg / ml), and the z-axis is viscosity (mPa-s)), Figure 3C shows a model of predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration in mg / mL (x-axis), and Figure 3D shows a model of estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). [Figure 3D] Figure 3B shows a PLS model demonstrating the effect of pH and protein concentration on viscosity. Figure 3B shows a PLS graph (the x-axis of the PLS graph is pH, the y-axis is protein concentration (mg / ml), and the z-axis is viscosity (mPa-s)), Figure 3C shows a model of predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration in mg / mL (x-axis), and Figure 3D shows a model of estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). [Figure 3E] 1 shows the effect of pH versus acetate concentration on viscosity. [Figure 3F] 1 shows the effect of NaCl versus sucrose on viscosity. [Figure 3G] Figure 1 shows the effect of Arg-HCl vs. Lys-HCl on viscosity. Viscosity units are in mPa-s. Arrows point to the regions of highest viscosity. Stars correspond to the regions of lowest viscosity. [Figure 4A] 1 shows the PLS1 model for the effect on high molecular weight (HMW) aggregates. [Figure 4B] 1 shows the effect of pH versus acetate on aggregation. [Figure 4C] The effect of sucrose versus NaCl concentration is shown. [Figure 4D] 1 shows the effect of Arg-HCl versus Lys-HCl on aggregation. [Figure 4E] 1 shows the effect of sucrose concentration versus Lys-HCl concentration. [Figure 5A] Expected versus measured loss of main peak at 2 weeks and 25° C. is shown. [Figure 5B] 1 shows the effect of pH and protein concentration on the loss of the main peak in the CEX profile. [Figure 5C] 1 shows the effect of pH and acetate concentration on the loss of the main peak in the CEX profile. [Figure 5D] 1 shows the effect of sucrose and NaCl concentrations on the loss of the main peak in the CEX profile. [Figure 5E] 1 shows the effect of Lys-HCl and sucrose concentrations on the loss of the main peak in the CEX profile. [Figure 6A] SEC shows loss of monomer upon agitation. [Figure 6B] SEC demonstrates loss of monomer upon freeze-thawing. [Figure 7A] Figure 1 shows that anti-TL1A antibodies bind to cynomolgus monkey and human TL1A, but not to mouse or rat TL1A. ELISAs for each protein were performed at least three times. Data from a representative experiment are shown and are the mean ± SD. Abbreviations: A = absorbance, Ab = antibody, Cyno = cynomolgus monkey, nm = nanometer, nM = nanomolar. [Figure 7B]Figure 1 shows the mean sTL1A levels that increased with increasing IV doses of anti-TL1A in cynomolgus monkeys, as measured by ELISA. Samples were assayed in triplicate on two separate occasions. Data presented are the mean TL1A concentrations ± SD for three animals per group. Samples collected from animals administered an isotype control antibody are indicated by circles, and samples collected from animals administered anti-TL1A are indicated by triangles and squares. Abbreviations: hr = hour, kg = kilogram, mg = milligram, mL = milliliter, ng = nanogram, TL1A = tumor necrosis factor-like cytokine 1A. [Figure 8] Figure 1 shows that TL1A drives inflammation and fibrosis through binding to DR3. [Figure 9] Figures 9A-9C show 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 Figure 9A, when injected alone, the rhTL1A SEC profile shows two peaks on SEC, representing the trimeric and monomeric forms of TL1A. In Figure 9B, preincubation of rhTL1A with a control reference antibody shifted the trimeric peak to the left, indicating greater complex formation between the reference antibody and trimeric rhTL1A. There was no shift in the monomeric peak, indicating that the reference antibody binds only to trimeric rhTL1A. In Figure 9C, preincubation of rhTL1A with A219 shifted both the trimeric and monomeric rhTL1A peaks, thus indicating that A219 binds to both the trimeric and monomeric forms of TL1A. [Figure 10A] A whole-body physiologically based pharmacokinetic (PBPK) model is shown. [Figure 10B] FIG. 1 shows a tissue-level diagram of the integrated whole-body PBPK model used to characterize the PK of a monoclonal antibody (mAb), a ligand, and the complex between the mAb and the ligand. [Figure 11A]A comparison of the mAb pharmacokinetics predicted by integrated whole-body PBPK (solid curve) and observed in healthy volunteers (various points with points from the same subject shown in the same format) is shown in each case after injection of A219 at the doses indicated. [Figure 11B] A comparison of the TL1A concentrations predicted by integrated whole-body PBPK with those observed in healthy volunteers is shown in each case after injection of A219 at the doses indicated. [Figure 12A] Figure 12A shows the observed concentrations of TL1A in serum after injection of (i) the anti-TL1A antibody A219, which binds both TL1A monomer and trimer (shown in red, the top of the two curves, and the observed data points associated with those curves), and (ii) a control reference anti-TL1A antibody that binds only the TL1A trimer (shown in blue, the bottom of the two curves, and the observed data points associated with those curves). In Figure 12A, the solid curves represent predictions from the model, and the various dots represent observations from subjects injected with the indicated antibodies. [Figure 12B] Shown in each case at basal levels (without injection of any anti-TL1A antibody) are the predicted total TL1A concentrations (monomers and trimers, solid curves and observed data points associated with such curves), monomeric TL1A concentrations (fine dotted lines), and trimeric TL1A concentrations (coarse dotted lines). [Figure 12C] Serum TL1A concentrations in healthy volunteers (NHVs) and UC patients predicted by the whole-body PBPK model (solid line, upper line for UC patients, and lower line for NHVs) and observed (various points) are shown. [Figure 13A]The fit of the model is demonstrated. Figure 13A shows the observed concentrations of TL1A (dots) in the serum of NHVs after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX3 = 3 times every 2 weeks. Figure 13B shows the observed concentrations of TL1A (dots) in the serum of UC patients after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX7 = 7 times every 2 weeks. [Figure 13B] The fit of the model is demonstrated. Figure 13A shows the observed concentrations of TL1A (dots) in the serum of NHVs after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX3 = 3 times every 2 weeks. Figure 13B shows the observed concentrations of TL1A (dots) in the serum of UC patients after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX7 = 7 times every 2 weeks. [Figure 13C] The concentrations of TL1A in the intestine of NHVs (two solid black lines predicted from the model, the bottom line, and the observed data points associated with such lines) and in the intestine of UC patients (two solid red lines, the top line) are shown. [Figure 14A] Baseline concentrations of TL1A based on various parameters of TL1A production in the intestine (14A) and serum (14B) are shown. In Figures 14A-14B, 1x is baseline in NHVs, and 25x, 50x, 75x, and 100x represent various parameters of TL1A overproduction in the intestine. [Figure 14B] Baseline concentrations of TL1A based on various parameters of TL1A production in the intestine (14A) and serum (14B) are shown. In Figures 14A-14B, 1x is baseline in NHVs, and 25x, 50x, 75x, and 100x represent various parameters of TL1A overproduction in the intestine. [Figure 15A]1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15B] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15C] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15D] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15E] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15F] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15G] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15H] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15I]1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15J] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15K] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15L] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15M] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15N] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15O] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15P] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15Q]1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15R] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15S] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15T] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15U] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15V] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15W] Figure 1 shows free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under the indicated dose regimens of a reference anti-TL1A antibody. [Figure 15X]Figures 15W-15Z show a comparison of modeled free soluble TL1A concentrations in subjects treated with a reference anti-TL1A antibody (red, upper curve of the two curves) or A219 (green, lower curve of the two curves). In Figures 15W-15Z, the light chain sequence of the reference antibody is SEQ ID NO: 382, ​​the heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses the observed rapid equilibration between the monomeric and trimeric forms of TL1A with a continuous 60:40 ratio of monomer to trimer. The solid black lines in Figures 15A-15Z show TL1A concentrations in tissues of NHVs. Q2W = every 2 weeks. Q4W = every 4 weeks. SC = subcutaneous. LD = loading dose (first dose). 4W = week 4. D1 = day 1. W2, 6, 10 = weeks 2, 6, and 10. W2, 4, 6, 10 = weeks 2, 4, 6, and 10. EOW = every other week. W4, 8, 12 = weeks 4, 8, and 12. W2, 4, 8, 12 = weeks 2, 4, 8, and 12. sTL1A = soluble TL1A. [Figure 15Y] Figures 15W-15Z show a comparison of modeled free soluble TL1A concentrations in subjects treated with a reference anti-TL1A antibody (red, upper curve of the two curves) or A219 (green, lower curve of the two curves). In Figures 15W-15Z, the light chain sequence of the reference antibody is SEQ ID NO: 382, ​​the heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses the observed rapid equilibration between the monomeric and trimeric forms of TL1A with a continuous 60:40 ratio of monomer to trimer. The solid black lines in Figures 15A-15Z show TL1A concentrations in tissues of NHVs. Q2W = every 2 weeks. Q4W = every 4 weeks. SC = subcutaneous. LD = loading dose (first dose). 4W = week 4. D1 = day 1. W2, 6, 10 = weeks 2, 6, and 10. W2, 4, 6, 10 = weeks 2, 4, 6, and 10. EOW = every other week. W4, 8, 12 = weeks 4, 8, and 12. W2, 4, 8, 12 = weeks 2, 4, 8, and 12. sTL1A = soluble TL1A. [Figure 15Z]Figures 15W-15Z show a comparison of modeled free soluble TL1A concentrations in subjects treated with a reference anti-TL1A antibody (red, upper curve of the two curves) or A219 (green, lower curve of the two curves). In Figures 15W-15Z, the light chain sequence of the reference antibody is SEQ ID NO: 382, ​​the heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses the observed rapid equilibration between the monomeric and trimeric forms of TL1A with a continuous 60:40 ratio of monomer to trimer. The solid black lines in Figures 15A-15Z show TL1A concentrations in tissues of NHVs. Q2W = every 2 weeks. Q4W = every 4 weeks. SC = subcutaneous. LD = loading dose (first dose). 4W = week 4. D1 = day 1. W2, 6, 10 = weeks 2, 6, and 10. W2, 4, 6, 10 = weeks 2, 4, 6, and 10. EOW = every other week. W4, 8, 12 = weeks 4, 8, and 12. W2, 4, 8, 12 = weeks 2, 4, 8, and 12. sTL1A = soluble TL1A. [Figure 16A] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16B] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16C] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16D] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16E] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16F] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16G] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16H] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 17A] A visual prediction check of the A219 concentrations predicted from the popPK model against the observed A219 concentrations is shown. [Figure 17B] The induction dose selected in the popPK model to rapidly achieve steady-state concentrations is shown. [Figure 18] Figure 1 shows the osmolality at 5°C measured for the stability of A219 samples in various formulations at TO, 3, and 6 months. [Figure 19] 1 shows the A219 protein concentration at 5° C. measured to assess the stability of A219 samples in various formulations at TO, 3, and 6 months. [Figure 20] 1 shows the pH at 5° C. measured to assess the stability A219 samples of various formulations at TO, 3, and 6 months. [Figure 21A] Figure 1 shows viscosity data at TO and 3M for formulations 1-5 at 25°C. [Figure 21B] Figure 1 shows viscosity data at TO and 3M for formulations 6-8 at 25°C. [Figure 22A] Figure 1 shows the monomer content of the formulations at 5°C as measured by SEC. [Figure 22B] Figure 1 shows the loss of monomer (main peak) per month of the formulations at 5°C as determined by SEC. [Figure 22C] Figure 1 shows the monomer content of the formulations at 25°C as measured by SEC. [Figure 22D] Figure 1 shows the loss of monomer (main peak) per month of the formulations at 5°C as determined by SEC. [Figure 23A] The relative area (%) of the main peak of the formulations at 5° C. as characterized by cation exchange chromatography is shown. [Figure 23B] Figure 1 shows the main peak (relative area (%) per month) of the formulation at 5°C as characterized by cation exchange chromatography. [Figure 23C] The relative area (%) of the main peak of the formulations at 25° C., characterized by cation exchange chromatography, is shown. [Figure 23D] The main peak (relative area (%) per month) of the formulation at 25° C. as characterized by cation exchange chromatography is shown. [Figure 24A] Predictions from a PLS model using monomer loss by SEC versus measurements are shown for samples stored at 25°C for 2 months as the endpoint. [Figure 24B] The effect of pH and protein is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored at 25° C. for 2 months. In Figure 24B, the sucrose concentration was fixed at 200 mM. [Figure 24C] The effect of pH and acetate is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored for 2 months at 25° C. In Figure 24C, the sucrose concentration was fixed at 200 mM. [Figure 24D] The effect of sucrose and lysine is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored at 25° C. for 2 months. In Figure 24D, the protein concentration was fixed at 150 mg / mL, pH at 5.5, and acetate at 20 mM. [Figure 24E] The effect of glycine and NaCl is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored at 25°C for 2 months. In Figure 24E, the protein concentration was fixed at 150 mg / mL, pH at 5.5, and acetate at 20 mM. In Figures 18, 19, 20, 21A-21B, 22A-22D, 23A-23D, and 24A-24E, Formulations 1-8 (F01-F08, Forms 1-8, or simply 1-8) referenced therein are Formulations 1-8 described in Table 31 of Example 31. [Figure 25] FIG. 1 shows the scheme of a double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of A219 in subjects with systemic sclerosis associated with interstitial lung disease (SSc-ILD). [Figure 26A] 1 shows the geometric mean serum A219 concentration-time profile (linear scale) following a single dose of A219 administered as an IV infusion (SAD study). [Figure 26B] 1 shows the geometric mean serum A219 concentration-time profiles (linear scale) after multiple doses of A219 Q2W administered as IV infusions on Day 29 (MAD study). Q2W = every 2 weeks. [Figure 27A]Geometric mean serum sTL1A concentrations versus nominal time (semi-log scale) following a single dose of A219 administered as an IV infusion (SAD study). [Figure 27B] Geometric mean serum sTL1A concentrations versus nominal time (semi-logarithmic scale) after multiple doses of A219 Q2W administered as an IV infusion (MAD study). [Figure 28A] Shown are central compartment total A219 concentrations (circulating) in SAD as predicted by the model (curves) and as determined in a phase I study (dots). [Figure 28B] Figure 1 shows total soluble TL1A (circulating) in the central compartment in SAD as predicted by the model (curve) and as determined in a phase I study. [Figure 28C] The central compartment total A219 concentration (in circulation) at the MAD is shown as predicted by the model (curve) and as determined in a phase I study (dots). [Figure 28D] Figure 1 shows the total soluble TL1A (circulating) in the central compartment at MAD as predicted by the model (curve) and as determined in a phase I study (dots). Predicted curve fitted to the measured data points. [Figure 28E] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 28F]Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 28G] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 28H] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 28I]Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 28J] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 28K] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 28E and 28F), (2) Phase I multiple ascending dose data (Figures 28G and 28H), and (3) Phase II data for PK and total sTL1A levels (Figures 28I and 28J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 28K). NR = non-responder, R = responder. [Figure 29A] 1 shows the dose of A219 determined from a validated model that can reduce the free TL1A concentration in diseased tissues of patients to below that of healthy subjects. [Figure 29B]Figure 1 shows the percent reduction of free TL1A in diseased tissue after administration of doses of A219 as determined from the model. IV_4x = 1000mg loading dose, 3x 500mg on days 14, 42, 70. SC administration 240mg Q1W or Q2W. [Figure 29C] Direct comparison in a validated model shows that anti-TL1A antibodies that bind to both TL1A monomers and trimers engage more (3.5-fold more) TL1A in the circulation than anti-TL1A antibodies that bind only to TL1A trimers. [Figure 29D] In a direct comparison in a validated model, anti-TL1A antibodies that bind to both TL1A monomers and trimers also resulted in a higher rate (approximately 100%) of TL1A reduction in diseased tissue when compared to anti-TL1A antibodies that only bind to TL1A trimers. [Figure 30A] A diagram of the popPK model is shown. [Figure 30B] 1 shows a comparison of A219 concentrations predicted from the popPK model and observed in a population of subjects from a Phase I clinical trial via a linear regression plot. [Figure 30C] 1 shows a comparison of predicted TL1A concentrations from the popPK model and observed TL1A concentrations in a population of subjects from a Phase I clinical trial via a linear regression plot. [Figure 30D] 1 shows a comparison of predicted A219 concentrations from the popPK model and observed A219 concentrations in a Phase I clinical trial subject population via a time series plot. [Figure 30E] 1 shows a comparison of predicted TL1A concentrations from the popPK model and observed TL1A concentrations in a Phase I clinical trial subject population via a time series plot. [Figure 31A]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31B]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31C]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31D]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31E]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31F]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31G]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31H]Figures 31A and 31B show the predicted A219 and TL1A engagement (serum TL1A concentrations) from the validated popPK model under various A219 doses. Figures 31A and 31B show circulating A219 (31A) and TL1A (31B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W extension (20 doses) from week 12 to week 52. Figures 31C and 31D show circulating A219 (31C) and TL1A (31D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W extension (10 doses) from week 12 to week 52. Figures 31E and 31F show circulating A219 (31E) and TL1A (31F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 31G and 31H show A219 (31G) and TL1A (31H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 32] Figure 32 shows bulk RNA-seq gene expression data (original data from Skaug B, et al., Ann Rheum Dis. 2020;79(3):379-86) analyzed by gene set variation analysis (GSVA). Figure 32 shows the upregulation of a set of TL1A-responsive signature genes in tissues from SSc patients compared to tissues from healthy control subjects. [Figure 33] Figure 33 shows the expression of TL1A and DR3 in cells derived from the skin of SSc patients. Gene expression data (RNA-seq) from SSc biopsy tissues show upregulation of the TL1A (TNFSF15) and DR3 (TNFRSF25) genes at the single-cell level in SSc patients. In Figure 33, TL1A was expressed in myeloid cells, and DR3 was expressed in fibroblasts, endothelial cells, keratinocytes, and T cells. [Figure 34A]We show TL1A and DR3 expression in skin-derived cells from SSc patients. Gene expression data (RNA-seq) and epigenetics (chromatin accessibility by ATAC-seq) from SSc biopsy tissue demonstrate upregulation of the TL1A (TNFSF15) and DR3 (TNFRSF25) genes at the single-cell level. TL1A is expressed in myeloid cells, and DR3 is expressed in T cells and myeloid cells. [Figure 34B] We show TL1A and DR3 expression in skin-derived cells from SSc patients. Gene expression data (RNA-seq) and epigenetics (chromatin accessibility by ATAC-seq) from SSc biopsy tissue demonstrate upregulation of the TL1A (TNFSF15) and DR3 (TNFRSF25) genes at the single-cell level. TL1A is expressed in myeloid cells, and DR3 is expressed in T cells and myeloid cells. DETAILED DESCRIPTION OF THE INVENTION

[0060] TL1A is a cytokine secreted by antigen-presenting cells, T cells, and endothelial cells. TL1A signals through death receptor 3 (DR3), a TNF family receptor found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphoid cells (ILCs), fibroblasts, and epithelial cells, and potently drives Th1, Th2, Th9, and Th17 responses. Furthermore, it is induced in antigen-presenting cells by toll-like receptor (TLR) ligands and FcR crosslinking, and in T cells by T cell receptor (TCR) stimulation.

[0061] Figure 8 demonstrates how TL1A binding to DR3 independently promotes inflammation and fibrosis. TL1A binding to DR3 on innate and T cells leads to an early cytokine response (release of IL-23, IL-1β, IL-17, IL-22, TNF-α, IFN-γ, and IL-13) that sets the stage for inflammation and stimulates innate and adaptive immune responses. For example, through binding to DR3, TL1A potentially drives inflammatory Th1 and Th17 responses. Furthermore, TL1A binding to DR3 on fibroblasts directly activates fibroblasts, leading to collagen dynamics and fibrosis independent of inflammation. While circulating TL1A levels are low in healthy subjects, they are elevated in patients with many autoimmune diseases, and TL1A has been shown to be upregulated in the mucosa and serum of patients with IBD. In mice, chronic TL1A expression leads to structural disease caused by increased collagen deposition. In dextran sulfate sodium (DSS) and adoptive transfer mouse models, TL1A transgenic mice developed more severe colitis than wild-type animals when challenged with DSS, and antibodies to TL1A reduced inflammation, reduced collagen levels, and reversed fibrosis, even when treatment was administered late in the disease course after inflammation and fibrosis had been established. Furthermore, TL1A polymorphisms have been shown to be associated with susceptibility to IBD and disease severity.

[0062] Fibrosis is an important clinical phenotype exhibited by IBD patients. 70% of patients with Crohn's disease (CD) develop strictures / perforations, and strictures are the leading indication for surgery in CD. Unfortunately, the use of anti-inflammatory agents over the past decade has not substantially changed the rate of structural disease or the need for surgery. Furthermore, in ulcerative colitis (UC), subclinical fibrosis significantly impacts patient symptoms. For example, subclinical fibrosis can contribute to symptoms of diarrhea, abdominal pain, urgency, and incontinence. Subclinical fibrosis is also a potential cause of persistent symptoms after resolution of inflammation. Furthermore, a Cleveland Clinic study of 89 consecutive colectomy specimens revealed submucosal fibrosis in 100% of specimens. Therefore, treatment of fibrosis constitutes an unmet need in IBD.

[0063] The potential of TL1A as a therapeutic target in intestinal fibrosis was demonstrated in studies evaluating the effects of anti-TL1A antibodies in mouse models of IBD. These studies utilized two mouse models of chronic colitis: adoptive T cell transfer and chronic DSS. In both models, a neutralizing TL1A monoclonal antibody (mAb) or an isotype control antibody was administered twice weekly to mice with established colitis (T cell transfer n = 14, DSS n = 28). In both disease models, treatment with TL1A mAb reduced colonic collagen deposition levels to those seen in healthy control mice, suggesting that blocking TL1A signaling not only prevented the progression of colonic fibrosis but also reversed established fibrosis to levels similar to those measured before the onset of inflammation. These data indicate that intestinal fibrosis mediated by increased levels of TL1A can be treated with anti-TL1A antibodies.

[0064] In one aspect, provided herein are methods of treating inflammation and / or fibrosis with anti-TL1A antibodies. In some embodiments, the treatment of fibrosis is independent of the treatment of inflammation. In some embodiments, the treatment of inflammation is independent of the treatment of fibrosis. In another aspect, provided herein are methods of treating pulmonary diseases and / or conditions with anti-TL1A antibodies. Non-limiting examples of indications for use with anti-TL1A antibodies herein include idiopathic interstitial pneumonia, pulmonary sarcoidosis, interstitial lung disease, bronchiolitis, alveolitis, vasculitis, interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, idiopathic organizing pneumonia, acute interstitial pneumonia, allergic rhinitis, emphysema, chronic bronchitis, primary biliary cholangitis, primary biliary cholangitis, Behçet's disease, systemic sclerosis-associated interstitial lung disease, and cystic fibrosis. In certain embodiments, the anti-TL1A antibodies bind with high affinity and specificity to both membrane-bound and soluble forms of TL1A and block the binding of TL1A to its functional receptor DR3.

[0065] The term "and / or" when used in a phrase including a list of members is intended to include all members individually and all combinations of a complete 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, A alone, and B alone. Similarly, the term "and / or" when 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.

[0066] 4.1 General Techniques The techniques and procedures described or referenced herein include those that are generally well understood and / or commonly employed by those of skill in the art using conventional methodology, such as, for example, the widely utilized methodology described in Sambrook et al., Molecular Cloning: A Laboratory Manual (3rd 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 Dubel eds., 2nd ed. 2010).

[0067] 4.2 Anti-TL1A antibody TL1A exists in both monomeric and trimeric forms in vivo and in vitro. The present disclosure provides that, although the trimeric form is the biologically active form that can bind to the physiological receptor, death receptor 3 ("DR3"), and induce 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. One of the inventors' estimates is that monomeric TL1A may represent 60% of the total TL1A in the circulation. The term "total TL1A" refers to both monomeric and trimeric TL1A. The present disclosure further provides that anti-TL1A antibodies that bind to both monomeric and trimeric TL1A are advantageous over antibodies that bind only to trimeric TL1A, even though monomeric TL1A is biologically inactive. As provided herein and further demonstrated in Section 5, such advantages include a more efficient reduction in TL1A concentration in a subject's diseased tissue, including the concentration of trimeric TL1A in the diseased tissue; a more efficient reduction in TL1A concentration in a subject's blood, including the concentration of trimeric TL1A in the blood; a more sustained reduction in TL1A concentration (including trimeric TL1A concentration) in a subject's diseased tissue; and / or a more sustained reduction in TL1A concentration (including trimeric TL1A concentration) in a subject's blood.

[0068] In one aspect, provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (for brevity, referred to herein as "TL1A," and such antibodies or antigen-binding fragments thereof, "anti-TL1A antibodies or antigen-binding fragments," or "anti-TL1A antibodies"), wherein the antibodies or antigen-binding fragments bind to both monomeric and trimeric TL1A. Additional embodiments of anti-TL1A antibodies, including embodiments with exemplary CDRs, framework sequences, constant region sequences, Fc mutations, variable regions, Fc regions, and other features, are provided further in this section (Section 4.2). Assays for screening, testing, and validation of anti-TL1A antibodies are provided in Section 4.3. Methods for generating, improving, mutating, cloning, expressing, and isolating anti-TL1A antibodies are provided in Section 4.4. Pharmaceutical compositions of anti-TL1A antibodies are described and provided in Section 4.5. Methods of using anti-TL1A antibodies are provided in Section 4.6. Further specific and validated embodiments of anti-TL1A antibodies and methods of using them are provided in Section 5. Accordingly, the present disclosure provides various combinations of anti-TL1A antibodies, pharmaceutical compositions of such anti-TL1A antibodies, methods of producing anti-TL1A antibodies, methods of assaying anti-TL1A antibodies, and methods of using anti-TL1A antibodies for therapy.

[0069] 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 binding of trimeric TL1A to DR3. In a further embodiment, the antibody or antigen-binding fragment blocks TL1A-mediated DR3 signaling. In yet another embodiment, the antibody or antigen-binding fragment blocks increased IFNγ secretion by various immune cells. In a specific embodiment, the antibody or antigen-binding fragment blocks increased IFNγ secretion by various B cells, T cells, natural killer cells, and / or peripheral blood mononuclear cells, including macrophages.

[0070] As described herein, the present disclosure provides anti-TL1A antibodies or antigen-binding fragments for binding to both monomeric and trimeric TL1A. Accordingly, in one embodiment of the various anti-TL1A antibodies or antigen-binding fragments thereof provided herein, the dissociation equilibrium constant (K D-monomer The binding affinity of an antibody or antigen-binding fragment to monomeric TL1A, as measured by the dissociation equilibrium constant (K D-trimer ) corresponds to the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A. D-monomer and / or K D-trimer can be determined via any of the methods known and practiced by those of skill in the art, as well as any of the applicable assays and methods described herein, including in this section (Section 4.2) and Section 5.

[0071] The term "bind" or "binding" refers to interactions between molecules, including, for example, forming a complex. The interaction can be a non-covalent interaction, including, for example, hydrogen bonding, ionic bonding, hydrophobic interactions, and / or van der Waals interactions. A complex can also include the association of two or more molecules held together by covalent or non-covalent bonds, interactions, or forces. The strength of all non-covalent interactions between a single antigen-binding site on an antibody and a single epitope on a target molecule, such as TL1A, is the affinity of the antibody or functional fragment for that epitope. The association rate (k on ) to the dissociation rate (k off ) ratio (k off / k on ) is the dissociation constant K, which is inversely proportional to the affinity D It is. K D The lower the value, the higher the affinity of the antibody. D The value of k varies for different complexes of antibody and antigen. on and k off The dissociation constant K of the antibodies provided herein depends on both Dcan be determined using any method provided herein or any other method known to those skilled in the art. The affinity at one binding site does not necessarily reflect the true strength of the interaction between the antibody and the antigen. When a complex antigen containing multiple repeating antigenic determinants, such as a multivalent TL1A trimer, contacts an antibody containing multiple binding sites, the interaction between the antibody and the antigen at one site will increase the probability of reaction at a second site. The strength of such multiple interactions between a multivalent antibody and an antigen is called avidity. The avidity of an antibody may be a better measure of its binding capacity than the affinity of its individual binding sites.

[0072] "Binding affinity" generally refers to the strength of the sum of non-covalent 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 otherwise indicated, as used herein, "binding affinity" refers to the intrinsic binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., an antibody and an antigen). As noted above, the affinity of a binding molecule X for a binding partner Y is generally determined by the dissociation constant (K D ) Affinity can be measured by common methods known in the art, including those described herein. Low affinity antibodies generally bind to antigens slowly and tend to dissociate easily, whereas high affinity antibodies generally tend to bind to antigens quickly and remain bound for a long time. Various methods for measuring binding affinity are known in the art, any of which may be used for the purposes of the present disclosure. Specific exemplary embodiments include the following. In one embodiment, "K D " or "K D The "K value" can be measured by assays known in the art, for example, by binding assays. D can be measured, for example, in an RIA performed using the Fab version of the antibody of interest and its antigen (Chen et al., 1999, J. Mol Biol 293:865-81). D or K DThe value can also be measured by using a surface plasmon resonance assay by Biacore®, for example, using a Biacore® TM-2000 or Biacore® TM-3000, or by biolayer interferometry, for example, using an Octet® QK384 system. "on rate" or "rate of association" or "association rate" or "k on " can also be determined with the same surface plasmon resonance or biolayer interferometry techniques as above, using, for example, a Biacore® TM-2000 or Biacore® TM-3000, or an Octet® QK384 system.

[0073] Therefore, the relative binding affinity of an anti-TL1A antibody or antigen-binding fragment for TL1A monomer and TL1A trimer is expressed as K D-monomer and K. D-trimer In one embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-monomer is K D-trimer In another embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, the K D-monomer is K D-trimer In further embodiments of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-trimer is K D-monomer In another embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, the K D-trimer is K D-monomer within 10%, 20%, 30%, 40%, or 50% of the

[0074] More specifically, in one embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-monomer is at most 5 × 10 -12 M, at most 6 × 10 -12 M, at most 7 × 10-12 M, at most 8 × 10 -12 M, at most 9 × 10 -12 M, at most 1 × 10 -11 M, at most 2 × 10 -11 M, at most 3 × 10 -11 M, at most 4 × 10 -11 M, at most 5 × 10 -11 M, at most 6 × 10 -11 M, at most 7 × 10 -11 M, at most 8 × 10 -11 M, at most 9 × 10 -11 M, at most 1 × 10 -10 M, at most 2 × 10 -10 M, at most 3 × 10 -10 M, at most 4 × 10 -10 M, at most 5 × 10 -10 M, at most 6 × 10 -10 M, at most 7 × 10 -10 M, at most 8 × 10 -10 M, at most 9 × 10 -10 M, or at most 1 × 10 -9 In another embodiment, K D-monomer is about 5 x 10 -12 M, about 6 x 10 -12 M, about 7 x 10 -12 M, about 8 x 10 -12 M, about 9 x 10 -12 M, about 1 x 10 -11 M, approx. 2 x 10 -11 M, about 3 x 10 -11 M, approx. 4 x 10 -11 M, about 5 x 10 -11 M, about 6 x 10 -11 M, about 7 x 10 -11 M, about 8 x 10 -11 M, about 9 x 10 -11 M, about 1 x 10 -10 M, approx. 2 x 10 -10 M, about 3 x 10 -10 M, approx. 4 x 10 -10 M, about 5 x 10 -10 M, about 6 x 10 -10 M, about 7 x 10 -10 M, about 8 x 10 -10 M, about 9 x 10 -10 M, or approximately 1 x 10-9 In further embodiments of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-trimer is at most 5 × 10 -12 M, at most 6 × 10 -12 M, at most 7 × 10 -12 M, at most 8 × 10 -12 M, at most 9 × 10 -12 M, at most 1 × 10 -11 M, at most 2 × 10 -11 M, at most 3 × 10 -11 M, at most 4 × 10 -11 M, at most 5 × 10 -11 M, at most 6 × 10 -11 M, at most 7 × 10 -11 M, at most 8 × 10 -11 M, at most 9 × 10 -11 M, at most 1 × 10 -10 M, at most 2 × 10 -10 M, at most 3 × 10 -10 M, at most 4 × 10 -10 M, at most 5 × 10 -10 M, at most 6 × 10 -10 M, at most 7 × 10 -10 M, at most 8 × 10 -10 M, at most 9 × 10 -10 M, or at most 1 × 10 -9 In yet another embodiment, K D-trimer is about 5 x 10 -12 M, about 6 x 10 -12 M, about 7 x 10 -12 M, about 8 x 10 -12 M, about 9 x 10 -12 M, about 1 x 10 -11 M, approx. 2 x 10 -11 M, about 3 x 10 -11 M, approx. 4 x 10 -11 M, about 5 x 10 -11 M, about 6 x 10 -11 M, about 7 x 10 -11 M, about 8 x 10 -11 M, about 9 x 10 -11 M, about 1 x 10 -10 M, approx. 2 x 10 -10 M, about 3 x 10 -10 M, approx. 4 x 10-10 M, about 5 x 10 -10 M, about 6 x 10 -10 M, about 7 x 10 -10 M, about 8 x 10 -10 M, about 9 x 10 -10 M, or approximately 1 x 10 -9 M. The present disclosure further provides D-monomer and K. D-trimer K, including this section (Section 4.2) and this paragraph. D-monomer and K. D-trimer It is provided that the value or range of

[0075] In a further particular embodiment, K D-monomer In another particular embodiment, K D-trimer In a further embodiment, K D-monomer is approximately 59 pM, and K D-trimer is about 59 pM. D-monomer In another particular embodiment, K D-trimer In a further embodiment, K D-monomer is approximately 60 pM, and K D-trimer is about 60 pM. In one particular embodiment, K D-monomer In another particular embodiment, K D-trimer In a further embodiment, K D-monomer is at most 60 pM, and K D-trimer is at most 60 pM.

[0076] In one aspect, provided herein is an antibody that binds to TL1A. In some embodiments, the antibody comprises an antigen-binding fragment, where an antigen-binding fragment refers to a portion of an antibody comprising the antigenic determining variable region of the 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, the antibody refers to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or a combination thereof, through at least one antigen recognition site within the variable region of the immunoglobulin molecule. In some embodiments, antibodies include intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (e.g., Fab, Fab', F(ab')2, and Fv fragments), single-chain Fv (scFv) variants, CDR-grafted antibodies, multispecific antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins containing antigenic determinants of an antibody, and any other modified immunoglobulin molecule containing an antigen recognition site, provided that the antibody exhibits the desired biological activity. Antibodies may be any of the five major immunoglobulin classes: IgA, IgD, IgE, IgG, and IgM, or their subclasses (isotypes) (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), based on the identity of their heavy chain constant domains, designated alpha, delta, epsilon, gamma, and mu, respectively. Different classes of immunoglobulins have distinct and known subunit structures and three-dimensional configurations. Antibodies may be naked or conjugated to other molecules, such as toxins, radioisotopes, etc.

[0077] In some embodiments, a humanized antibody refers to a form of a non-human (e.g., murine) antibody having a particular immunoglobulin chain, chimeric immunoglobulin, or fragment thereof that contains minimal non-human (e.g., murine) sequences. In a non-limiting example, a humanized antibody contains less than about 40% non-human sequences in the variable region. In some examples, a humanized antibody contains less than about 20% non-human sequences in the full-length antibody sequence. In a further non-limiting example, a humanized antibody contains less than about 20% non-human sequences in the framework regions of each of the heavy and light chain variable regions. For example, a humanized antibody contains 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 sequences in the framework regions of each of the heavy and light chain variable regions. In another example, a humanized antibody comprises less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequence in the framework regions of each of the heavy and light chain variable regions. In some examples, humanized antibodies are human immunoglobulins in which residues from a complementarity-determining region (CDR) are replaced by residues from a CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) having the desired specificity, affinity, and capacity. These humanized antibodies may contain one or more non-human species mutations, for example, the heavy chain may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework regions, and the light chain may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework regions. The humanized heavy chain variable domain may comprise an IGHV1-46*02 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations, or no amino acid mutations. The humanized light chain variable domain may comprise an IGKV3-20 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations, or no amino acid mutations.

[0078] In some embodiments, a chimeric antibody refers to an antibody in which the sequences of its immunoglobulin molecules are derived from two or more species. As a non-limiting example, the variable regions of both the light and heavy chains correspond to the variable regions of antibodies with the desired specificity, affinity, and capacity derived from one species of mammal (e.g., mouse, rat, rabbit, etc.), while the constant regions are homologous to antibody sequences derived from another species (usually human), thereby avoiding eliciting an immune response in that species.

[0079] The terms "complementarity-determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art to refer to non-contiguous sequences of amino acids in an antibody variable region that confer antigen specificity and / or binding affinity. Generally, there are three CDRs (CDR-H1, CDR-H2, CDR-H3) in each heavy chain variable region and three CDRs (CDR-L1, CDR-L2, CDR-L3) in each light chain variable region. The terms "framework region" and "FR" are known in the art to refer to the non-CDR portions of the heavy and light chain variable regions. Generally, there are four FRs (FR-H1, FR-H2, FR-H3, and FR-H4) in each full-length heavy chain variable region and four FRs (FR-L1, FR-L2, FR-L3, and FR-L4) in each full-length light chain variable region.The precise amino acid sequence boundaries of a given CDR or FR can be determined from 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) JMB273, 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 Pluckthun 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 modeling 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 may be defined by a method selected from Kabat, Chothia, IMGT, Aho, AbM, or a combination thereof.

[0080] In some embodiments, an antibody that specifically binds to a protein indicates that the antibody reacts or associates with the protein more frequently, more rapidly, for a longer period of time, with higher affinity, or some combination of the foregoing, than with other substances, including unrelated proteins.

[0081] In some embodiments, the terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to amino acid polymers of any length. The polymers may be linear or branched, may comprise modified amino acids, and may be interrupted by non-amino acids. The terms also encompass modified natural amino acid polymers or amino acid polymers modified by intervening modifications, such as disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or fusion and / or conjugation with another polypeptide, such as, for example, a labeling component. Also included within the definition are polypeptides containing, for example, one or more analogs of an amino acid (such as, for example, an unnatural amino acid), as well as other modifications known in the art.

[0082] In some embodiments, proteins such as antibodies described herein comprise hydrophobic amino acids. Non-limiting examples of hydrophobic amino acids include glycine (Gly), proline (Pro), phenylalanine (Phe), alanine (Ala), isoleucine (Ile), leucine (Leu), and valine (Val). In some embodiments, proteins such as antibodies described herein comprise hydrophilic amino acids. Non-limiting examples of 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, proteins such as antibodies described herein comprise amphipathic amino acids. Non-limiting examples of amphipathic amino acids include lysine (Lys), tryptophan (Trp), tyrosine (Tyr), and methionine (Met). In some embodiments, proteins such as antibodies described herein comprise aliphatic amino acids. Non-limiting examples of aliphatic amino acids include alanine (Ala), isoleucine (Ile), leucine (Leu), and valine (Val). In some embodiments, proteins such as antibodies described herein comprise aromatic amino acids. Non-limiting examples of aromatic amino acids include phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). In some embodiments, proteins such as antibodies described herein comprise acidic amino acids. Non-limiting examples of acidic amino acids include aspartic acid (Asp) and glutamic acid (Glu). In some embodiments, proteins such as antibodies described herein comprise basic amino acids. Non-limiting examples of basic amino acids include arginine (Arg), histidine (His), and lysine (Lys). In some embodiments, proteins such as antibodies described herein comprise hydroxyamino acids. Non-limiting examples of hydroxyamino acids include serine (Ser) and threonine (Thr). In some embodiments, proteins such as antibodies described herein comprise sulfur-containing amino acids.Non-limiting examples of sulfur-containing amino acids include cysteine ​​(Cys) and methionine (Met). In some embodiments, proteins such as antibodies described herein comprise amide amino acids. Non-limiting examples of amide amino acids include asparagine (Asn) and glutamine (Gln).

[0083] In some embodiments, "polynucleotide" or "nucleic acid" are used interchangeably herein to refer to a polymer of nucleotides of any length, including DNA and RNA. Nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by a DNA or RNA polymerase. Polynucleotides can also include modified nucleotides, such as, but not limited to, methylated nucleotides and their analogs or non-nucleotide components. Modifications to the nucleotide structure can be imparted before or after assembly of the polymer. Polynucleotides can be further modified after multimerization, such as by conjugation with a labeling component.

[0084] The percent sequence identity (%) to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical to those in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, without considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in a variety of known ways, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences, including the algorithm required to achieve maximum alignment over the entire length of the sequences being compared, can be determined. However, for purposes of this specification, percent amino acid sequence identity values ​​are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and the source code has been filed with user documentation at the U.S. Copyright Office, Washington, DC 20559, and 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 must be compiled for use on UNIX operating systems, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

[0085] In situations where ALIGN-2 is used for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can be rephrased as a given amino acid sequence A having or containing 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 Y is the total number of amino acid residues in B. It will be understood that if 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 otherwise specified, all % amino acid sequence identity values ​​used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0086] In some embodiments, the term "about" means within 10% of the specified amount. For example, an antibody variable region with about 80% identity to a reference variable region may have 72%-88% identity to the reference variable region.

[0087] In certain aspects, antibodies that specifically bind to TL1A are described herein (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, anti-TL1A antibodies are provided having a heavy chain comprising the following four heavy chain framework regions (HCFRs) and three heavy chain complementarity-determining regions (HCDRs): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3, and HCFR4; and a light chain comprising the following four light chain framework regions (LCFRs) and three light chain complementarity-determining regions (LCDRs): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3, and LCFR4. Anti-TL1A antibodies can comprise any of the regions provided herein, e.g., in the tables, examples, and sequences.

[0088] Exemplary Anti-TL1A CDRs In certain embodiments, an anti-TL1A antibody comprises an HCDR1 described by SEQ ID NO: 1. In certain embodiments, an anti-TL1A antibody comprises an HCDR2 described by any one of SEQ ID NOs: 2-5. In certain embodiments, an anti-TL1A antibody comprises an HCDR3 described by any one of SEQ ID NOs: 6-9. In certain embodiments, an anti-TL1A antibody comprises an LCDR1 described by SEQ ID NO: 10. In certain embodiments, an anti-TL1A antibody comprises an LCDR2 described by SEQ ID NO: 11. In certain embodiments, an anti-TL1A antibody comprises an LCDR3 described by any one of SEQ ID NOs: 12-15. In a non-limiting example, an anti-TL1A antibody comprises an HCDR1 described by SEQ ID NO: 1, an HCDR2 described by SEQ ID NO: 2, an HCDR3 described by SEQ ID NO: 6, an LCDR1 described by SEQ ID NO: 10, an LCDR2 described by SEQ ID NO: 11, and an LCDR3 described by SEQ ID NO: 12.

[0089] In certain embodiments, an anti-TL1A antibody comprises an HCDR1 described by SEQ ID NO: 401, 407, 413, or 450. In certain embodiments, an anti-TL1A antibody comprises an HCDR2 described by SEQ ID NO: 402, 408, 414, or 451. In certain embodiments, an anti-TL1A antibody comprises an HCDR3 described by SEQ ID NO: 403, 409, 415, or 452. In certain embodiments, an anti-TL1A antibody comprises an LCDR1 described by SEQ ID NO: 404, 410, 416, or 453. In certain embodiments, an anti-TL1A antibody comprises an LCDR2 described by SEQ ID NO: 405, 411, 417, or 454. In certain embodiments, an anti-TL1A antibody comprises an LCDR3 described by SEQ ID NO: 406, 412, 418, or 455.

[0090] In certain embodiments, the anti-TL1A antibody comprises an HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 selected from Table 6.

[0091] [Table 1]

[0092] In certain embodiments, the anti-TL1A antibody comprises the CDRs set forth in antibody A, B, C, D, E, F, G, H, I, A2, B2, C2, D2, E2, F2, G2, H2, I2, J, K, M, or N in Table 10.

[0093] [Table 2]

[0094] In certain embodiments, the anti-TL1A antibody comprises the heavy chain CDRs set forth in an antibody selected from Table 7.

[0095] [Table 3-1]

[0096] [Table 3-2]

[0097] [Table 3-3]

[0098] [Table 3-4]

[0099] [Table 3-5]

[0100] [Table 3-6]

[0101] [Table 3-7]

[0102] [Table 3-8]

[0103] In certain embodiments, the anti-TL1A antibody comprises the light chain CDRs set forth in an antibody selected from Table 8.

[0104] [Table 4-1]

[0105] [Table 4-2]

[0106]

Table 4-3

[0107]

Table 4-4

[0108] In certain embodiments, the anti-TL1A antibody comprises the CDRs set forth in any one of the antibodies in Table 1. For example, anti-TL1A antibodies include antibodies 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, A5 3, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A 68, 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, A9 9, A100, A101, A102, A103, A104, A105, A107, A108, A109, A110, A111, A1 12, A113, A114, A115, A116, A117, A118, A119, A120, A121, A122, A123, A 124, A125, A126, A127, A128, A129, A130, A132, A133, A134, A135, A136, A137, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A14 8, A149, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A1 60, A161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A 172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN CDRs.In a non-limiting example, the anti-TL1A antibody comprises the CDRs of antibody A219.

[0109] Antibody CDRs can be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0110] Exemplary Anti-TL1A Framework Regions In certain embodiments, an anti-TL1A antibody comprises a heavy chain (HC) framework 1 (FR1) set forth by SEQ ID NO: 304. In certain embodiments, an anti-TL1A antibody comprises a HC FR2 set forth by any one of SEQ ID NOs: 305 or 313. In certain embodiments, an anti-TL1A antibody comprises a HC FR3 set forth by any one of SEQ ID NOs: 306-307, 314-315. In certain embodiments, an anti-TL1A antibody comprises a HC FR4 set forth by SEQ ID NO: 308. In certain embodiments, an anti-TL1A antibody comprises a LC FR1 set forth by SEQ ID NO: 309. In certain embodiments, an anti-TL1A antibody comprises a LC FR2 set forth by SEQ ID NO: 310. In certain embodiments, an anti-TL1A antibody comprises a LC FR3 set forth by SEQ ID NO: 311. In certain embodiments, an anti-TL1A antibody comprises a LC FR4 set forth by SEQ ID NO: 312. In a non-limiting example, an anti-TL1A antibody comprises a HC FR1 described by SEQ ID NO: 304, a HC FR2 described by SEQ ID NO: 305, a HC FR3 described by SEQ ID NO: 306, a HC FR4 described by SEQ ID NO: 308, a LC FR1 described by SEQ ID NO: 309, a LC FR2 described by SEQ ID NO: 310, a LC FR3 described by SEQ ID NO: 311, and a LC FR4 described by SEQ ID NO: 312. In a non-limiting example, an anti-TL1A antibody comprises a HC FR1 described by SEQ ID NO: 304, a HC FR2 described by SEQ ID NO: 305, a HC FR3 described by SEQ ID NO: 307, a HC FR4 described by SEQ ID NO: 308, a LC FR1 described by SEQ ID NO: 309, a LC FR2 described by SEQ ID NO: 310, a LC FR3 described by SEQ ID NO: 311, and a LC FR4 described by SEQ ID NO: 312.

[0111] In certain embodiments, the anti-TL1A antibody comprises a heavy chain framework region described in an antibody selected from Table 7. In certain embodiments, the anti-TL1A antibody comprises a light chain framework region described in an antibody selected from Table 8. In certain embodiments, the anti-TL1A antibody comprises a framework region described in any one of the antibodies in Table 1.For example, anti-TL1A antibodies include antibodies 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, A6 8, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A 85, 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, A12 4, A125, A126, A127, A128, A129, A130, A132, A133, A134, A135, A136, A13 7, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A148, A1 49, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A160, A 161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A184, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN framework regions. In a non-limiting example, the anti-TL1A antibody comprises the framework region of antibody A219.

[0112] Antibody CDR and framework regions may be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0113] In some embodiments, 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 fewer than nine amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework. In some embodiments, the amino acid modification comprises (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, or a combination of two or more modifications selected from (a) to (h), according to the Aho or Kabat numbering. In some embodiments, the amino acid modification comprises (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L in the heavy chain variable region, or a combination of two or more modifications selected from (a)-(h), according to Aho or Kabat numbering. In some embodiments, the amino acid modification comprises A47R. In some embodiments, the amino acid modification comprises 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 modifications include R45K and A47R. In some embodiments, the amino acid modifications include R45K, A47R, V89A, and M91L. In some embodiments, the amino acid modifications include R45K, A47R, and M80I.In some embodiments, the amino acid modifications include 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 comprises R45. In some embodiments, the amino acid modification comprises R45K and V78A. In some embodiments, the amino acid modification comprises V78A. In some embodiments, the amino acid modification comprises V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. In some embodiments, the amino acid modification comprises V89A. In some embodiments, the amino acid modification comprises M80I. In some embodiments, the amino acid modification 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 according to Aho or Kabat numbering. In some embodiments, the amino acid modification comprises L54P in the light chain variable region according to Aho or Kabat numbering. In some embodiments, the amino acid modification comprises L55W in the light chain variable region according to Aho or Kabat numbering.

[0114] In some embodiments, the 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 examples, X1 is Q. In some examples, X1 = E. In some examples, X2 = R. In some examples, X2 = K. In some examples, X3 = A. In some examples, X3 = R. In some examples, X4 = M. In some embodiments, X4=I. In some embodiments, X5=V. In some embodiments, X5=A. In some embodiments, X6=M. In some embodiments, X6=I. In some embodiments, X7=R. In some embodiments, X7=T. In some embodiments, X8=V. In some embodiments, X8=A. In some embodiments, X9=M. In some embodiments, 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.

[0115] 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 about 1 to about 9 amino acid substitutions, or about 1 to 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 the 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; or (6) the anti-TL1A of any one of embodiments 2-4, wherein X2 = K. (7) Anti-TL1A of any one of embodiments 2 to 6, wherein X3=A. (8) Anti-TL1A of any one of embodiments 2 to 6, wherein X3=R. (9) Anti-TL1A of any one of embodiments 2 to 8, wherein X4=M. (10) Anti-TL1A of any one of embodiments 2 to 8, wherein X4=I. (11) Anti-TL1A of any one of embodiments 2 to 10, wherein X5=V. (12) Anti-TL1A of any one of embodiments 2 to 10, wherein X5=A. (13) Anti-TL1A of any one of embodiments 2 to 12, wherein X6=M. (14) Anti-TL1A of any one of embodiments 2 to 12, wherein X6=I. (15) Anti-TL1A of any one of embodiments 2 to 14, wherein X7=R. (16) Anti-TL1A of any one of embodiments 2 to 14, wherein X7=T. (17) The anti-TL1A of any one of embodiments 2 to 16, wherein X8 = V. (18) The anti-TL1A of any one of embodiments 2 to 16, wherein X8 = A. (19) The anti-TL1A of any one of embodiments 2 to 18, wherein X9 = M. (20) The anti-TL1A of any one of embodiments 2 to 4, wherein X9 = L. (21) The anti-TL1A of any one of embodiments 1 to 20, comprising antibody A. (22) The anti-TL1A of any one of embodiments 1 to 20, comprising antibody B. (23) The anti-TL1A of any one of embodiments 1 to 20, comprising antibody C.(24) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody D. (25) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody E. (26) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody F. (27) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody G or I. (28) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody H. (34) Anti-TL1A of any one of embodiments 1 to 33, comprising a light chain framework comprising IGKV3-20*01 or a variant thereof, wherein the variant comprises about 1 to about 2 substitutions, or about 1 to about 20 amino acid substitutions, or 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 to 36, wherein X11 is L. (38) The anti-TL1A antibody of any one of embodiments 34 to 36, wherein X11 is W.

[0116] In some embodiments, the anti-TL1A antibody comprises a light chain framework comprising SEQ ID NO: 303 (EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK). In some examples, X10 is L. In some examples, X10 is P. In some examples, X11 is L. In some examples, 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.

[0117] In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising IGHV1-46*02. In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising from about 1 to about 20 amino acid substitutions from SEQ ID NO: 316. In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising from about 1 to about 9 amino acid substitutions from SEQ ID NO: 316. In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising from 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 from SEQ ID NO: 316. In some examples, the heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises R45K as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises A47R as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises M55I as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises V78A as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises M80I as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises R82T as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises V89A as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises M91L as determined by Aho or Kabat numbering.

[0118] In some embodiments, the anti-TL1A antibody comprises a light chain framework comprising IGKV3-20*01. In some embodiments, the anti-TL1A antibody comprises a variant of IGKV3-20*01 comprising about 1 to about 20 amino acid substitutions from SEQ ID NO: 317. In some embodiments, the anti-TL1A antibody comprises a variant of IGKV3-20*01 comprising about 1 amino acid substitution from SEQ ID NO: 317. In some embodiments, the 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, the 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 in the framework from SEQ ID NO: 317. In some instances, the light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some instances, the light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

[0119] In some embodiments, the anti-TL1A antibody comprises a heavy chain FR1 described by SEQ ID NO: 304. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR2 described by SEQ ID NO: 305. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR2 described by SEQ ID NO: 313. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 306. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 307. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 314. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 315. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR4 described by SEQ ID NO: 308. In some embodiments, the anti-TL1A antibody comprises a light chain FR1 described by SEQ ID NO: 309. In some embodiments, the anti-TL1A antibody comprises a light chain FR2 described by SEQ ID NO: 310. In some embodiments, the anti-TL1A antibody comprises a light chain FR3 set forth by SEQ ID NO: 311. In some embodiments, the anti-TL1A antibody comprises a light chain FR4 set forth by SEQ ID NO: 312.

[0120] In some embodiments, the anti-TL1A antibody comprises the framework region of Table 9A.

[0121] [Table 5-1]

[0122] [Table 5-2]

[0123] Exemplary Anti-TL1A Variable Regions In one aspect, the present specification provides a heavy chain variable region comprising an amino acid sequence that is 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 to 169 or 420 to 427. and a light chain variable region that is 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.

[0124] Further provided herein is a first embodiment of an anti-TL1A antibody comprising a heavy chain variable region and a light chain variable region. Additional non-limiting 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 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%, 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 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 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 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 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 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 wherein 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 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 wherein 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 compared to SEQ ID NO: 108.(Embodiment 10) 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, or wherein 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 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 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 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 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 compared to SEQ ID NO: 113. (Embodiment 15) An 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 compared to SEQ ID NO: 114. (Embodiment 16) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 115. (Embodiment 17) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 116.(Embodiment 18) An 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 compared to SEQ ID NO: 117. (Embodiment 19) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 118. (Embodiment 20) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 119. (Embodiment 21) An 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 wherein 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 compared to SEQ ID NO: 120.(Embodiment 22) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 121. (Embodiment 23) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 122. (Embodiment 24) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 123. (Embodiment 25) 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 at least about 1, 2, 3, 4, 5, 6, 7, or 80% identical 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 wherein 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 compared to SEQ ID NO: 125. (Embodiment 27) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 126. (Embodiment 28) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 127. (Embodiment 29) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 128.(Embodiment 30) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 129. (Embodiment 31) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 130. (Embodiment 32) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 131. (Embodiment 33) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 132.(Embodiment 34) An 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 compared to SEQ ID NO: 133. (Embodiment 35) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 134. (Embodiment 36) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 135. (Embodiment 37) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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: 136, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 136.(Embodiment 38) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 137. (Embodiment 39) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 138. (Embodiment 40) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 139. (Embodiment 41) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 140.(Embodiment 42) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 141. (Embodiment 43) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 142. (Embodiment 44) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 143. (Embodiment 45) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 144.(Embodiment 46) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 145. (Embodiment 47) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 146. (Embodiment 48) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 147. (Embodiment 49) 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 at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 1 identical 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 wherein the heavy chain variable region comprises a sequence with about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 149. (Embodiment 51) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 150. (Embodiment 52) ​​An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 151. (Embodiment 53) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 152.(Embodiment 54) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 153. (Embodiment 55) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 154. (Embodiment 56) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 155. (Embodiment 57) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 156.(Embodiment 58) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 157. (Embodiment 59) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 158. (Embodiment 60) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 159. (Embodiment 61) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 160.(Embodiment 62) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 161. (Embodiment 63) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 162. (Embodiment 64) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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: 163, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 163. (Embodiment 65) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 164.(Embodiment 66) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 165. (Embodiment 67) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 166. (Embodiment 68) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 167. (Embodiment 69) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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 wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 168.(Embodiment 70) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is 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: 169, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 169.

[0125] (Embodiment 71) An anti-TL1A antibody of any one of embodiments 1 to 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 compared to SEQ ID NO: 201. (Embodiment 72) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 202. (Embodiment 73) An anti-TL1A antibody of any one of embodiments 1 to 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 compared to SEQ ID NO: 203. (Embodiment 74) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 204.(Embodiment 75) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 205. (Embodiment 76) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 206. (Embodiment 77) An anti-TL1A antibody of any one of embodiments 1 to 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: 207, or wherein 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 compared to SEQ ID NO: 207. (Embodiment 78) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 208.(Embodiment 79) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 209. (Embodiment 80) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 210. (Embodiment 81) An anti-TL1A antibody of any one of embodiments 1 to 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 compared to SEQ ID NO: 211. (Embodiment 82) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 212.(Embodiment 83) An anti-TL1A antibody of any one of embodiments 1 to 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 compared to SEQ ID NO: 213. (Embodiment 84) An anti-TL1A antibody of any one of embodiments 1 to 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 compared to SEQ ID NO: 214. (Embodiment 85) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 215. (Embodiment 86) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 216.(Embodiment 87) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 217. (Embodiment 88) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 218. (Embodiment 89) An anti-TL1A antibody of any one of embodiments 1 to 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 wherein 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 compared to SEQ ID NO: 219. (Embodiment 90) An anti-TL1A antibody of any one of embodiments 1 to 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: 220, or wherein 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 compared to SEQ ID NO: 220.

[0126] (Embodiment 91) An 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 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) An 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, or 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) An 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 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) An 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 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) An 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 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.

[0127] (Embodiment 96) An 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 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) An 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 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) An 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 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) An 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 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) An 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, or 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.

[0128] (Embodiment 101) An 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 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) An 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, or 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) An 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 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) An 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 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) An 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 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.

[0129] (Embodiment 106) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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.

[0130] (Embodiment 111) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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.

[0131] (Embodiment 116) An 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 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) An 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, or 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) An 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 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) An 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 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 120) An 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 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.

[0132] (Embodiment 121) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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.

[0133] (Embodiment 126) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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.

[0134] (Embodiment 131) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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.

[0135] (Embodiment 136) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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.

[0136] (Embodiment 141) An 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 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) An 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 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) An 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: 129, or 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) An 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 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) An 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 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.

[0137] (Embodiment 146) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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) An 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 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, or 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, or 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) An 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, or 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: 431.(Embodiment 157) An 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, or 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) An 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, or 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.

[0138] Exemplary Anti-TL1A Constant Regions 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 a variant Fc region. The Fc region may include the C-terminal region of an immunoglobulin heavy chain, which region includes a hinge region, a CH2 domain, a CH3 domain, or any combination thereof. As used herein, Fc region includes native-sequence Fc regions and variant Fc regions. A variant Fc region may comprise a human Fc region sequence (e.g., a human IgG1, IgG2, IgG3, or IgG4 Fc region) containing an amino acid modification (e.g., substitution, addition, or deletion) at one or more amino acid positions. In exemplary embodiments, the Fc region comprises any one of SEQ ID NOs: 320-367. In some embodiments, an anti-TL1A antibody comprises a constant region comprising any one of SEQ ID NOs: 319, 368-381.

[0139] In some embodiments, the antibodies of the present disclosure have reduced effector functions compared to human IgG. Effector function refers to biological events 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, downregulation of cell surface receptors (e.g., B cell receptors), and B cell activation. In some examples, antibody-dependent cell-mediated 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 antibodies on target cells and subsequently cause lysis of the target cells. In some examples, complement-dependent cytotoxicity (CDC) refers to the lysis of target cells in the presence of complement, where the complement pathway is initiated by the binding of C1q to target-bound antibodies.

[0140] Some Fc regions naturally lack effector function, and some Fc regions may contain mutations that reduce effector function: for example, IgG4 has reduced ADCC and CDC activity, and IgG2 has reduced ADCC activity.

[0141] The present disclosure provides antibodies comprising a non-variant Fc region, i.e., antibodies comprising an Fc region characterized by exhibiting reduced ADCC by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or more compared to an antibody having the same sequence identity except for the ADCC-reducing substitutions (e.g., human IgG1, SEQ ID NO: 320). The present disclosure provides antibodies comprising a non-variant Fc region, i.e., antibodies comprising an Fc region characterized by exhibiting reduced CDC by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or more compared to an antibody having the same sequence identity except for the CDC-reducing substitutions (e.g., human IgG1, SEQ ID NO: 320). In certain embodiments, antibodies of the present disclosure have reduced effector function compared to human IgG1. In certain embodiments, the antibodies herein have no detectable ADCC activity. In certain embodiments, the reduced and / or decreased ADCC activity may be due to a reduced affinity exhibited by the antibodies of the invention for Fc ligands and / or receptors. In certain embodiments, the antibodies herein do not exhibit detectable CDC activity. In certain embodiments, the reduced and / or decreased CDC activity may be due to a reduced affinity exhibited by the antibodies of the invention for Fc ligands and / or receptors. Measurement of effector function may be performed as described in Example 3.

[0142] In some embodiments, antibodies comprising an Fc region described herein exhibit reduced affinity for C1q relative to an unmodified antibody (e.g., a human IgG1 having SEQ ID NO: 320). In some embodiments, the antibodies herein exhibit 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, at least 100-fold, or at least 200-fold less affinity for the C1q receptor than the unmodified antibody. In some embodiments, the antibodies herein exhibit 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 affinity for C1q than the unmodified antibody.

[0143] In some embodiments, the antibodies of the present disclosure are variants that retain some, but not all, effector functions, making them promising candidates for applications where antibody half-life in vivo is important, but certain effector functions (such as complement and ADCC) are unnecessary or deleterious.

[0144] In vitro and / or in vivo cytotoxicity assays can be performed to confirm reduced / loss of CDC and / or ADCC activity. For example, Fc receptor (FcR) binding assays can be performed to confirm that the antibody lacks FcγR binding (and thus likely lacks ADCC activity) but retains FcRn binding ability. Measurement of effector function may be performed as described in Example 3.

[0145] In some embodiments, antibodies are tested for binding to Fcγ receptors and complement C1q by ELISA. In some embodiments, antibodies are tested for their ability to activate primary human immune cells in vitro, for example, by assessing their ability to induce expression of activation markers.

[0146] In some embodiments, assessing the ADCC activity of an anti-TL1A antibody involves adding the antibody to target cells in combination with immune effector cells. The immune effector cells can be activated by the antigen-antibody complex, resulting in cytolysis of the target cells. Cytolysis can be detected by the release of a label (e.g., a radioactive substrate, a fluorescent dye, or a natural intracellular protein) from the lysed cells. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMCs) 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; and Patel et al., 1995, J Immunol Methods 184:29-38. Alternatively, or additionally, ADCC activity of a subject antibody may be assessed in vivo, for example, in an animal model such as that disclosed in Clynes et al., 1998, PNAS USA 95:652-656.

[0147] In some embodiments, assessment of complement activation, a CDC assay, may be performed as described in Gazzano-Santoro et al., 1996, J. Immunol. Methods, 202:163.

[0148] 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 in IgG1, where the numbering system for the constant region is that of the EU index as described by Kabat. In certain embodiments, antibodies of the present disclosure have reduced effector function compared to human IgG1.

[0149] In some embodiments, the 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, 238F ... 37K, 237N, 237R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 25 4H, 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, 32 9Y, 330R, 339E, 339L, 343I, 343V, 373A, 373G, 373S, 376E, 376W, 376Y, 380D, 382D, 382P, 385 P, 424H, 424M, 424V, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, 440V.

[0150] In some embodiments, the antibody comprises an Fc region selected from the representative sequences disclosed in Table 3, Table 13, and Table 9B. In some embodiments, the antibody comprises an IgG1 Fc region comprising E233P according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising S228P and L235E. In some embodiments, the antibody comprises an IgG1 Fc region comprising L235E according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A and L235A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235A, and G237A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235A, and P329G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234F, L235E, and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235E, and G237A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235E, G237A, and P331S according to the Kabat numbering system. In some embodiments, the 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, the antibody comprises an IgG1 Fc region comprising L234A, L235A, and P329A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising G236R and L328R according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising G237A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising F241A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising V264A according to the Kabat numbering system.In some embodiments, the antibody comprises an IgG1 Fc region comprising D265A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D265A and N297A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D265A and N297G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D270A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297D according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297Q according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P329A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P329G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P329R according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising A330L according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P331A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region. In some embodiments, the antibody comprises an IgG4 Fc region. In some embodiments, the antibody comprises an IgG4 Fc region comprising S228P according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising S228P, F234A, and L235A according to the Kabat numbering system, hi some embodiments, the antibody comprises an IgG2-IgG4 cross-subclass (IgG2 / G4) Fc region.In some embodiments, the antibody comprises an IgG2-IgG3 cross-subclass Fc region. In some embodiments, the antibody comprises an IgG2 Fc region comprising H268Q, V309L, A330S, and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising V234A, G237A, P238S, H268A, V309L, A330S, and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an Fc region comprising high mannose glycosylation.

[0151] In some embodiments, the antibody comprises an IgG4 Fc region comprising an S228P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising an A330S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising a P331S substitution according to the Kabat numbering system.

[0152] In some embodiments, the antibody comprises an IgG2 Fc region comprising an A330S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising a P331S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising a 234A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising a 237A substitution according to the Kabat numbering system.

[0153] In certain embodiments, the anti-TL1A antibodies described herein comprise an Fc region as shown in Table 13.

[0154] [Table 6]

[0155] In certain embodiments, the anti-TL1A antibodies described herein comprise an Fc region comprising a sequence from Table 9B. In certain embodiments, the anti-TL1A antibodies described herein comprise an 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.

[0156] In some embodiments, the anti-TL1A antibodies 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.

[0157] Additional Non-Limiting Exemplary Anti-TL1A Antibody Embodiments CDR Embodiments In one aspect, a first embodiment of an anti-TL1A antibody is provided herein. As used herein, anti-TL1A antibody includes anti-TL1A antigen-binding fragments. Non-limiting additional embodiments include the following: (Embodiment 2) The anti-TL1A antibody of embodiment 1, comprising a heavy chain comprising an HCDR1 comprising SEQ ID NO: 1, 401, 407, 413, or 450, an HCDR2 comprising SEQ ID NO: 2, 3, 4, 5, 402, 408, 414, or 451, and an HCDR3 comprising SEQ ID NO: 6, 7, 8, 9, 403, 409, 415, or 452; and a light chain comprising an LCDR1 comprising SEQ ID NO: 10, 404, 410, 416, or 453, an LCDR2 comprising SEQ ID NO: 11, 405, 411, 417, or 454, and an LCDR3 comprising SEQ ID NO: 12, 13, 14, 15, 406, 412, 418, or 455. (Embodiment 3) The anti-TL1A antibody of embodiment 1, comprising an HCDR1 comprising SEQ ID NO: 1. (Embodiment 4) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising an HCDR2 comprising SEQ ID NO: 2. (Embodiment 5) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising an HCDR2 comprising SEQ ID NO: 3. (Embodiment 6) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising an HCDR2 comprising SEQ ID NO: 4. (Embodiment 7) The anti-TL1A antibody of embodiment 1 or embodiment 2, comprising an HCDR2 comprising SEQ ID NO: 5. (Embodiment 8) The anti-TL1A antibody of any one of embodiments 1 to 6, comprising an HCDR3 comprising SEQ ID NO: 6. (Embodiment 9) The anti-TL1A antibody of any one of embodiments 1 to 6, comprising an HCDR3 comprising SEQ ID NO: 7. (Embodiment 10) The anti-TL1A antibody of any one of embodiments 1 to 6, comprising an HCDR3 comprising SEQ ID NO: 8. (Embodiment 11) The anti-TL1A antibody of any one of embodiments 1 to 6, comprising an HCDR3 comprising SEQ ID NO: 9. (Embodiment 12) The anti-TL1A antibody of any one of Embodiments 1 to 10, comprising an LCDR1 comprising SEQ ID NO: 10. (Embodiment 13) The anti-TL1A antibody of any one of Embodiments 1 to 11, comprising an LCDR2 comprising SEQ ID NO: 11. (Embodiment 14) The anti-TL1A antibody of any one of Embodiments 1 to 12, comprising an LCDR3 comprising SEQ ID NO: 12. (Embodiment 15) The anti-TL1A antibody of any one of Embodiments 1 to 12, comprising an LCDR3 comprising SEQ ID NO: 13.(Embodiment 16) The anti-TL1A antibody of any one of embodiments 1 to 12, comprising an LCDR3 comprising SEQ ID NO: 14 or 15. (Embodiment 17) The anti-TL1A antibody of embodiment 1, comprising the CDRs of antibodies 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 the amino acid sequence set forth in SEQ ID NO: 1, (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2 to 5, and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 6 to 9, and a light chain variable region comprising (d) an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 10, (e) an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 11, and (f) an LCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12 to 15. (Embodiment 19) The anti-TL1A antibody of embodiment 1, comprising an HCDR1 set forth in SEQ ID NO: 1, an HCDR2 set forth in SEQ ID NO: 2, an HCDR3 set forth in SEQ ID NO: 6, an LCDR1 set forth in SEQ ID NO: 10, an LCDR2 set forth in SEQ ID NO: 11, and an LCDR3 set forth in SEQ ID NO: 12.

[0158] Framework embodiment (Embodiment 20) The anti-TL1A antibody of any one of embodiments 1 to 19, comprising a heavy chain framework comprising IGHV1-46*02. (Embodiment 21) The anti-TL1A antibody of any one of embodiments 1 to 19, comprising a heavy chain framework comprising a variant of IGHV1-46*02 comprising about 1 to about 20 amino acid substitutions from SEQ ID NO: 316. (Embodiment 22) The anti-TL1A antibody of any one of embodiments 1 to 19, comprising a heavy chain framework comprising a variant of IGHV1-46*02 comprising about 1 to about 9 amino acid substitutions from SEQ ID NO: 316. (Embodiment 23) The anti-TL1A antibody of any one of embodiments 1 to 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 in the framework from SEQ ID NO: 316. (Embodiment 24) The anti-TL1A antibody of any one of embodiments 21 to 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 to 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 to 25, wherein the heavy chain framework substitution comprises A47R, as determined by Aho or Kabat numbering. (Embodiment 27) The anti-TL1A antibody of any one of embodiments 21 to 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 to 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 to 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 to 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 to 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 to 31, wherein the heavy chain framework substitution comprises M91L, as determined by Aho or Kabat numbering.

[0159] (Embodiment 33) An anti-TL1A antibody of any one of embodiments 1 to 19, comprising a heavy chain framework comprising SEQ ID NO: 301. (Embodiment 34) An anti-TL1A antibody of embodiment 33, wherein X1 is Q. (Embodiment 35) An anti-TL1A antibody of embodiment 33, wherein X1 = E. (Embodiment 36) An anti-TL1A antibody of any one of embodiments 33 to 35, wherein X2 = R. (Embodiment 37) An anti-TL1A antibody of any one of embodiments 33 to 35, wherein X2 = K. (Embodiment 38) An anti-TL1A antibody of any one of embodiments 33 to 37, wherein X3 = A. (Embodiment 39) An anti-TL1A antibody of any one of embodiments 33 to 37, wherein X3 = R. (Embodiment 40) An anti-TL1A antibody of any one of embodiments 33 to 39, wherein X4 = M. (Embodiment 41) An anti-TL1A antibody of any one of embodiments 33 to 39, wherein X4 = I. (Embodiment 42) An anti-TL1A compound of any one of embodiments 33 to 41, wherein X5 = V. (Embodiment 43) An anti-TL1A compound of any one of embodiments 33 to 41, wherein X5 = A. (Embodiment 44) An anti-TL1A compound of any one of embodiments 33 to 43, wherein X6 = M. (Embodiment 45) An anti-TL1A compound of any one of embodiments 33 to 43, wherein X6 = I. (Embodiment 46) An anti-TL1A compound of any one of embodiments 33 to 45, wherein X7 = R. (Embodiment 47) An anti-TL1A compound of any one of embodiments 33 to 45, wherein X7 = T. (Embodiment 48) An anti-TL1A compound of any one of embodiments 33 to 47, wherein X8 = V. (Embodiment 49) An anti-TL1A compound of any one of embodiments 33 to 47, wherein X8 = A. (Embodiment 50) An anti-TL1A compound of any one of embodiments 33 to 49, wherein X9 = M. (Embodiment 51) An anti-TL1A antibody according to any one of embodiments 33 to 49, wherein X9=L.

[0160] (Embodiment 52) ​​The anti-TL1A antibody of any one of embodiments 1 to 51, comprising a light chain framework comprising IGKV3-20*01. (Embodiment 53) The anti-TL1A antibody of any one of embodiments 1 to 51, comprising a light chain framework comprising a variant of IGKV3-20*01 comprising about 1 to about 20 amino acid substitutions from SEQ ID NO: 317. (Embodiment 54) The anti-TL1A antibody of any one of embodiments 1 to 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 to 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 to 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 in the framework from SEQ ID NO: 317. (Embodiment 57) The anti-TL1A antibody of any one of embodiments 53 to 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 to 57, wherein the light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

[0161] (Embodiment 59) The anti-TL1A antibody of any one of embodiments 1 to 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 to 61, wherein X11 is L. (Embodiment 63) The anti-TL1A antibody of any one of embodiments 59 to 61, wherein X11 is W.

[0162] (Embodiment 64) The anti-TL1A antibody of any one of embodiments 1 to 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 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 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 comprises a modification at amino acid position 45 in the heavy chain variable region. (Embodiment 67) The antibody of any one of embodiments 64 to 66, wherein the amino acid modification comprises a modification at amino acid position 47 in the heavy chain variable region. (Embodiment 68) The antibody of any one of embodiments 64 to 67, wherein the amino acid modification comprises a modification at amino acid position 55 in the heavy chain variable region. (Embodiment 69) The antibody of any one of embodiments 64 to 68, wherein the amino acid modification comprises a modification at amino acid position 78 in the heavy chain variable region. (Embodiment 70) The antibody of any one of embodiments 64 to 69, wherein the amino acid modification comprises a modification at amino acid position 80 in the heavy chain variable region. (Embodiment 71) The antibody of any one of embodiments 64 to 70, wherein the amino acid modification comprises a modification at amino acid position 82 in the heavy chain variable region. (Embodiment 72) The antibody of any one of embodiments 64 to 71, wherein the amino acid modification comprises a modification at amino acid position 89 in the heavy chain variable region. (Embodiment 73) The antibody of any one of embodiments 64 to 72, wherein the amino acid modification comprises a modification at amino acid position 91 in the heavy chain variable region according to the Aho or Kabat numbering.(Embodiment 74) The antibody of any one of embodiments 64 to 65, wherein the amino acid modification in the heavy chain variable region comprises (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L, according to the 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 comprises A47R. (Embodiment 76) The antibody of embodiment 74, wherein the amino acid modifications 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 modifications comprise R45K and A47R. (Embodiment 78) The antibody of embodiment 74, wherein the amino acid modifications comprise R45K, A47R, V89A, and M91L. (Embodiment 79) The antibody of embodiment 74, wherein the amino acid modifications comprise R45K, A47R, and M80I. (Embodiment 80) The amino acid modifications are 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. The antibody of embodiment 74, wherein the amino acid modification comprises R45K. (Embodiment 82) The antibody of embodiment 74, wherein the amino acid modification comprises R45K. (Embodiment 83) The antibody of embodiment 74, wherein the amino acid modification comprises V78A. (Embodiment 84) The antibody of embodiment 74, wherein the amino acid modifications comprise V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. (Embodiment 85) The antibody of embodiment 74, wherein the amino acid modifications comprise V89A.(Embodiment 86) The antibody of embodiment 74, wherein the amino acid modification comprises M80I. (Embodiment 87) The antibody of any one of embodiments 64 to 86, wherein the amino acid modification 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 according to the Aho or Kabat numbering. (Embodiment 88) The antibody of embodiment 87, wherein the amino acid modification comprises L54P in the light chain variable region according to the Aho or Kabat numbering. (Embodiment 89) The antibody of embodiment 87 or 88, wherein the amino acid modification comprises L55W in the light chain variable region according to the Aho or Kabat numbering.

[0163] (Embodiment 90) The antibody of any one of embodiments 1 to 19, comprising a heavy chain FR1 as set forth in SEQ ID NO: 304. (Embodiment 91) The antibody of any one of embodiments 1 to 19 or 90, comprising a heavy chain FR2 as set forth in SEQ ID NO: 305. (Embodiment 92) The antibody of any one of embodiments 1 to 19 or 90, comprising a heavy chain FR2 as set forth in SEQ ID NO: 313. (Embodiment 93) The antibody of any one of embodiments 1 to 19 or 90 to 92, comprising a heavy chain FR3 as set forth in SEQ ID NO: 306. (Embodiment 94) The antibody of any one of embodiments 1 to 19 or 90 to 92, comprising a heavy chain FR3 as set forth in SEQ ID NO: 307. (Embodiment 95) The antibody of any one of embodiments 1 to 19 or 90 to 92, comprising a heavy chain FR3 as set forth in SEQ ID NO: 314. (Embodiment 96) The antibody of any one of embodiments 1 to 19 or 90 to 92, comprising a heavy chain FR3 as set forth in 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 in 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 in 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 in 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 in 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 in SEQ ID NO: 312. (Embodiment 102) The antibody of any one of embodiments 1-19, comprising an HC FR1 described by SEQ ID NO: 304, an HC FR2 described by SEQ ID NO: 305, an HC FR3 described by SEQ ID NO: 307, an HC FR4 described by SEQ ID NO: 308, an LC FR1 described by SEQ ID NO: 309, an LC FR2 described by SEQ ID NO: 310, an LC FR3 described by SEQ ID NO: 311, and an LC FR4 described by SEQ ID NO: 312.

[0164] Variable Region Embodiments (Embodiment 103) The antibody of embodiment 1, 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 to 169 or 420 to 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 to 220 or 430 to 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 to 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.

[0165] (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. (Embodiment 116) The antibody of any one of embodiments 112 to 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 to 116, wherein the light chain variable domain comprises an amino acid sequence at least about 99% identical to SEQ ID NO: 201. (Embodiment 118) An antibody of any one of embodiments 112 to 117, wherein the light chain variable domain comprises SEQ ID NO: 201.

[0166] Fc Region Embodiments (Embodiment 119) The antibody of any one of embodiments 1 to 118, comprising a crystallizable fragment (Fc) region. (Embodiment 120) The antibody of embodiment 119, comprising reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function compared to human IgG1 and / or reduced complement-dependent cytotoxicity (CDC) compared to human IgG1. (Embodiment 121) The antibody of embodiment 120, wherein the human IgG1 comprises SEQ ID NO: 320. (Embodiment 122) The antibody of embodiment 120 or embodiment 121, wherein the ADCC function of the Fc region comprising reduced ADCC is reduced by at least about 50% compared to human IgG1. (Embodiment 123) The antibody of any one of embodiments 120 to 122, wherein the CDC function of the Fc region comprising reduced ADCC is reduced by at least about 50% compared to human IgG1. (Embodiment 124) (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 or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R, (k) 331S, (l) 236F or 236R, (m) 238A, 238E, 238G, 238H, 238I, 238V, 238W, or 238Y, (n) 248A, (o) 254D, 254E, 254G, 2 54H, 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 are 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 P331 S, (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, The anti-TL1A antibody of any one of embodiments 119-123, comprising a human IgG1 Fc region comprising: (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). (Embodiment 125) The anti-TL1A antibody of any one of embodiments 119 to 123, comprising (i) a human IgG4 Fc region or (ii) a human IgG4 Fc region comprising (a) S228P, (b) S228P and L235E, or (c) S228P, F234A, and L235A according to the Kabat numbering. (Embodiment 126) The anti-TL1A antibody of any one of embodiments 119 to 123, comprising a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; an IgG2 comprising H268Q, V309L, A330S, and P331S (IgG2m4), or an IgG2 comprising V234A, G237A, P238S, H268A, V309L, A330S, and P331S (IgG2σ).The anti-TL1A antibody of any one of embodiments 119 to 123. (Embodiment 127) 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, and 265H according to the Kabat numbering system. , 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, and 440V. (Embodiment 128) An anti-TL1A antibody of any one of embodiments 119 to 123, comprising a heavy chain Fc region comprising an 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 to 362. (Embodiment 129) An anti-TL1A antibody of any one of embodiments 119 to 123, comprising a heavy chain Fc region comprising an 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: 368 to 380. (Embodiment 130) The anti-TL1A antibody of any one of embodiments 119 to 123, 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.

[0167] Additional antibody features (Embodiment 131) An anti-TL1A antibody of any one of embodiments 1 to 130, 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.

[0168] (Embodiment 132) The anti-TL1A antibody of any one of embodiments 1 to 131, 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% monomer fraction as determined by size exclusion chromatography. (Embodiment 133) The antibody of embodiment 132, wherein size exclusion chromatography comprises injecting the purified antibody into a size exclusion column, and the antibody is purified by protein A. (Embodiment 134) The antibody of embodiment 132 or 133, wherein the antibody is purified as described in Example 2. (Embodiment 135) The antibody of any one of embodiments 132 to 134, wherein the antibody is expressed under the conditions described in Example 2. (Embodiment 136) The antibody of any one of embodiments 132 to 135, wherein the size exclusion chromatography column has an inner diameter of 4.6 mm. (Embodiment 137) The antibody of any one of embodiments 132 to 136, wherein the size exclusion chromatography column has a length of 150 mm. (Embodiment 138) The antibody of any one of embodiments 132 to 137, wherein the size exclusion chromatography column has a pore size of 200 Å. (Embodiment 139) The antibody of any one of embodiments 132 to 138, wherein the size exclusion chromatography column has a particle size of 1.7 micrometers. (Embodiment 140) The antibody of any one of embodiments 132 to 139, wherein the size exclusion chromatography column is an ACQUITY UPLC BEH200 SEC column. (Embodiment 141) The antibody of any one of embodiments 132 to 140, wherein the antibody or antigen-binding fragment is injected in a total volume of 15 μL. (Embodiment 142) The antibody of any one of embodiments 132 to 141, wherein the antibody is injected at a concentration of about 0.1 μg / μL to about 1.0 μg / μL. (Embodiment 143) The antibody of any one of embodiments 132 to 142, wherein size exclusion chromatography is performed on a Shimadzu UPLC instrument. (Embodiment 144) The antibody of any one of embodiments 132 to 143, wherein size exclusion chromatography is performed at a flow rate of 0.2 mL / min.(Embodiment 145) The antibody of any one of embodiments 132 to 144, wherein size exclusion chromatography is performed at a column oven temperature of 30° C. (Embodiment 146) The antibody of any one of embodiments 132 to 145, wherein the percentage of monomer is calculated using Shimadzu software. (Embodiment 147) The antibody of any one of embodiments 132 to 146, wherein size exclusion chromatography is performed as described in Example 2.

[0169] (Embodiment 148) Anti-TL1A is at least about 2 μg / mL, about 2 μg / mL to about 60 μg / mL, about 5 μg / mL to about 60 μg / mL, about 10 μg / mL to 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, about 2 μg / mL to about 50 μg / mL, about 2 μg / mL to about 4 148. The anti-TL1A antibody of any one of embodiments 1 to 147, wherein the antibody is expressed at a concentration of about 0 μg / mL, about 2 μg / mL to about 30 μg / mL, about 2 μg / mL to about 20 μg / mL, about 5 μg / mL to about 50 μg / mL, about 5 μg / mL to about 40 μg / mL, about 5 μg / mL to about 30 μg / mL, about 10 μg / mL to about 50 μg / mL, about 10 μg / mL to about 40 μg / mL, or about 10 μg / mL to about 30 μg / mL. (Embodiment 149) The anti-TL1A antibody of any one of embodiments 1 to 147, 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 the methods disclosed herein. (Embodiment 150) The antibody of embodiment 148 or embodiment 149, wherein the antibody is expressed in FreeStyle293-F cells. (Embodiment 151) The antibody of any one of embodiments 148 to 150, wherein the antibody is expressed as described in Example 2. (Embodiment 152) The antibody of any one of embodiments 148 to 151, wherein the antibody expression level is quantified using enzyme-linked immunosorbent assay (ELISA). (Embodiment 153) The antibody of embodiment 152, wherein the ELISA comprises coating the surface of a substrate with a capture antibody that binds to the human or humanized antibody, applying an anti-TL1A antibody to the substrate, and applying a second antibody that binds to the human or humanized antibody to the substrate. (Embodiment 154) The antibody of embodiment 153, wherein the capture antibody comprises an anti-kappa antibody. (Embodiment 155) The antibody of embodiment 153 or embodiment 154, wherein the second antibody comprises an anti-Fc antibody. (Embodiment 156) The antibody of any one of embodiments 152 to 155, wherein the ELISA is performed as described in Example 2.

[0170] (Embodiment 157) A method of treating a pulmonary disease and / or condition in a subject in need thereof, comprising administering to the subject the antibody or antigen-binding fragment of any one of Embodiments 1 to 156. (Embodiment 158) The method of Embodiment 157, wherein the pulmonary disease and / or condition comprises idiopathic pulmonary fibrosis, viral-induced pulmonary fibrosis, asthma, or COPD, or a combination thereof. (Embodiment 159) A method of treating inflammation and / or fibrosis in a subject in need thereof, comprising administering to the subject the antibody or antigen-binding fragment of any one of Embodiments 1 to 156. (Embodiment 160) The method of Embodiment 159, wherein the subject has inflammatory bowel disease.

[0171] (Embodiment 161) A nucleic acid encoding the antibody of any one of embodiments 1 to 156. (Embodiment 162) A vector comprising the nucleic acid of embodiment 161. (Embodiment 163) A cell comprising the nucleic acid of embodiment 161. (Embodiment 164) A cell comprising the vector of embodiment 162.

[0172] Antibody properties The anti-TL1A antibodies described herein bind to specific regions or epitopes of human TL1A. In various embodiments, the binding affinity of the anti-TL1A antibodies provided herein for human TL1A is about 1E -7 , 1E -8 , 1E -9 , or 1E -10 In some cases, the binding affinity is less than about 1E -9 ~approx. 1E -10 In some embodiments, the binding affinity of the anti-TL1A antibodies provided herein to mouse TL1A and / or rat TL1A is about 1E -7 , 1E -8 , 1E -9 , 1E -10 , or 1E -11 The Kd is less than 0. Methods for determining binding affinity are exemplified herein, including in Example 2.

[0173] In various embodiments, the anti-TL1A antibodies provided herein are antagonists of TL1A receptors, such as, but not limited to, DR3 and TR6 / DcR3. In certain embodiments, the antibodies inhibit at least about 10%, at least about 20%, at least about 30%, at least about 50%, at least about 75%, at least about 90%, or about 100% of one or more activities of the TL1A receptor to which they bind. In certain embodiments, the anti-TL1A antibodies inhibit TL1A activation as measured by interferon-gamma release in human blood. In certain embodiments, the antibodies have an IC of about 1 nanomolar to about 30 picomolar. 50 In certain embodiments, the antibody has an IC of about 500 picomolar to about 30 picomolar and inhibits interferon gamma release in human blood. 50 In certain embodiments, the antibody has an IC of about 200 picomolar to about 30 picomolar. 50 In certain embodiments, the antibody inhibits interferon gamma release in human blood at an IC of about 200 picomolar or less. 50 In certain embodiments, the antibody inhibits interferon gamma release in human blood at an IC of about 100 picomolar or less. 50 It inhibits the release of interferon gamma in human blood.

[0174] In various embodiments, the anti-TL1A antibodies provided herein comprise at least about 80% monomer fraction after expression and purification, as described in Example 2 or elsewhere herein. In various embodiments, the anti-TL1A antibodies provided herein comprise at least about 85% monomer fraction after expression and purification, as described in Example 2 or elsewhere herein. In various embodiments, the anti-TL1A antibodies provided herein comprise at least about 90% monomer fraction after expression and purification, as described in Example 2 or elsewhere herein. In various embodiments, the anti-TL1A antibodies provided herein comprise at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% monomer fraction after expression and purification, as described in Example 2 or elsewhere herein.

[0175] In various embodiments, the anti-TL1A antibodies provided herein have an expression of at least about 2 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibodies have an expression of at least about 2 μg / mL to about 60 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibodies have an expression of at least about 5 μg / mL to about 60 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibodies have an expression of at least about 10 μg / mL to about 60 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibodies have an expression of at least about 5 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibodies express at least about 10 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibodies have an expression of at least about 15 μg / mL, as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibody has an expression of at least about 20 μg / mL as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibody has an expression of about 2 μg / mL to about 50 μg / mL, about 2 μg / mL to about 40 μg / mL, about 2 μg / mL to about 30 μg / mL, about 2 μg / mL to about 20 μg / mL, about 5 μg / mL to about 50 μg / mL, about 5 μg / mL to about 40 μg / mL, about 5 μg / mL to about 30 μg / mL, about 10 μg / mL to about 50 μg / mL, about 10 μg / mL to about 40 μg / mL, or about 10 μg / mL to about 30 μg / mL as determined by the methods disclosed herein. In some embodiments, the anti-TL1A antibody has an expression of 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 the methods disclosed herein. The methods disclosed herein include the methods described in Example 2.

[0176] In various embodiments, the anti-TL1A antibodies provided herein are humanized and have less than about 20% non-human sequences in the framework regions of each of the heavy and light chain variable regions. For example, a humanized antibody contains 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 sequences in the framework regions of each of the heavy and light chain variable regions. In another example, a humanized antibody contains less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequence in the framework regions of each of the heavy and light chain variable regions. The humanized heavy chain variable domain may comprise an IGHV1-46*02 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human mutations, or with no non-human mutations.The humanized light chain variable domain may comprise an IGKV3-20 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human mutations, or with no non-human mutations.

[0177] epitope In various embodiments, provided are anti-TL1A antibodies that bind to the same region of the TL1A protein or a portion thereof as a reference antibody, such as, for example, the anti-TL1A antibodies described herein. In some embodiments, the reference antibody comprises antibody A, B, C, D, E, F, G, H, A2, B2, C2, D2, E2, F2, G2, or H2, or a combination thereof. In some embodiments, provided herein are anti-TL1A antibodies that specifically bind to the same region of TL1A as the reference antibody, comprising a heavy chain sequence at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104 and a light chain comprising a sequence at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. In some embodiments, provided herein is an anti-TL1A antibody that specifically binds to the same region of TL1A as a reference antibody, comprising a heavy chain sequence at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107 and a light chain comprising a sequence at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0178] Non-limiting methods are provided for determining whether an anti-TL1A antibody (i.e., a test antibody) binds to the same TL1A protein or a portion thereof as the antibodies described herein. Exemplary embodiments include competitive assays. For example, a method includes determining whether a test antibody can compete for binding between a reference antibody and a TL1A protein or a portion thereof, or determining whether a reference antibody can compete for binding between a test antibody and a TL1A protein or a portion thereof. An exemplary method includes using surface plasmon resonance to assess whether an anti-TL1A antibody can compete for binding between TL1A and another anti-TL1A antibody. In some examples, surface plasmon resonance is utilized in a competitive assay. Non-limiting methods are described in the Examples.

[0179] In certain embodiments, disclosed herein are antibodies that compete for TL1A binding with the antibodies described herein. In certain embodiments, disclosed herein are antibodies that bind to a different epitope, where the different epitope overlaps with the epitope of TL1A bound by an antibody described herein. In certain embodiments, provided herein are antibodies that bind to the same epitope of TL1A and that overlap with the epitope of TL1A by one or more amino acid residues, or antibodies that compete for binding to an epitope of TL1A with an antibody or fragment thereof comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 104 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 201. In certain embodiments, provided herein are antibodies that bind to the same epitope of TL1A and that overlap with the epitope of TL1A by one or more amino acid residues, or antibodies that compete for binding to an epitope of TL1A with an antibody or fragment thereof comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 107 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 201.

[0180] 4.3 Assay An exemplary screening paradigm for identifying antibody variants that express well in mammalian cells and minimize the tendency for antibody aggregation while retaining TL1A-binding activity involves a five-step process. This screening was performed as detailed in the Examples. Briefly, (1) variants were cloned and transiently expressed as intact Ig in 293 cells using small-scale (3 mL, 6-well culture plate) transfection; (2) antibody expression levels were assessed in culture supernatants 96–120 hours posttransfection using an antibody quantification ELISA; (3) binding of the supernatant antibody variants to human TL1A was assessed by ELISA; (4) antibodies were purified in one step using Protein A; and (5) the material was analyzed by analytical SEC to assess monomer / aggregate content. This approach allowed for the identification of variants that expressed well, retained binding to TL1A, and exhibited high monomer content.

[0181] Also provided herein are methods for analyzing antibody solubility based on the percentage of monomer fraction, e.g., as described in Example 2.

[0182] Further provided herein are assays for quantifying antibody expression, e.g., as described in Example 2.

[0183] Also provided herein are assays for quantifying the immunogenicity of antibodies.

[0184] The antibodies described herein can be analyzed for specific binding by any method known in the art. Immunoassays that can be used include, but are not limited to, competitive and non-competitive assay systems using techniques such as BIAcore analysis, FACS analysis, immunofluorescence, immunocytochemistry, Western blots, radioimmunoassays, ELISAs, "sandwich" immunoassays, immunoprecipitation assays, precipitation reactions, gel diffusion precipitin reactions, immunodiffusion assays, agglutination assays, complement fixation assays, immunoradiometric assays, fluorescent immunoassays, and protein A immunoassays. Such assays are provided, for example, in Ausubel et al., eds., 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York.

[0185] 4.4 Methods for generating antibodies In various embodiments, monoclonal antibodies are produced using methods known in the art, such as the hybridoma method. The hybridoma method involves immunizing a host animal to induce lymphocyte production of antibodies that specifically bind to the immunizing antigen (Kohler and Milstein (1975) Nature 256:495). Hybridomas produce monoclonal antibodies specifically directed against a selected antigen. When grown either in vitro or in vivo, monoclonal antibodies are purified from the culture medium or ascites fluid by techniques known in the art.

[0186] In some embodiments, monoclonal antibodies are produced using recombinant DNA methods. Polynucleotides encoding the monoclonal antibodies are isolated from mature B cells or hybridoma cells. The isolated polynucleotides encoding the heavy and light chains are then cloned into a suitable expression vector. When the vector is transfected into host cells (e.g., E. coli cells, monkey COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells), the monoclonal antibody is produced. Polynucleotides encoding the monoclonal antibodies can be further modified in many different ways using recombinant DNA methods to generate additional antibodies.

[0187] In various embodiments, chimeric antibodies, molecules in which different portions are derived from different animal species, such as those having a variable region derived from a murine monoclonal antibody and a human immunoglobulin constant region (e.g., humanized antibodies), can be produced.

[0188] In some embodiments, the anti-TL1A monoclonal antibody is a humanized antibody, reducing antigenicity and HAMA (human anti-mouse antibody) responses when administered to a human subject. Humanized antibodies can be produced using various techniques known in the art. For example, antibodies are humanized by (1) determining the nucleotide and predicted amino acid sequence of the starting antibody light and heavy variable domains, (2) designing the humanized antibody, e.g., determining which antibody framework regions to use during the humanization process, (3) the actual humanization methodology / techniques, and (4) transfection and expression of the humanized antibody. In various embodiments, for human therapeutic purposes, humanized antibodies can be further optimized to maintain functional activity while reducing potential immunogenicity.

[0189] Humanized antibodies can also be produced in transgenic mice, which contain human immunoglobulin loci and are capable, upon immunization, of producing the full repertoire of human antibodies in the absence of endogenous immunoglobulin production. Humanized antibodies may also be obtained by genetic engineering methods that allow the production of affinity-matured, human-like polyclonal antibodies in large animals.

[0190] Fully humanized antibodies can be created by first designing variable region amino acid sequences containing CDRs from a non-human, e.g., rodent, species embedded in framework sequences from a human. The non-human CDRs provide the desired specificity. Therefore, in some instances, these residues are included in the reshaped variable region design essentially unchanged. Thus, in some instances, modifications are limited to a minimum and carefully monitored for changes in antibody specificity and affinity. On the other hand, theoretical framework residues can be derived from any human variable region. With the goal of creating a reshaped antibody that exhibits acceptable or even improved affinity, equally suitable human framework regions are selected for generating the reshaped variable regions and preserving antibody affinity. The human framework can be derived from germline or non-germline (e.g., mutated or affinity-matured) sequences. Genetic engineering techniques are known in the art and may be used, for example but not limited to, phage display of human antibody libraries, transgenic mice, human-human hybridomas, hybrid hybridomas, B-cell immortalization and cloning, single-cell RT-PCR, or HuRAb technology to generate humanized antibodies with hybrid DNA sequences containing human frameworks and non-human CDRs.

[0191] In certain embodiments, the anti-TL1A antibody is a human antibody. Human antibodies can be produced directly using various techniques known in the art. Immortalized human B lymphocytes can be produced by in vitro immunization or by isolated immortalized human B lymphocytes from immunized individuals that produce antibodies directed against a target antigen.

[0192] Chimeric, humanized, and human antibodies can be produced by recombinant expression. Recombinant polynucleotide constructs typically contain expression control sequences operably linked to the coding sequences for the antibody chains, including naturally associated promoter regions or heterologous promoter regions. In certain embodiments, it may be desirable to generate amino acid sequence variants of these humanized antibodies, particularly if the binding affinity or other biological properties of the antibody are to be improved.

[0193] In certain embodiments, antibody fragments are used to treat and / or ameliorate inflammation and / or fibrosis. In certain embodiments, antibody fragments are used to treat and / or ameliorate pulmonary diseases and / or conditions. Various techniques for producing antibody fragments are known. Generally, these fragments are derived by proteolytic digestion of intact antibodies (e.g., Morimoto et al., 1993, Journal of Biochemical and Biophysical Methods 24:107-117; Brennan et al., 1985, Science 229:81). Fab, Fv, and scFv antibody fragments can all be expressed in and secreted from E. coli or other host cells. Thus, large amounts of these fragments can be produced. Other techniques for producing antibody fragments will be apparent to those skilled in the art.

[0194] In accordance with the present disclosure, techniques can be adapted for the production of single-chain antibodies specific to TL1A. Furthermore, methods can be adapted for the construction of Fab expression libraries, which allow for the rapid and efficient identification of monoclonal Fab fragments, or derivatives, fragments, analogs, or homologs thereof, with the desired specificity for TL1A. Antibody fragments can be produced by techniques known in the art, including, but not limited to: (a) F(ab')2 fragments produced by pepsin digestion of antibody molecules, (b) Fab fragments generated by reduction of disulfide bridges in F(ab')2 fragments, (c) Fab fragments generated by treatment of antibody molecules with papain and a reducing agent, and (d) Fv fragments.

[0195] Also provided herein are modified antibodies comprising any type of variable region that provides for the association of the antibody with TL1A. Those skilled in the art will appreciate that modified antibodies can include antibodies (e.g., full-length antibodies or immunoreactive fragments thereof) in which at least a portion of one or more constant region domains has been deleted or otherwise altered to provide desired biochemical characteristics, such as reduced TL1A activity. In certain embodiments, the variable regions of both the heavy and light chains are altered by at least partial replacement of one or more CDRs, and, optionally, by substitution and sequence alteration of partial framework regions. In some embodiments, the replaced CDRs may be derived from antibodies of the same class or subclass, antibodies of a different class, e.g., antibodies from a different species, and / or combinations thereof. In some embodiments, the constant region of the modified antibody comprises a human constant region. Modifications to the constant region consistent with the present disclosure include the addition, deletion, or substitution of one or more amino acids in one or more domains.

[0196] In various embodiments, expression of the antibodies or antigen-binding fragments thereof described herein can occur in either prokaryotic or eukaryotic cells. Suitable hosts include bacterial hosts in vivo or in situ, or eukaryotic hosts, including yeast, insect, fungal, avian, and mammalian cells, or host cells of mammalian, insect, avian, or yeast origin. Mammalian cells or tissues may be of human, primate, hamster, rabbit, rodent, bovine, porcine, ovine, equine, caprine, canine, or feline origin, or any other mammalian cell may be used. In other embodiments, the antibodies or antigen-binding fragments thereof described herein may be transfected into a host.

[0197] In some embodiments, the expression vector is transfected into a recipient cell line for the production of chimeric, humanized, or composite human antibodies described herein. In various embodiments, mammalian cells may be useful as hosts for antibody protein production, including, but not limited to, fibroblast-derived cells such as Vero cells (ATCC CRL81) or CHO-K1 cells (ATCC CRL61), HeLa cells, and L cells. Exemplary eukaryotic cells that can be used to express polypeptides include COS cells, including COS7 cells; 293 cells, including 293-6E cells; CHO cells, including CHO-S cells and DG44 cells; PER.C6™ cells (Crucell); and NSO cells. In some embodiments, particular eukaryotic host cells are selected based on their ability to make desired post-translational modifications to the heavy and / or light chains.

[0198] Many suitable host cell lines capable of secreting intact heterologous proteins have been developed in the art, including, but not limited to, CHO cell lines, various COS cell lines, HeLa cells, L cells, and multiple myeloma cell lines.

[0199] Expression vectors carrying the chimeric, humanized, or composite human antibody constructs, antibodies, or antigen-binding fragments thereof described herein can be introduced into suitable host cells by any of a variety of suitable means, depending on the type of cellular host, including, but not limited to, transformation, transfection, lipofection, conjugation, electroporation, direct microinjection, and microprojectile bombardment, as known to those skilled in the art. Expression vectors for these cells can include expression control sequences, such as an origin of replication, a promoter, an enhancer, and necessary processing information sites, e.g., ribosome binding sites, RNA splice sites, polyadenylation sites, and transcription terminator sequences.

[0200] In various embodiments, yeast may also be utilized as hosts for the production of the antibody molecules or peptides described herein. In various other embodiments, bacterial strains may also be utilized as hosts for the production of the antibody molecules or peptides described herein. Examples of bacterial strains include, but are not limited to, E. coli, Bacillus species, Enterobacteriaceae, and various Pseudomonas species.

[0201] In some embodiments, one or more of the antibodies or antigen-binding fragments thereof described herein may be introduced in vivo into an animal that has been engineered (transgenic) or transfected with one or more nucleic acid molecules encoding the polypeptides according to any suitable method. For the generation of transgenic animals, the transgene may be microinjected into fertilized oocytes or may be integrated into the genome of an embryonic stem cell and the nucleus of such a cell introduced into an enucleated oocyte. Once expressed, the antibody may be purified according to standard methods in the art, including HPLC purification, column chromatography, gel electrophoresis, etc. (For an overview, see Scopes, Protein Purification (Springer-Verlag, NY, 1982)).

[0202] Once expressed in a host, whole antibodies, antibody fragments (e.g., individual light and heavy chains), or other immunoglobulin forms of the present disclosure may be recovered and purified by known techniques, such as immunoabsorption or immunoaffinity chromatography, chromatographic methods such as HPLC (high performance liquid chromatography), ammonium sulfate precipitation, gel electrophoresis, or any combination thereof. See generally, Scopes, PROTEIN PURIF. (Springer-Verlag, NY, 1982). Substantially pure immunoglobulins of at least about 90% to 95% homogeneity are advantageous, and, particularly for pharmaceutical uses, immunoglobulins of 98% to 99% or more homogeneity are preferred. Once purified, partially or to homogeneity as desired, the humanized or composite human antibodies can then be used therapeutically or in the development and implementation of assay tools, immunofluorescence staining, and the like. See generally, Vols. I & II Immunol. Meth. (Lefkovits & Pernis, eds., Acad. Press, NY, 1979 and 1981).

[0203] Various embodiments provide genetic constructs comprising nucleic acids encoding the anti-TL1A antibodies or fragments provided herein. The antibody genetic constructs may be in the form of expression cassettes, which may be suitable for expressing the encoded anti-TL1A antibodies or fragments. The genetic constructs may be introduced into host cells with or without a vector. For example, the genetic constructs may be incorporated into liposomes or viral particles. Alternatively, purified nucleic acid molecules may be directly inserted into host cells by methods known in the art. The genetic constructs may be directly introduced into the cells of a host subject by transfection, infection, electroporation, cell fusion, protoplast fusion, microinjection, or ballistic bombardment.

[0204] Various embodiments provide recombinant vectors comprising the gene constructs of the antibodies provided herein. The recombinant vectors may be plasmids, cosmids, or phages. The recombinant vectors may also include other functional elements, such as an appropriate promoter for initiating gene expression.

[0205] Various embodiments provide host cells comprising the genetic constructs and / or recombinant vectors described herein.

[0206] It is also advantageous to employ various host systems for expressing recombinant proteins. Examples of suitable mammalian host cell lines include the COS-7 monkey kidney cell line and other cell lines capable of expressing suitable vectors, including, for example, L cell lines, C127 cell lines, 3T3 cell lines, Chinese hamster ovary (CHO) cell lines, HeLa cell lines, and BHK cell lines. Mammalian expression vectors may also include non-transcribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other 5'- or 3'-flanking non-transcribed sequences, as well as 5'- or 3'-untranslated sequences, such as necessary ribosome binding sites, polyadenylation sites, splice donor and recipient sites, and transcription termination sequences.

[0207] Proteins produced by transformed hosts can be purified according to any appropriate method. Such standard methods include chromatography (e.g., ion exchange chromatography, affinity chromatography, and size column chromatography), centrifugation, differential solubility, or any other standard technique for protein purification. Affinity tags such as hexahistidine (SEQ ID NO: 391), maltose-binding domain, influenza coat sequence, and glutathione-S-transferase can be attached to the protein and easily purified by passage through an appropriate affinity column. Isolated proteins can be physically characterized using techniques such as proteolysis, nuclear magnetic resonance, and X-ray crystallography. Recombinant proteins produced in bacterial cultures may also be isolated.

[0208] Those skilled in the art will recognize that individual substitutions, deletions, or additions to a nucleic acid, peptide, polypeptide, or protein sequence that alter a single amino acid or a subset of amino acids in the encoded sequence, but which result in the substitution of an amino acid with a chemically similar amino acid, and which retain the ability to specifically bind to the target antigen, are "conservatively modified variants." Such conservatively modified variants are in addition to, and do not exclude, polymorphic variants, interspecies homologs, and alleles consistent with the present disclosure.

[0209] A given amino acid may be substituted with a residue having similar physicochemical characteristics, for example, by substituting one aliphatic residue for another (e.g., He, Val, Leu, or Ala for one another), or by substituting one polar residue for another (e.g., between Lys and Arg, between Glu and Asp, or between Gln and Asn). Other such conservative substitutions are known, for example, the substitution of entire regions with similar hydrophobic properties. Polypeptides containing conservative amino acid substitutions may be tested in any one of the assays described herein to confirm that the desired activity, e.g., antigen-binding activity and specificity of the native or reference polypeptide, is retained.

[0210] Specific conservative substitutions include, for example, Ala for Gly or Ser, Arg for Lys, Asn for Gin or His, Asp for Glu, Cys for Ser, Gin for Asn, Glu for Asp, Gly for Ala or Pro, His for Asn or Gin, Lie for Leu or Val, Leu for Lie or Val, Lys for Arg, Gin or Glu, Met for Leu, Tyr or Lie, Phe for Met, Leu or Tyr, Ser for Thr, Thr for Ser, Trp for Tyr, Tyr for Trp, and / or Phe for Val, Lie or Leu.

[0211] In some embodiments, the antibodies and / or antigen-binding fragments thereof described herein may be variants of the sequences described herein, e.g., conservatively substituted variants of antibody polypeptides. In some embodiments, the variants are conservatively modified variants. A variant refers to a polypeptide that is substantially homologous to a native or reference polypeptide but has an amino acid sequence that differs from the native or reference polypeptide by virtue of one or more deletions, insertions, or substitutions. DNA sequences encoding variant polypeptides include sequences that encode variant proteins or fragments thereof that contain one or more additions, deletions, or substitutions of nucleotides compared to the native or reference DNA sequence but retain activity, e.g., antigen-specific binding activity to a relevant target polypeptide.

[0212] Alterations to the native amino acid sequence can be accomplished by any of a number of techniques known to those skilled in the art. Mutations can be introduced at specific loci or by oligonucleotide-directed site-directed mutagenesis. Techniques for making such alterations are very well established, and include those disclosed by Walder et al. (Gene 42:133, 1986), Bauer et al. (Gene 37:73, 1985), Craik (BioTechniques, January 1985, 12-19), and Smith et al. (Genetic Engineering: Principles and Methods, Plenum Press, 1981).

[0213] Nucleic acid molecules encoding amino acid sequence variants of antibodies can be generated by a variety of methods known in the art, including, but not limited to, oligonucleotide-mediated (or site-directed) mutagenesis, PCR mutagenesis, and cassette mutagenesis of pre-generated antibody variants or non-variant forms of antibodies. Nucleic acid sequences encoding at least one antibody, moiety, or polypeptide described herein can be recombined with vector DNA according to conventional techniques, including, but not limited to, blunt or cohesive ends for ligation and restriction enzyme digestion. Techniques for such manipulations are disclosed, for example, in Maniatis et al., Molecular Cloning, Lab. Manual (Cold Spring Harbor Lab. Press, NY, 1982 and 1989), and can be used to construct nucleic acid sequences encoding monoclonal antibody molecules or antigen-binding regions.

[0214] In some embodiments, the nucleic acid encoding the antibody or antigen-binding fragment thereof described herein is contained in a vector. In some aspects described herein, the nucleic acid sequence of the antibody or antigen-binding fragment thereof described herein, or any module thereof, is operably linked to a vector. As used herein, the term "vector" refers to a nucleic acid construct designed for delivery to a host cell or for transfer between different host cells. As used herein, a vector may be viral or non-viral. The term "vector" encompasses any genetic element capable of replication when associated with appropriate control elements and any genetic element capable of transferring a gene sequence into a cell. Vectors include, but are not limited to, cloning vectors, expression vectors, plasmids, phages, transposons, cosmids, chromosomes, viruses, virions, etc.

[0215] As used herein, the term "expression vector" refers to a vector that directs the expression of RNA or polypeptides from sequences linked to transcriptional control sequences on the vector. The term "expression" refers to the cellular processes involved in the production of RNA and proteins, and optionally, protein secretion, including, but not limited to, transcription, transcript processing, translation, and protein folding, modification, and processing, as applicable. "Expression product" includes RNA transcribed from a gene and polypeptides obtained by translation of mRNA transcribed from a gene. The term "gene" refers to a nucleic acid sequence (DNA) that is transcribed into RNA in vitro or in vivo when operably linked to appropriate control sequences. A gene may or may not include regions preceding and following the coding region, e.g., 5' untranslated (5'UTR) or "leader" sequence and 3'UTR or "trailer" sequence, as well as intervening sequences (introns) between individual coding segments (exons).

[0216] As used herein, the term "viral vector" refers to a nucleic acid vector construct that contains at least one element of viral origin and is capable of being packaged into a viral vector particle. The viral vector can contain a nucleic acid encoding an antibody or antigen-binding portion thereof described herein in place of a non-essential viral gene. The vector and / or particle may be utilized to transfer any nucleic acid into cells, either in vitro or in vivo. Many forms of viral vectors are known in the art.

[0217] By "recombinant vector" is meant that the vector contains a heterologous nucleic acid sequence, or "transgene," that can be expressed in vivo.

[0218] 4.5 Pharmaceutical Compositions In one aspect, the anti-TL1A antibodies provided herein are formulated into pharmaceutical composi...

Claims

1. Use of an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody) in the manufacture of a formulation for the treatment of inflammation or fibrosis in a subject in need of such treatment, wherein the subject has systemic sclerosis-associated interstitial lung disease.

2. The use of claim 1, wherein the subject has inflammation or fibrosis in the lungs.

3. The use according to claim 1 or 2, wherein the fibrosis comprises idiopathic pulmonary fibrosis.

4. The use according to claim 1 or 2, wherein the fibrosis comprises viral-induced pulmonary fibrosis.

5. The use according to any one of claims 1 to 4, wherein the subject has asthma.

6. The use according to any one of claims 1 to 5, wherein the subject has chronic obstructive pulmonary disease (COPD).

7. The use according to any one of claims 1 to 6, wherein the subject has pneumonia.

8. 8. The use of any one of claims 1 to 7, wherein the subject has chronic lung disorder, idiopathic interstitial pneumonia, pulmonary sarcoidosis, interstitial lung disease, bronchiolitis, alveolitis, vasculitis, interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, idiopathic organizing pneumonia, acute interstitial pneumonia, allergic rhinitis, emphysema, chronic bronchitis, primary biliary cholangitis, Behcet's disease, systemic sclerosis-related interstitial lung disease, or cystic fibrosis, or a combination thereof.

9. The use according to any one of claims 1 to 8, wherein the anti-TL1A antibody is administered in a pharmaceutical composition.

10. The use of claim 9, wherein the pharmaceutical composition comprises the anti-TL1A antibody at a concentration of greater than about 95 mg / mL.

11. The use according to claim 9 or 10, wherein the pharmaceutical composition has a total volume of about 0.5 mL to about 5 mL.

12. The use according to any one of claims 9 to 11, wherein the pharmaceutical composition has a viscosity of less than about 20 cP.

13. The use according to any one of claims 9 to 12, wherein the pharmaceutical composition has an aggregation rate of anti-TL1A antibodies of less than about 5% of the total anti-TL1A antibodies in the pharmaceutical composition as measured by size exclusion chromatography.

14. The use according to any one of claims 9 to 13, wherein the pharmaceutical composition comprises a surfactant, a salt, a stabilizer, or a buffering agent, or a combination thereof.

15. The use of claim 14, wherein the pharmaceutical composition comprises a surfactant, the surfactant comprises a non-ionic surfactant, and the non-ionic surfactant comprises polysorbate-20.

16. The use according to claim 14 or 15, wherein the surfactant is present in a concentration of about 0.005% to about 0.05% of the pharmaceutical composition.

17. The use of any one of claims 14 to 16, wherein the pharmaceutical composition comprises a salt, the salt comprising sodium chloride, glycine, lysine hydrochloride, arginine hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof.

18. The use according to any one of claims 14 to 17, wherein the salt is present in the pharmaceutical composition at a concentration of from about 10 mM to about 100 mM.

19. 19. The use according to any one of claims 14 to 18, wherein the pharmaceutical composition comprises a stabilizer, the stabilizer comprising a sugar, a polyol, an amino acid, a polymer, or a cyclodextrin (e.g. HP-b-CD), or a combination thereof.

20. The use of claim 19, wherein the pharmaceutical composition comprises sugar, the sugar comprising sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof.

21. The use according to any one of claims 14 to 20, wherein the stabilizer is present in the pharmaceutical composition at a concentration of about 50 mM to about 300 mM.

22. The use of any one of claims 14 to 21, wherein the pharmaceutical composition comprises a buffering agent, the buffering agent comprising acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, tris (tris(hydroxymethyl)aminomethane), or diethanolamine, or a combination thereof.

23. The use according to any one of claims 14 to 22, wherein the buffering agent is present in the pharmaceutical composition at a concentration of from about 10 mM to about 50 mM.

24. The use according to any one of claims 9 to 23, wherein the pharmaceutical composition has a pH of about 4.5 to about 8.

0.

25. The use of any one of claims 1 to 24, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence described by SEQ ID NO:1, an HCDR2 comprising the amino acid sequence described by any one of SEQ ID NOs:2 to 5, and an HCDR3 comprising the amino acid sequence described by any one of SEQ ID NOs:6 to 9, and a light chain variable region comprising an LCDR1 comprising the amino acid sequence described by SEQ ID NO:10, an LCDR2 comprising the amino acid sequence described by SEQ ID NO:11, and an LCDR3 comprising the amino acid sequence described by any one of SEQ ID NOs:12 to 15.

26. 25. The use of any one of claims 1 to 24, 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 or do not comprise fewer than 9 amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

27. The anti-TL1A antibody has the sequence of SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS [HCDR1] WVX2QX3PGQGLEWX4G [HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [HCDR3] WGQGTTVTVSS, and a heavy chain variable region comprising SEQ ID NO: 303 and a light chain variable region comprising: EIVLTQSPGTLSLSPGERATLSC [LCDR1] WYQQKPGQAPRX10X11IY [LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [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; HCDR1 comprises the amino acid sequence set forth by SEQ ID NO: 1; 25. The use according to any one of claims 1 to 24, wherein CDR2 comprises the amino acid sequence described by any one of SEQ ID NOs: 2 to 5, HCDR3 comprises the amino acid sequence described by any one of SEQ ID NOs: 6 to 9, LCDR1 comprises the amino acid sequence described by SEQ ID NO: 10, LCDR2 comprises the amino acid sequence described by SEQ ID NO: 11, and LCDR3 comprises the amino acid sequence described by any one of SEQ ID NOs: 12 or 13.

28. The use according to any one of claims 1 to 24, wherein the anti-TL1A antibody comprises (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 104, and (b) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 201.