Anti-tl1a antibody compositions and methods of treatment in the kidney

Abstract

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

Description

ANTI-TL1A ANTIBODY COMPOSITIONS AND METHODS OF TREATMENT IN THE KIDNEYCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S Provisional Application No. 63 / 485,806 filed February 17, 2023.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML file, created on February 2, 2024 is named 2581 l-WO-PCT SL. xml and is 380,464 Ibytes in size.1. BACKGROUND

[0003] TL1 A is a cytokine that is secreted by antigen-presenting cells, T cells, and endothelial cells. TL1A signals through death receptor 3 (DR3), a TNF -family receptor that is found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphoid cells (ILC), fibroblasts, and epithelial cells and potently drives Thl, Th2, Th9 and Thl7 responses. In addition, it is induced in antigen-presenting cells by toll like receptor (TLR) ligands and FcR cross-linking and in T cells by T cell receptor (TCR) stimulation. TL1 A has been shown to be upregulated in mucosa and serum of patients with inflammatory bowel disease. In dextran sodium sulfate (DSS) and adoptive transfer mouse models, antibodies against TL1 A led to reduced inflammation and reversal of fibrosis, even when treatment was administered late in the course of disease, after inflammation and fibrosis has been established.2. SUMMARY

[0004] The present disclosure provides tumor necrosis factor ligand 1A (TL1 A) binding antibodies or antigen binding fragments thereof and compositions thereof for the treatment of inflammation and / or fibrosis, including diseases or conditions that present in the kidney of a subject. In various aspects, antibodies or antigen binding fragments thereof described herein possess features useful for therapeutic application such as low immunogenicity, and / or features that facilitate antibody or antigen binding fragmentmanufacture, such as high percentage of monomeric fraction as measured by size-exclusion chromatography, and / or high expression. In further aspects, antibodies or antigen binding fragments thereof described herein possess features useful for subcutaneous administration, such as low viscosity at highantibody or antigen binding fragment concentration. Further aspects of the antibodies or antigen binding fragments thereof and their formulations may include high solubility, low subvisible particles, low opalescence, no visible particulates, and any combination thereof.

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

[0006] In some embodiments, the subject has a chronic kidney disorder. In some embodiments, the subject has end stage renal disease. In some embodiments, the subject has tubulointerstitial renal fibrosis. In some embodiments, the subject has nephritis. In some embodiments, the subject has diabetic kidney disease. In some embodiments, the subject has polycystic kidney disease. In some embodiments, the subject has end-stage renal disease, tubulointerstitial renal fibrosis, glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, diabetic kidney diseases, lupus nephritis, Alport syndrome, or polycystic kidney disease, or a combination thereof.

[0007] In some embodiments, the anti-TLl A antibody or antigen binding fragment is administered in a pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises the anti-TLl A antibody or antigen binding fragment 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 about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, or 225 mg / mL. In some embodiments, the concentration is about 150 mg / mL to about 250 mg / mL. In some embodiments, the concentration is about 175 mg / mL to about 225 mg / mL. In one aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TLl A antibody or antigen binding fragment) at a concentration greater than about50 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 the anti-TLIA antibody or antigen binding fragment is present in the composition. In some embodiments, the composition has a total volume of less than or equal to 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. In some embodiments, the pharmaceutical composition comprises a therapeutically effective dose of the anti-TLIA antibody or antigen binding fragment. In some embodiments, the composition has a total volume less than or equal to 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, 4.9, 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. In some embodiments, the composition has a total volume of about 0.5 mL to about 1.5 mL. In some embodiments, a composition herein has a total volume of about 0.5 mL to about 2.5 mL. In some embodiments, a composition herein has a total volume of about 0.5 mL to about 3.5 mL. In some embodiments, a composition herein has a total volume of about 0.5 mL to about 4.5 mL. In some embodiments, a composition herein has a total volume of about 1 mL to about 1.5 mL. In some embodiments, a composition herein has a total volume of about 1 mL to about 2.5 mL. In some embodiments, a composition herein has a total volume of about 1 mL to about 3.5 mL. In some embodiments, a composition herein has a total volume of about 1 mL to about 4.5 mL. In some embodiments, the composition has a viscosity of less than about 20 cP. In some embodiments, the composition has a viscosity of less than about 15 cP. In some embodiments, the composition has a viscosity of less than about 10 cP. In some embodiments, the composition has a viscosity of less than about 9, 8, 7, 6, or 5 cP. In some embodiments, the composition has 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 composition has a viscosity of about 1 cP to about 10 cP. In some embodiments, the composition has 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 a percentage aggregation of anti-TLIA antibody or antigen binding fragment as measured by size exclusion chromatography of less than about 5% of the total anti-TLIA antibody or antigenbinding fragment in the composition. 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 nonionic surfactant. In some embodiments, the nonionic 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 at a concentration of about 10 mM to about 100 mM in the composition. In some embodiments, the salt is present at a concentration of about 25 mM in the composition. In some embodiments, the salt is present at a concentration of about 40 mM in the composition. In some embodiments, the composition comprises a stabilizer. In some embodiments, the stabilizer comprises a sugar, polyol, amino acid, or polymer, cyclodextrin (e.g., HP-b-CD), or a combination thereof. In some embodiments, the stabilizer comprises the 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 at a concentration of about 50 mM to about 300 mM in the composition. 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, the sucrose is present at a concentration of about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200mM, about 210 M, about 220 M, about 230 M, about 240 mM, or about 250 mM. In some embodiments, the glycine is present at a concentration of about 10 mM, about 15 m , 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 at a concentration of about 10 mM to about 50 mM in the composition. 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-TLl A antibody or antigen binding fragment is administered to the subject at a first dose up to about 1000 mg. In some embodiments, the anti-TLl A antibody or antigen binding fragment 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 a 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 anti-TLl A antibody or antigen binding fragment. 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-TLl A antibody or antigen binding fragment 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 anti-TLl A antibody or antigen binding fragment. 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-TLl A antibody or antigen binding fragment is administered to the subject at a 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 anti-TLl A antibody or antigen binding fragment. 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-TLl A antibody or antigen binding fragment is administered to the 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 anti-TLl A antibody or antigen binding fragment. 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-TLl A antibody or antigen binding fragment is administered to the 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 anti-TLIA antibody or antigen binding fragment. In some embodiments, the sixth dose comprises about 150 mg to about 1000 mg. In some embodiments, the sixth dose comprises about 150 mg to about 600 mg.

[0009] In some embodiments, an additional dose of the anti-TLIA antibody or antigen binding fragment is administered to the subject at one or more additional time points. In some embodiments, the one or more additional time points comprises 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 timepoints. 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 a previous time point. In some embodiments, each additional time point is independently about 1, 2, 3, or 4 weeks after a 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 anti-TLl A antibody or antigen binding fragment. In some embodiments, the additional dose comprises from about 150 mg to about 1000 mg anti-TLIA antibody or antigen binding fragment. In some embodiments, the additional dose is about 175 mg to about 300 mg anti-TLIA antibody or antigen binding fragment.

[0010] In one aspect, provided herein is an antibody or antigen binding fragment thereof that binds to tumor necrosis factor-like protein 1 A (“TL1 A,” and such antibody or antigen binding fragment thereof, “anti-TLIA antibody or antigen binding fragment”), wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A.

[0011] In some embodiments, the antibody or antigen binding fragment blocks interaction of TL1 A to Death Receptor 3 (“DR3”). In some embodiments, the binding affinity of the antibody or antigen binding fragment to monomeric TL1 A as measured by dissociation equilibrium constant (Ko-monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1 A as measured by dissociation equilibrium constant (Ko-trimer). In some embodiments, the KD -monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD -trim er. In some embodiments, the KD -monomer is no more than 0.06 nM. In some embodiments, the Ko-trimer is no more than 0.06 nM.

[0012] In one aspect, provided herein is method of neutralizing monomeric TL1A and trimeric TL1 A in a subject having kidney inflammation and / or kidney fibrosis comprising (a) administering an effective dose of anti-TLIA antibody or antigen binding fragment to the subject, wherein the antibody or antigen binding fragment binds to both monomeric TL1 A and trimeric TL1A, wherein the antibody or antigen binding fragment blocks interaction of TL1 A to DR3, wherein the concentration of TL1 A in a diseased tissue in the subject is reduced below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, and wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidneyfibrosis. In some embodiments, the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease. In some embodiments, the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

[0013] In one aspect, provide herein is a method of reducing the concentration of TL1 A in a diseased tissue in a subject with kidney inflammation and / or kidney fibrosis comprising (a) administering an effective dose of anti-TLl A antibody or antigen binding fragment to the subject, thereby reducing the concentration of TL1 A in the diseased tissue in the subject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0014] In one aspect, provide herein is a method of treating kidney inflammation and / or kidney fibrosis in a subject in need thereof comprising (a) administering an anti-TLl A antibody or antigen binding fragment to the subject, wherein the anti-TLl A antibody or antigen binding fragment is administered at an effective dose such that the concentration of TL1 A in a diseased tissue in the subject after step (a) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, and wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0015] In one aspect, provide herein is a method of treating kidney inflammation and / or kidney fibrosis in a subject in need thereof comprising (a) administering an anti-TLIA antibody or antigen binding fragment to the subject at an effective dose, and (b) reducing the concentration of TL1 A in a diseased tissue in the subject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron,renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

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

[0017] In some embodiments, the method further comprises (c) maintaining TL1 A in the diseased tissue in the subject at a concentration below the concentration of TL1 A in the corresponding tissue in the control subject.

[0018] In some embodiments, the TL1 A in the diseased tissue in the subject is maintained with a maintenance regimen of the anti-TLIA antibody or antigen binding fragment. In some embodiments, the induction regimen and the maintenance regimen are identical. 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, or more fold of TL1 A compared to the corresponding tissue in the control subject during the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject.

[0019] In some embodiments, the induction regimen comprises a one-time administration of the anti-TLIA antibody or antigen binding fragment. In some embodiments, the anti- TLIA 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-TLIA antibody or antigen binding fragment. In some embodiments, the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6,and 500 mg / dose on week 10; or (v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

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

[0022] In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject during the maintenance regimen. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

[0023] In some embodiments, the maintenance regimen comprises multiple administrations of the anti-TLl A antibody or antigen binding fragment. In some embodiments, the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0024] In some embodiments, the maintenance regimen comprises administration of the anti-TLl A 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 the anti-TLl A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks. In some embodiments, the maintenance regimen comprises administrations of the anti-TLl A antibody or antigen binding fragment at 250 mg / dose every 4 weeks. In some embodiments, the maintenance regimen comprises administrations of the anti-TLl A 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 TL1 A and trimeric TL1 A and wherein the antibody or antigen binding fragment blocks binding of TL1 A to DR3. In some embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TLIA antibody or antigen binding fragment. In some embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TLIA antibody or antigen binding fragment.

[0026] In some embodiments, the binding affinity of the antibody or antigen binding fragment to monomeric TL1A as measured by dissociation equilibrium constant (Ko-monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1A as measured by dissociation equilibrium constant (Ko-trimer). In some embodiments, the KD -monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the Ko-trimer. In some embodiments, the KD -monomer is no more than 0.06 nM. In some embodiments, the KD -trimer is no more than 0.06 nM.

[0027] In some embodiments, the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease.

[0028] In some embodiments, the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

[0029] In some embodiments, the effective dose or the induction regimen is determinedby a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue; (ii) integrating the parameters received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the effective dose or the induction regimen such that the concentration of TL1 A in diseased tissue in the subject after step (a) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis. In some embodiments, the parameter of TL1 A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold over-production comparing to TL1A production in the normal reference tissue.

[0030] In some embodiments, the maintenance regimen is determined by a dose determination method, wherein the dose determination method comprises: (i) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue; (ii) integrating the parameter received in (i) to an integrated whole - body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and (iii) determining the maintenance regimen such that the concentration of TL1 A in diseased tissue in the subject after step (c) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis. In some embodiments, the parameter of TL1A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more fold over-production comparing to TL1A production in the normal reference tissue.

[0031] In some embodiments, the step (i) in the dose determination method further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1 A (koff-mAb), synthesis rate of TL1 A in normal tissue (kSyn-normai), synthesis rate of TL1 A in diseased tissue (ksyn-disease), and / or degradation rate of TL1 A (kdeg- totai-TLiA). In some embodiments, the association rate of the antibody to TL1A (kon-mAb) comprises the association rate of the antibody to monomeric TL1A (k on-monomer ) and association rate of the antibody to trimeric TL1A (kon-trimer), wherein the dissociation rate of the antibody from TL1A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1 A (koff-monomer) and dissociation rate of the antibody from trimeric TL1 A (koff- trimer), and / or wherein the degradation rate of TL1A (kdeg-totai-TLiA) comprises degradation rate of monomeric TL1 A (kdeg-TLiA-monomer) and degradation rate of trimeric TL1 A (kdeg-TLiA-trimer).

[0032] In some embodiments, the step (i) in the dose determination method furthercomprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody- TL1 A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn), and / or dissociation rate of the antibody- TL1 A complex from FcRn (koff-(mAb-TLiA)-FcRn). In some embodiments, the association rate of the antibody- TL1 A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn) comprises association rate of the antibody-monomeric-TLl A complex to FcRn receptor (kon-(mAb-monoTLiA)-FcRn) and association rate of the antibody-trimeric-TLl A complex to FcRn receptor (kon-(mAb-triTLiA)- FcRn), and / or wherein the dissociation rate of the antibody- ILIA complex from FcRn (koff- (mAb-TLi A)-FcRn) comprises dissociation rate of the antibody-monomeric-TLIA complex from FcRn (koff-(mAb-monoTLiA)-FcRn) and dissociation rate of the antibody-trimeric-TLl A complex from FcRn (koff-(mAb-triTLlA)-FcRn).

[0033] In some embodiments, the step (i) in the dose determination method further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn). In some embodiments, the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TLIA complex (kdeg-(mAb-monoTLiA)-FcRn) and clearance rate of FcRn receptor bound by the antibody- trimeric-TLl A complex (kdeg-(mAb-triTLiA)-FcRn). In some embodiments, in the dose determination method: (1) kon-monomer and kon-trimer are identical or different; (2) koff- monomer and koff-trimer are identical or different; (3) kdeg-monomer and kdeg-trimer are identical or different; (4) kon-(mAb-monoTLlA)-FcRn and kOn-(mAb-triTLiA FcRn are identical or different; (5) kon-mAb-FcRn and kon- (mAb-monoTLiA>FcRn are identical or different; (6) kon-mAb-FcRn and kon-(mAb-triTLiA)-FcRn are identical or different; (7) koff-(mAb-monoTLiA)-FcRn and koff-(mAb-triTLiA)-FcRn are identical or different; (8) koff- mAb-FcRn and koff-(mAb-monoTLl A)-FcRn are identical Or different; (9) koff- mAb-FcRn and koff-(mAb- triTLi A)-FcRn are identical or different; (10) kdeg-(mAb-monoTLiA)-FcRn and kdeg-(mAb-triTLiA)-FcRn are identical or different; (11) kdeg-mAb-FcRn and kdeg-(mAb-triTLiA)-FcRn are identical or different; (12) kdeg-mAb-FcRn and kdeg-(mAb-monoTLi A)-FcRn are identical or different; (13) any combination of (1) to (12). In some embodiments, in the dose determination method: ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of kSyn-normai. In some embodiments, the step (i) in the dose determination method further comprises receiving rate of TL1 A trimerization (kon-TLiA- monomer-to-trimer ) and / or rate of TL1 A monomerization (koff-TLiA-trimer-to-monomer).

[0034] In one aspect, provided herein is a method of determining an effective dose regimen for administering an anti-TLl A antibody to a subject having kidney inflammation and / or kidney fibrosis, wherein the method comprises: (a) receiving a parameter of TL1 Aover-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (b) integrating the parameter received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model; and (c) determining the effective dose regimen of the anti-TLl A antibody with the PBPK model from (b) such that after administration of the effective dose regimen the concentration of TL1 A in a diseased tissue in the subject having kidney inflammation and / or kidney fibrosis is below the concentration of TL1A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0035] In one aspect, provided herein is a method of determining an effective dose regimen for administering an anti-TLl A antibody to a subject having kidney inflammation and / or kidney fibrosis, wherein the method comprises: (a) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1A production in a normal reference tissue; (b) integrating the parameter received in (a) to a population pharmacokinetic (popPK) model; and (c) determining the effective dose regimen of the anti-TLIA antibody with the popPK model from (b) such that after administration of the effective dose regimen the concentration of TL1 A in a diseased tissue in the subject having kidney inflammation and / or kidney fibrosis is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0036] In some embodiments of the dose determination methods, the parameter of TL1 A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 or more fold over-production comparing to TL1A production in the normal reference tissue. In some embodiments of the dose determination methods, the step (a) further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1 A in normal tissue (kSyn-normai), synthesis rate of TL1 A in diseased tissue (ksyn-disease), and / or degradation rate of TL1 A (kdeg-totai-TLiA).

[0037] In some embodiments of the dose determination methods, the association rate of the antibody to TL1 A (kon-mAb) comprises the association rate of the antibody to monomeric TL lA (k on-monomer ) and association rate of the antibody to trimeric TL1 A (kon-trimer), wherein the dissociation rate of the antibody from TL1 A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff-monomer) and dissociation rate of the antibody from trimeric TL1 A (koff-trimer), and / or wherein the degradation rate of TL1 A (kdeg-totai-TLiA) comprises degradation rate of monomeric TL1A (kdeg-TLiA -monomer ) and degradation rate of trimeric TL1A (kdeg-TLiA-trima-). In some embodiments of the dose determination methods, the step (a) comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody- TL1 A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn), and / or dissociation rate of the antibody- TL1 A complex from FcRn (koff-(mAb-TLiA)-FcRn).

[0038] In some embodiments of the dose determination methods, the association rate of the antibody- TL1 A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn) comprises association rate of the antibody-monomeric-TLl A complex to FcRn receptor (kon-(mAb-monoTLiA)-FcRn) and association rate of the antibody-trimeric-TLl A complex to FcRn receptor (kon-(mAb-triTLiA)- FcRn), and / or wherein the dissociation rate of the antibody- ILIA complex from FcRn (koff- (mAb-TLi A)-FcRn) comprises dissociation rate of the antibody-monomeric-TLIA complex from FcRn (koff-(mAb-monoTLiA)-FcRn) and dissociation rate of the antibody-trimeric-TLl A complex from FcRn (koff-(mAb-triTLlA)-FcRn).

[0039] In some embodiments of the dose determination methods, the step (a) further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn). In some embodiments of the dose determination methods, the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) further comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TLIA complex (kdeg-(mAb-monoTLiA)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TLl A complex (kdeg-(mAb-triTLiA)-FcRn).

[0040] In some embodiments of the dose determination methods, the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease. In some embodiments of the dose determination methods, the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

[0041] In some embodiments of the dose determination methods, in the dose determination methods, wherein: (1) kon-monomer and kon-trimer are identical or different; (2) koff- monomer and koff-trimer are identical or different; (3) kdeg -monomer and kdeg- trim er are identical or different; (4) on-(mAb-monoTLi A)-FcRn and on-(mAb-triTLi A)-FcRn are identical or different; (5) on- mAb-FcRn and kon-(mAb-monoTLi A)-FcRn are identical or different; (6) kon-mAb-FcRn and kon-(mAb-triTLl A)- FcRn are identical or different; (7) koff-(mAb-monoTLiA)-FcRn and koff-(mAb-triTLiA)-FcRn are identical or different; (8) koff- mAb-FcRn and koff-(mAb-monoTLiA)-FcRn are identical or different; (9) koff- mAb-FcRn and koff-(mAb-triTLl A)-FcRn are identical or different; (10) kdeg-(mAb-monoTLlA)-FcRn and kdeg-(mAb- triTLi A)-FcRn are identical or different; (11) kdeg-mAb-FcRn and kdeg-(mAb-triTLiA)-FcRn are identical or different; (12) kdeg-mAb-FcRn and kdeg-(mAb-monoTLiA)-FcRn are identical or different; or (13) any combination of (1) to (12).

[0042] In some embodiments of the dose determination methods, in the dose determination methods, wherein ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn -normal.

[0043] In some embodiments of the dose determination methods, the effective dose regimen comprises an induction regimen of the anti-TLIA antibody or antigen binding fragment. In some embodiments of the dose determination methods, the effective dose regimen comprises a maintenance regimen of the anti-TLIA antibody or antigen binding fragment. In some embodiments of the dose determination methods, the induction regimen and the maintenance regimen are identical. In some embodiments of the dose determination methods, the induction regimen and the maintenance regimen are different. In some embodiments of the dose determination methods, the maintenance regimen is administered after the induction regimen.

[0044] In some embodiments of the dose determination methods, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject during the induction regimen. In some embodiments of the dose determination methods, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen. In some embodiments of the dose determination methods, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject. In some embodiments of the dose determination methods, the induction regimen comprises a one-time administration of the anti-TLIA antibody or antigen bindingfragment. In some embodiments of the dose determination methods, the anti-TLIA 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 determination methods, the induction regimen comprises multiple administrations of the anti-TLIA antibody or antigen binding fragment. In some embodiments of the dose determination methods, the induction regimen comprises administrations of (i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10; (ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; (iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10; (iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or (v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

[0046] In some embodiments of the dose determination methods, 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 dose determination methods, the induction regimen comprises administration once every 2, 4, 6, or 8 weeks. In some embodiments of the dose determination methods, the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

[0047] In some embodiments of the dose determination methods, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject. In some embodiments of the dose determination methods, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject during the maintenance regimen. In some embodiments of the dose determination methods, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longerof start of the maintenance regimen.

[0048] In some embodiments of the dose determination methods, the maintenance regimen comprises multiple administrations of the anti-TLIA antibody or antigen binding fragment. In some embodiments of the dose determination methods, the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0049] In some embodiments of the dose determination methods, the maintenance regimen comprises administration of the anti-TLIA 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 determination methods, the maintenance regimen comprises administration of the anti-TLIA antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks. In some embodiments of the dose determination methods, the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at 250 mg / dose every 4 weeks. In some embodiments of the dose determination methods, the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at 100 mg / dose every 4 weeks. In some embodiments of the dose determination methods, 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 methods, the effective dose regimen maintains the concentration of TL1 A in diseased tissue in the subject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis for at least 4 weeks, 8 weeks, 12 weeks, 4 months, 5months, 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 methods, the step (a) further comprises receiving the rate of TL1 A trimerization (kon-TLiA-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TLIA-trimer-to-monomer).

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

[0053] In some embodiments, the anti-TLl A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6- 9; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10, an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15. In some cases, the anti-TLIA antibody comprises the CDRs of antibody J of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody J2 of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody K of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody M of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody N of Table 10.

[0054] In some embodiments, the anti-TLIA antibody comprises, a heavy chain variable framework region comprising a human IGHV1 -46*02 framework or a modified human IGHV1 -46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human IGHV 1 -46*02 framework and the human IGKV3-20 framework.

[0055] In some embodiments, the anti-TLIA antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 201-220. In some cases, the anti-TLIA antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 420, and alight chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 430. In some cases, the anti-TLIA antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 421, and a light chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 431. In some cases, the anti-TLIA antibody comprises a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 423, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 433. In some cases, the anti-TLIA antibody comprises a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 424, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434.

[0056] In some embodiments, the anti-TLIA antibody comprises a heavy chain variable region comprising SEQ ID NO: 301X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX1OX11IY[LCDR2]GIPDR FSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of XI -XI 1 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein HCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 1, HCDR2 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, HCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 6-9, LCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 10, LCDR2 comprises an amino acid sequence set forth by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 12 or 13. In some cases, the anti-TLIA antibody comprises the CDRs of antibody J of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody J2 of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody K of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody M of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody N of Table 10.

[0057] In some embodiments, the anti-TLIA antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by any one ofSEQ ID NOS: 401, 407, 413, or 450, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 402, 408, 414, or 451, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 403, 409, 415, or 452; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 404, 410, 416, or 453, an LCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 405, 411, 417, or 454, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 406, 412, 418, or 455.

[0058] In some embodiments, the anti-TLl A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 420-427, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 430-437.

[0059] Additional numbered embodiments are provided in the below paragraphs of this section.

[0060] Embodiment 1. An antibody or antigen binding fragment thereof that binds to tumor necrosis factor-like protein 1 A (anti-TLl A antibody or antigen binding fragment) for use in the treatment of inflammation in a subject in need thereof.

[0061] Embodiment 2. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 1, wherein the subject has inflammation in the kidney.

[0062] Embodiment 3. An antibody or antigen binding fragment thereof that binds to tumor necrosis factor-like protein 1 A (anti-TLl A antibody or antigen binding fragment) for use in the treatment of fibrosis in a subject in need thereof.

[0063] Embodiment 4. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 3, wherein the subject has fibrosis in the kidney.

[0064] Embodiment 5. An antibody or antigen binding fragment thereof that binds to tumor necrosis factor-like protein 1 A (anti-TLl A antibody or antigen binding fragment) for use in the treatment of a disease and / or condition of the kidney in a subject in need thereof.

[0065] Embodiment 6. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 1-5, wherein the subject has a chronic kidney disorder.

[0066] Embodiment 7. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 1-6, wherein the subject has end stage renal disease.

[0067] Embodiment 8. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 1-6, wherein the subject has tubulointerstitial renal fibrosis.

[0068] Embodiment 9. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 1-6, wherein the subject has nephritis.

[0069] Embodiment 10. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 1-6, wherein the subject has diabetic kidney disease.

[0070] Embodiment 11. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 1-6, wherein the subject has polycystic kidney disease.

[0071] Embodiment 12. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 1-6, wherein the subject has end-stage renal disease, tubulointerstitial renal fibrosis, glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, diabetic kidney diseases, lupus nephritis, Alport syndrome, or polycystic kidney disease, or a combination thereof.

[0072] Embodiment 13. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 1-12, wherein the anti-TLIA antibody or antigen binding fragment is administered in a pharmaceutical composition.

[0073] Embodiment 14. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 13, wherein the pharmaceutical composition comprises the anti-TLIA antibody or antigen binding fragment at a concentration greater than about 150 mg / mL.

[0074] Embodiment 15. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 14, wherein the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, or 250 mg / mL.

[0075] Embodiment 16. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 14, wherein the concentration is about 150 mg / mL to about 250 mg / mL.

[0076] Embodiment 17. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 14, wherein the concentration is about 175 mg / mL to about 225 mg / mL.

[0077] Embodiment 18. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 13-17, wherein the pharmaceutical composition is administered subcutaneously.

[0078] Embodiment 19. The anti-TLIA antibody or antigen-binding fragment for use of embodiment any one of embodiments 13-18, wherein about 150 mg to about 500 mg of the anti-TLIA antibody or antigen binding fragment is present in the composition.

[0079] Embodiment 20. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 13-19, wherein the composition has a total volume of less than or equal to about 2 mL.

[0080] Embodiment 21. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 13-20, wherein the pharmaceutical composition comprises a therapeutically effective dose of the anti-TLIA antibody or antigen binding fragment.

[0081] Embodiment 22. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-21, wherein the composition has a total volume less than or equal to about 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.

[0082] Embodiment 23. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-22, wherein the composition has a total volume of about 0.5 mL to about 1.5 mL.

[0083] Embodiment 24. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-23, wherein the composition has a viscosity of less than about 20 cP.

[0084] Embodiment 25. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 24, wherein the composition has a viscosity of less than about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or 5 cP.

[0085] Embodiment 26. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-25, wherein the composition has a viscosity of about 1 cP to about 20 cP.

[0086] Embodiment 27. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-26, wherein the pharmaceutical composition has a percentage aggregation of anti-TLIA antibody or antigen binding fragment as measured by size exclusion chromatography of less than about 5% of the total anti-TLIA antibody or antigen binding fragment in the composition.

[0087] Embodiment 28. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 27, wherein the aggregation is less than about 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5%.

[0088] Embodiment 29. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 13-27, wherein the composition comprises a surfactant.

[0089] Embodiment 30. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 29, wherein the surfactant comprises a nonionic surfactant.

[0090] Embodiment 31. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 30, wherein the nonionic surfactant comprises polysorbate-20.

[0091] Embodiment 32. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 29-31, wherein the surfactant is present at a concentration of about 0.005% to about 0.05% of the composition.

[0092] Embodiment 33. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 32, wherein the surfactant is present at a concentration of about 0.01% to about0.02% of the composition.

[0093] Embodiment 34. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 13-33, wherein the composition comprises a salt.

[0094] Embodiment 35. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 34, wherein the salt comprises sodium chloride, glycine, lysine-hydrochloride, arginine-hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof.

[0095] Embodiment 36. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 35, wherein the salt comprises sodium chloride.

[0096] Embodiment 37. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 35, wherein the salt comprises lysine-HCl.

[0097] Embodiment 38. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 34-37, wherein the salt is present at a concentration of about 10 mM to about 100 mM in the composition.

[0098] Embodiment 39. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 38, wherein the salt is present at a concentration of about 25 m in the composition.

[0099] Embodiment 40. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 38, wherein the salt is present at a concentration of about 40 mM in the composition.

[0100] Embodiment 41. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 13-40, wherein the composition comprises a stabilizer.

[0101] Embodiment 42. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 41, wherein the stabilizer comprises a sugar, polyol, amino acid, or polymer, cyclodextrin (e.g., HP-b-CD), or a combination thereof.

[0102] Embodiment 43. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 42, wherein the stabilizer comprises the sugar.

[0103] Embodiment 44. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 43, wherein the sugar comprises sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof.

[0104] Embodiment 45. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 44, wherein the sugar comprises sucrose.

[0105] Embodiment 46. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 41-45, wherein the stabilizer is present at a concentration of about50 mM to about 300 mM in the composition.

[0106] Embodiment 47. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 46, wherein the stabilizer is present at a concentration of about 200 mM to about 280 mM.

[0107] Embodiment 48. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 47, wherein the stabilizer is present at a concentration of about 220 to about 240 mM.

[0108] Embodiment 49. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-48, wherein the composition comprises a buffering agent.

[0109] Embodiment 50. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 49, wherein the buffering agent comprises acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, Tris (tris (hydroxymethyl) aminomethane), or diethanolamine, or a combination thereof.

[0110] Embodiment 51. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 50, wherein the buffering agent comprises acetate buffer.

[0111] Embodiment 52. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 49-51, wherein the buffering agent is present at a concentration of about 10 mM to about 50 mM in the composition.

[0112] Embodiment 53. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 52, wherein the composition comprises about 20 mM buffer.

[0113] Embodiment 54. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 13-53, wherein the composition has a pH of about 4.5 to about 8.0.

[0114] Embodiment 55. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 54, wherein the composition has a pH of about 4.5 to about 7.5.

[0115] Embodiment 56. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 55, wherein the composition has a pH of about 5 to about 5.5.

[0116] Embodiment 57. The anti-TLl A antibody or antigen-binding fragment for use of embodiment 56, wherein the composition has a pH of about 5.3.

[0117] Embodiment 58. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 1-57, wherein the anti-TLl A antibody or antigen binding fragment is administered to the subject at a first dose up to about 1000 mg.

[0118] Embodiment 59. The anti-TLl A antibody or antigen-binding fragment for use of any one of embodiments 1-57, wherein the anti-TLl A antibody or antigen binding fragment is administered to the subject at a first dose of about 150 mg to about 1000 mg.

[0119] Embodiment 60. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 59, wherein the first dose is about 500 mg to about 1000 mg.

[0120] Embodiment 61. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 60, wherein the first dose is about 500 mg or about 800 mg.

[0121] Embodiment 62. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 58-61, wherein the first dose is administered to the subject at a first time point, and a second dose is administered to the subject at a second time point.

[0122] Embodiment 63. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 62, wherein the second time point is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days after the first time point.

[0123] Embodiment 64. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 62, wherein the second time point is about 1, 2, 3, or 4 weeks after the first time point.

[0124] Embodiment 65. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 62-64, wherein the second dose comprises up to about 1000 mg anti-TLIA antibody or antigen binding fragment.

[0125] Embodiment 66. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 62-64, wherein the second dose comprises about 150 mg to about 1000 mg.

[0126] Embodiment 67. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 66, wherein the second dose comprises about 150 mg to about 600 mg.

[0127] Embodiment 68. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 62-67, wherein a third dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a third time point.

[0128] Embodiment 69. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 68, wherein 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.

[0129] Embodiment 70. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 68, wherein the third time point is about 1, 2, 3, or 4 weeks after the second time point.

[0130] Embodiment 71. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 68-70, wherein the third dose comprises up to about 1000 mg anti-TL1 A antibody or antigen binding fragment.

[0131] Embodiment 72. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 68-70, wherein the third dose comprises about 150 mg to about 1000 mg.

[0132] Embodiment 73. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 72, wherein the third dose comprises about 150 mg to about 600 mg.

[0133] Embodiment 74. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 68-73, wherein a fourth dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a fourth time point.

[0134] Embodiment 75. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 74, wherein 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.

[0135] Embodiment 76. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 74, wherein the fourth time point is about 1, 2, 3, or 4 weeks after the third time point.

[0136] Embodiment 77. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 74-76, wherein the fourth dose comprises up to about 1000 mg anti- TLIA antibody or antigen binding fragment.

[0137] Embodiment 78. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 74-76, wherein the fourth dose comprises about 150 mg to about 1000 mg.

[0138] Embodiment 79. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 78, wherein the fourth dose comprises about 150 mg to about 600 mg.

[0139] Embodiment 80. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 74-79, wherein a fifth dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a fifth time point.

[0140] Embodiment 81. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 80, wherein 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.

[0141] Embodiment 82. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 80, wherein the fifth time point is about 1, 2, 3, or 4 weeks after the fourth time point.

[0142] Embodiment 83. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 80-82, wherein the fifth dose comprises up to about 1000 mg anti- TLIA antibody or antigen binding fragment.

[0143] Embodiment 84. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 80-82, wherein the fifth dose comprises about 150 mg to about 1000 mg.

[0144] Embodiment 85. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 84, wherein the fifth dose comprises about 150 mg to about 600 mg.

[0145] Embodiment 86. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 80-85, wherein a sixth dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a sixth time point.

[0146] Embodiment 87. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 86, wherein 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.

[0147] Embodiment 88. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 86, wherein the sixth time point is about 1, 2, 3, or 4 weeks after the fifth time point.

[0148] Embodiment 89. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 86-88, wherein the sixth dose comprises up to about 1000 mg anti- TLIA antibody or antigen binding fragment.

[0149] Embodiment 90. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 86-88, wherein the sixth dose comprises about 150 mg to about 1000 mg.

[0150] Embodiment 91. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 90, wherein the sixth dose comprises about 150 mg to about 600 mg.

[0151] Embodiment 92. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 58-91, wherein an additional dose of the anti-TLIA antibody or antigen binding fragment is administered to the subject at each of the one or more additional time points.

[0152] Embodiment 93. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 92, wherein the one or more additional time points comprises 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.

[0153] Embodiment 94. The anti-TLIA antibody or antigen-binding fragment for use ofembodiment 92, wherein the composition is administered to the subject at about 12 additional time points.

[0154] Embodiment 95. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 92-94, wherein 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 a previous time point.

[0155] Embodiment 96. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 92-94, wherein each additional time point is independently about 1, 2, 3, or 4 weeks after a previous time point.

[0156] Embodiment 97. The anti-TLIA antibody or antigen-binding fragment for use of embodiment 96, wherein at least one of the additional time points is about 2 weeks after the previous time point.

[0157] Embodiment 98. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 92-97, wherein the additional dose comprises up to about 1000 mg anti-TLIA antibody or antigen binding fragment.

[0158] Embodiment 99. The anti-TLIA antibody or antigen-binding fragment for use of any one of embodiments 92-97, wherein the additional dose comprises from about 150 mg to about 1000 mg anti-TLIA antibody or antigen binding fragment.

[0159] Embodiment 100. The anti-TLIA antibody or antigen-binding fragment foruse of embodiment 99, wherein the additional dose is about 175 mg to about 300 mg anti-TLIA antibody or antigen binding fragment.

[0160] Embodiment 101. An anti-TLIA antibody or antigen binding fragment for use in neutralizing monomeric ILIA and trimeric ILIA in a subject having kidney inflammation and / or kidney fibrosis, wherein the anti-TLIA antibody or antigen binding fragment is formulated in an effective dose for administration to the subject, wherein the antibody or antigen binding fragment binds to both monomeric TL1 A and trimeric TL1A, wherein the antibody or antigen binding fragment blocks interaction of TL1 A to DR3, wherein the concentration of TL1 A in a diseased tissue in the subject is reduced below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, and wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron,renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0161] Embodiment 102. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 101, wherein the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease.

[0162] Embodiment 103. The anti-TLIA antibody or antigen-binding fragment foruse of embodiment 101 or 102, wherein the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

[0163] Embodiment 104. An anti-TLIA antibody or antigen binding fragment for use in reducing the concentration of TL1 A in a diseased tissue in a subject with kidney inflammation and / or kidney fibrosis, wherein the anti-TLIA antibody or antigen binding fragment is formulated in an effective dose for administration to the subject to reduce the concentration of TL1 A in the diseased tissue in the subject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0164] Embodiment 105. An anti-TLIA antibody or antigen binding fragment for use in the treatment of kidney inflammation and / or kidney fibrosis in a subject in need thereof, wherein the anti-TLIA antibody or antigen binding fragment is administered at an effective dose such that the concentration of TL1 A in a diseased tissue in the subject after the administration is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, and wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0165] Embodiment 106. An anti-TLl A antibody or antigen binding fragment for use in the treatment of kidney inflammation and / or kidney fibrosis in a subject in need thereof, wherein the anti-TLl A antibody or antigen binding fragment is administered in a method comprising:(a) administering an anti-TLl A antibody or antigen binding fragment to the subject at an effective dose, and(b) reducing the concentration of ILIA in a diseased tissue in the subject below the concentration of ILIA in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

[0166] Embodiment 107. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 101 to 106, wherein the effective dose comprises an induction regimen.

[0167] Embodiment 108. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 101 to 107, wherein anti-TLl A antibody or antigen -binding fragment is also for use in the maintenance of ILIA in the diseased tissue in the subject at a concentration below the concentration of ILIA in the corresponding tissue in the control subject.

[0168] Embodiment 109. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 108, wherein the ILIA in the diseased tissue in the subject is maintained with a maintenance regimen of the anti-TLl A antibody or antigen binding fragment.

[0169] Embodiment 110. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 109, wherein the induction regimen and the maintenance regimen are identical.

[0170] Embodiment 111. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 109, wherein the induction regimen and the maintenance regimen are different.

[0171] Embodiment 112. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 111, wherein the maintenance regimen is administered after the induction regimen.

[0172] Embodiment 113. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 102 to 112, wherein the diseased tissue in the subject produces up to50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject during the induction regimen.

[0173] Embodiment 114. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 102 to 112, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

[0174] Embodiment 115. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 102 to 112, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject.

[0175] Embodiment 116. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 107 to 115, wherein the induction regimen comprises a one-time administration of the anti-TLl A antibody or antigen binding fragment.

[0176] Embodiment 117. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 116, wherein the anti-TLl A 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.

[0177] Embodiment 118. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 107 to 115, wherein the induction regimen comprises multiple administrations of the anti-TLl A antibody or antigen binding fragment.

[0178] Embodiment 119. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 107 to 115 and 118, wherein the induction regimen comprises administrations of(i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10;(ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10;(iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10;(iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or(v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

[0179] Embodiment 120. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 107 to 115 and 118, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

[0180] Embodiment 121. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 107 to 115, 118, and 120, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

[0181] Embodiment 122. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 107 to 115, 118, and 120, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

[0182] Embodiment 123. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 108 to 122, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject.

[0183] Embodiment 124. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 108 to 119, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject during the maintenance regimen.

[0184] Embodiment 125. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 108 to 119, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

[0185] Embodiment 126. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 109 to 125, wherein the maintenance regimen comprises multiple administrations of the anti-TLIA antibody or antigen binding fragment.

[0186] Embodiment 127. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 109 to 126, wherein the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at(i) 500 mg / dose every 2 weeks,(ii) 400 mg / dose every 2 weeks,(iii) 300 mg / dose every 2 weeks,(iv) 250 mg / dose every 2 weeks,(v) 200 mg / dose every 2 weeks,(vi) 150 mg / dose every 2 weeks,(vii) 100 mg / dose every 2 weeks,(viii) 50 mg / dose every 2 weeks,(ix) 500 mg / dose every 4 weeks,(x) 400 mg / dose every 4 weeks,(xi) 300 mg / dose every 4 weeks,(xii) 250 mg / dose every 4 weeks,(xiii) 200 mg / dose every 4 weeks,(xiv) 150 mg / dose every 4 weeks,(xv) 100 mg / dose every 4 weeks,(xvi) 50 mg / dose every 4 weeks,(xvii) 500 mg / dose every 6 weeks,(xviii) 400 mg / dose every 6 weeks,(xix) 300 mg / dose every 6 weeks,(xx) 250 mg / dose every 6 weeks,(xxi) 200 mg / dose every 6 weeks,(xxii) 150 mg / dose every 6 weeks,(xxiii) 100 mg / dose every 6 weeks,(xxiv) 50 mg / dose every 6 weeks,(xxv) 500 mg / dose every 8 weeks,(xxvi) 400 mg / dose every 8 weeks,(xxvii) 300 mg / dose every 8 weeks,(xxviii) 250 mg / dose every 8 weeks,(xxix) 200 mg / dose every 8 weeks,(xxx) 150 mg / dose every 8 weeks,(xxxi) 100 mg / dose every 8 weeks, or(xxxii) 50 mg / dose every 8 weeks.

[0187] Embodiment 128. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 126, wherein the maintenance regimen comprises administration of the anti-TLl A 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.

[0188] Embodiment 129. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 126 and 128, wherein the maintenance regimen comprises administration of the anti-TLl A antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

[0189] Embodiment 130. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 129, wherein the maintenance regimen comprises administrations of the anti-TLl A antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

[0190] Embodiment 131. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 129, wherein the maintenance regimen comprises administrations of the anti-TLl A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

[0191] Embodiment 132. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 131, wherein the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

[0192] Embodiment 133. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 104 to 132, wherein the antibody or antigen binding fragment binds to both monomeric ILIA and trimeric ILIA and wherein the antibody or antigen binding fragment blocks binding of ILIA to DR3.

[0193] Embodiment 134. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 101 to 133, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric ILIA in the blood of the subject is occupied by the anti-TLIA antibody or antigen binding fragment.

[0194] Embodiment 135. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 101 to 134, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1 A in the blood of the subject is occupied by the anti-TLIA antibody or antigen binding fragment.

[0195] Embodiment 136. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 101 to 135, wherein binding affinity of the antibody or antigen binding fragment to monomeric ILIA as measured by dissociation equilibrium constant (KD- monomer ) is comparable to binding affinity of the antibody or antigen binding fragment totrimeric TL1A as measured by dissociation equilibrium constant (Ko-trimer).

[0196] Embodiment 137. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 136, wherein the KD -monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD -trim er.

[0197] Embodiment 138. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 136 or 137, wherein the KD -monomer is no more than 0.06 nM.

[0198] Embodiment 139. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 136 to 138, wherein the Ko-trimer is no more than 0.06 nM.

[0199] Embodiment 140. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 103 to 139, wherein the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease.

[0200] Embodiment 141. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 102 to 140, wherein the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

[0201] Embodiment 142. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 101 to 141, wherein the effective dose or the induction regimen is determined by a dose determination method, wherein the dose determination method comprises:(i) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue;(ii) integrating the parameters received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and(iii) determining the effective dose or the induction regimen such that the concentration of TL1 A in diseased tissue in the subject after step (a) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis.

[0202] Embodiment 143. The anti-TLIA antibody or antigen-binding fragment foruse of embodiment 142, wherein the parameter of TL1 A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold over-production comparing to TL1 A production in the normalreference tissue.

[0203] Embodiment 144. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 109 to 143, wherein the maintenance regimen is determined by a dose determination method, wherein the dose determination method comprises:(i) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue;(ii) integrating the parameter received in (i) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and(iii) determining the maintenance regimen such that the concentration of TL1 A in diseased tissue in the subject after step (c) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis.

[0204] Embodiment 145. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 144, wherein the parameter of TL1 A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more fold over-production comparing to TL1A production in the normal reference tissue.

[0205] Embodiment 146. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 142 to 145, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to TL1 A (kon-mAb), dissociation rate of the antibody from TL1 A (koff-mAb), synthesis rate of TL1 A in normal tissue (kSyn-normai), synthesis rate of TL1 A in diseased tissue (ksyn-disease), and / or degradation rate of TL1 A (kdeg- total-TLlA).

[0206] Embodiment 147. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment to 146, wherein the association rate of the antibody to TL1 A (kon-mAb) comprises the association rate of the antibody to monomeric ILIA (k on-monomer ) and association rate of the antibody to trimeric TL1 A (kon-trimer), wherein the dissociation rate of the antibody from TL1 A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1 A (koff- monomer) and dissociation rate of the antibody from trimeric TL1A (koff-trimer), and / or wherein the degradation rate of TL1 A (kdeg-totai-TLiA) comprises degradation rate of monomeric TL1 A (kdeg-TLIA -monomer ) and degradation rate of trimeric ILIA (kdeg-TLiA-trimer).

[0207] Embodiment 148. The anti-TLl A antibody or antigen-binding fragment foruse of any one of embodiments 142 to 147, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody-TL1 A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn), and / or dissociation rate of the antibody- TL1 A complex from FcRn (koff-(mAb-TLiA)-FcRn).

[0208] Embodiment 149. The anti-TLl A antibody or antigen-binding fragment foruse of embodiment 148, wherein the association rate of the antibody- TL1 A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn) comprises association rate of the antibody-monomeric-TLIA complex to FcRn receptor (kon-(mAb-monoTLiA)-FcRn) and association rate of the antibody- trimeric-TLlA complex to FcRn receptor (kon-(mAb-triTLiA)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TLiA)-FcRn) comprises dissociation rate of the antibody-monomeric-TLIA complex from FcRn (koff-(mAb-monoTLiA)- FcRn) and dissociation rate of the antibody-trimeric-TLl A complex from FcRn (koff-(mAb- triTLl A)-FcRn).

[0209] Embodiment 150. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 142 to 149, wherein the step (i) in the dose determination method further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb- FcRn).

[0210] Embodiment 151. The anti-TLIA antibody or antigen-binding fragment foruse of embodiment 150, wherein the clearance rate of FcRn receptor bound by the antibody (kdeg- mAb-FcRn) comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric- TLIA complex (kdeg-(mAb-monoTLiA)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TLl A complex (kdeg-(mAb-triTLiA)-FcRn).

[0211] Embodiment 152. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 146 to 151, wherein in the dose determination method:(1) kon-monomer and kon-trimer are identical or different;(2) koff- monomer and koff-trimer are identical or different;(3) kdeg -monomer and kdeg-trimer are identical or different;(4) kon-(mAb-monoTLlA)-FcRn and kon-(mAb-triTLi A)-FcRn are identical or different;(5) kon-mAb-FcRn and kon-(mAb-monoTLi A)-FcRn are identical or different;(6) kon-mAb-FcRn and kon-(mAb-triTLi A)-FcRn are identical or different;(7) koff-(mAb-monoTLiA)-FcRn and koff-(mAb-triTLiA)-FcRn are identical or different;(8) koff- mAb-FcRn and koff-(mAb-monoTLi A)-FcRn are identical or different;(9) koff- mAb-FcRn and k0ff-(mAb-triTLiA)-FcRn are identical or different;(10) kdeg-(mAb-monoTLi A)-FcRn and kdeg-(mAb-triTLi A)-FcRn are identical or different;(11) kdeg-mAb-FcRn and kdeg-(mAb-triTLi A)-FcRn are identical or different;(12) kdeg-mAb-FcRn and kdeg-(mAb-monoTLi A)-FcRn are identical or different;(13) any combination of (1) to (12).

[0212] Embodiment 153. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 142 to 152, wherein in the dose determination method: ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn-normai.

[0213] Embodiment 154. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 142 to 153, wherein step (i) in the dose determination method further comprises receiving rate of TL1 A trimerization (kon-TLiA-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TLIA-trimer-to-monomer).

[0214] Embodiment 155. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 102 to 154, wherein the concentration of TL1 A is the concentration of free ILIA.

[0215] Embodiment 156. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 1 to 155, wherein the anti-TLIA antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10, an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15.

[0216] Embodiment 157. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 1 to 156, wherein the anti-TLIA antibody comprises, a heavy chain variable framework region comprising a human IGHV1 -46*02 framework or a modified human IGHV1 -46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human IGHV1 -46*02 framework and the human IGKV3-20 framework.

[0217] Embodiment 158. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 1 to 157, wherein the anti-TLIA antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 201-220.

[0218] Embodiment 159. The anti-TLIA antibody or antigen-binding fragment foruse of any one of embodiments 1 to 158, wherein the anti-TLIA antibody comprises a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS, and a light chain variable region comprising SEQ ID NO: 303El VLTQ SPGTL SL SPGERATL SC [LCDR 1 ] W YQQKPGQ APRX 1 OX 111 Y[LCDR2]GIPDR FSGSGSGTDFTLHSRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of XI -XI 1 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein HCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 1, HCDR2 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, HCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 6-9, LCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 10, LCDR2 comprises an amino acid sequence set forth by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 12 or 13.3. BRIEF DESCRIPTION OF THE FIGURES

[0219] 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.

[0220] Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.

[0221] FIGS. 1A-1C show chromatograms for analytical size exclusion chromatography of anti-TLIA antibodies. The large peaks (main peak) correspond to monomeric fraction. The percentage of monomeric sample is indicated for each antibody. FIG. 1A shows chromatographs for antibodies A193, A194, and A195. FIG. IB shows chromatographs for antibodies A196, A197, and A198. FIG. 1C shows chromatographs for antibodies A199, A200, and A201.

[0222] FIG. 2 depicts inhibition of interferon gamma in human blood with anti-TLIA antibodies.

[0223] FIG. 3A depicts the comparison between the predicted and measured viscosity. FIGS. 3B-3D depict a PLS model demonstrating effect of pH and protein concentration onviscosity. FIG. 3B shows a PLS graph (x-axis is pH, y-axis is protein concentration (mg / ml), z-axis is viscosity (mPa-s) for the PLS graphs), FIG. 3C shows a model of the predicted viscosity (y-axis, mPa-s) versus anti-TLIA antibody concentration (x-axis) in mg / mL, and FIG. 3D shows a model of the estimated viscosity (y-axis, mPa-s) versus actual viscosity (x- axis, mPa-s). FIG. 3E depicts the effects of pH versus acetate concentration on viscosity. FIG. 3F shows the effect of sucrose versus NaCl on viscosity. FIG. 3G depicts the effect of Arg-HCl versus Lys-HCl on viscosity. Viscosity units are in mPa-s. The arrow points to the region of highest viscosity. The star corresponds to the region of lowest viscosity.

[0224] FIG. 4A depicts the PLS 1 model for the effect on high molecular weight (HMW) aggregates. FIG. 4B depicts the effect of pH versus acetate on aggregation. FIG. 4C depicts the effect of sucrose versus NaCl concentration. FIG. 4D depicts the effect of Arg-HCl versus Lys-HCl on aggregation. FIG. 4E depicts the effect of sucrose concentration versus Lys-HCl concentration.

[0225] FIG. 5A depicts the predicted versus measured loss of main peak at 2 weeks and 25°C. FIG. 5B depicts the effect of pH and protein concentration on the loss of main peak in the CEX profile. FIG. 5C depicts the effect of pH and acetate concentration on the loss of main peak in the CEX profile. FIG. 5D depicts the effect of sucrose and NaCl concentration on the loss of main peak in the CEX profile. FIG. 5E depicts the effect of Lys-HCl and sucrose concentration on the loss of main peak in the CEX profile.

[0226] FIG. 6A depicts the loss of monomer by SEC with agitation. FIG. 6B depicts the loss of monomer by SEC with freeze-thaw.

[0227] FIG. 7A depicts the binding of an anti-TLIA antibody to cynomolgus and human TL1 A, but not to mouse or rat ILIA. ELISA for each protein was performed at least three times. The data from a representative experiment are shown and are mean ± SD.Abbreviations: A=absorbance, Ab=antibody, Cyno=cynomolgus, nm=nanometer, nM=nanomolar. FIG. 7B depicts mean levels of sTLIA increased with increasing IV doses of anti-TLIA to cynomolgus monkeys, as measured in an ELISA. Samples were assayed in triplicate, on two separate occasions. Data presented are the mean ILIA concentrations of three animals per group ± SD. Samples collected from animals administered isotype control antibody are shown in circles, samples collected from animals administered anti-TLIA are shown in the triangles and square. Abbreviations: hr=hour, kg=kilogram, mg=milligram, mL=milliliter, ng=nanogram; IL lA=tumor necrosis factor-like cytokine 1A.

[0228] FIG. 8 demonstrates that TL1 A drives inflammation and fibrosis through binding to DR3.

[0229] FIGS. 9A-9C demonstrates size-exclusion chromatography (SEC) profiles of recombinant human TL1 A (rhTLl A). Briefly, rhTLl A was labeled with Alexa fluor 488 (AF488) and spiked into normal human serum (NHS). In FIG. 9A, when injected alone, rhTLl A SEC profile shows two peaks on SEC, representing trimeric and monomeric forms of TL1A. In FIG. 9B, when rhTLIA is pre-incubated with a control reference antibody, the trimeric peak was shifted leftward, indicating a larger complex formation of the reference antibody and trimeric rhTLIA. There was no shift in the monomeric peak, indicating that the reference antibody only binds to the trimeric rhTLIA. In FIG. 9C, when rhTLIA is preincubated with A219, both the trimeric and the monomeric rhTLIA peaks were shifted, thus indicating that A219 binds both trimeric and monomeric forms of TL1 A.

[0230] FIG. 10A depicts a whole-body physiologically based pharmacokinetic (PBPK) model. FIG. 10B depicts a tissue-level diagram of the integrated whole-body PBPK model used to characterize the PK of the monoclonal antibody (mAb), ligand, and complex between mAb and ligand.

[0231] FIG. 11A depicts the comparison of the pharmacokinetics of the mAb as predicted by the integrated whole-body PBPK (solid curve) with the pharmacokinetics of the mAb as observed in normal healthy volunteers (various points with points from the same subject shown by the same format), in each case after injection of A219 at the indicated dose. FIG. 11B depicts the comparison of the TL1 A concentration as predicted by the integrated whole-body PBPK with the TL1 A concentration as observed in normal healthy volunteers, in each case after injection of A219 at the indicated dose.

[0232] FIG. 12A depicts the observed concentration of TL1 A in serum after injecting (i) an anti-TLl A antibody A219 that binds to both TL1 A monomer and trimer (shown in red, top of the 2 curves, and the observed data points accompanying such curve) and (ii) a control reference anti-TLIA antibody that binds to only TL1A trimer (shown in blue, bottom of the 2 curves, and the observed data points accompanying such curve). In FIG. 12A, solid curves depict the prediction from the model and various dots depict the observations from subjects injected with the indicated antibodies. FIG. 12B depicts the predicted total TL1 A concentration (monomer and trimer, solid curve and the observed data points accompanying such curve), the monomer TL1 A concentration (fine dotted line), and the trimer TL1 A concentration (coarse dotted line), in each case at the basal level (no injection of any anti- TLIA antibodies). FIG. 12C depicts the serum TL1 A concentration in normal healthy volunteers (NHV) and UC patients, as predicted by the whole-body PBPK model (solid lines, upper line for UC patient and lower line for NHV) and as observed (various points).

[0233] FIGS. 13A-13B demonstrate the fitness of the model. FIG. 13A depicts the observed concentration of TL1 A in serum of NHVs after injecting an anti-TLl A antibody that binds to only TL1 A trimer (dots) and the prediction of the model (solid curve) that fits the observations at the indicated dose. Q2WX3= every 2 weeks for three times. FIG. 13B depicts the observed concentration of TL1A in serum of UC patients after injecting an anti- TLl A antibody that binds to only ILIA trimer (dots) and the prediction of the model (solid curve) that fits the observations at the indicated dose. Q2WX7= every 2 weeks for seven times. FIG. 13C depicts the concentration of TL1 A in intestine of NHV (black, solid, lower line of the two lines as predicted from the model and the observed data points accompanying such line) and the concentration of TL1A in the intestine of UC patient (red, solid, upper line of the two lines).

[0234] FIGS. 14A-14B depict the baseline concentration of TL1 A based on various parameters of ILIA production in intestine (14A) and in serum (14B). In FIGS. 14A-14B, l x would be the baseline in NHV; 25x, 50x, 75x, and 100x indicate various parameters of TL1A over-production in intestine.

[0235] FIGS 15A-15V depict the concentration of free soluble ILIA in tissue as determined by the whole-body PBPK model according to various parameters of ILIA overproduction under various dose regimen of anti-TLl A antibody A219 as indicated. FIG. 15W depicts the free soluble ILIA in tissue as determined by the whole-body PBPK model according to various parameters of ILIA overproduction under the dose regimen of a reference anti-TLl A antibody as indicated. FIGS. 15X-15Z depict the comparison of the modeled free soluble ILIA concentration in subjects treated with a reference anti-TLl A antibody (red, the upper curve of the two curves) or A219 (green, the lower curve of the two curves). In FIG. 15W-15Z, reference antibody light chain sequence is SEQ ID NO: 382, heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses a rapid equilibrium between the monomeric and trimeric form of ILIA with a continuous 60:40 ratio of monomer and trimer as observed. The black solid lines in FIGS. 15A-15Z indicate the TL1A concentration in the tissue of NHV. Q2W=every 2 weeks. Q4W=every 4 weeks. SC=subcutaneous. LD=loading dose (the first dose). 4W=week 4. Dl=day 1. W 2, 6, 10=week 2, week 6, and week 10. W 2, 4, 6, 10=week 2, week 4, week 6, and week 10. EOW=every other week. W 4, 8, 12=week 4, week 8, and week 12. W 2, 4, 8, 12=week 2, week 4, week 8, and week 12. sTLl A=soluble ILIA.

[0236] FIGS 16A-16H depict the goodness of fit plots for A219 with the population PK model.

[0237] FIG. 17A depicts the visual predictive check for the A219 concentration predicted from the popPK model against the observed A219 concentration. FIG. 17B depicts an induction dose selected in the popPK model to rapidly achieve steady state concentration.

[0238] FIG. 18 depicts osmotic pressures at 5 °C measured for the stability of A219 samples of various formulations at TO, 3 and 6 months.

[0239] FIG. 19 depicts A219 protein concentration at 5 °C measured for evaluating the stability of A219 samples of various formulations at TO, 3 and 6 months.

[0240] FIG. 20 depicts pH at 5 °C measured for the evaluating the stability A219 samples of various formulations at TO, 3 and 6 months.

[0241] FIG. 21A depicts viscosity data for TO and 3M for Formulations 1 to 5 at 25°C; FIG. 21B depicts viscosity data for TO and 3M for Formulations 6 to 8 at 25°C.

[0242] FIG. 22A depicts monomer contents for formulations at 5 °C as measured by SEC; FIG. 22B depicts loss of monomer (main peak) per month for the formulations at 5 °C as determined by SEC; FIG. 22C depicts monomer contents for formulations at 25 °C as measured by SEC; FIG. 22D depicts loss of monomer (main peak) per month for the formulations at 5 °C as determined by SEC.

[0243] FIG. 23A depicts the relative area (%) of the main peak for formulations at 5 °C as characterized by cation exchange chromatography; FIG. 23B depicts the loss of main peak (Rel. Area (%) per month) for the formulations at 5 °C as determined by cation exchange chromatography; FIG. 23C depicts the relative area (%) of the main peak for formulations at 25°C as characterized by cation exchange chromatography; FIG. 23D depicts the loss of main peak (Rel. Area (%) per month) for the formulations at 25 °C as determined by cation exchange chromatography.

[0244] FIG. 24A depicts predicted vs. measured values according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25 °C as the endpoint; FIG.24B depicts effect of pH and protein according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25 °C as the endpoint. In FIG. 24B, the sucrose concentration was fixed at 200 mM. FIG. 24C depicts effect of pH and acetate according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25 °C as the endpoint. In FIG. 24C, the sucrose concentration was fixed at 200 mM. FIG. 24D depicts effect of sucrose and lysine according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25 °C as the endpoint. In FIG. 24D, the protein concentration was fixed at 150 mg / mL, pH at 5.5 and acetate at 20 mM. FIG. 24E depicts effect of glycineand NaCl according to the PLS model using monomer loss by SEC for samples stored for 2 months at 25°C as the endpoint. In FIG. 24E, the protein concentration was fixed at 150 mg / mL, pH at 5.5 and acetate at 20 mM.

[0245] In FIGs. 18, 19, 20, 21A-21B, 22A-22D, 23A-23D, and 24A-24E, the formulations 1-8 (F01-F08, Form. 1-8, or simply 1-8) referenced therein are the formulations 1-8 as described in Table 31 of Example 24.

[0246] FIG. 25A shows geometric mean serum A219 concentration -time profiles following single doses of A219 administered as IV infusion (Linear Scale) (SAD study). FIG. 25B shows geometric mean serum A219 concentration-time profiles following multiple doses of A219 Q2W administered as IV infusion - day 29 (linear scale) (MAD study). Q2W=every 2 weeks.

[0247] FIG. 26A shows geometric mean serum sTLIA concentration versus nominal time following single dose of A219 administered as IV Infusion (semi-log scale) (SAD study). FIG. 26B geometric mean serum sTLIA concentration versus nominal time following multiple doses of A219 Q2W administered as IV infusion (semi -log scale) (MAD study).

[0248] FIG. 27A shows total A219 concentration in the central compartment (in circulation) in SAD as predicted by the model (curves) and as determined in the phase I trial (dots). FIG. 27B shows total soluble ILIA in the central compartment (circulation) in SAD as predicted by the model (curves) and as determined in the phase I trial. FIG. 27C shows total A219 concentration in the central compartment (in circulation) in MAD as predicted by the model (curves) and as determined in the phase I trial (dots). FIG. 27D shows total soluble ILIA in the central compartment (circulation) in MAD as predicted by the model (curves) and as determined in the phase I trial (dots). The predicted curves fitted with the measured data points. FIGS. 27E-27K show model prediction for and the data of a control reference antibody that binds only to ILIA trimer (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) with regard to (1) phase I single ascending dose data (FIGS. 27E and 27F), (2) phase I multiple ascending dose data (FIGS. 27G and 27H), and (3) phase II data on PK & total sTLIA levels (FIGS. 271 and 27 J). The IBD specific parameters were then calibrated to capture free tissue TL1 A levels in the gut (FIG. 27K) as observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383). NR=non -respond er and R=responder.

[0249] FIG. 28A shows doses of A219 determined from the validated model that canbring the free TL1A concentration in the patient’s diseased tissue to below the TL1A concentration of a healthy subject. FIG. 28B shows the percent reduction of the free TL1 A in the diseased tissue after administering doses of A219 as determined from the model. IV_4*= 1000 mg loading dose, 3 x 500 mg on days 14, 42, 70. SC dosing 240 mg Q1W or Q2W. FIG. 28C shows that, in a head-to-head comparison in the validated model, anti- TL1A antibodies that bind to both TL1A monomer and trimer engaged more (3.5 fold more) TL1A in circulation than anti-TLIA antibodies that only bind to TL1A trimer. FIG. 28D shows that, in a head-to-head comparison in the validated model, anti-TLIA antibodies that bind to both I IA monomer and trimer also resulted in higher percentage of I IA reduction of ILIA in diseased tissue (about 100%) when compared to anti-TLIA antibodies that only bind to ILIA trimer.

[0250] FIG. 29A shows the diagram of a popPK model. FIG. 29B shows the comparison of the A219 concentration predicted from the popPK model and the A219 concentration observed in the population of subjects in phase I clinical trial via a linear regression plot. FIG. 29C shows the comparison of the ILIA concentration predicted from the popPK model and the ILIA concentration observed in the population of subjects in phase I clinical trial via a linear regression plot. FIG. 29D shows the comparison of the A219 concentration predicted from the popPK model and the A219 concentration observed in the population of subjects in phase I clinical trial via a time series plot. FIG. 29E shows the comparison of the ILIA concentration predicted from the popPK model and the ILIA concentration observed in the population of subjects in phase I clinical trial via a time series plot.

[0251] FIGS. 30A-30H show the A219 and ILIA engagement (ILIA concentration in serum) predicted from the validated popPK model under various A219 doses. FIGS. 30A and 30B show A219 concentration (30 A) and ILIA concentration (30B) in circulation with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 500 mg Q2W from week 12 to week 52 (20 doses). FIGS. 30C and 30D show A219 concentration (30C) and ILIA concentration (30D) in circulation with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 500 mg Q4W from week 12 to week 52 (10 doses). FIGS. 30E and 30F show A219 concentration (30E) and TL1 A concentration (30F) in circulation with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 and extension with 100 mg Q2W from week 12 to week 52 (20 doses). FIGS. 30G and 30H show A219 concentration (30G) and ILIA concentration (30H) with a dosing regimen of induction with 500 mg Q2W (6 doses) up to week 10 andextension with 250 mg Q4W from week 12 to week 52 (10 doses).

[0252] FIGs. 31A-31D show in-situ hybridization for TNFSF 15 mRNA and TNFRSF25 mRNA in sections of kidney tissues from normal healthy volunteers (FIGs. 31A and 31B) and lupus nephritis (LN) patients (FIGs. 31C and 31D). Glomeruli of normal healthy kidney shows a non-diseased pathology (FIG. 31A). Surrounding the normal glomeruli (FIG. 31B) is a modest expression of TL1 A (lighter grey arrows in FIG. 31B) and DR3 (darker black arrows in FIG. 31B) Glomeruli from a LN donor (FIG. 31C) shows a necrotic pathology demonstrated by significate atrophy of the glomeruli core (indicating glomerulosclerosis). Clustered around the necrotic glomeruli (FIG. 31D) are increased positive cells for both TLA1 and DR3 expression, indicating that increased expression is associated with severe nephritic pathology. FIGs. 31A-31D show representative image of healthy control kidney (n=4) and LN kidney (n=4). FIG. 31B shows the enlarged view of the boxed areas of FIG. 31A and FIG. 31D shows the enlarged view of the boxed areas of FIG. 31C.4. DESCRIPTION OF THE INVENTION

[0253] ILIA is a cytokine that is secreted by antigen-presenting cells, T cells, and endothelial cells. ILIA signals through death receptor 3 (DR3), a TNF -family receptor that is found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphoid cells (ILC), fibroblasts, and epithelial cells and potently drives Thl, Th2, Th9 and Thl7 responses. In addition, it is induced in antigen-presenting cells by toll like receptor (TLR) ligands and FcR cross-linking and in T cells by T cell receptor (TCR) stimulation. FIG. 8 demonstrates how ILIA binding toDR3 independently drives inflammation and fibrosis. ILIA binding to DR3 on innate and T cells leads to an early cytokine response (release of IL-23, IL-ip, IL-17, IL- 22, TNF-a, IFN-y, IL-13) that sets the stage for inflammation, and stimulates innate and adaptive immune response. For instance, through binding to DR3, ILIA potentially drives inflammatory Thl and Th 17 responses. Further, binding of ILIA to DR3 on fibroblasts directly activates fibroblasts, and leads to collagen disposition and fibrosis independent of inflammation. While levels of circulating ILIA are low in healthy subjects, they are elevated in patients suffering from many auto-immune diseases, and ILIA has been shown to be upregulated in mucosa and serum of patients with IBD. In mice, chronic ILIA expression causes structuring disease caused by increased collagen deposition. In dextran sodium sulfate (DSS) and adoptive transfer mouse models, when challenged with DSS, ILIA transgenic mice develop more severe colitis than wild-type animals, and antibodies against ILIA led toreduced inflammation, lowered collagen levels, and reversal of fibrosis, even when treatment was administered late in the course of disease, after inflammation and fibrosis has been established. Furthermore, TL1 A polymorphisms have been shown to be associated with susceptibility to IBD and with disease severity.

[0254] Fibrosis is a significant clinical phenotype exhibited by IBD patients. Seventy percent of Crohn’s disease (CD) patients develop stricture / perforation, and stricture is the leading indication for surgery in CD. Unfortunately, anti-inflammatory agent use over the past decade has not materially changed the rate of structuring disease or need for surgery. Further, in ulcerative colitis (UC), subclinical fibrosis has significant implications on patient symptoms. For instance, subclinical fibrosis could contribute to symptoms of diarrhea, abdominal pain, urgency, and incontinence. Subclinical fibrosis is also the potential explanation for persistent symptoms after resolution of inflammation. In addition, a Cleveland Clinic study of 89 consecutive colectomy specimens revealed submucosal fibrosis in 100% of the specimens. Thus, treatment of fibrosis constitutes an unmet need in IBD .

[0255] The potential for TL1 A as a therapeutic target in intestinal fibrosis has been demonstrated in a study evaluating the effect of anti-TLIA antibodies in mouse models of IBD. In these studies, two mouse models of chronic colitis were utilized: adoptive T cell transfer and chronic DSS. In both models, a neutralizing TL1A monoclonal antibody (mAb) or an isotype control antibody was administered two times per week in mice (T cell transfer n=14; DSS n=28) with an established colitis. In both disease models, treatment with the TL1 A mAb reduced colonic collagen deposition levels back to those seen in healthy control mice, suggesting that blocking TL1A signaling not only prevented progression of colonic fibrosis, but also reversed established fibrosis to similar levels measured prior to the onset of inflammation. This data indicates that intestinal fibrosis mediated by increased levels of TL1A may be treated with an anti-TLIA antibody.

[0256] In one aspect, provided herein are methods of treating inflammation and / or fibrosis with anti-TLIA antibodies. In some embodiments, treatment of fibrosis is independent of treatment of inflammation. In some embodiments, treatment of inflammation is independent of treatment of fibrosis. In another aspect, provided herein are methods of treating a disease and / or condition of the kidney with anti-TLIA antibodies. Non-limiting examples of indications for use with the anti-TLIA antibodies herein include end-stage renal disease, tubulointerstitial renal fibrosis, glomerulonephritis, interstitial nephritis, acute interstitial nephritis, diabetic kidney diseases, lupus nephritis, Alport syndrome, and polycystic kidney disease. In certain embodiments, the anti-TLIA antibodies bind tomembrane-bound and soluble forms of TL1 A with high affinity and specificity and block the binding of TL1 A to its functional receptor DR3.

[0257] The term “ and / or’ ’ as used in a phrase with a list of members is intended to include all members individually and all combination of full or partial list of members. For example, a phrase such as “A and / or B” herein is intended to include both A and B; A or B; A (alone); and B (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).4.1 General Techniques

[0258] Techniques and procedures described or referenced herein include those that are generally well understood and / or commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual (3d ed. 2001); Current Protocols in Molecular Biology (Ausubel etal. 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 Diibel eds., 2d ed. 2010).4.2 Anti-TLIA Antibodies

[0259] ILIA exists in both monomeric and trimeric form in vivo and in vitro. The disclosure provides that although the trimeric form is the biologically active form that can bind to the physiological receptor, death receptor 3 (“DR3”) and trigger ILIA mediated signaling (e.g. Zhan, C et al., Structure 19: 162-171 (2011)), monomeric ILIA accounts for a large fraction of the ILIA pool in a subject. By one of the inventors’ estimates, the monomeric ILIA can be 60% of the total ILIA in the circulating blood. The term “total TL1 A” refers to both monomeric and trimeric ILIA. The disclosure further provides that, despite monomeric ILIA being biologically inactive, anti-TLl A antibodies binding to both monomeric and trimeric ILIA provide advantages over antibodies binding to only trimeric TL1 A. As provided herein and further demonstrated in Section 5, such advantages include more efficient reduction of the ILIA concentration in a diseased tissue in a subject including the concentration trimeric ILIA in the diseased tissue, more efficient reduction of the ILIA concentration in the blood in a subject including the concentration trimeric ILIA in the blood, more sustained reduction of ILIA concentration (including trimeric ILIA concentration) in a diseased tissue in a subject, and / or more sustained reduction of ILIA concentration (including trimeric ILIA concentration) in the blood in a subject.

[0260] In one aspect, provided herein are antibodies or antigen binding fragments thereof that bind to tumor necrosis factor-like protein 1 A (“TL1 A,” and such antibody or antigen binding fragment thereof, “anti-TLl A antibody or antigen binding fragment” or “anti-TLl A antibody(ies)” in the specification for simplicity), wherein the antibodies or antigen binding fragments bind to both monomeric TL1 A and trimeric TL1A. Further embodiments of the anti-TLl A antibodies, including embodiments with exemplary CDRs, framework sequences, constant region sequences, Fc mutations, variable regions, Fc regions, and other properties are further provided in this Section (Section 4.2). Assays for screening, testing, and validating the anti-TLl A antibodies are provided in Section 4.3. Methods for generating, improving, mutating, cloning, expressing, and isolating the anti-TLl A antibodies are provided in Section 4.4. Pharmaceutical compositions for the anti-TLl A antibodies are described and provided in Section 4.5. Methods of using the anti-TLIA antibodies are provided in Section 4.6. Further specific and validated embodiments for the anti-TLIA antibodies and the methods of using the same are provided in Section 5. As such, the disclosure provides the various combinations of the anti-TLIA antibodies, the pharmaceutical compositions of such anti-TLIA antibodies, the methods of generating the anti-TLIA antibodies, the methods of assaying the anti-TLIA antibodies, and the methods of using the anti-TLIA antibodies for treatment.

[0261] In one embodiment of the various anti-TLIA antibodies or antigen binding fragments thereof provided herein, the antibody or antigen binding fragment blocks binding of TL1 A to Death Receptor 3 (“DR3”). In another embodiment, the antibody or antigen binding fragment blocks the binding of trimeric TL1A to DR3. In a further embodiment, the antibody or antigen binding fragment blocks the signaling DR3 signaling mediated by TL1 A. In yet another embodiment, the antibody or antigen binding fragment blocks the increase of IFNy secretion by various immune cells. In a specific embodiment, the antibody or antigen binding fragment blocks the increase of IFNy secretion by peripheral blood mononuclear cells, including various B cells, T cells, natural killer cells, and / or macrophages.

[0262] As described herein, the disclosure provides anti-TLIA antibodies or antigen binding fragments for binding both monomeric and trimeric TL1A. Therefore, in one embodiment of the various anti-TLIA antibodies or antigen binding fragments thereof provided herein, binding affinity of the antibody or antigen binding fragment to monomeric TL1 A as measured by dissociation equilibrium constant (Ko-monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1 A as measured by dissociation equilibrium constant (Ko-trimer). Such KD -monomer and / or Ko-trimer can bedetermined via any of the methods known and practice by a skilled artisan in the field and via any of the applicable assays and methods described herein, including in this Section (Section 4.2) and Section 5.

[0263] The terms “binds” or “binding” refer to an interaction between molecules including, for example, to form a complex. Interactions can be, for example, non-covalent interactions including hydrogen bonds, ionic bonds, hydrophobic interactions, and / or van der Waals interactions. A complex can also include the binding of two or more molecules held together by covalent or non-covalent bonds, interactions, or forces. The strength of the total non-covalent interactions between a single antigen-binding site on an antibody and a single epitope of a target molecule, such as TL1 A, is the affinity of the antibody or functional fragment for that epitope. The ratio of dissociation rate (koff) to association rate (kon) of an antibody to a monovalent antigen (koff / kon) is the dissociation constant KD, which is inversely related to affinity. The lower the KD value, the higher the affinity of the antibody. The value of KD varies for different complexes of antibody and antigen and depends on both konand koff. The dissociation constant KD for an antibody provided herein can be determined using any method provided herein or any other method well known to those skilled in the art. The affinity at one binding site does not always reflect the true strength of the interaction between an antibody and an antigen. When complex antigens containing multiple, repeating antigenic determinants, such as a polyvalent TL1 A trimer, come in contact with antibodies containing multiple binding sites, the interaction of antibody with antigen at one site will increase the probability of a reaction at a second site. The strength of such multiple interactions between a multivalent antibody and antigen is called the avidity. The avidity of an antibody can be a better measure of its binding capacity than is the affinity of its individual binding sites.

[0264] “Binding affinity” generally refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., a binding protein such as an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1 :1 interaction between members of a binding pair (e.g., antibody and antigen). As described above, the affinity of a binding molecule X for its binding partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein. Low -affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend to remain bound longer. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present disclosure. Specificillustrative embodiments include the following. In one embodiment, the “KD” or “KD value” can be measured by assays known in the art, for example by a binding assay. The KD can be measured in a RIA, for example, performed with the Fab version of an antibody of interest and its antigen (Chen etal., 1999, J. Mol Biol 293:865-81). The KD or KD value can also be measured by using surface plasmon resonance assays by Biacore®, using, for example, a Biacore®TM-2000 or a Biacore®TM-3000, or by biolayer interferometry using, for example, the Octet®QK384 system. An “on-rate” or “rate of association” or “association rate” or “kon” can also be determined with the same surface plasmon resonance or biolayer interferometry techniques described above using, for example, a Biacore®TM-2000 or a Biacore®TM-3000, or the Octet®QK384 system.

[0265] Accordingly, the relative binding affinity of the anti-TLl A antibody or antigen binding fragment for the TL1A monomer and TL1A trimer can be described and provided by Ko-monomer and Ko-trimer. In one embodiment of the various anti-TLl A antibodies or antigen binding fragments provided herein, the Ko-monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the Ko-trimer. In another embodiment of the various anti-TLl A antibodies or antigen binding fragments provided herein, the Ko-monomer is within 10%, 20%, 30%, 40%, or 50% of the Ko-trimer. In a further embodiment of the various anti-TLl A antibodies or antigen binding fragments provided herein, the Ko-trimer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD- monomer. In another embodiment of the various anti-TLl A antibodies or antigen binding fragments provided herein, the Ko-trimer is within 10%, 20%, 30%, 40%, or 50% of the KD- monomer.

[0266] More specifically, in one embodiment of the various anti-TLl A antibodies or antigen binding fragments provided herein, KD -monomer is at most 5* IO-12M, at most 6* 10'12M, at most 7* 10'12M, at most 8* 10'12M, at most 9* 10'12M, at most I MO'11M, at most 2x i0'nM, at most 3x l0-11M, at most 4x l0-11M, at most 5x l0-11M, at most 6x l0'nM, at most 7x 10'11M, at most 8x l0'nM, at most 9x 10'11M, at most l x IO-10M, at most 2x 1 O'10M, at most 3x l0'10M, at most 4x lO'10M, at most 5x l0'10M, at most 6x lO'10M, at most 7x lO'10M, at most 8x 10'10M, at most 9x 10'10M, or at most 1 x 10'9M. In another embodiment, KD- monomer is about 5x l0-12M, about 6x 10'12M, about 7x 10'12M, about 8x l0'12M, about 9x 10'12M, about I x lO’11M, about 2x l0-11M, about 3x l0-11M, about 4x l0-11M, about 5x l0-11M, about 6x l0-11M, about 7x l0-11M, about 8x l0-11M, about 9x l0-11M, about Ix lO-10M, about 2x IO-10M, about 3x l0'10M, about 4x 10'10M, about 5x l0'10M, about 6x 10'10M, about 7x 1 O'10M, about 8x 10'10M, about 9x 10'10M, or about 1 x 10'9M. In a further embodiment of the various anti-TLl A antibodies or antigen binding fragments provided herein, Ko-trimer is atmost 5x l0'12M, at most 6x l0'12M, at most 7xl0'12M, at most 8 x 1 O’12M, at most 9xl0'12M, at most I x lO’11M, at most 2x l0'nM, at most 3x l0'nM, at most 4x l0'nM, at most 5x l0'nM, at most 6x l0'nM, at most 7x l0'nM, at most 8x l0'nM, at most 9x l0'nM, at most I x lO'10M, at most 2x lO'10M, at most 3x lO'10M, at most 4x lO'10M, at most 5x lO'10M, at most 6x lO'10M, at most 7x lO'10M, at most 8x lO'10M, at most 9x lO'10M, or at most I x lO'9M. In yet another embodiment, Ko-trimer is about 5x 10'12M, about 6x 10'12M, about 7x 10'12M, about 8x l0'12M, about 9x l0'12M, about I x lO'11M, about 2x l0'nM, about 3x l0'nM, about 4x l0'nM, about 5x l0'nM, about 6x l0'nM, about 7x l0'nM, about 8x l0'nM, about 9x 10'11M, about I x lO'10M, about 2x IO'10M, about 3x lO'10M, about 4x IO'10M, about 5x 10'10M, about 6x lO'10M, about 7x lO'10M, about 8x lO'10M, about 9x lO'10M, or about I x lO'9M. The disclosure further provides that the Ko-monomer and Ko-trimer can be any combination of the KD -monomer and Ko-trimer value or range as provided herein, including in this Section (Section 4.2) and this paragraph.

[0267] In a further specific embodiment, the KD -monomer is about 59 pM. In another specific embodiment, the Ko-trimer is about 59 pM. In a further embodiment, the KD -monomer is about 59 pM and the Ko-trimer is about 59 pM. In one specific embodiment, the KD -monomer is about 60 pM. In another specific embodiment, the Ko-trimer is about 60 pM. In a further embodiment, the Ko-monomer is about 60 pM and the Ko-trimer is about 60 pM. In one specific embodiment, the KD -monomer is at most 60 pM. In another specific embodiment, the KD -trimer is at most 60 pM. In a further embodiment, the Ko-monomer is at most 60 pM and the Ko-trimer is at most 60 pM.

[0268] In one aspect, provided herein are antibodies that bind to TL1 A. As used herein, the term “antibody” refers to any form of antibody that exhibits the desired biological or binding activity. Thus, it is used in the broadest sense and specifically covers, but is not limited to, monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized, fully human antibodies, chimeric antibodies and camelized single domain antibodies.

[0269] In general, the basic antibody structural unit comprises a tetramer. Each tetramer includes two identical pairs of polypeptide chains, each pair having one “light” (about 25 kDa) and one “heavy” chain (about 50-70 kDa). The amino-terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The carboxy -terminal portion of the heavy chain may define a constant region primarily responsible for effector function. Typically, human light chains are classified as kappa and lambda light chains. Furthermore, human heavy chains are typicallyclassified as mu, delta, gamma, alpha, or epsilon, and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Within light and heavy chains, the variable and constant regions are joined by a “J” region of about 12 or more amino acids, with the heavy chain also including a “D” region of about 10 more amino acids. See generally, Fundamental Immunology Ch. 7 (Paul, W., ed., 2nd ed. Raven Press, N.Y. (1989).

[0270] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, in general, an intact antibody has two binding sites. Except in bifunctional or bispecific antibodies, the two binding sites are, in general, the same.

[0271] Typically, the variable domains of both the heavy and light chains comprise three hypervariable regions, also called complementarity determining regions (CDRs), which are located within relatively conserved framework regions (FR). The CDRs are usually aligned by the framework regions, enabling binding to a specific epitope. In general, from N -terminal to C-terminal, both light and heavy chains variable domains comprise FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain is, generally, in accordance with the definitions of Sequences of Proteins of Immunological Interest, Kabat, et al:, National Institutes of Health, Bethesda, Md.; 5thed.; NIH Publ. No. 91-3242 (1991);Kabat (1978) Adv. Prot. Chem. 32:1-75; Kabat, etal., (1977) J. Biol. Chem. 252:6609-6616; Chothia, etal., (1987) J Mol. Biol. 196:901-917 or Chothia, etal., (1989) Nature 342:878- 883.

[0272] As used herein, unless otherwise indicated, “antibody fragment” or “antigen binding fragment” refers to antigen binding fragments of antibodies, i.e., antibody fragments that retain the ability to bind specifically to the antigen bound by the full-length antibody, e.g., fragments that retain one or more CDR regions. Examples of antibody binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules, e.g., sc-Fv; nanobodies and multispecific antibodies formed from antibody fragments.

[0273] In some embodiments, an antibody comprises an antigen-binding fragment that refers to a portion of an antibody having antigenic determining variable regions of an antibody. Examples of antigen-binding fragments include, but are not limited to Fab, Fab’, F(ab’)2, and Fv fragments, linear antibodies, single chain antibodies, and multispecific antibodies formed from antibody fragments. In some embodiments, an antibody refers to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulinmolecule. In some embodiments, an antibody includes intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab’, F(ab’)2, and Fv fragments), single chain Fv (scFv) mutants, a CDR-grafted antibody, multispecific antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins comprising an antigen determination portion of an antibody, and any other modified immunoglobulin molecule comprising an antigen recognition site so long as the antibodies exhibit the desired biological activity. An antibody can be of any the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2), based on the identity of their heavy -chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well-known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated to other molecules such as toxins, radioisotopes, etc.

[0274] In some embodiments, a humanized antibody refers to forms of non -human (e.g., murine) antibodies having specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. In a nonlimiting example, a humanized antibody comprises less than about 40% non-human sequence in the variable region. In some cases, a humanized antibody comprises less than about 20% non-human sequence in a full-length antibody sequence. In a further non-limiting example, a humanized antibody comprises less than about 20% non-human sequence in the framework region of each of the heavy chain and light chain variable regions. For instance, the humanized antibody comprises less than about 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% non-human sequence in the framework region of each of the heavy chain and light chain variable regions. As another example, the humanized antibody comprises about or less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequences in the framework region of each of the heavy chain and light chain variable regions. In some cases, humanized antibodies are human immunoglobulins in which residues from the complementarity determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and capability. These humanized antibodies may contain one or more non-human species mutations, e.g., the heavy chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework region, and the light chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 non-human species mutations in the framework region. The humanized heavy chain variable domain may comprise IGHV1 -46*02 framework with no or fewer than about 10, 9, 8, 7, 6, 5,4, 3, 2, or 1 amino acid mutations. The humanized light chain variable domain may comprise IGKV3-20 framework with no or fewer than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations.

[0275] In some embodiments, chimeric antibodies refer to antibodies wherein the sequence of the immunoglobulin molecule is derived from two or more species. As a nonlimiting example, the variable region of both light and heavy chains corresponds to the variable region of antibodies derived from one species of mammals (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies derived from another (usually human) to avoid eliciting an immune response in that species.

[0276] The terms “complementarity determining region,” and “CDR,” which are synonymous with “hypervariable region” or “HVR,” are known in the art to refer to noncontiguous sequences of amino acids within antibody variable regions, which confer antigen specificity and / or binding affinity. In general, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3). “Framework regions” and “FR” are known in the art to refer to the non-CDR portions of the variable regions of the heavy and light chains. In general, there are four FRs in each full-length heavy chain variable region (FR-H1, FR-H2, FR-H3, and FR-H4), and four FRs in each full-length light chain variable region (FR-L1, FR- L2, FR-L3, and FR-L4). The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme), Al-Lazikani et al., (1997) JMB 273,927-948 (“Chothia” numbering scheme);MacCallum et al., J. Mol. Biol. 262:732-745 (1996), “Antibody-antigen interactions: Contact analysis and binding site topography,” J. Mol. Biol. 262, 732-745.” (“Contact” numbering scheme); Lefranc MP et al.,“IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol, 2003 Jan;27(l):55-77 (“IMGT” numbering scheme); Honegger A and Pliickthun A, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J Mol Biol, 2001 Jun 8;309(3):657-70, (“Aho” numbering scheme); and Whitelegg NR and Rees AR, “WAM: an improved algorithm for modelling antibodies on the WEB,” Protein Eng. 2000 Dec;13(12):819-24 (“AbM” numbering scheme. In certain embodiments, the CDRs of the antibodies described herein can be defined by a methodselected from Kabat, Chothia, IMGT, Aho, AbM, or combinations thereof.

[0277] In some embodiments, an antibody that specifically binds to a protein indicates that the antibody reacts or associates more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of the above to the protein than with alternative substances, including unrelated proteins.

[0278] In some embodiments, the terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non -amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as fusion with another polypeptide and / or conjugation, e.g., with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (for example, unnatural amino acids, etc.), as well as other modifications known in the art.

[0279] In some embodiments, a protein such as an antibody described herein comprises a hydrophobic amino acid. Non-limiting exemplary hydrophobic amino acids include glycine (Gly), proline (Pro), phenylalanine (Phe), alanine (Ala), isoleucine (He), leucine (Leu), and valine (Vai). In some embodiments, a protein such as an antibody described herein comprises a hydrophilic amino acid. Non-limiting exemplary hydrophilic amino acids include serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), cysteine (Cys), asparagine (Asn), glutamine (Gin), arginine (Arg), and histidine (His). In some embodiments, a protein such as an antibody described herein comprises an amphipathic amino acid. Non-limiting exemplary amphipathic amino acids include lysine (Lys), tryptophan (Trp), tyrosine (Tyr), and methionine (Met). In some embodiments, a protein such as an antibody described herein comprises an aliphatic amino acid. Non-limiting exemplary aliphatic amino acids include alanine (Ala), isoleucine (He), leucine (Leu) and valine (Vai). In some embodiments, a protein such as an antibody described herein comprises an aromatic amino acid. Non-limiting exemplary aromatic amino acids include phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). In some embodiments, a protein such as an antibody described herein comprises an acidic amino acid. Non-limiting exemplary acidic amino acids include aspartic acid (Asp) and glutamic acid (Glu). In some embodiments, a protein such as an antibody described herein comprises a basic amino acid. Non-limiting exemplary basic amino acids include arginine (Arg), histidine (His), and lysine (Lys). In some embodiments, a protein such as anantibody described herein comprises a hydroxylic amino acid. Non-limiting exemplary hydroxylic amino acids include serine (Ser) and threonine (Thr). In some embodiments, a protein such as an antibody described herein comprises a sulfur-containing amino acid. Nonlimiting exemplary sulfur-containing amino acids include cysteine (Cys) and methionine (Met). In some embodiments, a protein such as an antibody described herein comprises an amidic amino acid. Non-limiting exemplary amidic amino acids include asparagine (Asn) and glutamine (Gin).

[0280] In some embodiments, “polynucleotide,” or “nucleic acid,” as used interchangeably herein, refer to polymers of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. A polynucleotide may comprise modified nucleotides, such as, but not limited to methylated nucleotides and their analogs or non -nucleotide components. Modifications to the nucleotide structure may be imparted before or after assembly of the polymer. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component.

[0281] Percent (%) sequence identity with respect to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are known for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences are able to be determined, including algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or may be compiled from the source code. The ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by theALIGN -2 program and do not vary.

[0282] In situations where ALIGN -2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0283] In some embodiments, the term “about” means within 10% of the stated amount. For instance, an antibody variable region comprising about 80% identity to a reference variable region may comprise 72% to 88% identity to the reference variable region.

[0284] In certain aspects, antibodies are described herein that specifically bind to ILIA (Entrez Gene: 9966; UniProtKB: 095150). In some embodiments, the antibodies specifically bind to soluble ILIA. In some embodiments, the antibodies specifically bind to membrane bound ILIA. In some embodiments, an anti-TLl A antibody is provided having a heavy chain comprising four heavy chain framework regions (HCFR) and three heavy chain complementarity-determining regions (HCDR): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3, and HCFR4; and a light chain comprising four light chain framework regions (LCFR) and three light chain complementarity -determining regions (LCDR): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3, and LCFR4. An anti-TLIA antibody may comprise any region provided herein, for example, as provided in the tables, the examples, and the sequences.

[0285] Exemplary anti-TLIA CDRs

[0286] In certain embodiments, an anti-TLIA antibody comprises a HCDRl as set forth by SEQ ID NO: 1. In certain embodiments, an anti-TLIA antibody comprises a HCDR2 as set forth by any one of SEQ ID NOS: 2-5. In certain embodiments, an anti-TLIA antibody comprises a HCDR3 as set forth by any one of SEQ ID NOS: 6-9. In certain embodiments, an anti-TLIA antibody comprises a LCDR1 as set forth by SEQ ID NO: 10. In certainembodiments, an anti-TLIA antibody comprises a LCDR2 as set forth by SEQ ID NO: 11. In certain embodiments, an anti-TLIA antibody comprises a LCDR3 as set forth by any one of SEQ ID NOS: 12-15. In a non-limiting example, an anti-TLIA antibody comprises a HCDR1 as set forth by SEQ ID NO: 1, a HCDR2 as set forth by SEQ ID NO: 2, a HCDR3 as set forth by SEQ ID NO: 6, a LCDR1 as set forth by SEQ ID NO: 10, a LCDR2 as set forth by SEQ ID NO: 11, and a LCDR3 as set forth by SEQ ID NO: 12. In some cases, the anti-TLIA antibody comprises the CDRs of antibody J of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody J2 of Table 10. In some cases, the anti-TLIA antibody comprises the CDRs of antibody K of Table 10.

[0287] In certain embodiments, an anti-TLIA antibody comprises a HCDRl as set forth by SEQ ID NOS: 401, 407, 413, or 450. In certain embodiments, an anti-TLIA antibody comprises a HCDR2 as set forth by SEQ ID NOS: 402, 408, 414, or 451. In certain embodiments, an anti-TLIA antibody comprises a HCDR3 as set forth by SEQ ID NOS: 403, 409, 415, or 452. In certain embodiments, an anti-TLIA antibody comprises a LCDR1 as set forth by SEQ ID NOS: 404, 410, 416, or 453. In certain embodiments, an anti-TLIA antibody comprises a LCDR2 as set forth by SEQ ID NOS: 405, 411, 417, or 454. In certain embodiments, an anti-TLIA antibody comprises a LCDR3 as set forth by SEQ ID NOS: 406, 412, 418, or 455.

[0288] In certain embodiments, an anti-TLIA antibody comprises a HCDRl, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 selected from Table 6.Table 6. Example CDR amino acid sequences

[0289] In certain embodiments, an anti-TLIA 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, 12, J, J2, K, M, orN ofTable 10Table 10. CDR sequences from example anti-TLIA antibodies

[0290] In certain embodiments, an anti-TLIA antibody comprises the heavy chain CDRs set forth in an antibody selected from Table 7.Table 7. Example heavy chain variable region sequences

[0291] In certain embodiments, an anti-TLIA antibody comprises the light chain CDRs set forth in an antibody selected from Table 8.Table 8. Example light chain variable region sequences

[0292] In certain embodiments, an anti-TLIA antibody comprises the CDRs set forth in any one of the antibodies of Table 1. For instance, an anti-TLIA antibody comprises the CDRs of antibody A15, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A107, A108, A109,A110, Al l i, A112, A113, A114, A115, A116, A117, A118, A119, A120, A121, A122, A123, A124, A125, A126, A127, A128, A129, A l 30, A132, A133, A134, A135, A136, A137, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A148, A149, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A160, A161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A184, A185, A186, A187, A188, A189, A190, A191, A192, A193, A194, A195, A196, A197, A198, A199, A200, A201, A202, A203, A204, A205, A206, A207, A208, A209, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN. In a non-limiting example, an anti-TLl A antibody comprises the CDRs of antibody A219.

[0293] Antibody CDRs may be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0294] Exemplary anti-TLl A Framework Regions

[0295] In certain embodiments, an anti-TLl A antibody comprises a heavy chain (HC) framework 1 (FR1) as set forth by SEQ ID NO: 304. In certain embodiments, an anti-TLIA antibody comprises a HC FR2 as set forth by any one of SEQ ID NOS: 305 or 313. In certain embodiments, an anti-TLIA antibody comprises a HC FR3 as set forth by any one of SEQ ID NOS: 306-307, 314-315. In certain embodiments, an anti-TLIA antibody comprises a HC FR4 as set forth by SEQ ID NO: 308. In certain embodiments, an anti-TLIA antibody comprises a LC FR1 as set forth by SEQ ID NO: 309. In certain embodiments, an anti-TLIA antibody comprises a LC FR2 as set forth by SEQ ID NO: 310. In certain embodiments, an anti-TLIA antibody comprises a LC FR3 as set forth by SEQ ID NO: 311. In certain embodiments, an anti-TLIA antibody comprises a LC FR4 as set forth by SEQ ID NO: 312. In a non-limiting example, an anti-TLIA antibody comprises a HC FR1 as set forth by SEQ ID NO: 304, a HC FR2 as set forth by SEQ ID NO: 305, a HC FR3 as set forth by SEQ ID NO: 306, a HC FR4 as set forth by SEQ ID NO: 308, a LC FR1 as set forth by SEQ ID NO: 309, a LC FR2 as set forth by SEQ ID NO: 310, a LC FR3 as set forth by SEQ ID NO: 311, and a LC FR4 as set forth by SEQ ID NO: 312. In a non-limiting example, an anti-TLIA antibody comprises a HC FR1 as set forth by SEQ ID NO: 304, a HC FR2 as set forth by SEQ ID NO: 305, a HC FR3 as set forth by SEQ ID NO: 307, a HC FR4 as set forth by SEQ ID NO: 308, a LC FR1 as set forth by SEQ ID NO: 309, a LC FR2 as set forth by SEQ ID NO: 310, a LC FR3 as set forth by SEQ ID NO: 311, and a LC FR4 as set forth by SEQ ID NO: 312.

[0296] In certain embodiments, an anti-TLIA antibody comprises the heavy chainframework regions set forth in an antibody selected from Table 7. In certain embodiments, an anti-TLl A antibody comprises the light chain framework regions set forth in an antibody selected from Table 8. In certain embodiments, an anti-TLl A antibody comprises the framework regions set forth in any one of the antibodies of Table 1. For instance, an anti- TLl A antibody comprises the framework regions of antibody A15, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A107, A108, A109, A110, Al l i, A112, A113, A114, A115,A116, A117, A118, A119, A120, A121, A122, A123, A124, A125, A126, A127, A128,A129, A l 30, A132, A133, A134, A135, A136, A137, A138, A139, A140, A141, A142,A143, A144, A145, A146, A147, A148, A149, A150, A151, A152, A153, A154, A155,A156, A157, A158, A159, A160, A161, A162, A163, A164, A165, A166, A167, A168,A169, A170, A171, A172, A173, A174, A175, A176, A177, A178, A179, A180, A181,A182, A183, A184, A185, A186, A187, A188, A189, A190, A191, A192, A193, A194,A195, A196, A197, A198, A199, A200, A201, A202, A203, A204, A205, A206, A207,A208, A209, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220,A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN. In a non-limiting example, an anti-TLl A antibody comprises the framework region of antibody A219. In another nonlimiting example, the anti-TLl A antibody comprises the framework region of an antibody comprising SESQ ID NOS: 420 and 430. In another non -limiting example, the anti-TLl A antibody comprises the framework region of an antibody comprising SESQ ID NOS: 421 and 431. In another non-limiting example, the anti-TLl A antibody comprises the framework region of an antibody comprising SESQ ID NOS: 424 and 434.

[0297] Antibody CDR and framework regions may be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0298] In some embodiments, an anti-TLl A antibody comprises a heavy chain variable framework region comprising a human IGHV1 -46*02 framework or a modified human IGHV1 -46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human IGHV 1 -46*02 framework and the human IGKV3-20 framework. In some embodiments, the amino acidmodification(s) comprise: (a) a modification at amino acid position 45 in the heavy chain variable region; (b) a modification at amino acid position 47 in the heavy chain variable region; (c) a modification at amino acid position 55 in the heavy chain variable region; (d) a modification at amino acid position 78 in the heavy chain variable region; (e) a modification at amino acid position 80 in the heavy chain variable region; (f) a modification at amino acid position 82 in the heavy chain variable region; (g) a modification at amino acid position 89 in the heavy chain variable region; or (h) a modification at amino acid position 91 in the heavy chain variable region, per Aho or Kabat numbering; or a combination of two or more modifications selected from (a) to (h). In some embodiments, the amino acid modification(s) comprise (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L in the heavy chain variable region, per Aho or Kabat numbering; or a combination of two or more modifications selected from (a) to (h). In some embodiments, the amino acid modification(s) comprise: A47R. In some embodiments, the amino acid modification(s) comprise: A47R, M55I, V78A, M80I, R82T, V89A, and M91L; A47R, M80I, and R82T; A47R, M80I, R82T, V89A, and M91L; or A47R, M55I, V78A, M80I, V89A, and M91L. In some embodiments, the amino acid modification(s) comprise: R45K and A47R. In some embodiments, the amino acid modification(s) comprise: R45K, A47R, V89A, and M91L. In some embodiments, the amino acid modification(s) comprise: R45K and A47R, and M80I. In some embodiments, the amino acid modification(s) comprise: R45K, A47R, M80I, and M91L; R45K, A47R, V78A, M80I, V89A, and M91L; R45K, A47R, M55I, V78A, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, V89A, and M91L; R45K, A47R, M55I, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, and V89A; R45K, A47R, M80I, R82T, V89A, M91L; or R45K, A47R, M55I, M80I, V89A, and M91L. In some embodiments, the amino acid modification(s) comprise: R45K. In some embodiments, the amino acid modification(s) comprise: R45K and V78A. In some embodiments, the amino acid modification(s) comprise: V78A. In some embodiments, the amino acid modification(s) comprise: V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. In some embodiments, the amino acid modification(s) comprise: V89A. In some embodiments, the amino acid modification(s) comprise: M80I. In some embodiments, the amino acid modification(s) comprises: (a) a modification at amino acid position 54 in the light chain variable region; and / or (b) a modification at amino acid position 55 in the light chain variable region, per Aho or Kabat numbering. In some embodiments, the amino acid modification(s) comprises L54P in the light chain variable region, per Aho or Kabat numbering. In some embodiments, the amino acid modification(s) comprises L55W in the light chain variable region, per Aho or Kabatnumbering.

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

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

[0301] In some embodiments, an anti-TLIA antibody comprises a light chain framework comprising SEQ ID NO: 303 (EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX1OX11IY[LCDR2]GIPDR FSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK). In some cases, X10 is L. In some cases, X10 is P. In some cases, XI 1 is L. In some cases, XI 1 is W. In some embodiments, X10 is at position 54 of IGKV3-20*01 as determined by Aho or Kabat numbering. In some embodiments, XI 1 is at position 55 of IGKV3-20*01 as determined by Aho or Kabat numbering.

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

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

[0304] In some embodiments, an anti-TLIA antibody comprises a heavy chain FR1 as set forth by SEQ ID NO: 304. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR2 as set forth by SEQ ID NO: 305. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR2 as set forth by SEQ ID NO: 313. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 306. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 307. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 314. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR3 as set forth by SEQ ID NO: 315. In some embodiments, an anti-TLIA antibody comprises a heavy chain FR4 as set forth by SEQ ID NO: 308. In some embodiments, an anti-TLIA antibody comprises a light chain FR1 as set forth by SEQ ID NO: 309. In some embodiments, an anti-TLIA antibody comprises a light chain FR2 as set forth by SEQ ID NO: 310. In some embodiments, an anti-TLIA antibody comprises a light chain FR3 as set forth by SEQ ID NO: 311. In some embodiments, an anti-TLIA antibody comprises a light chain FR4 as set forth by SEQ ID NO: 312.

[0305] In some embodiments, an anti-TLIA antibody comprises a framework region of Table 9ATable 9A. Example framework sequences

[0306] Exemplary anti-TLIA Variable Regions

[0307] In one aspect, provided herein is an anti-TLIA antibody comprising a heavy chain variable region comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 101-169 or 420-427; and a light chain variable region at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 201-220 or 430-437.

[0308] Further provided herein is a first embodiment of an anti-TLIA antibody comprising a heavy chain variable region and a light chain variable region. Non -limiting additional embodiments include: (Embodiment 2) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101 or a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 101. (Embodiment 3) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable regioncomprises a sequence at least about 80%, 81%, 82%, 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 as compared to SEQ ID NO: 102.(Embodiment 4) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 103. (Embodiment 5) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 104. (Embodiment 6) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 105. (Embodiment 7) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 106 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 106. (Embodiment 8) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 107. (Embodiment 9) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 108.(Embodiment 10) The anti-TLl A 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 heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:109. (Embodiment 11) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 110 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:110. (Embodiment 12) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 111 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:111. (Embodiment 13) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 112 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:112. (Embodiment 14) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 113 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:113. (Embodiment 15) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:114. (Embodiment 16) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 115 or the heavy chain variable region comprises a sequence having about 1,2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:115. (Embodiment 17) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:116. (Embodiment 18) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:117. (Embodiment 19) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 118 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:118. (Embodiment 20) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:119. (Embodiment 21) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 120 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:120. (Embodiment 22) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:121. (Embodiment 23) The anti-TLl A 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% identicalto SEQ ID NO: 122 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:122. (Embodiment 24) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 123 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:123. (Embodiment 25) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:124. (Embodiment 26) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 125 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:125. (Embodiment 27) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:126. (Embodiment 28) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:127. (Embodiment 29) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:128. (Embodiment 30) The anti-TLIA 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 heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:129. (Embodiment 31) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:130. (Embodiment 32) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 131 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:131. (Embodiment 33) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:132. (Embodiment 34) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 133 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:133. (Embodiment 35) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 134 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:134. (Embodiment 36) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 135 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:135. (Embodiment 37) The anti-TLIA antibody of embodiment 1, wherein the heavy chainvariable region comprises a sequence at least about 80%, 81%, 82%, 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 having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:136. (Embodiment 38) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 137 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:137. (Embodiment 39) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 138 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:138. (Embodiment 40) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 139 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:139. (Embodiment 41) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 140 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:140. (Embodiment 42) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 141 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:141. (Embodiment 43) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 142 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:142. (Embodiment 44) The anti-TLl A 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: 143 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:143. (Embodiment 45) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 144 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:144. (Embodiment 46) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 145 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:145. (Embodiment 47) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 146 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:146. (Embodiment 48) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 147 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:147. (Embodiment 49) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 148 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:148. (Embodiment 50) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 149 or the heavy chain variable region comprises a sequence having about 1,2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:149. (Embodiment 51) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 150 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:150. (Embodiment 52) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 151 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:151. (Embodiment 53) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 152 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:152. (Embodiment 54) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 153 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:153. (Embodiment 55) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 154 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:154. (Embodiment 56) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 155 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:155. (Embodiment 57) The anti-TLIA 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% identicalto SEQ ID NO: 156 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:156. (Embodiment 58) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 157 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:157. (Embodiment 59) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 158 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:158. (Embodiment 60) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 159 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:159. (Embodiment 61) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 160 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:160. (Embodiment 62) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 161 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:161. (Embodiment 63) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 162 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:162. (Embodiment 64) The anti-TLIA 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: 163 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:163. (Embodiment 65) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 164 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:164. (Embodiment 66) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 165 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:165. (Embodiment 67) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 166 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:166. (Embodiment 68) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 167 or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO:167. (Embodiment 69) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 168 or 169, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 168 or 169. (Embodiment 70) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, 421, or 422, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 420, 421, or 422.

[0309] (Embodiment 71) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 201. (Embodiment 72) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 202. (Embodiment 73) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 203 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 203. (Embodiment 74) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 204. (Embodiment 75) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 205. (Embodiment 76) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 206. (Embodiment 77) The anti-TLIA antibody of any one of embodiments 1- 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98%, 99%, or 100% identical to SEQ ID NO: 207 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 207. (Embodiment 78) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 208 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 208. (Embodiment 79) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 209 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 209. (Embodiment 80) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 210 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 210. (Embodiment 81) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 211 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 211. (Embodiment 82) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 212 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 212. (Embodiment 83) The anti-TLIA antibody of any one of embodiments 1- 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 213 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 213. (Embodiment 84) The anti-TLIA antibody of any one ofembodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 214 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 214. (Embodiment 85) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 215 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 215. (Embodiment 86) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 216 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 216. (Embodiment 87) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 217 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 217. (Embodiment 88) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 218 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 218. (Embodiment 89) The anti-TLIA antibody of any one of embodiments 1- 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 219 or 220, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 219 or 220. (Embodiment 90) The anti-TLIA antibody of any one of embodiments 1-70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430, 431, or432 or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions or deletions as compared to SEQ ID NO: 430, 431, or 432.

[0310] (Embodiment 91) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 92) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 93) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 94) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.(Embodiment 95) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0311] (Embodiment 96) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%identical to SEQ ID NO: 103, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 97) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 106, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 98) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 99) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.(Embodiment 100) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.

[0312] (Embodiment 101) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 102) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:109, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 103) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 203. (Embodiment 104) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.(Embodiment 105) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0313] (Embodiment 106) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 107) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:110, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 108) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 111, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 109) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 112, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.(Embodiment 110) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 113, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0314] (Embodiment 111) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 112) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 115, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 113) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 114) The anti-TLIA antibody of embodiment 1, wherein theheavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.(Embodiment 115) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 118, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0315] (Embodiment 116) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 117) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 118) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 119) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.(Embodiment 120) The anti-TLl A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0316] (Embodiment 121) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 122) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 123) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 120, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 124) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.(Embodiment 125) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.

[0317] (Embodiment 126) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 207. (Embodiment 127) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 123, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 128) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 129) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 125, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.(Embodiment 130) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.

[0318] (Embodiment 131) The anti-TLIA 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, and the light chain variable region comprises a sequence atleast about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 132) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 133) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 134) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 135) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0319] (Embodiment 136) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 137) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 138) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206. (Embodiment 139) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 140) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0320] (Embodiment 141) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 142) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206. (Embodiment 143) The anti-TLIA 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, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 144) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.(Embodiment 145) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 131, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.

[0321] (Embodiment 146) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 147) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 133, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 148) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 134, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 149) The anti-TLIA 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, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.(Embodiment 150) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 151) The anti- TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 152) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 153) The anti-TLIA antibody of embodiment 1, comprising A500. (Embodiment 154) The anti-TLIA antibody of embodiment 1, comprising A501. (Embodiment 155) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430. (Embodiment 156) The anti- TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 421, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or100% identical to SEQ ID NO: 431. (Embodiment 157) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 422, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 432. (Embodiment 158) The anti-TLIA antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 427, and the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 437.

[0322] Exemplary anti-TLIA Constant Regions

[0323] In some embodiments, one or more amino acid modifications may be introduced into the Fragment crystallizable (Fc) region of a human or humanized antibody, thereby generating an Fc region variant. An Fc region may comprise a C -terminal region of an immunoglobulin heavy chain that comprises a hinge region, CH2 domain, CH3 domain, or any combination thereof. As used herein, an Fc region includes native sequence Fc regions and variant Fc regions. The Fc region variant may comprise a human Fc region sequence (e.g., a human IgGl, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g., a substitution, addition, or deletion) at one or more amino acid positions. In an exemplary embodiment, the Fc region comprises any one of SEQ ID NOS: 320-367. In some embodiments, the anti-TLIA antibody comprises a constant region comprising any one of SEQ ID NOS: 319, 368-381.

[0324] In some embodiments, antibodies of this disclosure have a reduced effector function as compared to a human IgG. Effector function refers to a biological event resulting from the interaction of an antibody Fc region with an Fc receptor or ligand. Non-limiting effector functions include Clq binding, complement dependent cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), antibodydependent cellular phagocytosis (ADCP), cytokine secretion, immune complex -mediated antigen uptake by antigen presenting cells, down regulation of cell surface receptors (e.g., B cell receptor), and B cell activation. In some cases, antibody-dependent cell-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 boundantibody on a target cell, subsequently causing lysis of the target cell. In some cases, complement dependent cytotoxicity (CDC) refers to lysing of a target cells in the presence of complement, where the complement action pathway is initiated by the binding of Clq to antibody bound with the target.

[0325] Some Fc regions have a natural lack of effector function, and some Fc regions can comprise mutations that reduce effector functions. For instance, IgG4 has low ADCC and CDC activities and IgG2 has low ADCC activity.

[0326] The disclosure provides antibodies comprising Fc regions characterized by exhibiting ADCC that is reduced by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70% or more as compared to an antibody comprising a non-variant Fc region, i.e., an antibody with the same sequence identity but for the substitution(s) that decrease ADCC (such as human IgGl, SEQ ID NO: 320). The disclosure provides antibodies comprising Fc regions characterized by exhibiting CDC that is reduced by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70% or more as compared to an antibody comprising a non-variant Fc region, i.e., an antibody with the same sequence identity but for the substitution(s) that decrease CDC (such as human IgGl, SEQ ID NO: 320). In certain embodiments, the antibodies of this disclosure have reduced effector function as compared with human IgGl. In certain embodiments, antibodies herein have no detectable ADCC activity. In certain embodiments, the reduction and / or abatement of ADCC activity may be attributed to the reduced affinity antibodies of the invention exhibit for Fc ligands and / or receptors. In certain embodiments, antibodies herein exhibit no detectable CDC activities. In some embodiments, the reduction and / or abatement of CDC activity may be attributed to the reduced affinity antibodies of the invention exhibit for Fc ligands and / or receptors. Measurement of effector function may be performed as described in Example 3.

[0327] In some embodiments, antibodies comprising Fc regions described herein exhibit decreased affinities to Clq relative to an unmodified antibody (e.g., human IgGl having SEQ ID NO: 320). In some embodiments, antibodies herein exhibit affinities for Clq receptor that are at least 2 fold, or at least 3 fold, or at least 5 fold, or at least 7 fold, or at least 10 fold, or at least 20 fold, or at least 30 fold, or at least 40 fold, or at least 50 fold, or at least 60 fold, or at least 70 fold, or at least 80 fold, or at least 90 fold, or at least 100 fold, or at least 200 fold less than an unmodified antibody. In some embodiments, antibodies herein exhibit affinities for Clq that are at least 90%, at least 80%, at least 70%, at least 60%, at least 50%, at least 40%, at least 30%, at least 20%, at least 10%, or at least 5% less than an unmodifiedantibody.

[0328] In some embodiments, the antibodies of this disclosure are variants that possess some but not all effector functions, which make it a desirable candidate for applications in which the half-life of the antibody in vivo is important yet certain effector functions (such as complement and ADCC) are unnecessary or deleterious.

[0329] In vitro and / or in vivo cytotoxicity assays can be conducted to confirm the reduction / depletion of CDC and / or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks FcyR binding (hence likely lacking ADCC activity) but retains FcRn binding ability. Measurement of effector function may be performed as described in Example 3.

[0330] In some embodiments, antibodies are tested for binding to Fey receptors and complement Clq by ELISA. In some embodiments, antibodies are tested for the ability to activate primary human immune cells in vitro, for example, by assessing their ability to induce expression of activation markers.

[0331] In some embodiments, assessment of ADCC activity of an anti-TLIA antibody comprises adding the antibody to target cells in combination with immune effector cells, which may be activated by the antigen antibody complexes resulting in cytolysis of the target cell. Cytolysis may be detected by the release of label (e.g. radioactive substrates, fluorescent dyes or natural intracellular proteins) from the lysed cells. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Specific examples of in vitro ADCC assays are described in Wisecarver et al., 1985 79:277- 282; Bruggemann et al., 1987, J Exp Med 166:1351-1361; Wilkinson et al., 2001, J Immunol Methods 258:183-191; Patel et al., 1995 J Immunol Methods 184:29-38. Alternatively, or additionally, ADCC activity of the antibody of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al., 1998, PNAS USA 95:652-656.

[0332] In some embodiments, an assessment of complement activation, a CDC assay, may be performed as described in Gazzano- Santoro et al., 1996, J. Immunol. Methods, 202:163.

[0333] Non-limiting examples of Fc mutations in IgGl 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 IgGl, where the numbering system of the constant region is that of the EU index as set forth by Kabat. In certain embodiments, the antibodies of this disclosure have reduced effector function as compared with human IgGl.

[0334] In some embodiments, an antibody comprises an IgGl Fc region comprising one or more of the following substitutions according to the Kabat numbering system: N297A, N297Q, N297D, D265A, S228P, L235A, L237A, L234A, E233P, L234V, C236 deletion, P238A, A327Q, P329A, P329G, L235E, P331S, L234F, 235G, 235Q, 235R, 235S, 236F, 236R, 237E, 237K, 237N, 237R, 238A, 238E, 238G, 238H, 2381, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 2541, 254N, 254P, 254Q, 254T, 254V, 255N, 256H, 256K, 256R, 256V, 264S, 265H, 265K, 265S, 265Y, 267G, 267H, 2671, 267K, 268K, 269N, 269Q, 270A, 270G, 270M, 270N, 271T, 272N, 279F, 279K, 279L, 292E, 292F, 292G, 2921, 293S, 301W, 304E, 3 HE, 311G, 31 IS, 316F, 327T, 328V, 329Y, 330R, 339E, 339L, 3431, 343V, 373 A, 373G, 373S, 376E, 376W, 376Y, 380D, 382D, 382P, 385P, 424H, 424M, 424V, 4341, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, 440V.

[0335] In some embodiments, an antibody comprises a Fc region selected from the representative sequences disclosed in Table 3, Table 13, and Table 9B. In some embodiments, an antibody comprises an IgGl Fc region comprising E233P, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising S228P and L235E. In some embodiments, an antibody comprises an IgGl Fc region comprising L235E, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A and L235A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A, L235A, and G237A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A, L235A, P329G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234F, L235E, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A, L235E, and G237A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A, L235E, G237A, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A, L235A, G237A, P238S, H268A, A330S, and P331S (IgGlo), according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising L234A, L235A, and P329A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising G236R and L328R, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising G237A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc regioncomprising F241 A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising V264A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising D265A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising D265A and N297A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising D265A and N297G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising D270A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising N297A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising N297G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising N297D, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising N297Q, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising P329A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising P329G, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising P329R, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising A330L, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising P331A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgGl Fc region comprising P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region. In some embodiments, an antibody comprises an IgG4 Fc region. In some embodiments, an antibody comprises an IgG4 Fc region comprising S228P, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising S228P, F234A, and L235A, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2-IgG4 cross-subclass (IgG2 / G4) Fc region. In some embodiments, an antibody comprises an IgG2-IgG3 cross-subclass Fc region. In some embodiments, an antibody comprises an IgG2 Fc region comprising H268Q, V309L, A330S, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising V234A, G237A, P238S, H268A, V309L, A330S, and P331S, according to the Kabat numbering system. In some embodiments, an antibody comprises a Fc region comprising high mannose glycosylation.

[0336] In some embodiments, an antibody comprises an IgG4 Fc region comprising a S228P substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising an A330S substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG4 Fc region comprising a P331 S substitution, according to the Kabat numbering system.

[0337] In some embodiments, an antibody comprises an IgG2 Fc region comprising an A330S substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising an P331S substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising an 234A substitution, according to the Kabat numbering system. In some embodiments, an antibody comprises an IgG2 Fc region comprising an 237A substitution, according to the Kabat numbering system.

[0338] In certain embodiments, an anti-TLIA described herein comprises a Fc region as shown in Table 13.Table 13. Exemplary Fc Mutations

[0339] In certain embodiments, an anti-TLIA antibody described herein comprises a Fc region comprising a sequence from Table 9B. In certain embodiments, an anti-TLIA antibody described herein comprises a Fc region comprising any one of SEQ ID NOS: 320- 367 or a sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 320-367.

[0340] In some embodiments, anti-TLIA described herein comprise a light chainconstant 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.

[0341] Additional Non-limiting Example anti-TLIA Antibody Embodiments

[0342] CDR Embodiments

[0343] In one aspect, provided herein is a first embodiment of an anti-TLIA antibody. As used herein, an anti-TLIA antibody includes an anti-TLIA antigen binding fragment. Nonlimiting additional embodiments include: (Embodiment 2) The anti-TLIA antibody of embodiment 1, comprising a heavy chain comprising a HCDRl comprising SEQ ID NO: 1, 401, 407, 413, or 450, a HCDR2 comprising SEQ ID NO: 2, 3, 4, 5, 402, 408, 414, or 451, and a HCDR3 comprising SEQ ID NO: 6, 7, 8, 9, 403, 409, 415, or 452, and a light chain comprising a LCDRl comprising SEQ ID NO: 10, 404, 410, 416, or 453, a LCDR2 comprising SEQ ID NO: 11, 405, 411, 417, or 454, and a LCDR3 comprising SEQ ID NO: 12, 13, 14, 15, 406, 412, 418, or 455. (Embodiment 3) The anti-TLIA antibody of embodiment 1, comprising a HCDR1 comprising SEQ ID NO: 1. (Embodiment 4) The anti- TLIA antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 2. (Embodiment 5) The anti-TLIA antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 3. (Embodiment 6) The anti-TLIA antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 4. (Embodiment 7) The anti-TLIA antibody of embodiment 1 or embodiment 2, comprising a HCDR2 comprising SEQ ID NO: 5. (Embodiment 8) The anti-TLIA antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 6. (Embodiment 9) The anti-TLIA antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 7. (Embodiment 10) The anti-TLIA antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 8. (Embodiment 11) The anti-TLIA antibody of any one of embodiments 1-6, comprising a HCDR3 comprising SEQ ID NO: 9. (Embodiment 12) The anti-TLIA antibody of any one of embodiments 1-10, comprising a LCDR1 comprising SEQ ID NO: 10. (Embodiment 13) The anti-TLIA antibody of any one of embodiments 1-11, comprising a LCDR2 comprising SEQ ID NO: 11. (Embodiment 14) The anti-TLIA antibody of any one of embodiments 1-12, comprising a LCDR3 comprising SEQ ID NO: 12. (Embodiment 15) The anti-TLIA antibody of any one of embodiments 1-12, comprising a LCDR3 comprising SEQ ID NO: 13. (Embodiment 16) The anti-TLIA antibody of any one of embodiments 1-12, comprising a LCDR3 comprising SEQ ID NO: 14 or 15. (Embodiment 17) the anti-TLIA antibody of embodiment 1, comprising the CDRs of antibody A, B, C, D, E, F, G, H, I, A2, B2, C2, D2, E2, F2, G2, H2, 12, J, J2, K, M, or N(Table 10). (Embodiment 18) The anti-TLIA antibody of embodiment 1, comprising a heavy chain variable region comprising: (a) an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1; (b) an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5; and (c) an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and the light chain variable region comprises: (d) an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10; (e) an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11; and (f) an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15. (Embodiment 19) The anti-TLIA antibody of embodiment 1, comprising a HCDR1 as set forth by SEQ ID NO: 1, a HCDR2 as set forth by SEQ ID NO: 2, a HCDR3 as set forth by SEQ ID NO: 6, a LCDRl as set forth by SEQ ID NO: 10, a LCDR2 as set forth by SEQ ID NO: 11, and a LCDR3 as set forth by SEQ ID NO: 12

[0344] Framework Embodiments

[0345] (Embodiment 20) The anti-TLIA antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising IGHV1 -46*02. (Embodiment 21) The anti- TLIA antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising a variant of IGHV1 -46*02 comprising between about 1 and about 20 amino acid substitutions from SEQ ID NO: 316. (Embodiment 22) The anti-TLIA antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising a variant of IGHV1- 46*02 comprising between about 1 and about 9 amino acid substitutions from SEQ ID NO: 316. (Embodiment 23) The anti-TLIA antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising a variant of IGHV1-46*O2 comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from SEQ ID NO: 316 in the framework. (Embodiment 24) The anti-TLIA antibody of any one of embodiments 21-23, wherein the heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. (Embodiment 25) The anti-TLIA antibody of any one of embodiments 21-24, wherein the heavy chain framework substitution comprises R45K, as determined by Aho or Kabat numbering. (Embodiment 26) The anti-TLIA antibody of any one of embodiments 21-25, wherein the heavy chain framework substitution comprises A47R, as determined by Aho or Kabat numbering. (Embodiment 27) The anti- TLIA antibody of any one of embodiments 21-26, wherein the heavy chain framework substitution comprises M55I, as determined by Aho or Kabat numbering. (Embodiment 28) The anti-TLIA antibody of any one of embodiments 21-27, wherein the heavy chain framework substitution comprises V78A, as determined by Aho or Kabat numbering.Ill(Embodiment 29) The anti-TLl A antibody of any one of embodiments 21-28, wherein the heavy chain framework substitution comprises M80I, as determined by Aho or Kabat numbering. (Embodiment 30) The anti-TLl A antibody of any one of embodiments 21-29, wherein the heavy chain framework substitution comprises R82T, as determined by Aho or Kabat numbering. (Embodiment 31) The anti-TLl A antibody of any one of embodiments 21- 30, wherein the heavy chain framework substitution comprises V89A, as determined by Aho or Kabat numbering. (Embodiment 32) The anti-TLl A antibody of any one of embodiments 21-31, wherein the heavy chain framework substitution comprises M91L, as determined by Aho or Kabat numbering.

[0346] (Embodiment 33) The anti-TLIA antibody of any one of embodiments 1-19, comprising a heavy chain framework comprising SEQ ID NO: 301. (Embodiment 34) The anti-TLIA antibody of embodiment 33, wherein XI is Q. (Embodiment 35) The anti-TLIA of embodiment 33, wherein XI = E. (Embodiment 36) The anti-TLIA of any one of embodiments 33-35, wherein X2 = R. (Embodiment 37) The anti-TLIA of any one of embodiments 33-35, wherein X2 = K. (Embodiment 38) The anti-TLIA of any one of embodiments 33-37, wherein X3 = A. (Embodiment 39) The anti-TLIA of any one of embodiments 33-37, wherein X3 = R. (Embodiment 40) The anti-TLIA of any one of embodiments 33-39, wherein X4 = M. (Embodiment 41) The anti-TLIA of any one of embodiments 33-39, wherein X4 = I. (Embodiment 42) The anti-TLIA of any one of embodiments 33-41, wherein X5 = V. (Embodiment 43) The anti-TLIA of any one of embodiments 33-41, wherein X5 = A. (Embodiment 44) The anti-TLIA of any one of embodiments 33-43, wherein X6 = M. (Embodiment 45) The anti-TLIA of any one of embodiments 33-43, wherein X6 = I. (Embodiment 46) The anti-TLIA of any one of embodiments 33-45, wherein X7 = R. (Embodiment 47) The anti-TLIA of any one of embodiments 33-45, wherein X7 = T. (Embodiment 48) The anti-TLIA of any one of embodiments 33-47, wherein X8 = V. (Embodiment 49) The anti-TLIA of any one of embodiments 33-47, wherein X8 = A. (Embodiment 50) The anti-TLIA of any one of embodiments 33-49, wherein X9 = M. (Embodiment 51) The anti-TLIA of any one of embodiments 33-49, wherein X9 = L.

[0347] (Embodiment 52) The anti-TLIA antibody of any one of embodiments 1-51, comprising a light chain framework comprising IGKV3 -20*01. (Embodiment 53) The anti- TLIA antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3-20*01 comprising between about 1 and about 20 amino acid substitutions from SEQ ID NO: 317. (Embodiment 54) The anti-TLIA antibody of any oneof embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3- 20*01 comprising about 1 amino acid substitution from SEQ ID NO: 317. (Embodiment 55) The anti-TLIA antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3-20*01 comprising about 2 amino acid substitutions from SEQ ID NO: 317. (Embodiment 56) The anti-TLIA antibody of any one of embodiments 1-51, comprising a light chain framework comprising a variant of IGKV3- 20*01 comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions from SEQ ID NO: 317 in the framework. (Embodiment 57) The anti-TLIA antibody of any one of embodiments 53-56, wherein the light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. (Embodiment 58) The anti-TLIA antibody of any one of embodiments 53-57, wherein the light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

[0348] (Embodiment 59) The anti-TLIA antibody of any one of embodiments 1-51, comprising a light chain comprising a light chain framework comprising SEQ ID NO: 303. (Embodiment 60) The anti-TLIA antibody of embodiment 59, wherein X10 is L. (Embodiment 61) The anti-TLIA antibody of embodiment 59, wherein X10 is P.(Embodiment 62) The anti-TLIA antibody of any one of embodiments 59-61, wherein XI 1 is L. (Embodiment 63) The anti-TLIA antibody of any one of embodiments 59-61, wherein XI 1 is W.

[0349] (Embodiment 64) The anti-TLIA antibody of any one of embodiments 1-19, comprising a heavy chain variable framework region comprising a modified human IGHV 1 - 46*02 framework, and a light chain variable framework region comprising a human IGKV3 - 20 framework or a modified human IGKV3-20 framework, wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise at least one amino acid modification(s) as compared to the human IGHV1 -46*02 framework and the human IGKV3-20 framework. (Embodiment 65) The antibody of embodiment 64, wherein the at least one amino acid modification(s) is no more than about 13, 12, 11, 10, 9, or 8 amino acid modifications. (Embodiment 66) The antibody of embodiment 64 or embodiment 65, wherein the amino acid modification(s) comprise: a modification at amino acid position 45 in the heavy chain variable region. (Embodiment 67) The antibody of any one of embodiments 64-66, wherein the amino acid modification(s) comprise a modification at amino acid position 47 in the heavy chain variable region. (Embodiment 68) The antibody of any one of embodiments 64-67, wherein the amino acid modification(s) comprise a modification at amino acid position 55 in the heavy chain variable region. (Embodiment 69)The antibody of any one of embodiments 64-68, wherein the amino acid modification(s) comprise a modification at amino acid position 78 in the heavy chain variable region. (Embodiment 70) The antibody of any one of embodiments 64-69, wherein the amino acid modification(s) comprise a modification at amino acid position 80 in the heavy chain variable region. (Embodiment 71) The antibody of any one of embodiments 64-70, wherein the amino acid modification(s) comprise a modification at amino acid position 82 in the heavy chain variable region. (Embodiment 72) The antibody of any one of embodiments 64-71, wherein the amino acid modification(s) comprise a modification at amino acid position 89 in the heavy chain variable region. (Embodiment 73) The antibody of any one of embodiments 64- 72, wherein the amino acid modification(s) comprise a modification at amino acid position 91 in the heavy chain variable region, per Kabat numbering. (Embodiment 74) The antibody of any one of embodiments 64-65, wherein the amino acid modification(s) comprise (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L in the heavy chain variable region, per Kabat numbering; or a combination of two or more modifications selected from (a) to (h). (Embodiment 75) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: A47R. (Embodiment 76) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: A47R, M55I, V78A, M80I, R82T, V89A, and M91L; A47R, M80I, and R82T; A47R, M80I, R82T, V89A, and M91L; or A47R, M55I, V78A, M80I, V89A, and M91L. (Embodiment 77) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K and A47R. (Embodiment 78) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K, A47R, V89A, and M91L. (Embodiment 79) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K and A47R, and M80I. (Embodiment 80) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K, A47R, M80I, and M91L; R45K, A47R, V78A, M80I, V89A, and M91L; R45K, A47R, M55I, V78A, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, V89A, and M91L; R45K, A47R, M55I, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, and V89A; R45K, A47R, M80I, R82T, V89A, M91L; or R45K, A47R, M55I, M80I, V89A, and M91L. (Embodiment 81) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K. (Embodiment 82) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: R45K and V78A. (Embodiment 83) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: V78A. (Embodiment 84) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. (Embodiment 85) The antibody of embodiment 74, wherein theamino acid modification(s) comprise: V89A. (Embodiment 86) The antibody of embodiment 74, wherein the amino acid modification(s) comprise: M80I. (Embodiment 87) The antibody of any one of embodiments 64-86, wherein the amino acid modification(s) comprises: (a) a modification at amino acid position 54 in the light chain variable region; and / or (b) a modification at amino acid position 55 in the light chain variable region, per Kabat numbering. (Embodiment 88) The antibody of embodiment 87, wherein the amino acid modification(s) comprises L54P in the light chain variable region, per Aho or Kabat numbering. (Embodiment 89) The antibody of embodiment 87 or 88, wherein the amino acid modification(s) comprises L55W in the light chain variable region, per Aho or Kabat numbering.

[0350] (Embodiment 90) The antibody of any one of embodiments 1-19, comprising a heavy chain FR1 as set forth by SEQ ID NO: 304. (Embodiment 91) The antibody of any one of embodiments 1-19 or 90, comprising a heavy chain FR2 as set forth by SEQ ID NO: 305. (Embodiment 92) The antibody of any one of embodiments 1-19 or 90, comprising a heavy chain FR2 as set forth by SEQ ID NO: 313. (Embodiment 93) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 306. (Embodiment 94) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 307. (Embodiment 95) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 314. (Embodiment 96) The antibody of any one of embodiments 1-19 or 90-92, comprising a heavy chain FR3 as set forth by SEQ ID NO: 315. (Embodiment 97) The antibody of any one of embodiments 1-19 or 90-96, comprising a heavy chain FR4 as set forth by SEQ ID NO: 308. (Embodiment 98) The antibody of any one of embodiments 1-19 or 90-97, comprising a light chain FR1 as set forth by SEQ ID NO: 309. (Embodiment 99) The antibody of any one of embodiments 1-19 or 90-98, comprising a light chain FR2 as set forth by SEQ ID NO: 310. (Embodiment 100) The antibody of any one of embodiments 1-19 or 90-99, comprising a light chain FR3 as set forth by SEQ ID NO: 311. (Embodiment 101) The antibody of any one of embodiments 1-19 or 90-100, comprising a light chain FR4 as set forth by SEQ ID NO: 312. (Embodiment 102) The antibody of any one of embodiments 1 -19, comprising a HC FR1 as set forth by SEQ ID NO: 304, a HC FR2 as set forth by SEQ ID NO: 305, a HC FR3 as set forth by SEQ ID NO: 307, a HC FR4 as set forth by SEQ ID NO: 308, a LC FR1 as set forth by SEQ ID NO: 309, a LC FR2 as set forth by SEQ ID NO: 310, a LC FR3 as set forth by SEQ ID NO: 311, and a LC FR4 as set forth by SEQ ID NO: 312.

[0351] Variable Region Embodiments

[0352] (Embodiment 103) The antibody of embodiment 1, comprising a heavy chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 101-169 or 420-427, and a light chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 201-220 or 430-437. (Embodiment 104) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least 96% identical to SEQ ID NO: 104, and a light chain variable domain comprising an amino acid sequence at least 97% identical to SEQ ID NO: 201. (Embodiment 105) The antibody of embodiment 103, comprising an amino acid sequence at least 97% identical to SEQ ID NO: 104. (Embodiment 106) The antibody of embodiment 103, comprising an amino acid sequence at least 98% identical to SEQ ID NO: 104. (Embodiment 107) The antibody of embodiment 103, comprising an amino acid sequence at least 99% identical to SEQ ID NO: 104. (Embodiment 108) The antibody of embodiment 103, comprising SEQ ID NO: 104. (Embodiment 109) The antibody of any one of embodiments 103-108, comprising an amino acid sequence at least 98% identical to SEQ ID NO: 201. (Embodiment 110) The antibody of embodiment 109, comprising an amino acid sequence at least about 99% identical to SEQ ID NO: 201. (Embodiment 111) The antibody of embodiment 109, comprising SEQ ID NO: 201.

[0353] (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 112-115, wherein the light chain variable domain comprises an amino acid sequence at least about 98% identical to SEQ ID NO: 201. (Embodiment 117) The antibody of any one of embodiments 112-116, wherein the light chain variable domain comprises an amino acid sequence at least about 99% identical to SEQ ID NO: 201. (Embodiment 118) The antibody of any one of embodiments 112-117, wherein thelight chain variable domain comprises SEQ ID NO: 201. (Embodiment 119) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, and a light chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430. (Embodiment 120) The antibody of embodiment 103, comprising a heavy chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 421, and a light chain variable domain comprising an amino acid sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 431.

[0354] Fc region Embodiments

[0355] (Embodiment 121) The antibody of any one of embodiments 1-120, comprising a fragment crystallizable (Fc) region. (Embodiment 122) The antibody of embodiment 121, comprising reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgGl and / or reduced complement-dependent cytotoxicity (CDC) as compared to human IgGl. (Embodiment 123) The antibody of embodiment 122, wherein the human IgGl comprises SEQ ID NO: 320. (Embodiment 124) The antibody of embodiment 122 or embodiment 123, wherein the ADCC function of the Fc region comprising reduced ADCC is at least about 50% reduced as compared to human IgGl. (Embodiment 125) The antibody of any one of embodiments 122-124, wherein the CDC function of the Fc region comprising reduced ADCC is at least about 50% reduced as compared to human IgGl. (Embodiment 126) The anti-TLIA antibody of any one of embodiments 121-125, comprising a human IgGl Fc region comprising (a) 297A, 297Q, 297G, or 297D, (b) 279F, 279K, or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R, or 235S, (e) 237A, 237E, 237K, 237N, or 237R, (f) 234A, 234V, or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y, or 329R (k) 331S, (1) 236F or 236R, (m) 238A, 238E, 238G, 238H, 2381, 238V, 238W, or 238 Y, (n) 248 A, (o) 254D, 254E, 254G, 254H, 2541, 254N, 254P, 254Q, 254T, or 254V, (p) 255N, (q) 256H, 256K, 256R, or 256V, (r) 264S, (s) 265H, 265K, 265S, 265Y, or 265 A, (t) 267G, 267H, 2671, or 267K, (u) 268K, (v) 269N or 269Q, (w) 270A, 270G, 270M, or 270N, (x) 271T, (y) 272N, (z) 292E, 292F, 292G, or 2921, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 3 HE, 311G, or 31 IS, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii)3431 or 343V, (jj) 373 A, 373G, or 373S, (kk) 376E, 376W, or 376Y, (11) 380D, (mm) 382D or 382P, (nn) 385P, (oo) 424H, 424M, or 424V, (pp) 4341, (qq) 438G, (rr) 439E, 439H, or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T, or 440V, (tt) E233P, (uu) L235E, (vv) L234A and L235A, (ww) L234A, L235A, and G237A, (xx) L234A, L235A, and P329G, (yy) L234F, L235E, and P331S, (zz) L234A, L235E, and G237A, (aaa), L234A, L235E, G237A, and P331S (bbb) L234A, L235A, G237A, P238S, H268A, A330S, and P331S (IgGlo), (ccc) L234A, L235A, and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265 A, (iii) D265 A and N297A, (jjj) D265 A and N297G, (kkk) D270A, (111) A330L, (mmm) P331A or P331S, or (nnn) any combination of (a) - (uu), per Kabat numbering. (Embodiment 127) The anti-TLIA of any one of embodiments 121-125, comprising a (i) human IgG4 Fc region or (ii) a human IgG4 Fc region comprising (a) S228P, (b) S228P and L235E, or (c) S228P, F234A, and L235A, per Kabat numbering. (Embodiment 128) The anti-TLIA of any one of embodiments 121-125, comprising a human IgG2 Fc region; IgG2-IgG4 cross-subclass Fc region; IgG2-IgG3 cross-subclass Fc region; IgG2 comprising H268Q, V309L, A330S, P331S (IgG2m4); or IgG2 comprising V234A, G237A, P238S, H268A, V309L, A330S, P331S (IgG2c>). (Embodiment 129) The antibody of any one of embodiments 121-125, comprising a human IgGl comprising one or more substitutions selected from the group comprising 329A, 329G, 329Y, 33 IS, 236F, 236R, 238A, 238E, 238G, 238H, 2381, 238V, 238W, 238 Y, 248 A, 254D, 254E, 254G, 254H, 2541, 254N, 254P, 254Q, 254T, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 2671, 267K, 4341, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T, and 440V, per Kabat numbering. (Embodiment 130) The anti-TLIA of any one of embodiments 121-125, comprising a heavy chain Fc region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 320-362. (Embodiment 131) The anti- TLIA of any one of embodiments 121-125, comprising a heavy chain Fc region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 368-380. (Embodiment 132) The anti-TLIA of any one of embodiments 121-125, comprising a constant region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 381.

[0356] Additional antibody features

[0357] (Embodiment 133) The anti-TLIA antibody of any one of embodiments 1-132, comprising a light chain constant region comprising a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 319.

[0358] (Embodiment 134) The anti-TLIA antibody of any one of embodiments 1-133, comprising at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% monomeric fraction as determined by size exclusion chromatography. (Embodiment 135) , The antibody of embodiment 134, wherein the size exclusion chromatography comprises injecting purified antibody onto a size exclusion column, wherein the antibody is purified by protein A. (Embodiment 136) The antibody of embodiment 134 or 135, wherein the antibody is purified as described in Example 2. (Embodiment 137) The antibody of any one of embodiments 134-136, wherein the antibody is expressed under conditions described in Example 2. (Embodiment 138) The antibody of any one of embodiments 132-135, wherein the size exclusion chromatography column has an inner diameter of 4.6 mm, the size exclusion chromatography column has a length of 150 mm, or the size exclusion chromatography column has an inner diameter of 4.6 mm and a length of 150mm. (Embodiment 139) The antibody of any one of embodiments 134-138, wherein the size exclusion chromatography column has a pore size of 200 A, the size exclusion chromatography column has a particle size of 1.7 micrometer, or the size exclusion chromatography column has a pore size of 200 A and a particle size of 1.7 micrometer. (Embodiment 140) The antibody of any one of embodiments 134-139, wherein the size exclusion chromatography column is ACQUITY UPLC BEH200 SEC column. (Embodiment 141) The antibody of any one of embodiments 134-140, wherein the antibody or antigen binding fragment is injected at a total volume of 15 pL. (Embodiment 142) The antibody of any one of embodiments 134-141, wherein the antibody is injected at a concentration of about 0.1 pg / pL to about 1.0 pg / pL. (Embodiment 143) The antibody of any one of embodiments 134-142, wherein the size exclusion chromatography is performed on a Shimadzu UPLC instrument. (Embodiment 144) The antibody of any one of embodiments 134-143, wherein the size exclusion chromatography is performed at a flow rate of 0.2 mL / min. (Embodiment 145) The antibody of any one of embodiments 134-144, wherein the size exclusion chromatography is performed at a column oven temperature of 30°C. (Embodiment 146) The antibody of any one of embodiments 134-145, wherein the percentage of monomer is calculated using Shimadzu software. (Embodiment 147) The antibody of any one of embodiments 134-146, wherein the size exclusion chromatography isperformed as described in Example 2.

[0359] (Embodiment 148) The anti-TLIA antibody of any one of embodiments 1-147, wherein the anti-TLIA is expressed at a concentration of at least about 2 pg / mL, between about 2 pg / mL and about 60 pg / mL, between about 5 pg / mL and about 60 pg / mL, between about 10 pg / mL and about 60 pg / mL, at least about 5 pg / mL, at least about 10 pg / mL, at least about 15 pg / mL, at least about 20 pg / mL, between about 2 pg / mL and about 50 pg / mL, between about 2 pg / mL and about 40 pg / mL, between about 2 pg / mL and about 30 pg / mL, between about 2 pg / mL and about 20 pg / mL, between about 5 pg / mL and about 50 pg / mL, between about 5 pg / mL and about 40 pg / mL, between about 5 pg / mL and about 30 pg / mL, between about 10 pg / mL and about 50 pg / mL, between about 10 pg / mL and about 40 pg / mL, or between about 10 pg / mL and about 30 pg / mL, as determined by a method disclosed herein. (Embodiment 149) The anti-TLIA antibody of any one of embodiments 1- 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 pg / mL as determined by a method disclosed herein. (Embodiment 150) The antibody of embodiment 148 or embodiment 149, wherein the antibody is expressed in FreeStyle 293 -F cells. (Embodiment 151) The antibody of any one of embodiments 148-150, wherein the antibody is expressed as described in Example 2. (Embodiment 152) The antibody of any one of embodiments 148-151, 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 a surface of a substrate with a capture antibody that binds to a human or humanized antibody, applying the anti-TLIA antibody to the substrate, and applying to the substrate a second antibody that binds to a human or humanized antibody. (Embodiment 154) The antibody of embodiment 153, where the capture antibody comprises an anti-kappa antibody. (Embodiment 155) The antibody of embodiment 153 or embodiment 154, where the second antibody comprises an anti-Fc antibody. (Embodiment 156) The antibody of any one of embodiments 152-155, where the ELISA is performed as described in Example 2.

[0360] (Embodiment 157) A method of treating a disease and / or condition of the kidney in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-156. (Embodiment 158) The method of embodiment 157, wherein the disease and / or condition of the kidney comprises end-stage renal disease, tubulointerstitial renal fibrosis, glomerulonephritis, interstitial nephritis, acute interstitial nephritis, diabetic kidney diseases, lupus nephritis, Alport syndrome, or polycystic kidney disease, or a combination thereof. (Embodiment 159) Amethod of treating inflammation and / or fibrosis in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment of any one of embodiments 1-156. (Embodiment 160) the method of embodiment 159, wherein the subject has inflammatory bowel disease.

[0361] (Embodiment 161) A nucleic acid encoding the antibody of any one of embodiments 1-156. (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.

[0362] Antibody Properties

[0363] Anti-TLl A antibodies described herein bind to specific regions or epitopes of human ILIA. In various embodiments, an anti-TLIA antibody provided herein has a binding affinity to human ILIA of less than about IE'7, IE'8, IE'9, or IE'10Kd. In some cases, the binding affinity is from about IE-9to about IE-10Kd. In some embodiments, an anti-TLIA antibody provided herein has a binding affinity to murine TL1 A and / or rat TL1 A of less than about IE-7, IE-8, IE-9, IE-10, or IE-11Kd. Methods for determining binding affinity are exemplified herein, including in Example 2.

[0364] In various embodiments, an anti-TLIA antibody provided herein is an antagonist of a TL1 A receptor, such as, but not limited to, DR3 and TR6 / DcR3. In certain embodiments, the antibody inhibits 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 activity of the bound TL1A receptor. In certain embodiments, the anti-TLIA antibody inhibits TL1A activation as measured by interferon gamma release in human blood. In certain embodiments, the antibody inhibits interferon gamma release in human blood at an IC50 of between about 1 nanomolar and about 30 picomolar. In certain embodiments, the antibody inhibits interferon gamma release in human blood at an IC50 of between about 500 picomolar and about 30 picomolar. In certain embodiments, the antibody inhibits interferon gamma release in human blood at an IC50 of between about 200 picomolar and about 30 picomolar. In certain embodiments, the antibody inhibits interferon gamma release in human blood at an IC50 of less than or ...

Claims

CLAIMSWHAT IS CLAIMED IS:

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

2. The method of claim 1, wherein the subject has inflammation in the kidney.

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

4. The method of claim 3, wherein the subject has fibrosis in the kidney.

5. A method of treating a disease and / or condition of the kidney in a subject in need thereof, the method comprising administering to the subject an antibody or antigen binding fragment thereof that binds to tumor necrosis factor-like protein 1 A (anti- TLl A antibody or antigen binding fragment).

6. The method of any one of claims 1-5, wherein the subject has a chronic kidney disorder.

7. The method of any one of claims 1-6, wherein the subject has end stage renal disease.

8. The method of any one of claims 1-6, wherein the subject has tubulointerstitial renal fibrosis.

9. The method of any one of claims 1-6, wherein the subject has nephritis.

10. The method of any one of claims 1-6, wherein the subject has diabetic kidney disease.

11. The method of any one of claims 1-6, wherein the subject has polycystic kidney disease.

12. The method of any one of claims 1-6, wherein the subject has end-stage renal disease, tubulointerstitial renal fibrosis, glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, diabetic kidney diseases, lupus nephritis, Alport syndrome, or polycystic kidney disease, or a combination thereof.

13. The method of any one of claims 1-12, wherein the anti -ILIA antibody or antigen binding fragment is administered in a pharmaceutical composition.

14. The method of claim 13, wherein the pharmaceutical composition comprises the anti- TLl A antibody or antigen binding fragment at a concentration greater than about 150 mg / mL.

15. The method of claim 14, wherein the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, or 250 mg / mL.

16. The method of claim 14, wherein the concentration is about 150 mg / mL to about 250 mg / mL.

17. The method of claim 14, wherein the concentration is about 175 mg / mL to about 225 mg / mL.

18. The method of any one of claims 13-17, wherein the pharmaceutical composition is administered subcutaneously.

19. The method of claim any one of claims 13-18, wherein about 150 mg to about 500 mg of the anti-TLl A antibody or antigen binding fragment is present in the composition.

20. The method of any one of claims 13-19, wherein the composition has a total volume of less than or equal to about 2 mL.

21. The method of any one of claims 13-20, wherein the pharmaceutical composition comprises a therapeutically effective dose of the anti-TLl A antibody or antigen binding fragment.

22. The method of any one of claims 13-21, wherein the composition has a total volume less than or equal to about 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.

23. The method of any one of claims 13-22, wherein the composition has a total volume of about 0.5 mL to about 1.5 mL.

24. The method of any one of claims 13-23, wherein the composition has a viscosity of less than about 20 cP.

25. The method of claim 24, wherein the composition has a viscosity of less than about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or 5 cP.

26. The method of any one of claims 13-25, wherein the composition has a viscosity of about 1 cP to about 20 cP.

27. The method of any one of claims 13-26, wherein the pharmaceutical composition has a percentage aggregation of anti-TLl A antibody or antigen binding fragment as measured by size exclusion chromatography of less than about 5% of the total anti- TLl A antibody or antigen binding fragment in the composition.

28. The method of claim 27, wherein the aggregation is less than about 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5%.

29. The method of any one of claims 13-27, wherein the composition comprises a surfactant.

30. The method of claim 29, wherein the surfactant comprises a nonionic surfactant.

31. The method of claim 30, wherein the nonionic surfactant comprises polysorbate-20.

32. The method of any one of claims 29-31, wherein the surfactant is present at a concentration of about 0.005% to about 0.05% of the composition.

33. The method of claim 32, wherein the surfactant is present at a concentration of about 0.01% to about 0.02% of the composition.

34. The method of any one of claims 13-33, wherein the composition comprises a salt.

35. The method of claim 34, wherein the salt comprises sodium chloride, glycine, lysinehydrochloride, arginine-hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof.

36. The method of claim 35, wherein the salt comprises sodium chloride.

37. The method of claim 35, wherein the salt comprises lysine-HCl.

38. The method of any one of claims 34-37, wherein the salt is present at a concentration of about 10 mM to about 100 mM in the composition.

39. The method of claim 38, wherein the salt is present at a concentration of about 25 mM in the composition.

40. The method of claim 38, wherein the salt is present at a concentration of about 40 m in the composition.

41. The method of any one of claims 13-40, wherein the composition comprises a stabilizer.

42. The method of claim 41, wherein the stabilizer comprises a sugar, polyol, amino acid, or polymer, cyclodextrin (e.g., HP-b-CD), or a combination thereof.

43. The method of claim 42, wherein the stabilizer comprises the sugar.

44. The method of claim 43, wherein the sugar comprises sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof.

45. The method of claim 44, wherein the sugar comprises sucrose.

46. The method of any one of claims 41-45, wherein the stabilizer is present at a concentration of about 50 mM to about 300 mM in the composition.

47. The method of claim 46, wherein the stabilizer is present at a concentration of about 200 mM to about 280 mM.

48. The method of claim 47, wherein the stabilizer is present at a concentration of about 220 to about 240 mM.

49. The method of any one of claims 13-48, wherein the composition comprises a buffering agent.

50. The method of claim 49, wherein the buffering agent comprises acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, Tris (tris (hydroxymethyl) aminomethane), or diethanolamine, or a combination thereof.

51. The method of claim 50, wherein the buffering agent comprises acetate buffer.

52. The method of any one of claims 49-51, wherein the buffering agent is present at a concentration of about 10 mM to about 50 mM in the composition.

53. The method of claim 52, wherein the composition comprises about 20 mM buffer.

54. The method of any one of claims 13-53, wherein the composition has a pH of about 4.5 to about 8.0.

55. The method of claim 54, wherein the composition has a pH of about 4.5 to about 7.5.

56. The method of claim 55, wherein the composition has a pH of about 5 to about 5.5.

57. The method of claim 56, wherein the composition has a pH of about 5.3.

58. The method of any one of claims 1-57, wherein the anti-TLIA antibody or antigen binding fragment is administered to the subject at a first dose up to about 1000 mg.

59. The method of any one of claims 1-57, wherein the anti-TLIA antibody or antigen binding fragment is administered to the subject at a first dose of about 150 mg to about 1000 mg.

60. The method of claim 59, wherein the first dose is about 500 mg to about 1000 mg.

61. The method of claim 60, wherein the first dose is about 500 mg or about 800 mg.

62. The method of any one of claims 58-61, wherein the first dose is administered to the subject at a first time point, and a second dose is administered to the subject at a second time point.

63. The method of claim 62, wherein the second time point is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days after the first time point.

64. The method of claim 62, wherein the second time point is about 1, 2, 3, or 4 weeks after the first time point.

65. The method of any one of claims 62-64, wherein the second dose comprises up to about 1000 mg anti-TLIA antibody or antigen binding fragment.

66. The method of any one of claims 62-64, wherein the second dose comprises about 150 mg to about 1000 mg.

67. The method of claim 66, wherein the second dose comprises about 150 mg to about 600 mg.

68. The method of any one of claims 62-67, wherein a third dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a third time point.

69. The method of claim 68, wherein 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.

70. The method of claim 68, wherein the third time point is about 1, 2, 3, or 4 weeks after the second time point.

71. The method of any one of claims 68-70, wherein the third dose comprises up to about 1000 mg anti-TLIA antibody or antigen binding fragment.

72. The method of any one of claims 68-70, wherein the third dose comprises about 150 mg to about 1000 mg.

73. The method of claim 72, wherein the third dose comprises about 150 mg to about 600 mg.

74. The method of any one of claims 68-73, wherein a fourth dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a fourth time point.

75. The method of claim 74, wherein 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.

76. The method of claim 74, wherein the fourth time point is about 1, 2, 3, or 4 weeks after the third time point.

77. The method of any one of claims 74-76, wherein the fourth dose comprises up to about 1000 mg anti-TLIA antibody or antigen binding fragment.

78. The method of any one of claims 74-76, wherein the fourth dose comprises about 150 mg to about 1000 mg.

79. The method of claim 78, wherein the fourth dose comprises about 150 mg to about 600 mg.

80. The method of any one of claims 74-79, wherein a fifth dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a fifth time point.

81. The method of claim 80, wherein 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.

82. The method of claim 80, wherein the fifth time point is about 1, 2, 3, or 4 weeks after the fourth time point.

83. The method of any one of claims 80-82, wherein the fifth dose comprises up to about 1000 mg anti-TLl A antibody or antigen binding fragment.

84. The method of any one of claims 80-82, wherein the fifth dose comprises about 150 mg to about 1000 mg.

85. The method of claim 84, wherein the fifth dose comprises about 150 mg to about 600 mg.

86. The method of any one of claims 80-85, wherein a sixth dose of anti-TLIA antibody or antigen binding fragment is administered to the subject at a sixth time point.

87. The method of claim 86, wherein 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.

88. The method of claim 86, wherein the sixth time point is about 1, 2, 3, or 4 weeks after the fifth time point.

89. The method of any one of claims 86-88, wherein the sixth dose comprises up to about 1000 mg anti-TLIA antibody or antigen binding fragment.

90. The method of any one of claims 86-88, wherein the sixth dose comprises about 150 mg to about 1000 mg.

91. The method of claim 90, wherein the sixth dose comprises about 150 mg to about 600 mg.

92. The method of any one of claims 58-91, wherein an additional dose of the anti-TLIA antibody or antigen binding fragment is administered to the subject at each of the one or more additional time points.

93. The method of claim 92, wherein the one or more additional time points comprises 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.

94. The method of claim 92, wherein the composition is administered to the subject at about 12 additional time points.

95. The method of any one of claims 92-94, wherein 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 a previous time point.

96. The method of any one of claims 92-94, wherein each additional time point is independently about 1, 2, 3, or 4 weeks after a previous time point.

97. The method of claim 96, wherein at least one of the additional time points is about 2 weeks after the previous time point.

98. The method of any one of claims 92-97, wherein the additional dose comprises up to about 1000 mg anti-TLl A antibody or antigen binding fragment.

99. The method of any one of claims 92-97, wherein the additional dose comprises from about 150 mg to about 1000 mg anti-TLIA antibody or antigen binding fragment.

100. The method of claim 99, wherein the additional dose is about 175 mg to about 300 mg anti-TLIA antibody or antigen binding fragment.

101. A method of neutralizing monomeric TL1A and trimeric TL1A in a subject having kidney inflammation and / or kidney fibrosis comprising (a) administering an effective dose of anti-TLIA antibody or antigen binding fragment to the subject, wherein the antibody or antigen binding fragment binds to both monomeric TL1A and trimeric TL1A, wherein the antibody or antigen binding fragment blocks interaction of TL1 A to DR3, wherein the concentration of TL1 A in a diseased tissue in the subject is reduced below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, and wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

102. The method of claim 101, wherein the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease.

103. The method of claim 101 or 102, wherein the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

104. A method of reducing the concentration of TL1 A in a diseased tissue in a subject with kidney inflammation and / or kidney fibrosis comprising (a) administering an effective dose of anti-TLIA antibody or antigen binding fragment to the subject, thereby reducing the concentration of TL1 A in the diseased tissue in thesubject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

105. A method of treating kidney inflammation and / or kidney fibrosis in a subject in need thereof comprising (a) administering an anti-TLl A antibody or antigen binding fragment to the subject, wherein the anti-TLl A antibody or antigen binding fragment is administered at an effective dose such that the concentration of TL1 A in a diseased tissue in the subject after step (a) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, and wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

106. A method of treating kidney inflammation and / or kidney fibrosis in a subject in need thereof comprising(a) administering an anti-TLl A antibody or antigen binding fragment to the subject at an effective dose, and(b) reducing the concentration of TL1 A in a diseased tissue in the subject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis, wherein diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

107. The method of any one of claims 101 to 106, wherein the effective dose comprises an induction regimen.

108. The method of any one of claims 101 to 107, further comprising(c) maintaining TL1A in the diseased tissue in the subject at a concentration below the concentration of TL1 A in the corresponding tissue in the control subject.

109. The method of claim 108, wherein the TL1A in the diseased tissue in the subject is maintained with a maintenance regimen of the anti-TLl A antibody or antigen binding fragment.

110. The method of claim 109, wherein the induction regimen and the maintenance regimen are identical.

111. The method of claim 109, wherein the induction regimen and the maintenance regimen are different.

112. The method of any one of claims 109 to 111, wherein the maintenance regimen is administered after the induction regimen.

113. The method of any one of claims 102 to 112, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject during the induction regimen.

114. The method of any one of claims 102 to 112, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

115. The method of any one of claims 102 to 112, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject.

116. The method of any one of claims 107 to 115, wherein the induction regimen comprises a one-time administration of the anti-TLl A antibody or antigen binding fragment.

117. The method of claim 116, wherein the anti-TLl A 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.

118. The method of any one of claims 107 to 115, wherein the induction regimen comprises multiple administrations of the anti-TLl A antibody or antigen binding fragment.

119. The method of any one of claims 107 to 115 and 118, wherein the induction regimen comprises administrations of(i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10;(ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10;(iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10;(iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or(v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

120. The method of any one of claims 107 to 115 and 118, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

121. The method of any one of claims 107 to 115, 118, and 120, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

122. The method of any one of claims 107 to 115, 118, and 120, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first 2administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

123. The method of any one of claims 108 to 122, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject.

124. The method of any one of claims 108 to 119, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

125. The method of any one of claims 108 to 119, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

126. The method of any one of claims 109 to 125, wherein the maintenance regimen comprises multiple administrations of the anti-TLl A antibody or antigen binding fragment.

127. The method of any one of claims 109 to 126, wherein the maintenance regimen comprises administrations of the anti-TLl A antibody or antigen binding fragment at(i) 500 mg / dose every 2 weeks,(ii) 400 mg / dose every 2 weeks,(iii) 300 mg / dose every 2 weeks,(iv) 250 mg / dose every 2 weeks,(v) 200 mg / dose every 2 weeks,(vi) 150 mg / dose every 2 weeks,(vii) 100 mg / dose every 2 weeks,(viii) 50 mg / dose every 2 weeks,(ix) 500 mg / dose every 4 weeks,(x) 400 mg / dose every 4 weeks,(xi) 300 mg / dose every 4 weeks,(xii) 250 mg / dose every 4 weeks,(xiii) 200 mg / dose every 4 weeks,(xiv) 150 mg / dose every 4 weeks,(xv) 100 mg / dose every 4 weeks,(xvi) 50 mg / dose every 4 weeks,(xvii) 500 mg / dose every 6 weeks,(xviii) 400 mg / dose every 6 weeks,(xix) 300 mg / dose every 6 weeks,(xx) 250 mg / dose every 6 weeks,(xxi) 200 mg / dose every 6 weeks,(xxii) 150 mg / dose every 6 weeks,(xxiii) 100 mg / dose every 6 weeks,(xxiv) 50 mg / dose every 6 weeks,(xxv) 500 mg / dose every 8 weeks,(xxvi) 400 mg / dose every 8 weeks,(xxvii) 300 mg / dose every 8 weeks,(xxviii) 250 mg / dose every 8 weeks,(xxix) 200 mg / dose every 8 weeks,(xxx) 150 mg / dose every 8 weeks,(xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

128. The method of any one of claims 109 to 126, wherein the maintenance regimen comprises administration of the anti-TLIA 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.

129. The method of any one of claims 109 to 126 and 128, wherein the maintenance regimen comprises administration of the anti-TLIA antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

130. The method of any one of claims 109 to 129, wherein the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

131. The method of any one of claims 109 to 129, wherein the maintenance regimen comprises administrations of the anti-TLl A antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

132. The method of any one of claims 109 to 131, wherein the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

133. The method of any one of claims 104 to 132, wherein the antibody or antigen binding fragment binds to both monomeric TL1 A and trimeric TL1 A and wherein the antibody or antigen binding fragment blocks binding of TL1 A to DR3.

134. The method of any one of claims 101 to 133, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1 A in the blood of the subject is occupied by the anti-TLl A antibody or antigen binding fragment.

135. The method of any one of claims 101 to 134, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1 A in the blood of the subject is occupied by the anti-TLl A antibody or antigen binding fragment.

136. The method of any one of claims 101 to 135, wherein binding affinity of the antibody or antigen binding fragment to monomeric TL1 A as measured by dissociation equilibrium constant (Ko-monomer) is comparable to binding affinity of the antibody or antigen binding fragment to trimeric TL1A as measured by dissociation equilibrium constant (KD -trim er).

137. The method of claim 136, wherein the KD -monomer is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold of the KD -trim er.

138. The method of claim 136 or 137, wherein the KD -monomer is no more than 0.06 nM.

139. The method of any one of claims 136 to 138, wherein the KD- trim er is no more than 0.06 nM.

140. The method of any one of claims 103 to 139, wherein the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease.

141. The method of any one of claims 102 to 140, wherein the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

142. The method of any one of claims 101 to 141, wherein the effective dose or the induction regimen is determined by a dose determination method, wherein the dose determination method comprises:(i) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue;(ii) integrating the parameters received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and(iii) determining the effective dose or the induction regimen such that the concentration of TL1 A in diseased tissue in the subject after step (a) is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis.

143. The method of claim 142, wherein the parameter of TL1 A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold over-production comparing to TL1A production in the normal reference tissue.

144. The method of any one of claims 109 to 143, wherein the maintenance regimen is determined by a dose determination method, wherein the dose determination method comprises:(i) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue;(ii) integrating the parameter received in (i) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic model (popPK); and(iii) determining the maintenance regimen such that the concentration of TL1 A in diseased tissue in the subject after step (c) is below the concentration of TL1A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis.

145. The method of claim 144, wherein the parameter of TL1 A over-production is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more fold over-production comparing to TL1 A production in the normal reference tissue.

146. The method of any one of claims 142 to 145, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1A (koff-mAb), synthesis rate of TL1 A in normal tissue (kSyn-normai), synthesis rate of TL1 A in diseased tissue (ksyn- disease), and / or degradation rate of TL1 A (kdeg-totai-TLiA).

147. The method of claim to 146, wherein the association rate of the antibody to TL1 A (kon-mAb) comprises the association rate of the antibody to monomeric TL1 A(k on-monomer ) and association rate of the antibody to trimeric TL1 A (kon-trimer), wherein the dissociation rate of the antibody from TL1 A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff- monomer ) and dissociation rate of the antibody from trimeric TL1 A (koff-trimer), and / or wherein the degradation rate of TL1 A (kdeg-totai-TLiA) comprises degradation rate of monomeric TL1A (kdeg-TLiA -monomer ) and degradation rate of trimeric TL1A (kdeg-TLiA -trim er).

148. The method of any one of claims 142 to 147, wherein the step (i) in the dose determination method further comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb- FcRn), association rate of the antibody-TLl A complex to FcRn receptor (kon-(mAb-TLiA)- FcRn), and / or dissociation rate of the antibody-TLl A complex from FcRn (koff-(mAb- TLlA)-FcRn).

149. The method of claim 148, wherein the association rate of the antibody- ILIA complex to FcRn receptor (kon-(mAb-TLiA)-FcRn) comprises association rate of the antibody-monomeric-TLIA complex to FcRn receptor (kon-(mAb-monoTLiA)-FcRn) and association rate of the antibody-trimeric-TLIA complex to FcRn receptor (kon-(mAb- triTLi A)-FcRn), and / or wherein the dissociation rate of the antibody- ILIA complex fromFcRn (koff-(mAb-TLiA)-FcRn) comprises dissociation rate of the antibody-monomeric- TL1 A complex from FcRn (koff-(mAb-monoTLiA)-FcRn) and dissociation rate of the antibody-trimeric-TLIA complex from FcRn (koff-(mAb-triTLiA)-FcRn).

150. The method of any one of claims 142 to 149, wherein the step (i) in the dose determination method further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn).

151. The method of claim 150, wherein the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TLIA complex (kdeg-(mAb-monoTLiA FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TLIA complex (kdeg-(mAb-triTLiA)- FcRn).

152. The method of any one of claims 146 to 151, wherein in the dose determination method:(1) kon-monomer and kon-trimer are identical or different;(2) koff- monomer and koff-trimer are identical or different;(3) kdeg -monomer and kdeg-trimer are identical or different;(4) kon-(mAb-monoTLlA)-FcRn and kon-(mAb-triTLi A)-FcRn are identical or different;(5) kon-mAb-FcRn and kon-(mAb-monoTLi A)-FcRn are identical or different;(6) kon-mAb-FcRn and kon-(mAb-triTLi A)-FcRn are identical or different;(7) koff-(mAb-monoTLiA)-FcRn and koff-(mAb-triTLiA)-FcRn are identical or different;(8) koff. mAb-FcRn and koff-(mAb-monoTLi A)-FcRn are identical or different;(9) koff- mAb-FcRn and koff-(mAb-triTLi A)-FcRn are identical or different;(10) kdeg-(mAb-monoTLiA)-FcRn and kdeg-(mAb-triTLi A)-FcRn are identical or different;(11) kdeg-mAb-FcRn and kdeg-(mAb-triTLiA)-FcRn are identical or different;(12) kdeg-mAb-FcRn and kdeg-(mAb-monoTLiA)-FcRn are identical or different;(13) any combination of (1) to (12).

153. The method of any one of claims 142 to 152, wherein in the dose determination method: ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn- normal.

154. The method of any one of claims 142 to 153, wherein step (i) in the dose determination method further comprises receiving rate of TL1 A trimerization (kon- TLl A-monomer-to-trimer ) and / or rate of TL1 A monomerization (koff-TLiA -trimer-to-monomer).

155. A method of determining an effective dose regimen for administering an anti- TL1 A antibody to a subject having kidney inflammation and / or kidney fibrosis, wherein the method comprises:(a) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue;(b) integrating the parameter received in (a) to an integrated whole-body physiologically based pharmacokinetic (PBPK) model; and(c) determining the effective dose regimen of the anti-TLl A antibody with the PBPK model from (b) such that after administration of the effective dose regimen the concentration of TL1 A in a diseased tissue in the subject having kidney inflammation and / or kidney fibrosis is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosis wherein the diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

156. A method of determining an effective dose regimen for administering an anti- TLl A antibody to a subject having kidney inflammation and / or kidney fibrosis, wherein the method comprises:(a) receiving a parameter of TL1 A over-production in the diseased tissue comparing to TL1 A production in a normal reference tissue;(b) integrating the parameter received in (a) to a population pharmacokinetic (popPK) model; and(c) determining the effective dose regimen of the anti-TLl A antibody with the popPK model from (b) such that after administration of the effective dose regimen the concentration of TL1 A in a diseased tissue in the subject having kidney inflammation and / or kidney fibrosis is below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney fibrosiswherein the diseased tissue comprises any one or more selected from the group consisting of renal cortex, renal medulla, renal pyramid, renal column, renal papilla, nephron, renal corpuscle, Bowman’s capsule, glomerulus, a fibrotic tissue in the kidney, other tissues with kidney inflammation and / or kidney fibrosis, and other tissues of pathogenesis for the kidney inflammation and / or kidney fibrosis.

157. The method of claim 155 or 156, wherein 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 or more fold over-production comparing to TL1A production in the normal reference tissue.

158. The method of any one of claims 155 to 157, wherein the step (a) further comprises receiving association rate of the antibody to TL1A (kon-mAb), dissociation rate of the antibody from TL1 A (koff-mAb), synthesis rate of TL1 A in normal tissue (ksyn-norma i), synthesis rate of TL1 A in diseased tissue (ksyn-disease), and / or degradation rate of TL1 A (kdeg-totai-TLiA).

159. The method of claim to 158, wherein the association rate of the antibody to TL1 A (kon-mAb) comprises the association rate of the antibody to monomeric TL1 A(k on-monomer ) and association rate of the antibody to trimeric TL1 A (kon-trimer), wherein the dissociation rate of the antibody from TL1 A (koff-mAb) comprises the dissociation rate of the antibody from monomeric TL1A (koff- monomer ) and dissociation rate of the antibody from trimeric TL1A (koff-trimer), and / or wherein the degradation rate of TL1A (kdeg-totai-TLiA) comprises degradation rate of monomeric TL1A (kdeg-TLiA -monomer ) and degradation rate of trimeric TL1A (kdeg-TLiA -trim er).

160. The method of any one of claims 155 to 159, wherein the step (a) comprises receiving association rate of the antibody to FcRn receptor (kon-mAb-FcRn), dissociation rate of the antibody from FcRn (koff- mAb-FcRn), association rate of the antibody-TLl A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn), and / or dissociation rate of the antibody- TLl A complex from FcRn (koff-(mAb-TLiA)-FcRn).

161. The method of claim 160, wherein the association rate of the antibody- TL1A complex to FcRn receptor (kon-(mAb-TLiA)-FcRn) comprises association rate of the antibody-monomeric-TLIA complex to FcRn receptor (kon-(mAb-monoTLiA)-FcRn) and association rate of the antibody-trimeric-TLIA complex to FcRn receptor (kon-(mAb-triTLi A)-FcRn), and / or wherein the dissociation rate of the antibody- TL1A complex from FcRn (koff-(mAb-TLiA)-FcRn) comprises dissociation rate of the antibody-monomeric- TL1 A complex from FcRn (koff-(mAb-monoTLiA)-FcRn) and dissociation rate of the antibody-trimeric-TLIA complex from FcRn (koff-(mAb-triTLiA)-FcRn).

162. The method of any one of claims 155 to 161, wherein the step (a) further comprises receiving clearance rate of FcRn receptor bound by the antibody (kdeg-mAb- FcRn).

163. The method of claim 162, wherein the clearance rate of FcRn receptor bound by the antibody (kdeg-mAb-FcRn) further comprises clearance rate of the antibody to FcRn bound by the antibody-monomeric-TLl A complex (kdeg-(mAb-monoTLiA)-FcRn) and clearance rate of FcRn receptor bound by the antibody-trimeric-TLIA complex (kdeg- (mAb-triTLlA)-FcRn).

164. The method of any one of claims 155 to 163, wherein the subject has one or more inflammatory conditions selected from the group consisting of a chronic kidney disorder, end stage renal disease, tubulointerstitial renal fibrosis, nephritis, diabetic kidney disease, and polycystic kidney disease.

165. The method of any one of claims 155 to 164„ wherein the subject has glomerulonephritis, interstitial nephritis, IgA nephropathy, acute interstitial nephritis, lupus nephritis, or Alport syndrome, pyelonephritis, or a combination thereof.

166. The method of any one of claims 155 to 165, wherein:(1) kon-monomer and kon-trimer are identical or different;(2) koff- monomer and koff-trimer are identical or different;(3) kdeg -monomer and kdeg-trimer are identical or different;(4) kon-(mAb-monoTLlA)-FcRn and kon-(mAb-triTLi A)-FcRn are identical or different;(5) kon-mAb-FcRn and kon-(mAb-monoTLi A)-FcRn are identical or different;(6) kon-mAb-FcRn and kon-(mAb-triTLi A)-FcRn are identical or different;(7) koff-(mAb-monoTLi A)-FcRn and koff-(mAb-triTLiA)-FcRn are identical or different;(8) koff. mAb-FcRn and koff-(mAb-monoTLi A)-FcRn are identical or different;(9) koff. mAb-FcRn and koff-(mAb-triTLi A)-FcRn are identical or different;(10) kdeg-(mAb-monoTLi A)-FcRn and kdeg-(mAb-triTLi A)-FcRn are identical or different;(11) kdeg-mAb-FcRn and kdeg-(mAb-triTLiA)-FcRn are identical or different;(12) kdeg-mAb-FcRn and kdeg-(mAb-monoTLiA)-FcRn are identical or different; or(13) any combination of (1) to (12).

167. The method of any one of claims 155 to 166, wherein: ksyn-disease is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more fold of ksyn- normal.

168. The method of any one of claims 155 to 167, wherein the effective dose regimen comprises an induction regimen of the anti-TLl A antibody or antigen binding fragment.

169. The method of any one of claims 155 to 168, wherein the effective dose regimen comprises a maintenance regimen of the anti-TLl A antibody or antigen binding fragment.

170. The method of claim 169, wherein the induction regimen and the maintenance regimen are identical.

171. The method of claim 169, wherein the induction regimen and the maintenance regimen are different.

172. The method of any one of claims 169 to 171, wherein the maintenance regimen is administered after the induction regimen.

173. The method of any one of claims 168 to 172, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject during the induction regimen.

174. The method of any one of claims 168 to 173, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of start of the induction regimen.

175. The method of any one of claims 155 to 172, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100, or more fold of TL1 A compared to the corresponding tissue in the control subject.

176. The method of any one of claims 168 to 175, wherein the induction regimen comprises a one-time administration of the anti-TLIA antibody or antigen binding fragment.

177. The method of claim 176, wherein the anti-TLIA 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.

178. The method of any one of claims 168 to 175, wherein the induction regimen comprises multiple administrations of the anti-TLIA antibody or antigen binding fragment.

179. The method of any one of claims 168 to 175 and 178, wherein the induction regimen comprises administrations of(i) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 1000 mg / dose on week 10;(ii) 500 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10;(iii) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 1000 mg / dose on week 6, and 500 mg / dose on week 10;(iv) 1000 mg / dose on week 0, 1000 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10; or(v) 1000 mg / dose on week 0, 500 mg / dose on week 2, 500 mg / dose on week 6, and 500 mg / dose on week 10.

180. The method of any one of claims 168 to 175 and 178, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

181. The method of any one of claims 168 to 175, 178, and 180, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

182. The method of any one of claims 168 to 175, 178, and 180, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first 2 administrations and then once every 2, 4, 6, or 8 weeks for the remaining induction regimen.

183. The method of any one of claims 155 to 172 and 176 to 182, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1 A compared to the corresponding tissue in the control subject.

184. The method of any one of claims 169 to 183, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

185. The method of any one of claims 169 to 184, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50, or more fold of TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks, or longer of start of the maintenance regimen.

186. The method of any one of claims 169 to 185, wherein the maintenance regimen comprises multiple administrations of the anti-TLl A antibody or antigen binding fragment.

187. The method of any one of claims 169 to 186, wherein the maintenance regimen comprises administrations of the anti-TLl A antibody or antigen binding fragment at(i) 500 mg / dose every 2 weeks,(ii) 400 mg / dose every 2 weeks,(iii) 300 mg / dose every 2 weeks,(iv) 250 mg / dose every 2 weeks,(v) 200 mg / dose every 2 weeks,(vi) 150 mg / dose every 2 weeks,(vii) 100 mg / dose every 2 weeks,(viii) 50 mg / dose every 2 weeks,(ix) 500 mg / dose every 4 weeks,(x) 400 mg / dose every 4 weeks,(xi) 300 mg / dose every 4 weeks,(xii) 250 mg / dose every 4 weeks,(xiii) 200 mg / dose every 4 weeks,(xiv) 150 mg / dose every 4 weeks,(xv) 100 mg / dose every 4 weeks,(xvi) 50 mg / dose every 4 weeks,(xvii) 500 mg / dose every 6 weeks,(xviii) 400 mg / dose every 6 weeks,(xix) 300 mg / dose every 6 weeks,(xx) 250 mg / dose every 6 weeks,(xxi) 200 mg / dose every 6 weeks,(xxii) 150 mg / dose every 6 weeks,(xxiii) 100 mg / dose every 6 weeks,(xxiv) 50 mg / dose every 6 weeks,(xxv) 500 mg / dose every 8 weeks,(xxvi) 400 mg / dose every 8 weeks,(xxvii) 300 mg / dose every 8 weeks,(xxviii) 250 mg / dose every 8 weeks,(xxix) 200 mg / dose every 8 weeks,(xxx) 150 mg / dose every 8 weeks,(xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

188. The method of any one of claims 169 to 186, wherein the maintenance regimen comprises administration of the anti-TLIA 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.

189. The method of any one of claims 169 to 186 and 188, wherein the maintenance regimen comprises administration of the anti-TLIA antibody or antigen binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

190. The method of any one of claims 169 to 189, wherein the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at 250 mg / dose every 4 weeks.

191. The method of any one of claims 169 to 190, wherein the maintenance regimen comprises administrations of the anti-TLIA antibody or antigen binding fragment at 100 mg / dose every 4 weeks.

192. The method of any one of claims 169 to 191, wherein the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

193. The method of any one of claims 155 to 192, wherein the effective dose regimen maintains the concentration of TL1 A in diseased tissue in the subject below the concentration of TL1 A in a corresponding tissue in a control subject without kidney inflammation and / or kidney 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.

194. The method of any one of claims 155 to 193, wherein at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the monomeric TL1A in the blood of the subject is occupied by the anti-TLIA antibody or antigen binding fragment during the effective dose regimen.

195. The method of any one of claims 155 to 194, wherein at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the trimeric TL1 A in the blood of the subject is occupied by the anti-TLIA antibody or antigen binding fragment during the effective dose regimen.

196. The method of any one of claims 155 to 195, wherein step (a) further comprises receiving the rate of TL1A trimerization (kOn-TLiA-monomer-to-trimer) and / or rate of TL1A monomerization (koff-TLIA-trimer-to-monomer).

197. The method of any one of claims 102 to 196, wherein the concentration of TL1A is the concentration of free TL1A.

198. The method of any one of claims 1 to 197, wherein the anti-TLl A antibody comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 1, an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 6-9; and a light chain variable region comprising an LCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 10, an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 11, an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOS: 12-15.

199. The method of any one of claims 1 to 198, wherein the anti-TLl A antibody comprises, a heavy chain variable framework region comprising a human IGHV 1 - 46*02 framework or a modified human IGHV1 -46*02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region collectively comprise no or fewer than nine amino acid modification(s) from the human IGHV1 -46*02 framework and the human IGKV3-20 framework.

200. The method of any one of claims 1 to 199, wherein the anti-TLl A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOS: 201-220.

201. The method of any one of claims 1 to 200, wherein the anti-TLl A antibody comprises a heavy chain variable region comprising SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[H CDR2]RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTT VTVSS, and a light chain variable region comprising SEQ ID NO: 303 EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX1OX11IY[LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of Xl-Xl 1 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein HCDR1 comprises an amino acid sequence set forthby SEQ ID NO: 1, HCDR2 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 2-5, HCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 6-9, LCDR1 comprises an amino acid sequence set forth by SEQ ID NO: 10, LCDR2 comprises an amino acid sequence set forth by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence set forth by any one of SEQ ID NOS: 12 or 13.

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