Neutralizing anti-tl1a monoclonal antibodies

Abstract

Described herein are methods and pharmaceutical compositions for the treatment of inflammatory bowel disease (IBD), Crohn's Disease (CD), ulcerative colitis (UC) and medically refractive-ulcerative colitis (MR-UC). In particular, disclosed are anti-TL1A antibodies useful for the treatment of IBD.

What is claimed is: 
     
         1 . A nucleic acid encoding an antibody or antigen-binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL1A) polypeptide, wherein said antibody or antigen-binding fragment comprises:
 a) a heavy chain comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3), wherein
 i) the HCDR1 comprises a first amino acid sequence of DTYMH of SEQ ID NO. 6; 
 ii) the HCDR2 comprises a second amino acid sequence of PASGH of SEQ ID NO. 7; and 
 iii) the HCDR3 comprises a third amino acid sequence of SGGLPD of SEQ ID NO. 8; and 
   b) a light chain comprising a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3), wherein
 i) the LCDR1 comprises a fourth amino acid sequence of ASSSVSYMY of SEQ ID NO. 14; 
 ii) the LCDR2 comprises a fifth amino acid sequence of ATSNLAS of SEQ ID NO. 15; and 
 iii) the LCDR3 comprises a sixth amino acid sequence of GNPRT of SEQ ID NO. 16. 
   
     
     
         2 . The nucleic acid of  claim 1 , wherein the antibody or antigen-binding fragment is a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, or a combination thereof. 
     
     
         3 . The nucleic acid of  claim 1 , wherein the antibody or antigen-binding fragment is a humanized antibody. 
     
     
         4 . The nucleic acid of  claim 1 , wherein the antibody or antigen-binding fragment is an immunoglobulin G (IgG). 
     
     
         5 . The nucleic acid of  claim 4 , wherein the IgG comprises an IgG1. 
     
     
         6 . The nucleic acid of  claim 4 , wherein the IgG comprises an IgG2. 
     
     
         7 . A vector comprising the nucleic acid of  claim 1 . 
     
     
         8 . The vector of  claim 7 , wherein the vector is an expression vector. 
     
     
         9 . The vector of  claim 7 , wherein the vector is a recombinant vector. 
     
     
         10 . A host cell comprising the nucleic acid of  claim 1 . 
     
     
         11 . A host cell comprising the vector of  claim 7 .