Optimized anti-tl1a antibodies

Abstract

Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of inflammatory bowel disease (IBD), such as Crohn's Disease (CD) and ulcerative colitis (UC).

What is claimed is: 
     
         1 . A nucleic acid encoding an antibody, or antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the nucleic acid comprises:
 a nucleic acid sequence encoding a heavy chain variable region comprising: (a) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (b) a nucleic acid encoding a HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 554 to 564, or 574 to 577; and (c) a nucleic acid encoding a HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 565 to 568, or 579 to 581; and   a nucleic acid sequence encoding a light chain variable region comprising: (a) a nucleic acid encoding a LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 569 or 570; (b) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (c) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572.   
     
     
         2 . The nucleic acid encoding the antibody or antigen binding portion of  claim 1 , wherein the HCDR2 comprises the amino acid sequence as set forth by SEQ ID NO: 554. 
     
     
         3 . The nucleic acid encoding the antibody or antigen binding portion of  claim 1 , wherein the HCDR2 comprises the amino acid sequence as set forth by SEQ ID NO: 555. 
     
     
         4 . The nucleic acid encoding the antibody or antigen binding portion of  claim 1 , wherein the HCDR3 comprises the amino acid sequence as set forth by SEQ ID NO: 565. 
     
     
         5 . The nucleic acid encoding the antibody or antigen binding portion of  claim 1 , wherein the HCDR3 comprises the amino acid sequence as set forth by SEQ ID NO: 566. 
     
     
         6 . The nucleic acid encoding the antibody or antigen binding portion of  claim 1 , wherein the LCDR1 comprises the amino acid sequence as set forth by SEQ ID NO: 569. 
     
     
         7 . The nucleic acid encoding the antibody or antigen binding portion of  claim 1 , wherein the nucleic acid sequence encoding the heavy chain variable region comprises a nucleic acid encoding for a heavy chain constant region, and the nucleic acid sequence encoding the light chain variable region comprises a nucleic acid encoding for a light chain constant region. 
     
     
         8 . A recombinant vector comprising the nucleic acid of  claim 1 . 
     
     
         9 . The recombinant vector of  claim 8 , wherein the recombinant vector is a plasmid. 
     
     
         10 . The recombinant vector of  claim 8 , wherein the recombinant vector is an expression vector. 
     
     
         11 . A host cell comprising the recombinant vector of  claim 8 . 
     
     
         12 . A nucleic acid encoding an antibody, or antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the nucleic acid comprises:
 a nucleic acid sequence encoding a heavy chain variable region comprising: (a) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (b) a nucleic acid encoding a HCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 554; and (c) a nucleic acid encoding a HCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 565; and   a nucleic acid sequence encoding a light chain variable region comprising: (a) a nucleic acid encoding a LCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 569; (b) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (c) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572.   
     
     
         13 . The nucleic acid encoding the antibody or antigen binding portion of  claim 12 , wherein the nucleic acid sequence encoding the heavy chain variable region comprises a nucleic acid encoding for a heavy chain constant region, and the nucleic acid sequence encoding the light chain variable region comprises a nucleic acid encoding for a light chain constant region. 
     
     
         14 . A recombinant vector comprising the nucleic acid of  claim 12 . 
     
     
         15 . The recombinant vector of  claim 14 , wherein the recombinant vector is a plasmid. 
     
     
         16 . The recombinant vector of  claim 14 , wherein the recombinant vector is an expression vector. 
     
     
         17 . A host cell comprising the recombinant vector of  claim 14 . 
     
     
         18 . A method of producing an antibody, or an antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the method comprises
 (a) providing a host cell comprising an expression vector harboring a nucleic acid encoding the antibody, or the antibody binding portion thereof, wherein the nucleic acid comprises:   a nucleic acid sequence encoding a heavy chain variable region comprising: (i) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (ii) a nucleic acid encoding a HCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 554; and (iii) a nucleic acid encoding a HCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 565; and   a nucleic acid sequence encoding a light chain variable region comprising: (i) a nucleic acid encoding a LCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 569; (ii) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (iii) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572; and   (b) culturing the host cell under conditions to induce expression of the antibody or antibody portion from the host cell.   
     
     
         19 . The method of  claim 18 , further comprising harvesting the antibody or antigen binding portion. 
     
     
         20 . The method of  claim 19 , further comprising purifying the harvested antibody or antigen binding portion.