Anti-IP-10 Antibodies and Uses Thereof

Abstract

The invention relates to fully human antibodies, and fragments thereof, that bind to interferon-inducible-protein-10 (IP-10, CXCL10), thereby modulating the interaction between IP-10 and its receptor, CXCR3, and/or modulating the biological activities of IP-10. The invention also relates to the use of such anti-IP-10 antibodies in the prevention or treatment of immune-related disorders and in the amelioration of one or more symptoms associated with an immune-related disorder.

What is claimed is: 
     
         1 . An isolated fully human monoclonal anti-IP-10 antibody or fragment thereof, wherein said antibody comprises:
 (a) a V H  CDR1 region comprising the amino acid sequence of SEQ ID NO: 5, 34, 44, 64, 86, 95, or 127;   (b) a V H  CDR2 region comprising the amino acid sequence of SEQ ID NO: 6, 15, 35, 45, 65, 87, 96, or 128; and   (c) a V H  CDR3 region comprising the amino acid sequence of SEQ ID NO: 7, 21, 36, 46, 52, 57, 66, 78, 88, 97, 105, 129, 132 or 140,   wherein said antibody binds IP-10.   
     
     
         2 . The antibody of  claim 1 , wherein said antibody further comprises:
 (d) a V L  CDR1 region comprising the amino acid sequence of SEQ ID NO: 8, 16, 37, 47, 71, 79, 98, 106, 112, 119, 133 or 141;   (e) a V L  CDR2 region comprising the amino acid sequence of SEQ ID NO: 9, 38, 48, 58, 72, 80, 89, 99, 113, 120 or 142; and   (f) a V L  CDR3 region comprising the amino acid sequence of SEQ ID NO: 10, 24, 29, 39, 49, 59, 73, 81, 90, 100, 107, 114, 121, 126 or 143.   
     
     
         3 . The antibody of  claim 1 , wherein said antibody is an IgG isotype. 
     
     
         4 . The antibody of  claim 1 , wherein said antibody is an IgG1 isotype. 
     
     
         5 . The antibody of  claim 2 , wherein said antibody comprises a V H  CDR1 region comprising the amino acid sequence of SEQ ID NO: 5; a V H  CDR2 region comprising the amino acid sequence of SEQ ID NO:6, a V H  CDR3 region comprising the amino acid sequence of SEQ ID NO:7; a V L  CDR1 region comprising the amino acid sequence of SEQ ID NO: 8; a V L  CDR2 region comprising the amino acid sequence of SEQ ID NO:9; and a V L  CDR3 region comprising an amino acid sequence of SEQ ID NO:10. 
     
     
         6 . The antibody of  claim 5 , wherein said antibody comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:2 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:4. 
     
     
         7 . An isolated fully human monoclonal antibody comprising a heavy chain sequence comprising the amino acid sequence of SEQ ID NO:134 and a light chain sequence comprising the amino acid sequence of SEQ ID NO:135. 
     
     
         8 . The antibody of  claim 7 , wherein said antibody is an IgG1 isotype. 
     
     
         9 . An isolated fully human monoclonal antibody, wherein said antibody comprises a heavy chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 12, 18, 26, 31, 41, 51, 54, 61, 68, 75, 83, 92, 102, 109, 116, 123 and 137, wherein said antibody binds IP-10. 
     
     
         10 . The antibody of  claim 9 , wherein said antibody further comprises a light chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 4, 14, 23, 28, 33, 43, 56, 63, 70, 77, 85, 94, 104, 111, 118, 125, 139 and 145, wherein said antibody binds IP-10. 
     
     
         11 . The antibody of  claim 10 , wherein said antibody is an IgG isotype. 
     
     
         12 . The antibody of  claim 11 , wherein said antibody is an IgG1 isotype. 
     
     
         13 . An isolated fully human monoclonal antibody comprising a V H  CDR1 region comprising the amino acid sequence of SEQ ID NO: 5; a V H  CDR2 region comprising the amino acid sequence of SEQ ID NO:6, a V H  CDR3 region comprising the amino acid sequence of SEQ ID NO:7; a V L  CDR1 region comprising the amino acid sequence of SEQ ID NO: 8; a V L  CDR2 region comprising the amino acid sequence of SEQ ID NO:9; and a V L  CDR3 region comprising an amino acid sequence of SEQ ID NO:10. 
     
     
         14 . The antibody of  claim 13 , wherein said antibody is an IgG isotype. 
     
     
         15 . The antibody of  claim 14 , wherein said antibody is an IgG1 isotype. 
     
     
         16 . A pharmaceutical composition comprising the antibody of  claim 1  and a carrier. 
     
     
         17 . A method of alleviating a symptom of an autoimmune disease or inflammatory disorder, the method comprising administering the antibody according of  claim 1  to a subject in need thereof in an amount sufficient to alleviate the symptom of the autoimmune disease or inflammatory disorder in the subject. 
     
     
         18 . The method of  claim 17 , wherein said subject is a human. 
     
     
         19 . The method of  claim 17 , wherein said antibody comprises a V H  CDR1 region comprising the amino acid sequence of SEQ ID NO: 5; a V H  CDR2 region comprising the amino acid sequence of SEQ ID NO:6, a V H  CDR3 region comprising the amino acid sequence of SEQ ID NO:7; a V L  CDR1 region comprising the amino acid sequence of SEQ ID NO: 8; a V L  CDR2 region comprising the amino acid sequence of SEQ ID NO:9; and a V L  CDR3 region comprising an amino acid sequence of SEQ ID NO:10. 
     
     
         20 . The method of  claim 19 , wherein said antibody comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:2 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:4. 
     
     
         21 . The method of  claim 19 , wherein said antibody comprises a heavy chain sequence comprising the amino acid sequence of SEQ ID NO:134 and a light chain sequence comprising the amino acid sequence of SEQ ID NO:135.