Methods for treating visceral pain by administering antagonist antibodies directed against calcitonin gene-related peptide

Abstract

The invention features methods for preventing or treating visceral pain, including pain associated with functional bowel disorder, inflammatory bowel disease and interstitial cystitis, by administering an anti-CGRP antagonist antibody.

We claim: 
     
         1 . A method of treating visceral pain and/or one or more symptoms of visceral pain in an individual, comprising administration of a therapeutically effective amount of an anti-CGRP antagonist antibody to an individual suffering from or at risk for visceral pain. 
     
     
         2 . The method of  claim 1 , wherein the visceral pain is associated with a functional bowel disorder (FBD). 
     
     
         3 . The method of  claim 2 , wherein the FBD is selected from the group consisting of gastro-esophageal reflux, dyspepsia, irritable bowel syndrome (IBS) and functional abdominal pain syndrome (FAPS). 
     
     
         4 . The method of  claim 1 , wherein the visceral pain is associated with inflammatory bowel disease (IBD). 
     
     
         5 . The method of  claim 4 , wherein the IBD is selected from the group consisting of Crohn's disease, ileitis and ulcerative colitis. 
     
     
         6 . The method of  claim 1 , wherein the visceral pain is associated with renal colic, dysmenorrhea, cystitis, menstrual period, labor, menopause, prostatitis or pancreatitis. 
     
     
         7 . The method of  claim 6 , wherein the visceral pain is associated with interstitial cystitis (IC). 
     
     
         8 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody binds CGRP with a K D  of 50 nM or less (as measured by surface plasmon resonance at 37° C.); and/or has a half life in-vivo of at least 7 days. 
     
     
         9 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody specifically binds to the C-terminal region of CGRP. 
     
     
         10 . The method of  claim 9 , wherein the anti-CGRP antagonist antibody specifically recognizes the epitope defined by the sequence GSKAF (SEQ ID NO: 39). 
     
     
         11 . The method of  claim 1 , wherein the anti-CGRP antibody comprises a VH domain having the amino acid sequence shown in SEQ ID NO: 1 or 19. 
     
     
         12 . The method of  claim 1 , wherein the anti-CGRP antibody comprises a VL domain having the amino acid sequence shown in SEQ ID NO: 2 or 20. 
     
     
         13 . The method of  claim 1 , wherein the anti-CGRP antibody comprises at least one CDR selected from the group consisting of:
 (a) CDR H1 as set forth in SEQ ID NO: 3, 21, 33, 34, 36 or 37;   (b) CDR H2 as set forth in SEQ ID NO: 4, 22, 35 or 38;   (c) CDR H3 as set forth in SEQ ID NO: 5 or 23;   (d) CDR L1 as set forth in SEQ ID NO: 6 or 24;   (e) CDR L2 as set forth in SEQ ID NO: 7 or 25; and   (f) CDR L3 as set forth in SEQ ID NO: 8 or 26.   
     
     
         14 . The method of  claim 1 , wherein the anti-CGRP antibody comprises a VH domain having the amino acid sequence shown in SEQ ID NO: 1 and a VL domain having the amino acid sequence shown in SEQ ID NO: 2. 
     
     
         15 . The method of  claim 1 , wherein the anti-CGRP antibody is produced by the expression vectors with ATCC Accession Nos. PTA-6867 and/or PTA-6866. 
     
     
         16 . The method of  claim 1 , wherein the anti-CGRP antibody comprises:
 the antibody G1 heavy chain full antibody amino acid sequence shown in SEQ ID NO: 11, with or without the C-terminal lysine; and   the antibody G1 light chain full antibody amino acid sequence shown in SEQ ID NO: 12.   
     
     
         17 . The method of  claim 1 , wherein the anti-CGRP antibody comprises:
 the antibody G2 heavy chain full antibody amino acid sequence shown in SEQ ID NO: 29; and   the antibody G2 light chain full antibody amino acid sequence shown in SEQ ID NO: 30.   
     
     
         18 . A pharmaceutical composition for treatment and/or prevention of visceral pain and/or symptoms of visceral pain in an individual, comprising an anti-CGRP antagonist antibody and a pharmaceutically acceptable carrier wherein the composition is prepared to be peripherally administered.