METHODS FOR TREATING VISCERAL PAIN BY ADMINISTERING ANTAGONIST ANTIBODIES DIRECTED AGAINST CALCITONIN GENE-RELATED PEPTIDE
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.
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.