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 reducing incidence of or 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 the individual.
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:
(a) CDR H1 as set forth in SEQ ID NO: 3, 33, or 34; CDR H2 as set forth in SEQ ID NO: 4 or 35; CDR H3 as set forth in SEQ ID NO: 5; CDR L1 as set forth in SEQ ID NO: 6; CDR L2 as set forth in SEQ ID NO: 7; and CDR L3 as set forth in SEQ ID NO: 8;
(b) CDR H1 as set forth in SEQ ID NO: 21, 36, or 37; CDR H2 as set forth in SEQ ID NO: 22 or 38; CDR H3 as set forth in SEQ ID NO: 23; CDR L1 as set forth in SEQ ID NO: 24; CDR L2 as set forth in SEQ ID NO: 25; and CDR L3 as set forth in SEQ ID NO: 26; or
(c) a variant of an antibody according to (a) as shown in Table 6.
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. The method of claim 1 , wherein the anti-CGRP antagonist antibody is a human or humanized antibody.
19. The method of claim 1 , wherein the individual is human.