Methods of treating chronic pain

Abstract

The invention relates to an anti-CGRP antibody for use in the prevention and/or treatment of chronic pain and/or symptoms of chronic pain, and to a method of treating and/or preventing chronic pain and/or symptoms of chronic pain using an anti-CGRP antibody.

1 . A method of prevention and/or treatment of chronic pain and/or symptoms of chronic pain in an individual, the method comprising administering to the individual a therapeutically effective amount of an anti-CGRP antagonist antibody. 
     
     
         2 . The method according to  claim 1 , wherein the medicament is prepared to be peripherally administered. 
     
     
         3 . The method according to  claim 1 , wherein the medicament is administered peripherally. 
     
     
         4 . The method according to  claim 1 , wherein the medicament is prepared to be administered orally, sublingually, via inhalation, transdermally, subcutaneously, intravenously, intra-arterially, intra-articularly, peri-articularly, locally and/or intramuscularly. 
     
     
         5 . The method according to  claim 4 , wherein the medicament is prepared to be administered subcutaneously or intravenously. 
     
     
         6 . The method according to  claim 1 , wherein the anti-CGRP antagonist antibody acts peripherally on administration. 
     
     
         7 . The method according to  claim 1 , wherein the chronic pain comprises one or more of, chronic nociceptive pain, chronic neuropathic pain, chronic inflammatory pain, fibromyalgia, breakthrough pain and persistent pain. 
     
     
         8 . The method according to  claim 7 , wherein the chronic pain further comprises one or more of hyperalgesia, allodynia, central sensitisation, peripheral sensitisation, disinhibition and augmented facilitation. 
     
     
         9 . The method according to  claim 1 , wherein the chronic pain is cancer pain. 
     
     
         10 . The method according to  claim 9 , wherein the cancer pain is pain due to one or more of the following conditions: adenocarcinoma in glandular tissue, blastoma in embryonic tissue of organs, carcinoma in epithelial tissue, leukemia in tissues that form blood cells, lymphoma in lymphatic tissue, myeloma in bone marrow, sarcoma in connective or supportive tissue, adrenal cancer, AIDS-related lymphoma, anemia, bladder cancer, bone cancer, brain cancer, breast cancer, carcinoid tumours, cervical cancer, chemotherapy, colon cancer, cytopenia, endometrial cancer, esophageal cancer, gastric cancer, head cancer, neck cancer, hepatobiliary cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, Hodgkin's disease, lymphoma, non-Hodgkin's, nervous system tumours, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, skin cancer, stomach cancer, testicular cancer, thyroid cancer, urethral cancer, bone cancer, sarcomas cancer of the connective tissue, cancer of bone tissue, cancer of blood-forming cells, cancer of bone marrow, multiple myeloma, leukaemia, primary or secondary bone cancer, tumours that metastasize to the bone, tumours infiltrating the nerve and hollow viscus, and tumours near neural structures. 
     
     
         11 . The method according to  claim 1 , wherein the anti-CGRP antagonist antibody:
 (a) binds to CGRP;   (b) blocks CGRP from binding to its receptor;   (c) blocks or decreases CGRP receptor activation;   (d) inhibits blocks, suppresses or reduces CGRP biological activity;   (e) increases clearance of CGRP; and/or   (g) inhibits CGRP synthesis, production or release.   
     
     
         12 . The method according to  claim 1 , wherein the anti-CGRP antagonist antibody:
 (i) is a human antibody,   (ii) is a humanized antibody,   (iii) is a monoclonal antibody,   (iv) binds CGRP with a Kd of 50 nM or less (as measured by surface plasmon resonance at 37° C.); and/or   (v) has a half-life in-vivo of at least 7 days.   
     
     
         13 . The method according to  claim 1 , wherein the anti-CGRP antagonist antibody specifically binds to the C-terminal region of CGRP. 
     
     
         14 . The method according to  claim 12 , wherein the anti-CGRP antagonist antibody specifically recognises the epitope defined by the sequence GSKAF. 
     
     
         15 . The method according to  claim 1 , wherein the anti-CGRP antibody comprises a VH domain that is at least 90% identical in amino acid sequence to SEQ ID NO: 1 or 19. 
     
     
         16 . The method according to  claim 1 , wherein the anti-CGRP antibody comprises a VL domain that is at least 90% identical in amino acid sequence to SEQ ID NO: 2 or 20. 
     
     
         17 . The method according to  claim 16 , wherein the anti-CGRP antibody further comprises a VH domain that is at least 90% identical in amino acid sequence to SEQ ID NO: 1 or 19. 
     
     
         18 . The method according to  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;   (b) CDR H2 as set forth in SEQ ID NO: 4;   (c) CDR H3 as set forth in SEQ ID NO: 5;   (d) CDR L1 as set forth in SEQ ID NO: 6;   (e) CDR L2 as set forth in SEQ ID NO: 7;   (f) CDR L3 as set forth in SEQ ID NO: 8; and   (g) variants of L1, L2 and H2.   
     
     
         19 . The method according to  claim 1 , wherein the anti-CGRP antibody comprises a VH domain that is at least 90% identical in amino acid sequence to SEQ ID NO: 1 and a VL domain that is at least 90% identical in amino acid sequence to SEQ ID NO: 2. 
     
     
         20 - 22 . (canceled) 
     
     
         23 . The method according to  claim 1 , wherein the medicament is prepared for peripheral administration by sub-cutaneous or intra-venous injection between once, twice, three or four times per month. 
     
     
         24 - 33 . (canceled)