Use of anti-CGRP antibodies and antibody fragments to prevent or inhibit photophobia or light aversion in subjects in need thereof, especially migraine sufferers
The present invention is directed to methods of inhibiting or preventing photophobia in subjects in need thereof using anti-CGRP antibodies or antibody fragments that inhibit photophobia, especially CGRP-associated photophobia. These antibodies and fragments are useful in treating different disorders associated with photophobia such as migraine, cluster headaches and the like.
1. A method of inhibiting CGRP-associated photophobia or light aversion or precluding the onset of CGRP-associated photophobia or photoaversion associated with a migrainous condition or cluster headache condition in a subject comprising administering an effective amount of an anti-CGRP antibody or antibody fragment which comprises the variable light V L region CDR1, CDR2 and CDR3 of SEQ ID NOs: 55, 56 and 57 respectively, and the variable heavy V H region CDR1, CDR2 and CDR3 of SEQ ID NOs:58, 59 and 60 respectively.
2. The method of claim 1 , comprising the administration of an intact anti-CGRP antibody.
3. The method of claim 2 , wherein said intact antibody is human, humanized, or chimeric.
4. The method of claim 1 , comprising the administration of an anti-CGRP antibody fragment.
5. The method of claim 4 , wherein said antibody fragment is an scFv, camelbody, nanobody, IgNAR, Fab, Fab′, or F(ab′) 2 fragment.
6. The method of claim 1 , wherein the CGRP-associated photophobia is the result of a migraine or another headache condition associated with photophobia.
7. The method of claim 6 , wherein the CGRP-associated photophobia is caused by a condition selected from the group consisting of chronic migraine, hemiplegic migraine, cluster headache, migrainous neuralgia, menopausal migraine, menstrual migraine, headache-free migraine, and abdominal migraine.
8. The method of claim 1 , wherein the treated subject is a chronic migraine or cluster headache sufferer.
9. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment is humanized.
10. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment is human.
11. The method of claim 1 , wherein the anti-CGRP antibody comprises human constant regions.
12. The method of claim 11 , wherein the constant regions are selected from the group consisting of an IgG1, IgG2, IgG3 and IgG4 constant regions.
13. The method of claim 12 , wherein the anti-CGRP antibody comprises IgG1 constant regions.
14. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment is non-glycosylated.
15. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises a variable light (V L ) region polypeptide that possesses at least 90% sequence identity to the polypeptide of SEQ ID NO:31, 41 or 51.
16. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises a variable heavy (V H ) region polypeptide that possesses at least 90% sequence identity to the polypeptide of SEQ ID NO:33, 43 or 53.
17. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises a variable light (V L ) region polypeptide that possesses at least 95% sequence identity to the polypeptide of SEQ ID NO:31, 41 or 51.
18. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises a variable heavy (V H ) region polypeptide that possesses at least 95% sequence identity to the polypeptide of SEQ ID NO:33, 43 or 53.
19. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the variable light (V L ) region polypeptide of SEQ ID NO:31, 41 or 51.
20. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the variable heavy (V H ) chain polypeptide of SEQ ID NO:33, 43 or 53.
21. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the light chain polypeptide of SEQ ID NO:32, 42 or 52.
22. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the heavy chain polypeptide of SEQ ID NO:34, 44 or 54.
23. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the variable light (V L ) chain polypeptide of SEQ ID NO:31, 41 or 51 and the variable light (V L ) chain polypeptide of SEQ ID NO:33, 43 or 53.
24. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the variable light (V L ) chain polypeptide of SEQ ID NO:51 and the variable heavy (V H ) polypeptide of SEQ ID NO:53.
25. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the light chain polypeptide of SEQ ID NO:32, 42 or 52 and the heavy chain polypeptide of SEQ ID NO:34, 44 or 54.
26. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the light chain polypeptide of SEQ ID NO: 52 and the heavy chain polypeptide of SEQ ID NO: 54.
27. The method of claim 1 , the anti-CGRP antibody or antibody fragment comprises the light chain polypeptide of SEQ ID NO: 42 and the heavy chain polypeptide of SEQ ID NO: 44.
28. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment comprises the light chain polypeptide of SEQ ID NO: 32 and the heavy chain polypeptide of SEQ ID NO: 34.
29. The method of claim 1 , wherein the anti-CGRP antibody or antibody fragment binds to CGRP with an off-rate (K off ) of less than or equal to 10 −4 S −1 , 5×10 −5 S −1 , 10 −5 S −1 , 5×10 −6 S −1 , 10 −6 S −1 , 5×10 −7 S −1 , or 10 −7 S −1 .
30. The method of claim 1 , wherein the antibody or antibody fragment is administered intramuscularly, subcutaneously, intravenously, rectally, by infusion, orally, transdermally or via inhalation.
31. The method of claim 1 , wherein the antibody or antibody fragment is administered intravenously.
32. The method of claim 1 , which includes the administration of an active agent other than an antibody useful for treating migraine.
33. The method of claim 32 , wherein the other active agent is an analgesic, a triptan, topiramate, dihydroergotamine, or an opioid.
34. The method of claim 30 , wherein said anti-CGRP antibody or antibody fragment is a Fab fragment.
35. The method of claim 30 , wherein said anti-CGRP antibody is an intact antibody.
36. The method of claim 1 , wherein said anti-CGRP antibody or antibody fragment is entirely non-glycosylated or lacks N-glycosylation or comprises only mannose residues.
37. The method of claim 1 , wherein said anti-CGRP antibody or antibody fragment comprises a human constant domain.
38. The method of claim 35 , wherein said anti-CGRP antibody or antibody fragment comprises IgG1, IgG2, IgG3 or IgG4 constant domains.
39. The method of claim 35 , wherein said anti-CGRP antibody or antibody fragment comprises IgG1 constant domains.
40. The method of claim 36 , wherein said anti-CGRP antibody or antibody fragment contains an Fc region that has been modified to alter at least one of effector function, half-life, proteolysis, or glycosylation.
41. The method of claim 1 , wherein said anti-CGRP antibody or antibody fragment has an Fc region that contains a mutation that alters or eliminates all glycosylation.
42. The method of 41 , wherein the mutation reduces or eliminates N-glycosylation.