Use of anti-CGRP antibodies and antibody fragments to prevent or inhibit photophobia or light aversion in subjects in need thereof, especially migraine sufferers
View Patent ↗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.