Anti-CGRP compositions and use thereof
View Patent ↗The present invention is directed to antibodies and fragments thereof having binding specificity for CGRP. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V H , V L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-CGRP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-CGRP antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-CGRP antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with CGRP.
1. An isolated or recombinant anti-human calcitonin gene related polypeptide (CGRP) antibody or antibody fragment which specifically binds to human CGRP, wherein said anti-human CGRP antibody or antibody fragment comprises a V L polypeptide that comprises the V L complementarity determining regions (CDR) polypeptides CDR1, CDR2 and CDR3 respectively of SEQ ID NO: 55, SEQ ID NO:56 and SEQ ID NO:57, and comprises a V H polypeptide comprising the V H CDR polypeptides CDR1, CDR2 and CDR3 respectively of SEQ ID NO: 58, SEQ ID NO:59 and SEQ ID NO:60.
2. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide at least 90% identical to the polypeptide of SEQ ID NO: 51.
3. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V H polypeptide at least 90% identical to the polypeptide of SEQ ID NO: 53.
4. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide at least 95% identical to the polypeptide of SEQ ID NO: 51.
5. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V H polypeptide at least 95% identical to the polypeptide of SEQ ID NO: 53.
6. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide identical to the polypeptide of SEQ ID NO: 51.
7. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V H polypeptide identical to the polypeptide of SEQ ID NO: 53.
8. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide at least 90% identical to the polypeptide in SEQ ID NO:51 and a V H polypeptide at least 90% identical to the polypeptide in SEQ ID NO:53.
9. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide at least 95% identical to the polypeptide of SEQ ID NO:51 and a V H polypeptide at least 95% identical to the polypeptide of SEQ ID NO:53.
10. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide at least 98% identical to the polypeptide of SEQ ID NO:51 and a V H polypeptide at least 98% identical to the polypeptide of SEQ ID NO:53.
11. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a V L polypeptide of SEQ ID NO:51 and a V H polypeptide of SEQ ID NO:53.
12. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a light chain polypeptide of SEQ ID NO:52 and a heavy chain polypeptide of SEQ ID NO:54.
13. The anti-human CGRP antibody or antibody fragment of claim 1 , which comprises a human constant region or fragment thereof.
14. The anti-human CGRP antibody or antibody fragment of claim 12 , which comprises a human IgG1, IgG2, IgG3 or IgG4 constant region or fragment thereof.
15. The anti-human CGRP antibody or antibody fragment of claim 1 , which is aglycosylated or if glycosylated only contains only mannose residues.
16. The anti-human CGRP antibody or antibody fragment of claim 1 which is not N-glycosylated.
17. The anti-human CGRP antibody or antibody fragment of claim 1 which contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
18. The anti-human CGRP antibody or antibody fragment of claim 1 which is a humanized, single chain or chimeric antibody.
19. The anti-human CGRP antibody or fragment of claim 1 , which is directly or indirectly attached to a detectable label or therapeutic agent.
20. The anti-human CGRP antibody or fragment of claim 1 , wherein said 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 .
21. The anti-human CGRP antibody or fragment of claim 1 , wherein said fragment is selected from a Fab fragment, a Fab′ fragment, or a F(ab′) 2 fragment.
22. The anti-human CGRP antibody or antibody fragment of claim 21 , wherein said antibody or antibody fragment further comprises an effector moiety.
23. A pharmaceutical composition comprising an antibody or antibody fragment according to claim 1 .
24. A pharmaceutical composition comprising an antibody or antibody fragment according to claim 11 .
25. An isolated or recombinant anti-human calcitonin gene related polypeptide (CGRP) antibody or antibody fragment which specifically binds to human CGRP, wherein said anti-human CGRP antibody or antibody fragment comprises a VL polypeptide that comprises the V L complementarity determining regions (CDR) polypeptides CDR1, CDR2 and CDR3 respectively of SEQ ID NO: 55, SEQ ID NO:56 and SEQ ID NO:57, and comprises a V H polypeptide comprising the V H CDR polypeptides CDR1, CDR2 and CDR3 respectively of SEQ ID NO: 58, SEQ ID NO:59 and SEQ ID NO:60, wherein said anti-human CGRP antibody or antibody fragment is humanized or chimeric.
26. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises at least one of: a V L polypeptide at least 90% identical to the polypeptide of SEQ ID NO: 51, and a V H polypeptide at least 90% identical to the polypeptide of SEQ ID NO: 53.
27. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises at least one of: V L polypeptide at least 95% identical to the polypeptide of SEQ ID NO: 51, and a V H polypeptide at least 95% identical to the polypeptide of SEQ ID NO: 53.
28. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises a V L polypeptide identical to the polypeptide of SEQ ID NO: 51, and a V H polypeptide identical to the polypeptide of SEQ ID NO: 53.
29. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises at least one of: V L polypeptide at least 98% identical to the polypeptide of SEQ ID NO:51, and a V H polypeptide at least 98% identical to the polypeptide of SEQ ID NO:53.
30. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises a light chain polypeptide of SEQ ID NO:52 and a heavy chain polypeptide of SEQ ID NO:54.
31. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises a human constant region or fragment thereof.
32. The anti-human CGRP antibody or antibody fragment of claim 25 , which comprises a human IgG1, IgG2, IgG3 or IgG4 constant region or fragment thereof.
33. The anti-human CGRP antibody or antibody fragment of claim 25 , which is aglycosylated or if glycosylated only contains only mannose residues, and/or which is not N-glycosylated.
34. The anti-human CGRP antibody or antibody fragment of claim 25 which contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
35. The anti-human CGRP antibody or fragment of claim 25 , which is directly or indirectly attached to a detectable label or therapeutic agent.
36. The anti-human CGRP antibody or fragment of claim 25 , wherein said 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 .
37. The anti-human CGRP antibody or fragment of claim 25 , wherein said fragment is selected from a Fab fragment, a Fab′ fragment, or a F(ab′) 2 fragment.
38. The anti-human CGRP antibody or antibody fragment of claim 37 , wherein said antibody or antibody fragment further comprises an effector moiety.
39. A pharmaceutical composition comprising an antibody or antibody fragment according to claim 25 .
40. A pharmaceutical composition comprising an antibody or antibody fragment according to claim 28 .