Humanized anti-PACAP antibodies
The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the V H , V L , and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the invention contemplate using anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, photophobia, mast cell degranulation, and/or neuronal activation, would be therapeutically beneficial.
1. A humanized anti-Pituitary Adenylate Cyclase-Activating Polypeptide (“PACAP”) antibody or antigen binding fragment thereof comprising a heavy chain variable region polypeptide having at least 90% identity to SEQ ID NO: 962 and a light chain variable region polypeptide having at least 90% identity to SEQ ID NO: 982,
wherein said heavy chain variable region comprises the heavy chain complementarity-determining region (CDR) 1 polypeptide of SEQ ID NO: 964, the heavy chain CDR2 polypeptide of SEQ ID NO: 966, and the heavy chain CDR3 polypeptide of SEQ ID NO: 968, and
said light chain variable region comprises the light chain CDR1 polypeptide of SEQ ID NO: 984, the light chain CDR2 polypeptide of SEQ ID NO: 986, and the light chain CDR3 polypeptide of SEQ ID NO: 988.
2. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises the heavy chain variable region polypeptide of SEQ ID NO: 962.
3. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises the light chain variable region polypeptide of SEQ ID NO: 982.
4. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises the heavy chain variable region polypeptide of SEQ ID NO: 962 and the light chain variable region polypeptide of SEQ ID NO: 982.
5. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises a heavy chain polypeptide having at least 90% identity to SEQ ID NO: 961.
6. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises a light chain polypeptide having at least 90% identity to SEQ ID NO: 981.
7. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises a heavy chain polypeptide having at least 90% identity to SEQ ID NO: 961 and a light chain polypeptide having at least 90% identity to SEQ ID NO: 981.
8. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises the heavy chain polypeptide of SEQ ID NO: 961.
9. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises the light chain polypeptide of SEQ ID NO: 981.
10. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which comprises the heavy chain polypeptide of SEQ ID NO: 961 and the light chain polypeptide of SEQ ID NO: 981.
11. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 1 , which is expressed from the heavy chain encoding polynucleotide of SEQ ID NO: 971 and the light chain encoding polynucleotide of SEQ ID NO: 991.
12. The humanized anti-PACAP antibody or antigen binding fragment thereof of claim 11 , wherein said heavy chain encoding polynucleotide and said light chain encoding polynucleotide are expressed in a CHO cell.
13. A humanized anti-Pituitary Adenylate Cyclase-Activating Polypeptide (“PACAP”) antibody or antigen binding fragment thereof comprising a heavy chain variable region polypeptide having at least 95% identity to SEQ ID NO: 962 and a light chain variable region polypeptide having at least 95% identity to SEQ ID NO: 982,
wherein said heavy chain variable region comprises the heavy chain complementarity-determining region (CDR) 1 polypeptide of SEQ ID NO: 964, the heavy chain CDR2 polypeptide of SEQ ID NO: 966, and the heavy chain CDR3 polypeptide of SEQ ID NO: 968, and
said light chain variable region comprises the light chain CDR1 polypeptide of SEQ ID NO: 984, the light chain CDR2 polypeptide of SEQ ID NO: 986, and the light chain CDR3 polypeptide of SEQ ID NO: 988.
14. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 1 and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 4 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 7 and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 10 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 11 and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 12 and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising the humanized anti-PACAP antibody or antigen binding fragment thereof according to claim 13 and a pharmaceutically acceptable carrier.
21. The pharmaceutical composition of claim 14 which is suitable for intravenous administration.
22. The pharmaceutical composition of claim 15 which is suitable for intravenous administration.
23. The pharmaceutical composition of claim 16 which is suitable for intravenous administration.
24. The pharmaceutical composition of claim 17 which is suitable for intravenous administration.
25. The pharmaceutical composition of claim 18 which is suitable for intravenous administration.
26. The pharmaceutical composition of claim 19 which is suitable for intravenous administration.
27. The pharmaceutical composition of claim 20 which is suitable for intravenous administration.
28. The pharmaceutical composition of claim 14 which is suitable for subcutaneous administration.
29. The pharmaceutical composition of claim 15 which is suitable for subcutaneous administration.
30. The pharmaceutical composition of claim 16 which is suitable for subcutaneous administration.
31. The pharmaceutical composition of claim 17 which is suitable for subcutaneous administration.
32. The pharmaceutical composition of claim 18 which is suitable for subcutaneous administration.
33. The pharmaceutical composition of claim 19 which is suitable for subcutaneous administration.
34. The pharmaceutical composition of claim 20 which is suitable for subcutaneous administration.