Anti-PACAP antibodies

Patent metadata

Field	Value
Publication number	US-10981985-B2
Application number	US-202016787294-A
Country	US
Kind code	B2
Filing date	Feb 11, 2020
Priority date	Apr 16, 2015
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific VH, VL, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and/or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic 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, mast cell degranulation, and/or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

First claim

What is claimed is:

1. An anti-Pituitary Adenylate Cyclase-Activating Polypeptide (“PACAP”) antibody or antigen binding fragment thereof comprising:
(a) a heavy chain variable region (VH) polypeptide comprising the heavy chain complementarity-determining region (CDR) 1 polypeptide of SEQ ID NO: 404, the heavy chain CDR2 polypeptide of SEQ ID NO: 406, and the heavy chain CDR3 polypeptide of SEQ ID NO: 408; and
(b) a light chain variable region (VL) comprising the light chain CDR1 polypeptide of SEQ ID NO: 424, the light chain CDR2 polypeptide of SEQ ID NO: 426, and the light chain CDR3 polypeptide of SEQ ID NO: 428.

2. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which is humanized.

3. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which is chimerized.

4. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which is a human anti-PACAP antibody or antigen binding fragment thereof.

5. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , wherein the VH polypeptide comprises at least 90% sequence identity to the polypeptide of SEQ ID NO: 402.

6. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , wherein the VL polypeptide comprises at least 90% sequence identity to SEQ ID NO: 422.

7. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , wherein:
(a) the VH polypeptide comprises at least 90% sequence identity to SEQ ID NO: 402; and
(b) the VL polypeptide comprises at least 90% sequence identity to SEQ ID NO: 422.

8. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a heavy chain polypeptide having at least 90% sequence identity to SEQ ID NO: 401.

9. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a light chain polypeptide having at least 90% sequence identity to SEQ ID NO: 421.

10. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises:
(a) a heavy chain polypeptide having at least 90% sequence identity to SEQ ID NO: 401; and
(b) a light chain polypeptide having at least 90% sequence identity to SEQ ID NO: 421.

11. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a heavy chain polypeptide of SEQ ID NO: 401.

12. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a light chain polypeptide of SEQ ID NO: 421.

13. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a heavy chain polypeptide of SEQ ID NO: 401 and a light chain polypeptide of SEQ ID NO: 421.

14. The anti-PACAP antibody or antigen binding fragment thereof according to claim 13 , which is expressed from the heavy chain-encoding polynucleotide of SEQ ID NO: 411 and the light chain-encoding polynucleotide of SEQ ID NO: 431.

15. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a constant region of human IgG1, IgG2, IgG3, or IgG4.

16. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises an Fc region.

17. The anti-PACAP antibody or antigen binding fragment thereof according to claim 16 , wherein the Fc region comprises at least one mutation that alters or eliminates N- and/or O-glycosylation.

18. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which comprises a scFv, Fab, Fab′, or F(ab′) 2 antibody fragment.

19. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which is directly or indirectly attached to a detectable label or therapeutic agent.

20. The anti-PACAP antibody or antigen binding fragment thereof according to claim 1 , which is expressed in a CHO cell.

21. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 1 and a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 2 and a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 5 and a pharmaceutically acceptable carrier.

24. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 6 and a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 7 and a pharmaceutically acceptable carrier.

26. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 10 and a pharmaceutically acceptable carrier.

27. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 15 and a pharmaceutically acceptable carrier.

28. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 16 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 18 and a pharmaceutically acceptable carrier.

30. A pharmaceutical composition comprising the anti-PACAP antibody or antigen binding fragment thereof according to claim 19 and a pharmaceutically acceptable carrier.

Assignees

• H Lundbeck As

Inventors

• Loomis Maria-Cristina
• Garcia-Martinez Leon F
• Dutzar Benjamin H
• Allison Daniel S
• Hendrix Katherine Lee
• Ojala Ethan W
• Fan Pei
• Smith Jeffrey T L
• Latham John A
• Karasek Charlie
• Mulligan Jenny
• Scalley-Kim Michelle
• Stewart Erica
• Rubin Vanessa Lisbeth
• Billgren Jens J

Classifications

• A61K49/0008

  Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure · CPC title

• A61K49/0004

  Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions · CPC title

• C07K16/4241

  against anti-human or anti-animal Ig · CPC title

• A61K39/39566

  against immunoglobulins, e.g. anti-idiotypic antibodies · CPC title

• G01N33/74

  involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} · CPC title