PACAP antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11780914-B2
Application number	US-202017031674-A
Country	US
Kind code	B2
Filing date	Sep 24, 2020
Priority date	Dec 15, 2015
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

Abstract

The present invention relates to monoclonal antibodies that specifically bind to human pituitary adenylate cyclase activating polypeptide (PACAP) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the monoclonal antibodies are also described.

First claim

What is claimed:

1. An isolated monoclonal antibody or binding fragment thereof that specifically binds to human pituitary adenylate cyclase-activating polypeptide (PACAP) and inhibits PACAP-induced activation of human PAC1 receptor comprising (i) a light chain variable region comprising complementarity determining regions CDRL1, CDRL2, and CDRL3, and (ii) a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein:
(a) CDRL1, CDRL2, and CDRL3 have the sequences of SEQ ID NOs: 32, 37, and 42, respectively, and CDRH1, CDRH2, and CDRH3 have the sequences of SEQ ID NOs: 48, 53, and 59, respectively;
(b) CDRL1, CDRL2, and CDRL3 have the sequences of SEQ ID NOs: 33, 38, and 43, respectively, and CDRH1, CDRH2, and CDRH3 have the sequences of SEQ ID NOs: 49, 54, and 60, respectively; or
(c) CDRL1, CDRL2, and CDRL3 have the sequences of SEQ ID NOs: 34, 39, and 44, respectively, and CDRH1, CDRH2, and CDRH3 have the sequences of SEQ ID NOs: 50, 55, and 61, respectively.

2. The isolated monoclonal antibody or binding fragment thereof of claim 1 , wherein the monoclonal antibody or binding fragment comprises a light chain variable region comprising a sequence that is at least 90% identical to a sequence selected from SEQ ID NOs: 24, 26, or 28; and a heavy chain variable region comprising a sequence that is at least 90% identical to a sequence selected from SEQ ID NOs: 25, 27, or 29.

3. The isolated monoclonal antibody or binding fragment thereof of claim 1 , wherein the monoclonal antibody or binding fragment comprises:
(a) a light chain variable region comprising the sequence of SEQ ID NO: 24 and a heavy chain variable region comprising the sequence of SEQ ID NO: 25;
(b) a light chain variable region comprising the sequence of SEQ ID NO: 26 and a heavy chain variable region comprising the sequence of SEQ ID NO: 27; or
(c) a light chain variable region comprising the sequence of SEQ ID NO: 28 and a heavy chain variable region comprising the sequence of SEQ ID NO: 29.

4. The isolated monoclonal antibody or binding fragment thereof of claim 1 , wherein the monoclonal antibody or binding fragment thereof is a humanized antibody or binding fragment thereof.

5. The isolated monoclonal antibody of claim 4 , wherein the humanized monoclonal antibody comprises an Fc region from a human IgG1, IgG2, IgG3, or IgG4 antibody.

6. The isolated monoclonal antibody of claim 5 , wherein the humanized monoclonal antibody comprises an Fc region from a human IgG1 antibody.

7. The isolated monoclonal antibody of claim 6 , wherein the Fc region comprises a N297G mutation, wherein the amino acid position is according to EU numbering.

8. A composition comprising the monoclonal antibody or binding fragment thereof of claim 1 and a pharmaceutically acceptable diluent, excipient, or carrier.

9. An isolated polynucleotide encoding the monoclonal antibody or binding fragment thereof of claim 1 .

10. An expression vector comprising the polynucleotide of claim 9 .

11. A host cell comprising the expression vector of claim 10 .

12. A method of producing an anti-PACAP monoclonal antibody or binding fragment thereof comprising culturing the host cell of claim 11 under conditions that allow expression of the antibody or binding fragment; and recovering the antibody or binding fragment from the culture medium or host cell.

13. A method for inhibiting activation of human PAC1 receptor in a patient having a headache condition comprising administering to the patient an effective amount of a monoclonal antibody or binding fragment thereof of claim 1 .

14. A method for treating or reducing the occurrence of preventing a headache condition in a patient in need thereof comprising administering to the patient an effective amount of a monoclonal antibody or binding fragment thereof of claim 1 .

15. The method of claim 14 , wherein the headache condition is cluster headache.

16. The method of claim 14 , wherein the monoclonal antibody or binding fragment thereof is administered to the patient as a prophylactic treatment.

17. The method of claim 14 , wherein the headache condition is migraine.

18. The method of claim 17 , wherein the migraine is episodic migraine.

19. The method of claim 17 , wherein the migraine is chronic migraine.

Assignees

• Amgen Inc

Inventors

• Hamburger Agnes E
• Xu Cen
• Sun Hong
• Shih Yuan D
• Weeraratne Dohan

Classifications

• C07K16/26 Primary

  against hormones {; against hormone releasing or inhibiting factors} · CPC title

• A61P25/06

  Antimigraine agents · CPC title

• C07K16/4283

  against an allotypic or isotypic determinant on Ig · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K2039/505

  comprising antibodies · CPC title