ANTI-PACAP ANTIBODY

• US 20190100579A1
• Filed: 09/20/2018
• Published: 04/04/2019
• Est. Priority Date: 09/29/2017
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Patel, Chetankumar Natvarlal, Johnson, Michael Parvin, Beidler, Catherine Brautigam
• Granted Patent: US 10,519,225 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/1796 for hormones for neuromediators A61K38/1787
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

Antibodies to human pituitary adenylate cyclase-activating peptide, compositions comprising such antibodies, and methods of using such antibodies for the treatment of pain including headache and/or migraine.

Claims

1. An antibody that binds human pituitary adenylate cyclase-activating peptide comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the HCVR comprises complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3 and the LCVR comprises CDRs LCDR1, LCDR2, and LCDR3, wherein the amino acid sequence of HCDR1 is SEQ ID NO.3, the amino acid sequence of HCDR2 is SEQ ID NO.4, the amino acid sequence of HCDR3 is SEQ ID NO.5, the amino acid sequence of LCDR1 is SEQ ID NO.6, the amino acid sequence of LCDR2 is SEQ ID NO.7, and the amino acid sequence of LCDR3 is SEQ ID NO.8.

2. The antibody of claim 1, wherein HCDR2 comprises aspartic acid at residue 13;

HCDR3 comprises asparagine at residue 8;

LCDR1 comprises serine at residue 7; and

LCDR2 comprises leucine at residue 7.

3. The antibody of claim 1, wherein HCDR2 comprises alanine at residue 13;

HCDR3 comprises threonine at residue 8;

LCDR1 comprises tryptophan at residue 7; and

LCDR2 comprises phenylalanine at residue 7.

4. The antibody of claim 1, wherein HCDR2 comprises glutamic acid at residue 13;

HCDR3 comprises threonine at residue 8;

LCDR1 comprises tryptophan at residue 7; and

LCDR2 comprises phenylalanine at residue 7.

5. The antibody of claim 1, wherein HCDR2 comprises glutamine at residue 13;

HCDR3 comprises threonine at residue 8;

LCDR1 comprises tryptophan at residue 7; and

LCDR2 comprises phenylalanine at residue 7.

6. The antibody of claim 1, comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the amino acid sequence of the HCVR is SEQ ID NO.9 and the amino acid sequence of the LCVR is SEQ ID NO. 10.

7. The antibody of claim 6, wherein HCVR comprises aspartic acid at residue 62 and asparagine at residue 104, and wherein LCVR comprises serine at residue 30 and leucine at residue 55.

8. The antibody of claim 6, wherein HCVR comprises alanine at residue 62 and threonine at residue 104, and wherein LCVR comprises tryptophan at residue 30 and phenylalanine at residue 55.

9. The antibody of claim 6, wherein HCVR comprises glutamic acid at residue 62 and threonine at residue 104, and wherein LCVR comprises tryptophan at residue 30 and phenylalanine at residue 55.

10. The antibody of claim 6, wherein HCVR comprises glutamine at residue 62 and threonine at residue 104, and wherein LCVR comprises tryptophan at residue 30 and phenylalanine at residue 55.

16. A method of treating one of primary headache, secondary headache and migraine comprising administering to a patient in need thereof an effective amount of an antibody of claim 1.

17. The method of claim 16, wherein the primary headache is a trigeminal autonomic cephalalgias.

18. The method of claim 17, wherein the trigeminal autonomic cephalalgias is one of episodic cluster headache, chronic cluster headache, paroxysmal hemicranias, and unilateral neuralgiform headache attack.

11. An antibody that binds human pituitary adenylate cyclase-activating peptide comprising a heavy chain (HC) and a light chain (LC), wherein the amino acid sequence of the HC is SEQ ID NO.1 and the amino acid sequence of the LC is SEQ ID NO.2.

12. The antibody of claim 11, wherein HC comprises aspartic acid at residue 62, asparagine at residue 104, proline at residue 231, alanine at residue 237 and alanine at residue 238, and wherein LC comprises serine at residue 30 and leucine at residue 55.

13. The antibody of claim 11, wherein HC comprises alanine at residue 62, threonine at residue 104, proline at residue 231, alanine at residue 237 and alanine at residue 238, and wherein LC comprises tryptophan at residue 30 and phenylalanine at residue 55.

14. The antibody of claim 11, wherein HC comprises glutamic acid at residue 62, threonine at residue 104, proline at residue 231, alanine at residue 237 and alanine at residue 238, and wherein LC comprises tryptophan at residue 30 and phenylalanine at residue 55.

15. The antibody of claim 11, wherein HC comprises glutamine at residue 62, threonine at residue 104, proline at residue 231, alanine at residue 237 and alanine at residue 238, and wherein LC comprises tryptophan at residue 30 and phenylalanine at residue 55.