Methods for treating headache using antagonist antibodies directed against calcitonin gene-related peptide

• US 9,884,907 B2
• Filed: 05/05/2017
• Issued: 02/06/2018
• Est. Priority Date: 11/14/2005
• Status: Active Grant

• Current Assignee: Teva Pharmaceuticals International GmbH (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceuticals International GmbH (Teva Pharmaceutical Industries Limited)
• Inventors: Zeller, Joerg, Poulsen, Kristian T., Abdiche, Yasmina Noubia, Pons, Jaume, Collier, Sierra Jones, Rosenthal, Arnon
• Primary Examiner(s): Saoud, Christine J
• Assistant Examiner(s): LOCKARD, JON MCCLELLAND
• Application Number:
  US15/588,490
• Publication Number:
  US 20170240624A1
• Time in Patent Office: 277 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/26 against hormones ; against hormone releasing or inhibiting factors
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/70 : characterized by effect upon binding to a cell or to an antigen
• CPC Class Codes: C07K 2317/71 : Decreased effector function due to an Fc-modification
• 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

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms, including headaches (e.g., migraine, cluster headache, and tension headache) and hot flushes, by administering an anti-CGRP antagonist antibody. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

Claims

1. A method for treating headache in an individual, comprising:

administering to the individual an effective amount of a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody, comprising;

two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and

two light chains, each light chain comprising three CDRs and four framework regions;

wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO;

15 or SEQ ID NO;

43.

2. The method of claim 1, wherein the antibody is formulated with a pharmaceutically acceptable carrier, excipient, or stabilizer.

3. The method of claim 1, wherein the antibody is administered systemically, intravenously, subcutaneously, intramuscularly, or transdermally.

4. The method of claim 1, wherein the antibody is administered intravenously or subcutaneously.

5. The method of claim 1, wherein the headache is a migraine with or without aura, hemiplegic migraine, cluster headache, migrainous neuralgia, chronic headache, or tension headache.

6. The method of claim 1, wherein the headache is a migraine.

7. The method of claim 1, wherein the antibody is administered at a dose of at least 3 μ

g/kg.

8. The method of claim 1, wherein constant regions of the IgG heavy chains are IgG1 constant regions.

9. The method of claim 8, wherein the CDRs impart to the antibody specific binding to a fragment of the CGRP comprising amino acid residues 8 to 37 of SEQ ID NO:

15.

10. The method of claim 8, wherein the CDRs of the humanized monoclonal antibody are derived from mouse, rat, or rabbit CDRs.

11. The method of claim 1, wherein constant regions of the IgG heavy chains are IgG2 constant regions.

12. The method of claim 11, wherein the CDRs impart to the antibody specific binding to a fragment of the CGRP comprising amino acid residues 8 to 37 of SEQ ID NO:

15.

13. The method of claim 11, wherein the CDRs impart to the antibody specific binding to a fragment of the CGRP comprising amino acid residues 33 to 37 of SEQ ID NO:

15.

14. The method of claim 11, wherein the CDRs of the humanized monoclonal antibody are derived from mouse, rat, or rabbit CDRs.

15. The method of claim 1, wherein constant regions of the IgG heavy chains are IgG4 constant regions.

16. The method of claim 15, wherein the CDRs impart to the antibody specific binding to a fragment of the CGRP comprising amino acid residues 8 to 37 of SEQ ID NO:

15.

17. The method of claim 15, wherein the CDRs of the humanized monoclonal antibody are derived from mouse, rat, or rabbit CDRs.

18. The method of claim 15, wherein a constant region of the antibody comprises a mutation in an oligosaccharide attachment amino acid residue that is part of an N-glycosylation recognition sequence in the constant region.