METHODS FOR TREATING BONE CANCER BY ADMINISTERING A NERVE GROWTH FACTOR ANTAGONIST ANTIBODY

• US 20120315271A1
• Filed: 06/13/2012
• Published: 12/13/2012
• Est. Priority Date: 04/07/2004
• Status: Active Grant

• Current Assignee: Rinat Neuroscience Corp. (Pfizer Inc.), Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Pfizer Inc.
• Inventors: Shelton, David L., Mantyh, Patrick William
• Granted Patent: US 8,557,245 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• 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

Abstract

The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

Claims

1. A method for treating moderate to severe bone cancer pain in an individual comprising administering to the individual an effective amount of a nerve growth factor (NGF) antagonist.

2. The method of claim 1, wherein the bone cancer pain is from cancer originated in bone.

3. The method of claim 2, wherein the bone cancer pain is from osteosarcoma.

4. The method of claim 1, wherein the bone cancer pain is from cancer metastasized to bone.

5. The method of claim 4, wherein the bone cancer pain is from prostate cancer metastasized to bone.

6. The method of claim 4, wherein the bone cancer pain is from breast cancer metastasized to bone.

7. The method of claim 4, wherein the bone cancer pain is from lung cancer metastasized to bone.

8. The method of claim 4, wherein the bone cancer pain is from sarcoma metastasized to bone.

9. The method of claim 4, wherein the bone cancer pain is from renal cancer metastasized to bone.

10. The method of claim 1, wherein the NGF antagonist is an anti-NGF antagonist antibody.

11. The method of claim 10, wherein the anti-NGF antagonist antibody is a monoclonal antibody.

12. The method of claim 10, wherein the anti-NGF antagonist antibody is a humanized or human antibody.

13. The method of claim 10, wherein the anti-NGF antagonist antibody binds human NGF.

16. The method of claim 10, wherein the anti-NGF antagonist antibody comprises:

a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2, and VH CDR3 of the VH sequence shown in SEQ ID NO;

1; and

a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL sequence shown in SEQ ID NO;

2.

17. The method of claim 16, wherein the VH CDR1, VH CDR2, and VH CDR3 of the anti-NGF antagonist antibody are Kabat, Chothia, or a combination of Kabat and Chothia CDRs of the VH sequence shown in SEQ ID NO:

1.

18. The method of claim 16, wherein the VH region comprises the amino acid sequence shown in SEQ ID NO:

1 or a variant with one or several conservative amino acid substitutions in residues that are not within a CDR and the VL region comprises the amino acid sequence shown in SEQ ID NO;

2 or a variant thereof with one or several amino acid substitutions in amino acids that are not within a CDR.

19. The method of claim 1 or 16, wherein the NGF-antagonist is not co-administered with an opioid analgesic.

14. The method of claim 14, wherein the anti-NGF antagonist antibody further binds rodent NGF.

15. The method of claim 14, wherein the anti-NGF antagonist antibody binds human NGF with a K_D of about 0.1 nM or less than about 0.1 nM.