Compositions and methods for the prevention or treatment of cancer and bone loss associated with cancer

• US 20060019887A1
• Filed: 09/22/2004
• Published: 01/26/2006
• Est. Priority Date: 09/03/1999
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Dunstan, Colin R.
• Application Number:
  US10/948,053
• Publication Number:
  US 20060019887A1
• Time in Patent Office: Days
• US Class Current: 424/178.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• 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 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention relates to compositions and methods for the prevention and/or treatment of bone loss associated with cancer. More particularly, the invention relates to OPG compositions and methods for the prevention and/or treatment of bone loss comprising said compositions. The invention also relates to the use of OPG compositions for the treatment of multiple myeloma.

Claims

1. (canceled)

2. A method for preventing the metastasis of cancer to bone comprising administering a therapeutically effective amount of an OPG polypeptide.

4. The method of claim 2 further comprising administering a therapeutically effective amount of a cancer therapy agent.

5. The method of claim 2 wherein the OPG polypeptide comprises an amino acid sequence as shown in FIG. 2 (SEQ ID NO:

2) or a truncated polypeptide thereof.

6. The method of claim 4 wherein the OPG polypeptide comprises a carboxy terminal truncation of part or all of amino acid residues 186-401 as shown in FIG. 2 (SEQ ID NO:

2).

7. The method of claim 4 wherein the OPG polypeptide comprises amino acid residues 22-194 inclusive as shown in FIG. 2 (SEQ ID NO:

2).

8. The method of claims 5, 6 or 7 wherein the OPG polypeptide is an OPG fusion polypeptide.

9. The method of claim 8 wherein the OPG fusion polypeptide comprises a fusion of an Fc region to the N-terminal or C-terminal end of the OPG polypeptide.

10. The method of claim 9 wherein the OPG fusion polypeptide comprises an Fc region fused to amino acid residues 22-194 of FIG. 2 (SEQ ID NO:

2).

11. The method of claim 10 wherein the OPG fusion polypeptide consists of the amino acid sequence as shown in FIG. 5 or in FIG. 8 (SEQ ID NO:

5 or

     8).

12. The method of claim 4 wherein the OPG polypeptide is administered prior to, concurrent with, or subsequent to administration of a cancer therapy agent.

15. The method of claim 4 wherein the cancer therapy agent is selected from the group consisting of radiation, chemotherapy, antibodies, or non-antibody polypeptides.

16. The method of claim 15 wherein chemotherapy comprises anthracyclines, taxol, tamoxifene, doxorubicin, and 5-fluorouracil.

17. The method of claim 15 wherein the antibodies bind to Her2, CDC20, CDC33, mucin-like glycoprotein, or epidermal growth factor receptor (EGFR) on the surface of tumor cells.

18. The method of claim 15 wherein the cancer therapy agent comprises a luteinizing hormone-releasing hormone (LHRH) antagonist.

19. The method of claim 18 wherein the LHRH antagonist comprises the following structure:

A-B-C-D-E-F-G-H-I-J

wherein

A is pyro-glu, Ac-D-Nal, Ac-D-Qal;

Ac-Sar, or Ac-D-Pal;

B is His or 4-Cl-D-Phe;

C is Trp, D-Pal, D-Nal, L-Nal-D-Pal(N-O), or D-Trp;

D is Ser;

E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile;

F is

wherein R and X are independently, H and alkyl; and

Y comprises a small polar entity.

G is Leu or Trp;

H is Lys(iPr), Gln, Met, or Arg;

I is Pro; and

J is Gly-NH2 or D-Ala-NH2;

or a pharmaceutically acceptable salt thereof.

20. The method of claim 18 wherein the LHRH antagonist comprises the peptide:

N-Ac-D-Nal-4-Cl-Phe-D-Pal-Ser-N-Me-Tyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH2.

21. The method of claim 2 wherein the therapeutically effective amount of an OPG polypeptide or an OPG fusion polypeptide is between 0.1 mg/kg and 10 mg/kg.

23. The method of claim 2 wherein the cancer is selected from the group consisting of breast cancer, prostate cancer, thyroid cancer, cancer of the kidney, lung cancer, esophogeal cancer, rectal cancer, bladder cancer, cervical cancer, ovarian cancer, liver cancer, cancer of the gastrointestinal tract, multiple myeloma, and lymphoma.

3. (canceled)

13. (canceled)

14. (canceled)

22. (canceled)