METHODS FOR PREVENTING AND TREATING CANCER METASTASIS AND BONE LOSS ASSOCIATED WITH CANCER METASTASIS

• US 20090246208A1
• Filed: 01/04/2007
• Published: 10/01/2009
• Est. Priority Date: 01/05/2006
• Status: Abandoned Application

• Current Assignee: Xoma Technology Ltd. (Xoma Corp.)
• Original Assignee: Novartis Ag, Xoma Technology Ltd. (Xoma Corp.)
• Inventors: Kavanaugh, Michael, Liu, Cheng
• Application Number:
  US12/159,665
• Publication Number:
  US 20090246208A1
• Time in Patent Office: Days
• US Class Current: 424/158.100
• 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 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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

Abstract

Methods for preventing and treating osteolysis, cancer metastasis and bone loss associated with cancer metastasis by administering an M-CSF-antagonist in combination with a therapeutic agent to a subject are provided.

Claims

1. A method of treating a patient suffering from an osteolytic disorder comprising the steps of administering to said patient an anti-M-CSF antibody at a monotherapeutically effective dose and an osteoclast inhibitor at a monotherapeutically effective dose.

3. The method of claim 1 wherein the osteoclast inhibitor is a RANKL inhibitor.

6. The method of any of the preceding claims wherein the osteolytic disorder is osteoporosis, bone loss associated with cancer metastasis, Padget'"'"'s disease, or periprosthetic bone loss.

7. The method of any of the preceding claims wherein the osteoclast inhibitor and the MCSF antibody are administered simultaneously

9. The method of claims 3, 4, 6, and 7 wherein the anti-RANK antibody is AMG-162.

26. The method of any of the preceding claims wherein the anti-MCSF antibody comprises at least two of the CDRs from murine RX1 antibody of SEQ ID NO:

5 and SEQ ID NO;

6.

27. The method of any of the preceding claims wherein the anti-MCSF antibody-comprises at least three of the CDRs from murine RX1 antibody of SEQ ID NO:

5 and SEQ ID NO;

6.

28. The method of any of the preceding claims wherein the anti-MCSF antibody competes with murine RX1 antibody for binding to M-CSF of SEQ ID NO:

5 and SEQ ID NO;

6 by at least 75%.

2. A method of treating a patient suffering from an osteolytic disorder comprising the steps of administering to said patient an anti-M-CSF antibody at a monotherapeutically effective dose and a bisphosphonate at a monotherapeutically effective dose.

4. The method of claim 2 wherein the anti-MCSF antibody is RX1-derived antibody, an MC1-derived antibody, an MC3 derived antibody, or 5H4-derived antibody.

5. The method of claim 2 wherein the anti-MCSF antibody is heRX1.

10. The method of claims 2, 4, 6 and 7 wherein the bisphosphonate is selected from the group consisting of is zoledronate, pamidronate, clodronate, etidronate, tiludronate, alendronate, ibandronate, and risedronate.

11. The method of claim 10 wherein the bisphosphonate is zoledronate.

31. The method according to claims 4, 6, 8, 10, 11, or 12 wherein the anti-MCSF antibody binds to the same epitope as RX1, MC1, MC3, or 5B4 antibodies.

8. The method of claim wherein the RANKL inhibitor is selected from the group consisting of an anti-RANKL antibody, a soluble RANKL receptor, and a RANKL vaccine.

12. A method of treating a patient suffering from an osteolytic disorder comprising the steps of administering to said patient an anti-M-CSF antibody at a monotherapeutically-effective dose and a bisphosphonate at a monotherapeutically effective dose for a transition period.

13. The method of claim 12 wherein the osteoclast inhibitor is a bisphosphonate or a RANKL inhibitor.

14. The method of claim 13 wherein the transition period is approximately 1-7 days.

15. The method of claim 13 wherein the transition period is 1 week to 1 month.

16. The method of claim 13 wherein the transition period is 1 month to 3 months.

17. The method of claim 13 wherein the transition period is 3 to 6 months.

18. The method of claim 13 wherein the transition period is 6 to 12 months.

19. The method of claim 13 further comprising the step of discontinuing the bisphosphonate therapy after the transition period.

20. The method of claim 13 further comprising the step of reducing the dose of bisphosphonate after the transition period.

21. The method of claim 13 wherein the dose of bisphosphonate is reduced immediately after the transition period.

22. The method of claim 13 further comprising the step of reducing the dose of anti-MCSF antibody after the transition period.

24. The method of claim 13 wherein the dose of anti-MCSF antibody is reduced immediately after the transition period.

25. The method of claim 13 wherein the bisphosphonate is administered at least one-time after the transition period.

29. A method of claims 6, 13, and 20, wherein the osteoclast inhibitor is zoledronate and the MCSF antibody is an RX1-derived antibody.

30. The method of claim 29 wherein the zoledrorate is administered at a dose of between 0.5 mg and 4 mg.