TREATMENT OF OSTEOLYTIC DISORDERS AND CANCER USING CSF1R EXTRACELLULAR DOMAIN FUSION MOLECULES

• US 20100136006A1
• Filed: 11/25/2009
• Published: 06/03/2010
• Est. Priority Date: 11/26/2008
• Status: Active Grant

• Current Assignee: Five Prime Therapeutics, Inc. (Amgen Inc.)
• Original Assignee: Five Prime Therapeutics, Inc. (Amgen Inc.)
• Inventors: Long, Li, LIN, Haishan
• Granted Patent: US 8,183,207 B2
• Time in Patent Office: Days
• US Class Current: 424/134.100
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/70567 Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
• 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

Methods of using colony stimulating factor receptor (CSF1R) extracellular domain (ECD) fusion molecules to treat treating osteolytic bone loss, cancer metastasis, cancer metastasis-induced osteolytic bone loss, and tumor growth are provided. CSF1R ECD fusion molecules, polynucleotides encoding CSF1R ECD fusion molecules, and methods of making CSF1R ECD fusion molecules are also provided.

Claims

1. A method of treating osteolytic bone loss in a patient comprising administering to the patient a therapeutically effective amount of a CSF1R ECD fusion molecule, wherein the amino acid sequence of the CSF1R ECD fusion molecule comprises SEQ ID NO:

2 and excludes the last six C-terminal amino acid residues of SEQ ID NO;

1.

2. The method of claim 1, wherein the amino acid sequence of the CSF1R ECD consists of SEQ ID NO:

2.

3. The method of claim 1, wherein the one or more fusion partners is selected from an Fc, albumin, and polyethylene glycol.

4. The method of claim 3, wherein the one or more fusion partners is an Fc.

5. The method of claim 3, wherein the one or more fusion partners is polyethylene glycol.

6. The method of claim 3, wherein the one or more fusion partners is an Fc and polyethylene glycol.

7. The method of claim 1, wherein the polypeptide portion of the CSF1R ECD fusion molecule is produced from a Chinese hamster ovary (CHO) cell.

8. The method of claim 1, wherein the CSF1R ECD comprises a signal peptide.

9. The method of claim 1, wherein the fusion molecule comprises a linker between the CSF1R ECD and one or more fusion partners.

10. The method of claim 1, wherein the CSF1R ECD fusion molecule comprises SEQ ID NO:

6.

11. The method of claim 10, wherein the CSF1R ECD fusion molecule consists of SEQ ID NO:

6.

12. The method of claim 10, wherein the fusion molecule is produced from a CHO cell.

13. A method of inhibiting cancer metastasis comprising administering to the patient a therapeutically effective amount of a CSF1R ECD fusion molecule, wherein the amino acid sequence of the CSF1R ECD fusion molecule comprises SEQ ID NO:

2 and excludes the last six C-terminal amino acid residues of SEQ ID NO;

1.

14. The method of claim 13, wherein the amino acid sequence of the CSF1R ECD consists of SEQ ID NO:

2.

15. The method of claim 13, wherein the one or more fusion partners is selected from an Fc, albumin, and polyethylene glycol.

16. The method of claim 15, wherein the one or more fusion partners is an Fc.

17. The method of claim 15, wherein the one or more fusion partners is polyethylene glycol.

18. The method of claim 15, wherein the one or more fusion partners is an Fc and polyethylene glycol.

19. The method of claim 13, wherein the polypeptide portion of the CSF1R ECD fusion molecule is produced from a Chinese hamster ovary (CHO) cell.

20. The method of claim 13, wherein the CSF1R ECD comprises a signal peptide.

21. The method of claim 13, wherein the fusion molecule comprises a linker between the CSF1R ECD and one or more fusion partners.

22. The method of claim 13, wherein the CSF1R ECD fusion molecule comprises SEQ ID NO:

6.

23. The method of claim 22, wherein the CSF1R ECD fusion molecule consists of SEQ ID NO:

6.

24. The method of claim 22, wherein the fusion molecule is produced from a CHO cell.

25. A method of inhibiting CSF1- and/or IL34-dependent tumor growth in a patient comprising administering to the patient a therapeutically effective amount of a CSF1R ECD fusion molecule, wherein the amino acid sequence of the CSF1R ECD fusion molecule comprises SEQ ID NO:

2 and excludes the last six C-terminal amino acid residues of SEQ ID NO;

1.

26. The method of claim 25, wherein the amino acid sequence of the CSF1R ECD consists of SEQ ID NO:

2.

27. The method of claim 25, wherein the one or more fusion partners is selected from an Fc, albumin, and polyethylene glycol.

28. The method of claim 27, wherein the one or more fusion partners is an Fc.

29. The method of claim 27, wherein the one or more fusion partners is polyethylene glycol.

30. The method of claim 27, wherein the one or more fusion partners is an Fc and polyethylene glycol.

31. The method of claim 25, wherein the polypeptide portion of the CSF1R ECD fusion molecule is produced from a Chinese hamster ovary (CHO) cell.

32. The method of claim 25, wherein the CSF1R ECD comprises a signal peptide.

33. The method of claim 25, wherein the fusion molecule comprises a linker between the CSF1R ECD and one or more fusion partners.

34. The method of claim 25, wherein the CSF1R ECD fusion molecule comprises SEQ ID NO:

6.

35. The method of claim 34, wherein the CSF1R ECD fusion molecule consists of SEQ ID NO:

6.

36. The method of claim 34, wherein the fusion molecule is produced from a CHO cell.