CSF1R EXTRACELLULAR DOMAIN FUSION MOLECULES AND TREATMENTS USING SAME

• US 20100136007A1
• 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 8,080,246 B2
• Time in Patent Office: Days
• US Class Current: 424/134.100
• 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: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/7153 for colony-stimulating factors [CSF]
• 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 specific CSF1R ECD fusion molecules that exhibit improved therapeutic properties. The invention also relates to polypeptide and polynucleotide sequences, vectors, host cells, and compositions comprising or encoding such molecules. The invention also relates to methods of making and using the CSF1R ECD fusion molecules. The invention further relates to methods of treatment using the CSF1R ECD fusion molecules. For example, certain CSF1R ECDs of the invention may be used to treat rheumatoid arthritis (RA) or multiple sclerosis (MS).

Claims

1. A colony stimulating factor 1 receptor (CSF1R) extracellular domain (ECD) fusion molecule comprising a CSF1R ECD and one or more fusion partners, 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 CSF1R ECD fusion molecule of claim 1, wherein the one or more fusion partners is selected from an Fe, albumin, and polyethylene glycol.

3. The CSF1R ECD fusion molecule of claim 2, wherein the one or more fusion partners is an Fc.

4. The CSF1R ECD fusion molecule of claim 2, wherein the one or more fusion partners is an Fc and polyethylene glycol.

5. The CSF1R ECD fusion molecule of claim 2, wherein the one or more fusion partners is polyethylene glycol.

6. The CSF1R ECD fusion molecule of claim 1, wherein the CSF1R ECD comprises a signal peptide.

7. The CSF1R ECD fusion molecule of claim 1, wherein the CSF1R ECD amino acid sequence consists of SEQ ID NO:

2.

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

9. The CSF1R ECD fusion molecule of claim 1, wherein the polypeptide portion of the fusion molecule is expressed in Chinese hamster ovary (CHO) cells.

20. A polynucleotide comprising a nucleic acid sequence that encodes the CSF1R ECD fusion molecule of claim 1.

25. A method of producing the CSF1R ECD fusion molecule of claim 1, comprising:

(a) culturing Chinese hamster ovary (CHO) cells comprising a vector wherein the vector comprises a polynucleotide with a nucleic acid sequence encoding the CSF1R ECD fusion molecule; and

(b) recovering the CSF1R ECD fusion molecule.

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

6.

27. The method of claim 26, wherein the nucleic acid sequence encodes the CSF1R ECD fusion molecule of SEQ ID NO:

16.

28. A method of treating multiple sclerosis in a patient comprising administering to the patient a therapeutically effective amount of the CSF1R ECD fusion molecule of claim 1.

29. The method of claim 28, wherein the CSF1R ECD fusion molecule comprises SEQ ID NO:

6.

30. A method of treating rheumatoid arthritis in a patient comprising administering to the patient a therapeutically effective amount of the CSF1R ECD fusion molecule of claim 1.

31. The method of claim 30, wherein the CSF1R ECD fusion molecule comprises SEQ ID NO:

6.

32. A method of depleting peripheral blood monocytes in a patient comprising administering to the patient a therapeutically effective amount of the CSF1R ECD fusion molecule of claim 1.

33. The method of claim 32, wherein the CSF1R ECD fusion molecule comprises SEQ ID NO:

6.

10. A CSF1R ECD fusion molecule comprising a CSF1R ECD and an Fc, wherein the amino acid sequence of the CSF1R ECD fusion molecule comprises SEQ ID NO.:

6.

11. The CSF1R ECD fusion molecule of claim 10, wherein the fusion molecule is expressed in Chinese hamster ovary (CHO) cells.

12. The CSF1R ECD fusion molecule of claim 10, wherein the CSF1R ECD comprises a signal peptide.

13. The CSF1R ECD fusion molecule of claim 10, wherein the amino acid sequence of the CSF1R ECD fusion molecule consists of SEQ ID NO.:

6.

21. A polynucleotide comprising a nucleic acid sequence that encodes the CSF1R ECD fusion molecule of claim 13.

22. The polynucleotide of claim 21, wherein the nucleic acid sequence encodes the CSF1R ECD fusion molecule of SEQ ID NO:

16.

23. The polynucleotide of claim 21, wherein the nucleic acid sequence comprises SEQ ID NO:

39.

24. The polynucleotide of claim 21, wherein the nucleic acid sequence comprises SEQ ID NO:

40.

14. The CSF1R ECD fusion molecule of claim 14, wherein the fusion molecule is expressed in CHO cells.

15. A CSF1R ECD fusion molecule comprising a CSF1R ECD, an Fc, and polyethylene glycol, wherein the amino acid sequence of the CSF1R ECD fusion molecule comprises SEQ ID NO.:

6.

16. The CSF1R ECD fusion molecule of claim 15, wherein the CSF1R ECD comprises a signal peptide.

17. The CSF1R ECD fusion molecule of claim 15, wherein the polypeptide portion of the fusion molecule is expressed in Chinese hamster ovary (CHO) cells.

18. The CSF1R ECD fusion molecule of claim 15, wherein the amino acid sequence of the CSF1R ECD fusion molecule consists of SEQ ID NO.:

6.

19. The CSF1R ECD fusion molecule of claim 18, wherein the polypeptide portion of the fusion molecule is expressed in CHO cells.