ERYTHROPOIETIN RECEPTOR PEPTIDE FORMULATIONS AND USES

• US 20090221510A1
• Filed: 08/21/2008
• Published: 09/03/2009
• Est. Priority Date: 06/03/2005
• Status: Abandoned Application

• Current Assignee: Affymax Incorporated, Takeda Pharmaceutical Company Limited
• Original Assignee: Affymax Incorporated, Takeda Pharmaceutical Company Limited
• Inventors: DULIEGE, ANNE-MARIE, LANG, WILLIAM, STEAD, RICHARD, IWASHITA, JULIA, LEONG, ROBERT HONG CHOON, WEINBERG, MARK A.
• Application Number:
  US12/195,832
• Publication Number:
  US 20090221510A1
• Time in Patent Office: Days
• US Class Current: 514/10.300
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• 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 47/665 the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
• CPC Class Codes: A61K 51/02 characterised by the carrier , i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 14/505 Erythropoietin [EPO]

Abstract

The present invention relates to novel uses of peptide compounds that are agonists of the erythropoietin receptor (EPO-R). The invention also relates to methods of using such peptide compounds to treat disorders associated with insufficient or defective red blood cell production, including chemotherapy induced anemia. Pharmaceutical compositions, which comprise the peptide compounds of the invention, are also provided. Also provided are kits and articles of manufacture comprising such compounds.

Claims

1. A method of treating a disorder characterized by deficiency of erythropoietin or a low or defective red blood cell population in a patient who is undergoing, has undergone, or will undergo, chemotherapy for lung, breast or prostate cancer, comprising administering to the patient a therapeutically effective amount of a compound comprising:

(a) a first and second peptide monomer comprising the amino acid sequence (AcG)GLYACHMGPIT(1-nal)VCQPLR (SEQ ID NO;

     14);

(b) a linker moiety covalently bonding the first peptide monomer to the second peptide monomer; and

(c) a spacer moiety covalently joining the linker moiety and a poly(ethylene glycol) (PEG) moiety, said PEG moiety comprising a linear, unbranched PEG having a molecular weight from about 10,000 Daltons to about 60,000 Daltons.

2. The method of claim 1, wherein the amino acid sequence of the first and/or second peptide monomer additionally comprises (MeG), K, or (MeG)K at the C-terminus.

3. The method of claim 2, wherein the amino acid sequence of the first and/or second peptide monomer is (AcG)GLYACHMGPIT(1-nal)VCQPLRK (SEQ ID NO:

1).

4. The method of claim 2, wherein the amino acid sequence of the first and/or second peptide monomer is (AcG)GLYACHMGPIT(1-nal)VCQPLR(MeG) (SEQ ID NO:

3).

5. The method of claim 2, wherein the amino acid sequence of the first and/or second monomer is (AcG)GLYACHMGPIT(1-nal)VCQPLR(MeG)K (SEQ ID NO:

2).

6. The method of claim 1, wherein two cysteine residues of the first and/or second peptide monomer are bonded together through a disulfide bridge.

7. The method of claim 1, wherein the linker moiety comprises an amide derivative of a lysine residue.

8. The method of claim 7, wherein the amide derivative of a lysine residue is covalently bonded through the nitrogen atom of its side chain.

9. The method of claim 1, wherein the linker moiety is defined by the formula:

10. The method of claim 1, wherein the spacer moiety is defined by the formula:

11. The method of claim 1, wherein the compound is further defined by the formula:

12. The method of claim 11, wherein the compound is:

13. The method of claim 1, wherein the PEG moiety has a molecular weight from about 10,000 Dalton to about 50,000 Daltons.

14. The method of claim 13, wherein the PEG moiety has a molecular weight from about 20,000 Daltons to about 40,000 Daltons.

15. The method of claim 1, wherein the disorder is anemia.

16. The method of claim 15, wherein the disorder is chemotherapy-induced anemia.

17. The method of claim 1, wherein the patient is undergoing, has undergone, or will undergo, chemotherapy for lung cancer.

18. The method of claim 17, where the lung cancer is non-small cell lung cancer.

19. The method of claim 1, wherein the patient is undergoing, has undergone, or will undergo, chemotherapy for prostate cancer.

20. The method of claim 1, wherein the patient is undergoing, has undergone, or will undergo, chemotherapy for breast cancer.

21. The method of claim 1, wherein the patient is a primate.

22. The method of claim 1, wherein the patient is a human.

23. The method of claim 1, further comprising identifying a patient in need of treatment.

24. The method of claim 1, wherein the compound is administered locally.

25. The method of claim 1, wherein the compound is administered systemically.

26. The method of claim 25, wherein the compound is administered intravenously, intra-arterially, intramuscularly, intraperitoneally, subcutaneously or orally.

27. The method of claim 1, wherein the therapeutically effective amount is a dosage from about 0.01 milligram to about 1,000 milligram of the compound per kilogram of body weight of the patient.

28. The method of claim 27, wherein the therapeutically effective amount is a dosage from about 0.025 milligram to about 0.5 milligram of the compound per kilogram of body weight of the patient.

29. The method of claim 27, wherein the therapeutically effective amount is a dosage from about 0.025 milligram to about 0.2 milligram of the compound per kilogram of body weight of the patient.

30. The method of claim 27, wherein the therapeutically effective amount is a dosage from about 0.05 milligram to about 0.1 milligram of the compound per kilogram of body weight of the patient.

31. The method of claim 27, wherein the therapeutically effective amount is administered in a single dose per day.

32. The method of claim 27, wherein the therapeutically effective amount is administered in two or more doses per day.

33. The method of claim 27, wherein the therapeutically effective amount is administered once every 3 to 4 weeks.

34. A pharmaceutical composition for preventing or treating a disorder characterized by deficiency of erythropoietin or a low or defective red blood cell population in a patient who is undergoing, has undergone, or will undergo, chemotherapy for lung, breast or prostate cancer, which comprises a compound comprising:

(a) a first and second peptide monomer comprising the amino acid sequence (AcG)GLYACHMGPIT(1-nal)VCQPLR (SEQ ID NO;

     14);

(b) a linker moiety covalently bonding the first peptide monomer to the second peptide monomer; and

(c) a spacer moiety covalently joining the linker moiety and a poly(ethylene glycol) (PEG) moiety, said PEG moiety comprising a linear, unbranched PEG having a molecular weight from about 10,000 Daltons to about 60,000 Daltons.