Erythropoietin receptor peptide formulations and uses

• US 7,906,485 B2
• Filed: 06/05/2006
• Issued: 03/15/2011
• Est. Priority Date: 06/03/2005
• Status: Expired due to Fees

• Current Assignee: Affymax Incorporated
• Original Assignee: Affymax Incorporated
• Inventors: Woodburn, Kathryn Wynne, Duliege, Anne-Marie, Stead, Richard, Leuther, Kerstin, Naso, Robert Barnett
• Primary Examiner(s): Russel; Jeffrey E
• Application Number:
  US11/916,416
• Publication Number:
  US 20090136442A1
• Time in Patent Office: 1,744 Days
• Field of Search: None
• US Class Current: 514/13.5
• 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 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones
• 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: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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 peptide compounds that are agonists of the erythropoietin receptor (EPO-R). The invention also relates to therapeutic methods using such peptide compounds to treat disorders associated with insufficient or defective red blood cell production, including pure red cell aplasia (PRCA). Pharmaceutical compositions, which comprise the peptide compounds of the invention, and dosages are also provided.

Claims

1. A method for treating a patient having pure red cell aplasia (PRCA), which method comprises administering once every 3 to 4 weeks to the patient a therapeutically effective amount of a compound that binds to an activates the erythropoietin receptor (EPO-R) wherein the compound comprises:

(a) a first peptide monomer and a second peptide monomer, each of said first and second peptide monomers 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 molecular weight of 10,000 to 60,000 Daltons.

2. The method of claim 1, wherein the amino acid sequence additionally comprises (MeG), K, or (MeG)K.

3. The method of claim 2, wherein the amino acid sequence is (AcG)GLYACHMGPIT(1-nal)VCQPLRK (SEQ ID NO:

1).

4. The method of claim 2, wherein the amino acid sequence is (AcG)GLYACHMGPIT(1-nal)VCQPLR(MeG) (SEQ ID NO:

3).

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

2).

6. The method of claim 1, wherein the spacer moiety is an iminodiacetic moiety.

7. The method of claim 1, wherein the spacer moiety has the formula:

8. The method of claim 1, wherein the linker moiety is lysine.

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

10. The method of claim 9, wherein the PEG moiety has a molecular weight of 20,000 to 40,000 Daltons.

11. The method of claim 1, wherein the compound is administered with a pharmaceutically acceptable carrier.

13. The method of claim 1 or 12, wherein the PRCA is accompanied by a deficiency of erythropoietin or a low or defective red blood cell population.

14. The method of claim 1 or 12, wherein the therapeutically effective amount is 0.025 to 0.5 milligram of the compound per kilogram body weight of the patient.

12. A method for treating a patient having pure red cell aplasia (PRCA), which method comprises administering once every 3 to 4 weeks to the patient a therapeutically effective amount of a compound that binds to and activates the erythropoietin receptor (EPO-R), wherein the compound is: