Methods of treating anemia by inhibition of vascular endothelial growth factor (VEGF)

• US 7,351,411 B2
• Filed: 03/10/2006
• Issued: 04/01/2008
• Est. Priority Date: 03/11/2005
• Status: Active Grant

• Current Assignee: Regeneron Pharmaceuticals Incorporated
• Original Assignee: Regeneron Pharmaceuticals Incorporated
• Inventors: Rudge, John, Yancopoulos, George D., Stahl, Neil, Cedarbaum, Jesse M., Holash, Jocelyn
• Primary Examiner(s): Saoud; Christine J
• Assistant Examiner(s): LOCKARD, JON MCCLELLAND
• Application Number:
  US11/373,358
• Publication Number:
  US 20060210566A1
• Time in Patent Office: 753 Days
• Field of Search: None
• US Class Current: 424/134.1
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07K 14/71 for growth factors; for growth regulators
• 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 treating anemic disorders in human subjects comprising administering a VEGF antagonist comprising a fusion polypeptide having an immunoglobulin-like (Ig) domain 2 of the VEGF receptor Flt1 and Ig domain 3 of the VEGF receptor Flk1 or Flt4, and a multimerizing component. Further included are methods of preventing anemia, increasing hematocrit levels, and increasing or stimulating erythropoietin, particularly in subjects being treated for cancer with chemotherapeutic agents and/or radiation.

Claims

1. A method of treating an anemic disorder in a human subject in need thereof, comprising administering to the human subject a vascular endothelial growth factor (VEGF) antagonist capable of blocking, inhibiting, or ameliorating VEGF-mediated activity, wherein the VEGF antagonist is fusion polypeptide VEGRF1R2-FcΔ

C1(a) (SEQ ID NO;

4).

2. The method of claim 1, wherein the anemic disorder is characterized by a reduced hematocrit level.

3. The method of claim 1, wherein the anemic disorder is associated with chronic renal failure, cancer, cancer chemotherapy, radiation treatment, antiviral therapy, nutritional iron-deficiency, blood-loss, or hemolysis.

4. The method of claim 3, wherein the anemic disorder results from treatment with chemotherapy or radiation.

5. The method of claim 1, wherein administration is subcutaneous or intravenous.

6. The method of claim 5 wherein administration is a single dose or multiple doses.

7. A method of treating anemia expected to result from cancer treatment in a human subject at risk, comprising administering to the human subject fusion polypeptide VEGRF1R2-FcΔ

C1(a) (SEQ ID NO;

4).

8. The method of claim 7, wherein cancer treatment is treatment with radiation and/or chemotherapy.

9. A method of increasing hematocrit level in a human subject in need thereof, comprising administering to the human subject a vascular endothelial growth factor (VEGF) antagonist comprising fusion polypeptide VEGRF1R2-FcΔ

C1(a) (SEQ ID NO;

4).

10. The method of claim 9, wherein the hematocrit level in a subject in need thereof is less than about 33% of total blood volume and administration of the fusion polypeptide is in an amount sufficient to increase the hematocrit level above 33% of total blood volume.

11. A method of increasing erythropoietin levels in a human subject in need thereof, comprising administering to the human subject a vascular endothelial growth factor (VEGF) antagonist comprising fusion polypeptide VEGRF1R2-FcΔ

C1(a) (SEQ ID NO;

4).

12. A method of stimulating erythropoiesis in a human subject in need thereof, comprising administering to the human subject a vascular endothelial growth factor (VEGF) antagonist comprising fusion polypeptide VEGRF1R2-FcΔ

C1(a) (SEQ ID NO;

4).