Use of angiopoietins in promoting blood coagulation and in the treatment of blood coagulation disorders

Patent metadata

Field	Value
Publication number	US-10588940-B2
Application number	US-201615773498-A
Country	US
Kind code	B2
Filing date	Nov 4, 2016
Priority date	Nov 6, 2015
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

The present invention provides methods for promoting blood coagulation and/or treating blood coagulation disorders in a subject in need thereof. The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an angiopoietin protein or a modified angiopoietin protein molecule such as AngF1-Fc-F1 or AngF2-Fc-F2.

First claim

What is claimed is:

1. A method of treating, preventing or ameliorating at least one symptom, indication or complication of a blood coagulation disorder, comprising administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a fusion protein comprising angiopoietin-1 or a portion thereof fused to an immunoglobulin Fc fragment, and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition stimulates blood coagulation in the subject.

2. The method of claim 1 , wherein the blood coagulation disorder is selected from the group consisting of inborn platelet pathologies, platelet disorders caused by insufficient production, platelet disorders caused by destruction by the immune system, coagulation factor disorders, and disorders associated with warfarin treatment, aspirin treatment, surgery, or injury.

3. The method of claim 1 , wherein the angiopoietin protein binds purified soluble extracellular domain of thrombomodulin with an EC 50 value of less than 100 nM.

4. The method of claim 1 , wherein the angiopoietin protein is administered intravenously.

5. The method of claim 1 , wherein the angiopoietin protein is administered subcutaneously.

6. The method of claim 1 , wherein the fusion protein comprises at least one fibrinogen-like domain of angiopoietin-1 fused to an Fc fragment.

7. The method of claim 6 , wherein the fusion protein comprises:
i) a first fibrinogen-like domain of angiopoietin-1 fused at the C-terminal end to the N-terminal end of an Fc fragment, and
ii) the Fc fragment fused at the C-terminal end to the N-terminal end of a second fibrinogen-like domain of angiopoietin-1.

8. The method of claim 7 , wherein the fusion protein is AngF1-Fc-F1.

9. The method of claim 8 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 2.

10. The method of claim 2 , wherein the blood coagulation disorder is an inborn platelet pathology selected from the group consisting of: thrombasthenia of Glanzmann and Naegeli, Bernard-Soulier syndrome, gray platelet syndrome, delta storage pool deficiency, and Von Willebrand disease.

11. The method of claim 2 , wherein the blood coagulation disorder is a platelet disorder selected from the group consisting of: myelodysplastic syndrome and immune thrombocytopenic purpura.

12. The method of claim 2 , wherein the blood coagulation disorder is a coagulation factor disorder selected from the group consisting of: hemophilia, deficiency of Vitamin K, a Factor XII mutation, thrombocytopenia, uremia, and congenital afibrinogenemia.

13. The method of claim 12 , wherein the hemophilia is selected from the group consisting of hemophilia A, hemophilia B, and hemophilia C.

14. The method of claim 2 , wherein the blood coagulation disorder is a liver failure disorder selected from the group consisting of acute liver failure, chronic liver failure, early liver failure, and end-stage liver failure.

15. The method of claim 2 , wherein the blood coagulation disorder is associated with warfarin treatment, aspirin treatment, surgery, or injury.

Assignees

• Regeneron Pharma

Inventors

• Daly Christopher
• Davis Samuel

Classifications

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• G01N33/86

  involving blood coagulating time {or factors, or their receptors} · CPC title

• C07K14/515

  Angiogenesic factors; Angiogenin · CPC title

• A61K38/1891 Primary

  Angiogenesic factors; Angiogenin · CPC title