von Willebrand factor (vWF)-containing preparations, and methods, kits, and uses related thereto

• US 8,759,293 B2
• Filed: 11/12/2010
• Issued: 06/24/2014
• Est. Priority Date: 11/13/2009
• Status: Active Grant

• Current Assignee: Grifols Therapeutics LLC (Grifols SA)
• Original Assignee: Grifols Therapeutics Incorporated (Grifols SA)
• Inventors: Barnett, Thomas
• Primary Examiner(s): Alstrum Acevedo, James H
• Assistant Examiner(s): D' AMBROSIO, THEA
• Application Number:
  US13/509,309
• Publication Number:
  US 20120289468A1
• Time in Patent Office: 1,320 Days
• Field of Search: None
• US Class Current: 514/14.1
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C07K 14/755 Factors VIII , e.g. factor VIII C (AHF), factor VIII Ag (VWF)

Abstract

The present invention relates to methods, compositions and kits for preparing FVIII and employing same. Also provided are vWF polypeptides and nucleic acid molecules encoding same.

Claims

1. An isolated von Willebrand factor (vWF) polypeptide comprising a Factor VIII (FVIII) binding domain, with the proviso that the polypeptide lacks one of vWF domain A1, A2, A3, D4, B1, B2, B3, C1, C2, CK, or a combination thereof, wherein the polypeptide further comprises an immunoglobulin Fc amino acid sequence comprising at least a hinge region, wherein the polypeptide exhibits binding to the FVIII, wherein the Factor VIII (FVIII) binding domain comprises the amino acid sequence as set forth in SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

33, SEQ ID NO;

34, or SEQ ID NO;

35.

3. The polypeptide of claim 1, wherein the polypeptide is capable of forming a dimer.

4. The polypeptide of claim 1, wherein the immunoglobulin Fc amino acid sequence has the sequence set forth in SEQ ID NO:

16.

5. A composition comprising the polypeptide of claim 1.

6. A protein complex comprising the polypeptide of claim 1 bound to the FVIII.

7. A composition comprising the protein complex of claim 6.

8. A cell expressing the polypeptide of claim 1.

9. A cell expressing the protein complex of claim 6.

10. A composition comprising the protein complex of claim 6, and a pharmaceutically acceptable carrier.

2. An isolated von Willebrand factor (vWF) polypeptide comprising a Factor VIII (FVIII) binding domain, with the proviso that the polypeptide lacks one of vWF domain A1, A2, A3, D4, B1, B2, B3, C1, C2, CK, or a combination thereof, wherein the polypeptide further comprises an immunoglobulin Fc amino acid sequence comprising at least a hinge region, wherein the polypeptide exhibits binding to the FVIII, wherein the polypeptide comprises the sequence set forth in SEQ ID NO:

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

36, SEQ ID NO;

38, or SEQ ID NO;

39.