Adeno-associated vector compositions for expression of Factor VIII

• US 7,351,577 B2
• Filed: 08/01/2003
• Issued: 04/01/2008
• Est. Priority Date: 10/20/1998
• Status: Expired due to Fees

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Qian, Xiaobing, Couto, Linda B., Colosi, Peter C.
• Primary Examiner(s): WHITEMAN, BRIAN A
• Application Number:
  US10/632,645
• Publication Number:
  US 20050276787A1
• Time in Patent Office: 1,705 Days
• Field of Search: 424/93.2, 435/320.1
• US Class Current: 435/320.1
• CPC Class Codes: A61K 38/37 Factors VIII
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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)
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2799/025 where the vector is derived from a parvovirus
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination
• CPC Class Codes: C12N 2830/42 being an intron or intervening sequence for splicing and/or stability of RNA
• CPC Class Codes: C12N 2830/85 mammalian

Abstract

One form of a composition has two types of recombinant adeno-associated virus. The first type encodes a portion of Factor VIII operably linked to an expression control element; and the second type encodes a different portion of Factor VIII operably linked to an expression control element. The first and second nucleotide sequences collectively encode a functional Factor VIII protein. Another form of the composition is a recombinant adeno-associated virus containing a nucleotide sequence encoding functional Factor VIII light or heavy chain operably linked to a tissue-specific promoter.

Claims

1. A pharmaceutical composition comprising a recombinant adeno-associated virus (AAV) virion comprising a nucleotide sequence encoding a functional Factor VIII protein, wherein said recombinant adeno-associated virus virion lacks AAV rep and cap genes, wherein said Factor VIII protein is B domain-deleted, and wherein said nucleotide sequence comprises SEQ ID NO:

13.

2. A pharmaceutical composition comprising a recombinant adeno-associated virus (AAV) virion comprising a nucleotide sequence encoding a functional Factor VIII protein, wherein said recombinant adeno-associated virus virion lacks AAV rep and cap genes, wherein said Factor VIII protein is B domain-deleted, and, wherein said nucleotide sequence comprises SEQ ID NO:

14.