Claims
- 1. A method of treating hemophilia in a mammal, comprising:
providing a pharmaceutical composition comprising recombinant adeno-associated virus virions, said virions comprising a nucleotide sequence encoding a Factor VIII protein lacking at least a portion of the B domain, said nucleotide sequence operably linked to expression control elements; and administering said pharmaceutical composition to a mammal under conditions that result in the expression of the Factor VIII protein at a level that provides a therapeutic effect in said mammal.
- 2. The method of claim 9, wherein said Factor VIII protein is expressed in the liver.
- 3. The method of claim 9, wherein said recombinant adeno-associated virus virions are administered to the liver.
- 4. The method of claim 9, wherein said expression control elements comprise a tissue-specific promoter.
- 5. The method of claim 12 wherein said expression control elements comprise a liver-specific promoter.
- 6. The method of claim 9 wherein said expression control elements comprise a human growth hormone polyadenylation sequence.
- 7. The method of claim 9, wherein said recombinant adeno-associated virus virions are administered via intravenous administration.
- 8. The method of claim 15, wherein said intravenous administration is via the portal vein.
- 9. The method of claim 9, wherein said recombinant adeno-associated virus virions are administered via intraarterial administration.
- 10. The method of claim 17, wherein said recombinant adeno-associated virus virions are administered via the hepatic artery.
- 11. The method of claim 9, wherein said nucleotide sequence encoding Factor VIII comprises a light chain and a heavy chain and wherein said light chain and heavy chain are operably linked by a junction.
- 12. The method of claim 19, wherein said nucleotide sequence is SEQ ID 13, such that said junction has the amino acid sequence Ser-Phe.
- 13. The method of claim 19, wherein said nucleotide sequence is SEQ ID 14, such that said junction has the amino acid sequence Ser-Phe-Ser-Gln-Asn-Pro-Pro-Val-Leu-Lys-Arg-His-Gln-Arg.
- 14. The method of claim 19, wherein said expression control elements comprise a liver-specific promoter, and wherein said recombinant adeno-associated virus virions are administered to the liver of said mammal.
RELATED APPLICATIONS
[0001] This Application is a Continuation of U.S. application Ser. No. 10/007,968, filed Nov. 16, 2001, now abandoned, which is a divisional of U.S. application Ser. No. 09/740,211, filed Dec. 18, 2000, which is a continuation of U.S. application Ser. No. 09/470,618, filed Dec. 22, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/364,862, filed Jul. 30, 1999, which claims benefit under 35 U.S.C. §119(e) of U.S. Provisional Application Nos. 60/125,974 and 60/104,994, filed Mar. 24, 1999 and Oct. 20, 1998, respectively. All of these prior applications are hereby incorporated by reference in their entireties.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60125974 |
Mar 1999 |
US |
|
60104994 |
Oct 1998 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09740211 |
Dec 2000 |
US |
Child |
10007968 |
Nov 2001 |
US |
Continuations (2)
|
Number |
Date |
Country |
Parent |
10007968 |
Nov 2001 |
US |
Child |
10293400 |
Nov 2002 |
US |
Parent |
09470618 |
Dec 1999 |
US |
Child |
09740211 |
Dec 2000 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09364862 |
Jul 1999 |
US |
Child |
09470618 |
Dec 1999 |
US |