Claims for Patent: 6,461,606

Summary for Patent: 6,461,606

Title:	Materials and methods for gene therapy
Abstract:	The subject invention concerns materials and methods for gene therapy. One aspect of the invention pertains to vectors which can be used to effect genetic therapy in animals or humans having genetic disorders where expression of high levels of a protein of interest are required to treat or correct the disorder. The subject invention also pertains to methods for treating animals or humans in need of gene therapy to treat or correct a genetic disorder. The materials and methods of the invention can be used to provide therapeutically effective levels of a protein that is non-functional, or that is absent or deficient in the animal or human to be treated. In one embodiment, the materials and methods can be used to treat alpha-1-antitrypsin deficiency.
Inventor(s):	Flotte; Terence R. (Gainesville, FL), Song; Sihong (Gainesville, FL), Byrne; Barry J. (Gainesville, FL), Morgan; Michael (Gainesville, FL)
Assignee:	University of Florida Research Foundation (Gainesville, FL)
Application Number:	09/299,141
Patent Claims:	1. A method for providing a mammal with a therapeutically effective amount of an alpha-1-antitrypsin protein, comprising introducing into suitable cells of said mammal an effective amount of an adeno-associated viral vector or an adeno-associated viral particle that comprises said vector; wherein said vector comprises a polynucleotide encoding an alpha-1-antitrypsin protein wherein said protein is expressed in said cell. 2. The method of claim 1, wherein said vector comprises a promoter operably linked to said polynucleotide. 3. The method of claim 2, wherein said promoter is selected from the group consisting of a CMV promoter, a hybrid CMV enhancer/.beta.-actin promoter, an EF1 promoter, an U1a promoter and an U1b promoter. 4. The method of claim 2, wherein said promoter is an inducible promoter selected from the group consisting of a Tet-inducible promoter and a VP16-LexA promoter. 5. The method of claim 2, wherein said vector further comprises an enhancer sequence operably linked to said promoter. 6. The method of claim 5, wherein said enhancer is a CMV enhancer. 7. The method of claim 5, wherein said enhancer is a synthetic enhancer. 8. The method of claim 7, wherein said enhancer is a muscle-specific enhancer. 9. The method of claim 1, wherein said vector comprises an intron sequence. 10. The method of claim 9, wherein said intron sequence is intron II from a human alpha-1-antitrypsin gene. 11. The method of claim 1, wherein said vector comprises a polynucleotide encoding a human alpha-1-antitrypsin protein. 12. The method of claim 1, wherein said vector is selected from the group consisting of dE-AT (SEQ ID NO:3), E-AT (SEQ ID NO:2), C-AT (SEQ ID NO:1), C-AT2 (SEQ ID NO:7), p43C-AT (SEQ ID NO:4), p43CB-AT (SEQ ID NO:6), p43C-AT-IN (SEQ ID NO:5), p43msENC-AT (SEQ ID NO:8), p43rmsENC-AT (SEQ ID NO:9), p43msENCB-AT (SEQ ID NO:10) and p43rmsENCB-AT (SEQ ID NO:11). 13. The method of claim 1, wherein said mammal has a condition that results in a defective alpha-1-antitrypsin protein. 14. The method of claim 1, wherein said mammal has a condition that results in a deficiency of said alpha-1-antitrypsin protein. 15. The method of claim 1, wherein said mammal is a human. 16. The method of claim 1, wherein said adeno-associated viral vector or adeno-associated viral particle is introduced into myofibers, myoblasts, hepatocytes, or lung cells of said mammal. 17. The method of claim 1, wherein the adeno-associated viral particle is introduced into said cells by infection. 18. The method of claim 1, wherein the adeno-associated viral vector is introduced into said cells by transfection. 19. The method of claim 1, wherein said adeno-associated viral particle or adeno-associated viral vector is introduced into cells of said mammal in vitro and the transduced cells are then introduced into said mammal. 20. The method of claim 1, wherein said adeno-associated viral particle or adeno-associated viral vector is introduced into said cells in vivo. 21. The method of claim 20, wherein said adeno-associated viral particle or adeno-associated viral vector is injected into a muscle of said mammal. 22. The method of claim 20, wherein said adeno-associated viral particle or adeno-associated viral vector is injected into a portal or peripheral vein of said mammal. 23. The method of claim 20, wherein said adeno-associated viral particle or adeno-associated viral vector is injected intratracheally or inhaled into the lungs of said mammal. 24. A method for treating alpha-1-antitrypsin deficiency in a mammal, comprising introducing into suitable cells of said mammal an effective amount of an adeno-associated viral vector or an adeno-associated viral particle that comprises said vector; wherein said vector comprises a polynucleotide encoding an alpha-1-antitrypsin protein wherein said protein is expressed in said cell. 25. The method of claim 24, wherein said mammal is a human. 26. The method of claim 24, wherein said vector comprises a polynucleotide encoding a human alpha-1-antitrypsin protein. 27. The method of claim 24, wherein said alpha-1-antitrypsin deficiency is caused by a defective alpha-1-antitrypsin protein.

Details for Patent 6,461,606

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2018-04-24
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2018-04-24
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2018-04-24