Claims for Patent: 7,132,277

Summary for Patent: 7,132,277

Title:	Helper dependent vector system for gene therapy
Abstract:	The present invention features helper-dependent adenoviral vector elements, and helper adenoviral elements, that enhance the production and isolation of helper-dependent adenoviral vectors. Such elements include a modified packaging signal having low homology to, and preferably less activity than, a wild-type packaging signal, an E4 non-coding segment directly joined to the 5\' ITR that confers a selective advantage, and stuffer region(s) that provide a helper-dependent adenoviral vector with a GC content of about 50% to about 60%. The modified packaging signal is preferably used in a helper virus to decrease recombination and generation of the virus. The E4 non-coding segment and the stuffer region(s) are preferably used in a helper-dependent adenoviral vector to provide the vector with a growth advantage over a helper virus.
Inventor(s):	Bett; Andrew (Lansdale, PA), Sandig; Volker (Berlin, DE), Youil; Rima (North Wales, PA)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	09/890,836
Patent Claims:	1. A nucleic acid molecule comprising a packaging signal cassette flanked by a recombinase recognition sequence, wherein said packaging signal cassette comprises a modified adenovirus packaging signal having two to six A elements having a consensus sequence of ATTTGN.sub.8CG (SEQ ID NO:1), wherein N.sub.8 of each A element is replaced by the N.sub.8 sequence of a different A element, and wherein the resulting A element is different from both the wild-type packaging signal A element and from each other. 2. The nucleic acid of claim 1, wherein said modified adenovirus packaging signal contains from three to five A elements. 3. The nucleic acid of claim 1, wherein said recombinase recognition sequence is loxP. 4. The nucleic acid of claim 1, wherein said recombinase recognition sequence is frt. 5. The nucleic acid of claim 1, wherein said wild-type packaging signal is human adenovirus serotype 5 packaging signal. 6. The nucleic acid of claim 1, wherein the modified packaging signal comprises at a maximum 23 bp of contiguous sequence homology relative to a wild-type packaging signal. 7. The nucleic acid of claim 1, wherein said modified adenovirus packaging signal further comprises SEQ ID NO:3. 8. The nucleic acid of claim 1, wherein said modified packaging signal comprises an A element 21 bp after AII. 9. The nucleic acid of claim 1, wherein said nucleic acid is a plasmid. 10. The nucleic acid of claim 1 further comprising elements for use as an adenoviral helper virus vector. 11. The nucleic acid of claim 10, wherein said helper virus vector does not contain an E1 gene. 12. The nucleic acid of claim 11, wherein said helper virus vector comprises an E3 region with an insert of about 2.9 kb. 13. The nucleic acid of claim 12, wherein said insert does not contain a promoter sequence. 14. The nucleic acid of claim 13 wherein the E3 region has an insert of at least about 2.7 kb, provided that said insertion does not contain a promoter sequence. 15. The nucleic acid of claim 14, wherein said insert is a human intron sequence.

Details for Patent 7,132,277

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		2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2039-02-26