Claims for Patent: 8,142,794

Summary for Patent: 8,142,794

Title:	Hepatitis C virus vaccine
Abstract:	The present invention features Ad6 vectors and a nucleic acid encoding a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide containing an inactive NS5B RNA-dependent RNA polymerase region. The nucleic acid is particularly useful as a component of an adenovector or DNA plasmid vaccine providing a broad range of antigens for generating an HCV specific cell mediated immune (CMI) response against HCV.
Inventor(s):	Emini; Emilio A. (Wayne, PA), Kaslow; David C. (Rancho Santa Fe, CA), Bett; Andrew J. (Lansdale, PA), Shiver; John W. (Chalfont, PA), Nicosia; Alfredo (Rome, IT), Lahm; Armin (Rome, IT), Luzzago; Alessandra (Rome, IT), Cortese; Riccardo (Rome, IT), Colloca; Stefano (Rome, IT)
Assignee:	Merck Sharp & Dohme Corp. (Rahway, NJ)
Application Number:	12/396,747
Patent Claims:	1. A method of treating a HCV infection or inducing an immune response in a patient comprising the step of administering to said patient an effective amount of an expression vector comprising a nucleotide sequence encoding a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide substantially similar to SEQ ID NO: 1, provided that said polypeptide has sufficient protease activity to process itself to produce an NS5B protein and said NS5B protein is enzymatically inactive, wherein said polypeptide consists of SEQ ID NO: 1 or a sequence substantially similar to SEQ ID NO: 1, wherein said sequence substantially similar to SEQ ID NO: 1 differs from SEQ ID NO: 1 by 1-20 amino acids and maintains all or most T-cell antigen regions present in SEQ ID NO: 1, wherein said expression vector expresses said polypeptide from said nucleotide sequence in said patient. 2. The method of claim 1, wherein said patient is a human. 3. The method of claim 2, wherein said patient is not infected with HCV. 4. The method of claim 2, wherein said patient is infected with HCV. 5. The method of claim 2, wherein said polypeptide consists of SEQ ID NO: 1. 6. The method of claim 2, wherein said polypeptide differs from SEQ ID NO: 1 by 1-10 amino acids and maintains all T-cell antigen regions present in SEQ ID NO: 1. 7. The method of claim 2, wherein said nucleotide sequence is the coding sequence of either SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 10 or SEQ ID NO: 11. 8. The method of claim 2, wherein said nucleotide sequence is the coding sequence of either SEQ ID NO: 2 or SEQ ID NO: 3. 9. The method of claim 2, wherein said nucleotide sequence is the coding sequence for SEQ ID NO: 2 or differs from SEQ ID NO: 2 by 1 to 50 nucleotides. 10. A method of treating a HCV infection or inducing an immune response in a patient comprising the step of administering to said patient an effective amount of a nucleic acid comprising a gene expression cassette that expresses a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide substantially similar to SEQ ID NO: 1 in a human cell, provided that said polypeptide can process itself to produce an NS5B protein and said NS5B protein is enzymatically inactive, said expression cassette comprising: a) a promoter transcriptionally coupled to a nucleotide sequence encoding said polypeptide; b) a 5' ribosome binding site functionally coupled to said nucleotide sequence, c) a terminator joined to the 3' end of said nucleotide sequence, and d) a 3' polyadenylation signal functionally coupled to said nucleotide sequence, wherein said patient is a human and said polypeptide consists of SEQ ID NO: 1 or a sequence substantially similar to SEQ ID NO: 1, wherein said sequence substantially similar to SEQ ID NO: 1 differs from SEQ ID NO: 1 by 1-20 amino acids and maintains all or most T-cell antigen regions present in SEQ ID NO: 1. 11. The method of claim 10, wherein and said nucleic acid is a plasmid suitable for administration into said patient and further comprises a prokaryotic origin of replication and a gene coding for a selectable marker. 12. The method of claim 11, wherein said nucleotide sequence encodes for a polypeptide of SEQ ID NO: 1. 13. The method of claim 12, wherein said nucleotide sequence is the coding sequence of either SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 10, or SEQ ID NO: 11. 14. The method of claim 13, wherein said nucleotide sequence is the coding sequence of SEQ ID NO: 2 or SEQ ID NO: 3. 15. The method of claim 13, wherein said promoter is the human intermediate early cytomegalovirus promoter (intron A), said 5' ribosome binding site consists of SEQ ID NO: 12, and said 3' polyadenylation is the bovine growth hormone (BGH) polyadenylation signal. 16. The method of claim 10, wherein said nucleic acid is an adenovector. 17. The method of claim 16, wherein said adenovector consists of: a) a first adenovirus region from about base pair 1 to about base pair 450 corresponding to either Ad5 or Ad6; b) said gene expression cassette in a E1 parallel or E1 anti-parallel orientation joined to said first region; c) a second adenovirus region from about base pair 3511 to about base pair 5548 corresponding to Ad5 or from about base pair 3508 to about base pair 5541 corresponding to Ad6, joined to said expression cassette; d) a third adenovirus region from about base pair 5549 to about base pair 28133 corresponding to Ad5 or from about base pair 5542 to about base pair 28156 corresponding to Ad6, joined to said second region; e) a fourth adenovirus region from about base pair 30818 to about base pair 33966 corresponding to Ad5 or from about base pair 30789 to about base pair 33784 corresponding to Ad6, joined to said third region; and f) a fifth adenovirus region from about base pair 33967 to about base pair 35935 corresponding to Ad5 or from about base pair 33785 to about base pair 35759 corresponding to Ad6, joined to said fourth region. 18. The method of claim 17, wherein said first region corresponds to Ad5, said second region corresponds to Ad5, said third region corresponds to Ad5, said fourth region corresponds to Ad5, and said fifth region corresponds to Ad5. 19. The method of claim 18, wherein said promoter is the human intermediate early cytomegalovirus promoter, said 5' ribosome binding site consists of SEQ ID NO: 12, and said 3' polyadenylation is the BGH polyadenylation signal. 20. The method of claim 19, wherein said expression cassette is in an E1 anti parallel orientation and said nucleotide sequence is either SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 10, or SEQ ID NO: 11. 21. The method of claim 17, wherein said first region corresponds to Ad5 or Ad6, said second region corresponds to Ad5 or Ad6, said third region corresponds to Ad6, said fourth region corresponds to Ad6, and said fifth region corresponds to Ad5 or Ad6. 22. The method of claim 21, where said promoter is the human intermediate early cytomegalovirus promoter, said 5' ribosome binding site consists of SEQ ID NO: 12, and said 3' polyadenylation is the BGH polyadenylation signal. 23. The method of claim 22, wherein said expression cassette is in an E1 anti parallel orientation and said nucleotide sequence is SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 10, or SEQ ID NO: 11. 24. The method of claim 23, wherein said nucleotide sequence is SEQ ID NO: 2 or SEQ ID NO: 3. 25. The method of claim 16, wherein said adenovector consists of: a) a first adenovirus region from about base pair 1 to about base pair 450 corresponding to either Ad5 or Ad6; b) a second adenovirus region from about base pair 3511 to about base pair 5548 corresponding to Ad5 or from about base pair 3508 to about base pair 5541 corresponding to Ad6, joined to said first region; c) a third adenovirus region from about base pair 5549 to about base pair 28133 corresponding to Ad5 or from about base pair 5542 to about base pair 28156 corresponding to Ad6, joined to said second region; d) said gene expression cassette in a E3 parallel or E3 anti-parallel orientation joined to said third region; e) a fourth adenovirus region from about base pair 30818 to about base pair 33966 corresponding to Ad5 or from about base pair 30789 to about base pair 33784 corresponding to Ad6, joined to said gene expression cassette; and f) a fifth adenovirus region from about base pair 33967 to about base pair 35935 corresponding to Ad5 or from about base pair 33785 to about base pair 35759 corresponding to Ad6, joined to said fourth region. 26. The method of claim 16, wherein said polypeptide differs from SEQ ID NO: 1 by 1-10 amino acids and maintains all T-cell antigen regions present in SEQ ID NO: 1. 27. The method of claim 16, wherein said polypeptide consists of SEQ ID NO: 1.

Details for Patent 8,142,794

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		2021-10-11
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2021-10-11
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2021-10-11