Back to results
US 7,598,362 B2Granted
Hepatitis C virus vaccine
AssigneesMerck & Co., Inc., Istituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.
InventorsEmilio A. Emini, David C. Kaslow, Andrew J. Bett, John W. Shiver, Alfredo Nicosia, Armin Lahm, Alessandra Luzzago, Riccardo Cortese, Stefano Colloca
Life of this patent
Estimating the term…
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.
Claims50
A nucleic acid 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 T-cell antigen regions present in SEQ ID NO:
- 1.
3 more elements
A nucleic acid comprising a gene expression cassette able to express 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 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 T-cell eptitope regions present in SEQ ID NO:
- 1.
8 more elements
An adenovector consisting of:
- a) a first adenovirus region from about base pair 1 to about base pair 450 corresponding to either Ad5 or Ad6;
- b) a 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, wherein
- said gene expression cassette is able to express 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 polypeptide consists of SEQ ID NO:
- 1 or a sequence substantially similar to SEQ ID NO:
- 1, wherein said substantially similar to SEQ ID NO:
- 1 differs from SEQ ID NO:1 by 1-20 amino acids and maintains all T-cell epitope regions present in SEQ ID NO:
- 1.
15 more elements
A pharmaceutical composition comprising:
- an effective amount of a nucleic acid comprising a gene expression cassette able to express a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide in a human cell, wherein said polypeptide consists of SEQ ID NO:
- 1 or a sequence substantially similar to SEQ ID NO:
- 1, 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 sequence substantially similar to SEQ ID NO:
- 1 differs from SEQ ID NO:
- 1 by 1-20 amino acids and maintains all T-cell antigen regions present in SEQ ID NO:
- 1;
- and
- a pharmaceutically acceptable carrier.
10 more elements
A pharmaceutical composition comprising:
- an effective amount of a nucleic acid comprising a gene expression cassette able to express a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide in a human cell, wherein said polypeptide consists of SEQ ID NO:
- 1 or a sequence substantially similar to SEQ ID NO:
- 1, 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 substantially similar to SEQ ID NO:
- 1 differs from SEQ ID NO:
- 1 by 1 to amino acids and maintains all T-cell epitope regions present in SEQ ID NO:
- 1;
- and
- a pharmaceutically acceptable carrier;
- wherein said nucleic acid is an adenovector consisting 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 more elements
A pharmaceutical composition comprising:
- an effective amount of a nucleic acid comprising a gene expression cassette able to express a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide in a human cell, wherein said polypeptide consists of SEQ ID NO:
- 1 or a sequence substantially similar to SEQ ID NO:
- 1, 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 sequence substantially similar to SEQ ID NO:
- 1 differs from SEQ ID NO:
- 1 by 1 to 20 amino acids and maintains all T-cell epitope regions present in SEQ ID NO:
- 1;
- and
- a pharmaceutically acceptable carrier;
- wherein said nucleic acid is an adenovector consisting 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.
18 more elements
Dependencies are inferred from the claim text.