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1.发明公开
公开(公告)号：EP0920514A1
公开(公告)日：1999-06-09
申请号：EP97938497.0
申请日：1997-08-21
申请人： GENVEC, INC.
CPC分类号： C12N7/00 , A61K38/00 , A61K48/00 , C07K14/005 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/60
摘要： The present invention provides a chimeric adenovirus fiber protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence in a conformationally-restrained manner. Such a chimeric adenovirus fiber protein according to the invention is able to direct entry into cells of a vector comprising the chimeric fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than the chimeric adenovirus fiber protein. The nonnative amino acid sequences encode a peptide motif that comprises an epitope for an antibody, or a ligand for a cell surface receptor, that can be employed in cell targeting. The present invention also pertains to vectors comprising such a chimeric adenovirus fiber protein, and to methods of using such vectors.
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公开(公告)号：EP1112372A1
公开(公告)日：2001-07-04
申请号：EP99945627.0
申请日：1999-09-10
申请人： GENVEC, INC.
IPC分类号： C12N15/861 , C07K14/075 , C12N7/00
CPC分类号： C07K14/005 , A61K48/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/6018 , C12N2830/008
摘要： The present invention provides a recombinant protein having an amino terminus of an adenoviral fiber protein and having a trimerization domain. A fiber incorporating such a protein exhibits reduced affinity for a native substrate than does a wild-type adenoviral fiber trimer. The present invention further provides an adenovirus incorporating the recombinant protein of the present invention.
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公开(公告)号：EP0863987A2
公开(公告)日：1998-09-16
申请号：EP96940927.0
申请日：1996-11-27
申请人： GENVEC, INC.
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C07K2319/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/60
摘要： The present invention provides a chimeric adenovirus coat protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence. Such a chimeric adenovirus coat protein according to the invention is able to direct entry into cells of a vector comprising the coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than the chimeric adenovirus coat protein. The chimeric coat protein preferably is a fiber, hexon, or penton protein. The present invention also provides an adenoviral vector that comprises the chimeric adenovirus coat protein, as well as methods of constructing and using such a vector.
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公开(公告)号：EP0811069B1
公开(公告)日：2008-05-28
申请号：EP96906417.9
申请日：1996-02-13
发明人： WICKHAM, Thomas, J. , FALCK-PEDERSEN, Erik , ROELVINK, Petrus, W. , BRUDER, Joseph, T. , GALL, Jason , KOVESDI, Imre
IPC分类号： C12N15/62 , C12N15/86 , C07K14/075 , A61K48/00
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C07K2319/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/405 , C12N2810/6018 , C12N2830/00 , C12N2830/60
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5.发明授权
公开(公告)号：EP0920514B1
公开(公告)日：2008-01-02
申请号：EP97938497.1
申请日：1997-08-21
申请人： GENVEC, INC.
IPC分类号： C12N15/34 , C12N15/86 , C07K14/075 , A61K48/00
CPC分类号： C12N7/00 , A61K38/00 , A61K48/00 , C07K14/005 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/60
摘要： The present invention provides a chimeric adenovirus fiber protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence in a conformationally-restrained manner. Such a chimeric adenovirus fiber protein according to the invention is able to direct entry into cells of a vector comprising the chimeric fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than the chimeric adenovirus fiber protein. The nonnative amino acid sequences encode a peptide motif that comprises an epitope for an antibody, or a ligand for a cell surface receptor, that can be employed in cell targeting. The present invention also pertains to vectors comprising such a chimeric adenovirus fiber protein, and to methods of using such vectors.
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公开(公告)号：EP1597377A2
公开(公告)日：2005-11-23
申请号：EP04712409.4
申请日：2004-02-18
IPC分类号： C12N15/861 , C12N15/86 , A61K48/00
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/405 , C12N2810/50
摘要： The invention provides a method of expressing an exogenous nucleic acid in a mammal. The method comprises slowly releasing into the bloodstream a dose of replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes. The normalized average bloodstream concentration of the adenovirus over 24 hours post-administration is at least about 1%. Alternatively, the normalized average bloodstream concentration over 24 hours post-administration is at least about 5-fold greater than the normalized average bloodstream concentration for an equivalent dose of a wild-type adenoviral vector. A method of destroying tumor cells in a mammal also is provided.
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公开(公告)号：EP0811069A1
公开(公告)日：1997-12-10
申请号：EP96906417.0
申请日：1996-02-13
发明人： WICKHAM, Thomas, J. , FALCK-PEDERSEN, Erik , ROELVINK, Petrus, W. , BRUDER, Joseph, T. , GALL, Jason , KOVESDI, Imre
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C07K2319/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/405 , C12N2810/6018 , C12N2830/00 , C12N2830/60
摘要： A recombinant adenovirus comprising a chimeric fiber protein and a therapeutic gene, a method of gene therapy involving the use of such an adenovirus, and an adenoviral transfer vector for the generation of such a recombinant adenovirus are provided.
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公开(公告)号：EP1649028B1
公开(公告)日：2012-08-22
申请号：EP04779179.3
申请日：2004-07-26
申请人： GENVEC, INC. , The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services
发明人： GALL, Jason G., D. , WICKHAM, Thomas, J. , ENRIGHT, William, J. , BROUGH, Douglas, E. , ZUBER, Mohammed , KING, C., Richter , NABEL, Gary J. , CHENG, Cheng
IPC分类号： C12N15/861 , A61K39/235
CPC分类号： C12N15/86 , A61K48/00 , A61K2039/5256 , C07K2319/00 , C12N2710/10343 , C12N2710/10345
摘要： The invention provides a method of inducing an immune response in a mammal. The method comprises administering to the mammal a non-subgroup C adenoviral vector comprising an adenoviral fiber protein having an amino acid sequence comprising about 80 % or more identity to an amino acid sequence encoding a subgroup C adenoviral fiber protein. The adenoviral vector further comprises a nucleic acid sequence encoding an antigen which is expressed in the mammal to induce an immune response. The invention further comprises a method of producing an adenoviral vector, and a composition comprising a serotype 41 or a serotype 35 adenoviral vector and a carrier. The invention also provides an adenoviral vector comprising a nucleic acid sequence encoding an adenoviral pIX protein operably linked to a heterologous expression control sequence, as well as a method of enhancing the stability and/or packaging capacity of an adenoviral vector.
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公开(公告)号：EP1301612A2
公开(公告)日：2003-04-16
申请号：EP01939660.5
申请日：2001-05-30
申请人： GENVEC, INC.
发明人： WICKHAM, Thomas, J. , KOVESDI, Imre , ROELVINK, Petrus, W. , EINFELD, David , BROUGH, Douglas, E. , LIZONOVA, Alena
IPC分类号： C12N15/86 , C07K14/705
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/60 , C12N2810/80 , C12N2830/008
摘要： The invention provides adenoviral coat proteins comprising various non-native ligands. Further, the present invention provides an adenoviral vector that elicits less reticulo-endothelial system (RES) clearance in a host animal than a corresponding wild-type adenovirus. Also provided by the invention is a system comprising a cell having a non-native cell-surface receptor and a virus having a non-native ligand, wherein the non-native ligand of the virus binds the non-native cell-surface receptor of the cell. Using this system, a virus can be propagated. Further provided by the invention is a method of controlled gene expression utilizing selectively replication competence, a method of assaying for gene function, a method of isolating a nucleic acid, and a method of identifying functionally related coding sequences. Additionally, the invention provides a cell-surface receptor, which facilitates internalization.
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公开(公告)号：EP1254212A2
公开(公告)日：2002-11-06
申请号：EP01907171.1
申请日：2001-02-09
申请人： GENVEC, INC.
发明人： KOVESDI, Imre , MCVEY, Duncan, L. , WICKHAM, Thomas, J. , BRUDER, Joseph, T. , BROUGH, Douglas, E.
IPC分类号： C12N5/10
CPC分类号： C12N15/1093 , A61K48/00 , C12N15/86 , C12N2710/10343 , C12N2710/10345 , C12N2810/40
摘要： The present invention provides a library of viral vectors, wherein each member comprises a first heterologous DNA encoding a first gene product and a second heterologous DNA encoding a second gene product. The first heterologous DNA is common to each member of the library, while the second heterologous DNA varies between members of the library. The present invention additionally provides a method of constructing a library of viral vectors. The method comprises carrying out homologous recombination between a first DNA molecule and a second DNA molecule to form a pool of intermediate viral vector genomes. One or more linear third DNA molecules are ligated into the pool of intermediate viral geneomes to produce a library of viral vector genomes. Alternatively, homologous recombination between linear DNA molecules and recipient DNA molecules produces a library of viral vector genomes. The library of viral vector genomes is converted into a library of viral vectors.
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