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21. 发明授权

US06225113B1 Use of trans-activation and cis-activation to modulate the persistence of expression of a transgene in an at least E4-deficient adenovirus 失效
标题翻译：使用反式活化和顺式活化来调节至少E4缺陷型腺病毒中转基因表达的持续性
公开(公告)号：US06225113B1
公开(公告)日：2001-05-01
申请号：US09205014
申请日：1998-12-04
申请人： Douglas E. Brough , Imre Kovesdi
发明人： Douglas E. Brough , Imre Kovesdi
IPC分类号： C12N1586
CPC分类号： C12N15/86 , C07K14/005 , C12N15/63 , C12N2710/10322 , C12N2710/10345 , C12N2710/16622 , C12N2830/60 , C12N2840/60
摘要： The present invention provides a method of modulating the persistence of expression of a trans gene in an at least E4&Dgr; adenoidal vector in a cell. In one embodiment, the method comprises contacting the cell with an at least E4&Dgr; adenoidal vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. In another embodiment, the method comprises contacting the cell simultaneously or sequentially with (i) an at least E4&Dgr; adenoidal vector comprising a transgene and (ii) a viral vector comprising a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. In addition, the present invention provides a recombinant at least E4&Dgr; adenoviral vector for use in the method and a composition comprising the vector and a carrier therefor. Also provided by the present invention is a system for modulation of a recombinant at least E4&Dgr; adenoviral vector for use in the method and a composition comprising the system and a carrier there for.
摘要翻译：本发明提供了调节细胞中至少E4DELTA adenoida载体中trans基因的表达持续性的方法。在一个实施方案中，该方法包括使细胞与至少E4DELTA腺嘌呤载体接触，所述载体包含（i）转基因和（ii）编码反式作用因子的基因，其不是来自腺病毒的E4区域，并且其调节持续表达的转基因。在另一个实施方案中，该方法包括使细胞与（i）包含转基因的至少E4DELTA腺嘌呤载体同时或相继接触，和（ii）包含编码反作用因子的基因的病毒载体，所述反式作用因子不是来自E4区的腺病毒，并且其调节转基因表达的持续性。此外，本发明提供了用于该方法的重组至少E4DELTA腺病毒载体和包含载体及其载体的组合物。本发明还提供了一种用于调节用于该方法的重组至少E4DELTA腺病毒载体的系统，以及包含该系统和该载体的组合物。

22. 发明授权

US06649373B2 Use of trans-activation and CIS-activation to modulate the persistence of expression of a transgene 失效
标题翻译：使用反式激活和CIS激活来调节转基因表达的持续性
公开(公告)号：US06649373B2
公开(公告)日：2003-11-18
申请号：US09873486
申请日：2001-06-04
申请人： Douglas E. Brough , Imre Kovesdi
发明人： Douglas E. Brough , Imre Kovesdi
IPC分类号： C12N1509
CPC分类号： C12N15/86 , C07K14/005 , C12N15/63 , C12N2710/10322 , C12N2710/10345 , C12N2710/16622 , C12N2830/60 , C12N2840/60
摘要： Provided are methods of modulating the persistence of the expression in a cell of a transgene, such as a transgene in a non-Herpes vector or in at least E4&Dgr; adenoviral vector, and related systems. One method comprises contacting the cell with a non-Herpes vector comprising and expressing a gene encoding HSV ICP0, whereupon expression of HSV ICP0 the persistence of expression of the transgene is modulated. Further provided is a system for modulating the persistence of expression of a transgene, which system comprises a non-Herpes vector comprising (i) a gene encoding HSV ICP0 and (ii) a transgene, wherein the HSV ICP0 modulates the persistence of expression of the transgene and either the non-Herpes vector comprises the transgene or the system further comprises a vector, in which case the vector comprises the transgene.
摘要翻译：提供了调节在非疱疹载体或至少E4Delta腺病毒载体中的转基因细胞中表达的持续性的方法，例如转基因和相关系统。一种方法包括使细胞与包含编码HSV ICP0的基因的非疱疹载体接触，于是HSV ICP0的表达调节转基因表达的持续性。进一步提供了一种用于调节转基因表达持久性的系统，该系统包含非疱疹载体，其包含（i）编码HSV ICP0的基因和（ii）转基因，其中HSV ICP0调节持续的表达转基因，非疱疹载体包含转基因，或者系统还包含载体，在这种情况下，载体包含转基因。

23. 发明授权

US5965541A Vectors and methods for gene transfer to cells 失效
公开(公告)号：US5965541A
公开(公告)日：1999-10-12
申请号：US563368
申请日：1995-11-28
申请人： Thomas J. Wickham , Imre Kovesdi , Douglas E. Brough
发明人： Thomas J. Wickham , Imre Kovesdi , Douglas E. Brough
IPC分类号： A61K38/00 , A61K48/00 , C07K14/075 , C12N15/34 , C12N15/861 , C12P21/04 , A01N43/04
CPC分类号： C12N15/86 , A61K38/00 , A61K48/00 , C07K2319/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/60 , C12N2810/6018
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.

24. 发明授权

US06951755B2 Vectors and methods for gene transfer 失效
标题翻译：用于基因转移的载体和方法
公开(公告)号：US06951755B2
公开(公告)日：2005-10-04
申请号：US09999724
申请日：2001-10-24
申请人： Thomas J. Wickham , Imre Kovesdi , Douglas E. Brough
发明人： Thomas J. Wickham , Imre Kovesdi , Douglas E. Brough
IPC分类号： A61K38/00 , A61K48/00 , C07K14/075 , C07K14/705 , C12N1/21 , C12N7/00 , C12N15/861 , C12N15/866 , C12N15/87 , C12N7/01
CPC分类号： C12N15/87 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/70546 , C07K2319/00 , C12N7/00 , C12N15/86 , C12N2710/10321 , C12N2710/10322 , C12N2710/10332 , C12N2710/10343 , C12N2710/10345 , C12N2710/10351 , C12N2710/14143 , C12N2810/40 , C12N2810/405 , C12N2810/60 , C12N2810/6018 , C12N2810/855 , C12N2810/856 , C12N2810/859
摘要： The present invention provides a recombinant adenovirus comprising coat proteins that lack native binding. In particular, the present invention provides a recombinant adenovirus comprising a penton base protein and a fiber protein, wherein the penton base protein and the fiber protein lack native binding. The present invention further provides a recombinant adenovirus comprising (a) a penton base protein that lacks native binding and (b) a nonnative amino acid sequence that binds a cell-surface binding site.
摘要翻译：本发明提供了包含缺少天然结合的外壳蛋白的重组腺病毒。特别地，本发明提供了包含五邻体蛋白质和纤维蛋白质的重组腺病毒，其中五聚体碱基蛋白质和纤维蛋白质缺乏天然结合。本发明还提供一种重组腺病毒，其包含（a）缺乏天然结合的五邻碱基蛋白，和（b）结合细胞表面结合位点的非氨基酸序列。

25. 发明授权

US06682929B2 Adenovector complementing cells 有权
标题翻译： Adenovector补体细胞
公开(公告)号：US06682929B2
公开(公告)日：2004-01-27
申请号：US09910828
申请日：2001-07-23
申请人： Douglas E. Brough , Jason G. D. Gall , Imre Kovesdi
发明人： Douglas E. Brough , Jason G. D. Gall , Imre Kovesdi
IPC分类号： C12N510
CPC分类号： C12N15/86 , C12N7/00 , C12N2710/10343 , C12N2710/10352
摘要： The invention provides cells, particularly NCI-H460 cells and Calu-1 cells, for the propagation of replication-deficient adenoviral vectors. The cells are lung carcinomas with either a wild-type p53 gene or a heterozygous K-ras mutation. The cells comprise at least one adenoviral nucleic acid sequence, which upon expression produces a gene product that complements for at least one essential gene function of one or more regions of an adenoviral genome so as to propagate a replication-deficient adenoviral vector comprising an adenoviral genome deficient in the at least one essential gene function of the one or more regions when present in the cell.
摘要翻译：本发明提供用于增殖复制缺陷型腺病毒载体的细胞，特别是NCI-H460细胞和Calu-1细胞。细胞是具有野生型p53基因或杂合K-ras突变的肺癌。细胞包含至少一种腺病毒核酸序列，其在表达时产生补充腺病毒基因组的一个或多个区域的至少一个必需基因功能的基因产物，以便繁殖包含腺病毒基因组的复制缺陷型腺病毒载体当存在于细胞中时，一个或多个区域的至少一个必需基因功能缺陷。

26. 发明授权

US06465253B1 Vectors and methods for gene transfer to cells 失效
标题翻译：用于基因转移到细胞的载体和方法
公开(公告)号：US06465253B1
公开(公告)日：2002-10-15
申请号：US09101751
申请日：1999-01-29
申请人： Thomas J. Wickham , Imre Kovesdi , Douglas E. Brough
发明人： Thomas J. Wickham , Imre Kovesdi , Douglas E. Brough
IPC分类号： C12N15861
CPC分类号： C12N15/87 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/70546 , C07K2319/00 , C12N7/00 , C12N15/86 , C12N2710/10321 , C12N2710/10322 , C12N2710/10332 , C12N2710/10343 , C12N2710/10345 , C12N2710/10351 , C12N2710/14143 , C12N2810/40 , C12N2810/405 , C12N2810/60 , C12N2810/6018 , C12N2810/855 , C12N2810/856 , C12N2810/859
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.
摘要翻译：本发明提供了通过引入非氨基酸序列与野生型外壳蛋白不同的嵌合腺病毒外壳蛋白。根据本发明的这种嵌合腺病毒外壳蛋白能够引入包含外壳蛋白的载体的细胞，该载体比除了含有野生型腺病毒外壳蛋白的载体以外的载体的细胞进入更有效，而不是嵌合腺病毒外壳蛋白。嵌合外壳蛋白优选为纤维，六邻体或戊烯隆蛋白。本发明还提供了包含嵌合腺病毒外壳蛋白的腺病毒载体，以及构建和使用这种载体的方法。

27. 发明授权

US06458578B1 Recombinant cell line produces adenoviral gene products E1 and DEF-A, and/or DEF-B 失效
标题翻译：重组细胞系产生腺病毒基因产物E1和DEF-A，和/或DEF-B
公开(公告)号：US06458578B1
公开(公告)日：2002-10-01
申请号：US09748044
申请日：2000-12-22
申请人： Douglas E. Brough , Imre Kovesdi
发明人： Douglas E. Brough , Imre Kovesdi
IPC分类号： C12N700
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343
摘要： The present invention provides a recombinant cell line, specifically one that produces adenoviral E1 and DEF-A and/or DEF-B gene products.
摘要翻译：本发明提供重组细胞系，特别是产生腺病毒E1和DEF-A和/或DEF-B基因产物的细胞系。

28. 发明授权

US6113913A Recombinant adenovirus 失效
标题翻译：重组腺病毒
公开(公告)号：US6113913A
公开(公告)日：2000-09-05
申请号：US105515
申请日：1998-06-26
申请人： Douglas E. Brough , Imre Kovesdi
发明人： Douglas E. Brough , Imre Kovesdi
IPC分类号： C12N15/09 , A61K35/76 , A61K39/235 , A61K48/00 , C12N5/10 , C12N7/00 , C12N7/01 , C12N15/861 , A61K39/12 , C12N15/00
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343
摘要： The present invention provides a recombinant adenovirus having a genome with a deficiency in the E1 region and a mutation in the MLP. The invention also provides stocks of such viruses and compositions including the inventive viruses. The invention also provides cell lines for propagating the recombinant adenoviruses.
摘要翻译：本发明提供了具有E1区域缺陷的基因组和MLP突变的重组腺病毒。本发明还提供包含本发明病毒的这种病毒和组合物的种群。本发明还提供用于繁殖重组腺病毒的细胞系。

29. 发明授权

US06913927B2 Non-adenoviral gene product-based complementing cells for adenoviral vectors 失效
标题翻译：用于腺病毒载体的非腺病毒基因产物互补细胞
公开(公告)号：US06913927B2
公开(公告)日：2005-07-05
申请号：US10695605
申请日：2003-10-28
申请人： Douglas E. Brough , Jason G. D. Gall , Imre Kovesdi
发明人： Douglas E. Brough , Jason G. D. Gall , Imre Kovesdi
IPC分类号： C12N5/08 , C12N5/10 , C12N7/00 , C12N7/01 , C12N7/02 , C12N15/63 , C12N15/64 , C12N15/861
CPC分类号： C12N7/00 , C12N2710/10051 , C12N2710/10052 , C12N2710/10351 , C12N2710/10352
摘要： The invention provides cells and methods of using the cells for the propagation of replication-deficient adenoviral vectors. The cells comprise at least one heterologous nucleic acid sequence which upon expression produces at least one non-adenoviral gene product that complements in trans for a deficiency in at least one essential gene function of one or more regions of an adenoviral genome so as to propagate a replication-deficient adenoviral vector comprising an adenoviral genome deficient in the at least one essential gene function of the one or more regions when present in the cell.
摘要翻译：本发明提供了细胞和使用细胞促进复制缺陷型腺病毒载体的方法。所述细胞包含至少一种异源核酸序列，其在表达时产生至少一种非腺病毒基因产物，所述非腺病毒基因产物在腺病毒基因组的一个或多个区域的至少一个必需基因功能缺陷中互补互补，从而传播复制缺陷型腺病毒载体，其包含存在于细胞中时所述一个或多个区域的至少一个必需基因功能缺陷的腺病毒基因组。

30. 发明授权

US06677156B2 Non-adenoviral gene product-based complementing cells for adenoviral vectors 有权
公开(公告)号：US06677156B2
公开(公告)日：2004-01-13
申请号：US09911011
申请日：2001-07-23
申请人： Douglas E. Brough , Jason G. D. Gall , Imre Kovesdi
发明人： Douglas E. Brough , Jason G. D. Gall , Imre Kovesdi
IPC分类号： C12N510
CPC分类号： C12N7/00 , C12N2710/10051 , C12N2710/10052 , C12N2710/10351 , C12N2710/10352
摘要： The invention provides cells and methods of using the cells for the propagation of replication-deficient adenoviral vectors. The cells comprise at least one heterologous nucleic acid sequence which upon expression produces at least one non-adenoviral gene product that complements in trans for a deficiency in at least one essential gene function of one or more regions of an adenoviral genome so as to propagate a replication-deficient adenoviral vector comprising an adenoviral genome deficient in the at least one essential gene function of the one or more regions when present in the cell.

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