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1. 发明申请

WO2011057254A3 SIMIAN ADENOVIRAL VECTOR-BASED VACCINES 审中-公开
标题翻译：基于SIMIAN腺病毒的基于矢量的疫苗
公开(公告)号：WO2011057254A3
公开(公告)日：2011-08-18
申请号：PCT/US2010056004
申请日：2010-11-09
申请人： US HEALTH , GENVEC INC , NABEL GARY J , CHENG CHENG , KO SUNG-YOUL , GALL JASON G D , KONG WING-PUI , BROUGH DOUGLAS E , MCVEY DUNCAN L , KAHL CHRISTOPH , WEI CHIH-JEN
发明人： NABEL GARY J , CHENG CHENG , KO SUNG-YOUL , GALL JASON G D , KONG WING-PUI , BROUGH DOUGLAS E , MCVEY DUNCAN L , KAHL CHRISTOPH , WEI CHIH-JEN
IPC分类号： A61K35/76 , C07K14/11 , C07K14/16 , C07K14/35 , C12N15/861
CPC分类号： C12N15/86 , A61K39/12 , A61K39/145 , A61K39/21 , A61K2039/5256 , A61K2039/5258 , A61K2039/54 , A61K2039/545 , C12N2710/10332 , C12N2710/10343 , C12N2740/16134 , C12N2760/16134
摘要： The invention relates to a replication-deficient simian adenoviral vector construct comprising a nucleic acid sequence which encodes an antigen of a pathogen, such as an HIV antigen or an influenza virus antigen. The invention also provides a method of inducing an immune response against a pathogen, such as HIV or influenza, in a mammal using a composition comprising the simian adenoviral vector construct. The invention also provides a monkey adenovirus which is capable of propagation in a human cell.
摘要翻译：本发明涉及复制缺陷型猿猴腺病毒载体构建体，其包含编码病原体如HIV抗原或流感病毒抗原的抗原的核酸序列。本发明还提供了使用包含猿猴腺病毒载体构建体的组合物在哺乳动物中诱导抗病原体如HIV或流感病毒的免疫应答的方法。本发明还提供了能够在人类细胞中增殖的猴腺病毒。

2. 发明申请

WO0158494A3 GENE THERAPY FOR TREATING OCULAR-RELATED DISORDERS 审中-公开
标题翻译：用于治疗与眼睛有关的疾病的基因治疗
公开(公告)号：WO0158494A3
公开(公告)日：2002-04-04
申请号：PCT/US0104203
申请日：2001-02-09
申请人： GENVEC INC , KOVESDI IMRE , BROUGH DOUGLAS E , MCVEY DUNCAN L , WEI LISA
发明人： KOVESDI IMRE , BROUGH DOUGLAS E , MCVEY DUNCAN L , WEI LISA
IPC分类号： C12N15/09 , A61K35/76 , A61K48/00 , A61P27/02 , C07K14/71 , C07K14/81 , C12N15/861 , C07K14/515
CPC分类号： A61K48/0075 , A61K48/005 , C07K14/71 , C07K14/811 , C12N15/86 , C12N2710/10343
摘要： The present invention is directed to a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder, e.g., ocular neovascularization or age-related macular degeneration. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and the same or different nucleic acid sequence encoding a neurotrophic agent. The method also can comprise contacting an ocular cell with different expression vectors, each comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a nucleic acid sequence encoding a neurotrophic agent. In addition, the present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof.
摘要翻译：本发明涉及一种预防性或治疗性地治疗动物至少一种与眼部相关的疾病，例如眼睛新生血管形成或年龄相关性黄斑变性的方法。该方法包括使眼细胞与包含编码血管生成抑制剂的核酸序列和编码神经营养剂的相同或不同核酸序列的表达载体接触。该方法还可以包括使眼细胞与不同的表达载体接触，每种表达载体包含编码血管生成抑制剂的核酸序列和/或编码神经营养剂的核酸序列。此外，本发明提供了包含编码色素上皮衍生因子（PEDF）的核酸序列或其治疗片段的病毒载体。

3. 发明申请

WO2007073513A3 METHOD FOR PROPAGATING ADENOVIRAL VECTORS ENCODING INHIBITORY GENE PRODUCTS 审中-公开
标题翻译：传播腺病毒载体的方法，用于编码抑制基因产物
公开(公告)号：WO2007073513A3
公开(公告)日：2007-09-27
申请号：PCT/US2006060732
申请日：2006-11-08
申请人： GENVEC INC , GALL JASON G D , BROUGH DOUGLAS E , RICHTER KING C
发明人： GALL JASON G D , BROUGH DOUGLAS E , RICHTER KING C
IPC分类号： C12N5/10 , C12N15/63 , C12N15/861
CPC分类号： C12N15/635 , C12N7/00 , C12N15/86 , C12N2710/10343 , C12N2710/10352 , C12N2830/006
摘要： The invention provides a method of propagating an adenoviral vector. The method comprises (a) providing a cell comprising a cellular genome comprising a nucleic acid sequence encoding a tetracycline operon repressor protein (tetR), and (h) contacting the cell with an adenoviral vector comprising a heterologous nucleic acid sequence encoding a toxic protein. The heterologous nucleic acid sequence is operably linked to a promoter and one or more tetracycline operon operator sequences (tetO), and expression of the heterologous nucleic acid sequence is inhibited in the presence of tetR, such that the adenoviral vector is propagated. The invention also provides a system comprising the aforementioned cell and adenoviral vector.
摘要翻译：本发明提供了一种繁殖腺病毒载体的方法。该方法包括（a）提供包含含有编码四环素操纵子阻遏蛋白（tetR）的核酸序列的细胞基因组的细胞，和（h）使细胞与包含编码毒性蛋白的异源核酸序列的腺病毒载体接触。异源核酸序列与启动子和一个或多个四环素操纵子操纵子序列（tetO）可操作地连接，并且异源核酸序列的表达在tetR存在下被抑制，使得腺病毒载体得到增殖。本发明还提供了包含上述细胞和腺病毒载体的系统。

4. 发明申请

WO2005012537A3 ADENOVIRAL VECTOR-BASED VACCINES 审中-公开
标题翻译：基于腺病毒的基于矢量的疫苗
公开(公告)号：WO2005012537A3
公开(公告)日：2005-06-09
申请号：PCT/US2004024002
申请日：2004-07-26
申请人： GENVEC INC , GALL JASON G D , WICKHAM THOMAS J , ENRIGHT WILLIAM J , BROUGH DOUGLAS E , ZUBER MOHAMMED , KING C RICHTER
发明人： GALL JASON G D , WICKHAM THOMAS J , ENRIGHT WILLIAM J , BROUGH DOUGLAS E , ZUBER MOHAMMED , KING C RICHTER
IPC分类号： A61K39/235 , A61K48/00 , C12N15/861
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.
摘要翻译：本发明提供了在哺乳动物中诱导免疫应答的方法。该方法包括向哺乳动物施用包含腺病毒纤维蛋白的非亚群C腺病毒载体，所述腺病毒纤维蛋白具有与编码亚群C腺病毒纤维蛋白的氨基酸序列具有约80％或更多同一性的氨基酸序列。腺病毒载体进一步包含编码在哺乳动物中表达以诱导免疫应答的抗原的核酸序列。本发明进一步包括生产腺病毒载体的方法和包含血清型41或血清型35腺病毒载体和载体的组合物。本发明还提供了包含编码可操作地连接至异源表达控制序列的腺病毒pIX蛋白的核酸序列的腺病毒载体，以及增强腺病毒载体稳定性和/或包装能力的方法。

5. 发明申请

WO2004050027A3 MATERIALS AND METHODS FOR TREATING OCULAR-RELATED DISORDERS 审中-公开
标题翻译：用于治疗眼睛相关疾病的材料和方法
公开(公告)号：WO2004050027A3
公开(公告)日：2004-12-02
申请号：PCT/US0338169
申请日：2003-12-01
申请人： GENVEC INC , MCVEY DUNCAN L , BROUGH DOUGLAS E , KOVESDI IMRE , WEI LISA
发明人： MCVEY DUNCAN L , BROUGH DOUGLAS E , KOVESDI IMRE , WEI LISA
IPC分类号： A61K20060101 , A61K9/00 , A61K31/203 , A61K31/7088 , A61K38/55 , A61K45/06 , A61K48/00 , C12N15/85 , C12N15/86 , C12N15/861
CPC分类号： A61K48/005 , A61K9/0048 , A61K31/203 , A61K31/7088 , A61K38/57 , A61K45/06 , A61K48/00 , A61K48/0058 , A61K48/0075 , A61K48/0083 , C12N15/86 , C12N2710/10343 , C12N2799/022 , A61K2300/00
摘要： The invention is directed to a method of delivering a gene product to an animal. The method comprises administering an expression vector comprising a nucleic acid sequence operably linked to a promoter and encoding a gene product, and upregulating transcription of the nucleic acid sequence in the ocular cell. The expression vector can be an adenoviral vector. The invention further provides a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a neurotrophic agent. In one aspect, the method further comprises upregulating transcription of the nucleic acid sequence. Preferably, if 2x10 adenoviral particles of the inventive method are administered to a mouse, the level of expression of the nucleic acid sequence is not diminished more than tenfold at 28 days post-administration.
摘要翻译：本发明涉及将基因产物递送至动物的方法。该方法包括施用表达载体，所述表达载体包含与启动子可操作连接并编码基因产物的核酸序列，并且上调核酸序列在眼细胞中的转录。表达载体可以是腺病毒载体。本发明进一步提供了预防性或治疗性治疗动物以治疗至少一种眼部相关病症的方法。该方法包括使眼细胞与包含编码血管生成抑制剂和/或神经营养剂的核酸序列的表达载体接触。一方面，该方法还包括上调核酸序列的转录。优选地，如果将本发明方法的2×10 8个腺病毒颗粒给予小鼠，则核酸序列的表达水平在给药后28天不会减少超过10倍。

6. 发明申请

WO9856937A2 CHIMERIC VECTORS COMPRISING A PHAGE PACKAGING SITE AND A PORTION DERIVED FROM A GENOME OF A EUKARYOTIC VIRUS 审中-公开
标题翻译：包含噬菌体包装场所的重要载体和从原始病毒的基因衍生的部分
公开(公告)号：WO9856937A2
公开(公告)日：1998-12-17
申请号：PCT/US9812158
申请日：1998-06-09
申请人： GENVEC INC , MCVEY DUNCAN L , BROUGH DOUGLAS E , ZUBER MOHAMMED , KOVESDI IMRE
发明人： MCVEY DUNCAN L , BROUGH DOUGLAS E , ZUBER MOHAMMED , KOVESDI IMRE
IPC分类号： C12N1/21 , C12N7/00 , C12N7/01 , C12N15/86 , C12N15/861
CPC分类号： C12N15/86 , C12N2710/10343 , C12N2710/10344 , C12N2795/10344 , C12N2810/405 , C12N2830/002 , C12N2830/005 , C12N2830/15 , C12N2830/55
摘要： The present invention provides an improved method of making eukaryotic gene transfer vectors comprising homologous recombining lambdid vectors with a second DNA in a bacterium to generate novel recombinant eukaryotic viral gene transfer vectors as well as a novel lambdid vector used in the inventive method and an inventive system comprising the novel lambdid vector.
摘要翻译：本发明提供了一种制备包含同源重组羊羔载体的真核基因转移载体与细菌中的第二DNA以产生新的重组真核病毒基因转移载体以及用于本发明方法和本发明系统的新型羔羊载体的改进方法包括新的小鼠载体。

7. 发明申请

WO0034496A3 USE OF TRANS-ACTIVATION AND CIS-ACTIVATION TO MODULATE THE PERSISTENCE OF EXPRESSION OF A TRANSGENE 审中-公开
标题翻译：使用转移激活和CIS激活来调节转基因表达的持续性
公开(公告)号：WO0034496A3
公开(公告)日：2000-09-14
申请号：PCT/US9928637
申请日：1999-12-03
申请人： GENVEC INC , BROUGH DOUGLAS E , KOVESDI IMRE
发明人： BROUGH DOUGLAS E , KOVESDI IMRE
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K48/00 , A61P31/00 , A61P35/00 , C07K14/035 , C07K14/075 , C12N15/35 , C12N15/63 , C12N15/861 , C12N15/38
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 DELTA 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. Another method comprises contacting the cell with an at least E4 DELTA adenoviral vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, wherein the trans-acting factor modulates the persistence of expression of the transgene and the gene encoding the trans-acting factor is not from the E4 region of an adenovirus. Yet another method comprises contacting a cell simultaneously or sequentially with (i) an at least E4 DELTA adenoviral 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. Also provided is a system for modulating the persistence of expression of a transgene in an at least E4 DELTA adenoviral vector, which system comprises (i) an at least E4 DELTA adenoviral vector comprising a transgene and (ii) a gene encoding a trans-acting factor, wherein the gene encoding the trans-acting factor is not from the E4 region of an adenovirus, the trans-acting factor modulates the persistence of expression of the transgene, and either the at least E4 DELTA adenoviral vector comprises the gene encoding the trans-acting factor or the system comprises a viral vector, in which case the viral vector comprises the gene encoding the trans-acting factor.
摘要翻译：提供了调节转基因（例如非疱疹病毒载体或至少E4Δ腺病毒载体中的转基因）细胞中表达持续存在的方法，以及相关系统。一种方法包括使细胞与包含和表达编码HSV ICP0的基因的非疱疹载体接触，于是HSV ICP0的表达调节了转基因表达的持续性。进一步提供了用于调节转基因表达持续存在的系统，所述系统包含非疱疹载体，所述非疱疹载体包含（i）编码HSV ICP0的基因和（ii）转基因，其中HSV ICP0调节所述转基因表达的持续存在转基因，并且非疱疹载体包含转基因或该系统还包含载体，在这种情况下，载体包含转基因。另一种方法包括使细胞与包含（i）转基因和（ii）编码反式作用因子的基因的至少E4Δ腺病毒载体接触，其中反式作用因子调节转基因和基因表达的持续存在编码反式作用因子不是来自腺病毒的E4区。另一种方法包括将细胞同时或依次与（i）包含转基因的至少E4Δ腺病毒载体和（ii）包含编码反式作用因子的基因的病毒载体接触，所述反式作用因子不来自腺病毒，并调节转基因表达的持续存在。还提供了用于调节至少E4ΔTA腺病毒载体中转基因表达的持续存在的系统，所述系统包含（i）包含转基因的至少E4ΔΔ腺病毒载体和（ii）编码反式作用的基因因子，其中编码反式作用因子的基因不是来自腺病毒的E4区，反式作用因子调节转基因表达的持久性，并且至少E4ΔΔ腺病毒载体包含编码反式作用因子的基因或该系统包含病毒载体，在这种情况下病毒载体包含编码反式作用因子的基因。

8. 发明申请

WO2004076626A3 METHODS OF GENE THERAPY FOR TREATING DISORDERS OF THE EAR BY ADMINISTERING A VECTOR ENCODING AN ATONAL-ASSOCIATED FACTOR 审中-公开
标题翻译：通过管理编码相关因子的矢量来治疗耳朵疾病的基因治疗方法
公开(公告)号：WO2004076626A3
公开(公告)日：2004-10-28
申请号：PCT/US2004004891
申请日：2004-02-19
申请人： GENVEC INC , BROUGH DOUGLAS E
发明人： BROUGH DOUGLAS E
IPC分类号： A61K38/00 , A61K48/00 , A61P27/00 , C12N15/861 , C12N15/86
CPC分类号： A61K38/17 , A61K38/00 , A61K48/005 , C07K14/4702 , C12N7/00 , C12N15/86 , C12N2501/60 , C12N2710/10343
摘要： The invention is directed to a method of changing the sensory perception of an animal. The method comprises administering an expression vector comprising a nucleic acid sequence encoding an atonal-associated factor, which is expressed to produce the atonal-associated factor resulting in generation of hair cells that allow perception of stimuli in the inner ear. Also provided is a method of generating a hair cell in differentiated sensory epithelia in vivo. The method comprises contacting differentiated sensory epithelial cells with an adenoviral vector (a) deficient in one or more replication-essential gene functions of the El region and E4 region, (b) comprising a spacer in the E4 region, and (c) comprising a nucleic acid sequence encoding an atonal-associated factor. The nucleic acid sequence is expressed to produce the atonal-associated factor such that a hair cell is generated. An adenoviral vector encoding an atonal-associated factor also is provided.
摘要翻译：本发明涉及一种改变动物的感觉知觉的方法。所述方法包括施用包含编码无关联因子的核酸序列的表达载体，所述核酸序列被表达以产生导致产生能够感知内耳中的刺激的毛细胞的无关性因子。还提供了一种在体内在分化感觉上皮细胞中产生毛细胞的方法。该方法包括使分化的感觉上皮细胞与E1区和E4区的一个或多个复制必需基因功能缺陷的腺病毒载体（a）接触，（b）在E4区中包含间隔基，和（c）包含编码无关联因子的核酸序列。表达核酸序列以产生无关联因子，使得产生毛细胞。还提供了编码无关联因子的腺病毒载体。

9. 发明申请

WO0192549A3 METHOD AND COMPOSITION FOR TARGETING AN ADENOVIRAL VECTOR 审中-公开
标题翻译：用于靶向腺病毒载体的方法和组合物
公开(公告)号：WO0192549A3
公开(公告)日：2003-01-16
申请号：PCT/US0117391
申请日：2001-05-30
申请人： GENVEC INC , WICKHAM THOMAS J , KOVESDI IMRE , ROELVINK PETRUS W , EINFELD DAVID , BROUGH DOUGLAS E , LIZONOVA ALENA
发明人： WICKHAM THOMAS J , KOVESDI IMRE , ROELVINK PETRUS W , EINFELD DAVID , BROUGH DOUGLAS E , LIZONOVA ALENA
IPC分类号： C12N15/09 , A61K35/76 , A61K48/00 , A61P35/00 , C07K14/075 , C07K14/705 , C12N5/10 , C12N7/00 , C12N7/02 , C12N15/861 , C12Q1/02 , C12N15/86
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.
摘要翻译：本发明提供了包含各种非天然配体的腺病毒外壳蛋白。此外，本发明提供了一种腺病毒载体，其在宿主动物中比相应的野生型腺病毒引起较少的网状内皮系统（RES）清除。本发明还提供了一种包含具有非天然细胞表面受体的细胞和具有非天然配体的病毒的系统的系统，其中所述病毒的非天然配体结合所述非天然细胞表面受体的非天然细胞表面受体细胞。使用该系统可以传播病毒。本发明进一步提供了利用选择性复制能力的受控基因表达的方法，基因功能测定方法，分离核酸的方法和识别功能相关编码序列的方法。另外，本发明提供了促进内化的细胞表面受体。

10. 发明申请

WO9720051A3 VECTORS AND METHODS FOR GENE TRANSFER TO CELLS 审中-公开
标题翻译：用于基因转移到细胞的载体和方法
公开(公告)号：WO9720051A3
公开(公告)日：1997-08-28
申请号：PCT/US9619150
申请日：1996-11-27
申请人： GENVEC INC , WICKHAM THOMAS J , KOVESDI IMRE , BROUGH DOUGLAS E
发明人： WICKHAM THOMAS J , KOVESDI IMRE , BROUGH DOUGLAS E
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , C07K14/075 , C07K19/00 , C12N5/10 , C12N7/01 , C12N15/00 , C12N15/34 , C12N15/62 , C12N15/86 , C12N15/861 , C12R1/92
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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