公开(公告)号：US20050277193A1

公开(公告)日：2005-12-15

申请号：US11155845

申请日：2005-06-17

申请人： Thomas Wickham ,  Imre Kovesdi ,  Douglas Brough

发明人： Thomas Wickham ,  Imre Kovesdi ,  Douglas Brough

IPC分类号： A61K38/00 ,  A61K48/00 ,  C07K14/075 ,  C07K14/705 ,  C12N1/21 ,  C12N7/00 ,  C12N15/861 ,  C12N15/866 ,  C12N15/87

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.

公开(公告)号：US20050101018A1

公开(公告)日：2005-05-12

申请号：US10965324

申请日：2004-10-14

申请人： Imre Kovesdi ,  Douglas Brough ,  Duncan McVey ,  Lisa Wei

发明人： Imre Kovesdi ,  Douglas Brough ,  Duncan McVey ,  Lisa Wei

IPC分类号： C12N15/09 ,  A61K35/76 ,  A61K48/00 ,  A61P27/02 ,  C07K14/71 ,  C07K14/81 ,  C12N15/861 ,  C12N7/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K48/005 ,  A61K48/0075 ,  C07K14/71 ,  C07K14/811 ,  C12N2710/10343 ,  C12N2799/022

摘要： The present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof. The nucleic acid sequence is operably linked to regulatory sequences necessary for expression of PEDF or a therapeutic fragment thereof. Preferably, the viral vector is an adenoviral vector or an adeno-associated viral vector. Also preferably, the viral vector further comprises one or more additional nucleic acid sequences encoding therapeutic substances other than PEDF.

摘要翻译： 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。 核酸序列可操作地连接到表达PEDF或其治疗片段所需的调节序列。 优选地，病毒载体是腺病毒载体或腺相关病毒载体。 还优选地，病毒载体还包含编码除PEDF之外的治疗物质的一种或多种另外的核酸序列。

公开(公告)号：US20050220768A1

公开(公告)日：2005-10-06

申请号：US11138931

申请日：2005-05-26

申请人： Duncan McVey ,  Douglas Brough ,  Imre Kovesdi ,  Lisa Wei

发明人： Duncan McVey ,  Douglas Brough ,  Imre Kovesdi ,  Lisa Wei

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 2×108 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 ten-fold 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。 该方法包括施用包含与启动子可操作地连接并编码基因产物的核酸序列的表达载体，以及上调眼细胞中核酸序列的转录。 表达载体可以是腺病毒载体。 本发明还提供了预防性或治疗性地治疗动物至少一种眼部相关疾病的方法。 该方法包括使眼细胞与包含编码血管发生抑制剂和/或神经营养剂的核酸序列的表达载体接触。 在一个方面，该方法还包括上调核酸序列的转录。 优选地，如果向小鼠施用本发明方法的2×10 8个腺病毒颗粒，则在给药后28天，核酸序列的表达水平不会降低10倍以上。

公开(公告)号：US20070098692A1

公开(公告)日：2007-05-03

申请号：US11610364

申请日：2006-12-13

申请人： Imre Kovesdi ,  Douglas Brough ,  Lisa Wei ,  Duncan McVey

发明人： Imre Kovesdi ,  Douglas Brough ,  Lisa Wei ,  Duncan McVey

IPC分类号： A61K48/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K48/005 ,  A61K48/0075 ,  C07K14/71 ,  C07K14/811 ,  C12N2710/10343 ,  C12N2799/022

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。

公开(公告)号：US20080112929A1

公开(公告)日：2008-05-15

申请号：US11947771

申请日：2007-11-30

申请人： Imre Kovesdi ,  Susan Hedley ,  Nikolay Korokhov

发明人： Imre Kovesdi ,  Susan Hedley ,  Nikolay Korokhov

IPC分类号： A61K48/00 ,  C12N15/861 ,  C07K14/075

CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/33 ,  C07K2319/74 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/85 ,  C12N2810/859 ,  C12N2830/008

摘要： The present invention encompasses replication deficient or a replication competent adenoviral vectors which may comprise moieties covering and shielding the vector from the effects of humoral immune responses, as well as a method of constructing and using such vectors. The preferred viral constructs may incorporate the shielding moieties into the pIX coat protein of the adenovirus vectors. The invention also provides recombinant viral vectors with both shielding and specific targeting abilities. Preferably, the viral vector may comprise a nucleic acid sequence, which codes for therapeutically important genes. Methods for treating of a host with an effective amount of adenovirus vector of the present invention are also provided.

摘要翻译： 本发明包括复制缺陷型或复制型腺病毒载体，其可以包含覆盖和屏蔽载体免受体液免疫应答影响的部分，以及构建和使用这些载体的方法。 优选的病毒构建体可以将屏蔽部分并入腺病毒载体的pIX外壳蛋白中。 本发明还提供具有屏蔽和特异性靶向能力的重组病毒载体。 优选地，病毒载体可以包含编码治疗重要基因的核酸序列。 还提供了用有效量的本发明的腺病毒载体处理宿主的方法。

公开(公告)号：US06756044B1

公开(公告)日：2004-06-29

申请号：US09617569

申请日：2000-07-17

申请人： Petrus W. Roelvink ,  Joseph T. Bruder ,  Imre Kovesdi ,  Thomas J. Wickham

发明人： Petrus W. Roelvink ,  Joseph T. Bruder ,  Imre Kovesdi ,  Thomas J. Wickham

IPC分类号： A61K4500

CPC分类号： C40B40/02 ,  A61K47/6901 ,  A61K2039/5256 ,  A61K2039/5258 ,  C12N15/1037 ,  C12N2799/022

摘要： The present invention provides a complex that includes a virion having a ligand that recognizes an epitope present on an immune effector cell surface and at least a first nucleic acid encoding a first non-native antigen. The invention also provides a library including a plurality of such complexes, in which antigens of at least two of the plurality are different. Using such reagents, the invention provides a method of precipitating an immune response within an immune effector cell, wherein such a complex is delivered to the cell under conditions sufficient for the cell to mount an immune response to the antigen. When applied in vivo, the method can serve to immunize an animal from the pathogen. Moreover, using a library including a plurality of complexes, which contains at least one test antigen, the invention provides a method of assessing the antigenicity of the test antigen.

摘要翻译： 本发明提供了一种复合物，其包括具有识别存在于免疫效应细胞表面上的表位的配体和至少编码第一非天然抗原的第一核酸的病毒粒子。 本发明还提供了包含多个这样的复合物的文库，其中至少两个的抗原是不同的。 使用这样的试剂，本发明提供了在免疫效应细胞内沉淀免疫应答的方法，其中这种复合物在足以使细胞对抗原产生免疫应答的条件下递送至细胞。 当应用于体内时，该方法可用于从病原体免疫动物。 此外，使用包含至少一种测试抗原的多个复合物的文库，本发明提供了评估测试抗原的抗原性的方法。

公开(公告)号：US06579522B1

公开(公告)日：2003-06-17

申请号：US09604694

申请日：2000-06-27

申请人： Douglas E. Brough ,  C. Richter King ,  Imre Kovesdi ,  Jasper J. Schaible

发明人： Douglas E. Brough ,  C. Richter King ,  Imre Kovesdi ,  Jasper J. Schaible

IPC分类号： A01N6300

CPC分类号： C12N15/86 ,  A61K38/191 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2810/40

摘要： An adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a radiation inducible promoter operably linked to the nucleic acid sequence coding for TNF. This invention also provides an adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a spacer element of at least 15 base pairs in the E4 region of the adenoviral genome. A method of producing an adenoviral vector and a method of treating a tumor or cancer in a host comprising administering an anti-cancer or anti-tumor effective amount of the adenoviral vector of the present invention also is provided.

摘要翻译： 一种腺病毒载体，其包含（a）在腺病毒基因组的E4区域缺失的腺病毒基因组，（b）编码TNF的核酸序列，和（c）与编码TNF的核酸序列可操作地连接的放射诱导型启动子。 本发明还提供了一种腺病毒载体，其包含（a）在腺病毒基因组的E4区域缺失的腺病毒基因组，（b）编码TNF的核酸序列，和（c）至少15个碱基对的间隔元件， E4区域的腺病毒基因组。 本发明提供了生产腺病毒载体的方法和治疗宿主中的肿瘤或癌症的方法，包括给予抗癌或抗肿瘤有效量的本发明的腺病毒载体。

公开(公告)号：US06440728B1

公开(公告)日：2002-08-27

申请号：US09450972

申请日：1999-11-30

申请人： Duncan L. McVey ,  Douglas E. Brough ,  Mohammed Zuber ,  Imre Kovesdi

发明人： Duncan L. McVey ,  Douglas E. Brough ,  Mohammed Zuber ,  Imre Kovesdi

IPC分类号： C12N1563

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。

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。

公开(公告)号：US6057155A

公开(公告)日：2000-05-02

申请号：US130225

申请日：1998-08-06

申请人： Thomas J. Wickham ,  Petrus W. Roelvink ,  Imre Kovesdi

发明人： Thomas J. Wickham ,  Petrus W. Roelvink ,  Imre Kovesdi

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K48/00 ,  C07K14/075 ,  C12N5/10 ,  C12N15/34 ,  C12N15/861 ,  C12P21/04 ,  C12R1/92 ,  C12N15/86

CPC分类号： C12N7/00 ,  C07K14/005 ,  C12N15/86 ,  A61K38/00 ,  A61K48/00 ,  C07K2319/00 ,  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 encodes 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.