公开(公告)号：US06821775B1

公开(公告)日：2004-11-23

申请号：US09599997

申请日：2000-06-23

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

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

IPC分类号： C12N15861

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：US20090018100A1

公开(公告)日：2009-01-15

申请号：US12237036

申请日：2008-09-24

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

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

IPC分类号： A61K31/711 ,  A61P27/02

CPC分类号： C07K14/811 ,  A61K48/005 ,  A61K48/0075 ,  C07K14/71 ,  C12N2799/022 ,  H04L45/02 ,  H04L49/355 ,  H04L49/358

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：US20090041759A1

公开(公告)日：2009-02-12

申请号：US12119258

申请日：2008-05-12

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

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

IPC分类号： A61K39/395 ,  A61K31/7088 ,  A61K48/00 ,  A61K38/47

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：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：US20140314809A1

公开(公告)日：2014-10-23

申请号：US13866116

申请日：2013-04-19

申请人： Joseph T. Bruder ,  Imre Kovesdi ,  Duncan L. McVey ,  Douglas E. Brough ,  C. Richter King ,  Denise Louise Doolan ,  Joao Carlos Aguair ,  Daniel John Carucci ,  Martha Sedegah ,  Walter R. Weiss ,  Keith Limbach

发明人： Joseph T. Bruder ,  Imre Kovesdi ,  Duncan L. McVey ,  Douglas E. Brough ,  C. Richter King ,  Denise Louise Doolan ,  Joao Carlos Aguair ,  Daniel John Carucci ,  Martha Sedegah ,  Walter R. Weiss ,  Keith Limbach

IPC分类号： G01N33/50

CPC分类号： G01N33/505

摘要： The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.

摘要翻译： 本发明提供了鉴定来自病原体或疾病抗原的抗原的方法，其包括使用包含两种或多种不同腺病毒载体的腺病毒载体阵列，其中每个腺病毒载体包含编码病原体的不同抗原的核酸序列。 腺病毒载体在体外或动物体内施用于抗原呈递细胞（APC）。 通过体外筛选来自效应T淋巴细胞的免疫应答并通过筛选在体内不存在病原体诱发的疾病来测量抗原的免疫原性。

公开(公告)号：US07070930B2

公开(公告)日：2006-07-04

申请号：US10162043

申请日：2002-06-03

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： C12Q1/68 ,  C12N5/00 ,  C12N5/02 ,  C12N15/00 ,  C12N15/09

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.

公开(公告)号：US06475757B2

公开(公告)日：2002-11-05

申请号：US09905758

申请日：2001-07-13

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

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

IPC分类号： C12N1563

CPC分类号： C12N15/86 ,  C12N15/65 ,  C12N2710/10343 ,  C12N2800/30 ,  C12N2830/001 ,  C12N2830/15 ,  C12N2830/55

摘要： The present invention provides a dual selection cassette (DSC) comprising first and second DNA segments having homology to a eukaryotic viral vector, positive and negative selection genes, each operably linked to their own promoter, and one or more unique restriction enzyme sites (URES) or sitey-directed homologous recombination sites. The present invention also provides a plasmid, pN/P, comprising an independent positive selection marker gene, an origin of replication, and a dual selection cassette. The dual selection cassette and pN/P plasmid can be used to produce eukaryotic gene transfer vectors without requiring temporally-linked double recombination events or the use of specialized bacterial strains that allow the replication of plasmids comprising defective origins of replication. This method usefully increases the ratio of desired to undesired plasmid and vector constructs. Additionally, this invention provides a method for the creation of eukaryotic viral vector libraries.

公开(公告)号：US5994106A

公开(公告)日：1999-11-30

申请号：US757023

申请日：1996-11-26

申请人： Imre Kovesdi ,  Douglas E. Brough ,  Duncan L. McVey ,  Joseph T. Bruder ,  Alena Lizonova

发明人： Imre Kovesdi ,  Douglas E. Brough ,  Duncan L. McVey ,  Joseph T. Bruder ,  Alena Lizonova

IPC分类号： C12N15/09 ,  A61K35/76 ,  A61K38/00 ,  A61K48/00 ,  A61P43/00 ,  C07K14/075 ,  C07K14/47 ,  C12N5/10 ,  C12N15/00 ,  C12N15/12 ,  C12N15/34 ,  C12N15/86 ,  C12N15/861 ,  C12Q1/68 ,  C12R1/92 ,  C12N15/64

CPC分类号： C12N7/00 ,  C07K14/005 ,  C07K14/4712 ,  C12N15/86 ,  A61K2039/5256 ,  A61K38/00 ,  A61K48/00 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10352 ,  C12N2810/60 ,  C12N2810/6081 ,  C12N2830/002 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44 ,  Y10S977/799

摘要： The present invention provides multiply deficient adenoviral vectors and complementing cell lines. Also provided are recombinants of the multiply deficient adenoviral vectors and a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such recombinants.

摘要翻译： 本发明提供多重缺陷型腺病毒载体和补体细胞系。 还提供了多重缺陷型腺病毒载体的重组体和涉及使用这种重组体的基因治疗，疫苗接种等的治疗方法。

公开(公告)号：US5559099A

公开(公告)日：1996-09-24

申请号：US303162

申请日：1994-09-08

申请人： Thomas J. Wickham ,  Imre Kovesdi ,  Douglas E. Brough ,  Duncan L. McVey ,  Joseph T. Brader

发明人： Thomas J. Wickham ,  Imre Kovesdi ,  Douglas E. Brough ,  Duncan L. McVey ,  Joseph T. Brader

IPC分类号： C12N15/09 ,  A61K35/76 ,  A61K38/00 ,  A61K48/00 ,  C07K14/075 ,  C07K14/705 ,  C12N7/00 ,  C12N7/01 ,  C12N15/861 ,  C12N15/866 ,  C12N15/87 ,  C12P21/04 ,  C12N15/00

CPC分类号： C12N15/87 ,  C07K14/005 ,  C07K14/70546 ,  C12N15/86 ,  C12N7/00 ,  A61K48/00 ,  C07K2319/00 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2710/14043 ,  C12N2710/14143 ,  C12N2810/40 ,  C12N2810/405 ,  C12N2810/60 ,  C12N2810/6018 ,  C12N2810/80 ,  C12N2810/855 ,  C12N2810/856 ,  C12N2810/859

摘要： A recombinant adenovirus comprising a chimeric penton base protein, which includes a nonpenton base sequence, and a therapeutic gene, a method of gene therapy involving the use of such adenovirus, and adenoviral transfer vectors for the generation of such recombinant adenovirus are provided.

摘要翻译： 提供了包含嵌合五羟色胺基蛋白的重组腺病毒，其包含非戊基碱基序列和治疗基因，涉及使用这种腺病毒的基因治疗方法和用于产生这种重组腺病毒的腺病毒转移载体。

公开(公告)号：US09651543B2

公开(公告)日：2017-05-16

申请号：US13866116

申请日：2013-04-19

申请人： Joseph T. Bruder ,  Imre Kovesdi ,  Duncan L. McVey ,  Douglas E. Brough ,  C. Richter King ,  Denise Louise Doolan ,  Joao Carlos Aguair ,  Daniel John Carucci ,  Martha Sedegah ,  Walter R. Weiss ,  Keith Limbach

发明人： Joseph T. Bruder ,  Imre Kovesdi ,  Duncan L. McVey ,  Douglas E. Brough ,  C. Richter King ,  Denise Louise Doolan ,  Joao Carlos Aguair ,  Daniel John Carucci ,  Martha Sedegah ,  Walter R. Weiss ,  Keith Limbach

IPC分类号： G01N33/50

CPC分类号： G01N33/505

摘要： The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.