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    SHIELDED ADENOVIRAL VECTORS AND METHODS OF USE
    1.
    发明申请
    SHIELDED ADENOVIRAL VECTORS AND METHODS OF USE 审中-公开
    屏蔽腺病毒载体及其使用方法

    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。

    Antigenic complexes and methods
    3.
    发明授权
    Antigenic complexes and methods 有权
    抗原复合物和方法

    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。

    Replication deficient adenoviral TNF vector
    4.
    发明授权
    Replication deficient adenoviral TNF vector 失效
    复制缺陷型腺病毒TNF载体

    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。

    Use of trans-activation and cis-activation to modulate the persistence of expression of a transgene in an at least E4-deficient adenovirus
    6.
    发明授权
    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
    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。