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    Non-adenoviral gene product-based complementing cells for adenoviral vectors
    21.
    发明申请
    Non-adenoviral gene product-based complementing cells for adenoviral vectors 有权
    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：US20030017595A1

    公开(公告)日：2003-01-23

    申请号：US09911011

    申请日：2001-07-23

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough ,  Jason G. D. Gall ,  Imre Kovesdi

    IPC: C12N015/861 ,  C12N007/01 ,  C12N005/08

    CPC classification number: C12N7/00 ,  C12N2710/10051 ,  C12N2710/10052 ,  C12N2710/10351 ,  C12N2710/10352

    Abstract: 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.

    Abstract translation: 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。

    Use of trans-activation and CIS-activation to modulate the persistence of expression of a transgene
    23.
    发明申请
    Use of trans-activation and CIS-activation to modulate the persistence of expression of a transgene 失效

    公开(公告)号：US20020031823A1

    公开(公告)日：2002-03-14

    申请号：US09873486

    申请日：2001-06-04

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough ,  Imre Kovesdi

    IPC: A61K048/00 ,  C12N015/86

    CPC classification number: C12N15/86 ,  C07K14/005 ,  C12N15/63 ,  C12N2710/10322 ,  C12N2710/10345 ,  C12N2710/16622 ,  C12N2830/60 ,  C12N2840/60

    Abstract: 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 E4null 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 E4null 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 E4null 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 E4null adenoviral vector, which system comprises (i) an at least E4null 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 E4null 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.

    Replication deficient adenoviral TNF vector
    25.
    发明申请
    Replication deficient adenoviral TNF vector 审中-公开

    公开(公告)号：US20030175245A1

    公开(公告)日：2003-09-18

    申请号：US10424638

    申请日：2003-04-25

    Applicant: GenVec, Inc.

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

    IPC: A61K048/00 ,  C12N007/00 ,  C12N015/861

    CPC classification number: C12N15/86 ,  A61K38/191 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2810/40

    Abstract: 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.

    Method and composition for targeting an adenoviral vector
    26.
    发明申请
    Method and composition for targeting an adenoviral vector 审中-公开
    用于靶向腺病毒载体的方法和组合物

    公开(公告)号：US20030099619A1

    公开(公告)日：2003-05-29

    申请号：US10304160

    申请日：2002-11-25

    Applicant: GenVec, Inc.

    Inventor： Thomas J. Wickham ,  Imre Kovesdi ,  Petrus W. Roelvink ,  David Einfeld ,  Douglas E. Brough ,  Alena Lizonova

    IPC: A61K048/00 ,  C12Q001/70 ,  C12N015/861 ,  C07K014/705 ,  C07K014/075

    CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/40 ,  C12N2810/405 ,  C12N2810/60 ,  C12N2810/80 ,  C12N2830/008

    Abstract: 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.

    Abstract translation: 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。

    Adenovector complementing cells
    27.
    发明申请
    Adenovector complementing cells 有权
    Adenovector补体细胞

    公开(公告)号：US20030054553A1

    公开(公告)日：2003-03-20

    申请号：US09910828

    申请日：2001-07-23

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough ,  Jason G.D. Gall ,  Imre Kovesdi

    IPC: C12N015/861 ,  C12N007/00 ,  C12N005/08

    CPC classification number: C12N15/86 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2710/10352

    Abstract: 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.

    Abstract translation: 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。

    Targeting adenovirus with use of constrained peptide motifs
    29.
    发明申请
    Targeting adenovirus with use of constrained peptide motifs 有权
    使用受限肽基序靶向腺病毒

    公开(公告)号：US20020151027A1

    公开(公告)日：2002-10-17

    申请号：US09969192

    申请日：2001-10-01

    Applicant: GenVec, Inc.

    Inventor： Thomas J. Wickham ,  Petrus W. Roelvink ,  Imre Kovesdi

    IPC: C12N015/861 ,  C12N009/50 ,  C12N007/01

    CPC classification number: C12N7/00 ,  A61K38/00 ,  A61K48/00 ,  C07K14/005 ,  C07K2319/00 ,  C12N15/86 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/40 ,  C12N2810/405 ,  C12N2810/60

    Abstract: 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.

    Abstract translation: 本发明提供了一种嵌合腺病毒纤维蛋白，其通过以构象约束的方式引入非氨基酸序列而与野生型外壳蛋白不同。 根据本发明的这种嵌合腺病毒纤维蛋白能够直接进入包含嵌合纤维蛋白质的载体的细胞，该载体比除了包含野生型腺病毒纤维蛋白的载体的细胞进入更有效，而不是包含野生型腺病毒纤维蛋白 比嵌合腺病毒纤维蛋白。 非氨基酸序列编码包含可用于细胞靶向的抗体表位或细胞表面受体配体的肽基序。 本发明还涉及包含这种嵌合腺病毒纤维蛋白的载体，以及使用这些载体的方法。

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