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    Cell-specific expression/replication vector
    2.
    发明授权
    Cell-specific expression/replication vector 有权
    细胞特异性表达/复制载体

    公开(公告)号：US07785870B2

    公开(公告)日：2010-08-31

    申请号：US10500173

    申请日：2002-12-26

    申请人： Katsuhito Takahashi ,  Hisako Yamamura

    发明人： Katsuhito Takahashi ,  Hisako Yamamura

    IPC分类号： C12N15/00 ,  A61K31/70

    CPC分类号： C12N15/86 ,  A61K38/45 ,  A61K48/00 ,  A61K48/0058 ,  C12N15/85 ,  C12N2710/10343 ,  C12N2710/16643 ,  C12N2830/00 ,  C12N2830/008 ,  C12N2830/85 ,  C12N2840/203

    摘要： The present invention provides a cell-specific expression/replication vector, and a method of treatment comprising introducing a cell-specific expression/replication vector into specific cells such as malignant tumors in order to selectively disrupt the specific cells. A vector according to the invention is constructed by: obtaining a transcriptional initiation regulatory region of human calponin gene that is specifically expressed in smooth muscle cell; linking the above region upstream to a replication-related gene of a virus such as ICP4 and the like; linking DNA that encodes a protein such as suppressive factor for tumor angiogenesis or apoptosis-related factors and the like via IRES to the replication-related gene of the virus; and integrating a thymidine kinase gene in an intact state into the viral DNA.

    摘要翻译： 本发明提供细胞特异性表达/复制载体和包括将细胞特异性表达/复制载体导入特异性细胞例如恶性肿瘤以选择性破坏特定细胞的方法。 根据本发明的载体构建为：获得在平滑肌细胞中特异性表达的人calponin基因的转录起始调节区; 将上述区域上游连接到诸如ICP4等病毒的复制相关基因; 将编码蛋白质的DNA，例如通过IRES的肿瘤血管生成抑制因子或凋亡相关因子等连接到病毒的复制相关基因; 并将完整状态的胸苷激酶基因整合到病毒DNA中。

    Replication vector showing cell-specific expression
    4.
    发明授权
    Replication vector showing cell-specific expression 失效
    显示细胞特异性表达的复制载体

    公开(公告)号：US07696332B2

    公开(公告)日：2010-04-13

    申请号：US10477797

    申请日：2002-04-30

    申请人： Katsuhito Takahashi ,  Hisako Yamamura ,  Shin-ichi Miyatake

    发明人： Katsuhito Takahashi ,  Hisako Yamamura ,  Shin-ichi Miyatake

    IPC分类号： C07H21/02 ,  C07H21/04 ,  A61K31/70

    CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2710/16643 ,  C12N2830/008 ,  C12N2830/85

    摘要： The present invention provides a cell-specific replication-competent vector system, which does not target normal cells. The vector system is constructed by linking a transcriptional initiation regulatory promoter region upstream of a viral replication-related gene that integrates the linked region into a viral DNA vector. The constructed vector, when introduced into malignant tumor cells, selectively injures only tumor cells or proliferating smooth muscle cells of tumor neovascular tissue due to the selective expression of the regulatory promoter region upstream of a viral replication-related gene. In particular, the present invention relates to a transcriptional initiation regulatory region of the human calponin gene that can selectively express in tumor cells or proliferating smooth muscle cells of tumor neovascular tissue. The present invention also relates to methods of constructing the cell-specific replication-competent vector system and to treatment methods using the vector system by introducing the vector system into particular living tissues or cells such as malignant tumors and the like.

    摘要翻译： 本发明提供了不针对正常细胞的细胞特异性复制能力的载体系统。 通过将病毒复制相关基因上游的转录起始调节启动子区域连接到病毒DNA载体中来构建载体系统。 构建的载体在引入恶性肿瘤细胞时，由于选择性地表达病毒复制相关基因上游的调节启动子区域，因此选择性地仅损伤肿瘤新生血管组织的肿瘤细胞或增殖平滑肌细胞。 特别地，本发明涉及人钙调蛋白基因的转录起始调控区域，其可以选择性地在肿瘤细胞或肿瘤新生血管组织的增殖平滑肌细胞中表达。 本发明还涉及构建细胞特异性复制能力载体系统的方法和使用载体系统通过将载体系统引入特定活组织或细胞如恶性肿瘤等中的治疗方法。

    AGENTS FOR TREATING MALIGNANT MESOTHELIOMA
    5.
    发明申请
    AGENTS FOR TREATING MALIGNANT MESOTHELIOMA 审中-公开
    用于治疗恶性淋巴细胞的药剂

    公开(公告)号：US20100003220A1

    公开(公告)日：2010-01-07

    申请号：US12309675

    申请日：2007-07-27

    申请人： Katsuhito Takahashi ,  Hisako Yamamura

    发明人： Katsuhito Takahashi ,  Hisako Yamamura

    IPC分类号： A61K45/00 ,  C12N5/08 ,  C12N7/00 ,  A61P35/00

    CPC分类号： C12N5/0693 ,  A61K35/763 ,  C07K14/46 ,  C07K14/4728 ,  C12N2510/00 ,  C12N2710/16632 ,  C12N2830/008 ,  C12N2830/85

    摘要： The present invention provides an effective therapeutic composition for malignant mesothelioma. Specifically, the present invention provides a therapeutic composition for mesothelioma, comprising a calponin-targeting and tumor-lysing variant of herpes simplex virus (HSV-1), preferably a strain d12.CALPfΔRR. The present invention further provides a method for generating a cell for treating mesothelioma, which comprises infecting mesothelioma cells removed from a patient with an F-type variant of herpes simplex virus proliferating with targeting a calponin gene, preferably a strain d12.CALPfΔRR. Also provided are a cell obtainable by the method, and a calponin-targeting and tumor-lysing variant of herpes simplex virus (HSV-1), preferably a strain d12.CALPfΔRR.

    摘要翻译： 本发明提供了恶性间皮瘤的有效治疗组合物。 具体地，本发明提供了一种间皮瘤治疗组合物，其包含单纯疱疹病毒（HSV-1）的calponin靶向和肿瘤裂解变体，优选菌株d12.CALPfDeltaRR。 本发明还提供了一种用于产生用于治疗间皮瘤的细胞的方法，其包括用靶向calponin基因，优选菌株d12.CALPfDeltaRR以增殖的单纯疱疹病毒的F型变体感染从患者中除去的间皮瘤细胞。 还提供了可通过该方法获得的细胞，以及单纯疱疹病毒（HSV-1）的calponin靶向和肿瘤裂解变体，优选菌株d12.CALPfDeltaRR。

    Cell-specific expression/replication vector
    6.
    发明申请
    Cell-specific expression/replication vector 有权
    细胞特异性表达/复制载体

    公开(公告)号：US20050032214A1

    公开(公告)日：2005-02-10

    申请号：US10500173

    申请日：2002-12-26

    申请人： Katsuhito Takahashi ,  Hisako Yamamura

    发明人： Katsuhito Takahashi ,  Hisako Yamamura

    IPC分类号： C12N15/09 ,  A61K35/76 ,  A61K38/00 ,  A61K38/45 ,  A61K48/00 ,  A61P1/16 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P13/12 ,  A61P15/00 ,  A61P27/02 ,  A61P35/00 ,  A61P35/04 ,  A61P43/00 ,  C12N7/00 ,  C12N15/85 ,  C12N15/861 ,  C12N15/869 ,  C12Q1/48

    CPC分类号： C12N15/86 ,  A61K38/45 ,  A61K48/00 ,  A61K48/0058 ,  C12N15/85 ,  C12N2710/10343 ,  C12N2710/16643 ,  C12N2830/00 ,  C12N2830/008 ,  C12N2830/85 ,  C12N2840/203

    摘要： The present invention is to provide a method wherein a cell-specific expression/replication vector that express and replicate a gene specifically in specific cells such as malignant tumors and the like and does not injure normal cells, particularly a vector that can suppress the expression/replication at a desired period after the expression/replication is constructed, for the use in therapies for such as malignant tumors and the like, and treatment is conducted by introducing the vector to a particular living cell such as malignant tumor and the like for expression. A cell-specific expression/replication vector that does not act to adult normal cells is constructed by: a transcriptional initiation regulatory region of human calponin gene that is expressed in smooth muscle cell specifically is obtained; said region is linked upstream of the replication-related gene of virus such as ICP4 and the like; a DNA that encodes proteins such as suppressive factor for tumor angiogenesis or apoptosis-related factors and the like is linked via IRES to said replication-related gene of the virus; and thyimidine kinase gene in an intact state is integrated into a viral DNA. This vector thus constructed is infected and introduced to malignant tumor cells, and malignant tumor cells are selectively disrupted.

    摘要翻译： 本发明提供一种方法，其中特异性表达/复制载体在特异性细胞如恶性肿瘤等中特异性表达和复制，并且不损伤正常细胞，特别是可抑制表达/ 在构建表达/复制后的所需期间进行复制，用于恶性肿瘤等的治疗，并且通过将载体导入特定的活细胞如恶性肿瘤等进行表达来进行治疗。 通过以下方法构建不对成年正常细胞起作用的细胞特异性表达/复制载体：通过特异性在平滑肌细胞中表达的人calponin基因的转录起始调节区获得; 所述区域与病毒的复制相关基因如ICP4等连接在上游; 编码蛋白质如肿瘤血管生成抑制因子或凋亡相关因子等的DNA通过IRES与病毒的所述复制相关基因相连接; 并且完整状态的甲嘧啶激酶基因整合到病毒DNA中。 这样构建的载体被感染并导入恶性肿瘤细胞，恶性肿瘤细胞被选择性地破坏。