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    Multimerization of HIV-1 Vif protein as a therapeutic target
    3.
    发明授权
    Multimerization of HIV-1 Vif protein as a therapeutic target 有权
    HIV-1 Vif蛋白多聚化作为治疗靶点

    公开(公告)号：US07226741B2

    公开(公告)日：2007-06-05

    申请号：US10688100

    申请日：2003-10-17

    申请人： Hui Zhang ,  Roger J. Pomerantz ,  Bin Yang

    发明人： Hui Zhang ,  Roger J. Pomerantz ,  Bin Yang

    IPC分类号： C12Q1/68

    CPC分类号： C07K14/005 ,  A61K38/00 ,  C12N2740/16322 ,  Y10S530/826

    摘要： One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle. In preferred embodiments, the compound or compounds that interactively block the multimerization domain of Vif are Vif antagonists. Pharmaceutical compositions comprising these compounds are also disclosed.

    摘要翻译： 治疗感染HIV-1的个体的一种方法是向这些个体施用直接干扰和干预HIV-1在人细胞内自身复制的机制的化合物。 虽然HIV-1病毒蛋白Vif在病毒生命周期中的具体作用尚不清楚，但vif基因对于体内慢病毒的致病性复制至关重要。 本发明涉及用于治疗暴露于或感染HIV-1的个体的方法。 被鉴定为暴露于HIV-1或感染HIV-1的个体通过干扰HIV-1病毒蛋白Vif的复制或其它基本功能来抑制或阻止所述HIV-1复制的治疗有效量的一种或多种化合物 交互阻断Vif的多聚化结构域，从而阻止Vif蛋白的多聚化，这对于慢病毒生命周期中的Vif功能是重要的。 在优选的实施方案中，交互式阻断Vif的多聚化结构域的化合物是Vif拮抗剂。 还公开了包含这些化合物的药物组合物。

    Multimerization of HIV-1 Vif protein as a therapeutic target
    4.
    发明授权
    Multimerization of HIV-1 Vif protein as a therapeutic target 有权
    HIV-1 Vif蛋白多聚化作为治疗靶点

    公开(公告)号：US06653443B2

    公开(公告)日：2003-11-25

    申请号：US10118575

    申请日：2002-04-08

    申请人： Hui Zhang ,  Roger J. Pomerantz ,  Bin Yang

    发明人： Hui Zhang ,  Roger J. Pomerantz ,  Bin Yang

    IPC分类号： A61K3804

    CPC分类号： C07K14/005 ,  A61K38/00 ,  C12N2740/16322 ,  Y10S530/826

    摘要： One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif, by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle. In preferred embodiments, the compound or compounds that interactively block the multimerization domain of Vif are Vif antagonists. Pharmaceutical compositions comprising these compounds are also disclosed.

    摘要翻译： 治疗感染HIV-1的个体的一种方法是向这些个体施用直接干扰和干预HIV-1在人细胞内自身复制的机制的化合物。 虽然HIV-1病毒蛋白Vif在病毒生命周期中的具体作用尚不清楚，但vif基因对于体内慢病毒的致病性复制至关重要。 本发明涉及用于治疗暴露于或感染HIV-1的个体的方法。 鉴定为暴露于HIV-1或感染HIV-1的个体被施用治疗有效量的一种或多种化合物，其通过干扰HIV-1病毒蛋白Vif的复制或其它基本功能来抑制或阻止所述HIV-1的复制， 通过交互阻断Vif的多聚化结构域，从而防止Vif蛋白的多聚化，这对于慢病毒生命周期中的Vif功能是重要的。 在优选的实施方案中，交互式阻断Vif的多聚化结构域的化合物是Vif拮抗剂。 还公开了包含这些化合物的药物组合物。

    Multimerization of HIV-1 vif protein as a therapeutic target
    5.
    发明申请
    Multimerization of HIV-1 vif protein as a therapeutic target 有权
    HIV-1 vif蛋白多聚化作为治疗靶点

    公开(公告)号：US20080167199A1

    公开(公告)日：2008-07-10

    申请号：US11809953

    申请日：2007-06-04

    申请人： Hui Zhang ,  Roger J. Pomerantz ,  Bin Yang

    发明人： Hui Zhang ,  Roger J. Pomerantz ,  Bin Yang

    IPC分类号： C40B30/04 ,  G01N33/566 ,  G01N33/53

    CPC分类号： C07K14/005 ,  A61K38/00 ,  C12N2740/16322 ,  Y10S530/826

    摘要： The HIV-1 protein Vif comprises a multimerization domain that allows Vif-Vif interaction and Vif multimerization, which is important for Vif function in the HIV-1 life-cycle. A method for screening for an antagonist of Vif comprises contacting the multimerization domain of Vif with a test compound that specifically binds the multimerization domain. Antagonists identified by the screening assay inhibit Vif multimerization. The antagonists inhibit essential functions of Vif and accordingly are useful as inhibitors of HIV-1 replication.

    摘要翻译： HIV-1蛋白Vif包含允许Vif-Vif相互作用和Vif多聚化的多聚化结构域，这对HIV-1生命周期中的Vif功能是重要的。 筛选Vif拮抗剂的方法包括使Vif的多聚化结构域与特异性结合多聚化结构域的测试化合物接触。 通过筛选测定鉴定的拮抗剂抑制Vif多聚化。 拮抗剂抑制Vif的基本功能，因此可用作HIV-1复制的抑制剂。

    Method for treating a human immunodeficiency virus infection
    7.
    发明授权
    Method for treating a human immunodeficiency virus infection 失效
    治疗人类免疫缺陷病毒感染的方法

    公开(公告)号：US06251868B1

    公开(公告)日：2001-06-26

    申请号：US09069809

    申请日：1998-04-30

    申请人： Satoshi Kubota ,  Roger J. Pomerantz ,  Shigehisa Kitahara

    发明人： Satoshi Kubota ,  Roger J. Pomerantz ,  Shigehisa Kitahara

    IPC分类号： C07K5072

    CPC分类号： A61K38/05

    摘要： The present invention provides a method for preventing or treating a human immunodeficiency virus (HIV) infection, including a new or an asymptomatic infection as well as AIDS, comprising administering to a mammal in need thereof a HIV infection preventing or treating effective amount of a &ggr;-L-glutamnyl-L-cysteine ester compound of formula (I): wherein R is a straight chain, branched or cyclic hydrocarbon group having 1-10 carbon atoms, or a straight chain or branched hydrocarbon group having 1-5 carbon atoms substituted with an aromatic group; or the oxidized dimer obtained by dehydrogenation between two &ggr;-L-glutamyl-L-cysteine esters having formula (I).

    摘要翻译： 本发明提供了一种预防或治疗人类免疫缺陷病毒（HIV）感染的方法，包括新的或无症状的感染以及AIDS，包括向有需要的哺乳动物施用预防或治疗有效量的γ的HIV感染 -L-谷氨酰基-L-半胱氨酸酯化合物：其中R是具有1-10个碳原子的直链，支链或环状烃基或具有1-5个碳原子的直链或支链烃基取代的 带有芳香族基团; 或通过在具有式（I）的两个γ-L-谷氨酰基-L-半胱氨酸酯之间脱氢获得的氧化二聚体。

    Ribozyme-mediated gene replacement
    8.
    发明授权
    Ribozyme-mediated gene replacement 失效
    核酶介导的基因置换

    公开(公告)号：US6077705A

    公开(公告)日：2000-06-20

    申请号：US856331

    申请日：1997-05-14

    申请人： Lingxun Duan ,  Mark A. Zern ,  Roger J. Pomerantz

    发明人： Lingxun Duan ,  Mark A. Zern ,  Roger J. Pomerantz

    IPC分类号： A61K38/17 ,  A61K38/43 ,  A61K48/00 ,  C12N15/113 ,  C07H21/04 ,  C12N15/85 ,  C12Q1/68

    CPC分类号： C12N15/113 ,  A61K38/57 ,  A61K48/00 ,  C12N2310/111 ,  C12N2310/121

    摘要： Methods of gene therapy, particular ribozyme-mediated gene replacement methods, are disclosed. Method of treating patients suffering from a disease associated with expression of an abnormal form of a gene, such as alpha-1 antitrypsin mutations, are disclosed. The methods comprise the steps of administering to such a patient a nucleic acid construct encoding a ribozyme and a nucleic acid construct comprising a ribozyme resistant gene encoding a wild type form of the gene product. Recombinant vectors and pharmaceutical compositions for practicing the methods are disclosed.

    摘要翻译： 公开了基因治疗方法，特别是核酶介导的基因替代方法。 公开了治疗患有与表达异常形式的基因例如α-1抗胰蛋白酶突变相关的疾病的患者的方法。 所述方法包括以下步骤：向所述患者施用编码核酶的核酸构建体和包含编码野生型形式的基因产物的核酶抗性基因的核酸构建体。 公开了用于实施该方法的重组载体和药物组合物。

    Cellular Targets for Treatment of Retroviral Infection
    10.
    发明申请
    Cellular Targets for Treatment of Retroviral Infection 审中-公开
    用于治疗逆转录病毒感染的细胞靶标

    公开(公告)号：US20110086423A1

    公开(公告)日：2011-04-14

    申请号：US12815125

    申请日：2010-06-14

    申请人： Rene Daniel ,  Anna Marie Skalka ,  Gary D. Kao ,  Giuseppe Nunnari ,  Roger J. Pomerantz

    发明人： Rene Daniel ,  Anna Marie Skalka ,  Gary D. Kao ,  Giuseppe Nunnari ,  Roger J. Pomerantz

    IPC分类号： C12N5/071

    CPC分类号： C12Q1/485 ,  C12Q1/18

    摘要： Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

    摘要翻译： 公开了用于抗逆转录病毒药物开发的细胞靶标。 基于逆转录病毒DNA整合的最终步骤所需的ATR激酶的鉴定，细胞靶标包含ATR激酶及其相关底物。 公开了通过ATR激酶途径鉴定逆转录病毒整合的调节剂的测定，以及通过这些测定法鉴定的调节剂。 还公开了其用于治疗逆转录病毒感染的药物制剂及其用途。