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    Non-Human Animal Models for B-cell Non-Hodgkin's Lymphoma and Uses Thereof
    5.
    发明申请
    Non-Human Animal Models for B-cell Non-Hodgkin's Lymphoma and Uses Thereof 审中-公开
    B细胞非霍奇金淋巴瘤的非人类动物模型及其用途

    公开(公告)号：US20080070256A1

    公开(公告)日：2008-03-20

    申请号：US11829058

    申请日：2007-07-26

    申请人： Yosef Refaeli ,  Brian Turner ,  Ryan Young

    发明人： Yosef Refaeli ,  Brian Turner ,  Ryan Young

    IPC分类号： A01K67/00 ,  C12N5/00 ,  C12N5/02 ,  C12Q1/68

    CPC分类号： A01K67/0275 ,  A01K2227/105 ,  A01K2267/0331 ,  A61K47/6849 ,  A61K49/0008 ,  C07K14/82 ,  C07K16/40 ,  C12N9/2462 ,  C12N2830/006

    摘要： Disclosed are non-human animal models, and preferably, rodent models, and more preferably, mouse models, of B-cell Non-Hodgkin's Lymphoma (NHL). In particular, the present invention provides animal models of B cell NHL including, B cell chronic lymphocytic leukemia/lymphoma (B-CLL), Burkitt's lymphoma (BL), Follicular-like lymphoma (FLL) and Diffuse large B-cell lymphoma (DLBCL), as well as various methods for producing these non-human animal models. These animal models, as well as cell lines produced from or derived from these models, are useful tools for a variety of methods, including, but not limited to, preclinical testing of drug candidates, and particularly drug candidates that are specific for human proteins, and any research, development, pharmaceutical, or clinical purpose, including but not limited to, the identification, development, and/or testing of drugs (therapeutics, prophylactics, etc.), targets, markers, and/or research tools for use in the diagnosis of, study of, or treatment of any Non-Hodgkin's Lymphoma, such as those described herein, or for any related condition.

    摘要翻译： 公开了非人动物模型，优选是啮齿动物模型，更优选地是B细胞非霍奇金淋巴瘤（NHL）的小鼠模型。 特别是本发明提供B细胞NHL的动物模型，包括B细胞慢性淋巴细胞白血病/淋巴瘤（B-CLL），伯基特淋巴瘤（BL），滤泡样淋巴瘤（FLL）和弥漫性大B细胞淋巴瘤（DLBCL ），以及用于生产这些非人动物模型的各种方法。 这些动物模型以及从这些模型产生或源自这些模型的细胞系是多种方法的有用工具，包括但不限于药物候选物的临床前测试，特别是对人蛋白质特异性的候选药物， 以及任何研究，开发，制药或临床目的，包括但不限于用于药物（治疗，预防等），靶标，标记物和/或研究工具的鉴定，开发和/或测试 任何非霍奇金淋巴瘤的诊断，研究或治疗，如本文所述的那些，或任何相关病症。

    VPR function and activity
    7.
    发明授权
    VPR function and activity 失效
    VPR功能和活动

    公开(公告)号：US06838236B1

    公开(公告)日：2005-01-04

    申请号：US08167608

    申请日：1993-12-15

    申请人： David B. Weiner ,  David Nathan Levy ,  Yosef Refaeli

    发明人： David B. Weiner ,  David Nathan Levy ,  Yosef Refaeli

    IPC分类号： A61K38/00 ,  A61K47/48 ,  C07K14/16 ,  G01N33/569 ,  C12Q1/70

    CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K47/62 ,  C12N2740/16322 ,  G01N33/56988

    摘要： Pharmaceutical compositions comprising the HIV protein vpr or nucleic acid molecule encoding vpr are disclosed. Also disclosed are methods of treating patients suffering from diseases characterized by hyperproliferating undifferentiated cells such as cancer by administering such compositions. Methods of identifying compounds which have anti-HIV activity are disclosed, in particular, methods of identifying compounds which modulate the activity of vpr and of identifying compounds which inhibit vpr binding to the HIV protein gag.

    摘要翻译： 公开了包含HIV蛋白质vpr或编码vpr的核酸分子的药物组合物。 还公开了通过施用这样的组合物治疗患有特征在于通过过度增殖未分化细胞例如癌症的患者的方法。 公开了鉴定具有抗HIV活性的化合物的方法，特别是鉴定调节vpr活性的化合物和鉴定抑制vpr与HIV蛋白质凝胶结合的化合物的方法。

    Methods for the identification of compounds capable of inducing the nuclear translocation of a receptor complex comprising the glucocoticoid receptor type II and viral protein R interacting protein
    8.
    发明授权
    Methods for the identification of compounds capable of inducing the nuclear translocation of a receptor complex comprising the glucocoticoid receptor type II and viral protein R interacting protein 失效
    用于鉴定能够诱导受体复合物的核易位的化合物的方法，所述受体复合物包含II型糖基血糖受体和病毒蛋白R相互作用蛋白

    公开(公告)号：US5763190A

    公开(公告)日：1998-06-09

    申请号：US309644

    申请日：1994-09-21

    申请人： David B. Weiner ,  Yosef Refaeli

    发明人： David B. Weiner ,  Yosef Refaeli

    IPC分类号： A61K38/00 ,  A61K38/16 ,  A61K48/00 ,  C07K14/16 ,  G01N33/53 ,  C12N15/00 ,  C12P21/06

    CPC分类号： C07K14/005 ,  A61K38/162 ,  A61K48/00 ,  C12N2710/14143 ,  C12N2740/16322

    摘要： Human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus contain, in addition to the canonical gag/pol/env genes, additional small open reading frames encoding gene products, including the 96-amino acid 15-kDa virion associated HIV-1 Vpr gene product. The conservation of the vpr open reading frame in primate lentiviruses suggests that vpr is critical to viral replication. A biologically active recombinant HIV-1 Vpr protein was employed as a ligand to identify its cellular targets. A novel 41-kDa cytosolic protein was identified and termed the viral protein R interacting protein, or Rip-1. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-II-stimulating steroids. Vpr and Rip-1 coimmunoprecipitated with the human GR as part of a receptor complex. The present invention discloses methods for the identification of compounds capable of inducing GR-II/Rip-1 receptor complex cytosolic to nuclear translocation.

    摘要翻译： 除了典型的gag / pol / env基因之外，人类免疫缺陷病毒（HIV）-1，HIV-2和猿猴免疫缺陷病毒还包含编码基因产物的其他小型开放阅读框，包括96-氨基酸15-kDa病毒粒子 相关的HIV-1 Vpr基因产物。 灵长类动物慢病毒的vpr开放阅读框的保护表明vpr对于病毒复制至关重要。 使用生物活性的重组HIV-1 Vpr蛋白作为配体来鉴定其细胞靶标。 鉴定了一种新型的41-kDa胞质蛋白，称为病毒蛋白R相互作用蛋白或Rip-1。 Rip-1显示广泛的组织分布，包括HIV感染的相关目标。 Vpr蛋白诱导Rip-1的核易位，糖皮质激素受体（GR）-II刺激类固醇也是如此。 Vpr和Rip-1与作为受体复合物的一部分的人GR共免疫沉淀。 本发明公开了鉴定能够诱导细胞核移位的GR-II / Rip-1受体复合物的化合物的方法。

    Method and kit for identification of antiviral agents capable of abrogating HIV Vpr-Rip-1 binding interactions
    9.
    发明授权
    Method and kit for identification of antiviral agents capable of abrogating HIV Vpr-Rip-1 binding interactions 失效
    用于鉴定能够消除HIV Vpr-Rip-1结合相互作用的抗病毒剂的方法和试剂盒

    公开(公告)号：US5639598A

    公开(公告)日：1997-06-17

    申请号：US246177

    申请日：1994-05-19

    申请人： David B. Weiner ,  Yosef Refaeli ,  David N. Levy

    发明人： David B. Weiner ,  Yosef Refaeli ,  David N. Levy

    IPC分类号： A61K38/00 ,  C07K14/16 ,  C07K16/10 ,  G01N33/569 ,  C12Q1/70 ,  G01N33/53

    CPC分类号： C07K14/005 ,  C07K16/1072 ,  G01N33/56988 ,  A61K38/00 ,  C12N2740/16322 ,  Y10S514/01

    摘要： Human and simian immunodeficiency viruses (HIV/SIVs) contain, in addition to the canonical gag/pol/env genes, additional small open reading frames (ORFs) encoding gene products, including the 96-amino acid 15-kDa virion-associated HIV-1 Vpr gene product. Vpr functions as a regulator of cellular processes related to HIV replication. A biologically active recombinant HIV-1 Vpr protein was employed as a ligand to identify its cognate cellular target(s). A novel 41-kDa cytosolic viral protein R interacting protein, designated Rip-1, was identified using the recited assay. Rip-1 displays a wide-tissue distribution, including relevant targets of HIV infection. HIV-1 Vpr induced nuclear translocation of Rip-1. This invention provides novel biochemical reagents and methods that will facilitate the identification of antiviral agents.

    摘要翻译： 除了典型的gag / pol / env基因之外，人和猿免疫缺陷病毒（HIV / SIV）还包含编码基因产物的其他小型开放阅读框（ORF），包括96-氨基酸15-kDa病毒体相关的HIV- 1 Vpr基因产物。 Vpr作为与HIV复制有关的细胞过程的调节剂。 使用生物活性的重组HIV-1 Vpr蛋白作为配体来鉴定其同源细胞靶标。 使用所述测定法鉴定了一种名为Rip-1的新型41-kDa胞质病毒蛋白R相互作用蛋白。 Rip-1显示广泛的组织分布，包括艾滋病毒感染的相关目标。 HIV-1Vpr诱导Rip-1的核易位。 本发明提供了促进抗病毒剂鉴定的新型生物化学试剂和方法。