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    INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX
    1.
    发明申请
    INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX 有权
    USP1 DEBIQUITINATING ENZYME复合物的抑制剂

    公开(公告)号：US20100330599A1

    公开(公告)日：2010-12-30

    申请号：US12835559

    申请日：2010-07-13

    申请人： Alan D'Andrea

    发明人： Alan D'Andrea

    IPC分类号： C12Q1/37

    CPC分类号： G01N33/57496 ,  C12Q1/37 ,  G01N33/5011 ,  G01N2500/00

    摘要： The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.

    摘要翻译： 本发明提供用于抑制USP1去泛素酶活性并鉴定USP1去泛素酶的新抑制剂的组合物和方法。 抑制剂可用于治疗或预防癌症，骨髓衰竭，以及由遗传毒性因子如抗肿瘤药物（包括化学治疗剂和辐射）导致的细胞或DNA的损伤。 抑制剂包括用于抑制USP1或UAF1表达的siRNA，这是与USP1形成异二聚体复合物的蛋白质。 如果在辐射暴露之前或之后施用，抑制剂可用于增强细胞存活。 还提供了增强癌症化学疗法或放射疗法并增强DNA修复的方法。 提供转基因敲除动物和敲低细胞，其USP1表达受损。

    Method for determination and quantification of radiation or genotoxin exposure
    3.
    发明申请
    Method for determination and quantification of radiation or genotoxin exposure 有权
    辐射或基因毒素暴露的测定和定量方法

    公开(公告)号：US20090186355A1

    公开(公告)日：2009-07-23

    申请号：US12315368

    申请日：2008-12-01

    申请人： Alan D'Andrea

    发明人： Alan D'Andrea

    IPC分类号： C12Q1/68

    CPC分类号： C07K14/47 ,  C07K16/18 ,  G01N33/5014 ,  G01N2800/52

    摘要： The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.

    摘要翻译： 本发明公开了一种用于检测活体受体对基因毒物的暴露的方法，检测对遗传毒性试剂的敏感性，以及确定由暴露于药剂引起的DNA损伤的方法，包括从所述受试者收集的样品中检测含FANCD2的病灶的存在 。 浓缩灶的存在表明DNA损伤，并且病灶形成程度与暴露程度相关。 诊断试剂含有与可检测标记物相关的人FANCD2结合的配体。 用于检测生物样品中DNA损伤的试剂盒含有这样的诊断试剂和信号检测组分。 本发明还公开了用于鉴定调节含FANCD2的灶的形成能力的试剂的方法。 除此之外，这些试剂是潜在有用的化学增感剂或可以赋予针对由遗传毒性剂引起的损伤的保护。

    Recombinant erythropoietin receptor protein
    4.
    发明授权
    Recombinant erythropoietin receptor protein 失效
    重组促红细胞生成素受体蛋白

    公开(公告)号：US5378808A

    公开(公告)日：1995-01-03

    申请号：US75069

    申请日：1993-06-10

    申请人： Alan D'Andrea ,  Gordon G. Wong ,  Simon S. Jones

    发明人： Alan D'Andrea ,  Gordon G. Wong ,  Simon S. Jones

    IPC分类号： A61K38/00 ,  C07K14/505 ,  C07K14/71 ,  C07K16/22 ,  C12N15/12 ,  C12P21/08 ,  C07K13/00

    CPC分类号： C07K16/22 ,  C07K14/505 ,  C07K14/71 ,  A61K38/00

    摘要： The invention described encompasses an isolated DNA sequence encoding all or a portion thereof of a cell surface receptor murine and human erythropoietin (hereinafter EPO-R), along with the isolated polypeptide expressed by the DNA sequence (i.e., isolated EPO-R). The invention also encompasses host cells containing the above-described DNA sequence, preferably, host cells which express the polypeptide encoded by the DNA sequence (EPO-R) at a significantly higher level than that produced by normal red blood cell precursors. The invention further encompasses DNA sequences encoding secreted forms of the human EPO-R and polypeptides corresponding thereto. The EPO-receptor in all of the disclosed forms can be used as models for designing drugs or in pharmaceutical compositions for treating anemias.

    摘要翻译： 描述的发明包括编码细胞表面受体鼠和人促红细胞生成素（以下称为EPO-R）的全部或一部分的分离的DNA序列，以及由DNA序列表达的分离的多肽（即分离的EPO-R）。 本发明还包括含有上述DNA序列的宿主细胞，优选表达由DNA序列（EPO-R）编码的多肽的宿主细胞，其水平高于由正常红细胞前体产生的水平。 本发明还包括编码人EPO-R分泌形式的DNA序列和与其对应的多肽。 所有公开形式的EPO-受体可用作设计药物的模型或用于治疗贫血的药物组合物。

    Inhibitors of USP1 Deubiquitinating Enzyme Complex
    5.
    发明授权
    Inhibitors of USP1 Deubiquitinating Enzyme Complex 有权
    USP1去泛素化酶复合物的抑制剂

    公开(公告)号：US07754463B2

    公开(公告)日：2010-07-13

    申请号：US11820674

    申请日：2007-06-20

    申请人： Alan D'Andrea

    发明人： Alan D'Andrea

    IPC分类号： C12N9/64

    CPC分类号： G01N33/57496 ,  C12Q1/37 ,  G01N33/5011 ,  G01N2500/00

    摘要： The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.

    摘要翻译： 本发明提供用于抑制USP1去泛素酶活性并鉴定USP1去泛素酶的新抑制剂的组合物和方法。 抑制剂可用于治疗或预防癌症，骨髓衰竭，以及由遗传毒性因子如抗肿瘤药物（包括化学治疗剂和辐射）引起的细胞或DNA的损伤。 抑制剂包括用于抑制USP1或UAF1表达的siRNA，这是与USP1形成异二聚体复合物的蛋白质。 如果在辐射暴露之前或之后施用，抑制剂可用于增强细胞存活。 还提供了增强癌症化学疗法或放射疗法并增强DNA修复的方法。 提供转基因敲除动物和敲低细胞，其USP1表达受损。

    Method for determination and quantification of radiation or genotoxin exposure
    6.
    发明申请
    Method for determination and quantification of radiation or genotoxin exposure 有权
    辐射或基因毒素暴露的测定和定量方法

    公开(公告)号：US20050255502A1

    公开(公告)日：2005-11-17

    申请号：US11046346

    申请日：2005-01-28

    申请人： Alan D'Andrea

    发明人： Alan D'Andrea

    IPC分类号： C07K14/47 ,  C07K16/18 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/53

    CPC分类号： C07K14/47 ,  C07K16/18 ,  G01N33/5014 ,  G01N2800/52

    摘要： The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.

    摘要翻译： 本发明公开了一种用于检测活体受体对基因毒物的暴露的方法，检测对遗传毒性试剂的敏感性，以及确定由暴露于药剂引起的DNA损伤的方法，包括从所述受试者收集的样品中检测含FANCD2的病灶的存在 。 浓缩灶的存在表明DNA损伤，并且病灶形成程度与暴露程度相关。 诊断试剂含有与可检测标记物相关的人FANCD2结合的配体。 用于检测生物样品中DNA损伤的试剂盒含有这样的诊断试剂和信号检测组分。 本发明还公开了用于鉴定调节含FANCD2的灶的形成能力的试剂的方法。 除此之外，这些试剂是潜在有用的化学增感剂或可以赋予针对由遗传毒性剂引起的损伤的保护。

    Recombinant DNA endoding an erythropoietin receptor
    7.
    发明授权
    Recombinant DNA endoding an erythropoietin receptor 失效
    重组DNA代替红细胞生成素受体

    公开(公告)号：US5278065A

    公开(公告)日：1994-01-11

    申请号：US678877

    申请日：1991-03-25

    申请人： Alan D'Andrea ,  Gordon G. Wong ,  Simon S. Jones

    发明人： Alan D'Andrea ,  Gordon G. Wong ,  Simon S. Jones

    IPC分类号： A61K38/00 ,  C07K14/505 ,  C07K14/71 ,  C07K16/22 ,  C12N15/12 ,  C12P21/08 ,  C12N15/63

    CPC分类号： C07K16/22 ,  C07K14/505 ,  C07K14/71 ,  A61K38/00

    摘要： The invention described encompasses an isolated DNA sequence encoding all or a portion thereof of a cell surface receptor for murine and human erythropoietin (hereinafter EPO-R), along with the isolated polypeptide expressed by the DNA sequence (i.e., isolated EPO-R). The invention also encompasses host cells containing the above-described DNA sequence, preferably, host cells which express the polypeptide encoded by the DNA sequence (EPO-R) at a significantly higher level than that produced by normal red blood cell precursors. The invention further encompasses DNA sequences encoding secreted forms of the human EPO-R and polypeptides corresponding thereto. The EPO-receptor in all of the disclosed forms can be used as models for designing drugs or in pharmaceutical compositions for treating anemias.

    摘要翻译： 描述的发明包括编码鼠和人促红细胞生成素（以下称为EPO-R）的细胞表面受体的全部或一部分的分离的DNA序列，以及由DNA序列表达的分离的多肽（即分离的EPO-R）。 本发明还包括含有上述DNA序列的宿主细胞，优选表达由DNA序列（EPO-R）编码的多肽的宿主细胞，其水平高于由正常红细胞前体产生的水平。 本发明还包括编码人EPO-R分泌形式的DNA序列和与其对应的多肽。 所有公开形式的EPO-受体可用作设计药物的模型或用于治疗贫血的药物组合物。

    Inhibitors of USP1 deubiquitinating enzyme complex
    8.
    发明申请
    Inhibitors of USP1 deubiquitinating enzyme complex 有权
    USP1去泛素化酶复合物的抑制剂

    公开(公告)号：US20080167229A1

    公开(公告)日：2008-07-10

    申请号：US11820674

    申请日：2007-06-20

    申请人： Alan D'Andrea

    发明人： Alan D'Andrea

    IPC分类号： A61K38/00 ,  C12Q1/37

    CPC分类号： G01N33/57496 ,  C12Q1/37 ,  G01N33/5011 ,  G01N2500/00

    摘要： The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.

    摘要翻译： 本发明提供用于抑制USP1去泛素酶活性并鉴定USP1去泛素酶的新抑制剂的组合物和方法。 抑制剂可用于治疗或预防癌症，骨髓衰竭，以及由遗传毒性因子如抗肿瘤药物（包括化学治疗剂和辐射）引起的细胞或DNA的损伤。 抑制剂包括用于抑制USP1或UAF1表达的siRNA，这是与USP1形成异二聚体复合物的蛋白质。 如果在辐射暴露之前或之后施用，抑制剂可用于增强细胞存活。 还提供了增强癌症化学疗法或放射疗法并增强DNA修复的方法。 提供转基因敲除动物和敲低细胞，其USP1表达受损。