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1. 发明申请

WO2003072041A3 ASSAYS TO MONITOR AMYLOID PRECURSOR PROTEIN PROCESSING 审中-公开
公开(公告)号：WO2003072041A3
公开(公告)日：2003-09-04
申请号：PCT/US2003/005458
申请日：2003-02-23
申请人： MERCK & CO., INC. , ESPESETH, Amy, S. , FERRER, Marc , FLORES, Osvaldo, A. , HAZUDA, Daria, J. , INGLESE, James , MILLER, Michael, D. , REGISTER, Bruce , SHI, Xiao-Ping , SIMON, Adam, J. , ZUCK, Paul, D.
发明人： ESPESETH, Amy, S. , FERRER, Marc , FLORES, Osvaldo, A. , HAZUDA, Daria, J. , INGLESE, James , MILLER, Michael, D. , REGISTER, Bruce , SHI, Xiao-Ping , SIMON, Adam, J. , ZUCK, Paul, D.
IPC分类号： C07H21/02 , C12P21/06 , C12N1/20 , C12N15/00
摘要： The present invention provides DNA constructs, genetically engineered host cells, and methods for identifying inhibitors of amyloid precursor protein (APP) processing. The methods provide for the convenient identification, in a single assay, of inhibitors of β-secretase and γ-secretase as well as other forms of APP processing. The methods rely on fusion proteins of APP and transcription factors in which APP processing releases the transcription factors, allowing the transcription factors to activate transcription of a reporter gene. Inhibitors are identified as substances that block or diminish transcription factor release from the fusion protein, thereby causing a diminution of reporter gene readout.

2. 发明申请

WO2009117409A3 A HIGH THROUGHPUT PROTEIN INTERACTION ASSAY 审中-公开
标题翻译：高通量蛋白质相互作用测定
公开(公告)号：WO2009117409A3
公开(公告)日：2009-12-30
申请号：PCT/US2009037390
申请日：2009-03-17
申请人： MERCK & CO INC , CAULFIELD MICHAEL J , MILLER MICHAEL D , JOYCE JOSEPH , ZUCK PAUL D , GETTY KRISTA L , DUDKIN VADIM , OTTINGER ELIZABETH A
发明人： CAULFIELD MICHAEL J , MILLER MICHAEL D , JOYCE JOSEPH , ZUCK PAUL D , GETTY KRISTA L , DUDKIN VADIM , OTTINGER ELIZABETH A
IPC分类号： C40B30/04
CPC分类号： G01N33/564 , C07D211/60 , C07D211/62 , C07D401/12 , C12Q1/18 , G01N2333/162 , G01N2333/18 , G01N2333/22 , G01N2500/02
摘要： A method to identify small molecules useful as therapeutics and/or vaccines to prevent, alleviate or ameliorate a pathogenic infection or an autoimmune disorder. The method can be used to screen small molecule test compounds for the ability to disrupt particular antigen- antibody interactions of interest. In one embodiment, the antigen is a pathogen-derived antigen and the antibody decreases or inhibits virulence of the pathogen when bound to the antigen (e.g., a neutralizing antibody, antibody with serum bactericidal activity, etc.). In another embodiment, the antigen is a self-antigen (autoantigen) and the antibody is an autoantibody that is known to be associated with a pathological condition (e.g., autoimmune disorder). Compounds that bind to the antigen or antibody disrupt binding can be used as therapeutics to decrease or inhibit the autoimmune disorder.
摘要翻译：用于鉴定可用作治疗剂和/或疫苗以预防，减轻或改善病原体感染或自身免疫性疾病的小分子的方法。该方法可用于筛选小分子测试化合物以破坏感兴趣的特定抗原 - 抗体相互作用的能力。在一个实施方案中，抗原是病原体衍生的抗原，当与抗原结合时，抗体降低或抑制病原体的毒力（例如，中和抗体，具有血清杀菌活性的抗体等）。在另一个实施方案中，抗原是自身抗原（自身抗原），抗体是已知与病理状况（例如自身免疫性疾病）相关的自身抗体。与抗原或抗体结合的化合物破坏结合可用作治疗剂以减少或抑制自身免疫性疾病。

3. 发明申请

WO2009117409A2 A HIGH THROUGHPUT PROTEIN INTERACTION ASSAY 审中-公开
标题翻译：高通量蛋白质相互作用测定
公开(公告)号：WO2009117409A2
公开(公告)日：2009-09-24
申请号：PCT/US2009/037390
申请日：2009-03-17
申请人： MERCK & CO., INC. , CAULFIELD, Michael, J. , MILLER, Michael, D. , JOYCE, Joseph , ZUCK, Paul, D. , GETTY, Krista, L. , DUDKIN, Vadim , OTTINGER, Elizabeth, A.
发明人： CAULFIELD, Michael, J. , MILLER, Michael, D. , JOYCE, Joseph , ZUCK, Paul, D. , GETTY, Krista, L. , DUDKIN, Vadim , OTTINGER, Elizabeth, A.
IPC分类号： C12Q1/70
CPC分类号： G01N33/564 , C07D211/60 , C07D211/62 , C07D401/12 , C12Q1/18 , G01N2333/162 , G01N2333/18 , G01N2333/22 , G01N2500/02
摘要： The present invention relates to a method to identify small molecules that can be used as therapeutics and/or vaccines to prevent, alleviate or ameliorate a pathogenic infection or an autoimmune disorder. The assay of the invention can be used to screen small molecule test compounds for the ability to disrupt particular antigen-antibody interactions of interest. In one embodiment, the antigen is a pathogen-derived antigen and the antibody decreases or inhibits virulence of the pathogen when bound to the antigen (e.g., a neutralizing antibody, antibody with serum bactericidal activity, etc.). Compounds that bind to the antibody to inhibit its binding to antigen can be used as immunogens to elicit production of endogenously produced antibodies having the ability to decrease or inhibit virulence of the pathogen. Compounds that bind to the antigen to inhibit antibody binding can be used as therapeutics to decrease or inhibit pathogen virulence. In another embodiment, the antigen is a self-antigen (autoantigen) and the antibody is an autoantibody that is known to be associated with a pathological condition (e.g., autoimmune disorder). Compounds that bind to the antigen or antibody disrupt binding can be used as therapeutics to decrease or inhibit the autoimmune disorder.
摘要翻译：本发明涉及鉴定可用作治疗剂和/或疫苗以预防，缓解或改善病原性感染或自身免疫性疾病的小分子的方法。本发明的测定可用于筛选小分子测试化合物以破坏感兴趣的特定抗原 - 抗体相互作用的能力。在一个实施方案中，抗原是病原体衍生的抗原，当与抗原结合时，抗体降低或抑制病原体的毒力（例如，中和抗体，具有血清杀菌活性的抗体等）。结合抗体以抑制其与抗原结合的化合物可用作免疫原，以引起具有降低或抑制病原体毒性能力的内源性产生抗体的产生。与抗原结合以抑制抗体结合的化合物可用作降低或抑制病原体毒力的治疗剂。在另一个实施方案中，抗原是自身抗原（自身抗原），抗体是已知与病理状况（例如自身免疫性疾病）相关的自身抗体。与抗原或抗体结合的化合物破坏结合可用作治疗剂以减少或抑制自身免疫性疾病。

4. 发明申请

WO2003089672A1 HEPATITIS C VIRUS ASSAY SYSTEMS 审中-公开
标题翻译： HEPATITIS C病毒检测系统
公开(公告)号：WO2003089672A1
公开(公告)日：2003-10-30
申请号：PCT/US2003/012509
申请日：2003-04-11
申请人： MERCK & CO., INC. , FLORES, Osvaldo, A. , GROBLER, Jay , MURRAY, Edward, M. , ZUCK, Paul, D.
发明人： FLORES, Osvaldo, A. , GROBLER, Jay , MURRAY, Edward, M. , ZUCK, Paul, D.
IPC分类号： C12Q1/70
CPC分类号： G01N33/502 , C07K14/005 , C12N15/86 , C12N2730/10122 , C12N2840/203 , C12Q1/34 , C12Q1/6897 , C12Q1/707 , G01N33/5008 , G01N33/5067 , G01N33/5767 , G01N2333/18
摘要： The present invention features assays employing a beta-lactamase reporter system, an HCV replicon enhanced cell, and/or a chimeric HCV replicon containing a 3' UTR based on the HCV-1a 3' UTR. These features can be employed alone or together, and are preferably combined together to measure HCV replicon activity and the affect of compounds on such activity
摘要翻译：本发明的特征在于使用β-内酰胺酶报告系统，HCV复制子增强细胞和/或含有基于HCV-1a 3'UTR的3'UTR的嵌合HCV复制子。这些特征可以单独或一起使用，并且优选组合在一起以测量HCV复制子活性和化合物对这种活性的影响

5. 发明申请

WO2003072041A2 ASSAYS TO MONITOR AMYLOID PRECURSOR PROTEIN PROCESSING 审中-公开
标题翻译：测定AMYLOID前驱蛋白加工
公开(公告)号：WO2003072041A2
公开(公告)日：2003-09-04
申请号：PCT/US2003/005458
申请日：2003-02-23
申请人： MERCK & CO., INC. , ESPESETH, Amy, S. , FERRER, Marc , FLORES, Osvaldo, A. , HAZUDA, Daria, J. , INGLESE, James , MILLER, Michael, D. , REGISTER, Bruce , SHI, Xiao-Ping , SIMON, Adam, J. , ZUCK, Paul, D.
发明人： ESPESETH, Amy, S. , FERRER, Marc , FLORES, Osvaldo, A. , HAZUDA, Daria, J. , INGLESE, James , MILLER, Michael, D. , REGISTER, Bruce , SHI, Xiao-Ping , SIMON, Adam, J. , ZUCK, Paul, D.
IPC分类号： A61K
CPC分类号： C07K14/47 , C07K14/4702 , C07K14/4711 , C07K2319/00 , C07K2319/50 , G01N2500/10
摘要： The present invention provides DNA constructs, genetically engineered host cells, and methods for identifying inhibitors of amyloid precursor protein (APP) processing. The methods provide for the convenient identification, in a single assay, of inhibitors of β-secretase and γ-secretase as well as other forms of APP processing. The methods rely on fusion proteins of APP and transcription factors in which APP processing releases the transcription factors, allowing the transcription factors to activate transcription of a reporter gene. Inhibitors are identified as substances that block or diminish transcription factor release from the fusion protein, thereby causing a diminution of reporter gene readout.
摘要翻译：本发明提供了DNA构建体，遗传工程化宿主细胞和用于鉴定淀粉样前体蛋白（APP）处理抑制剂的方法。该方法提供了在单次测定中方便地鉴定β-分泌酶和γ-分泌酶抑制剂以及其它形式的APP处理。该方法依赖于APP和转录因子的融合蛋白，其中APP处理释放转录因子，允许转录因子激活报道基因的转录。抑制剂被鉴定为阻断或减少转录因子从融合蛋白释放的物质，从而导致报告基因读出的减少。

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