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1. 发明申请

WO2013142298A1 STABLE PEPTIDE MIMETICS OF THE HIV-1 GP41 PRE-HAIRPIN INTERMEDIATE 审中-公开
标题翻译： HIV-1 GP41 PRE-HAIRPIN中间体的稳定肽组蛋白
公开(公告)号：WO2013142298A1
公开(公告)日：2013-09-26
申请号：PCT/US2013/031831
申请日：2013-03-15
申请人： MERCK SHARP & DOHME CORP. , JOYCE, Joseph, G. , WU, Chengwei , OTTINGER, Elizabeth, A. , GARSKY, Victor
发明人： JOYCE, Joseph, G. , WU, Chengwei , OTTINGER, Elizabeth, A. , GARSKY, Victor
IPC分类号： A61K39/21 , C12N7/00 , G01N33/53 , A61K38/00
CPC分类号： C07K14/005 , A61K38/16 , A61K39/12 , A61K39/21 , A61K2039/55505 , A61K2039/55577 , A61K2039/64 , A61K2039/70 , C12N7/00 , C12N2740/16122 , C12N2740/16134
摘要： The present invention relates to a gp41 trivalent peptide mimetic having three gp41 N-peptides on a chemical scaffold which conformationally constrains the N-peptides into a trimeric coiled-coil to mimic gp41 presentation. The present invention also relates to N-peptides having the entire HIV gp41 NH2-terminal heptad repeat region and which are capable of forming gp41 peptide mimetics. Such peptide mimetics of HIV-1 gp41 pre-hairpin intermediates can be utilized in a vaccine for the treatment or prevention of HIV-1 infection through eliciting neutralizing antibodies.
摘要翻译：本发明涉及在化学支架上具有三个gp41 N-肽的gp41三价肽模拟物，其将N肽构象地约束成三聚盘旋线圈以模拟gp41呈递。本发明还涉及具有完整的HIV gp41 NH2-末端七重复区域并且能够形成gp41肽模拟物的N-肽。 HIV-1 gp41前发夹中间体的这种肽模拟物可以用于通过引发中和抗体来治疗或预防HIV-1感染的疫苗。

2. 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。

3. 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。

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