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1. 发明申请

WO2009100318A1 1B20 PCSK9 ANTAGONISTS 审中-公开
公开(公告)号：WO2009100318A1
公开(公告)日：2009-08-13
申请号：PCT/US2009/033369
申请日：2009-02-06
申请人： MERCK & CO., INC. , CONDRA, Jon, H. , CUBBON, Rose, M. , HAMMOND, Holly, A. , MCCABE, Timothy , PANDIT, Shilpa , PETERSON, Laurence, B. , SANTORO, Joseph, C. , SITLANI, Ayesha , WOOD, Dana, D. , MACH, Henryk , YODER, Heidi , GREGORY, Sonia, M. , BLUE, Jeffrey, T. , WANG, Kevin , LUO, Peter , NAWROCKI, Denise, K. , ZHONG, Pingyu , DONG, Feng , LI, Yan
发明人： CONDRA, Jon, H. , CUBBON, Rose, M. , HAMMOND, Holly, A. , MCCABE, Timothy , PANDIT, Shilpa , PETERSON, Laurence, B. , SANTORO, Joseph, C. , SITLANI, Ayesha , WOOD, Dana, D. , MACH, Henryk , YODER, Heidi , GREGORY, Sonia, M. , BLUE, Jeffrey, T. , WANG, Kevin , LUO, Peter , NAWROCKI, Denise, K. , ZHONG, Pingyu , DONG, Feng , LI, Yan
IPC分类号： C07K16/40 , C12N9/64 , A61K39/395 , C12N15/13 , A61P3/06
CPC分类号： C07K16/40 , A61K2039/505 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C12N9/6424
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ('PCSK9') are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.
摘要翻译：公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（'PCSK9'）的拮抗剂。所公开的拮抗剂在抑制PCSK9功能方面是有效的，因此，呈现用于治疗与PCSK9活性相关的病症的所需拮抗剂。本发明还公开了编码所述拮抗剂，载体，宿主细胞和包含拮抗剂的组合物的核酸。还公开了制备PCSK9特异性拮抗剂的方法以及使用拮抗剂抑制或拮抗PCSK9功能的方法，并且形成了本公开的重要的附加方面。

2. 发明申请

WO2009100297A1 1D05 PCSK9 ANTAGONISTS 审中-公开
公开(公告)号：WO2009100297A1
公开(公告)日：2009-08-13
申请号：PCT/US2009/033341
申请日：2009-02-06
申请人： MERCK & CO., INC. , ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE S.P.A. , CONDRA, Jon, H. , CUBBON, Rose, M. , HAMMOND, Holly, A. , ORSATTI, Laura , PANDIT, Shilpa , PETERSON, Laurence, B. , SANTORO, Joseph, C. , SITLANI, Ayesha , WOOD, Dana, D. , MACH, Henryk , YODER, Heidi , GREGORY, Sonia, M. , BLUE, Jeffrey, T. , WANG, Kevin , LUO, Peter , NAWROCKI, Denise, K. , ZHONG, Pingyu , DONG, Feng , LI, Yan
发明人： CONDRA, Jon, H. , CUBBON, Rose, M. , HAMMOND, Holly, A. , ORSATTI, Laura , PANDIT, Shilpa , PETERSON, Laurence, B. , SANTORO, Joseph, C. , SITLANI, Ayesha , WOOD, Dana, D. , MACH, Henryk , YODER, Heidi , GREGORY, Sonia, M. , BLUE, Jeffrey, T. , WANG, Kevin , LUO, Peter , NAWROCKI, Denise, K. , ZHONG, Pingyu , DONG, Feng , LI, Yan
IPC分类号： C07K16/40 , C12N9/64 , A61K39/395 , C12N15/13 , A61P3/06
CPC分类号： C07K16/40 , A61K2039/505 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C12N9/6424
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ('PCSK9') are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.
摘要翻译：公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（'PCSK9'）的拮抗剂。所公开的拮抗剂在抑制PCSK9功能方面是有效的，因此，呈现用于治疗与PCSK9活性相关的病症的所需拮抗剂。本发明还公开了编码所述拮抗剂，载体，宿主细胞和包含拮抗剂的组合物的核酸。还公开了制备PCSK9特异性拮抗剂的方法以及使用拮抗剂抑制或拮抗PCSK9功能的方法，并且形成了本公开的重要的附加方面。

3. 发明申请

WO2008057457A2 ANTAGONISTS OF PCSK9 审中-公开
公开(公告)号：WO2008057457A2
公开(公告)日：2008-05-15
申请号：PCT/US2007/023212
申请日：2007-11-02
申请人： MERCK & CO., INC. , SPARROW, Carl, P. , SITLANI, Ayesha , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
发明人： SPARROW, Carl, P. , SITLANI, Ayesha , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
IPC分类号： A61K39/395
CPC分类号： C07K16/40 , C07K2317/55 , C07K2317/56 , C07K2317/76 , C07K2317/92
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

4. 发明申请

WO2008063382A2 ANTAGONISTS OF PCSK9 审中-公开
公开(公告)号：WO2008063382A2
公开(公告)日：2008-05-29
申请号：PCT/US2007/023223
申请日：2007-11-02
申请人： MERCK & CO., INC. , SITLANI, Ayesha , SPARROW, Carl, P. , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
发明人： SITLANI, Ayesha , SPARROW, Carl, P. , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
IPC分类号： A61K39/395
CPC分类号： C07K16/40 , C07K2317/55 , C07K2317/56 , C07K2317/76 , C07K2317/92
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

5. 发明申请

WO2008057459A2 ANTAGONISTS OF PCSK9 审中-公开
公开(公告)号：WO2008057459A2
公开(公告)日：2008-05-15
申请号：PCT/US2007/023214
申请日：2007-11-02
申请人： MERCK & CO., INC. , SPARROW, Carl, P. , SITLANI, Ayesha , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
发明人： SPARROW, Carl, P. , SITLANI, Ayesha , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
IPC分类号： A61K39/395
CPC分类号： C07K16/40 , C07K2317/55 , C07K2317/56 , C07K2317/76 , C07K2317/92
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

6. 发明申请

WO2008057458A3 ANTAGONISTS OF PCSK9 审中-公开
公开(公告)号：WO2008057458A3
公开(公告)日：2008-05-15
申请号：PCT/US2007/023213
申请日：2007-11-02
申请人： MERCK & CO., INC. , SPARROW, Carl, P. , SITLANI, Ayesha , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
发明人： SPARROW, Carl, P. , SITLANI, Ayesha , PANDIT, Shilpa , CONDRA, Jon, H. , HAMMOND, Holly, A.
IPC分类号： A61K39/395 , C07K16/40
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

7. 发明申请

WO2008133647A2 ANTAGONISTS OF PCSK9 审中-公开
标题翻译： PCSK9的拮抗剂
公开(公告)号：WO2008133647A2
公开(公告)日：2008-11-06
申请号：PCT/US2007/023169
申请日：2007-11-02
申请人： MERCK & CO., INC. , SITLANI, Ayesha , SPARROW, Carl, P. , PANDIT, Shilpa , CONDRA, Jon, H. , WOOD, Dana, D. , FISHER, Timothy, S.
发明人： SITLANI, Ayesha , SPARROW, Carl, P. , PANDIT, Shilpa , CONDRA, Jon, H. , WOOD, Dana, D. , FISHER, Timothy, S.
IPC分类号： A61K39/395
CPC分类号： C07K16/40 , C07K2317/55 , C07K2317/56 , C07K2317/76 , C07K2317/92
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.
摘要翻译：披露了人类前蛋白转化酶枯草杆菌蛋白酶 - kexin 9型的拮抗剂（“PCSK9”）。所公开的拮抗剂在抑制PCSK9功能方面是有效的，并因此提供了用于治疗与PCSK9活性相关的病症的理想拮抗剂。本发明还公开了编码所述拮抗剂，载体，宿主细胞和包含拮抗剂的组合物的核酸。还公开了制备PCSK9特异性拮抗剂的方法以及使用拮抗剂抑制或拮抗PCSK9功能的方法，并且形成本公开的重要的另外方面。

8. 发明申请

WO2010068526A1 PCSK9 IMMUNOASSAY 审中-公开
标题翻译： PCSK9免疫
公开(公告)号：WO2010068526A1
公开(公告)日：2010-06-17
申请号：PCT/US2009/066303
申请日：2009-12-02
申请人： MERCK SHARP & DOHME CORP. , NI, Yan , SITLANI, Ayesha , PANDIT, Shilpa , LEWIS, Dale , SHEN, Xun , LOBO, Sharon , MCCABE, Timothy , CONDRA, Jon , CUBBON, Rose
发明人： NI, Yan , SITLANI, Ayesha , PANDIT, Shilpa , LEWIS, Dale , SHEN, Xun , LOBO, Sharon , MCCABE, Timothy , CONDRA, Jon , CUBBON, Rose
IPC分类号： G01N33/53
CPC分类号： C07K16/40 , C07K2317/55 , G01N33/543 , G01N33/573 , G01N2333/96433
摘要： Methods of using PCSK9 antagonists More specifically, methods for measuring circulating PCSK9 levels in a biological sample by means of an immunoassay The immunoassay used can be a solid phase immunoassay, such as a dissociation-enhanced lanthanide fluorescence immunoassay utilizing an E07 capture antibody or coating and a G08 or H23 detecting antibody.
摘要翻译：使用PCSK9拮抗剂的方法更具体地，通过免疫测定法测量生物样品中的循环PCSK9水平的方法所用的免疫测定可以是固相免疫测定，例如利用E07捕获抗体或涂层的解离增强镧系荧光免疫测定， G08或H23检测抗体。

9. 发明申请

WO2011037791A1 ANTAGONISTS OF PCSK9 审中-公开
标题翻译： PCSK9的拮抗剂
公开(公告)号：WO2011037791A1
公开(公告)日：2011-03-31
申请号：PCT/US2010/048849
申请日：2010-09-15
申请人： MERCK SHARP & DOHME CORP. , SHEN, Xun , LOBO, Sharon , NI, Yan , SITLANI, Ayesha , PANDIT, Shilpa , LEWIS, Dale , MCCABE, Timothy , CONDRA, Jon , WANG, Fubao , CUBBON, Rose
发明人： SHEN, Xun , LOBO, Sharon , NI, Yan , SITLANI, Ayesha , PANDIT, Shilpa , LEWIS, Dale , MCCABE, Timothy , CONDRA, Jon , WANG, Fubao , CUBBON, Rose
IPC分类号： C07K16/40 , C07H21/00
CPC分类号： C07K16/40 , C07K2317/76
摘要： Antagonists of human proprotein convertase subtilisin-kexin type 9 (PCSK9) are disclosed. Said antagonists are effective in the inhibition of PCSK9 function and thereby provide compositions of matter useful for the treatment of conditions associated with PCSK9 activity. The present invention further discloses nucleic acids encoding PCSK9 antagonists as well as methods of making and using PCSK9 antagonists.
摘要翻译：公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（PCSK9）的拮抗剂。所述拮抗剂在抑制PCSK9功能方面是有效的，从而提供可用于治疗与PCSK9活性相关的病症的物质组合物。本发明还公开了编码PCSK9拮抗剂的核酸以及制备和使用PCSK9拮抗剂的方法。

10. 发明申请

WO2008118386A2 METHOD FOR DETECTING AUTOPROCESSED, SECRETED PCSK9 审中-公开
标题翻译：检测自动加工，分泌PCSK9的方法
公开(公告)号：WO2008118386A2
公开(公告)日：2008-10-02
申请号：PCT/US2008/003800
申请日：2008-03-21
申请人： MERCK & CO., INC. , SITLANI, Ayesha , FISHER, Timothy, S. , SANTORO, Joseph, C.
发明人： SITLANI, Ayesha , FISHER, Timothy, S. , SANTORO, Joseph, C.
IPC分类号： G01N33/53
CPC分类号： C12Q1/37 , C12N9/6424
摘要： The present invention provides a method for detecting autoprocessed, secreted PCSK9, a protein involved in cholesterol homeostasis, and for effectively identifying compounds that inhibit autocleavage and secretion from cells. The disclosed method involves the insertion of an epitope tag into a PCSK9 expression construct immediately C-terminal to the pro domain ending at an amino acid residue corresponding to Q152 of human PCSK9. Upon autoprocessing, the epitope tag is exposed and capable of recognition by anti-epitope antibodies or other suitable identification system, allowing for the selective and exclusive identification and/or quantification of processed PCSK9. The present disclosure thus advances the goal of providing enabling technology to the art for the effective identification of therapeutics effective in combating coronary heart disease.
摘要翻译：本发明提供了用于检测自体处理的分泌型PCSK9（一种参与胆固醇稳态的蛋白质）并用于有效鉴定抑制自细胞分裂和分泌的化合物的方法。所公开的方法涉及将表位标签插入PCSK9表达构建体中，紧邻C末端至前结构域，终止于对应于人PCSK9的Q152的氨基酸残基。在自动处理后，表位标签暴露并且能够被抗表位抗体或其他合适的鉴定系统识别，从而允许选择性和排他地鉴定和/或定量处理的PCSK9。本公开因此推进了为本领域提供有效识别有效治疗冠心病的治疗剂的技术的目标。

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