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1. 发明授权

US08697070B2 1D05 PCSK9 antagonists 失效
标题翻译： 1D05 PCSK9拮抗剂
公开(公告)号：US08697070B2
公开(公告)日：2014-04-15
申请号：US13466439
申请日：2012-05-08
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Pixley , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peizhi (Peter) Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Pixley , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peizhi (Peter) Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： A61K38/00
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，并形成了本公开的重要的附加方面。

2. 发明授权

US08957194B2 1B20 PCSK9 antagonists 有权
标题翻译： 1B20 PCSK9拮抗剂
公开(公告)号：US08957194B2
公开(公告)日：2015-02-17
申请号：US13466433
申请日：2012-05-08
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Pixley , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peizhi (Peter) Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Pixley , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peizhi (Peter) Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： C12N15/13 , C12N5/10 , C12N15/63 , C07K16/40 , C12N9/64 , A61K39/00
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，并形成了本公开的重要的附加方面。

3. 发明申请

US20120301461A1 1D05 PCSK9 ANTAGONISTS 失效
公开(公告)号：US20120301461A1
公开(公告)日：2012-11-29
申请号：US13466439
申请日：2012-05-08
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peizhi (Peter) Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peizhi (Peter) Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： C07K16/40 , C12N15/13 , C12N1/21 , A61P9/00 , C12N7/01 , C12N5/10 , C12P21/00 , A61K39/395 , C12N1/19
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，并形成了本公开的重要的附加方面。

4. 发明授权

US08188234B2 1D05 PCSK9 antagonists 有权
标题翻译： 1D05 PCSK9拮抗剂
公开(公告)号：US08188234B2
公开(公告)日：2012-05-29
申请号：US12322867
申请日：2009-02-06
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： C07K16/00 , A61K39/395 , C12N5/07 , C12N5/16
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，并形成了本公开的重要的附加方面。

5. 发明申请

US20090246192A1 1D05 PCSK9 antagonists 有权
标题翻译： 1D05 PCSK9拮抗剂
公开(公告)号：US20090246192A1
公开(公告)日：2009-10-01
申请号：US12322867
申请日：2009-02-06
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Laura Orsatti , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： A61K39/395 , C07K16/18 , C07H21/04 , C12N15/63 , C12N5/16 , C12P21/06
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，并形成了本公开的重要的附加方面。

6. 发明申请

US20130071379A1 1B20 PCSK9 ANTAGONISTS 有权
公开(公告)号：US20130071379A1
公开(公告)日：2013-03-21
申请号：US13466433
申请日：2012-05-08
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： A61K39/395 , C07K16/40 , C07K16/30 , C12P21/02 , C12N5/07
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，并形成了本公开的重要的附加方面。

7. 发明授权

US08188233B2 1B20 PCSK9 antagonists 有权
标题翻译： 1B20 PCSK9拮抗剂
公开(公告)号：US08188233B2
公开(公告)日：2012-05-29
申请号：US12322861
申请日：2009-02-06
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： C07K16/00 , A61K39/395 , C12N5/07 , C12N5/16
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，并形成了本公开的重要的附加方面。

8. 发明申请

US20090232795A1 1B20 PCSK9 ANTAGONISTS 有权
公开(公告)号：US20090232795A1
公开(公告)日：2009-09-17
申请号：US12322861
申请日：2009-02-06
申请人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
发明人： Jon H. Condra , Rose M. Cubbon , Holly A. Hammond , Timothy McCabe , Shilpa Pandit , Laurence B. Peterson , Joseph C. Santoro , Ayesha Sitlani , Dana D. Wood , Henryk Mach , Heidi Yoder , Sonia M. Gregory , Jeffrey T. Blue , Kevin Wang , Peter Luo , Denise K. Nawrocki , Pingyu Zhong , Feng Dong , Yan Li
IPC分类号： A61K39/395 , C07K16/00 , C07H21/04 , C12N15/63 , C12N5/00 , C12P21/06
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，并形成了本公开的重要的附加方面。

9. 发明申请

US20100113575A1 METHOD FOR DETECTING AUTOPROCESSED, SECRETED PCSK9 有权
标题翻译：检测自动分析的PCSK9的方法
公开(公告)号：US20100113575A1
公开(公告)日：2010-05-06
申请号：US12593342
申请日：2008-03-21
申请人： Ayesha Sitlani , Timothy S. Fisher , Joseph C. Santoro
发明人： Ayesha Sitlani , Timothy S. Fisher , Joseph C. Santoro
IPC分类号： A61K31/7088 , C12Q1/68 , C12N9/48 , G01N33/53 , A61P35/00
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：本发明提供一种用于检测自身加工的分泌的PCSK9，参与胆固醇体内平衡的蛋白质以及有效地鉴定抑制细胞自噬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到终止于对应于人PCSK9的Q152的氨基酸残基的pro结构域的C末端的PCSK9表达构建体中。在自动加工中，表位标签被暴露并且能够通过抗表位抗体或其他合适的识别系统识别，允许对加工的PCSK9的选择性和排他性鉴定和/或定量。因此，本公开内容提供了为本领域提供有用的技术以有效鉴定有效对抗冠心病的治疗剂的目标。

10. 发明授权

US08263353B2 Method for detecting autoprocessed, secreted PCSK9 有权
标题翻译：检测自动加工，分泌的PCSK9的方法
公开(公告)号：US08263353B2
公开(公告)日：2012-09-11
申请号：US12593342
申请日：2008-03-21
申请人： Ayesha Sitlani , Timothy S. Fisher , Joseph C. Santoro
发明人： Ayesha Sitlani , Timothy S. Fisher , Joseph C. Santoro
IPC分类号： G01N33/573 , G01N33/567
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：本发明提供一种用于检测自身加工的分泌的PCSK9，参与胆固醇体内平衡的蛋白质以及有效地鉴定抑制细胞自噬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到终止于对应于人PCSK9的Q152的氨基酸残基的pro结构域的C末端的PCSK9表达构建体中。在自动加工中，表位标签被暴露并且能够通过抗表位抗体或其他合适的识别系统识别，允许对加工的PCSK9的选择性和排他性鉴定和/或定量。因此，本公开内容提供了为本领域提供有用的技术以有效鉴定有效对抗冠心病的治疗剂的目标。

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