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1. 发明申请

US20140121123A1 METHODS FOR DIVERSIFYING ANTIBODIES, ANTIBODIES DERIVED THEREFROM AND USES THEREOF 审中-公开
标题翻译：用于分化抗体的方法，其衍生的抗体及其用途
公开(公告)号：US20140121123A1
公开(公告)日：2014-05-01
申请号：US13882285
申请日：2011-10-24
申请人： Kevin Caili Wang , Yan Li , Mark Hsieh , Xinwei Wang , Xinwei Wang , Feng Dong , Peizhi (Peter) Luo , Pingyu Zhong
发明人： Kevin Caili Wang , Yan Li , Mark Hsieh , Xinwei Wang , Xinwei Wang , Feng Dong , Peizhi (Peter) Luo , Pingyu Zhong
IPC分类号： C12N15/10
CPC分类号： C12N15/1055 , C07K16/00 , C07K16/005 , C07K16/087 , C07K16/2863 , C07K16/2866 , C07K16/32 , C07K2317/21 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6845
摘要： The invention provides methods of introducing diversity into antibody molecules comprising introducing or substituting at least one amino acid sequence in the CDR of the target antibody together with at least one amino acid in the FW region spanning the 3 amino acid adjoining the CRD on each side. The resulting diverse antibodies with variant CDRs and FW region sequences comprising diverse amino acid sequences are also described. These polypeptides regions, herein referred to as 3+CDR3+, that form the gist of the invention contribution described herein provide a flexible and simple source of sequence diversity that can be used as a source for expressing and identifying diverse antibodies or antigen binding polypeptides. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided. A method of producing diverse antibodies comprising amino acid substitutions in one of the CDR region and the FW region comprising 3 contiguous FW sequence amino acids adjacent to each CDR on either side is described herein. The substitutions are relative to database or germline sequences. Not all substitution are preserved in conservative regions.
摘要翻译：本发明提供了将多样性引入抗体分子的方法，包括在靶抗体的CDR中引入或取代至少一个氨基酸序列以及跨越与CRD相邻的3个氨基酸的FW区域中的至少一个氨基酸。还描述了所得到的具有包含不同氨基酸序列的变体CDR和FW区序列的多种抗体。形成本文所述发明要点的这些多肽区域（本文称为3 + CDR3 +）提供了可用作表达和鉴定多种抗体或抗原结合多肽的来源的灵活和简单的序列多样性来源。还提供了包含多个这些多肽的文库。此外，提供了用于产生和使用这些多肽和文库的方法和组合物。本文描述了在包含与任一侧上的每个CDR相邻的3个连续的FW序列氨基酸的CDR区域和FW区域之一中产生包含氨基酸取代的多种抗体的方法。替代是相对于数据库或种系序列。并非所有替代都保留在保守区域。

2. 发明申请

US20120231005A1 AX1 AND AX189 PSCK9 ANTAGONISTS AND VARIANTS 有权
标题翻译： AX1和AX189 PSCK9 ANTAGONISTS和变量
公开(公告)号：US20120231005A1
公开(公告)日：2012-09-13
申请号：US13503726
申请日：2010-10-29
申请人： Peter Peizhi Luo , Kevin Caili Wang , Pingyu Zhong , Mark Hsieh , Yan Li , Xinwei Wang , Feng Dong , Andrei Golosov , Yan Ni , Weirong Wang , Laurence B. Peterson , Rose Cubbon
发明人： Peter Peizhi Luo , Kevin Caili Wang , Pingyu Zhong , Mark Hsieh , Yan Li , Xinwei Wang , Feng Dong , Andrei Golosov , Yan Ni , Weirong Wang , Laurence B. Peterson , Rose Cubbon
IPC分类号： C07K16/40 , C12N9/99 , C12N1/21 , C12N15/13 , C12N5/10 , C12P21/02 , A61K39/395 , C12N15/63 , C12N1/19
CPC分类号： C07K16/40 , C07K2317/21 , C07K2317/34 , C07K2317/41 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/90 , C07K2317/92 , C07K2317/94
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. 发明授权

US07175983B2 Adapter-directed display systems 有权
标题翻译：适配器导向显示系统
公开(公告)号：US07175983B2
公开(公告)日：2007-02-13
申请号：US10033399
申请日：2001-11-02
申请人： Caili Wang , Pingyu Zhong , Xinwei Wang
发明人： Caili Wang , Pingyu Zhong , Xinwei Wang
IPC分类号： C12Q1/68
CPC分类号： C40B40/02 , C12N15/1037
摘要： The present invention provides adapter-directed display systems for expressing exogenous polypeptide within a host cell and/or displaying the exogenous polypeptide on the outer surface of a genetic package. This subject systems are particularly useful for displaying a genetically diverse repertoire of monomeric and multimeric polypeptides. The invention also provides both expression and helper vectors and kits containing components of the subject display systems. Also provided are genetic packages displaying the exogenous polypeptides of particular interest. Further provided by the invention are methods of using the subject display systems.
摘要翻译：本发明提供了用于在宿主细胞内表达外源多肽的和/或在遗传包装的外表面上显示外源多肽的适配器指导显示系统。该主题系统对于显示基因多样的单体和多聚体多肽的组成特别有用。本发明还提供表达和辅助载体和包含受试显示系统的组分的试剂盒。还提供显示特别感兴趣的外源多肽的遗传包。本发明进一步提供的是使用对象显示系统的方法。

4. 发明授权

US06833441B2 Compositions and methods for generating chimeric heteromultimers 有权
标题翻译：用于产生嵌合异源多聚体的组合物和方法
公开(公告)号：US06833441B2
公开(公告)日：2004-12-21
申请号：US09921144
申请日：2001-08-01
申请人： Caili Wang , Pingyu Zhong , Shengjiang Liu , Peizhi Luo , Shengfeng Li , Xinwei Wang
发明人： Caili Wang , Pingyu Zhong , Shengjiang Liu , Peizhi Luo , Shengfeng Li , Xinwei Wang
IPC分类号： C07K1600
CPC分类号： C07K16/00 , C07K2317/56 , C07K2319/00
摘要： The present invention provides a technique for specific assembly of monomeric polypeptides to form a heteromultimer. This technique is particularly useful for generating a genetically diverse repertoire of heteromultimers such as antigen-binding units. The invention also provides both non-single-chain and single-chain antigen-binding units that are assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subject antigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.
摘要翻译：本发明提供了用于特异性组装单体多肽以形成异源多聚体的技术。该技术对于产生诸如抗原结合单位的异源多聚体的遗传多样性谱特别有用。本发明还提供通过本文所述技术组装的非单链和单链抗原结合单元。本发明还提供重组多核苷酸，载体，宿主细胞和用于产生受试者抗原结合单位的试剂盒。本发明进一步提供的是使用受试者抗原结合单元的方法。

5. 发明授权

US07910350B2 Adaptor-directed helper systems 有权
标题翻译：适配器导向的辅助系统
公开(公告)号：US07910350B2
公开(公告)日：2011-03-22
申请号：US11313270
申请日：2005-12-19
申请人： Caili Wang , Pingyu Zhong , Xinwei Wang
发明人： Caili Wang , Pingyu Zhong , Xinwei Wang
IPC分类号： C12N7/01
CPC分类号： C40B40/02 , C12N15/1037
摘要： The present invention provides adapter-directed display systems for expressing exogenous polypeptide within a host cell and/or displaying the exogenous polypeptide on the outer surface of a genetic package. This subject systems are particularly useful for displaying a genetically diverse repertoire of monomeric and multimeric polypeptides. The invention also provides both expression and helper vectors and kits containing components of the subject display systems. Also provided are genetic packages displaying the exogenous polypeptides of particular interest. Further provided by the invention are methods of using the subject display systems.
摘要翻译：本发明提供了用于在宿主细胞内表达外源多肽的和/或在遗传包装的外表面上显示外源多肽的适配器指导显示系统。该主题系统对于显示基因多样的单体和多聚体多肽的组成特别有用。本发明还提供表达和辅助载体和包含受试显示系统的组分的试剂盒。还提供显示特别感兴趣的外源多肽的遗传包。本发明进一步提供的是使用对象显示系统的方法。

6. 发明授权

US07429652B2 Compositions and methods for generating chimeric heteromultimers 有权
标题翻译：用于产生嵌合异源多聚体的组合物和方法
公开(公告)号：US07429652B2
公开(公告)日：2008-09-30
申请号：US10911127
申请日：2004-08-03
申请人： Caili Wang , Pingyu Zhong , Shengjiang Liu , Peizhi Luo , Shengfeng Li , Xinwei Wang
发明人： Caili Wang , Pingyu Zhong , Shengjiang Liu , Peizhi Luo , Shengfeng Li , Xinwei Wang
IPC分类号： C07H21/04 , C12Q1/70 , C12P21/04 , C12N7/00 , C12N15/00 , C12N5/06 , A61K39/395 , C12P21/08
CPC分类号： C07K16/00 , C07K2317/56 , C07K2319/00
摘要： The present invention provides a technique for specific assembly of monomeric polypeptides to form a heteromultimer. This technique is particularly useful for generating a genetically diverse repertoire of heteromultimers such as antigen-binding units. The invention also provides both non-single-chain and single-chain antigen-binding units that are assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subject antigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.
摘要翻译：本发明提供了用于特异性组装单体多肽以形成异源多聚体的技术。该技术对于产生诸如抗原结合单位的异源多聚体的遗传多样性谱特别有用。本发明还提供通过本文所述技术组装的非单链和单链抗原结合单元。本发明还提供重组多核苷酸，载体，宿主细胞和用于产生受试者抗原结合单位的试剂盒。本发明进一步提供的是使用受试者抗原结合单元的方法。

7. 发明申请

US20060281181A1 Adaptor-directed helper systems 有权
标题翻译：适配器导向的辅助系统
公开(公告)号：US20060281181A1
公开(公告)日：2006-12-14
申请号：US11313270
申请日：2005-12-19
申请人： Caili Wang , Pingyu Zhong , Xinwei Wang
发明人： Caili Wang , Pingyu Zhong , Xinwei Wang
IPC分类号： C12N15/86 , C12N15/74
CPC分类号： C40B40/02 , C12N15/1037
摘要： The present invention provides adapter-directed display systems for expressing exogenous polypeptide within a host cell and/or displaying the exogenous polypeptide on the outer surface of a genetic package. This subject systems are particularly useful for displaying a genetically diverse repertoire of monomeric and multimeric polypeptides. The invention also provides both expression and helper vectors and kits containing components of the subject display systems. Also provided are genetic packages displaying the exogenous polypeptides of particular interest. Further provided by the invention are methods of using the subject display systems.
摘要翻译：本发明提供了用于在宿主细胞内表达外源多肽的和/或在遗传包装的外表面上显示外源多肽的适配器指导显示系统。该主题系统对于显示基因多样的单体和多聚体多肽的组成特别有用。本发明还提供表达和辅助载体和包含受试显示系统的组分的试剂盒。还提供显示特别感兴趣的外源多肽的遗传包。本发明进一步提供的是使用对象显示系统的方法。

8. 发明申请

US20050009139A1 Compositions and methods for generating chimeric heteromultimers 有权
标题翻译：用于产生嵌合异源多聚体的组合物和方法
公开(公告)号：US20050009139A1
公开(公告)日：2005-01-13
申请号：US10911127
申请日：2004-08-03
申请人： Caili Wang , Pingyu Zhong , Shengjiang Liu , Peizhi Luo , Shengfeng Li , Xinwei Wang
发明人： Caili Wang , Pingyu Zhong , Shengjiang Liu , Peizhi Luo , Shengfeng Li , Xinwei Wang
IPC分类号： G01N33/53 , C07K14/705 , C07K16/00 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12P21/08 , G01N33/566 , C12P21/02 , C07H21/04 , C07K16/44 , C12N5/06
CPC分类号： C07K16/00 , C07K2317/56 , C07K2319/00
摘要： The present invention provides a technique for specific assembly of monomeric polypeptides to form a heteromultimer. This technique is particularly useful for generating a genetically diverse repertoire of heteromultimers such as antigen-binding units. The invention also provides both non-single-chain and single-chain antigen-binding units that are assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subject antigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.
摘要翻译：本发明提供了用于特异性组装单体多肽以形成异源多聚体的技术。该技术对于产生诸如抗原结合单位的异源多聚体的遗传多样性谱特别有用。本发明还提供通过本文所述技术组装的非单链和单链抗原结合单元。本发明还提供重组多核苷酸，载体，宿主细胞和用于产生受试者抗原结合单位的试剂盒。本发明进一步提供的是使用受试者抗原结合单元的方法。

9. 发明授权

US08802827B2 AX1 PCSK9 antagonists 有权
标题翻译： AX1 PCSK9拮抗剂
公开(公告)号：US08802827B2
公开(公告)日：2014-08-12
申请号：US13503726
申请日：2010-10-29
申请人： Peter Peizhi Luo , Kevin Caili Wang , Pingyu Zhong , Mark Hsieh , Yan Li , Xinwei Wang , Feng Dong , Andrei Golosov , Yan Ni , Weirong Wang , Laurence B. Peterson , Rose Cubbon
发明人： Peter Peizhi Luo , Kevin Caili Wang , Pingyu Zhong , Mark Hsieh , Yan Li , Xinwei Wang , Feng Dong , Andrei Golosov , Yan Ni , Weirong Wang , Laurence B. Peterson , Rose Cubbon
IPC分类号： C07K16/40 , C07K16/00 , A61K39/395
CPC分类号： C07K16/40 , C07K2317/21 , C07K2317/34 , C07K2317/41 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/90 , C07K2317/92 , C07K2317/94
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。

10. 发明授权

US08877900B2 AX132 PCSK9 antagonists 有权
标题翻译： AX132 PCSK9拮抗剂
公开(公告)号：US08877900B2
公开(公告)日：2014-11-04
申请号：US13503729
申请日：2010-10-29
申请人： Peter Peizhi Luo , Kevin Caili Wangr , Pingyu Zhong , Mark Hsieh , Yan Li , Xinwei Wang , Feng Dong , Andrei Golosov , Yan Ni , Weirong Wang , Laurence B. Peterson , Rose Cubbon , Sujata Sharma , Jon Condra , Jun Lu , Gopalakrishnan Parthasarathy , Stephen Soisson , Noel Byrne
发明人： Peter Peizhi Luo , Kevin Caili Wangr , Pingyu Zhong , Mark Hsieh , Yan Li , Xinwei Wang , Feng Dong , Andrei Golosov , Yan Ni , Weirong Wang , Laurence B. Peterson , Rose Cubbon , Sujata Sharma , Jon Condra , Jun Lu , Gopalakrishnan Parthasarathy , Stephen Soisson , Noel Byrne
IPC分类号： C07K16/40 , C07K16/00 , A61K39/395
CPC分类号： C07K16/40 , C07K2299/00 , C07K2317/21 , C07K2317/52 , C07K2317/55 , C07K2317/76 , C07K2317/94 , C07K2319/00
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。

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