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1. 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。

2. 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。

3. 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。

4. 发明申请

US20110124528A1 Generation and affinity maturation of antibody library in silico 审中-公开
标题翻译：抗体库的生成和亲和力成熟
公开(公告)号：US20110124528A1
公开(公告)日：2011-05-26
申请号：US12916077
申请日：2010-10-29
申请人： Peizhi Luo , Mark Hsieh , Pingyu Zhong , Caili Wang , Yicheng Cao , Shengjiang Liu
发明人： Peizhi Luo , Mark Hsieh , Pingyu Zhong , Caili Wang , Yicheng Cao , Shengjiang Liu
IPC分类号： C40B50/02
CPC分类号： C07K16/22 , B01J2219/00689 , B01J2219/00695 , B01J2219/007 , B01J2219/00725 , C07K16/00 , C07K2299/00 , C07K2317/21 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C40B40/10 , G16B35/00 , G16C20/60
摘要： The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.
摘要翻译：本发明提供了一种用于有效地产生和筛选具有所需生物学功能的优化蛋白质的蛋白质文库的方法，例如改善对生物和/或治疗重要的靶分子的结合亲和力。该过程以高通量方式通过开发不断扩大的所有生物体，特别是人的蛋白质序列数据库进行。在一个实施方案中，构建设计蛋白质文库的方法，包括以下步骤：提供衍生自铅蛋白的氨基酸序列，所述氨基酸序列指定为引导序列; 将引导序列与多个测试蛋白序列进行比较; 以及从所述多个测试蛋白序列中选择与所述引物序列具有至少15％序列同一性的至少两个肽片段，所选择的肽片段形成命中文库; 并通过用命中库替换引导序列形成设计蛋白质的文库。设计的蛋白质文库可以在体外或体内表达，以产生重组蛋白文库，该文库可以筛选出超过铅蛋白质的新的或改进的功能，例如针对治疗重要靶标的抗体。

5. 发明申请

US20070037214A1 Generation and selection of protein library in silico 审中-公开
标题翻译：蛋白质库的生成和选择
公开(公告)号：US20070037214A1
公开(公告)日：2007-02-15
申请号：US11502838
申请日：2006-08-10
申请人： Peizhi Luo , Mark Hsieh , Pingyu Zhong , Caili Wang , Yicheng Cao , Shengjiang Liu
发明人： Peizhi Luo , Mark Hsieh , Pingyu Zhong , Caili Wang , Yicheng Cao , Shengjiang Liu
IPC分类号： C40B30/06 , C40B40/10
CPC分类号： C07K16/22 , B01J2219/00689 , B01J2219/00695 , B01J2219/007 , B01J2219/00725 , C07K16/00 , C07K2299/00 , C07K2317/21 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C40B40/10 , G16B35/00 , G16C20/60
摘要： The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.
摘要翻译：本发明提供了一种用于有效地产生和筛选具有所需生物学功能的优化蛋白质的蛋白质文库的方法，例如改善对生物和/或治疗重要的靶分子的结合亲和力。该过程以高通量方式通过开发不断扩大的所有生物体，特别是人的蛋白质序列数据库进行。在一个实施方案中，构建设计蛋白质文库的方法，包括以下步骤：提供衍生自铅蛋白的氨基酸序列，所述氨基酸序列指定为引导序列; 将引导序列与多个测试蛋白序列进行比较; 以及从所述多个测试蛋白序列中选择与所述引物序列具有至少15％序列同一性的至少两个肽片段，所选择的肽片段形成命中文库; 并通过用命中库替换引导序列形成设计蛋白质的文库。设计的蛋白质文库可以在体外或体内表达，以产生重组蛋白文库，该文库可以筛选出超过铅蛋白质的新的或改进的功能，例如针对治疗重要靶标的抗体。

6. 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。

7. 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。

8. 发明授权

US08637435B2 Eukaryotic cell display systems 有权
标题翻译：真核细胞显示系统
公开(公告)号：US08637435B2
公开(公告)日：2014-01-28
申请号：US12291889
申请日：2008-11-14
申请人： Kevin Caili Wang , Peter Peizhi Luo , Pingyu Zhong , Jian Wang
发明人： Kevin Caili Wang , Peter Peizhi Luo , Pingyu Zhong , Jian Wang
IPC分类号： C40B40/02 , C40B50/06
CPC分类号： C12N15/1037 , C40B40/02
摘要： The present invention provides expression vectors and helper display vectors which can be used in various combinations as vector sets for display of polypeptides on the outer surface of eukaryotic host cells. The expression vector of the invention can be used alone for soluble expression without having to change or reengineer the display vectors. The display systems of the invention are particularly useful for displaying a genetically diverse repertoire or library of polypeptides on the surface of yeast cells, and mammalian cells.
摘要翻译：本发明提供了可用于各种组合的表达载体和辅助显示载体，作为用于在真核宿主细胞的外表面上显示多肽的载体组。本发明的表达载体可以单独用于可溶性表达，而不必改变或重新构建显示载体。本发明的显示系统特别可用于在酵母细胞和哺乳动物细胞的表面上显示遗传多样的多肽或多肽文库。

9. 发明申请

US20090136523A1 ANTI-CD26 ANTIBODIES AND METHODS OF USE THEREOF 有权
标题翻译：抗CD26抗体及其使用方法
公开(公告)号：US20090136523A1
公开(公告)日：2009-05-28
申请号：US12263919
申请日：2008-11-03
申请人： Teikichi Aoyagi , Peter Peizhi Luo , Pingyu Zhong , Mark Hsieh , Yan Li , Kevin Caili Wang , Chikao Morimoto
发明人： Teikichi Aoyagi , Peter Peizhi Luo , Pingyu Zhong , Mark Hsieh , Yan Li , Kevin Caili Wang , Chikao Morimoto
IPC分类号： A61K39/395 , C07K16/18 , C12N15/11 , C12N15/00 , C12N5/06
CPC分类号： C07K16/2896 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/92 , G01N33/574 , G01N2333/70596 , G01N2500/00 , Y02A50/473
摘要： The present invention provides novel anti-CD26 antibodies and other, related polypeptides, as well as novel polynucleotides encoding the antibodies and polypeptides. The invention also provides methods of making the antibodies and polypeptides. Compositions and cells comprising the antibodies or polypeptides are further provided. Methods of using the antibodies and/or polypeptides, such as to inhibit cell proliferation and in the treatment of conditions associated with CD26, are also provided.
摘要翻译：本发明提供新的抗CD26抗体和其它相关多肽，以及编码抗体和多肽的新型多核苷酸。本发明还提供了制备抗体和多肽的方法。进一步提供包含抗体或多肽的组合物和细胞。还提供了使用抗体和/或多肽的方法，例如抑制细胞增殖和治疗与CD26相关的病症。

10. 发明申请

US20120129702A1 Structure-Based Selection and Affinity Maturation of Antibody Library 审中-公开
标题翻译：基于结构的选择和亲和力成熟的抗体库
公开(公告)号：US20120129702A1
公开(公告)日：2012-05-24
申请号：US12914105
申请日：2010-10-28
申请人： Peizhi Luo , Mark Hsieh , Pingyu Zhong , Caili Wang
发明人： Peizhi Luo , Mark Hsieh , Pingyu Zhong , Caili Wang
IPC分类号： C40B10/00
CPC分类号： C07K16/00 , B01J2219/00689 , B01J2219/00695 , B01J2219/007 , B01J2219/00725 , C07K16/005 , C07K16/22 , C07K2299/00 , C07K2317/21 , C07K2317/24 , C07K2317/565 , C07K2317/622 , C07K2319/00 , C12N15/1089 , C40B40/10 , G16B35/00 , G16C20/60
摘要： The present invention provides a structure-based methodology for efficiently generating and screening a library of recombinant antibodies for optimized antibodies with desirable functions, such as higher binding affinity or low immunogenicity. In one embodiment, a method is provided for constructing a library of antibody sequences based on a three dimensional structure of a lead antibody. The method comprises: providing a lead structural template comprising the amino acid sequence of the variable region of the heavy chain (VH) or light chain (VL) of a lead antibody, comparing the lead template sequence with a plurality of tester protein sequences; selecting a hit library from the tester protein sequences; determining if a member of the hit library is structurally compatible with the lead structural template using a scoring function; selecting members for the hit library that score equal to or better than the lead sequence and screening members for improved function(s).
摘要翻译：本发明提供了一种基于结构的方法，用于有效地产生和筛选重组抗体文库，以获得具有所需功能的优化抗体，例如较高的结合亲和力或低免疫原性。在一个实施方案中，提供了一种基于铅抗体的三维结构构建抗体序列文库的方法。该方法包括：提供包含铅抗体的重链（VH）或轻链（VL）的可变区的氨基酸序列的引导结构模板，将引导模板序列与多个测试蛋白序列进行比较; 从测试蛋白序列中选择一个命中库; 确定命中库的成员是否使用得分函数在结构上与引导结构模板兼容; 选择得分等于或优于前导序列的命中库的成员，并筛选成员以改进功能。

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