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1. 发明申请

WO2003099999A3 GENERATION AND SELECTION OF PROTEIN LIBRARY IN SILICO 审中-公开
公开(公告)号：WO2003099999A3
公开(公告)日：2003-12-04
申请号：PCT/US2003/016037
申请日：2003-05-20
申请人： ABMAXIS, INC. , LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
发明人： LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
IPC分类号： G06F19/00
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.

2. 发明申请

WO2003099999A2 GENERATION AND SELECTION OF PROTEIN LIBRARY IN SILICO 审中-公开
标题翻译：生成和选择硅胶中的蛋白质图书馆
公开(公告)号：WO2003099999A2
公开(公告)日：2003-12-04
申请号：PCT/US2003/016037
申请日：2003-05-20
申请人： ABMAXIS, INC. , LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
发明人： LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
IPC分类号： C12N
CPC分类号： C40B50/02 , C07K16/00 , C07K16/22 , C07K2317/24 , C07K2317/622 , C07K2319/00 , G06F19/18 , G06F19/22
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。

3. 发明申请

WO2003012069A2 COMPOSITIONS AND METHODS FOR GENERATING CHIMERIC HETEROMULTIMERS 审中-公开
标题翻译：组合物和方法用于生成CHIMERIC HETERMULTIMERS
公开(公告)号：WO2003012069A2
公开(公告)日：2003-02-13
申请号：PCT/US2002/024582
申请日：2002-07-31
申请人： ABMAXIS, INC. , WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
发明人： WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
IPC分类号： C12N
CPC分类号： C07K16/00 , C07K2317/56 , C07K2319/00
摘要： The present invention provides a technique for specific assembly of monomericpolypeptides to form a heteromultimer. This technique is particularly useful for generatinga genetically diverse repertoire of heteromultimers such as antigen-binding units. Theinvention also provides both non-single-chain and single-chain antigen-binding units thatare assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subjectantigen-binding units. Further provided by the invention are methods of using thesubject 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。这种技术对于产生异源多聚体如抗原结合单位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主要抗原结合单元的试剂盒。本发明进一步提供的是使用主题抗原结合单元的方法。

4. 发明申请

WO2003012069A3 COMPOSITIONS AND METHODS FOR GENERATING CHIMERIC HETEROMULTIMERS 审中-公开
公开(公告)号：WO2003012069A3
公开(公告)日：2003-02-13
申请号：PCT/US2002/024582
申请日：2002-07-31
申请人： ABMAXIS, INC. , WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
发明人： WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
IPC分类号： C07K16/00
摘要： The present invention provides a technique for specific assembly of monomericpolypeptides 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 subjectantigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.

5. 发明申请

WO2003060065A3 ADAPTER-DIRECTED DISPLAY SYSTEM 审中-公开
公开(公告)号：WO2003060065A3
公开(公告)日：2003-07-24
申请号：PCT/US2002/035287
申请日：2002-11-01
申请人： ABMAXIS, INC. , WANG, Caili , ZHONG, Pingyu , WANG, Xinwei
发明人： WANG, Caili , ZHONG, Pingyu , WANG, Xinwei
IPC分类号： C12N15/00
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.

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