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1. 发明授权

US07981843B2 Antibody specificity transfer using minimal essential binding determinants 有权
标题翻译：使用最小必需结合决定簇的抗体特异性转移
公开(公告)号：US07981843B2
公开(公告)日：2011-07-19
申请号：US11040159
申请日：2005-01-20
申请人： Peter Flynn , Kenneth Luehrsen , Robert F. Balint , Jeng-Horng Her , Christopher R. Bebbington , Geoffrey T. Yarranton
发明人： Peter Flynn , Kenneth Luehrsen , Robert F. Balint , Jeng-Horng Her , Christopher R. Bebbington , Geoffrey T. Yarranton
IPC分类号： C40B30/04 , C07H21/04
CPC分类号： C07K16/00 , A61K2039/505 , C07K16/1214 , C07K2317/21 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/92
摘要： The present invention provides methods of making antibodies having the binding specificity of a reference antibody. Antibodies generated by the methods of the inventions have at least one minimal essential binding specificity determinant from a heavy chain or light chain CDR3 from the reference antibody. The method can be used, e.g., in humanization procedures. The invention also provides libraries and antibodies made in accordance with the methods.
摘要翻译：本发明提供了制备具有参考抗体结合特异性的抗体的方法。通过本发明的方法产生的抗体具有来自参照抗体的重链CDR1或轻链CDR3的至少一种最小的必需结合特异性决定簇。该方法可以用于例如人源化程序中。本发明还提供了根据该方法制备的文库和抗体。

2. 发明申请

US20050255552A1 Antibody specificity transfer using minimal essential binding determinants 有权
标题翻译：使用最小必需结合决定簇的抗体特异性转移
公开(公告)号：US20050255552A1
公开(公告)日：2005-11-17
申请号：US11040159
申请日：2005-01-20
申请人： Peter Flynn , Kenneth Luehrsen , Robert Balint , Jeng-Horng Her , Christopher Bebbington , Geoffrey Yarranton
发明人： Peter Flynn , Kenneth Luehrsen , Robert Balint , Jeng-Horng Her , Christopher Bebbington , Geoffrey Yarranton
IPC分类号： C07K16/00 , C07K16/12 , C07K16/44 , C12N5/06 , C12N15/09 , C12P21/06
CPC分类号： C07K16/00 , A61K2039/505 , C07K16/1214 , C07K2317/21 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/92
摘要： The present invention provides methods of making antibodies having the binding specificity of a reference antibody. Antibodies generated by the methods of the inventions have at least one minimal essential binding specificity determinant from a heavy chain or light chain CDR3 from the reference antibody. The method can be used, e.g., in humanization procedures. The invention also provides libraries and antibodies made in accordance with the methods.
摘要翻译：本发明提供了制备具有参考抗体结合特异性的抗体的方法。通过本发明的方法产生的抗体具有来自参照抗体的重链CDR1或轻链CDR3的至少一种最小的必需结合特异性决定簇。该方法可以用于例如人源化程序中。本发明还提供了根据该方法制备的文库和抗体。

3. 发明授权

US07335478B2 Reactivation-based molecular interaction sensors 失效
标题翻译：基于重新激活的分子相互作用传感器
公开(公告)号：US07335478B2
公开(公告)日：2008-02-26
申请号：US10208730
申请日：2002-07-29
申请人： Robert F. Balint , Jeng-Horng Her
发明人： Robert F. Balint , Jeng-Horng Her
IPC分类号： G01N33/53
CPC分类号： G01N33/542
摘要： This invention provides methods and systems for linking the functional activation of a responder molecule to the interaction of two or more binding ensemble members of interest either in vitro or in vivo, and thereby producing a signal, phenotype, or other functional output in response to the interaction of the binding ensemble members. The systems comprise a responder, an inhibitor of the responder, and an inhibitor of the inhibitor, or “reactivator” of the responder, and interacting components. Two binding ensemble members are complexed to the other components of the system in such a way that interaction of the binding ensemble members, either directly or via additional ensemble members, causes a shift in the equilibrium of inhibitor binding from the responder to the reactivator, thereby functionally activating the responder.
摘要翻译：本发明提供了用于将应答者分子的功能活化与体外或体内两种或更多感兴趣的结合整体成员的相互作用连接起来的方法和系统，从而产生响应于该功能的信号，表型或其他功能性输出绑定集合成员的相互作用。该系统包括应答者，应答者的抑制剂和抑制剂的抑制剂或应答者的“再激活剂”以及相互作用的组分。两个结合的整体成员以系统的其他组分复合，使得结合整体成员的直接或经由另外的整体成员的相互作用导致抑制剂结合从应答者到再活化剂的平衡的转变，由此功能激活应答者。

4. 发明授权

US07432063B2 Methods for affinity maturation 失效
标题翻译：亲和力成熟的方法
公开(公告)号：US07432063B2
公开(公告)日：2008-10-07
申请号：US10677131
申请日：2003-09-30
申请人： Robert F. Balint , Jeng-Horng Her
发明人： Robert F. Balint , Jeng-Horng Her
IPC分类号： G01N33/53 , C07H21/04
CPC分类号： G01N33/542
摘要： This invention provides methods of obtaining a binding molecule, e.g., an antibody, that has enhanced affinity for a binding partner relative to a reference binding molecule.
摘要翻译：本发明提供了获得相对于参考结合分子对结合配偶体具有增强的亲合力的结合分子例如抗体的方法。

5. 发明授权

US07544477B2 Circularly permutated, interaction-activated proteins 有权
标题翻译：循环置换的相互作用的蛋白质
公开(公告)号：US07544477B2
公开(公告)日：2009-06-09
申请号：US09764163
申请日：2001-01-16
申请人： Robert F. Balint , Jeng-Horng Her
发明人： Robert F. Balint , Jeng-Horng Her
IPC分类号： C40B30/08 , C40B30/04
CPC分类号： G01N33/6842 , C07K16/00 , C07K16/2878 , C07K16/32 , C07K2317/622 , C07K2319/00 , C12N9/0036 , C12N15/1055 , G01N33/535 , G01N33/6803 , G01N2333/986
摘要： Interaction-activated circularly permutated proteins are disclosed that depend for their functional reassembly into the parent protein on the interaction of heterologous polypeptides or other molecules which have been genetically or chemically conjugated to the break-point termini of engineered enzymes. In addition, methods are provided for identifying circularly permutated marker proteins that will optimally reassemble into a functional parent protein, and which are dependent on the association of heterologous interactor domains. The invention is exemplified by circular permutations of a Class A β-lactamase (TEM-1 of E. coli). Circularly permutated marker proteins that comprise molecular interaction-dependent enzymes particularly find use in (1) cell-based sensors for activation or inhibition of metabolic or signal transduction pathways for high-efficiency, (2) high-throughput screening for agonists/antagonists of the target pathway and in high-throughput mapping of pair-wise protein-protein interactions within and between the proteomes of cells, tissues, and pathogenic organisms, and in (3) cell-based screens for high-throughput selection of inhibitors of any protein-protein interaction.
摘要翻译：公开了相互作用激活的环状置换的蛋白质，其依赖于将异源多肽或已经在遗传或化学上缀合至工程化酶的断点末端的其它分子的相互作用上将其功能重新组装到母体蛋白质中。另外，提供了用于鉴定循环置换的标记蛋白的方法，其将最佳地重新组装成功能亲本蛋白，并且这取决于异源相互作用域的缔合。本发明以A类β-内酰胺酶（大肠杆菌的TEM-1）的圆形排列为例。包括分子相互作用依赖性酶的循环置换标记蛋白特别适用于（1）基于细胞的传感器，用于激活或抑制代谢或信号转导途径，用于高效率，（2）高通量筛选激动剂/拮抗剂目标途径以及在细胞，组织和致病生物体的蛋白质组之间和之间的成对蛋白质 - 蛋白质相互作用的高通量测绘中，以及（3）基于细胞的筛选，用于高通量选择任何蛋白质 - 蛋白质相互作用。

6. 发明授权

US08148110B2 Detection of molecular interactions by β-lactamase reporter fragment complementation 有权
标题翻译：通过β-内酰胺酶报道片段互补检测分子相互作用
公开(公告)号：US08148110B2
公开(公告)日：2012-04-03
申请号：US10330811
申请日：2002-12-26
申请人： Helen M. Blau , Robert F. Balint , Thomas S. Wehrman , Jeng-Horng Her
发明人： Helen M. Blau , Robert F. Balint , Thomas S. Wehrman , Jeng-Horng Her
IPC分类号： C12P21/04
CPC分类号： C12Q1/34 , G01N33/542 , G01N2333/986
摘要： Methods and compositions for detecting molecular interactions, particularly protein-protein interactions, using at least two inactive, weakly-complementing β-lactamase fragments are provided. The invention allows detection of such interactions in eukaryotic and mammalian cells, in situ or in vitro. Detection of molecular interactions in mammalian cells is not limited to the nuclear compartment, but can be accomplished in the cytoplasm, cell surface, organelles, or between these entities. Methods provided utilize novel compositions comprising fusion proteins between molecules of interest and inactive, weakly-complementing β-lactamase fragments. Association of the molecules of interest brings the corresponding complementary β-lactamase fragments into close enough proximity for complementation to occur and β-lactamase activity to be observed. The invention is useful in the study of protein-protein interactions, functional genomics, agonist and antagonist screening and drug discovery.
摘要翻译：提供了使用至少两个无活性的弱互补的β-内酰胺酶片段来检测分子相互作用，特别是蛋白质 - 蛋白质相互作用的方法和组合物。本发明允许在原位或体外在真核和哺乳动物细胞中检测这种相互作用。哺乳动物细胞中分子相互作用的检测不限于核隔室，而是可以在细胞质，细胞表面，细胞器或这些实体之间完成。提供的方法利用了新型组合物，其包含感兴趣的分子和无活性的弱互补的β-内酰胺酶片段之间的融合蛋白。关联分子的关联使相应的互补和β-内酰胺酶片段足够接近以进行补体发生和观察β-内酰胺酶活性。本发明可用于研究蛋白质 - 蛋白质相互作用，功能基因组学，激动剂和拮抗剂筛选和药物发现。

7. 发明申请

US20120219968A1 GPCR Expressing Cell Lines and Antibodies 审中-公开
标题翻译： GPCR表达细胞系和抗体
公开(公告)号：US20120219968A1
公开(公告)日：2012-08-30
申请号：US13470665
申请日：2012-05-14
申请人： Helena S. Mancebo , Jeng-Horng Her , Samuel X. Li , Jianfu L. Wang
发明人： Helena S. Mancebo , Jeng-Horng Her , Samuel X. Li , Jianfu L. Wang
IPC分类号： G01N33/566 , G01N21/64 , G01N33/577
CPC分类号： C07K14/705 , G01N2800/52
摘要： The present invention provides expression vectors that facilitate high levels of expression of GPCR proteins. Encompassed by the invention are methods and compositions for recombinant cell lines expressing GPCR proteins with the aid of the expression vectors of the instant invention. The recombinant cell lines of the instant invention express GPCR proteins at levels of at least about 150,000 copies of the protein per cell. The present invention also provides methods and compositions for raising antibodies against GPCR proteins using the high expressing recombinant cells of the instant invention.
摘要翻译：本发明提供促进GPCR蛋白表达水平高的表达载体。本发明所涵盖的是借助于本发明的表达载体表达GPCR蛋白的重组细胞系的方法和组合物。本发明的重组细胞系以每个细胞至少约15万拷贝的蛋白质的量表达GPCR蛋白质。本发明还提供使用本发明的高表达重组细胞提高针对GPCR蛋白的抗体的方法和组合物。

8. 发明申请

US20100330591A1 GPCR Expressing Cell Lines and Antibodies 有权
标题翻译： GPCR表达细胞系和抗体
公开(公告)号：US20100330591A1
公开(公告)日：2010-12-30
申请号：US12820987
申请日：2010-06-22
申请人： Helena S. Mancebo , Jeng-Horng Her , Samuel X. Li , Jianfu L. Wang
发明人： Helena S. Mancebo , Jeng-Horng Her , Samuel X. Li , Jianfu L. Wang
IPC分类号： G01N33/53 , C12N15/63 , C12N5/10 , C12P21/00
CPC分类号： G01N33/68 , G01N33/5008 , G01N33/502 , G01N33/6845 , G01N33/6851 , G01N2333/726 , G01N2500/00 , G01N2800/52
摘要： The present invention provides expression vectors that facilitate high levels of expression of GPCR proteins. Encompassed by the invention are methods and compositions for recombinant cell lines expressing GPCR proteins with the aid of the expression vectors of the instant invention. The recombinant cell lines of the instant invention express GPCR proteins at levels of at least about 150,000 copies of the protein per cell. The present invention also provides methods and compositions for raising antibodies against GPCR proteins using the high expressing recombinant cells of the instant invention.
摘要翻译：本发明提供促进GPCR蛋白表达水平高的表达载体。本发明所涵盖的是借助于本发明的表达载体表达GPCR蛋白的重组细胞系的方法和组合物。本发明的重组细胞系以每个细胞至少约15万拷贝的蛋白质的量表达GPCR蛋白质。本发明还提供使用本发明的高表达重组细胞提高针对GPCR蛋白的抗体的方法和组合物。

9. 发明申请

US20050008625A1 Antibody affinity engineering by serial epitope-guided complementarity replacement 审中-公开
标题翻译：通过连续表位引导互补替代的抗体亲和力工程
公开(公告)号：US20050008625A1
公开(公告)日：2005-01-13
申请号：US10778726
申请日：2004-02-13
申请人： Robert Balint , Jeng-Horng Her
发明人： Robert Balint , Jeng-Horng Her
IPC分类号： A61K48/00 , C07K16/28 , C12N20060101
CPC分类号： C07K16/2878 , C07K2317/21 , C07K2317/55
摘要： This invention provides for a novel means for obtaining human idiologs for any non-human antibody to any target by epitope guided replacement of variable regions using competitive cell-based methods in which the competitor can be either the reference antibody or a ligand that binds to the same epitope on the target as the reference antibody.
摘要翻译：本发明提供了一种用于通过使用基于竞争性细胞的方法的表位引导替换可变区获得对任何靶的任何非人抗体的人类特征的新手段，其中竞争者可以是参照抗体或与其结合的配体靶标上与参照抗体相同的表位。

10. 发明授权

US08178346B2 GPCR expression vector 有权
标题翻译： GPCR表达载体
公开(公告)号：US08178346B2
公开(公告)日：2012-05-15
申请号：US12820987
申请日：2010-06-22
申请人： Helena S. Mancebo , Jeng-Horng Her , Samuel X. Li , Jianfu L. Wang
发明人： Helena S. Mancebo , Jeng-Horng Her , Samuel X. Li , Jianfu L. Wang
IPC分类号： C12N15/00 , C12N1/20 , C12N5/00 , C12N5/02 , C12N15/74 , C12P21/06 , C07K1/00 , C07K14/00 , C07K17/00
CPC分类号： G01N33/68 , G01N33/5008 , G01N33/502 , G01N33/6845 , G01N33/6851 , G01N2333/726 , G01N2500/00 , G01N2800/52
摘要： The present invention provides expression vectors that facilitate high levels of expression of GPCR proteins. Encompassed by the invention are methods and compositions for recombinant cell lines expressing GPCR proteins with the aid of the expression vectors of the instant invention. The recombinant cell lines of the instant invention express GPCR proteins at levels of at least about 150,000 copies of the protein per cell. The present invention also provides methods and compositions for raising antibodies against GPCR proteins using the high expressing recombinant cells of the instant invention.
摘要翻译：本发明提供促进GPCR蛋白表达水平高的表达载体。本发明所涵盖的是借助于本发明的表达载体表达GPCR蛋白的重组细胞系的方法和组合物。本发明的重组细胞系以每个细胞至少约15万拷贝的蛋白质的量表达GPCR蛋白质。本发明还提供使用本发明的高表达重组细胞提高针对GPCR蛋白的抗体的方法和组合物。

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