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1. 发明申请

WO2003058197A2 DETECTION OF MOLECULAR INTERACTIONS BY BETA-LACTAMASE REPORTER FRAGMENT COMPLEMENTATION 审中-公开
标题翻译：通过BETA-LACTAMASE报告片段补体检测分子相互作用
公开(公告)号：WO2003058197A2
公开(公告)日：2003-07-17
申请号：PCT/US2002/041587
申请日：2002-12-26
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , BLAU, Helen, M. , BALINT, Robert, F. , WEHRMAN, Thomas, S. , HER, Jeng-Horng
发明人： BLAU, Helen, M. , BALINT, Robert, F. , WEHRMAN, Thomas, S. , HER, Jeng-Horng
IPC分类号： G01N
CPC分类号： G01N33/542 , G01N2333/986
摘要： Methods and compositions for detecting molecular interactions, particularly, protein-protein interactions, using at least two inactive, weakly-complementing ß-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-ßlactamase fragments. Association of the molecules of interest brings the corresponding complementary ß-lactamase fragments into close enough proximity for complementation to occur and ß-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。提供的方法利用包含目标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的新型组合物。关联分子的关联使相应的互补的β-内酰胺酶片段足够接近以进行互补发生，并观察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。

2. 发明申请

WO9730150A3 MOLECULES FOR THE INDUCTION OF IMMUNOLOGICAL TOLERANCE 审中-公开
标题翻译：诱导免疫耐受性的分子
公开(公告)号：WO9730150A3
公开(公告)日：1997-10-09
申请号：PCT/EP9700777
申请日：1997-02-17
申请人： PANGENETICS BV , BALINT ROBERT F , WAUBEN MARCA HENRIETTE MICHAEL
发明人： BALINT ROBERT F , WAUBEN MARCA HENRIETTE MICHAEL
IPC分类号： A61K38/00 , C07K14/47 , C12N15/01 , C12N15/10 , A61K38/17
CPC分类号： C12N15/1058 , A61K38/00 , C07K14/4713 , C12N15/102
摘要： The invention relates to a population of protein molecules having a distribution of specific mutations in the amino acid sequence as compared to a parent protein, which population of protein molecules is obtainable by establishing the parental amino acid sequence of the protein to be mutated and deriving therefrom a parental nucleotide sequence encoding the amino acid sequence, optionally selecting sites within this parental amino acid sequence, mutation of which is more desirable or less desirable, designing overlapping oligonucleotides encoding parts of the protein and harbouring one or more codon changes as compared to the corresponding parental nucleotide sequence, composing of the overlapping oligonucleotides a population of mutated nucleotide sequences encoding mutated versions of the parent protein thus establishing a library, and expressing the mutated versions of the mutated nucleotide sequences to obtain a population of mutated proteins.

3. 发明申请

WO1997030150A2 MOLECULES FOR THE INDUCTION OF IMMUNOLOGICAL TOLERANCE 审中-公开
标题翻译：诱导免疫耐受性的分子
公开(公告)号：WO1997030150A2
公开(公告)日：1997-08-21
申请号：PCT/EP1997000777
申请日：1997-02-17
申请人： PANGENETICS B.V. , BALINT, Robert, F. , WAUBEN, Marca, Henriëtte, Michaela
发明人： PANGENETICS B.V.
IPC分类号： C12N15/01
CPC分类号： C12N15/1058 , A61K38/00 , C07K14/4713 , C12N15/102
摘要： The invention relates to a population of protein molecules having a distribution of specific mutations in the amino acid sequence as compared to a parent protein, which population of protein molecules is obtainable by establishing the parental amino acid sequence of the protein to be mutated and deriving therefrom a parental nucleotide sequence encoding the amino acid sequence, optionally selecting sites within this parental amino acid sequence, mutation of which is more desirable or less desirable, designing overlapping oligonucleotides encoding parts of the protein and harbouring one or more codon changes as compared to the corresponding parental nucleotide sequence, composing of the overlapping oligonucleotides a population of mutated nucleotide sequences encoding mutated versions of the parent protein thus establishing a library, and expressing the mutated versions of the mutated nucleotide sequences to obtain a population of mutated proteins.
摘要翻译：本发明涉及与亲本蛋白相比具有氨基酸序列中特异性突变分布的蛋白质分子群体，蛋白质分子的群体可以通过建立待突变的蛋白质的亲本氨基酸序列并从其衍生得到编码氨基酸序列的亲本核苷酸序列，任选地选择该亲本氨基酸序列内的位点，其突变是更期望的或不理想的，设计与编码蛋白质部分并且与相应的蛋白质相比具有一个或多个密码子变化的重叠寡核苷酸亲本核苷酸序列，构成重叠寡核苷酸，编码突变型母体蛋白的突变核苷酸序列群，从而建立文库，并表达突变型突变型核苷酸序列以获得突变型蛋白质群体。

4. 发明申请

WO2009079618A1 ENZYME ENGINEERING SYSTEMS AND METHODS 审中-公开
标题翻译： ENZYME工程系统与方法
公开(公告)号：WO2009079618A1
公开(公告)日：2009-06-25
申请号：PCT/US2008/087342
申请日：2008-12-18
申请人： CYTODESIGN, INC. , BALINT, Robert F. , HER, Jeng-Horng
发明人： BALINT, Robert F. , HER, Jeng-Horng
IPC分类号： G01N33/53 , C12P21/06 , C40B40/10
CPC分类号： C12N15/1086 , C12Q1/37 , G01N33/573 , G01N2333/95
摘要： The invention relates to cell-based biosensors of proteolytic activity and methods for using them to engineer desired proteolytic activities into proteins such as antibodies. In one embodiment of the invention, the biosensor is comprised of a target polypeptide linked to an auto-inhibited reporter in such a manner that cleavage of the target leads to activation of the reporter. The preferred reporter confers a selectable phenotype on cells expressing both the biosensor and any member of a population of candidate proteases which efficiently and specifically cleaves the target. The selectable phenotype allows candidates with desired target-cleaving activities to be recovered efficiently from large populations of candidates.
摘要翻译：本发明涉及蛋白水解活性的基于细胞的生物传感器以及使用它们将期望的蛋白水解活性加工成蛋白质如抗体的方法。在本发明的一个实施方案中，生物传感器以与自身抑制的报告物连接的靶多肽包含，使靶标的切割导致报告物的活化。优选的记录者在表达生物传感器和候选蛋白酶群体的任何成员的细胞上赋予可选择的表型，其有效且特异性地切割靶标。可选择的表型允许从大量候选者有效地回收具有期望的靶切割活性的候选物。

5. 发明申请

WO2005069970A3 ANTIBODY SPECIFICITY TRANSFER USING MINIMAL ESSENTIAL BINDING DETERMINANTS 审中-公开
标题翻译：使用最小限度绑定决定因素的抗体特异性转移
公开(公告)号：WO2005069970A3
公开(公告)日：2009-03-12
申请号：PCT/US2005002072
申请日：2005-01-20
申请人： KALOBIOS INC , FLYNN PETER , LUEHRSEN KENNETH , BALINT ROBERT F , HER JENG-HORNG , BEBBINGTON CHRISTOPHER R , YARRANTON GEOFFREY T
发明人： FLYNN PETER , LUEHRSEN KENNETH , BALINT ROBERT F , HER JENG-HORNG , BEBBINGTON CHRISTOPHER R , YARRANTON GEOFFREY T
IPC分类号： G01N33/53 , C07K16/00 , C07K16/12 , C07K16/44 , C12N5/06 , C12N15/09 , C12P21/06 , C12Q1/70
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。

6. 发明申请

WO2005069970A2 ANTIBODY SPECIFICITY TRANSFER USING MINIMAL ESSENTIAL BINDING DETERMINANTS 审中-公开
标题翻译：使用最小限度绑定决定因素的抗体特异性转移
公开(公告)号：WO2005069970A2
公开(公告)日：2005-08-04
申请号：PCT/US2005/002072
申请日：2005-01-20
申请人： KALOBIOS, INC. , FLYNN, Peter , LUEHRSEN, Kenneth , BALINT, Robert, F. , HER, Jeng-Horng , BEBBINGTON, Christopher, R. , YARRANTON, Geoffrey, T.
发明人： FLYNN, Peter , LUEHRSEN, Kenneth , BALINT, Robert, F. , HER, Jeng-Horng , BEBBINGTON, Christopher, R. , YARRANTON, Geoffrey, T.
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。本发明还提供了根据该方法制备的文库和抗体。

7. 发明申请

WO2004072266A2 ANTIBODY AFFINITY ENGINEERING BY SERIAL EPITOPE-GUIDED COMPLEMENTARITY REPLACEMENT 审中-公开
标题翻译：通过串联EPITOPE引导的补充替代物的抗体活性工程
公开(公告)号：WO2004072266A2
公开(公告)日：2004-08-26
申请号：PCT/US2004/004232
申请日：2004-02-13
申请人： KALOBIOS INC. , HER, Jeng-Horng , BALINT, Robert, F.
发明人： HER, Jeng-Horng , BALINT, Robert, F.
IPC分类号： C12N
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。

8. 发明申请

WO2003069312A3 MOLECULAR SENSORS BY COMPETITIVE ACTIVATION 审中-公开
公开(公告)号：WO2003069312A3
公开(公告)日：2003-08-21
申请号：PCT/US2003/004928
申请日：2003-02-14
申请人： KALOBIOS, INC. , BALINT, Robert, F. , HER, Jeng-Horng
发明人： BALINT, Robert, F. , HER, Jeng-Horng
IPC分类号： C12Q1/68
摘要： The current invention provides methods and systems for detecting the presence of a target molecule either in vitro or in vivo . The systems of the invention comprise interacting components, a reporter and a low-affinity inhibitor of the reporter, each of which is fused to a member of a binding pair. A target molecule that interferes with binding of the binding pair members can therefore be identified by detecting activation of the reporter molecule.

9. 发明申请

WO0236738A3 AFFINITY MATURATION BY COMPETITIVE SELECTION 审中-公开
标题翻译：竞争性选择的亲和力成熟
公开(公告)号：WO0236738A3
公开(公告)日：2002-07-04
申请号：PCT/US0145371
申请日：2001-10-30
申请人： HORIZON BIOTECHNOLOGIES INC , BALINT ROBERT F , HER JENG-HORNG , LARRICK JAMES W
发明人： BALINT ROBERT F , HER JENG-HORNG , LARRICK JAMES W
IPC分类号： G01N33/50 , C12N1/21 , C12N15/09 , C12N15/10 , C12Q1/02 , C12Q1/68 , C40B30/04 , G01N33/15 , G01N33/566 , G01N33/68 , A61K38/00 , C07H21/04 , C12N15/00 , C12N15/34 , C12N15/63 , C12N15/70 , G01N33/53 , G01N33/537 , G01N33/543 , G01N33/567
CPC分类号： C40B30/04 , C12N15/1055 , C12Q1/02 , G01N33/6845 , G01N33/6854
摘要： The present invention provides a method of selecting binding pair members with enhanced binding affinity for the cognate binding partner relative to a reference binding pair member (see Figure 2). In particular, the invention provides methods of selecting antibodies with enhanced affinity for antigen relative to a reference antibody. This process, "affinity maturation", thereby provides antibodies with superior binding capabilities.
摘要翻译：本发明提供了选择具有增强的同源结合伴侣相对于参考结合对成员的结合亲和力的结合对成员的方法（参见图2）。特别地，本发明提供了相对于参照抗体选择具有增强的抗原亲和力的抗体的方法。该方法“亲和力成熟”，从而为抗体提供优异的结合能力。

10. 发明申请

WO2004072266A3 ANTIBODY AFFINITY ENGINEERING BY SERIAL EPITOPE-GUIDED COMPLEMENTARITY REPLACEMENT 审中-公开
标题翻译：通过串联EPITOPE引导的补充替代物的抗体活性工程
公开(公告)号：WO2004072266A3
公开(公告)日：2006-01-26
申请号：PCT/US2004004232
申请日：2004-02-13
申请人： KALOBIOS INC , HER JENG-HORNG , BALINT ROBERT F
发明人： HER JENG-HORNG , BALINT ROBERT F
IPC分类号： A61K48/00 , C07K16/28 , C12N20060101 , C12N15/10 , C07K14/705 , C07K16/00 , C12N9/02 , C12N9/38 , C12N15/62 , C12N15/70 , C12Q1/02 , C12Q1/68 , G01N33/50 , G01N33/68
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。

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