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1. 发明申请

WO0234886A9 ISOLATION OF BINDING PROTEINS WITH HIGH AFFINITY TO LIGANDS 审中-公开
标题翻译：分离与配体具有高度亲和力的结合蛋白
公开(公告)号：WO0234886A9
公开(公告)日：2003-02-13
申请号：PCT/US0146795
申请日：2001-10-26
申请人： UNIV TEXAS , CHEN GANG , HAYHURST ANDREW , THOMAS JEFFREY G , IVERSON BRENT L , GEORGIOU GEORGE
发明人： CHEN GANG , HAYHURST ANDREW , THOMAS JEFFREY G , IVERSON BRENT L , GEORGIOU GEORGE
IPC分类号： C12N15/09 , C12N15/10 , C12N5/00
CPC分类号： C12N15/1034
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides via "display-less" library screening. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in soluble form in the periplasmic space of gram negative bacteria, such as Escherichia coli, and are mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the surface-expression of ligand fusion proteins employed with phage display.
摘要翻译：本发明通过提供一种通过“无需显示”文库筛选来分离能够结合小分子和肽的结合蛋白的快速方法克服了现有技术的不足。在该技术中，候选结合蛋白如抗体序列的文库以可溶形式在革兰氏阴性细菌如大肠杆菌的周质空间中表达，并与标记的配体混合。在表达对配体具有亲和性的重组多肽的克隆中，与结合蛋白结合的标记配体的浓度增加并且允许从文库的其余部分分离细胞。在使用靶标配体的荧光标记的情况下，可以通过荧光激活细胞分选（FACS）分离细胞。该方法比现有技术方法更快并且避免了与噬菌体展示中使用的配体融合蛋白的表面表达相关的问题。

2. 发明申请

WO0234886A3 ISOLATION OF BINDING PROTEINS WITH HIGH AFFINITY TO LIGANDS 审中-公开
标题翻译：分离具有高亲和力的结合蛋白
公开(公告)号：WO0234886A3
公开(公告)日：2003-07-31
申请号：PCT/US0146795
申请日：2001-10-26
申请人： UNIV TEXAS , CHEN GANG , HAYHURST ANDREW , THOMAS JEFFREY G , IVERSON BRENT L , GEORGIOU GEORGE
发明人： CHEN GANG , HAYHURST ANDREW , THOMAS JEFFREY G , IVERSON BRENT L , GEORGIOU GEORGE
IPC分类号： C12N15/09 , C12N15/10 , C12N5/00
CPC分类号： C12N15/1034
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides via "display-less" library screening. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in soluble form in the periplasmic space of gram negative bacteria, such as Escherichia coli, and are mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the surface-expression of ligand fusion proteins employed with phage display.
摘要翻译：本发明通过提供通过“无显示”文库筛选分离能够结合小分子和肽的结合蛋白的快速方法来克服现有技术的缺陷。在该技术中，候选结合蛋白（例如抗体序列）的文库以可溶形式表达在革兰氏阴性细菌如大肠杆菌的周质空间中，并与标记的配体混合。在表达对配体具有亲和性的重组多肽的克隆中，与结合蛋白结合的标记配体的浓度增加，并允许细胞与文库的其余部分分离。当使用靶配体的荧光标记时，可以通过荧光激活细胞分选（FACS）分离细胞。该方法比现有技术方法更快速，并避免与噬菌体展示所用配体融合蛋白的表面表达相关的问题。

3. 发明申请

WO2005103074A3 COMBINATORIAL PROTEIN LIBRARY SCREENING BY PERIPLASMIC EXPRESSION 审中-公开
标题翻译：通过外周表达组合蛋白图书馆筛选
公开(公告)号：WO2005103074A3
公开(公告)日：2006-05-04
申请号：PCT/US2005009190
申请日：2005-03-18
申请人： UNIV TEXAS , GEORGIOU GEORGE , JEONG KI JUN , IVERSON BRENT L
发明人： GEORGIOU GEORGE , JEONG KI JUN , IVERSON BRENT L
IPC分类号： C07K14/195 , C12N15/10 , C40B40/02
CPC分类号： C12N15/1086 , C07K2319/02 , C07K2319/03 , C07K2319/034 , C07K2319/21 , C12N15/1037 , C40B40/02 , G01N33/5082 , G01N33/56911 , G01N33/6803
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, may be expressed in the periplasm of gram negative bacteria with at least one target ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the ligand becomes bound and retained by the cell even after removal of the outer membrane, allowing the cell to be isolated from cells not expressing a binding polypeptide with affinity for the target ligand. The target ligand may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient screening techniques such as fluorescence activated cell sorting (FACS). The approach is more rapid and robust than prior art methods and avoids problems associated with the outer surface expression of ligand fusion proteins employed with phage display.
摘要翻译：本发明通过提供用于分离能够结合小分子和肽的结合蛋白的快速方法来克服现有技术的缺陷。在该技术中，候选结合蛋白（例如抗体序列）的文库可以用至少一种靶配体在革兰氏阴性细菌的周质中表达。在表达具有对配体具有亲和力的重组多肽的克隆中，甚至在去除外膜后，配体也被细胞结合并保留，允许细胞从不表达具有对靶配体的亲和力的结合多肽的细胞中分离。可以以多种方式检测靶配体，包括使用荧光标记的直接荧光或二次抗体，允许使用有效的筛选技术，例如荧光激活细胞分选（FACS）。该方法比现有技术方法更快速和鲁棒，并且避免与噬菌体展示使用的配体融合蛋白的外表面表达相关的问题。

4. 发明申请

WO2006137938A3 ANTIBODY FRAGMENTS FOR PROTECTION FROM PATHOGEN INFECTION AND METHODS OF USE THEREOF 审中-公开
标题翻译：用于保护病原体感染的抗体片段及其使用方法
公开(公告)号：WO2006137938A3
公开(公告)日：2009-04-16
申请号：PCT/US2005040658
申请日：2005-11-08
申请人： UNIV TEXAS AT AUSTIN , IVERSON BRENT L , GEORGIOU GEORGE , MABRY ROBERT
发明人： IVERSON BRENT L , GEORGIOU GEORGE , MABRY ROBERT
IPC分类号： C07H21/00 , A61K38/00
CPC分类号： C07K16/1278 , A61K2039/505 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/76
摘要： Methods and compositions are provided for an antibody fragment or functional fragment thereof, which fragments do not contain an Fc region. The invention also describes in vitro and in vivo treatment of a subject exposed to a pathogen, pathogen infection, or pathogen protein product by administering to the subject a therapeutically effective amount of the described antibody fragments and functional fragments thereof.
摘要翻译：提供了抗体片段或其功能片段的方法和组合物，其片段不含有Fc区。本发明还描述了暴露于病原体，病原体感染或病原体蛋白质产物的受试者的体外和体内治疗，其通过向受试者施用治疗有效量的所述抗体片段及其功能性片段。

5. 发明申请

WO2005095988A3 SELECTION OF BACTERIAL INNER-MEMBRANE ANCHOR POLYPEPTIDES 审中-公开
标题翻译：选择细菌内膜锚固多糖
公开(公告)号：WO2005095988A3
公开(公告)日：2006-03-02
申请号：PCT/US2005009009
申请日：2005-03-18
申请人： UNIV TEXAS , GEORGIOU GEORGE , HARVEY BARRETT R , JEONG KI JUN , IVERSON BRENT L
发明人： GEORGIOU GEORGE , HARVEY BARRETT R , JEONG KI JUN , IVERSON BRENT L
IPC分类号： G01N33/569 , C12N15/10 , C40B40/02 , G01N33/68
CPC分类号： C12N15/1086 , C07K2319/034 , C12N15/1037 , C40B40/02
摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FAGS).
摘要翻译：本发明克服了现有技术的缺陷，提供了一种用于分离能够将异源多肽固定在细菌内膜上的多肽的快速方法。在该技术中，候选锚多肽的文库表达为与异源多肽的融合，当与内膜结合时能够被检测。在表达功能性锚定序列的细菌中，异源多肽与内膜的外表面结合。具有功能性锚定序列的细菌可以通过除去外膜以除去非锚定的异源多肽，然后检测锚定的异源多肽来鉴定。可以以多种方式检测这样的细菌，包括使用荧光标记的直接荧光或二级抗体，允许使用有效技术，例如荧光激活细胞分选（FAGS）。

6. 发明申请

WO9849286A2 DIRECTED EVOLUTION OF ENZYMES AND ANTIBODIES 审中-公开
标题翻译：酶和抗体的指导性进化
公开(公告)号：WO9849286A2
公开(公告)日：1998-11-05
申请号：PCT/US9808714
申请日：1998-04-30
申请人： UNIV TEXAS , IVERSON BRENT , GEORGIOU GEORGE , CHEN GANG , OLSEN MARK J , DAUGHERTY PATRICK S
发明人： IVERSON BRENT , GEORGIOU GEORGE , CHEN GANG , OLSEN MARK J , DAUGHERTY PATRICK S
IPC分类号： C12N15/10 , C40B40/02 , A61K39/40 , C07K16/16 , C07K16/42 , C12N9/00 , C12N15/62 , G01N33/554
CPC分类号： C40B40/02 , C07K2319/035 , C12N15/1037
摘要： The invention relates to methods of selecting proteins, out of large libraries, having desirable characteristics. Exemplified are methods of expressing enzymes and antibodies on the surface of host cells and selecting for desired activities. These methods have the advantage of speed and ease of operation when compared with current methods. They also provide, without additional cloning, a source of significant quantities of the protein of interest.
摘要翻译：本发明涉及从具有所需特征的大型文库中选择蛋白质的方法。示例是在宿主细胞表面上表达酶和抗体并选择所需活性的方法。与当前的方法相比，这些方法具有速度快和易操作的优点。他们还提供了大量的目标蛋白质来源，无需额外的克隆。

7. 发明申请

WO9849286A9 DIRECTED EVOLUTION OF ENZYMES AND ANTIBODIES 审中-公开
标题翻译：有针对性地进化酶和抗体
公开(公告)号：WO9849286A9
公开(公告)日：1999-04-29
申请号：PCT/US9808714
申请日：1998-04-30
申请人： UNIV TEXAS , IVERSON BRENT , GEORGIOU GEORGE , CHEN GANG , OLSEN MARK J , DAUGHERTY PATRICK S
发明人： IVERSON BRENT , GEORGIOU GEORGE , CHEN GANG , OLSEN MARK J , DAUGHERTY PATRICK S
IPC分类号： C12N15/10 , C40B40/02 , A61K39/40 , C07K16/16 , C07K16/42 , C12N9/00 , C12N15/62 , G01N33/554
CPC分类号： C40B40/02 , C07K2319/035 , C12N15/1037
摘要： The invention relates to methods of selecting proteins, out of large libraries, having desirable characteristics. Exemplified are methods of expressing enzymes and antibodies on the surface of host cells and selecting for desired activities. These methods have the advantage of speed and ease of operation when compared with current methods. They also provide, without additional cloning, a source of significant quantities of the protein of interest.
摘要翻译：本发明涉及从大型文库中选择具有期望特征的蛋白质的方法。举例说明在宿主细胞表面表达酶和抗体并选择所需活性的方法。与目前的方法相比，这些方法具有速度快并且易于操作的优点。它们还提供了无需额外克隆的大量目的蛋白质的来源。

8. 发明申请

WO9856930A2 METHODS FOR PRODUCING HETEROLOGOUS DISULFIDE BOND-CONTAINING POLYPEPTIDES IN BACTERIAL CELLS 审中-公开
标题翻译：在细菌细胞中生产含有异源结合物的多肽的方法
公开(公告)号：WO9856930A2
公开(公告)日：1998-12-17
申请号：PCT/US9812004
申请日：1998-06-09
申请人： UNIV TEXAS , GEORGIOU GEORGE , QIU JI , BESSETTE PAUL , SWARTZ JAMES R
发明人： GEORGIOU GEORGE , QIU JI , BESSETTE PAUL , SWARTZ JAMES R
IPC分类号： C12N15/09 , C07K14/47 , C07K14/65 , C07K14/81 , C12N1/21 , C12N9/02 , C12N9/64 , C12N9/72 , C12N15/70 , C12P21/02
CPC分类号： C12N9/0051 , C07K14/4743 , C07K14/8117 , C12N9/6459 , C12N15/70 , C12Y304/21069
摘要： Disclosed are methods and compositions for producing heterologous disulfide bond containing polypeptides in bacterial cells. In preferred embodiments, the methods involve co-expression of a prokaryotic disulfide isomerase, such as DsbC or DsbG and a gene encoding a recombinant eukaryotic polypeptide. Exemplary polypeptides disclosed include tissue plasminogen activator.
摘要翻译：公开了用于在细菌细胞中产生含异源二硫键的多肽的方法和组合物。在优选的实施方案中，所述方法涉及原核二硫键异构酶如DsbC或DsbG的共表达和编码重组真核多肽的基因。公开的示例性多肽包括组织纤溶酶原激活剂。

9. 发明申请

WO2010051533A3 COMPOSITIONS OF ENGINEERED HUMAN ARGINASES AND METHODS FOR TREATING CANCER 审中-公开
标题翻译：工程人员的组成和治疗癌症的方法
公开(公告)号：WO2010051533A3
公开(公告)日：2010-08-19
申请号：PCT/US2009062969
申请日：2009-11-02
申请人： UNIV TEXAS , GEORGIOU GEORGE , STONE EVERETT
发明人： GEORGIOU GEORGE , STONE EVERETT
IPC分类号： C12N9/50 , A61K38/48 , A61P35/00 , C07K19/00 , C12N15/57 , C12N15/62
CPC分类号： A61K38/50 , A61K33/24 , A61K38/00 , A61K47/48215 , A61K47/60 , C12N9/78 , C12Y305/03001
摘要： Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.
摘要翻译：描述了用于治疗癌症的组合物和方法，更优选地描述了在精氨酸琥珀酸合成酶中不表达或以其它方式缺乏的癌症的治疗，其中所述酶在血清中消耗L-精氨酸。在一个实施方案中，本发明考虑了与天然人精氨酸酶I相比，包含至少一个氨基酸取代和金属辅因子的精氨酸酶蛋白，例如人精氨酸酶I蛋白，所述蛋白质包含增加的催化活性。

10. 发明申请

WO2011146514A3 RAPID ISOLATION OF MONOCLONAL ANTIBODIES FROM ANIMALS 审中-公开
标题翻译：从动物快速分离单克隆抗体
公开(公告)号：WO2011146514A3
公开(公告)日：2012-11-22
申请号：PCT/US2011036852
申请日：2011-05-17
申请人： UNIV TEXAS , REDDY SAI , GE XIN , BOUTZ DANNY , ELLINGTON ANDREW D , MARCOTTE EDWARD M , LAVINDER JASON , GEORGIOU GEORGE
发明人： REDDY SAI , GE XIN , BOUTZ DANNY , ELLINGTON ANDREW D , MARCOTTE EDWARD M , LAVINDER JASON , GEORGIOU GEORGE
IPC分类号： G01N33/68 , C07K16/18 , C12Q1/68
CPC分类号： G06F19/24 , C07K16/065 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/92 , C12Q1/6881 , C12Q2600/16 , C40B30/04 , G01N33/6857
摘要： Methods and compositions for identification of candicate antigen-specific variable regions as well as generation of antibodies or antigen-binding fragments that could have desired antigen specificity are provided. For example, in certain aspects methods for determining amino acid sequences of serum antibody CDR and abundancy level are described. In some aspects, methods for determining nucleic acid sequences of antibody variable region sequences and frequency are provided. Furthermore, the invention provides methods for identification and generation of antibody or antigen-binding fragments that comprise highly-represented CDR.
摘要翻译：提供了用于鉴定可以具有希望的抗原特异性的抗体特异性可变区的方法和组合物以及抗体或抗原结合片段的产生。例如，在某些方面，描述了确定血清抗体CDR的氨基酸序列和丰度水平的方法。在一些方面，提供了用于确定抗体可变区序列和频率的核酸序列的方法。此外，本发明提供了用于鉴定和产生包含高度表示的CDR的抗体或抗原结合片段的方法。

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