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21. 发明授权

US06180341B2 In vitro scanning saturation mutagenesis of proteins 失效
标题翻译：蛋白质的体外扫描饱和诱变
公开(公告)号：US06180341B2
公开(公告)日：2001-01-30
申请号：US09070408
申请日：1998-04-30
申请人： Brent L. Iverson , George Georgiou , Elizabeth A. Burks
发明人： Brent L. Iverson , George Georgiou , Elizabeth A. Burks
IPC分类号： C12Q168
CPC分类号： C12N15/1093 , C07K16/00 , C07K16/16 , C07K2317/622 , C12N15/102
摘要： The present invention combines PCR™ mutagenesis with in vitro transcription/translation and ELISA for the rapid generation and characterization of protein mutants. The PCR™ products are used directly as the template for the in vitro transcription/translation reactions and because no cloning steps are required, the in vitro saturation mutagenesis of one residue can be completed in duplicate within a week by a single investigator. This high throughput enables the saturation mutagenesis of numerous residues of interest, a process that can be described as in vitro scanning saturation mutagenesis. Compositions and methods of use of such a process are described herein.
摘要翻译：本发明将PCR（TM）诱变与体外转录/翻译和ELISA结合用于快速产生和表征蛋白质突变体。 PCR TM产物直接用作体外转录/翻译反应的模板，并且由于不需要克隆步骤，一个残基的体外饱和诱变可以在一周内由单个研究者重复完成。这种高通量使得许多感兴趣的残基的饱和诱变可以被描述为体外扫描饱和诱变的过程。本文描述了这种方法的组合物和使用方法。

22. 发明授权

US5508192A Bacterial host strains for producing proteolytically sensitive polypeptides 失效
标题翻译：用于产生蛋白水解敏感多肽的细菌宿主菌株
公开(公告)号：US5508192A
公开(公告)日：1996-04-16
申请号：US153855
申请日：1993-11-18
申请人： George Georgiou , Francois Baneyx
发明人： George Georgiou , Francois Baneyx
IPC分类号： C12N1/21 , C12N15/01 , C12N15/70 , C12N1/20
CPC分类号： C12N15/01 , C12N15/70
摘要： The invention relates to methods of producing recombinant polypeptides in protease-deficient bacterial hosts. Constructs of single, double, triple and quadruple protease deficient and protease/rpoH mutants of E. coli are described. Proteolytically sensitive polypeptides may be expressed and secreted in such cells, providing significantly increased yields compared with expression in wild-type strains.
摘要翻译：本发明涉及在蛋白酶缺陷的细菌宿主中产生重组多肽的方法。描述了大肠杆菌的单，双，三重和四倍蛋白酶缺陷型和蛋白酶/ rpoH突变体的构建体。蛋白水解敏感多肽可以在这样的细胞中表达和分泌，与野生型菌株中的表达相比，提供显着增加的产量。

23. 发明授权

US5264365A Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides 失效
标题翻译：用于产生蛋白水解敏感多肽的蛋白酶缺陷型细菌菌株
公开(公告)号：US5264365A
公开(公告)日：1993-11-23
申请号：US612696
申请日：1990-11-09
申请人： George Georgiou , Francois Baneyx
发明人： George Georgiou , Francois Baneyx
IPC分类号： C12N1/21 , C12N15/01 , C12N15/70 , C12N1/20 , C12P21/00
CPC分类号： C12N15/01 , C12N15/70
摘要： The invention relates to the construction of protease-deficient Escherichia coli hosts which when combined with an expression system are useful for the production of proteolytically sensitive polypeptides. The invention also includes examples of particular mutant EscherichiaThe United States Government may have certain rights in the present invention pursuant to the terms of Grant No. CBT-8657471 awarded by the National Science Foundation.
摘要翻译：本发明涉及当与表达系统组合时可用于生产蛋白水解敏感多肽的蛋白酶缺陷型大肠杆菌宿主的构建。本发明还包括缺陷多达四种蛋白酶的特异性突变大肠杆菌的实例。

24. 发明申请

US20210128703A1 Compositions Of Engineered Human Arginases And Methods For Treating Cancer 有权
公开(公告)号：US20210128703A1
公开(公告)日：2021-05-06
申请号：US17096379
申请日：2020-11-12
申请人： George Georgiou , Everett Stone
发明人： George Georgiou , Everett Stone
IPC分类号： A61K38/50 , A61K47/60 , C12N9/78 , A61K33/24 , A61K47/64
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.

25. 发明授权

US09090674B2 Rapid isolation of monoclonal antibodies from animals 有权
标题翻译：从动物中快速分离单克隆抗体
公开(公告)号：US09090674B2
公开(公告)日：2015-07-28
申请号：US13109467
申请日：2011-05-17
申请人： Sai Reddy , Xin Ge , Jason Lavinder , Daniel Boutz , Andrew D. Ellington , Edward M. Marcotte , George Georgiou
发明人： Sai Reddy , Xin Ge , Jason Lavinder , Daniel Boutz , Andrew D. Ellington , Edward M. Marcotte , George Georgiou
IPC分类号： C40B30/04 , C07K16/06 , G01N33/68 , 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 candidate 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：提供了用于鉴定候选抗原特异性可变区以及产生可能具有所需抗原特异性的抗体或抗原结合片段的方法和组合物。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。

26. 发明申请

US20120148559A1 COMPOSITIONS AND METHOD FOR DEIMMUNIZATION OF PROTEINS 审中-公开
标题翻译：蛋白质去除组合物和方法
公开(公告)号：US20120148559A1
公开(公告)日：2012-06-14
申请号：US13307715
申请日：2011-11-30
申请人： George Georgiou , Jason Cantor , Tae Hyeon Yoo
发明人： George Georgiou , Jason Cantor , Tae Hyeon Yoo
IPC分类号： A61K38/50 , C07H21/04 , C12N5/10 , C12N15/63 , C12Q1/68 , C12N9/78
CPC分类号： C12N9/82 , A61K38/00 , C07K2319/23 , C07K2319/31 , C12Y305/01001 , G01N33/5023 , G01N2500/10
摘要： The invention provides deimmunized mutant proteins having reduced immunogenicity while exhibiting substantially the same or greater biological activity as the proteins of interst from which they are derived, as exemplified by mutant L-asparaginase that comprises amino acid substitutions compared to wild type L-asparaginase. The invention further provides methods for screening mutant deimmunized proteins that have substantially the same or greater biological activity as a protein of interest, and methods for reducing immunogenicity, without substantially reducing biological activity, of a protein of interest.The invention's compositions and methods are useful in, for example, therapeutic applications by minimizing adverse immune responses by the host mammalian subjects to the protein of interest. Thus, the invention further provides methods for treating disease comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising at least one of the mutant deimmunized proteins produced by the invention's methods.
摘要翻译：本发明提供具有降低的免疫原性的解除免疫的突变蛋白，同时表现出与它们衍生的中间蛋白基本上相同或更大的生物学活性，如与野生型L-天冬酰胺酶相比包含氨基酸取代的突变L-天冬酰胺酶所示例。本发明还提供了用于筛选与目的蛋白质具有基本相同或更大的生物学活性的突变体去免疫化蛋白质的方法，以及降低免疫原性而不显着降低目的蛋白质的生物学活性的方法。本发明的组合物和方法在例如治疗应用中可用于通过使宿主哺乳动物受试者对感兴趣的蛋白质的不良免疫应答最小化。因此，本发明还提供了治疗疾病的方法，包括向受试者施用治疗有效量的药物组合物，其包含本发明方法产生的至少一种突变型去免疫化蛋白质。

27. 发明授权

US08059663B1 Gateway-based system and method for tandem free operation 有权
标题翻译：基于网关的系统和方法，用于串联自由操作
公开(公告)号：US08059663B1
公开(公告)日：2011-11-15
申请号：US10616679
申请日：2003-07-10
申请人： Manish Mangal , George Georgiou , Anand Chakraborty
发明人： Manish Mangal , George Georgiou , Anand Chakraborty
IPC分类号： H04L12/28 , H04L12/56
CPC分类号： H04W36/0033 , H04W28/06 , H04W76/10 , H04W88/16
摘要： Mobile switching centers (MSCs) in serving systems are interconnected by gateways for tandem free operation. The serving systems route calls involving two mobile stations that use the same compressed digital format through the gateways. The gateways carry the media exchanged during the call in the compressed digital format in order to avoid tandem transcoding. When a serving system hands off a mobile station involved in a tandem free call, the call pathway is extended through the gateways so that the call remains tandem free.
摘要翻译：服务系统中的移动交换中心（MSC）通过网关互连，实现串联自由运行。服务系统通过网关路由涉及使用相同压缩数字格式的两个移动台的呼叫。网关在呼叫期间以压缩数字格式携带媒体交换，以避免串联转码。当服务系统切断涉及无线电通话的移动台时，呼叫路径通过网关延伸，使得呼叫保持串通。

28. 发明授权

US07902344B2 Antibodies with increased affinities for anthrax antigens 有权
标题翻译：具有增加的炭疽抗原亲和力的抗体
公开(公告)号：US07902344B2
公开(公告)日：2011-03-08
申请号：US11179244
申请日：2005-07-12
申请人： Barrett R. Harvey , George Georgiou , Brent L. Iverson
发明人： Barrett R. Harvey , George Georgiou , Brent L. Iverson
IPC分类号： C07H21/02 , C07H21/04 , A61K39/395 , A61K39/00 , A61K39/02 , A61K39/07
CPC分类号： C07K16/005 , C07K2317/622 , C07K2317/92 , C12N15/1034 , C12Q1/025 , G01N33/6845
摘要： The invention overcomes the deficiencies of the prior art by providing antibody compositions having improved affinities for Bacillus anthracis antigens. The compositions have important thereapeutic and diagnostic applications, including treatment or detection of infection by Bacillus anthracis.
摘要翻译：本发明通过提供具有改善的炭疽芽孢杆菌抗原亲和力的抗体组合来克服现有技术的缺陷。该组合物具有重要的治疗和诊断应用，包括炭疽杆菌感染的治疗或检测。

29. 发明授权

US07816117B2 Prokaryotic host cells for expressing proteins rich in disulfide bonds 有权
标题翻译：用于表达富含二硫键的蛋白质的原核宿主细胞
公开(公告)号：US07816117B2
公开(公告)日：2010-10-19
申请号：US11411988
申请日：2006-04-26
申请人： Jonathan Beckwith , Daniel Ritz , Melinda Faulkner , Stephanie Gon , George Georgiou
发明人： Jonathan Beckwith , Daniel Ritz , Melinda Faulkner , Stephanie Gon , George Georgiou
IPC分类号： C12N1/12 , C12N9/02 , C12P21/04
CPC分类号： C12N9/0065 , C12N2500/44 , C12N2501/70 , C12N2510/02
摘要： The invention provides composition and methods for producing proteins of interest which comprise at least one disulfide bond, include proteins which in their mature form do not contain disulfide bonds, but whose precursor molecule contained at least one disulfide bond. The methods employ a host cell modified to more efficiently produce properly folded disulfide bond containing proteins. The host cells generally contain a mutation in one or more reductase genes, and can be further genetically modified to increase their growth rate, and are further optionally modified to increase the expression of a catalyst of disulfide bond formation. Host cells, methods for u sing such to produce proteins of interest, proteins of interest produced by these methods are within the scope of the invention.
摘要翻译：本发明提供用于产生包含至少一个二硫键的感兴趣蛋白质的组合物和方法，包括其成熟形式不含二硫键但其前体分子含有至少一个二硫键的蛋白质。该方法使用修饰的宿主细胞以更有效地产生适当折叠的含二硫键的蛋白质。宿主细胞通常在一个或多个还原酶基因中含有突变，并且可进行进一步遗传修饰以增加其生长速率，并进一步任选地修饰以增加二硫键形成催化剂的表达。宿主细胞，用于产生感兴趣的蛋白质的方法，通过这些方法生产的感兴趣的蛋白质在本发明的范围内。

30. 发明申请

US20070065913A1 ISOLATION OF BINDING PROTEINS WITH HIGH AFFINITY TO LIGANDS 有权
标题翻译：分离具有高亲和力的结合蛋白
公开(公告)号：US20070065913A1
公开(公告)日：2007-03-22
申请号：US11461757
申请日：2006-08-01
申请人： Gang Chen , Andrew Hayhurst , Jeffrey Thomas , Brent Iverson , George Georgiou
发明人： Gang Chen , Andrew Hayhurst , Jeffrey Thomas , Brent Iverson , George Georgiou
IPC分类号： C12P21/06 , C07H21/04 , C12N9/00 , C12N1/21 , C07K14/195 , C12N15/74
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。

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