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51. 发明授权

US09150850B2 Compositions and methods for analyzing protein interactions 有权
标题翻译：分析蛋白质相互作用的组成和方法
公开(公告)号：US09150850B2
公开(公告)日：2015-10-06
申请号：US12064292
申请日：2006-08-22
申请人： Matthew DeLisa , George Georgiou , Dujduan Waraho
发明人： Matthew DeLisa , George Georgiou , Dujduan Waraho
IPC分类号： C40B30/04 , C12N15/10 , G01N33/50
CPC分类号： C12N15/1055 , C40B30/04 , G01N33/5032
摘要： The present invention relates to compositions and methods for analyzing and modulating (e.g., enhancing or inhibiting) protein-protein interactions. In particular, compositions and methods of the present invention find use in identifying, reconstituting and characterizing protein-protein interactions, identifying binding subunits, and drug screening. The methods and compositions of the invention may also be used to identify agents that may agonize or antagonize a protein-protein interaction (e.g., using test compounds).
摘要翻译：本发明涉及用于分析和调节（例如，增强或抑制）蛋白质 - 蛋白质相互作用的组合物和方法。特别地，本发明的组合物和方法用于鉴定，重组和表征蛋白质 - 蛋白质相互作用，鉴定结合亚基和药物筛选。本发明的方法和组合物还可用于鉴定可能激动或拮抗蛋白质 - 蛋白质相互作用的试剂（例如，使用测试化合物）。

52. 发明授权

US08952132B2 Engineered immunoglobulin FC polypeptides 有权
标题翻译：工程化的免疫球蛋白FC多肽
公开(公告)号：US08952132B2
公开(公告)日：2015-02-10
申请号：US13367063
申请日：2012-02-06
申请人： George Georgiou , Sang Taek Jung , William Kelton , Tae Hyun Kang
发明人： George Georgiou , Sang Taek Jung , William Kelton , Tae Hyun Kang
IPC分类号： C07K17/00 , C07K16/00 , C07K1/00 , C07K16/28 , C12P21/08
CPC分类号： C07K16/283 , C07K16/32 , C07K2317/14 , C07K2317/41 , C07K2317/52 , C07K2317/72 , C07K2317/732 , C07K2317/92 , C07K2319/30
摘要： Methods and compositions involving polypeptides having an aglycosylated antibody Fc domain. In certain embodiments, polypeptides have an aglycosylated Fc domain that contains one or more substitutions compared to a native Fc domain. Additionally, some embodiments involve an Fc domain that is binds some Fc receptors but not others. For example, polypeptides are provided with an aglycosylated Fc domain that selectively binds FcγRIIa, but that is significantly reduced for binding to the highly homologous FcγRIIb receptors. Furthermore, methods and compositions are provided for promoting antibody-dependent cell-mediated toxicity (ADCC) using a polypeptide having a modified aglycosylated Fc domain and a second non-Fc binding domain, which can be an antigen binding region of an antibody or a non-antigen binding region. Some embodiments concern antibodies with such polypeptides, which may have the same or different non-Fc binding domain.
摘要翻译：涉及具有糖基化抗体Fc结构域的多肽的方法和组合物。在某些实施方案中，多肽具有与天然Fc结构域相比含有一个或多个取代的糖基化Fc结构域。另外，一些实施方案涉及结合一些Fc受体而不是其它Fc受体的Fc结构域。例如，提供了多肽选择性结合FcγRIIa的糖基化Fc结构域，但是与结合高度同源的FcγRIIb受体相比显着降低。此外，提供了使用具有修饰的糖基化Fc结构域和第二非Fc结合结构域的多肽来促进抗体依赖性细胞介导的毒性（ADCC）的方法和组合物，其可以是抗体或非抗体的抗原结合区域 - 抗原结合区。一些实施方案涉及具有这样的多肽的抗体，其可以具有相同或不同的非Fc结合结构域。

53. 发明授权

US08440184B2 Compositions of engineered human arginases and methods for treating cancer 有权
公开(公告)号：US08440184B2
公开(公告)日：2013-05-14
申请号：US12610685
申请日：2009-11-02
申请人： George Georgiou , Everett Stone
发明人： George Georgiou , Everett Stone
IPC分类号： A61K38/46 , C12N9/14 , C12N9/78 , C12N9/96 , C07H21/04
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.

54. 发明授权

US08426187B2 Immunoglobulin libraries 有权
标题翻译：免疫球蛋白文库
公开(公告)号：US08426187B2
公开(公告)日：2013-04-23
申请号：US13288767
申请日：2011-11-03
申请人： George Georgiou , Yariv Mazor
发明人： George Georgiou , Yariv Mazor
IPC分类号： C12Q1/68
CPC分类号： G01N33/566 , C07K14/245 , C07K16/00 , C07K16/005 , C07K16/1278 , C07K16/16 , C07K16/18 , C07K2317/565 , C07K2319/00 , C12N15/1037 , C40B30/06
摘要： Methods and compositions for the screening and isolation of ligand-binding polypeptides, such as antibodies. In some aspects, methods of the invention enable the isolation of intact soluble antibodies comprising a constant domain. Screening methods that employ genetic packages such as bacteria and bacteriophages enable high through-put identification of ligand binding molecules.
摘要翻译：用于筛选和分离配体结合多肽（例如抗体）的方法和组合物。在一些方面，本发明的方法能够分离包含恒定结构域的完整可溶性抗体。使用遗传包装如细菌和噬菌体的筛选方法可以实现配体结合分子的高通量鉴定。

55. 发明申请

US20120108466A1 IMMUNOGLOBULIN LIBRARIES 有权
标题翻译：免疫球蛋白图书馆
公开(公告)号：US20120108466A1
公开(公告)日：2012-05-03
申请号：US13288767
申请日：2011-11-03
申请人： George Georgiou , Yariv Mazor
发明人： George Georgiou , Yariv Mazor
IPC分类号： C40B40/02 , C40B50/06 , C40B30/04 , C40B10/00 , C12N7/01 , C12Q1/70
CPC分类号： G01N33/566 , C07K14/245 , C07K16/00 , C07K16/005 , C07K16/1278 , C07K16/16 , C07K16/18 , C07K2317/565 , C07K2319/00 , C12N15/1037 , C40B30/06
摘要： Methods and compositions for the screening and isolation of ligand-binding polypeptides, such as antibodies. In some aspects, methods of the invention enable the isolation of intact soluble antibodies comprising a constant domain. Screening methods that employ genetic packages such as bacteria and bacteriophages enable high through-put identification of ligand binding molecules.
摘要翻译：用于筛选和分离配体结合多肽（例如抗体）的方法和组合物。在一些方面，本发明的方法能够分离包含恒定结构域的完整可溶性抗体。使用遗传包装如细菌和噬菌体的筛选方法可以实现配体结合分子的高通量鉴定。

56. 发明申请

US20110312505A1 Rapid Isolation of Monoclonal Antibodies from Animals 有权
标题翻译：从动物快速分离单克隆抗体
公开(公告)号：US20110312505A1
公开(公告)日：2011-12-22
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： C40B20/00 , C12Q1/68 , C07K16/00 , G01N33/68 , C12Q1/34 , G01N33/53
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。

57. 发明授权

US07419783B2 Engineering of leader peptides for the secretion of recombinant proteins in bacteria 有权
标题翻译：用于在细菌中分泌重组蛋白的前导肽的工程
公开(公告)号：US07419783B2
公开(公告)日：2008-09-02
申请号：US10289135
申请日：2002-11-05
申请人： George Georgiou , Matthew DeLisa
发明人： George Georgiou , Matthew DeLisa
IPC分类号： C12Q1/68 , C12P21/00 , C07H21/04 , C07K14/00 , C07K14/195
CPC分类号： C12N15/1051 , C07K2319/034 , C07K2319/60 , C07K2319/61 , C07K2319/95 , C12N15/1086 , C12N15/625
摘要： The present invention provides methods of isolating of leader peptides capable of directing export of heterologous proteins from the bacterial cytoplasm. The methods rely on the screening of libraries of putative leader peptides or of leader peptide mutants for sequences that allow rapid export and thus can rescue a short-lived reporter protein from degradation in the cytoplasm. The mutant leader peptides identified herein are shown to confer significantly higher steady state levels of export not only for short-lived reporter protein but also for other stable, long-lived proteins. These leader peptides can be used to direct or enhance protein secretion. The present invention further discloses methods for the export of cytoplasmically folded protein via the Tat pathway. Proteins having disulfide bonds are first folded within the cytoplasm in suitable oxidizing mutant strains. Such cytoplasmically pre-folded proteins containing disulfide bonds are then exported via the Tat pathway.
摘要翻译：本发明提供了能够引导异源蛋白从细菌细胞质导出的前导肽的分离方法。这些方法依赖于筛选出推定的前导肽或前导肽突变体的文库，用于允许快速出口的序列，从而可以拯救短命的报道蛋白免于细胞质中的降解。本文鉴定的突变体前导肽显示出不仅对于短寿命报道蛋白而且对于其他稳定的长寿命蛋白质也具有显着更高的稳态出口水平。这些前导肽可用于引导或增强蛋白质分泌。本发明还公开了通过Tat途径输出细胞质折叠的蛋白质的方法。具有二硫键的蛋白质首先在合适的氧化突变株中在细胞质内折叠。然后通过Tat途径输出含有二硫键的这种细胞质上预折叠的蛋白质。

58. 发明申请

US20070258954A1 Directed evolution of enzymes and antibodies 审中-公开
标题翻译：酶和抗体的定向进化
公开(公告)号：US20070258954A1
公开(公告)日：2007-11-08
申请号：US11317680
申请日：2005-12-22
申请人： Brent Iverson , George Georgiou , Gang Chen , Mark Olsen , Patrick Daugherty
发明人： Brent Iverson , George Georgiou , Gang Chen , Mark Olsen , Patrick Daugherty
IPC分类号： G01N33/554 , C07K16/00 , C12N1/00
CPC分类号： C07K14/245 , C07K16/00 , C07K16/16 , C07K16/44 , C07K2317/565 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/035 , C12N9/16 , C12N9/86 , C12N15/1037 , C12N15/625 , C40B40/02
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。

59. 发明申请

US20070099267A1 COMBINATORIAL PROTEIN LIBRARY SCREENING BY PERIPLASMIC EXPRESSION 审中-公开
标题翻译：通过周边表达组合蛋白图书馆筛选
公开(公告)号：US20070099267A1
公开(公告)日：2007-05-03
申请号：US11466352
申请日：2006-08-22
申请人： Barrett Harvey , George Georgiou , Brent Iverson
发明人： Barrett Harvey , George Georgiou , Brent Iverson
IPC分类号： C12P21/06 , C07H21/04 , C12N15/74 , C07K14/245
CPC分类号： C12N15/1034 , C07K2319/034 , C12N15/1037 , C12N15/1086 , C40B40/02
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, are expressed in the periplasm of gram negative bacteria and 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 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）的文库在革兰氏阴性细菌的周质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，并且避免了与噬菌体展示一起使用的配体融合蛋白的外表面表达相关的问题。

60. 发明申请

US20060030022A1 Compositions and methods for production of disulfide bond containing proteins in host cells 有权
标题翻译：用于在宿主细胞中生产含二硫键的蛋白质的组合物和方法
公开(公告)号：US20060030022A1
公开(公告)日：2006-02-09
申请号：US11058926
申请日：2005-02-16
申请人： Jonathan Beckwith , Fredrik Aslund , Paul Bessette , George Georgiou , Daniel Ritz , Jackie Lim
发明人： Jonathan Beckwith , Fredrik Aslund , Paul Bessette , George Georgiou , Daniel Ritz , Jackie Lim
IPC分类号： C12N1/21 , C12N15/74
CPC分类号： C12N9/0004 , C12P21/02
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 using 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，使用其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。

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