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公开(公告)号：US20120117669A1
公开(公告)日：2012-05-10
申请号：US12837454
申请日：2010-07-15
Applicant: Raju KUCHERLAPATI , Aya Jakobovits , Daniel G. Brenner , Daniel J. Capon , Sue Klapholz
Inventor： Raju KUCHERLAPATI , Aya Jakobovits , Daniel G. Brenner , Daniel J. Capon , Sue Klapholz
IPC: A01K67/027 , C12P21/00
CPC classification number: C07K16/2863 , A01K2217/05 , A01K2217/075 , A61K38/00 , C07K16/00 , C07K16/1282 , C07K16/22 , C07K16/241 , C07K16/244 , C07K16/248 , C07K16/2812 , C07K16/2854 , C07K16/2875 , C07K2317/21 , C07K2317/24
Abstract: Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
Abstract translation: 针对特定抗原的完全人抗体可以通过将抗原施用于转基因动物来制备，所述转基因动物已经被修饰以响应于抗原性攻击而产生这样的抗体，但其内源性位点已被禁用。 可以进行各种随后的操作以获得本身或其类似物的抗体。
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2.发明申请Transgenic mammals having human Ig loci including plural VH and VK regions and antibodies produced therefrom 有权具有人Ig基因座的转基因哺乳动物包括多个VH和VK区以及由其产生的抗体公开(公告)号：US20080235814A1
公开(公告)日：2008-09-25
申请号：US11250805
申请日：2005-10-14
Applicant: Aya Jakobovits , Raju Kucherlapati , Susan Klapholz , Michael J. Mendez , Larry Green
Inventor： Aya Jakobovits , Raju Kucherlapati , Susan Klapholz , Michael J. Mendez , Larry Green
IPC: A01K67/027 , C12N5/06 , C12P21/08
CPC classification number: A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A61K39/00 , C07K14/415 , C07K16/00 , C07K16/005 , C07K16/241 , C07K16/244 , C07K16/2863 , C07K2317/21 , C07K2317/24 , C07K2317/73 , C07K2317/92 , C12N15/8509 , C12N2800/206
Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and Vκ) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.
Abstract translation: 本发明涉及被工程化以含有人免疫球蛋白基因座的转基因非人动物。 特别地，根据本发明的动物具有包含多个可变（V H H P和V kappa）基因区的人Ig位点。 有利地，包含多个可变区基因增强了由动物产生的人抗体的特异性和多样性。 此外，这些区域的包含增强和重建动物的B细胞发育，使得动物具有丰富的分泌极高亲和力抗体的成熟B细胞。
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3.发明申请Transgenic mammals having human Ig loci including plural Vh and Vk regions and antibodies produced therefrom 有权具有人Ig位点的转基因哺乳动物包括多个Vh和Vk区以及由其产生的抗体公开(公告)号：US20080098490A1
公开(公告)日：2008-04-24
申请号：US11894779
申请日：2007-08-20
Applicant: Aya Jakobovits , Raju Kucherlapati , Susan Klapholz , Michael Mendez , Larry Green
Inventor： Aya Jakobovits , Raju Kucherlapati , Susan Klapholz , Michael Mendez , Larry Green
IPC: A01K67/00
CPC classification number: A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A61K39/00 , C07K14/415 , C07K16/00 , C07K16/005 , C07K16/241 , C07K16/244 , C07K16/2863 , C07K2317/21 , C07K2317/24 , C07K2317/73 , C07K2317/92 , C12N15/8509 , C12N2800/206
Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and Vκ) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.
Abstract translation: 本发明涉及被工程化以含有人免疫球蛋白基因座的转基因非人动物。 特别地，根据本发明的动物具有包含多个可变（V H H P和V kappa）基因区的人Ig位点。 有利地，包含多个可变区基因增强了由动物产生的人抗体的特异性和多样性。 此外，这些区域的包含增强和重建动物的B细胞发育，使得动物具有丰富的分泌极高亲和力抗体的成熟B细胞。
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公开(公告)号：US06657103B1
公开(公告)日：2003-12-02
申请号：US08923138
申请日：1997-09-04
Applicant: Raju Kucherlapati , Aya Jakobovits , Sue Klapholz , Daniel G. Brenner , Daniel J. Capon
Inventor： Raju Kucherlapati , Aya Jakobovits , Sue Klapholz , Daniel G. Brenner , Daniel J. Capon
IPC: C12P2100
CPC classification number: C12N15/90 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2267/01 , A01K2267/0381 , A61K38/00 , A61K2039/505 , C07K16/00 , C07K16/1282 , C07K16/22 , C07K16/241 , C07K16/244 , C07K16/248 , C07K16/2812 , C07K16/2854 , C07K16/2875 , C07K16/462 , C07K2317/21 , C07K2317/24 , C07K2317/565 , C12N15/8509 , C12N15/87 , C12N2840/203
Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
Abstract translation: 具有针对特异性抗原的完全人可变区的抗体可以通过将抗原施用于转基因动物来制备，所述转基因动物已经被修饰以响应于抗原性攻击而产生这样的抗体，但其内源性位点已被禁用。 可以进行各种随后的操作以获得本身或其类似物的抗体。
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公开(公告)号：US6075181A
公开(公告)日：2000-06-13
申请号：US486857
申请日：1995-06-07
Applicant: Raju Kucherlapati , Aya Jakobovits , Sue Klapholz , Daniel G. Brenner , Daniel J. Capon
Inventor： Raju Kucherlapati , Aya Jakobovits , Sue Klapholz , Daniel G. Brenner , Daniel J. Capon
CPC classification number: C07K16/1282 , C07K16/241 , C07K16/244 , C07K16/248 , C07K16/2812 , C07K16/2854 , C07K16/2875 , A01K2217/05 , A01K2217/075 , C07K2317/21 , C07K2317/24
Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
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Patent Agency Ranking
6.发明授权Transgenic mammals having human Ig loci including plural VH and Vκ regions and antibodies produced therefrom 有权具有人Ig位点的转基因哺乳动物包括多个VH和V＆Kgr; 区域和抗体公开(公告)号：US08809051B2
公开(公告)日：2014-08-19
申请号：US11894779
申请日：2007-08-20
Applicant: Aya Jakobovits , Raju Kucherlapati , Susan Klapholz , Michael J Mendez , Larry Green
Inventor： Aya Jakobovits , Raju Kucherlapati , Susan Klapholz , Michael J Mendez , Larry Green
IPC: C12N5/0735 , C12N5/0781 , C12N5/10 , A01K67/027
CPC classification number: A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A61K39/00 , C07K14/415 , C07K16/00 , C07K16/005 , C07K16/241 , C07K16/244 , C07K16/2863 , C07K2317/21 , C07K2317/24 , C07K2317/73 , C07K2317/92 , C12N15/8509 , C12N2800/206
Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and Vκ) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.
Abstract translation: 本发明涉及被工程化以含有人免疫球蛋白基因座的转基因非人动物。 特别地，根据本发明的动物具有包含多个可变（VH和V＆Kgr。）基因区的人Ig基因座。 有利地，包含多个可变区基因增强了由动物产生的人抗体的特异性和多样性。 此外，这些区域的包含增强和重建动物的B细胞发育，使得动物具有丰富的分泌极高亲和力抗体的成熟B细胞。
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公开(公告)号：US20130117871A1
公开(公告)日：2013-05-09
申请号：US13561449
申请日：2012-07-30
Applicant: Raju Kucherlapati , Aya Jakobovits , Daniel G. Brenner , Daniel J. Capon , Sue Klapholz
Inventor： Raju Kucherlapati , Aya Jakobovits , Daniel G. Brenner , Daniel J. Capon , Sue Klapholz
IPC: C07K16/28
CPC classification number: C07K16/2863 , A01K2217/05 , A01K2217/075 , A61K38/00 , C07K16/00 , C07K16/1282 , C07K16/22 , C07K16/241 , C07K16/244 , C07K16/248 , C07K16/2812 , C07K16/2854 , C07K16/2875 , C07K2317/21 , C07K2317/24
Abstract: Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
Abstract translation: 针对特定抗原的完全人抗体可以通过将抗原施用于转基因动物来制备，所述转基因动物已经被修饰以响应于抗原性攻击而产生这样的抗体，但其内源性位点已被禁用。 可以进行各种随后的操作以获得本身或其类似物的抗体。
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公开(公告)号：US20060040363A1
公开(公告)日：2006-02-23
申请号：US10656623
申请日：2003-09-04
Applicant: Raju Kucherlapati , Aya Jakobovits , Sue Klapholz , Daniel Brenner , Daniel Capon
Inventor： Raju Kucherlapati , Aya Jakobovits , Sue Klapholz , Daniel Brenner , Daniel Capon
CPC classification number: C12N15/90 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2267/01 , A01K2267/0381 , A61K38/00 , A61K2039/505 , C07K16/00 , C07K16/1282 , C07K16/22 , C07K16/241 , C07K16/244 , C07K16/248 , C07K16/2812 , C07K16/2854 , C07K16/2875 , C07K16/462 , C07K2317/21 , C07K2317/24 , C07K2317/565 , C12N15/8509 , C12N15/87 , C12N2840/203
Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
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9.发明授权Homologous recombination for universal donor cells and chimeric mammalian hosts 失效用于通用供体细胞和嵌合哺乳动物宿主的同源重组
公开(公告)号：US5574205A
公开(公告)日：1996-11-12
申请号：US175469
申请日：1993-12-30
Applicant: Raju Kucherlapati , Beverly H. Koller , Oliver Smithies , Robert B. Dubridge , Gary Greenburg , Daniel J. Capon , Steven R. Williams , Mariona L. A. De Rafael
Inventor： Raju Kucherlapati , Beverly H. Koller , Oliver Smithies , Robert B. Dubridge , Gary Greenburg , Daniel J. Capon , Steven R. Williams , Mariona L. A. De Rafael
IPC: A01K67/027 , A61K35/12 , A61K38/21 , A61K45/00 , C07H21/04 , C07K14/74 , C12N5/02 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/85 , C12Q1/68 , G01N33/53 , A61K48/00 , A61K49/00 , C12N5/00
CPC classification number: A01K67/0271 , A01K67/0275 , A01K67/0276 , C07K14/70539 , C12N15/00 , C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/075 , A01K2227/105 , A01K2267/025 , A01K2267/03 , A01K2267/0381
Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, each of the .beta..sub.2- microglobulin gene and the IFN-.gamma.R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.
Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，每个β2-微球蛋白基因和IFN-γR基因被灭活以减少或消除功能性MHC抗原的表达。 所得细胞可用作通用供体细胞。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源，或作为药物和移植疗法的模型。 还描述了在非转化的哺乳动物体细胞中同源重组的方法。
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10.发明授权Homologous recombination for universal donor cells and chimeric mammalian hosts 失效用于通用供体细胞和嵌合哺乳动物宿主的同源重组
公开(公告)号：US5413923A
公开(公告)日：1995-05-09
申请号：US990879
申请日：1992-12-11
Applicant: Raju Kucherlapati , Beverly H. Koller , Oliver Smithies
Inventor： Raju Kucherlapati , Beverly H. Koller , Oliver Smithies
IPC: A01K67/027 , C12N15/00 , C12N15/85 , C12N5/00
CPC classification number: C12N15/8509 , A01K67/0271 , A01K67/0276 , C12N15/00 , A01K2217/075 , A01K2227/105 , A01K2267/03
Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2 -microglobulin gene is inactivated for reducing or eliminating Class I MHC antigens. The resulting cells may be used as universal donors. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies.
Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，β2-微球蛋白基因被灭活用于减少或消除I类MHC抗原。 所得细胞可用作通用供体。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源，或作为药物和移植疗法的模型。
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