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1. 发明公开

EP1399575A2 METHODS OF MODIFYING EUKARYOTIC CELLS 有权
标题翻译：方法进行修饰真核细胞
公开(公告)号：EP1399575A2
公开(公告)日：2004-03-24
申请号：EP01992495.0
申请日：2001-10-31
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： ECONOMIDES, Aris, N. , MURPHY, Andrew, J. , VALENZUELA, David, M. , FRENDEWEY, David , YANCOPOULOS, George, D.
IPC分类号： C12N15/90
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2227/105 , C12N15/907
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous genes(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

2. 发明授权

EP3191512B1 TREATMENT OF FIBRODYSPLASIA OSSIFICANS PROGRESSIVA 有权
公开(公告)号：EP3191512B1
公开(公告)日：2019-07-24
申请号：EP15775835.0
申请日：2015-09-14
申请人： Regeneron Pharmaceuticals, Inc.
发明人： HATSELL, Sarah, J. , ECONOMIDES, Aris, N. , IDONE, Vincent, J.
IPC分类号： C07K16/22 , A61K38/17 , A61K31/519 , C07K16/28 , A61P19/00

3. 发明公开

EP2494047A1 MULTIFUNCTIONAL ALLELES 有权
标题翻译： MULTIFUNKTIONELLE ALLELE
公开(公告)号：EP2494047A1
公开(公告)日：2012-09-05
申请号：EP10774391.6
申请日：2010-10-29
申请人： Regeneron Pharmaceuticals, Inc.
发明人： ECONOMIDES, Aris, N. , MURPHY, Andrew, J. , LENGYEL, Peter, Matthew , YANG, Peter, H., A.
IPC分类号： C12N15/10 , C12N15/90
CPC分类号： C12N15/907 , A01K2217/15 , A01K2217/20 , C12N9/00 , C12N15/63 , C12N2800/30 , C12N2800/60 , C12N2840/44
摘要： Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINS. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.
摘要翻译：提供了核酸构建体和用于对基因组进行修饰的方法，其中所述修饰包含无效等位基因，条件等位基因和包含COINs的无效等位基因。提供多功能等位基因（MFA）以及制备它们的方法，其提供单次靶向引入可用于产生无效等位基因，条件等位基因或等位基因的等位基因的能力并且还包括一个COIN。 MFAs包括成对的同源重组酶识别位点，启动序列和/或药物选择盒，以及目的核苷酸序列和COIN，其中在重组酶的作用下，形成了具有COIN的条件等位基因。在另一个实施方案中，第二重组酶的作用形成仅包含正义取向的COIN的等位基因。在另一个实施方案中，由第三重组酶的作用形成仅含义义方向的致动序列的等位基因。

4. 发明公开

EP1105477A1 DCR5, A BMP-BINDING PROTEIN, AND APPLICATIONS THEREOF 审中-公开
标题翻译： DCR5：蛋白质，一个BMP的关系，及其用途
公开(公告)号：EP1105477A1
公开(公告)日：2001-06-13
申请号：EP99940969.1
申请日：1999-08-12
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： ECONOMIDES, Aris, N. , STAHL, Neil
IPC分类号： C12N15/12 , C12N15/62 , C12N5/10 , C12N1/21 , C12N1/19 , C07K14/475 , C07K16/22 , A61K38/18 , A61K39/395
CPC分类号： C07K14/475 , A61K38/00 , C07K2319/02
摘要： DCR5, a protein related to DAN (Differential-screening-selected gene Aberrative in Neuroblastoma) and related nucleic acids are provided. Included are natural DCR5 homologs from several species and proteins comprising a DCR5 domain having specific activity, particularly the ability to antagonize a bone morphogenetic protein. The proteins may be produced recombinantly from transformed host cells with the subject nucleic acids. Also provided are isolated hybridization probes and primers capable of specifically hybridizing with the disclosed genes, specific binding agents and methods of making and using the subject compositions.

5. 发明授权

EP2262898B1 ES CELL-DERIVED MICE FROM DIPLOID HOST EMBRYO INJECTION 有权
标题翻译： ES细胞衍生的小鼠从双胞胎宿主胚胎注射
公开(公告)号：EP2262898B1
公开(公告)日：2018-01-24
申请号：EP09718915.3
申请日：2009-03-06
申请人： Regeneron Pharmaceuticals, Inc.
发明人： POUEYMIROU, William , DECHIARA, Thomas, M. , AUERBACH, Wojtek , ECONOMIDES, Aris, N. , GALE, Nicholas, W. , FRENDEWEY, David , VALENZUELA,David, M.
IPC分类号： A01K67/027 , C12N15/85 , C12N15/90 , C12N5/10 , A61D19/00 , C12N5/16
CPC分类号： A01K67/0271 , A01K67/0275 , A01K2207/12 , A01K2217/00 , A01K2217/05 , A01K2217/07 , A01K2217/15 , A01K2217/203 , A01K2217/30 , A01K2227/105 , A01K2267/02 , C12N5/16 , C12N15/8509 , C12N15/907 , C12N2510/00 , C12N2517/02
摘要： Genetically modified mice and nucleic acid constructs for making the genetically modified mice are described. A first mouse having a gene encoding an activator (such as a Cre recombinase) operably linked to a developmentally-regulated promoter (such as a Nanog promoter) is provided. A second mouse having a toxic responder gene (such as a gene encoding diphtheria toxin A) is provided, where the toxic gene is expressed only in the presence of an activator, Embryos from a mating of the first and the second mouse are provided as host embryos suitable for generating mice from donor cells introduced into the host embryos. Ablating the ICM of a mouse embryo physically, chemically, or genetically is described, as well as making F0 generation mice that are substantially or in full derived from donor cells, employing a host mouse embryo with an ablated or nonproliferating ICM.

6. 发明公开

EP1003860A1 MODIFIED DORSAL TISSUE AFFECTING FACTOR AND COMPOSITIONS 失效
标题翻译：影响DORSALGEWEBE因素
公开(公告)号：EP1003860A1
公开(公告)日：2000-05-31
申请号：EP98936850.1
申请日：1998-07-17
申请人： REGENERON PHARMACEUTICALS, INC. , The Regent of the University of California
发明人： STAHL, Neil , HARLAND, Richard, M. , ECONOMIDES, Aris, N.
IPC分类号： C12N15/12 , C07K14/475 , A61K38/18
CPC分类号： C07K14/475 , A61K38/00
摘要： Described are modified Noggin muteins, compositions comprising the muteins, and DNA or RNA sequences comprising coding (sense) or antisense sequences for the muteins.

7. 发明授权

EP2494047B1 MULTIFUNCTIONAL ALLELES 有权
标题翻译：多功能等位基因
公开(公告)号：EP2494047B1
公开(公告)日：2017-01-04
申请号：EP10774391.6
申请日：2010-10-29
申请人： Regeneron Pharmaceuticals, Inc.
发明人： ECONOMIDES, Aris, N. , MURPHY, Andrew, J. , LENGYEL, Peter, Matthew , YANG, Peter, H., A.
IPC分类号： C12N15/10 , C12N15/90
CPC分类号： C12N15/907 , A01K2217/15 , A01K2217/20 , C12N9/00 , C12N15/63 , C12N2800/30 , C12N2800/60 , C12N2840/44
摘要： Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINS. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.

8. 发明授权

EP1399575B1 METHODS OF MODIFYING EUKARYOTIC CELLS 有权
标题翻译：方法进行修饰真核细胞
公开(公告)号：EP1399575B1
公开(公告)日：2006-07-05
申请号：EP01992495.0
申请日：2001-10-31
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： ECONOMIDES, Aris, N. , MURPHY, Andrew, J. , VALENZUELA, David, M. , FRENDEWEY, David , YANCOPOULOS, George, D.
IPC分类号： C12N15/90
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2227/105 , C12N15/907
摘要： A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous genes(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

9. 发明公开

EP1392111A1 METHOD FOR TARGETING TRANSCRIPTIONALLY ACTIVE LOCI 审中-公开
标题翻译：用于标定可转换活动LOCI的方法
公开(公告)号：EP1392111A1
公开(公告)日：2004-03-03
申请号：EP02741823.5
申请日：2002-06-05
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： ECONOMIDES, Aris, N. , DECHIARA, Thomas, M. , YANCOPOULOS, George, D.
IPC分类号： A01K67/00 , C12N15/00 , C07H21/02
CPC分类号： C12N15/8509 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0393 , C12N15/907 , C12N2800/30 , C12N2830/00
摘要： The present invention is a method of targeting promoter-less selection cassettes into transcriptionally active loci. In particular, the invention is a method for targeting promoter-less selection cassettes into transcriptionally active loci in stem cells or other eukaryotic cells with much greater efficiency than previously observed with other methods, thus reducing or eliminating the need to screen for targeted cells. The invention also encompasses the DNA targeting vectors, the targeted cells, as well as non-human organisms, especially mice, created from the targeted cells.
摘要翻译：本发明是将无启动子选择盒靶向转录活性基因座的方法。特别地，本发明是一种以比先前用其他方法观察到的效率高得多的效率将无启动子选择盒靶向至干细胞或其他真核细胞中的转录活性基因座的方法，因此减少或消除筛选靶细胞的需要。本发明还包括由靶向细胞产生的DNA靶向载体，靶向细胞以及非人生物体，尤其是小鼠。

10. 发明授权

EP1003860B1 MODIFIED DORSAL TISSUE AFFECTING FACTOR AND COMPOSITIONS 失效
标题翻译：改进的影响DORSALGEWEBE因素
公开(公告)号：EP1003860B1
公开(公告)日：2003-10-22
申请号：EP98936850.1
申请日：1998-07-17
申请人： REGENERON PHARMACEUTICALS, INC. , The Regents of the University of California
发明人： STAHL, Neil , HARLAND, Richard, M. , ECONOMIDES, Aris, N.
IPC分类号： C12N15/12 , C07K14/475 , A61K38/18
CPC分类号： C07K14/475 , A61K38/00
摘要： Described are modified Noggin muteins, compositions comprising the muteins, and DNA or RNA sequences comprising coding (sense) or antisense sequences for the muteins.

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