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41. 发明专利

ZA200202727B Converting diploidy to haploidy for genetic diagnosis. 未知
公开(公告)号：ZA200202727B
公开(公告)日：2003-04-08
申请号：ZA200202727
申请日：2002-04-08
申请人： UNIV JOHNS HOPKINS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , YAN HAI , PAPADOPOULOS NICHOLAS
IPC分类号： C12N20060101 , C12N5/26 , C12Q20060101 , C12Q1/68 , C12Q , C12N
摘要： Detection of mutations associated with hereditary diseases is complicated by the diploid nature of human cells. Mutations present in one allele are often masked by the wild-type sequence of the other allele. Individual alleles can be isolated from every chromosome within somatic cell hybrids generated from a single fusion. Nucleic acids from the hybrids can be analyzed for mutations in an unambiguous manner. This approach was used to detect two cancer-causing mutations that had previously defied genetic diagnosis. One of the families studied, Warthin Family G, was the first kindred with a hereditary colon cancer syndrome described in the biomedical literature.

42. 发明公开

EP3186399A4 METHODS FOR RAPID AND SENSITIVE DETECTION OF HOTSPOT MUTATIONS 有权
公开(公告)号：EP3186399A4
公开(公告)日：2018-07-18
申请号：EP15837033
申请日：2015-08-24
申请人： UNIV DUKE
发明人： YAN HAI , HE YIPING , YANG RUI , DIPLAS BILL H , HANSEN LANDON , BIGNER DARELL
IPC分类号： C12Q1/68 , C12N15/10 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , C12Q2600/166
摘要： Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.

43. 发明公开

EP3099776A4 MUTATATIONS DEFINE CLINICAL SUBGROUPS OF GLIOMAS 审中-公开
标题翻译： MUTATATIONEN ZUR的定义KLINISCHER SUBGRUPPEN VON GLIOMEN
公开(公告)号：EP3099776A4
公开(公告)日：2017-10-04
申请号：EP15743712
申请日：2015-01-26
申请人： UNIV DUKE
发明人： YAN HAI , BIGNER DARELL , KILLELA PATRICK , REITMAN ZACHARY
IPC分类号： C12M1/34 , C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156

44. 发明申请

WO2013130487A2 NOVEL OXIDOREDUCTASES FOR ENANTIOSELECTIVE REACTIONS 审中-公开
标题翻译：用于观察反应的新型氧化还原剂
公开(公告)号：WO2013130487A2
公开(公告)日：2013-09-06
申请号：PCT/US2013027836
申请日：2013-02-27
申请人： UNIV DUKE
发明人： REITMAN ZACHARY JAMES , YAN HAI , CHOI BRYAN DAEHAHN , SAMPSON JOHN HOWARD
IPC分类号： C12N9/00
CPC分类号： C12N15/52 , C07K2319/21 , C12N9/0006 , C12N9/0008
摘要： Described herein are compositions and methods for generating oxidoreductases for enantioselective reactions. Described herein are compositions and methods for generating neomorphic (R)-2-hydroxyacid dehydrogenases capable of enzymatically converting a 1- carboxy-2-ketoacid to a l-carboxy-(R)-2-hydroxyacid, or the reverse reaction. Illustrative examples include (a) (R)-2-hydroxyadipate dehydrogenase and uses thereof for converting 2- oxoadipate to (R)-2-hydroxyadipate, or the reverse reaction; and (b) (R)-2-hydroxyglutarate dehydrogenase and uses thereof for converting 2-oxoglutarate to (R)-2-hydroxyglutarate, or the reverse reaction. Also described herein are compositions and methods for generating non- natural microbial organisms to enzymatically convert 2-oxoadipate to (E)-2-hexenedioate or adipate, or to enzymatically convert 2-oxoglutarate to (E)-2-pentenedioate or glutarate, or the respective reverse reactions.
摘要翻译：本文描述了用于产生用于对映选择性反应的氧化还原酶的组合物和方法。本文描述了用于产生能够将1-羧基-2-酮酸酶催化转化成1-羧基 - （R）-2-羟基酸的新型（R）-2-羟基酸脱氢酶或逆反应的组合物和方法。说明性实例包括（a）（R）-2-羟基己二酸脱氢酶及其用于将2-氧代己二酸转化为（R）-2-羟基己二酸或其逆反应的用途; 和（b）（R）-2-羟基戊二酸脱氢酶及其用于将2-酮戊二酸转化为（R）-2-羟基戊二酸的用途或逆反应。本文还描述了用于产生非天然微生物有机体以将2-氧代己二酸酶酶促转化成（E）-2-己烯二酸盐或己二酸盐或将2-氧代戊二酸酶催化转化成（E）-2-戊烯二酸盐或戊二酸盐的组合物和方法，或各自的逆向反应。

45. 发明申请

WO2012054915A3 HOMOZYGOUS AND HETEROZYGOUS IDH1 GENE-DEFECTIVE HUMAN ASTROCYTOMA CELL LINES 审中-公开
标题翻译：异基因和异源IDH1基因缺陷人类ASTROCYTOMA细胞系
公开(公告)号：WO2012054915A3
公开(公告)日：2012-07-19
申请号：PCT/US2011057466
申请日：2011-10-24
申请人： UNIV DUKE , YAN HAI , BIGNER DARELL , GENGLIN JIN
发明人： YAN HAI , BIGNER DARELL , GENGLIN JIN
IPC分类号： C12N5/071 , C12N5/10 , C12Q1/02
CPC分类号： C12N5/0693
摘要： We provide IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous and IDH1R132H homozygous) derived from dissociated human astrocytoma samples. The cells can be used alone or in combination with each other or other cell types as a tool for determining the impact of IDH1R132H on cellular biology, tumorigenesis, and metabolic profiles. The cell lines may be used to test and identify therapeutic targets and to screen for molecular therapeutic agents.
摘要翻译：我们提供衍生自解离的人类星形细胞瘤样品的IDH1基因缺陷型细胞系（例如，IDH1R132H杂合型和IDH1R132H纯合子）。细胞可以单独使用，也可以彼此组合使用，也可以作为确定IDH1R132H对细胞生物学，肿瘤发生和代谢特征影响的工具。细胞系可用于测试和鉴定治疗靶标并筛选分子治疗剂。

46. 发明公开

EP2820141A4 NOVEL OXIDOREDUCTASES FOR ENANTIOSELECTIVE REACTIONS 有权
标题翻译： NEUARTIGE OXIDOREDUKTASENFÜRENANTIOSETIVEKING REAKENEN
公开(公告)号：EP2820141A4
公开(公告)日：2016-01-27
申请号：EP13755329
申请日：2013-02-27
申请人： UNIV DUKE
发明人： REITMAN ZACHARY JAMES , YAN HAI , CHOI BRYAN DAEHAHN , SAMPSON JOHN HOWARD
IPC分类号： C12N9/04 , C12N1/00 , C12N1/20 , C12P7/00 , C12P7/40
CPC分类号： C12N15/52 , C07K2319/21 , C12N9/0006 , C12N9/0008
摘要： Described herein are compositions and methods for generating oxidoreductases for enantioselective reactions. Described herein are compositions and methods for generating neomorphic (R)-2-hydroxyacid dehydrogenases capable of enzymatically converting a 1-carboxy-2-ketoacid to a 1-carboxy-(R)-2-hydroxyacid, or the reverse reaction. Illustrative examples include (a) (R)-2-hydroxyadipate dehydrogenase and uses thereof for converting 2-oxoadipate to (R)-2-hydroxyadipate, or the reverse reaction; and (b) (R)-2-hydroxyglutarate dehydrogenase and uses thereof for converting 2-oxoglutarate to (R)-2-hydroxyglutarate, or the reverse reaction. Also described herein are compositions and methods for generating non-natural microbial organisms to enzymatically convert 2-oxoadipate to (E)-2-hexenedioate or adipate, or to enzymatically convert 2-oxoglutarate to (E)-2-pentenedioate or glutarate, or the respective reverse reactions.
摘要翻译：本文描述了用于产生对映选择性反应的氧化还原酶的组合物和方法。本文描述的是用于产生能够将1-羧基-2-酮酸酸化为1-羧基 - （R）-2-羟基酸或逆反应的新型（R）-2-羟基酸脱氢酶的组合物和方法。示例性实例包括（a）（R）-2-羟基己二酸脱氢酶及其用于将2-氧代己二酸转化为（R）-2-羟基己二酸酯的用途或反向反应; 和（b）（R）-2-羟基戊二酸脱氢酶及其用于将2-氧戊二酸转化为（R）-2-羟基戊二酸的反应或其反应。本文还描述了用于产生非天然微生物生物体以将2-氧代己二酸酯酶化转化为（E）-2-己烯二酸酯或己二酸酯，或将2-氧戊二酸酯酶促转化为（E）-2-戊烯二酸酯或戊二酸酯的组合物和方法，或各自的反向反应。

47. 发明申请

WO2012061105A3 HOMOZYGOUS AND HETEROZYGOUS IDH1 GENE-DEFECTIVE CELL LINES DERIVED FROM HUMAN COLORECTAL CELLS 审中-公开
公开(公告)号：WO2012061105A3
公开(公告)日：2012-06-28
申请号：PCT/US2011057615
申请日：2011-10-25
申请人： UNIV DUKE , YAN HAI , BIGNER DARELL , DUNCAN CHRISTOPHER GENTRY
发明人： YAN HAI , BIGNER DARELL , DUNCAN CHRISTOPHER GENTRY
IPC分类号： C12N5/10 , A01K67/027 , C12N5/09 , C12N15/85
CPC分类号： C12N15/85 , C12N5/0693 , C12N15/902 , C12N2510/00 , C12N2799/025 , C12N2800/30
摘要： IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous) have been made from a robust cell line, HCT116. The IDH1 gene-defective cell lines can be used to determine the effect of IDH1R132H on cell biology, tumorigenesis, and cellular metabolic profiles. These cell lines can be used to test potential therapeutic targets and to screen potential therapeutic agents. Kits and xenografts are also contemplated.

48. 发明申请

WO2012061105A2 HOMOZYGOUS AND HETEROZYGOUS IDH1 GENE-DEFECTIVE CELL LINES DERIVED FROM HUMAN COLORECTAL CELLS 审中-公开
标题翻译：人类和异源性IDH1从人类细胞细胞衍生的基因缺陷细胞系
公开(公告)号：WO2012061105A2
公开(公告)日：2012-05-10
申请号：PCT/US2011057615
申请日：2011-10-25
申请人： UNIV DUKE , YAN HAI , BIGNER DARRELL , DUNCAN CHRIS
发明人： YAN HAI , BIGNER DARRELL , DUNCAN CHRIS
IPC分类号： C12N5/10 , A01K67/027 , C12N5/09 , C12N15/85
CPC分类号： C12N15/85 , C12N5/0693 , C12N15/902 , C12N2510/00 , C12N2799/025 , C12N2800/30
摘要： IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous) have been made from a robust cell line, HCT116. The IDH1 gene-defective cell lines can be used to determine the effect of IDH1R132H on cell biology, tumorigenesis, and cellular metabolic profiles. These cell lines can be used to test potential therapeutic targets and to screen potential therapeutic agents. Kits and xenografts are also contemplated.
摘要翻译： IDH1基因缺陷型细胞系（例如，IDH1R132H杂合子）已经从稳健的细胞系HCT116制备出来。 IDH1基因缺陷细胞系可用于确定IDH1R132H对细胞生物学，肿瘤发生和细胞代谢特征的影响。这些细胞系可用于测试潜在的治疗靶标并筛选潜在的治疗剂。也可以考虑试剂盒和异种移植物。

49. 发明专利

AU2015306907C9 Methods for rapid and sensitive detection of hotspot mutations 未知
公开(公告)号：AU2015306907C9
公开(公告)日：2019-11-21
申请号：AU2015306907
申请日：2015-08-24
申请人： UNIV DUKE
发明人： YAN HAI , HE YIPING , YANG RUI , DIPLAS BILL H , HANSEN LANDON , BIGNER DARELL
IPC分类号： C12Q1/68 , C12N15/10 , C12P19/34
摘要： Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.

50. 发明专利

AU2015306907B2 Methods for rapid and sensitive detection of hotspot mutations 未知
公开(公告)号：AU2015306907B2
公开(公告)日：2018-07-19
申请号：AU2015306907
申请日：2015-08-24
申请人： UNIV DUKE
发明人： YAN HAI , HE YIPING , YANG RUI , DIPLAS BILL H , HANSEN LANDON , BIGNER DARELL
IPC分类号： C12Q1/68 , C12N15/10 , C12P19/34
摘要： Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.

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