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公开(公告)号：US06545137B1
公开(公告)日：2003-04-08
申请号：US09060299
申请日：1998-04-15
申请人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C.J. Twells
发明人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C.J. Twells
IPC分类号： C07H2104
CPC分类号： C07K14/705 , A61K38/00 , A61K48/00
摘要： A novel receptor, “LDL-receptor related protein-3” (“LRP-3”), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.
摘要翻译： 提供了新的受体“LDL-受体相关蛋白-3”（“LRP-3”）以及编码核酸。 该基因与1型糖尿病（胰岛素依赖性糖尿病）相关，实验证据表明其是IDDM易感基因IDDM4。 在各个方面，本发明提供核酸，包括编码序列，寡核苷酸引物和探针，多肽，药物组合物，诊断或预后的方法，以及与该基因相关并基于该基因的其它方法，包括治疗其中基因 可能涉及自身免疫性疾病，例如肾小球性肾炎，涉及细胞内吞和/或抗原呈递破坏的疾病和病症，涉及细胞因子清除和/或炎症的疾病和病症，病毒感染，游离脂肪酸升高或高胆固醇血症，骨质疏松症，阿尔茨海默病 疾病和糖尿病。
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公开(公告)号：US07244577B2
公开(公告)日：2007-07-17
申请号：US10331907
申请日：2002-12-31
申请人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C. J. Twells
发明人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C. J. Twells
IPC分类号： G01N33/567
CPC分类号： C07K14/705 , A61K38/00 , A61K48/00
摘要： A novel receptor, “LDL-receptor-related protein-5” (“LRP-5”), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.
摘要翻译： 提供了新的受体“LDL-受体相关蛋白-5”（“LRP-5”）以及编码核酸。 该基因与1型糖尿病（胰岛素依赖性糖尿病）相关，实验证据表明其是IDDM易感基因IDDM4。 在各个方面，本发明提供核酸，包括编码序列，寡核苷酸引物和探针，多肽，药物组合物，诊断或预后的方法，以及与该基因相关并基于该基因的其它方法，包括治疗其中基因 可能涉及自身免疫性疾病，例如肾小球性肾炎，涉及细胞内吞和/或抗原呈递破坏的疾病和病症，涉及细胞因子清除和/或炎症的疾病和病症，病毒感染，游离脂肪酸升高或高胆固醇血症，骨质疏松症，阿尔茨海默病 疾病和糖尿病。
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公开(公告)号：US06555654B1
公开(公告)日：2003-04-29
申请号：US09402923
申请日：2000-02-14
申请人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C. J. Twells
发明人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C. J. Twells
IPC分类号： C07K1400
CPC分类号： C07K14/705 , A61K38/00 , A61K48/00
摘要： A novel receptor, “LDL-receptor related protein-3” (“LRP-3”), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.
摘要翻译： 提供了新的受体“LDL-受体相关蛋白-3”（“LRP-3”）以及编码核酸。 该基因与1型糖尿病（胰岛素依赖性糖尿病）相关，实验证据表明其是IDDM易感基因IDDM4。 在各个方面，本发明提供核酸，包括编码序列，寡核苷酸引物和探针，多肽，药物组合物，诊断或预后的方法，以及与该基因相关并基于该基因的其它方法，包括治疗其中基因 可能涉及自身免疫性疾病，例如肾小球性肾炎，涉及细胞内吞和/或抗原呈递破坏的疾病和病症，涉及细胞因子清除和/或炎症的疾病和病症，病毒感染，游离脂肪酸升高或高胆固醇血症，骨质疏松症，阿尔茨海默病 疾病和糖尿病。
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4.发明授权3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing 有权3'-OH未封闭，快速可光切割的终止核苷酸和用于核酸测序的方法公开(公告)号：US08889860B2
公开(公告)日：2014-11-18
申请号：US13615284
申请日：2012-09-13
申请人： Brian Stupi , Hong Li , Weidong Wu , Megan N. Hersh , David Hertzog , Sidney E. Morris , Michael L. Metzker
发明人： Brian Stupi , Hong Li , Weidong Wu , Megan N. Hersh , David Hertzog , Sidney E. Morris , Michael L. Metzker
IPC分类号： C07D487/00 , C07D239/02 , C07H19/173 , C07H19/20 , C07H19/14 , C12Q1/68 , C07H19/073 , C07H19/10
CPC分类号： C12Q1/6869 , B01L3/5027 , B01L2300/0654 , B01L2300/168 , C07H19/073 , C07H19/10 , C07H19/14 , C07H19/173 , C07H19/20 , C12Q1/6874 , C12Q1/6883 , C12Q2525/117 , C12Q2600/156 , C12Q2600/16
摘要： The present invention relates generally to 3′-OH unblocked, labeled and unlabeled nucleotides and nucleosides with 5-methoxy-substituted nitrobenzyl-based photocleavable terminating groups for use in methods and systems related to DNA and RNA sequencing and analysis. These compounds, which may be represented by the following formulas: wherein the variables are defined herein, may be used as reversible terminators as they exhibit fast nucleotide incorporation kinetics, single-base termination, high nucleotide selectivity, and rapid terminating group cleavage that results in a naturally occurring nucleotide.
摘要翻译： 本发明一般涉及用于与DNA和RNA测序和分析相关的方法和系统中的5'-甲氧基取代的基于硝基苄基的可光切割终止基团的3'-OH未封闭，标记和未标记的核苷酸和核苷。 可以由下式表示的这些化合物：其中变量在本文中定义，可用作可逆终止子，因为它们表现出快速的核苷酸掺入动力学，单碱基终止，高核苷酸选择性和快速终止基团切割 天然存在的核苷酸。
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5.发明申请3'-OH UNBLOCKED NUCLEOTIDES AND NUCLEOSIDES BASE MDIFIED WITH NON-CLEAVABLE, TERMINATING GROUPS AND METHODS FOR THEIR USE IN DNA SEQUENCING 审中-公开3'-OH未结核的核酸和核苷酸基因，其具有不可清除的终止组以及用于DNA测序的方法公开(公告)号：US20130095471A1
公开(公告)日：2013-04-18
申请号：US13467885
申请日：2012-05-09
CPC分类号： C12Q1/6869 , C07H19/20 , C07H21/04
摘要： Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a non-cleavable terminating group. The non-cleavable-fluorescent group is designed to terminate DNA synthesis so that DNA oligomers can be sequenced efficiently in a parallel format. These reagents and methods will lead to more accurate identification of polymorphisms and other valuable genetic information.
摘要翻译： 提供本文所述的新型核苷酸，核苷及其衍生物，其可用于DNA测序技术和其他类型的DNA分析。 在一个实施方案中，具有未保护的3'-OH基团的核苷酸或核苷酸在核碱基处被衍生化，以包括通过接头连接至不可切割终止基团的荧光染料。 非可切割荧光基团被设计用于终止DNA合成，使得DNA寡聚体可以以平行格式有效排序。 这些试剂和方法将导致更准确地鉴定多态性和其他有价值的遗传信息。
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6.发明申请PHOTOCLEAVABLE LABELED NUCLEOTIDES AND NUCLEOSIDES AND METHODS FOR THEIR USE IN DNA SEQUENCING 有权可照射的标记核酸和核苷酸及其在DNA测序中的使用方法公开(公告)号：US20090081686A1
公开(公告)日：2009-03-26
申请号：US12268876
申请日：2008-11-11
CPC分类号： C07H19/23 , C07H17/02 , C07H19/10 , C07H19/20 , C07H21/04 , C12Q1/6869 , C12Q2535/101
摘要： Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.
摘要翻译： 提供本文所述的新型核苷酸，核苷及其衍生物，其可用于DNA测序技术和其他类型的DNA分析。 在一个实施方案中，具有未被保护的3'-OH基团的核苷酸或核苷酸在核碱基处被衍生化，以包括经由连接体连接至可光切割终止基团的荧光染料。 可光致透照荧光基团被设计用于终止DNA合成以及被切割，使得DNA寡聚体可以以并行格式有效排序。 在核苷酸和核苷上的快速切割荧光基团的设计可以提高DNA大尺寸寡聚体平行测序的速度和准确性，以便快速进行全基因组测序，以及鉴定多态性和其他有价值的遗传信息，以及允许 进一步操纵和分析在荧光基团裂解后的天然状态的核酸分子。
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公开(公告)号：US06762042B2
公开(公告)日：2004-07-13
申请号：US10148806
申请日：2002-06-05
申请人： Xiaomei Liu , Chang Bai , Michael L. Metzker
发明人： Xiaomei Liu , Chang Bai , Michael L. Metzker
IPC分类号： C12N900
CPC分类号： C12N9/90
摘要： The present invention disclosed isolated nucleic acid molecules (polynucleotides) which encode NHL, a putative DNA helicase. The present invention in turn relates to recombinant vectors and recombinant hosts which contain a DNA fragment encoding NHL, substantially purified forms of associated NHL, associated mutant proteins, and methods associated with identifying compounds which modulate NHL, which will be useful in the treatment of various neoplastic disorders. Both a genomic clone containing regulatory and intron sequences, as well as the exon structure and open reading frame of human NHL are disclosed.
摘要翻译： 本发明公开了编码NHL的分离的核酸分子（多核苷酸），即推定的DNA解旋酶。 本发明又涉及重组载体和重组宿主，其含有编码NHL的DNA片段，基本上纯化的相关NHL形式，相关的突变型蛋白质，以及与识别调节NHL的化合物相关的方法，其可用于各种治疗 肿瘤性疾病。 公开了含有调节和内含子序列的基因组克隆，以及人NHL的外显子结构和开放阅读框。
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8.发明授权Photocleavable labeled nucleotides and nucleosides and methods for their use in DNA sequencing 有权可光清洗标记的核苷酸和核苷及其用于DNA测序的方法公开(公告)号：US08969535B2
公开(公告)日：2015-03-03
申请号：US13592917
申请日：2012-08-23
CPC分类号： C07H19/23 , C07H17/02 , C07H19/10 , C07H19/20 , C07H21/04 , C12Q1/6869 , C12Q2535/101
摘要： Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.
摘要翻译： 提供本文所述的新型核苷酸，核苷及其衍生物，其可用于DNA测序技术和其他类型的DNA分析。 在一个实施方案中，具有未被保护的3'-OH基团的核苷酸或核苷酸在核碱基处被衍生化，以包括经由连接体连接至可光切割终止基团的荧光染料。 可光致透照荧光基团被设计用于终止DNA合成以及被切割，使得DNA寡聚体可以以并行格式有效排序。 在核苷酸和核苷上的快速切割荧光基团的设计可以提高DNA大尺寸寡聚体平行测序的速度和准确性，以便快速进行全基因组测序，以及鉴定多态性和其他有价值的遗传信息，以及允许 进一步操纵和分析在荧光基团裂解后的天然状态的核酸分子。
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9.发明授权3'-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing 有权3'-OH未封闭的核苷酸和用不可切割的终止基团修饰的核苷碱基及其用于DNA测序的方法公开(公告)号：US08198029B2
公开(公告)日：2012-06-12
申请号：US12986810
申请日：2011-01-07
CPC分类号： C12Q1/6869 , C07H19/20 , C07H21/04
摘要： Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a non-cleavable terminating group. The non-cleavable-fluorescent group is designed to terminate DNA synthesis so that DNA oligomers can be sequenced efficiently in a parallel format. These reagents and methods will lead to more accurate identification of polymorphisms and other valuable genetic information.
摘要翻译： 提供本文所述的新型核苷酸，核苷及其衍生物，其可用于DNA测序技术和其他类型的DNA分析。 在一个实施方案中，具有未保护的3'-OH基团的核苷酸或核苷酸在核碱基处被衍生化，以包括通过接头连接至不可切割终止基团的荧光染料。 非可切割荧光基团被设计用于终止DNA合成，使得DNA寡聚体可以以平行格式有效排序。 这些试剂和方法将导致更准确地鉴定多态性和其他有价值的遗传信息。
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10.发明授权3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing 有权3'-OH未封端，核苷酸和核苷，用可光裂解修饰的碱基，终止基团及其用于DNA测序的方法公开(公告)号：US07897737B2
公开(公告)日：2011-03-01
申请号：US11567189
申请日：2006-12-05
CPC分类号： C07H19/23 , C07H17/02 , C07H19/10 , C07H19/20 , C07H21/04 , C12Q1/6869 , C12Q2535/101
摘要： Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.
摘要翻译： 提供本文所述的新型核苷酸，核苷及其衍生物，其可用于DNA测序技术和其他类型的DNA分析。 在一个实施方案中，具有未被保护的3'-OH基团的核苷酸或核苷酸在核碱基处被衍生化，以包括经由连接体连接至可光切割终止基团的荧光染料。 可光致透照荧光基团被设计用于终止DNA合成以及被切割，使得DNA寡聚体可以以并行格式有效排序。 在核苷酸和核苷上的快速切割荧光基团的设计可以提高DNA大尺寸寡聚体平行测序的速度和准确性，以便快速进行全基因组测序，以及鉴定多态性和其他有价值的遗传信息，以及允许 进一步操纵和分析在荧光基团裂解后的天然状态的核酸分子。
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