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21.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：US07893227B2
公开(公告)日：2011-02-22
申请号：US11567193
申请日：2006-12-05
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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22.发明申请Labeled nucleotides and nucleosides and methods for their use in DNA sequencing 有权标记的核苷酸和核苷及其用于DNA测序的方法公开(公告)号：US20080131952A1
公开(公告)日：2008-06-05
申请号：US11567193
申请日：2006-12-05
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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公开(公告)号：US06995841B2
公开(公告)日：2006-02-07
申请号：US09941165
申请日：2001-08-28
CPC分类号： G01J3/4406 , G01J3/021 , G01J3/10 , G01N21/6428 , G01N21/6458 , G01N2021/6419 , G01N2021/6441
摘要： The present invention provides a technology called Pulse-Multiline Excitation or PME. This technology provides a novel approach to fluorescence detection with application for high-throughput identification of informative SNPs, which could lead to more accurate diagnosis of inherited disease, better prognosis of risk susceptibilities, or identification of sporadic mutations. The PME technology has two main advantages that significantly increase fluorescence sensitivity: (1) optimal excitation of all fluorophores in the genomic assay and (2) “color-blind” detection, which collects considerably more light than standard wavelength resolved detection. Successful implementation of the PME technology will have broad application for routine usage in clinical diagnostics, forensics, and general sequencing methodologies and will have the capability, flexibility, and portability of targeted sequence variation assays for a large majority of the population.
摘要翻译： 本发明提供了一种称为脉冲 - 多重激发或PME的技术。 该技术提供了一种新的荧光检测方法，可应用于信息性SNP的高通量鉴定，这可以导致对遗传疾病的更准确的诊断，更好的预后风险易感性或散发性突变的鉴定。 PME技术有两个显着增加荧光灵敏度的主要优点：（1）基因组测定中所有荧光团的最佳激发和（2）“色盲”检测，其比标准波长分辨检测收集明显更多的光。 PME技术的成功实施将广泛应用于临床诊断，取证和一般测序方法中的常规应用，并将为大多数人群提供靶向序列变异测定的能力，灵活性和可移植性。
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公开(公告)号：US5614386A
公开(公告)日：1997-03-25
申请号：US494216
申请日：1995-06-23
CPC分类号： C12Q1/6816 , C07H21/00 , C12Q1/6869
摘要： Methods for the use of a class of dyes for improved DNA sequencing are provided. A new class of dyes, BODIPY.RTM. fluorophore, has been described recently. The parent heterocyclic molecule of the BODIPY.RTM. fluorophore is a dipyrrometheneboron difluoride compound which is modified to create a broad class of spectrally-discriminating fluorophores. The present invention provides methods for the use of BODIPY.RTM. fluorophore-labeled DNA. BODIPY.RTM. fluorophore have improved spectral characteristics compared to conventional fluorescein and rhodamine dyes. BODIPY.RTM. fluorophore have narrower band width, insensitivity to solvent or pH, and improved photostability, thus, BODIPY.RTM. fluorophores lead to improved DNA sequencing and/or detection in any method where electrophoresis and detection of DNA is required. Additionally, the spectral properties of the BODIPY.RTM. fluorophores are sufficiently similar in wavelength and intensity to be used with conventional equipment known in the art.
摘要翻译： 提供了使用一类染料来改进DNA测序的方法。 最近已经描述了一类新的染料BODIPY TM荧光团。 BODIPY TM荧光团的母体杂环分子是二吡咯亚甲基二氟化物化合物，其被修饰以产生广泛类别的光谱鉴别荧光团。 本发明提供了使用BODIPY TM荧光团标记的DNA的方法。 与常规荧光素和罗丹明染料相比，BODIPY TM荧光团具有改进的光谱特征。 BODIPY TM荧光团具有较窄的带宽，对溶剂或pH不敏感以及改善的光稳定性，因此，BODIPY TM荧光团可以在需要电泳和检测DNA的任何方法中导致改进的DNA测序和/或检测。 此外，BODIPY TM荧光团的光谱性质在本领域已知的常规设备中与波长和强度足够相似。
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25.发明申请PHOTOCLEAVABLE LABELED NUCLEOTIDES AND NUCLEOSIDES AND METHODS FOR THEIR USE IN IN DNA SEQUENCING 有权可折叠标记的核苷酸和核苷酸及其在DNA序列中的使用方法公开(公告)号：US20130072388A1
公开(公告)日：2013-03-21
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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26.发明申请公开(公告)号：US20130035237A1
公开(公告)日：2013-02-07
申请号：US13406934
申请日：2012-02-28
CPC分类号： C12Q1/6869 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C12Q2525/117 , C12Q2563/107
摘要： The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.
摘要翻译： 本发明一般涉及标记和未裂解的可切割终止基团以及用于DNA测序和其他类型的DNA分析的方法。 更具体地，本发明部分地涉及具有化学可裂解，可光切割，可酶切割或不可光裂解的基团的核苷酸和核苷，以及它们用于DNA测序的方法及其在生物医学研究中的应用。
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27.发明授权公开(公告)号：US08148503B2
公开(公告)日：2012-04-03
申请号：US12483080
申请日：2009-06-11
CPC分类号： C12Q1/6869 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C12Q2525/117 , C12Q2563/107
摘要： The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.
摘要翻译： 本发明一般涉及标记和未裂解的可切割终止基团以及用于DNA测序和其他类型的DNA分析的方法。 更具体地，本发明部分地涉及具有化学可裂解，可光切割，可酶切割或不可光裂解的基团的核苷酸和核苷，以及它们用于DNA测序的方法及其在生物医学研究中的应用。
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28.发明申请3'-OH unblocked uncleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA squencing 有权3'-OH未封闭的非核苷酸和用不可裂解末端基团修饰的核苷碱基及其用于DNA沉默的方法公开(公告)号：US20110200988A1
公开(公告)日：2011-08-18
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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29.发明授权Substituted 4,4-difluoro-4-bora-3A,4A-diaza-s-indacene compounds for homogenous amplification/detection assays 失效用于均质扩增/检测测定的取代的4,4-二氟-4-硼酸-3A，4A-二氮杂-s-引达省
公开(公告)号：US5994063A
公开(公告)日：1999-11-30
申请号：US612036
申请日：1996-03-07
CPC分类号： C07H21/00 , C12Q1/6816 , C12Q1/6869
摘要： The use of BODIPY.RTM. fluorophores for detecting a target nucleic acid is described. The parent heterocyclic molecule of the BODIPY.RTM. fluorophores is a dipyrrometheneboron difluoride compound which is modified to create a broad class of spectrally-discriminating fluorophores. The present invention provides oligonucleotides labelled with substituted 4,4-difluoro-4-bora-3A,4A-diaza-s-indacene (BODIPY.RTM. fluorophore) compounds for performing the Taqman assay.
摘要翻译： 描述了使用BODIPY TM荧光团检测靶核酸。 BODIPY TM荧光团的母体杂环分子是二吡咯亚甲基二氟化物化合物，其被修饰以产生广泛类别的光谱鉴别荧光团。 本发明提供了用用于进行Taqman测定的用取代的4,4-二氟-4-硼酸-3A，4A-二氮杂 - 引信否（BODIPY TM荧光团）化合物标记的寡核苷酸。
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公开(公告)号：US5861287A
公开(公告)日：1999-01-19
申请号：US540228
申请日：1995-10-06
CPC分类号： C07H21/00 , C12Q1/6816 , C12Q1/6869
摘要： Methods for the use of a class of dyes for improved DNA sequencing are provided. A new class of dyes, BODIPY.RTM. fluorophores, has been described recently. The parent heterocyclic molecule of the BODIPY.RTM. fluorophores is a dipyrrometheneboron difluoride compound which is modified to create a broad class of spectrally-discriminating fluorophores. The present invention provides methods for the use of BODIPY.RTM. fluorophore-labeled DNA for dye-primer sequencing in which the BODIPY.RTM.s are attached to the 5' end of sequencing primers. BODIPY.RTM. fluorophores have improved spectral characteristics compared to conventional fluorescein and rhodamine dyes. BODIPY.RTM. fluorophores have narrower band width, insensitivity to solvent or pH, and improved photostability, thus, BODIPY.RTM. fluorophores lead to improved DNA sequencing and/or detection in any method where electrophoresis and detection of DNA is required. Additionally, the spectral properties of the BODIPY.RTM. fluorophores are sufficiently similar in wavelength and intensity to be used with conventional equipment known in the art.
摘要翻译： 提供了使用一类染料来改进DNA测序的方法。 最近已经描述了一类新的染料BODIPY TM荧光团。 BODIPY TM荧光团的母体杂环分子是二吡咯亚甲基二氟化物化合物，其被修饰以产生广泛类别的光谱鉴别荧光团。 本发明提供了使用BODIPY TM荧光团标记的DNA进行染色 - 引物测序的方法，其中BODIPY TM连接于测序引物的5'末端。 与传统的荧光素和罗丹明染料相比，BODIPY TM荧光团具有改进的光谱特性。 BODIPY TM荧光团具有较窄的带宽，对溶剂或pH的敏感性和改善的光稳定性，因此，BODIPY TM荧光团在需要电泳和检测DNA的任何方法中导致改进的DNA测序和/或检测。 此外，BODIPY TM荧光团的光谱性质在本领域已知的常规设备中与波长和强度足够相似。
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