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21. 发明申请

US20090118485A1 OLIGONUCLEOTIDES AND ANALOGS LABELED WITH ENERGY TRANSFER DYES 审中-公开
标题翻译：标识与能量转运染色体的寡核苷酸和模拟物
公开(公告)号：US20090118485A1
公开(公告)日：2009-05-07
申请号：US12205817
申请日：2008-09-05
申请人： Linda G. LEE , Sandra L. Spurgeon , Barnett B. Rosenblum
发明人： Linda G. LEE , Sandra L. Spurgeon , Barnett B. Rosenblum
IPC分类号： C07H21/00
CPC分类号： C07H21/04 , C07H21/00 , C09B11/24 , C12Q1/6818
摘要： Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R28 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.
摘要翻译：提供了用于将供体染料与能量转移荧光染料中的受体染料连接的新型接头。这些连接器有助于在能量转移染料中的供体和受体染料之间的能量的有效转移。用于将供体染料与能量转移荧光染料中的受体染料连接的这些接头之一具有通式结构R21Z1C（O）R22R28，其中R21是与供体染料连接的C 1-5烷基，C（O）是羰基 Z1是NH，硫或氧，R22是包含烯烃，二烯烃，炔烃，具有至少一个不饱和键的五元和六元环或连接到羰基碳上的稠环结构的取代基，R28 包括将接头连接到受体染料的官能团。

22. 发明授权

US07504496B2 Water-soluble rhodamine dye conjugates 有权
标题翻译：水溶性罗丹明染料共轭物
公开(公告)号：US07504496B2
公开(公告)日：2009-03-17
申请号：US11059035
申请日：2005-02-14
申请人： Linda G. Lee , Ronald J. Graham , William E. Werner , Elana Swartzman , Lily Lu
发明人： Linda G. Lee , Ronald J. Graham , William E. Werner , Elana Swartzman , Lily Lu
IPC分类号： C07G3/00 , C07H21/02 , C07H21/00 , C07H21/04 , C07H19/04 , C12Q1/68
CPC分类号： C07D491/04 , C07D311/80 , C07D491/06 , C07H19/207 , C07H21/00 , C09B11/24 , G01N33/582 , G01N2458/00 , Y10S436/80
摘要： The present invention provides novel, water-soluble, red-emitting fluorescent rhodamine dyes and red-emitting fluorescent energy-transfer dye pairs, as well as labeled conjugates comprising the same and methods for their use. The dyes, energy-transfer dye pairs and labeled conjugates are useful in a variety of aqueous-based applications, particularly in assays involving staining of cells, protein binding, and/or analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.
摘要翻译：本发明提供新颖的水溶性红色荧光罗丹明染料和红色发光荧光能量转移染料对，以及包含其的标记共轭物及其使用方法。染料，能量转移染料对和标记的缀合物可用于各种水基应用，特别是涉及细胞染色，蛋白质结合和/或核酸分析的测定，如杂交测定和核酸测序。

23. 发明授权

US07432058B2 Methods of labeling nucleic acids with energy transfer dyes 有权
标题翻译：用能量转移染料标记核酸的方法
公开(公告)号：US07432058B2
公开(公告)日：2008-10-07
申请号：US11618663
申请日：2006-12-29
申请人： Linda G. Lee , Sandra L. Spurgeon , Barnett Rosenblum
发明人： Linda G. Lee , Sandra L. Spurgeon , Barnett Rosenblum
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/00 , C07H21/02 , C07H21/04 , C07H19/04
CPC分类号： C07H21/04 , C07D311/82 , C07D311/90 , C07D405/12 , C07D405/14 , C07H21/00 , C09B11/04 , C09B11/24 , C09B23/083 , C09B69/00 , C12Q1/6818 , C12Q1/6869 , C12Q2563/107 , C12Q2535/101 , C12Q2565/1015
摘要： Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R28 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.
摘要翻译：提供了用于将供体染料与能量转移荧光染料中的受体染料连接的新型接头。这些连接器有助于在能量转移染料中的供体和受体染料之间的能量的有效转移。用于将供体染料与能量转移荧光染料中的受体染料连接的这些接头之一具有通式结构R 21 R 1 C（O）R 22 其中R 21是与供体染料连接的C 1-5烷基，C（O）是羰基（C 1 -C 4）烷基，基团Z 1是NH，硫或氧，R 22是包括烯烃，二烯烃，炔烃，具有至少一个碳原子的五元和六元环的取代基不饱和键或与羰基碳连接的稠合环结构，R 28包括将接头连接于受体染料的官能团。

24. 发明授权

US06849745B2 Energy transfer dyes with enhanced fluorescence 失效
公开(公告)号：US06849745B2
公开(公告)日：2005-02-01
申请号：US10014743
申请日：2001-10-29
申请人： Linda G. Lee , Sandra L. Spurgeon , Barnett Rosenblum
发明人： Linda G. Lee , Sandra L. Spurgeon , Barnett Rosenblum
IPC分类号： C07D231/12 , C07D233/54 , C07D233/60 , C07D261/18 , C07D311/82 , C07H21/00 , C07H21/02 , C07H21/04 , C09B11/04 , C09B11/24 , C09B23/08 , C09B69/00 , C12Q1/68 , G01N33/53
CPC分类号： C07H21/04 , C07D311/82 , C07D311/90 , C07D405/12 , C07D405/14 , C07H21/00 , C09B11/04 , C09B11/24 , C09B23/083 , C09B69/00 , C12Q1/6818 , C12Q1/6869 , C12Q2563/107 , C12Q2535/101 , C12Q2565/1015
摘要： Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R28 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.

25. 发明授权

US06835827B2 Labelled oligonucleotides synthesized on solid-supports 有权
标题翻译：在固体支持物上合成标记的寡核苷酸
公开(公告)号：US06835827B2
公开(公告)日：2004-12-28
申请号：US10371985
申请日：2003-02-20
申请人： Ravi S. Vinayak , Linda G. Lee , Khairuzzaman B. Mullah , Barnett B. Rosenblum
发明人： Ravi S. Vinayak , Linda G. Lee , Khairuzzaman B. Mullah , Barnett B. Rosenblum
IPC分类号： C07H2100
CPC分类号： C07H21/00 , C07H19/10 , C07H19/20 , Y02P20/55
摘要： Methods and compositions to label oligonucleotides and analogs directly on a solid-support having the structure where S is a solid-support, A is a cleavable linker, X is a moiety with three or more attachment sites, L is a label, Y is a nucleophile, i.e. O, NH, NR or S, and P1 is an acid cleavable protecting group are provided. The labelled solid-support is reacted in a cyclical fashion to synthesize a labelled oligonucleotide on a solid-support in the 5′ to 3′ direction, having the structure: Labelled oligonucleotides are also synthesized by reacting: (i) a label reagent bearing functionality consisting of carboxylic acid, sulfonic acid, phosphonic acid, or phosphoric acid, (ii) an oligonucleotide on solid support with nucleophilic functionality, and (iii) a coupling reagent, whereby an ester, amide, thioester, sulfonamide, sulfonate, phosphonate, phosphoramidate, phosphorothioate, or phosphate bond is formed. The labelling reaction may be conducted at label sites including the 5′ terminus, the 3′ terminus, a nucleobase, an internucleotide linkage, a sugar, amino, sulfide, hydroxyl, and carboxyl.
摘要翻译：方法和组合物直接在具有其中S是固体支持物的结构的固体支持物上标记寡核苷酸和类似物，A是可切割的接头，X是具有三个或更多个连接位点的部分，L是标记，Y是亲核试剂，即O，NH，NR或S，并且P1是可酸切割的保护基。标记的固体支持物以循环方式反应以在5'至3'方向的固体支持物上合成标记的寡核苷酸，具有以下结构：标记的寡核苷酸还通过以下方式合成：（i）标记试剂载体官能团包括羧酸，磺酸，膦酸或磷酸，（ii）具有亲核官能团的固体支持物上的寡核苷酸，和（iii）偶联剂，其中酯，酰胺，硫酯，磺酰胺，磺酸酯，膦酸酯，氨基磷酸酯，硫代磷酸酯或磷酸酯键。标记反应可以在包括5'末端，3'末端，核碱基，核苷酸间键，糖，氨基，硫化物，羟基和羧基的标记位点进行。

26. 发明授权

US06750024B2 Nitro-substituted non-fluorescent asymmetric cyanine dye compounds 有权
标题翻译：硝基取代的非荧光不对称花青染料化合物
公开(公告)号：US06750024B2
公开(公告)日：2004-06-15
申请号：US10404404
申请日：2003-03-31
申请人： Linda G. Lee , Ronald J. Graham , Khairuzzaman B. Mullah , Francis T. Haxo
发明人： Linda G. Lee , Ronald J. Graham , Khairuzzaman B. Mullah , Francis T. Haxo
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C09B23/02
摘要： The invention provides an asymmetric cyanine dye compound having the structure including substituted forms thereof, wherein, at least one of R1 and R2 is linking group, X is O, S, or Se, and n ranges from 0 to 2. The invention further provides reporter-quencher dye pairs comprising the asymmetric cyanine dyes, dye-labelled polynucleotides incorporating the asymmetric cyanine dyes, and hybridization detection methods utilizing the dye-labelled polynucleotides.
摘要翻译：本发明提供具有其取代形式的不对称花青染料化合物，其中R1和R2中的至少一个是连接基团，X是O，S或Se，n在0至2的范围内。本发明进一步提供报道包括不对称花青染料的染色体染料，掺入不对称花青染料的染料标记的多核苷酸，以及利用染料标记的多核苷酸的杂交检测方法。

27. 发明授权

US06541618B1 Nitro-substituted non-fluorescent asymmetric cyanine dye compounds 有权
标题翻译：硝基取代的非荧光不对称花青染料化合物
公开(公告)号：US06541618B1
公开(公告)日：2003-04-01
申请号：US09602544
申请日：2000-06-21
申请人： Linda G. Lee , Ronald J. Graham , Khairuzzaman B. Mullah , Francis T. Haxo
发明人： Linda G. Lee , Ronald J. Graham , Khairuzzaman B. Mullah , Francis T. Haxo
IPC分类号： C07H2102
CPC分类号： C07H21/00 , C09B23/02
摘要： The invention provides an asymmetric cyanine dye compound having the structure including substituted forms thereof, wherein, at least one of R1 and R2 is linking group, X is O, S, or Se, and n ranges from 0 to 2. The invention further provides reporter-quencher dye pairs comprising the asymmetric cyanine dyes, dye-labelled polynucleotides incorporating the asymmetric cyanine dyes, and hybridization detection methods utilizing the dye-labelled polynucleotides.
摘要翻译：本发明提供具有其取代形式的不对称花青染料化合物，其中R1和R2中的至少一个是连接基团，X是O，S或Se，n在0至2的范围内。本发明进一步提供报道包括不对称花青染料的染色体染料，掺入不对称花青染料的染料标记的多核苷酸，以及利用染料标记的多核苷酸的杂交检测方法。

28. 发明授权

US06525183B2 Multiple-labelled oligonucleotides synthesized on solid-supports 有权
标题翻译：在固体支持物上合成多重标记的寡核苷酸
公开(公告)号：US06525183B2
公开(公告)日：2003-02-25
申请号：US10010717
申请日：2001-11-07
申请人： Ravi S. Vinayak , Linda G. Lee , Khairuzzaman B. Mullah , Barnett B. Rosenblum
发明人： Ravi S. Vinayak , Linda G. Lee , Khairuzzaman B. Mullah , Barnett B. Rosenblum
IPC分类号： C07H1900
CPC分类号： C07H21/00 , C07H19/10 , C07H19/20 , Y02P20/55
摘要： Methods and compositions to label oligonucleotides and analogs directly on a solid-support having the structure where S is a solid-support, A is a cleavable linker, X is a moiety with three or more attachment sites, L is a label, Y is a nucleophile, i.e. O, NH, NR or S, and P1 is an acid cleavable protecting group are provided. The labelled solid-support is reacted in a cyclical fashion to synthesize a labelled oligonucleotide on a solid-support in the 5′ to 3′ direction, having the structure: Labelled oligonucleotides are also synthesized by reacting: (i) a label reagent bearing functionality consisting of carboxylic acid, sulfonic acid, phosphonic acid, or phosphoric acid, (ii) an oligonucleotide on solid support with nucleophilic functionality, and (iii) a coupling reagent, whereby an ester, amide, thioester, sulfonamide, sulfonate, phosphonate, phosphoramidate, phosphorothioate, or phosphate bond is formed. The labelling reaction may be conducted at label sites including the 5′ terminus, the 3′ terminus, a nucleobase, an internucleotide linkage, a sugar, amino, sulfide, hydroxyl, and carboxyl.
摘要翻译：方法和组合物直接在具有其中S是固体支持物的结构的固体支持物上标记寡核苷酸和类似物，A是可切割的接头，X是具有三个或更多个连接位点的部分，L是标记，Y是亲核试剂，即O，NH，NR或S，并且P1是可酸切割的保护基。标记的固体支持物以循环方式反应以在5'至3'方向的固体支持物上合成标记的寡核苷酸，具有以下结构：标记的寡核苷酸还通过以下方式合成：（i）标记试剂载体官能团包括羧酸，磺酸，膦酸或磷酸，（ii）具有亲核官能团的固体支持物上的寡核苷酸，和（iii）偶联剂，其中酯，酰胺，硫酯，磺酰胺，磺酸酯，膦酸酯，氨基磷酸酯，硫代磷酸酯或磷酸酯键。标记反应可以在包括5'末端，3'末端，核碱基，核苷酸间键，糖，氨基，硫化物，羟基和羧基的标记位点进行。

29. 发明授权

US06348596B1 Non-fluorescent asymmetric cyanine dye compounds useful for quenching reporter dyes 有权
标题翻译：用于猝灭报道染料的非荧光不对称花青染料化合物
公开(公告)号：US06348596B1
公开(公告)日：2002-02-19
申请号：US09357740
申请日：1999-07-20
申请人： Linda G. Lee , Ronald J. Graham , Khairuzzaman B. Mullah , Francis T. Haxo
发明人： Linda G. Lee , Ronald J. Graham , Khairuzzaman B. Mullah , Francis T. Haxo
IPC分类号： C07D29300
CPC分类号： C07H21/00 , C09B23/02
摘要： The invention provides asymmetric cyanine dye compounds having the general formula: including substituted forms thereof, which are non-fluorescent quencher molecules. The invention further provides reporter-quencher dye pairs, wherein the asymmetric cyanine dyes are the quenchers, polynucleotides incorporating the asymmetric cyanine dyes, and nucleic acid hybridization detection methods utilizing the dye-labeled polynucleotides.
摘要翻译：本发明提供了具有以下通式的不对称花青染料化合物：包括其取代形式，它们是非荧光猝灭剂分子。本发明进一步提供报道猝灭剂染料对，其中不对称花青染料是猝灭剂，掺入不对称花青染料的多核苷酸，以及利用染料标记的多核苷酸的核酸杂交检测方法。

30. 发明授权

US06335440B1 Method for detecting oligonucleotides using energy transfer dyes with long stoke shift 有权
标题翻译：使用能量转移染料长时间移动检测寡核苷酸的方法
公开(公告)号：US06335440B1
公开(公告)日：2002-01-01
申请号：US09272097
申请日：1999-03-18
申请人： Linda G. Lee , Sandra L. Spurgeon , Barnett Rosenblum
发明人： Linda G. Lee , Sandra L. Spurgeon , Barnett Rosenblum
IPC分类号： C07H2104
CPC分类号： C07H21/04 , C07D311/82 , C07D311/90 , C07D405/12 , C07D405/14 , C07H21/00 , C09B11/04 , C09B11/24 , C09B23/083 , C09B69/00 , C12Q1/6818 , C12Q1/6869 , C12Q2563/107 , C12Q2535/101 , C12Q2565/1015
摘要： Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R26 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.
摘要翻译：提供了用于将供体染料与能量转移荧光染料中的受体染料连接的新型接头。这些连接器有助于在能量转移染料中的供体和受体染料之间的能量的有效转移。用于将能量转移荧光染料中的供体染料与受体染料连接的这些接头之一具有通式结构R21Z1C（O）R22R26，其中R21是与供体染料连接的C 1-5烷基，C（O）是羰基 Z1是NH，硫或氧，R22是包含烯烃，二烯烃，炔烃，具有至少一个不饱和键的五元和六元环或连接到羰基碳上的稠环结构的取代基，R28 包括将接头连接到受体染料的官能团。

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