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41. 发明授权

US08586718B2 Multi-chromophoric quencher constructs for use in high sensitivity energy transfer probes 有权
标题翻译：用于高灵敏度能量转移探针的多发色猝灭剂构建体
公开(公告)号：US08586718B2
公开(公告)日：2013-11-19
申请号：US11226069
申请日：2005-09-14
申请人： Scott C. Benson , Steven M. Menchen , Krishna G. Upadhya
发明人： Scott C. Benson , Steven M. Menchen , Krishna G. Upadhya
IPC分类号： C09B62/83 , C09B35/037
CPC分类号： C07C245/08 , C07C50/18 , C07D311/90 , C07H21/00 , C07H21/04 , C09B6/00 , C09B11/08 , C09B33/02 , C09B35/021 , C09B35/50 , G01N33/542
摘要： Dark quencher constructs, termed “multi-chromophoric quenchers” are described herein that comprise at least two dark quenching moieties, which can be the same or different, linked together by at least one multivalent linking moiety. The structure of the multi-chromophoric quenchers can be varied to selectively enhance quenching within a specific range of reporter emission wavelengths. This can be accomplished by linking together, into a single molecule, two or more identical quenchers, by reacting the quenchers with a multivalent linker. The structure of the multi-chromophoric quencher can also be varied to quench a broader range of reporter emission wavelengths than previously possible. This can be accomplished by linking together, into a single molecule, two or more different quenchers, by reacting the quenchers with a multivalent linker. The structure of the multi-chromophoric quencher can also be varied to simultaneously broaden the absorption range and increase the total absorption within the absorption range. This can be done by combining the two concepts described above. In other words, multiple types of quenching moieties can be employed to increase the absorption range and a multiple number of each type of quenching moiety can be used to increase the total absorptivity within the absorption range. The multi-chromophoric quenchers can be tethered to probes for biomolecules, insoluble supports and/or fluorescent dyes for use in a wide variety of biomolecular assays.
摘要翻译：本文描述了称为“多发色猝灭剂”的暗猝灭剂构建体，其包含至少两个可通过至少一个多价连接部分连接在一起的相同或不同的猝灭部分。可以改变多发色猝灭剂的结构以选择性地增强在特定范围的报道发射波长内的猝灭。这可以通过将猝灭剂与多价连接体反应而连接在一起，形成单个分子，两个或多个相同的猝灭剂。多发色猝灭剂的结构也可以改变以淬灭比之前可能的更广泛的报告基因发射波长。这可以通过将猝灭剂与多价连接体反应而连接在一起成为单个分子，两个或多个不同的猝灭剂。多色猝灭剂的结构也可以改变，以同时扩大吸收范围并增加吸收范围内的总吸收。这可以通过组合上述两个概念来完成。换句话说，可以使用多种类型的淬灭部分来增加吸收范围，并且可以使用多个每种类型的淬灭部分来增加吸收范围内的总吸收率。多发色猝灭剂可以连接到用于生物分子，不溶性载体和/或荧光染料的探针，用于各种生物分子测定。

42. 发明授权

US08383841B2 Phenyl xanthene dyes 有权
标题翻译：苯基呫吨染料
公开(公告)号：US08383841B2
公开(公告)日：2013-02-26
申请号：US12351504
申请日：2009-01-09
申请人： Joe Y. L. Lam , Steven M. Menchen , Ruiming Zou , Scott C. Benson
发明人： Joe Y. L. Lam , Steven M. Menchen , Ruiming Zou , Scott C. Benson
IPC分类号： C09B11/06 , C09B11/24
CPC分类号： C09B11/24 , C07D311/82 , C07D491/14 , C09B11/06 , C09B11/12 , C09B11/22 , C09B11/26 , C09B13/00 , C09B57/00 , C09B62/0025
摘要： Fluorescent phenyl xanthene dyes are described that comprise any fluorescein, rhodamine or rhodol comprising a particular C9 phenyl ring. One or both of the ortho groups on the lower C9 phenyl ring is ortho substituted with a group selected from alkyl, heteroalkyl, alkoxy, halo, haloalkyl, amino, mercapto, alkylthio, cyano, isocyano, cyanato, mercaptocyanato, nitroso, nitro, azido, sulfeno, sulfinyl, and sulfino. In one embodiment, halo and/or hydroxy groups are used. Optimal dyes contain a lower C9 phenyl ring in which both ortho groups are the same and the lower ring exhibits some form a symmetry relative to an imaginary axis running from the phenyl rings point of attachment to the remainder of the xanthene dye through a point para to the point of attachment. The phenyl xanthene dyes may be activated. Furthermore, the phenyl xanthene dyes may be conjugated to one or more substances including other dyes. The phenyl xanthene dyes are useful for a number of purposes, including labels for use in automated DNA sequencing as well the formation of fluorescent “bar codes” for polymeric particles used in the multiplexed analysis of analytes.
摘要翻译：描述了包含任何含有特定C 9苯环的任何荧光素，罗丹明或若丹明的荧光苯基呫吨染料。下C9苯环上的一个或两个邻基被选自烷基，杂烷基，烷氧基，卤素，卤代烷基，氨基，巯基，烷硫基，氰基，异氰基，氰基，巯基氰基，亚硝基，硝基，叠氮基，磺酰亚胺基，亚磺酰基和亚磺酰基。在一个实施方案中，使用卤素和/或羟基。最佳染料含有较低的C 9苯环，其中两个邻基团相同，并且下环表现出相对于从苯环连接点到呫吨染料的其余部分的假想轴的对称性。附件点。苯基呫吨染料可以被活化。此外，苯基呫吨染料可以与一种或多种包括其它染料的物质共轭。苯基呫吨染料可用于许多目的，包括用于自动DNA测序的标记，以及在分析物多重分析中使用的聚合物颗粒的荧光条形码的形成。

43. 发明授权

US08124746B2 Methods and kits using extended rhodamine dyes 有权
标题翻译：使用延长罗丹明染料的方法和试剂盒
公开(公告)号：US08124746B2
公开(公告)日：2012-02-28
申请号：US12846773
申请日：2010-07-29
申请人： Joe Y. L. Lam , Scott C. Benson , Steven M. Menchen
发明人： Joe Y. L. Lam , Scott C. Benson , Steven M. Menchen
IPC分类号： C12P19/34
CPC分类号： C12Q1/6869 , C07D209/60 , C07D221/08 , C07D221/10 , C07D471/06 , C07D487/06 , C07D491/14 , C07H19/04 , C07H21/00 , C09B11/24 , C12Q1/68 , C12Q1/6816 , Y10S435/968 , Y10S435/975 , Y10S436/80 , Y10T436/143333
摘要： Extended rhodamine compounds exhibiting favorable fluorescence characteristics having the structure are disclosed. In addition, novel intermediates for synthesis of these dyes are disclosed, such intermediates having the structure In addition, methods of making and using the dyes as fluorescent labels are disclosed.
摘要翻译：本发明公开了具有良好荧光特性的罗丹明化合物。此外，公开了用于合成这些染料的新型中间体，具有这种结构的中间体。此外，公开了制备和使用染料作为荧光标记的方法。

44. 发明授权

US07776568B2 Methods and kits using extended rhodamine dyes 有权
标题翻译：使用延长罗丹明染料的方法和试剂盒
公开(公告)号：US07776568B2
公开(公告)日：2010-08-17
申请号：US10925411
申请日：2004-08-24
申请人： Joe Y. L. Lam , Scott C. Benson , Steven M. Menchen
发明人： Joe Y. L. Lam , Scott C. Benson , Steven M. Menchen
IPC分类号： C12P19/34
CPC分类号： C12Q1/6869 , C07D209/60 , C07D221/08 , C07D221/10 , C07D471/06 , C07D487/06 , C07D491/14 , C07H19/04 , C07H21/00 , C09B11/24 , C12Q1/68 , C12Q1/6816 , Y10S435/968 , Y10S435/975 , Y10S436/80 , Y10T436/143333
摘要： Extended rhodamine compounds exhibiting favorable fluorescence characteristics having the structure are disclosed. In addition, novel intermediates for synthesis of these dyes are disclosed, such intermediates having the structure In addition, methods of making and using the dyes as fluorescent labels are disclosed.
摘要翻译：本发明公开了具有良好荧光特性的罗丹明化合物。此外，公开了用于合成这些染料的新型中间体，具有这种结构的中间体。此外，公开了制备和使用染料作为荧光标记的方法。

45. 发明申请

US20090072197A1 FLUORESCENT POLYMERIC MATERIALS CONTAINING LIPID SOLUBLE RHODAMINE DYES 审中-公开
标题翻译：含有可溶性罗丹明染色体的荧光聚合材料
公开(公告)号：US20090072197A1
公开(公告)日：2009-03-19
申请号：US12240194
申请日：2008-09-29
申请人： Joe Y.L. LAM , Steven M. Menchen , Ruiming Zou , Scott C. Benson
发明人： Joe Y.L. LAM , Steven M. Menchen , Ruiming Zou , Scott C. Benson
IPC分类号： C08K5/1545 , C09K11/00
CPC分类号： C09K11/025 , C07D311/80 , C09B11/24 , C09B67/0092 , C09B67/0097 , C09B69/103 , C09K11/06 , C09K2211/1088 , C09K2211/1416 , C09K2211/145
摘要： Fluorescent polymeric materials are disclosed comprising a polymer and one or more lipid soluble rhodamine dyes. The materials are especially useful in the preparation of multicolored microparticles, especially multicolored polystyrene microparticle, for use in the multiplexed analysis of a plurality of analytes in a single sample. When excited by a light source, the materials give off a unique emission based on the nature, concentration and ratio of the dyes therein. Methods of preparing and using said materials are also disclosed.
摘要翻译：公开了包含聚合物和一种或多种脂溶性罗丹明染料的荧光聚合物材料。这些材料在制备多彩色微粒，特别是多色聚苯乙烯微粒中是特别有用的，用于在单个样品中多个分析物的多重分析。当被光源激发时，材料基于其中染料的性质，浓度和比例发出独特的发射。还公开了制备和使用所述材料的方法。

46. 发明授权

US06326153B2 Polynucleotides labeled with dibenzorhodamine dyes 有权
标题翻译：用二苄唑胺染料标记的多核苷酸
公开(公告)号：US06326153B2
公开(公告)日：2001-12-04
申请号：US09784943
申请日：2001-02-14
申请人： Scott C. Benson , Joe Y. L. Lam , Steven Michael Menchen
发明人： Scott C. Benson , Joe Y. L. Lam , Steven Michael Menchen
IPC分类号： C12Q168
CPC分类号： C09B11/24 , C07D209/60 , C07D221/10 , C07D311/78 , C07D491/14 , C07D491/147 , C07H19/10 , C07H19/20 , C07H21/00 , C07H21/04 , C09B11/02 , C12Q1/6869 , Y10T436/143333 , C12Q2563/107 , C12Q2527/125
摘要： Dibenzorhodamine compounds having the structure are disclosed, including nitrogen and aryl-substituted forms thereof. In addition, two intermediates useful for synthesizing such compounds are disclosed, a first intermediate having the structure including nitrogen- and aryl-substituted forms thereof, and a second intermediate having the structure including nitrogen- and aryl-substituted forms thereof, wherein substituents at positions C-14 to C18 taken separately are selected from the group consisting of hydrogen, chlorine, fluorine, lower alkyl, carboxylic acid, sulfonic acid, —CH2OH, alkoxy, phenoxy, linking group, and substituted forms thereof. The invention further includes energy transfer dyes comprising the dibenzorhodamine compounds, nucleosides labeled with the dibenzorhodamine compounds, and nucleic acid analysis methods employing the dibenzorhodamine compounds.
摘要翻译：公开了具有结构的二苄唑胺化合物，包括其氮和芳基取代形式。此外，公开了可用于合成这些化合物的两个中间体，具有包括其氮和芳基取代形式的结构的第一中间体和具有包括其氮和芳基取代形式的结构的第二中间体，其中位置C- 14至C18分别选自氢，氯，氟，低级烷基，羧酸，磺酸，-CH 2 OH，烷氧基，苯氧基，连接基团及其取代形式。本发明还包括包含二苄基罗丹胺化合物的能量转移染料，用二苯并呋喃胺化合物标记的核苷，以及使用二苯并呋喃胺化合物的核酸分析方法。

47. 发明授权

US6020481A Asymmetric benzoxanthene dyes 失效
标题翻译：不对称苯并氧杂蒽染料
公开(公告)号：US6020481A
公开(公告)日：2000-02-01
申请号：US626085
申请日：1996-04-01
申请人： Scott C. Benson , Steven M. Menchen , Peter D. Theisen , Kevin M. Hennessey , Vergine C. Furniss , Joan Hauser
发明人： Scott C. Benson , Steven M. Menchen , Peter D. Theisen , Kevin M. Hennessey , Vergine C. Furniss , Joan Hauser
IPC分类号： C12N15/00 , C07C39/14 , C07C39/38 , C07D311/78 , C07F9/24 , C07H19/06 , C07H19/16 , C07H21/00 , C09B11/00 , C09B11/08 , C09B11/28 , C09K11/06 , C12N15/09 , C12Q1/68 , G01N33/533 , C07H21/04
CPC分类号： C07H21/00 , C07C39/38 , C09B11/00 , C09B11/08 , C12Q1/6869
摘要： A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having the structure ##STR1## wherein Y.sub.1 and Y.sub.2 are individually hydroxyl amino, imminium, or oxygen, R.sub.1 -R.sub.8 are hydrogen, fluorine, chlorine, alkyl, alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinations thereof, and R.sub.9 is acetylene, alkane, alkene, cyano, substituted phenyl, and combinations thereof. The invention further includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having the general structure ##STR2## where substituents R.sub.3 -R.sub.7 correspond to like-referenced substituents in the structure of described above, and Y.sub.2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates. In yet another aspect, the present invention includes reagents labeled with the asymmetric benzoxanthene dye compounds, including deoxynucleotides, dideoxynucleotides, phosphoramidites, and polynucleotides. In an additional aspect, the invention includes methods utilizing such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.
摘要翻译：公开了一类用作荧光染料的不对称单苯并氧蒽化合物，其结构是其中Y 1和Y 2分别是羟基氨基，亚氨基或氧，R 1 -R 8是氢，氟，氯，烷基，烯烃，炔烃，磺酸酯，氨基，酰胺基腈，烷氧基，连接基团及其组合，R 9为乙炔，烷烃，烯烃，氰基，取代的苯基及其组合。本发明还包括可用于合成具有通式结构的不对称苯并氧杂蒽化合物的新型中间体化合物，其中取代基R 3〜R 7对应于上述结构中的相同取代基，Y 2为羟基或胺。另一方面，本发明包括合成上述染料化合物和中间体的方法。在另一方面，本发明包括用不对称苯并氧杂蒽染料化合物标记的试剂，包括脱氧核苷酸，双脱氧核苷酸，亚磷酰胺和多核苷酸。在另一方面，本发明包括利用这种染料化合物的方法和包括双脱氧多核苷酸测序和片段分析方法的试剂。

48. 发明授权

US5840999A Asymmetric benzoxanthene dyes 失效
标题翻译：不对称苯并氧杂蒽染料
公开(公告)号：US5840999A
公开(公告)日：1998-11-24
申请号：US824102
申请日：1997-03-26
申请人： Scott C. Benson , Steven M. Menchen , Peter D. Theisen , Kevin M. Hennessey , Vergine C. Furniss , Joan Hauser
发明人： Scott C. Benson , Steven M. Menchen , Peter D. Theisen , Kevin M. Hennessey , Vergine C. Furniss , Joan Hauser
IPC分类号： C12N15/00 , C07C39/14 , C07C39/38 , C07D311/78 , C07F9/24 , C07H19/06 , C07H19/16 , C07H21/00 , C09B11/00 , C09B11/08 , C09B11/28 , C09K11/06 , C12N15/09 , C12Q1/68 , G01N33/533 , C07C37/68
CPC分类号： C07H21/00 , C07C39/38 , C09B11/00 , C09B11/08 , C12Q1/6869
摘要： A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having the structure ##STR1## wherein Y.sub.1, and Y.sub.2 are individually hydroxyl, amino, imminium, or oxygen, R.sub.1 -R.sub.8 are hydrogen, fluorine, chlorine, alkyl alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinations thereof, and R.sub.9 is acetylene, alkane, alkene, cyano, substituted phenyl and combinations thereof The invention ftrther includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having the general structure ##STR2## where substituents R.sub.3 -R.sub.7 correspond to like-referenced substituents in the structure of described above, and Y.sub.2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates. In yet another aspect, the present invention includes reagents labeled with the asymmetric benzoxanthene dye compounds, including deoxynucleotides, dideoxynucleotides, phosphoramidites, and polynucleotides. In an additional aspect, the invention includes methods utilizing such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.
摘要翻译：公开了一类用作荧光染料的不对称单苯并氧蒽化合物，其结构为：其中Y 1和Y 2分别是羟基，氨基，亚氨基或氧，R 1 -R 8是氢，氟，氯，烷基烯烃，炔烃磺酸盐氨基，酰氨基，腈，烷氧基，连接基团及其组合，并且R 9是乙炔，烷烃，烯烃，氰基，取代的苯基及其组合。本发明包括可用于合成具有一般性的不对称苯并氧杂蒽化合物的新型中间体化合物结构其中取代基R3-R7对应于上述结构中的相同取代基，而Y2是羟基或胺。另一方面，本发明包括合成上述染料化合物和中间体的方法。在另一方面，本发明包括用不对称苯并氧杂蒽染料化合物标记的试剂，包括脱氧核苷酸，双脱氧核苷酸，亚磷酰胺和多核苷酸。在另一方面，本发明包括利用这种染料化合物的方法和包括双脱氧多核苷酸测序和片段分析方法的试剂。

49. 发明授权

US5783687A Dyes designed for high sensitivity detection of double-stranded DNA 失效
公开(公告)号：US5783687A
公开(公告)日：1998-07-21
申请号：US708666
申请日：1996-09-05
申请人： Alexander N. Glazer , Scott C. Benson
发明人： Alexander N. Glazer , Scott C. Benson
IPC分类号： C07D221/12 , C07D405/12 , C07D417/06 , C07D417/14 , C09B23/04 , C12Q1/68 , G01N27/447 , C07H21/02
CPC分类号： C07D221/12 , C07D405/12 , C07D417/06 , C07D417/14 , C09B23/04 , C12Q1/6816 , G01N27/44726 , G01N27/44747
摘要： Novel fluorescent dyes are provided, characterized by having a fluorophore joined to a cationic chain. The dyes are found to provide for high enhancement upon binding to nucleic acid and have strong binding affinities to the nucleic acid, as compared to the fluorophore without the polycationic chain. The dyes find use in detection of dsDNA in gel electrophoresis and solution at substantially higher sensitivities using substantially less dye.

50. 发明授权

US5646264A DNA complexes with dyes designed for energy transfer as fluorescent markers 失效
标题翻译： DNA复合物与设计用于能量转移的染料作为荧光标记物
公开(公告)号：US5646264A
公开(公告)日：1997-07-08
申请号：US340749
申请日：1995-01-23
申请人： Alexander N. Glazer , Scott C. Benson
发明人： Alexander N. Glazer , Scott C. Benson
IPC分类号： G01N33/58 , C07D221/12 , C07D405/12 , C07D417/06 , C07D417/14 , C07H21/04 , C09B23/04 , C12N15/09 , C12Q1/68 , G01N27/447 , C07H21/00 , C07H19/04
CPC分类号： C07D417/14 , C07D221/12 , C07D405/12 , C07D417/06 , C09B23/04 , C12Q1/6816 , C12Q1/6818 , G01N27/44726 , G01N27/44747
摘要： Heteromultimeric fluorophores are provided for binding to DNA, which allow for the detection of DNA in electrical separations and preparation of probes having high-fluorescent efficiencies and large Stokes shifts. In addition, by appropriate choice of fluorescent molecules, one can use a single narrow wavelength band excitation light source, while obtaining fluorescent emissions having sufficient separation to be readily discriminated.
摘要翻译：提供了异源多聚体荧光团用于结合DNA，其允许在电分离中检测DNA并制备具有高荧光效率和大的斯托克斯位移的探针。此外，通过适当选择荧光分子，可以使用单个窄波长带激发光源，同时获得具有足够分离的荧光发射以易于鉴别。

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