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1. 发明申请

WO2012027625A9 SCAFFOLD-BASED POLYMERASE ENZYME SUBSTRATES 审中-公开
公开(公告)号：WO2012027625A9
公开(公告)日：2012-03-01
申请号：PCT/US2011/049249
申请日：2011-08-25
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC. , SHEN, Gene , SEBO, Lubomir , YUE, Stephen , SUN, David , BROGLEY, Louis , FEDEROV, Andrei
发明人： SHEN, Gene , SEBO, Lubomir , YUE, Stephen , SUN, David , BROGLEY, Louis , FEDEROV, Andrei
IPC分类号： C12N11/00 , C07D403/04 , C07D251/12 , C12Q1/68 , C12Q1/25 , G01N33/52
摘要： The invention provides a novel class of scaffold-based labeled polymerase enzyme substrates. The polymerase enzyme substrates have a multivalent core or scaffold to which is attached fluorescent dye moieties and nucleoside phosphate moities. The polymerase enzyme substrates have multiple fluorescent dye moities and/or multiple nucleoside phosphate moieties. Preferred multivalent cores comprise trifunctional six membered aromatic moities. The invention also provides for sequencing methods and kits with scaffold-based labeled polymerase enzyme substrates.

2. 发明申请

WO2017087973A1 MODIFIED NUCLEOTIDE REAGENTS 审中-公开
标题翻译：修饰的核苷酸试剂
公开(公告)号：WO2017087973A1
公开(公告)日：2017-05-26
申请号：PCT/US2016/063176
申请日：2016-11-21
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： SHEN, Gene , YUE, Stephen , SEBO, Lubomir , BROGLEY, Louis
IPC分类号： C12Q1/68 , C12N15/09 , G01N21/64 , G01N33/53
CPC分类号： C12Q1/6876 , C07H19/10 , C07H19/207 , C12Q1/6869
摘要： Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
摘要翻译：提供了包含至少一种抗生物素蛋白，至少一种染料标记的化合物和至少一种核苷酸化合物的标记的核苷酸类似物。这些类似物可用于各种基于荧光的分析方法，包括高密度分析大量高度多重光学反应，如单分子实时核酸测序反应。类似物在理想的波长处以高灵敏度可检测。它们含有调节类似物与DNA聚合酶相互作用的结构成分，从而减少光损伤并改善测序反应中类似物的动力学和其他性质。还提供了主题类似物的核苷酸和染料标记的化合物，以及可用于制备化合物和类似物的中间体。还提供了包含所述化合物的组合物，所述中间体，化合物和类似物的合成方法以及突变型DNA聚合酶。

3. 发明申请

WO2015021079A1 PROTECTED FLUORESCENT REAGENT COMPOUNDS 审中-公开
标题翻译：保护荧光试剂化合物
公开(公告)号：WO2015021079A1
公开(公告)日：2015-02-12
申请号：PCT/US2014/049833
申请日：2014-08-05
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： SEBO, Lubomir , HANES, Jeremiah , SHEN, Gene , BROGLEY, Louis , YUE, Stephen , ZHENG, Frank , LAPIN, Yuri , LYLE, John , OSUNA, Honey , FEDOROV, Andrei
IPC分类号： C12Q1/68 , G01N21/64 , G01N23/223
CPC分类号： C07H19/10 , C07F9/65586 , C07F9/65616 , C09B23/04 , C09B23/06
摘要： Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.
摘要翻译：提供了受保护的荧光试剂化合物及其合成方法。该化合物可用于各种基于荧光的分析方法，包括以高密度大量多重光学反应的分析，如单分子实时核酸测序反应。这些化合物含有荧光染料元素，其允许以期望波长的高灵敏度检测化合物，允许化合物由靶生物分子特异性识别的结合元件以及减少荧光染料元件之间的不期望接触的保护屏蔽元件和结合的靶生物分子，因此由荧光染料元素降低结合的靶生物分子的光损伤。

4. 发明申请

WO2013123258A1 POLYMERASE ENZYME SUBSTRATES WITH PROTEIN SHIELD 审中-公开
标题翻译：具有蛋白质屏蔽的聚合酶基质
公开(公告)号：WO2013123258A1
公开(公告)日：2013-08-22
申请号：PCT/US2013/026222
申请日：2013-02-14
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： BJORNSON, Keith , HANES, Jeremiah , MILLER, Erik , KAMTEKAR, Satwik , SEBO, Lubomir , BROGLEY, Louis
IPC分类号： C12N9/10 , C12N15/54 , C12Q1/68 , C12M1/38
CPC分类号： C07H21/04 , C07H19/06 , C07H19/16 , C07K14/36 , C12N9/10 , C12Q1/6869 , C12Q1/6874 , C12Q2523/313 , C12Q2535/113 , C12Q2563/107 , C12Q2563/131 , G01N33/582 , G01N33/583
摘要： Compositions and methods are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The protein prevents the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.
摘要翻译：提供了包含用于提高单分子实时测序中酶光稳定性的蛋白质屏蔽物的核苷酸类似物的组合物和方法。本发明的核苷酸类似物在染料部分和类似物的核苷酸部分之间具有蛋白质屏蔽。蛋白质可以防止染料部分与进行核苷酸合成的酶直接相互作用，从而防止酶对光的损伤。本发明的核苷酸类似物可以具有多个染料和多个核苷酸部分。

5. 发明申请

WO2017087975A1 LABELED NUCLEOTIDE ANALOGS, REACTION MIXTURES, AND METHODS AND SYSTEMS FOR SEQUENCING 审中-公开
标题翻译：标记的核苷酸类似物，反应混合物以及用于测序的方法和系统
公开(公告)号：WO2017087975A1
公开(公告)日：2017-05-26
申请号：PCT/US2016/063178
申请日：2016-11-21
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： SEBO, Lubomir , SHEN, Gene , YUE, Stephen , OSUNA, Honey , LAPIN, Yuri , BROGLEY, Louis , FEDOROV, Andrei
IPC分类号： A61F2/06 , A61F2/82 , A61L31/08 , C08L67/02 , C08L67/04 , C08L67/06
CPC分类号： C12Q1/6869 , C07H19/10 , C07K19/00 , C12Q2563/107
摘要： Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
摘要翻译：提供了包含至少一种抗生物素蛋白，至少一种染料标记的化合物和至少一种核苷酸化合物的标记的核苷酸类似物。这些类似物可用于各种基于荧光的分析方法，包括高密度分析大量高度多重光学反应，如单分子实时核酸测序反应。类似物在理想的波长处以高灵敏度可检测。它们含有调节类似物与DNA聚合酶相互作用的结构成分，从而减少光损伤并改善测序反应中类似物的动力学和其他性质。还提供了主题类似物的核苷酸和染料标记的化合物，以及可用于制备化合物和类似物的中间体。还提供了包含所述化合物的组合物，所述中间体，化合物和类似物的合成方法以及突变型DNA聚合酶。

6. 发明申请

WO2016126941A1 MULTIMERIC PROTECTED FLUORESCENT REAGENTS 审中-公开
标题翻译：多元保护荧光试剂
公开(公告)号：WO2016126941A1
公开(公告)日：2016-08-11
申请号：PCT/US2016/016564
申请日：2016-02-04
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： ZHENG, Frank , HANES, Jeremiah , SHEN, Gene , BROGLEY, Louis , YUE, Stephen , LAPIN, Yuri , LYLE, John , OSUNA, Honey , FEDOROV, Andrei , SEBO, Lubomir
IPC分类号： A61K38/00 , A61K38/02 , C07K14/435 , C12Q1/68 , G01N33/58
CPC分类号： C09B23/105 , C09B23/06 , C09B69/00 , C09B69/105 , G01N33/533
摘要： Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.
摘要翻译：提供了多聚体保护的荧光试剂及其合成方法。这些试剂可用于各种基于荧光的分析方法，包括以高密度大量多重光学反应的分析，如单分子实时核酸测序反应。试剂含有荧光染料元素，其允许以期望波长的高灵敏度检测化合物，允许化合物被目标生物分子特异性识别的结合元件以及减少荧光染料元件之间不希望的接触的保护屏蔽元件和结合的靶生物分子，因此由荧光染料元素降低结合的靶生物分子的光损伤。试剂还含有偶联元件将单体化合物连接成多聚体形式，从而增加亮度。

7. 发明申请

WO2017087975A9 LABELED NUCLEOTIDE ANALOGS, REACTION MIXTURES, AND METHODS AND SYSTEMS FOR SEQUENCING 审中-公开
公开(公告)号：WO2017087975A9
公开(公告)日：2017-05-26
申请号：PCT/US2016/063178
申请日：2016-11-21
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： SEBO, Lubomir , SHEN, Gene , YUE, Stephen , OSUNA, Honey , LAPIN, Yuri , BROGLEY, Louis , FEDOROV, Andrei
IPC分类号： A61F2/06 , A61F2/82 , A61L31/08 , C08L67/02 , C08L67/04 , C08L67/06
摘要： Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

8. 发明公开

EP3590948A1 POLYMERASE ENZYME SUBSTRATES WITH PROTEIN SHIELD 审中-公开
公开(公告)号：EP3590948A1
公开(公告)日：2020-01-08
申请号：EP19182978.7
申请日：2013-02-14
申请人： Pacific Biosciences of California, Inc.
发明人： BJORNSON, Keith , HANES, Jeremiah , MILLER, Erik , KAMTEKAR, Satwik , SEBO, Lubomir , BROGLEY, Louis
IPC分类号： C07H19/00 , C07K14/36 , C07K14/465 , C12N9/10 , C12N9/22 , C12Q1/6869 , C12Q1/6874
摘要： Polymerase enzyme substrates comprising nucleotide analogs with protein shields for improving enzyme photostability in single molecule real time sequencing are disclosed. Nucleotide analogs of the invention have a protein shield of at least 60 amino acids between the dye moieties and nucleotide moieties of the analog. The protein further prevents the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties. Further claimed are methods for sequencing and optical detecting systems employing the nucleotide analogs.

9. 发明公开

EP3377658A1 MODIFIED NUCLEOTIDE REAGENTS 审中-公开
公开(公告)号：EP3377658A1
公开(公告)日：2018-09-26
申请号：EP16867350.7
申请日：2016-11-21
申请人： Pacific Biosciences Of California, Inc.
发明人： SHEN, Gene , YUE, Stephen , SEBO, Lubomir , BROGLEY, Louis
IPC分类号： C12Q1/68 , C12N15/09 , G01N21/64 , G01N33/53
CPC分类号： C12Q1/6876 , C07H19/10 , C07H19/207 , C09B69/105 , C12Q1/6869
摘要： Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

10. 发明公开

EP3376997A1 LABELED NUCLEOTIDE ANALOGS, REACTION MIXTURES, AND METHODS AND SYSTEMS FOR SEQUENCING 审中-实审转让
公开(公告)号：EP3376997A1
公开(公告)日：2018-09-26
申请号：EP16867352.3
申请日：2016-11-21
申请人： Pacific Biosciences Of California, Inc.
发明人： SEBO, Lubomir , SHEN, Gene , YUE, Stephen , OSUNA, Honey , LAPIN, Yuri , BROGLEY, Louis , FEDOROV, Andrei
IPC分类号： A61F2/06 , A61F2/82 , A61L31/08 , C08L67/02 , C08L67/04 , C08L67/06
CPC分类号： C12Q1/6869 , C07H19/10 , C07H19/207 , C07K19/00 , C09B69/105 , C12Q2563/107
摘要： Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

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