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1. 发明申请

WO2013123220A1 METHOD FOR RELATIVE QUANTIFICATION OF NUCLEIC ACID SEQUENCE, EXPRESSION, OR COPY CHANGES, USING COMBINED NUCLEASE, LIGATION, AND POLYMERASE REACTIONS 审中-公开
标题翻译：使用组合核酸酶，引物和聚合酶反应的核酸序列，表达或复制变化相对定量的方法
公开(公告)号：WO2013123220A1
公开(公告)日：2013-08-22
申请号：PCT/US2013/026180
申请日：2013-02-14
申请人： CORNELL UNIVERSITY , BARANY, Francis , SPIER, Eugene , MIR, Alain
发明人： BARANY, Francis , SPIER, Eugene , MIR, Alain
IPC分类号： C12Q1/68
CPC分类号： G01N33/5308 , C12Q1/6806 , C12Q1/6813 , C12Q1/6851 , C12Q1/6853 , C12Q1/6855 , C12Q2521/501 , C12Q2525/00 , C12Q2525/301 , C12Q2533/107 , C12Q2521/319 , C12Q2525/113 , C12Q2525/161 , C12Q2565/101 , C12Q2565/514 , C12Q2521/301
摘要： The present invention is directed to methods for identifying the presence of one or more target nucleotide sequences in a sample that involve a nuclease-ligation reaction. In some embodiments, the ligation products formed in the nuclease-ligation process of the present invention are subsequently amplified using a polymerase chain reaction. The ligated product sequences or extension products thereof are detected, and the presence of one or more target nucleotide sequences in the sample is identified based on the detection.
摘要翻译：本发明涉及用于鉴定涉及核酸酶连接反应的样品中一种或多种靶核苷酸序列的存在的方法。在一些实施方案中，随后使用聚合酶链式反应扩增在本发明的核酸酶连接方法中形成的连接产物。检测连接的产物序列或其延伸产物，并且基于检测鉴定样品中一个或多个靶核苷酸序列的存在。

2. 发明申请

WO2013012440A2 METHODS AND DEVICES FOR DNA SEQUENCING AND MOLECULAR DIAGNOSTICS 审中-公开
标题翻译：用于DNA测序和分子诊断的方法和装置
公开(公告)号：WO2013012440A2
公开(公告)日：2013-01-24
申请号：PCT/US2012/000329
申请日：2012-07-23
申请人： CORNELL UNIVERSITY , BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICL COLLEGE , BARANY, Francis, A. , SOPER, Steven, A. , GRILLS, George , CHENG, Yu-wei , HUANG, Jianmin , WANG, Hong , WITEK, Malgorzata, A. , PARK, Daniel, Sang-won , MURPHY, Michael, C , MCCARLEY, Robin, Lindsey , HUPERT, Mateusz, L.
发明人： BARANY, Francis, A. , SOPER, Steven, A. , GRILLS, George , CHENG, Yu-wei , HUANG, Jianmin , WANG, Hong , WITEK, Malgorzata, A. , PARK, Daniel, Sang-won , MURPHY, Michael, C , MCCARLEY, Robin, Lindsey , HUPERT, Mateusz, L.
IPC分类号： C12Q1/16
CPC分类号： C12Q1/6874 , C12Q1/6806 , G01N33/585 , C12Q2525/197 , C12Q2525/313 , C12Q2535/122 , C12Q2563/131 , C12Q2565/543
摘要： The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.
摘要翻译：本发明涉及捕获，扩增和鉴定样品中的多个靶核苷酸序列中的一个或多个的方法。本发明进一步涉及包含固体支持物的装置，所述固体支持物具有多个孔或柱和连接至孔或柱的多个寡核苷酸。本发明的其他方面涉及制造这种装置的方法。

3. 发明申请

WO0026381A3 HIGH FIDELITY THERMOSTABLE LIGASE AND USES THEREOF 审中-公开
标题翻译：高保暖性热稳定性用途及其应用
公开(公告)号：WO0026381A3
公开(公告)日：2000-11-09
申请号：PCT/US9925437
申请日：1999-10-29
申请人： CORNELL RES FOUNDATION INC , BARANY FRANCIS , CAO WEIGUO , TONG JIE
发明人： BARANY FRANCIS , CAO WEIGUO , TONG JIE
IPC分类号： C12N15/09 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/00 , C12N9/12 , C12Q1/68 , C12N15/52
CPC分类号： C12N9/93
摘要： The present invention is directed to a thermostable ligase having substantially higher fidelity than either T4 ligase or Thermus thermophilus ligase. The DNA molecule encoding this enzyme as well as expression systems and host cells containing it are also disclosed. The thermostable ligase of the present invention is useful in carrying out a ligase detection reaction process and a ligase chain reaction process.
摘要翻译：本发明涉及具有比T4连接酶或嗜热栖热菌连接酶高得多的保真度的热稳定连接酶。还公开了编码该酶的DNA分子以及含有它的表达系统和宿主细胞。本发明的热稳定连接酶可用于进行连接酶检测反应过程和连接酶链式反应过程。

4. 发明申请

WO2013012440A3 METHODS AND DEVICES FOR DNA SEQUENCING AND MOLECULAR DIAGNOSTICS 审中-公开
标题翻译：用于DNA测序和分子诊断的方法和装置
公开(公告)号：WO2013012440A3
公开(公告)日：2013-05-10
申请号：PCT/US2012000329
申请日：2012-07-23
申请人： UNIV CORNELL , UNIV LOUISIANA STATE , BARANY FRANCIS A , SOPER STEVEN A , GRILLS GEORGE , CHENG YU-WEI , HUANG JIANMIN , WANG HONG , WITEK MALGORZATA A , PARK DANIEL SANG-WON , MURPHY MICHAEL C , MCCARLEY ROBIN LINDSEY , HUPERT MATEUSZ L
发明人： BARANY FRANCIS A , SOPER STEVEN A , GRILLS GEORGE , CHENG YU-WEI , HUANG JIANMIN , WANG HONG , WITEK MALGORZATA A , PARK DANIEL SANG-WON , MURPHY MICHAEL C , MCCARLEY ROBIN LINDSEY , HUPERT MATEUSZ L
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12Q1/6806 , G01N33/585 , C12Q2525/197 , C12Q2525/313 , C12Q2535/122 , C12Q2563/131 , C12Q2565/543
摘要： The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.
摘要翻译：本发明涉及用于捕获，扩增和鉴定样品中的多个靶核苷酸序列中的一个或多个的方法。本发明进一步涉及包含固体支持物的装置，所述固体支持物具有多个孔或柱和连接至孔或柱的多个寡核苷酸。本发明的其他方面涉及制造这种装置的方法。

5. 发明申请

WO2013012440A8 METHODS AND DEVICES FOR DNA SEQUENCING AND MOLECULAR DIAGNOSTICS 审中-公开
标题翻译：用于DNA测序和分子诊断的方法和设备
公开(公告)号：WO2013012440A8
公开(公告)日：2013-03-07
申请号：PCT/US2012000329
申请日：2012-07-23
申请人： UNIV CORNELL , UNIV LOUISIANA STATE , BARANY FRANCIS A , SOPER STEVEN A , GRILLS GEORGE , CHENG YU-WEI , HUANG JIANMIN , WANG HONG , WITEK MALGORZATA A , PARK DANIEL SANG-WON , MURPHY MICHAEL C , MCCARLEY ROBIN LINDSEY , HUPERT MATEUSZ L
发明人： BARANY FRANCIS A , SOPER STEVEN A , GRILLS GEORGE , CHENG YU-WEI , HUANG JIANMIN , WANG HONG , WITEK MALGORZATA A , PARK DANIEL SANG-WON , MURPHY MICHAEL C , MCCARLEY ROBIN LINDSEY , HUPERT MATEUSZ L
IPC分类号： C12Q1/16
CPC分类号： C12Q1/6874 , C12Q1/6806 , G01N33/585 , C12Q2525/197 , C12Q2525/313 , C12Q2535/122 , C12Q2563/131 , C12Q2565/543
摘要： The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.
摘要翻译：本发明涉及用于捕获，扩增和鉴定样品中多个靶核苷酸序列中的一个或多个的方法。本发明进一步涉及包括具有多个孔或柱的固体支持物和连接到孔或支柱上的多个寡核苷酸的装置。本发明的其它方面涉及制造这种装置的方法。

6. 发明申请

WO2009126678A3 DETECTION OF TARGET NUCLEIC ACID SEQUENCES USING FLUORESCENCE RESONANCE ENERGY TRANSFER 审中-公开
标题翻译：使用荧光共振能量转移检测目标核酸序列
公开(公告)号：WO2009126678A3
公开(公告)日：2009-12-30
申请号：PCT/US2009039855
申请日：2009-04-08
申请人： UNIV CORNELL , PURDUE RESEARCH FOUNDATION , BARANY FRANCIS , PINGLE MANEESH , BERGSTROM DONALD
发明人： BARANY FRANCIS , PINGLE MANEESH , BERGSTROM DONALD
IPC分类号： C40B20/04 , C40B30/04
CPC分类号： C12Q1/6827 , Y10T436/143333 , C12Q2561/125 , C12Q2527/107 , C12Q2525/301
摘要： A method for identifying a plurality of target nucleic acid molecules in a sample. The method provides a plurality of oligonucleotide probe sets. Each set comprises a first and a second probe, each having a target-specific portion and a tunable portion with an acceptor or a donor group. The first probe further comprises an endcapped hairpin. A reaction comprises a denaturation and hybridization cycle. Under the hybridization, the set of probes hybridize in a base-specific manner to their respective target nucleotide sequences, and ligate to one another to form a ligation product. Under conditions that permit hybridization of the tunable portions of the ligation product to one another, an internally hybridized ligation product formed, which allows the detection of the fluorescence resonance energy transfer (FRET). A method comprising PCR amplification is also disclosed.
摘要翻译：用于鉴定样品中多个靶核酸分子的方法。该方法提供多个寡核苷酸探针组。每组包括第一和第二探针，每个具有目标特异性部分和具有受体或供体基团的可调部分。第一探针还包含封端的发夹。反应包括变性和杂交循环。在杂交下，探针组以碱基特异性方式与其各自的靶核苷酸序列杂交，并且彼此连接以形成连接产物。在允许连接产物的可调部分彼此杂交的条件下，形成内部杂交的连接产物，其允许检测荧光共振能量转移（FRET）。还公开了包括PCR扩增的方法。

7. 发明申请

WO2009126678A2 DETECTION OF TARGET NUCLEIC ACID SEQUENCES USING FLUORESCENCE RESONANCE ENERGY TRANSFER 审中-公开
标题翻译：使用荧光共振能量转移检测目标核酸序列
公开(公告)号：WO2009126678A2
公开(公告)日：2009-10-15
申请号：PCT/US2009/039855
申请日：2009-04-08
申请人： CORNELL UNIVERSITY , PURDUE RESEARCH FOUNDATION , BARANY, Francis , PINGLE, Maneesh , BERGSTROM, Donald
发明人： BARANY, Francis , PINGLE, Maneesh , BERGSTROM, Donald
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , Y10T436/143333 , C12Q2561/125 , C12Q2527/107 , C12Q2525/301
摘要： The present invention is directed to a method for identifying one or more of a plurality of target nucleic acid molecules in a sample. This method includes providing a sample potentially containing one or more target nucleic acid molecules and a plurality of oligonucleotide probe sets. Each probe set is characterized by (a) a first oligonucleotide probe, having a target-specific portion and a tunable portion with an endcapped hairpin and (b) a second oligonucleotide probe having a target specific portion and a tunable portion. One of the first and second oligonucleotide probe has an acceptor group and the other of the first and second probe has a donor group. A ligase is provided and blended with the sample and the plurality of oligonucleotide probe sets to form a ligase detection reaction mixture. The mixture is subjected to one or more ligase detection reaction cycles with each cycle comprising a denaturation and hybridization treatment. During the denaturation treatment any hybridized oligonucleotides are separated from the target nucleic acid sequences, and, during the hybridization treatment, the set of oligonucleotide probes hybridize in a base-specific manner to their respective target nucleotide sequences, if present in the sample, and ligate to one another to form a ligation product. The ligation product contains the tunable portions, the endcapped hairpin, the target-specific portions, the acceptor group, and the donor group. The ligation products are subjected to conditions effective to permit hybridization of the tunable portions of the ligation product to one another to form an internally hybridized ligation product. The fluorescence resonance energy transfer (FRET) between the donor and acceptor groups of the internally hybridized ligation product is detected, thereby indicating the presence of a target nucleic acid molecule in the sample. An alternative embodiment of the present invention involves the use of an initial PCR amplification procedure with primers provided with universal tails. Finally, FRET detection can be carried out through the use of the above-described oligonucleotide probes without any ligation.
摘要翻译：本发明涉及用于鉴定样品中多个靶核酸分子中的一种或多种的方法。该方法包括提供潜在地含有一个或多个靶核酸分子和多个寡核苷酸探针组的样品。每个探针组的特征在于：（a）具有靶特异性部分的第一寡核苷酸探针和具有封端发夹的可调部分，和（b）具有目标特异部分和可调部分的第二寡核苷酸探针。第一和第二寡核苷酸探针之一具有受体基团，第一和第二探针中的另一个具有供体基团。提供连接酶并与样品和多个寡核苷酸探针组混合以形成连接酶检测反应混合物。将混合物进行一个或多个连接酶检测反应循环，每个循环包含变性和杂交处理。在变性处理期间，将任何杂交的寡核苷酸与靶核酸序列分离，并且在杂交处理期间，寡核苷酸探针组如果存在于样品中，则以碱基特异性方式与其各自的靶核苷酸序列杂交，并连接彼此形成连接产物。连接产物包含可调部分，封端的发夹，靶特异性部分，受体基团和供体基团。连接产物经受有效的条件，允许连接产物的可调部分彼此杂交以形成内部杂交的连接产物。检测内部杂交连接产物的供体和受体组之间的荧光共振能量转移（FRET），从而表明样品中存在靶核酸分子。本发明的替代实施方案涉及使用具有通用尾部的引物的初始PCR扩增程序。最后，可以通过使用上述寡核苷酸探针而不进行任何连接来进行FRET检测。

8. 发明申请

WO0179548A3 METHOD OF DESIGNING ADDRESSABLE ARRAY FOR DETECTION OF NUCLEIC ACID SEQUENCE DIFFERENCES USING LIGASE DETECTION REACTION 审中-公开
标题翻译：设计可寻址阵列的方法，用于检测使用LIGASE检测反应的核酸序列差异
公开(公告)号：WO0179548A3
公开(公告)日：2003-02-06
申请号：PCT/US0110958
申请日：2001-04-04
申请人： CORNELL RES FOUNDATION INC , BARANY FRANCIS , ZIRVI MONIB , GERRY NORMAN P , FAVIS REYNA , KLIMAN RICHARD
发明人： BARANY FRANCIS , ZIRVI MONIB , GERRY NORMAN P , FAVIS REYNA , KLIMAN RICHARD
IPC分类号： G01N33/53 , C12M1/00 , C12N15/09 , C12Q1/25 , G01N33/569 , G01N37/00 , C12Q1/68
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q1/6874 , C12Q1/6886 , C12Q2527/107 , C12Q2521/501 , C12Q2521/319 , C12Q2565/501
摘要： The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the set differs from all other tetramers in the set by at least two nucleotide bases, (2) no two tetramers within a set are complementary to one another, (3) no tetramers within a set are palindromic or dinucleotide repeats, and (4) no tetramer within a set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units. From the collection of multimer units, all multimer units formed from the same tetramer and all multimer units having a melting temperature in DEG C of less than 4 times the number of tetramers forming a multimer unit are removed to form a modified collection of multimer units. The modified collection of multimer units is arranged in a list in order of melting temperature. The order of the modified collection of multimer units is randomized in 2 DEG C increments of melting temperature.
摘要翻译：本发明涉及一种设计多个捕获寡核苷酸探针的方法，所述多个捕获寡核苷酸探针用于互补寡核苷酸探针与少量错配杂交的载体上，其中多个捕获寡核苷酸探针具有在窄范围内的熔融温度。该方法的第一步包括提供连接在一起的四个核苷酸的多个四聚体的第一组，其中（1）组中的每个四聚体与组中的所有其它四聚体不同，至少两个核苷酸碱基，（2）否一组内的两个四聚体彼此互补，（3）一组内的四聚体没有回归或二核苷酸重复，以及（4）组内的四聚体没有一个或多个或三个或更多个G或C核苷酸。来自第一组的4至4个四聚体的组连接在一起以形成多聚体单元的集合。从多聚体单元的收集中，除去由相同的四聚体形成的所有多聚体单元和具有小于组成多聚体单元的四聚体数目的4倍的熔点的聚合温度的所有多聚体单元以形成多聚体单元的修改的集合。修改的多聚体单元的集合按照熔融温度的顺序排列在列表中。多聚体单元的修改收集的顺序是以2℃的熔融温度增量随机化。

9. 发明申请

WO1991017239A1 A THERMOSTABLE LIGASE MEDIATED DNA AMPLIFICATION SYSTEM FOR THE DETECTION OF GENETIC DISEASES 审中-公开
标题翻译：用于检测遗传病的热稳定基因介导的DNA扩增系统
公开(公告)号：WO1991017239A1
公开(公告)日：1991-11-14
申请号：PCT/US1991002968
申请日：1991-04-29
申请人： CORNELL RESEARCH FOUNDATION, INC. , CALIFORNIA INSTITUTE OF TECHNOLOGY , BARANY, Francis , ZEBALA, John , NICKERSON, Deborah, A. , KAISER, Robert, J., Jr. , HOOD, Leroy
发明人： CORNELL RESEARCH FOUNDATION, INC. , CALIFORNIA INSTITUTE OF TECHNOLOGY
IPC分类号： C12M01/18
CPC分类号： C12Q1/6858 , C12N9/93 , C12N15/10 , C12Q1/6862 , C12Q2600/156 , C12Q2531/137 , C12Q2535/131 , C12Q2527/101 , C12Q2521/501
摘要： The present invention relates to the cloning of the gene of a thermophilic DNA ligase, from Thermus aquaticus strain HB8, and the use of this ligase for the detection of specific sequences of nucleotides in a variety of nucleic acid samples, and more particularly in those samples containing a DNA sequence characterized by a difference in the nucleic acid sequence from a standard sequence including single nucleic acid base pair changes, deletions, insertions or translocations.
摘要翻译：本发明涉及从水生栖热菌菌株HB8的嗜热DNA连接酶的基因的克隆，以及使用该连接酶检测各种核酸样品中特定的核苷酸序列，更具体地，在那些样品中其含有以包含单个核酸碱基对变化，缺失，插入或易位的标准序列的核酸序列差异为特征的DNA序列。

10. 发明申请

WO2014160199A1 METHOD FOR RELATIVE QUANTIFICATION OF CHANGES IN DNA METHYLATION, USING COMBINED NUCLEASE, LIGATION, AND POLYMERASE REACTIONS 审中-公开
标题翻译：使用组合核酸酶，引物和聚合酶反应相关量化DNA甲基化变化的方法
公开(公告)号：WO2014160199A1
公开(公告)日：2014-10-02
申请号：PCT/US2014/026027
申请日：2014-03-13
申请人： CORNELL UNIVERSITY , BARANY, Francis , SPIER, Eugene
发明人： BARANY, Francis , SPIER, Eugene
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/683 , C12Q1/6858 , C12Q1/6886 , C12Q2600/154 , C12Q2521/331 , C12Q2521/501 , C12Q2525/191
摘要： The present invention is directed to methods for identifying the presence of one or more methylated or unmethylated target nucleotide sequences in a sample that involve a nuclease-ligation reaction. In some embodiments, the ligation products formed in the nuclease-ligation process of the present invention are subsequently amplified using a polymerase chain reaction. The ligated product sequences or extension products thereof are detected, and the presence of one or more methylated or unmethylated target nucleotide sequences in the sample is identified based on the detection.
摘要翻译：本发明涉及用于鉴定涉及核酸酶连接反应的样品中一种或多种甲基化或非甲基化靶核苷酸序列的存在的方法。在一些实施方案中，随后使用聚合酶链式反应扩增在本发明的核酸酶连接方法中形成的连接产物。检测连接的产物序列或其延伸产物，并且基于检测鉴定样品中一个或多个甲基化或未甲基化的靶核苷酸序列的存在。

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