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1. 发明申请

WO1998003673A1 HIGH FIDELITY DETECTION OF NUCLEIC ACID DIFFERENCES BY LIGASE DETECTION REACTION 审中-公开
标题翻译：通过检测反应检测核酸差异的高度检测
公开(公告)号：WO1998003673A1
公开(公告)日：1998-01-29
申请号：PCT/US1997012195
申请日：1997-07-15
申请人： CORNELL RESEARCH FOUNDATION, INC. , PURDUE RESEARCH FOUNDATION
发明人： CORNELL RESEARCH FOUNDATION, INC. , PURDUE RESEARCH FOUNDATION , BARANY, Francis , LUO, Jianying , KHANNA, Marilyn , BERGSTROM, Donald, E.
IPC分类号： C12P19/34
CPC分类号： C12Q1/6827 , C07K14/82 , C12N9/93 , C12Q1/6837 , C12Q1/6862 , C12Q2531/113 , C12Q2561/125 , C12Q2565/501
摘要： Ligase detection reaction is utilized to distinguish minority template in the presence of an excess of normal template with a thermostable ligase. This process can be carried out with a mutant ligase, thermostable ligase, or a modified oligonucleotide probe. This procedure is particularly useful for the detection of cancer-associated mutations. It has the advantage of providing a quantitative measure of the amount or ratio of minority template.
摘要翻译：利用连接酶检测反应在常规模板过量存在下用热稳定连接酶区分少数模板。该过程可以用突变连接酶，热稳定连接酶或修饰的寡核苷酸探针进行。该过程对癌症相关突变的检测特别有用。它具有提供少量模板数量或比例的定量测量的优点。

2. 发明申请

WO2005076837A3 METHOD FOR DETECTION OF PROMOTER METHYLATION STATUS 审中-公开
公开(公告)号：WO2005076837A3
公开(公告)日：2005-08-25
申请号：PCT/US2005/002803
申请日：2005-02-02
申请人： CORNELL RESEARCH FOUNDATION, INC.
发明人： BARANY, Francis , CHENG, YuWei , SHAWBER, Carrie
IPC分类号： C12Q1/68
摘要： The present invention relates to the detection of promoter methylation status using a combination of either modification of methylated DNA or restriction endonuclease digestion, multiplex polymerase chain reaction, ligase detection reaction, and a universal array or capillary electrophoresis detection.

3. 发明申请

WO2005026329A2 METHODS FOR IDENTIFYING TARGET NUCLEIC ACID MOLECULES 审中-公开
标题翻译：鉴定目标核酸分子的方法
公开(公告)号：WO2005026329A2
公开(公告)日：2005-03-24
申请号：PCT/US2004/029856
申请日：2004-09-10
申请人： CORNELL RESEARCH FOUNDATION, INC.
发明人： BARANY, Francis , TURNER, Daniel, John , PINGLE, Maneesh , PINCAS, Hanna
IPC分类号： C12N
CPC分类号： C12Q1/6827 , C12Q1/6837 , Y02A50/55 , Y02A50/57 , Y02A50/58 , C12Q2561/125 , C12Q2565/102 , C12Q2563/155
摘要： The present invention relates to methods for identifying target nucleic acid molecules differing by one or more single-base changes, insertions, deletions, or translocations; and identifying one or more target mRNA molecules differing by one or more splice site variations in a plurality of mRNA molecules. Also disclosed is a method of generating a linearly amplified representation of a whole genome. Other aspects of the present invention relate to labeled detection oligonucleotide probes and translational oligonucleotide probes as well as to methods of designing such probes.
摘要翻译：本发明涉及用于鉴定不同于一个或多个单碱基变化，插入，缺失或易位的靶核酸分子的方法; 以及鉴定由多个mRNA分子中的一个或多个剪接位点变异而不同的一个或多个靶mRNA分子。还公开了一种产生全基因组的线性放大表示的方法。本发明的其它方面涉及标记的检测寡核苷酸探针和翻译寡核苷酸探针以及设计这种探针的方法。

4. 发明申请

WO1997045559A1 DETECTION OF NUCLEIC ACID SEQUENCE DIFFERENCES USING COUPLED LIGASE DETECTION AND POLYMERASE CHAIN REACTIONS 审中-公开
标题翻译：使用联合寡核苷酸检测和聚合酶链反应检测核酸序列差异
公开(公告)号：WO1997045559A1
公开(公告)日：1997-12-04
申请号：PCT/US1997009012
申请日：1997-05-27
申请人： CORNELL RESEARCH FOUNDATION, INC. , BELGRADER, Phillip
发明人： CORNELL RESEARCH FOUNDATION, INC. , BARANY, Francis , LUBIN, Matthew
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6876 , C12Q1/6813 , C12Q1/6827 , C12Q1/683 , C12Q1/6851 , C12Q1/6853 , C12Q1/6858 , C12Q1/686 , C12Q1/6862 , C12Q1/6869 , C12Q1/6881 , C12Q2600/156 , C12Q2600/16 , C12Q2561/125 , C12Q2531/113 , C12Q2525/161 , C12Q2545/114 , C12Q2535/131 , C12Q2521/501 , C12Q2537/143 , C12Q2533/107 , C12Q2525/131 , C12Q2525/125 , C12Q2521/319 , C12Q2521/531 , C12Q2525/155
摘要： The present invention relates to the detection of nucleic acid sequence differences using coupled ligase detection reaction and polymerase chain reaction. One aspect of the present invention involves use of a ligase detection reaction coupled to a polymerase chain reaction. Another aspect of the present invention relates to the use of a primary polymerase chain reaction coupled to a secondary polymerase chain reaction coupled to a ligase detection reaction. A third aspect of the present invention involves a primary polymerase chain reaction coupled to a secondary polymerase chain reaction. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence differences.
摘要翻译：本发明涉及使用偶联连接酶检测反应和聚合酶链反应检测核酸序列差异。本发明的一个方面涉及使用与聚合酶链式反应偶联的连接酶检测反应。本发明的另一方面涉及与连接酶检测反应偶联的二级聚合酶链反应偶联的初级聚合酶链式反应的用途。本发明的第三方面涉及与第二聚合酶链反应偶联的初级聚合酶链式反应。连接酶检测反应和聚合酶链式反应的这种偶联允许核酸序列差异的多重检测。

5. 发明申请

WO2008077095A2 USE OF LECITHIN:RETINOL ACYL TRANSFERASE GENE PROMOTER METHYLATION IN EVALUATING THE CANCER STATE OF A SUBJECT 审中-公开
标题翻译：卵磷脂的使用：视黄酸转移酶基因启动子甲基化在评价受试者癌症状态中的应用
公开(公告)号：WO2008077095A2
公开(公告)日：2008-06-26
申请号：PCT/US2007/088116
申请日：2007-12-19
申请人： CORNELL RESEARCH FOUNDATION, INC. , SLOAN KETTERING CANCER CENTER , UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY , BARANY, Francis , CHENG, Yu-Wei , PATY, Philip , NOTTERMAN, Daniel
发明人： BARANY, Francis , CHENG, Yu-Wei , PATY, Philip , NOTTERMAN, Daniel
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/16
摘要： The present invention relates to a method of evaluating the cancer state of a subject using lecithin:retinol acyl transferase (LRAT) gene promoter methylation status. Methods of analyzing and quantifying LRAT gene promoter methylation level are also disclosed. The present invention also relates to methods of determining the prognosis for s subject having cancer by assessing LRAT mRNA expression and LRAT protein expression. Methods of cancer detection, diagnosis, prognosis, and treatment are also disclosed.
摘要翻译：本发明涉及使用卵磷脂：视黄醇酰基转移酶（LRAT）基因启动子甲基化状态评估受试者的癌症状态的方法。还公开了分析和量化LRAT基因启动子甲基化水平的方法。本发明还涉及通过评估LRAT mRNA表达和LRAT蛋白质表达来确定患有癌症的患者的预后的方法。还披露了癌症检测，诊断，预后和治疗的方法。

6. 发明申请

WO2006023919A2 DETECTION OF NUCLEIC ACID DIFFERENCES USING ENDONUCLEASE CLEAVAGE/LIGAS RELEASING REACTIONS AND CAPILLARY ELECTROPHORESIS OR MICROARRAYS 审中-公开
标题翻译：检测使用内切酶清除/释放反应和毛细管电泳或微量滴定的核酸不同
公开(公告)号：WO2006023919A2
公开(公告)日：2006-03-02
申请号：PCT/US2005/029966
申请日：2005-08-23
申请人： CORNELL RESEARCH FOUNDATION, INC. , BARANY, Francis , PINCAS, Hanna , HUANG, Jianmin
发明人： BARANY, Francis , PINCAS, Hanna , HUANG, Jianmin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/683 , B82Y5/00 , B82Y10/00 , C12Q2537/143 , C12Q2521/501 , C12Q2521/301 , C12Q2549/119 , C12Q2531/113 , C12Q2521/514
摘要： The present invention is directed to various methods for detecting DNA sequence differences, including single nucleotide mutations or polymorphisms, one or more nucleotide insertions, and one or more nucleotide deletions. Labeled heteroduplex PCR fragments containing base mismatches are prepared. Endonuclease cleaves the heteroduplex PCR fragments both at the position containing the variation (one or more mismatched bases) and, to a lesser extent, at non-variant (perfectly matched) positions. Ligation of the cleavage products with a DNA ligase corrects non-variant cleavages and thus substantially reduces background. This is then followed by a detection step in which the reaction products are detected, and the position of the sequence variations are determined.
摘要翻译：本发明涉及用于检测DNA序列差异的各种方法，包括单核苷酸突变或多态性，一个或多个核苷酸插入和一个或多个核苷酸缺失。制备含有碱基错配的标记的异源双链PCR片段。核酸内切酶在含有变异（一个或多个错配碱基）的位置和在非变体（完全匹配的）位置上较少程度地切割异源双链PCR片段。用DNA连接酶连接切割产物校正非变体切割，从而大大减少背景。然后进行检测步骤，其中检测反应产物，并确定序列变异的位置。

7. 发明申请

WO1995011996A1 DETECTION ASSAY FOR LISTERIA AND ERWINIA MICROORGANISMS 审中-公开
标题翻译：赖斯和艾滋病微生物的检测测定
公开(公告)号：WO1995011996A1
公开(公告)日：1995-05-04
申请号：PCT/US1994012508
申请日：1994-10-26
申请人： CORNELL RESEARCH FOUNDATION, INC.
发明人： CORNELL RESEARCH FOUNDATION, INC. , BATT, Carl, A. , WEIDMAN, Martin , BARANY, Francis
IPC分类号： C12Q01/68
CPC分类号： C12Q1/689 , C12Q1/6862
摘要： A polymerase chain reaction-coupled ligase chain reaction is described for the identification of microorganisms based upon single-base-pair differences in the genetic information of each organism.
摘要翻译：描述了基于每个生物体的遗传信息中的单碱基对差异来鉴定微生物的聚合酶链反应偶联连接酶链反应。

8. 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。

9. 发明申请

WO2012154213A1 COFLUORONS AND METHODS OF MAKING AND USING THEM 审中-公开
标题翻译： COFLORONS AND METHODS OF MAKING AND USING THEM
公开(公告)号：WO2012154213A1
公开(公告)日：2012-11-15
申请号：PCT/US2012/000198
申请日：2012-04-09
申请人： CORNELL UNIVERSITY , PURDUE RESEARCH FOUNDATION , COFERON, INC. , BARANY, Francis , PINGLE, Maneesh , BERGSTROM, Donald , GIARDINA, Sarah, F. , ARNOLD, Lee, Daniel
发明人： BARANY, Francis , PINGLE, Maneesh , BERGSTROM, Donald , GIARDINA, Sarah, F. , ARNOLD, Lee, Daniel
IPC分类号： C40B30/04 , C40B30/06 , C40B40/04
CPC分类号： G01N33/573 , C07D211/26 , C07D263/06 , C07D401/06 , C07D405/06 , C07D491/107 , C07F5/025 , C40B30/04 , C40B30/06 , C40B50/10 , C40B50/16
摘要： The present invention is directed to method of using a collection of monomers capable of forming multimers as a fluorescence reporter in different applications such as ligand detection/screening, disease diagnosis, drug discovery or screening, fluorescent labeling and imaging, or other fluorescent methodologies. Each monomer in the collection includes one or more ligand elements useful for binding to a target molecule with a dissociation constant of less than 300 μΜ and a linker element connected to the ligand elements directly or indirectly through a connector. Association of linker elements of different combinations of monomers, with their ligand elements bound to the target molecule to form a multimer, will generate a unique fluorescent signature different from that produced by those monomers either alone or in association with each other in the absence of the target molecule, when subjected to electromagnetic excitement.
摘要翻译：本发明涉及在不同应用如配体检测/筛选，疾病诊断，药物发现或筛选，荧光标记和成像或其它荧光方法中使用能够形成多聚体的单体的集合的方法。收集物中的每个单体包括一个或多个配体元件，其用于结合靶分子，解离常数小于300μ？以及通过连接器直接或间接连接到配体元件的连接体元件。不同单体组合的连接体元件与其与靶分子结合以形成多聚体的连接体元件的关联将产生独特的荧光特征，其不同于单独或彼此相关联的单体，不存在目标分子，当受到电磁兴奋时。

10. 发明申请

WO2011043817A1 COFERONS AND METHODS OF MAKING AND USING THEM 审中-公开
标题翻译：制作和使用它们的公司及方法
公开(公告)号：WO2011043817A1
公开(公告)日：2011-04-14
申请号：PCT/US2010/002708
申请日：2010-10-07
申请人： CORNELL UNIVERSITY , PURDUE RESEARCH FOUNDATION , COFERON, INC. , BARANY, Francis , PINGLE, Maneesh , BERGSTROM, Donald , GIARDINA, Sarah, F. , ARNOLD, Lee, D.
发明人： BARANY, Francis , PINGLE, Maneesh , BERGSTROM, Donald , GIARDINA, Sarah, F. , ARNOLD, Lee, D.
IPC分类号： A61F2/00
CPC分类号： C07D319/14 , C07D207/12 , C07D207/24 , C07D209/52 , C07D239/42 , C07D239/54 , C07D241/36 , C07D263/20 , C07D295/18 , C07D307/80 , C07D317/10 , C07D317/44 , C07D319/12 , C07D403/06 , C07D403/14 , C07D405/14 , C07D413/06 , C07D471/14 , C07D491/04 , C07D491/10 , C07D491/14 , C07F5/025 , C40B30/04
摘要： The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.
摘要翻译：本发明涉及可用于制备治疗化合物的单体。单体包括一个或多个药效团，其可以以小于300μM的解离常数潜在地结合靶分子，并连接到药效团。连接体元件具有小于500道尔顿的分子量，通过连接器直接或间接连接到药效团。

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