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41. 发明授权

US08597891B2 Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions 失效
公开(公告)号：US08597891B2
公开(公告)日：2013-12-03
申请号：US13543365
申请日：2012-07-06
申请人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
发明人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
IPC分类号： C12Q1/68 , C12P19/34
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 a method for identifying a target nucleotide sequence. This method involves forming a ligation product on a target nucleotide sequence in a ligation detection reaction mixture, amplifying the ligation product to form an amplified ligation product in a polymerase chain reaction (PCR) mixture, detecting the amplified ligation product, and identifying the target nucleotide sequence. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence difference.

42. 发明授权

US08288521B2 Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays 有权
标题翻译：使用具有可寻址阵列的连接酶检测反应检测核酸序列差异
公开(公告)号：US08288521B2
公开(公告)日：2012-10-16
申请号：US13072442
申请日：2011-03-25
申请人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
发明人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
IPC分类号： C07H21/04 , C12N15/11
CPC分类号： C12Q1/6827 , B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00711 , B01J2219/00722 , B01J2219/00729 , B82Y30/00 , C12Q1/6816 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C40B40/06 , C40B60/14 , Y02A50/58 , C12Q2565/501 , C12Q2561/125 , C12Q2537/143 , C12Q2565/514
摘要： The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support.
摘要翻译：本发明描述了用于鉴定多个靶核苷酸序列中一个或多个单碱基变化，插入，缺失或易位不同的多个序列中的一个或多个的方法。该方法包括连接阶段，捕获阶段和检测阶段。连接阶段利用具有目标序列特异性部分的一个寡核苷酸探针与可寻址阵列特异性部分之间的连接检测反应和具有靶序列特异性部分和可检测标记的第二寡核苷酸探针。在连接阶段之后，捕获阶段通过将连接的寡核苷酸探针与具有固定化捕获寡核苷酸阵列的固体支持物杂交进行，其中至少一些与可寻址阵列特异性部分互补。捕获阶段完成后，进行检测阶段以检测与固体支持物杂交的连接的寡核苷酸探针的标记。

43. 发明申请

US20110257034A1 METHODS FOR IDENTIFYING GENES WHICH PREDICT DISEASE OUTCOME FOR PATIENTS WITH COLON CANCER 审中-公开
标题翻译：识别患有结肠癌患者预防疾病的基因的方法
公开(公告)号：US20110257034A1
公开(公告)日：2011-10-20
申请号：US13123689
申请日：2009-10-13
申请人： Francis Barany , Owen Parker , Manny D. Bacolod , Sarah F. Giardina , Yu-wei Cheng , Daniel A. Notterman , Gunter S. Schemmann , Philip B. Paty , Monib Zirvi
发明人： Francis Barany , Owen Parker , Manny D. Bacolod , Sarah F. Giardina , Yu-wei Cheng , Daniel A. Notterman , Gunter S. Schemmann , Philip B. Paty , Monib Zirvi
IPC分类号： C40B30/04 , C40B40/06 , G01N33/53 , C40B40/08 , C12Q1/68 , G01N33/566
CPC分类号： G01N33/57419
摘要： Closures for containers and methods for using same are provided. In a general embodiment/the present disclosure provides a closure having a top portion (12), a bottom portion (14) and a side portion (16), an aperture (18) extending though the closure, a projection (20) extending from the closure and at least two rib members (36) on an interior of the projection. The projection may also include a cover (22). In another embodiment, a method for using a closure includes inserting a. spike member into a projection, piercing a membrane that hermetically seals a medical container, pushing rib members within the projection to center the spike member inserted into the projection, and tearing the membrane to create a vent hole in the membrane.
摘要翻译：提供容器的封闭件和使用容器的方法。在一般实施例中，本公开提供了一种具有顶部部分（12），底部部分（14）和侧部部分（16）的封闭件，通过封闭件延伸的孔口（18）所述封闭件和所述突起的内部上的至少两个肋构件（36）。突起还可以包括盖（22）。在另一个实施例中，一种使用闭合件的方法包括：突出部件突入，刺穿密封医疗容器的膜，推动突起内的肋构件以使插入突起中的钉构件居中，并撕裂膜以在隔膜中形成通气孔。

44. 发明授权

US07893233B2 Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays 有权
标题翻译：使用具有可寻址阵列的连接酶检测反应检测核酸序列差异
公开(公告)号：US07893233B2
公开(公告)日：2011-02-22
申请号：US12725230
申请日：2010-03-16
申请人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
发明人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
IPC分类号： C07H21/04 , C12N15/11
CPC分类号： C12Q1/6827 , B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00711 , B01J2219/00722 , B01J2219/00729 , B82Y30/00 , C12Q1/6816 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C40B40/06 , C40B60/14 , Y02A50/58 , C12Q2565/501 , C12Q2561/125 , C12Q2537/143 , C12Q2565/514
摘要： The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support.
摘要翻译：本发明描述了用于鉴定多个靶核苷酸序列中一个或多个单碱基变化，插入，缺失或易位不同的多个序列中的一个或多个的方法。该方法包括连接阶段，捕获阶段和检测阶段。连接阶段利用具有目标序列特异性部分的一个寡核苷酸探针与可寻址阵列特异性部分之间的连接检测反应和具有靶序列特异性部分和可检测标记的第二寡核苷酸探针。在连接阶段之后，捕获阶段通过将连接的寡核苷酸探针与具有固定化捕获寡核苷酸阵列的固体支持物杂交进行，其中至少一些与可寻址阵列特异性部分互补。捕获阶段完成后，进行检测阶段以检测与固体支持物杂交的连接的寡核苷酸探针的标记。

45. 发明授权

US07556924B2 Detection of nucleic acid sequence differences using coupled ligase detection with padlock probes and polymerase chain reactions 有权
标题翻译：使用挂锁探针和聚合酶链反应的偶联连接酶检测检测核酸序列差异
公开(公告)号：US07556924B2
公开(公告)日：2009-07-07
申请号：US11931403
申请日：2007-10-31
申请人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
发明人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
IPC分类号： C12Q1/68 , C12P19/34
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 a method for identifying a target nucleotide sequence. This method involves forming a ligation product on a target nucleotide sequence in a ligase detection reaction mixture, amplifying the ligation product to form an amplified ligation product in a polymerase chain reaction (PCR) mixture, detecting the amplified ligation product, and identifying the target nucleotide sequence. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence differences.
摘要翻译：本发明涉及鉴定靶核苷酸序列的方法。该方法包括在连接酶检测反应混合物中的靶核苷酸序列上形成连接产物，扩增连接产物以在聚合酶链式反应（PCR）混合物中形成扩增的连接产物，检测扩增的连接产物，并鉴定靶核苷酸序列。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。

46. 发明授权

US07364858B2 Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions 有权
公开(公告)号：US07364858B2
公开(公告)日：2008-04-29
申请号：US11590529
申请日：2006-10-31
申请人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
发明人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
IPC分类号： C12Q1/68 , C12P19/34
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 a method for identifying a target nucleotide sequence. This method involves forming a ligation product on a target nucleotide sequence in a ligase detection reaction mixture, amplifying the ligation product to form an amplified ligation product in a polymerase chain reaction (PCR) mixture, detecting the amplified ligation product, and identifying the target nucleotide sequence. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence differences.

47. 发明授权

US07332285B2 Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions 有权
公开(公告)号：US07332285B2
公开(公告)日：2008-02-19
申请号：US11590383
申请日：2006-10-31
申请人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
发明人： Francis Barany , Matthew Lubin , George Barany , Robert P. Hammer
IPC分类号： C12Q1/68 , C12P19/34
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 a method for identifying a target nucleotide sequence. This method involves forming a ligation product on a target nucleotide sequence in a ligase detection reaction mixture, amplifying the ligation product to form an amplified ligation product in a polymerase chain reaction (PCR) mixture, detecting the amplified ligation product, and identifying the target nucleotide sequence. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence differences.

48. 发明申请

US20060024731A1 Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions 有权
标题翻译：使用偶联连接酶检测和聚合酶链反应检测核酸序列差异
公开(公告)号：US20060024731A1
公开(公告)日：2006-02-02
申请号：US11229366
申请日：2005-09-16
申请人： Francis Barany , Matthew Lubin , George Barany , Robert Hammer
发明人： Francis Barany , Matthew Lubin , George Barany , Robert Hammer
IPC分类号： C12Q1/68 , C12P19/34
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 a method for identifying a target nucleotide sequence. This method involves forming a ligation product on a target nucleotide sequence in a ligase detection reaction mixture, amplifying the ligation product to form an amplified ligation product in a polymerase chain reaction (PCR) mixture, detecting the amplified ligation product, and identifying the target nucleotide sequence. Such coupling of the ligase detection reaction and the polymerase chain reaction permits multiplex detection of nucleic acid sequence differences.
摘要翻译：本发明涉及鉴定靶核苷酸序列的方法。该方法包括在连接酶检测反应混合物中的靶核苷酸序列上形成连接产物，扩增连接产物以在聚合酶链式反应（PCR）混合物中形成扩增的连接产物，检测扩增的连接产物，并鉴定靶核苷酸序列。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。

49. 发明申请

US20050266487A1 High fidelity thermostable ligase and uses thereof 有权
标题翻译：高保真热稳定连接酶及其用途
公开(公告)号：US20050266487A1
公开(公告)日：2005-12-01
申请号：US11167048
申请日：2005-06-24
申请人： Francis Barany , Weiguo Cao , Jie Tong
发明人： Francis Barany , Weiguo Cao , Jie Tong
IPC分类号： C07H21/04 , C12N9/00 , C12N9/22 , C12Q1/68
CPC分类号： C12N9/93
摘要： The present invention is directed to a mutant thermostable ligase having substantially higher fidelity than either T4 ligase or Thermus thermophilus ligase. The ligase of the present invention is a mutant of a wild-type thermostable ligase having a histidine adjacent a KXDG motif, where the mutant thermostable ligase has a mutation in its amino sequence where the histidine adjacent the KXDG motif in the wild-type thermostable ligase is replaced with an arginine, and wherein X is any amino acid. 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：本发明涉及一种具有比T4连接酶或Thermus thermophilus连接酶具有更高保真度的突变热稳定连接酶。本发明的连接酶是具有与KXDG基序相邻的组氨酸的野生型热稳定连接酶的突变体，其中突变热稳定连接酶在其氨基序列中具有突变，其中野生型热稳定连接酶中KXDG基序相邻的组氨酸被精氨酸代替，其中X是任何氨基酸。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反应过程。

50. 发明申请

US20050227265A1 Method for detection of promoter methylation status 有权
标题翻译：检测启动子甲基化状态的方法
公开(公告)号：US20050227265A1
公开(公告)日：2005-10-13
申请号：US11049446
申请日：2005-02-02
申请人： Francis Barany , YuWei Cheng , Carrie Shawber
发明人： Francis Barany , YuWei Cheng , Carrie Shawber
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6813 , C12Q1/6858 , C12Q2537/143 , C12Q2537/164
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.
摘要翻译：本发明涉及使用甲基化DNA的修饰或限制性内切核酸酶消化，多重聚合酶链反应，连接酶检测反应和通用阵列或毛细管电泳检测的组合来检测启动子甲基化状态。

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