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1. 发明授权

US09353412B2 Conformational probes and methods for sequencing nucleic acids 有权
标题翻译：构象探针和核酸测序方法
公开(公告)号：US09353412B2
公开(公告)日：2016-05-31
申请号：US13162325
申请日：2011-06-16
申请人： Molly He , Cheng-Yao Chen , Eric Kool , Mostafa Ronaghi , Michael Previte , Rigo Pantoja
发明人： Molly He , Cheng-Yao Chen , Eric Kool , Mostafa Ronaghi , Michael Previte , Rigo Pantoja
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6818 , C12Q2565/133 , C12Q2563/125 , C12Q2525/101 , C12Q2565/1015
摘要： This disclosure provides a method of determining a sequence of nucleotides for a nucleic acid template. The method can include the steps of contacting the nucleic acid template with a conformationally labeled polymerase and at least four different nucleotide species under conditions wherein the conformationally labeled polymerase catalyzes sequential addition of the nucleotide species to form a nucleic acid complement of the nucleic acid template, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of changes in the signal from the conformationally labeled polymerase under the conditions; and determining the rates or time durations for the changes in the signal, thereby determining the sequence of nucleotides for the nucleic acid template.
摘要翻译：本公开提供了确定核酸模板的核苷酸序列的方法。该方法可以包括以下步骤：使构象标记的聚合酶和至少四种不同的核苷酸物种在其中所述构象标记的聚合酶催化核苷酸物种的顺序加入以形成核酸模板的核酸补体的条件下接触，其中每个不同核苷酸类型的顺序加入从所述构象标记的聚合酶产生构象信号变化，并且其中所述构象信号变化的速率或持续时间对于每个不同的核苷酸种类是可区分的; 在条件下检测来自构象标记的聚合酶的信号的一系列变化; 并确定信号变化的速率或时间，从而确定核酸模板的核苷酸序列。

2. 发明申请

US20070065360A1 Nonpolar thymidine analogs 失效
标题翻译：非极性胸苷类似物
公开(公告)号：US20070065360A1
公开(公告)日：2007-03-22
申请号：US11519385
申请日：2006-09-11
申请人： Eric Kool
发明人： Eric Kool
IPC分类号： A61K51/00 , C12Q1/68 , C07D473/02 , C07H21/04
CPC分类号： C07D307/20 , A61K51/0491 , C07H21/04
摘要： Nonpolar thymidine analogs are provided comprising a dihalogenated or trihalogenated base of the structure: where R1 is a sugar moiety; R2 is H or CH3; an imaging moiety or a cytotoxic moiety and X1 and X2 are independently selected from I, Cl, Br, and F, with the proviso that not more than one F will be present at these positions.
摘要翻译：提供非极性胸苷类似物，其包含以下结构的二卤代或三卤代碱：其中R 1是糖部分; R 2是H或CH 3 N; 成像部分或细胞毒素部分，X 1和X 2独立地选自I，Cl，Br和F，条件是不超过一个F将在这些位置出席。

3. 发明申请

US20110312529A1 CONFORMATIONAL PROBES AND METHODS FOR SEQUENCING NUCLEIC ACIDS 有权
标题翻译：用于测序核酸的合成探针和方法
公开(公告)号：US20110312529A1
公开(公告)日：2011-12-22
申请号：US13162325
申请日：2011-06-16
申请人： MOLLY HE , CHENG-YAO CHEN , ERIC KOOL , MOSTAFA RONAGHI , MICHAEL PREVITE , RIGO PANTOJA
发明人： MOLLY HE , CHENG-YAO CHEN , ERIC KOOL , MOSTAFA RONAGHI , MICHAEL PREVITE , RIGO PANTOJA
IPC分类号： C40B30/04 , C40B30/00
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6818 , C12Q2565/133 , C12Q2563/125 , C12Q2525/101 , C12Q2565/1015
摘要： This disclosure provides a method of determining a sequence of nucleotides for a nucleic acid template. The method can include the steps of contacting the nucleic acid template with a conformationally labeled polymerase and at least four different nucleotide species under conditions wherein the conformationally labeled polymerase catalyzes sequential addition of the nucleotide species to form a nucleic acid complement of the nucleic acid template, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of changes in the signal from the conformationally labeled polymerase under the conditions; and determining the rates or time durations for the changes in the signal, thereby determining the sequence of nucleotides for the nucleic acid template.
摘要翻译：本公开提供了确定核酸模板的核苷酸序列的方法。该方法可以包括以下步骤：使构象标记的聚合酶和至少四种不同的核苷酸物种在其中所述构象标记的聚合酶催化核苷酸物种的顺序加入以形成核酸模板的核酸补体的条件下接触，其中每个不同核苷酸类型的顺序加入从所述构象标记的聚合酶产生构象信号变化，并且其中所述构象信号变化的速率或持续时间对于每个不同的核苷酸种类是可区分的; 在条件下检测来自构象标记的聚合酶的信号的一系列变化; 并确定信号变化的速率或时间，从而确定核酸模板的核苷酸序列。

4. 发明申请

US20070233853A1 Displaying users connected to computer servers 失效
标题翻译：显示连接到计算机服务器的用户
公开(公告)号：US20070233853A1
公开(公告)日：2007-10-04
申请号：US11395462
申请日：2006-03-30
申请人： Kanchuki Sarma , Mai-Ian Bukovec , Eric Watson , Ryan Elliott , Eric Kool-Brown
发明人： Kanchuki Sarma , Mai-Ian Bukovec , Eric Watson , Ryan Elliott , Eric Kool-Brown
IPC分类号： G06F15/16 , G06F15/173
CPC分类号： H04L41/5035 , H04L41/0893 , H04L41/22 , H04L67/22
摘要： User connection information can be displayed. User connection information can represent user connections to a plurality of computer servers of a multi-server system. User connection information can be received from a plurality of computer servers, user details can be obtained, and a representation of the user connection information for the plurality of computer servers can be displayed. Users connected to computer servers can be notified by displaying a representation of user connection information, displaying a user-notification task, receiving a selection of the user notification task, and notifying the users of an event. User connection information can be retrieved and displayed by retrieving user connection information from a plurality computer servers of a multi-server system, storing the retrieved user connection information, and displaying a representation of the user connection information based on the stored user connection information.
摘要翻译：可以显示用户连接信息。用户连接信息可以表示到多服务器系统的多个计算机服务器的用户连接。可以从多个计算机服务器接收用户连接信息，可以获得用户细节，并且可以显示用于多个计算机服务器的用户连接信息的表示。可以通过显示用户连接信息的表示，显示用户通知任务，接收用户通知任务的选择以及通知用户事件来通知连接到计算机服务器的用户。可以通过从多服务器系统的多个计算机服务器检索用户连接信息来存储检索到的用户连接信息，并且基于存储的用户连接信息显示用户连接信息的表示来检索和显示用户连接信息。

5. 发明申请

US20060160125A1 Compositions and methods for nonenzymatic ligation of oligonucleotides and detection of genetic polymorphisms 审中-公开
公开(公告)号：US20060160125A1
公开(公告)日：2006-07-20
申请号：US11373534
申请日：2006-03-10
申请人： Eric Kool
发明人： Eric Kool
IPC分类号： C12Q1/68 , C07F9/6512
CPC分类号： C12Q1/6827 , C12Q2523/109 , C12Q2525/101 , C12Q2561/125
摘要： The invention is directed to novel compositions and methods for nonenzymatic ligation of oligonucleotides. In one aspect of the invention, the nonenzymatic ligation is selenium-mediated or tellurium mediated ligation. In another aspect, the invention provides for the use of fluorescence resonance energy transfer (FRET) to detect the nonenzymatic ligation.

6. 发明申请

US20060154889A1 Polyfluorinated nucleoside analogs and methods of use thereof 审中-公开
标题翻译：多氟化核苷类似物及其使用方法
公开(公告)号：US20060154889A1
公开(公告)日：2006-07-13
申请号：US11295306
申请日：2005-12-05
申请人： Eric Kool
发明人： Eric Kool
IPC分类号： A61K48/00 , C07H21/04 , C07H19/04
CPC分类号： C07H19/04 , C07H21/04
摘要： Nucleoside analogs comprising polyfluorinated benzene, pyrrole, pyridine, indole, isoindole, or benzoimidazole rings are shown to provide for selective base pairing with self, or other polyfluorinated analogs, in preference to native nucleic acid bases. The analogs of the invention stabilize the stacking of helices, and increase hydrophobicity when introduced into an oligonucleotide.
摘要翻译：显示包含多氟化苯，吡咯，吡啶，吲哚，异吲哚或苯并咪唑环的核苷类似物优于天然核酸碱提供与自身或其他多氟化类似物的选择性碱基配对。本发明的类似物稳定螺旋的堆叠，并且当引入寡核苷酸时增加疏水性。

7. 发明申请

US20060199192A1 Universal linker compositions for the release or transfer of chemical agents from a polynucleotide 有权
标题翻译：用于从多核苷酸释放或转移化学试剂的通用接头组合物
公开(公告)号：US20060199192A1
公开(公告)日：2006-09-07
申请号：US11218961
申请日：2005-09-01
申请人： Eric Kool , Hiroshi Abe
发明人： Eric Kool , Hiroshi Abe
IPC分类号： C12Q1/68 , C07F9/02 , C07H19/04 , A61K48/00
CPC分类号： C07F9/2429 , C07F9/08 , C07F9/2408 , Y10S977/792
摘要： A universal linker structure is provided, in which a functional group and activating leaving group are placed on a tether, allowing the placement of an electrophile at the end of any nucleic acid sequence. The electrophile on the tether can react with a second nucleic acid carrying a nucleophile when the two nucleic acids are hybridized near one another, resulting in release of the leaving group, and creation of a functional change. The linker can be designed to destabilize the ligation product without slowing the rate of reaction. This lowers product inhibition, and the target DNA or RNA can become a catalyst for isothermally generating multiple signals for detection. This enhanced signal is demonstrated in solution experiments and in solid supported assays. The universal linkers of the present invention are simple and inexpensive to prepare, and can be appended to any polynucleotide in automated steps on a standard DNA synthesizer.
摘要翻译：提供通用接头结构，其中功能基团和活化离去基团置于系链上，允许在任何核酸序列末端放置亲电子试剂。当两个核酸彼此相互杂交时，系链上的亲电子体可以与携带亲核试剂的第二核酸反应，导致离去基团的释放和功能变化的产生。连接体可以被设计成使连接产物不稳定而不减慢反应速率。这降低了产物抑制，目标DNA或RNA可以成为用于等温生成多个用于检测的信号的催化剂。在溶液实验和固体支持的测定中证明了这种增强的信号。本发明的通用接头是简单且廉价的制备，并且可以在标准DNA合成仪上以自动步骤附加到任何多核苷酸。

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