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1. 发明申请

WO9907896A3 DETECTION AND CONFIRMATION OF NUCLEIC ACID SEQUENCES BY USE OF OLIGONUCLEOTIDES COMPRISING A SUBSEQUENCE HYBRIDIZING EXACTLY TO A KNOWN TERMINAL SEQUENCE AND A SUBSEQUENCE HYBRIDIZING TO AN UNIDENTIFIED SEQUENCE 审中-公开
标题翻译：核苷酸序列的检测和确认通过使用包含随机杂交的寡核苷酸完全杂交到已知的终末序列和随机杂交到未经鉴别的序列
公开(公告)号：WO9907896A3
公开(公告)日：1999-04-29
申请号：PCT/US9816548
申请日：1998-08-07
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , DEEM MICHAEL W , SIMPSON JOHN W
发明人： ROTHBERG JONATHAN M , DEEM MICHAEL W , SIMPSON JOHN W
IPC分类号： C12N15/09 , C12N15/10 , C12Q1/68
CPC分类号： C12N15/1093 , C12Q1/6809 , C12Q1/6813 , C12Q1/6855 , C12Q2525/191 , C12Q2565/125
摘要： The present invention discloses a methodology which is directed to providing positive confirmation that nucleic acids, possessing putatively identified sequences predicted to generate observed GeneCalling signals, are actually present within the sample from which the signal was originally derived. The putatively identified nucleic acid fragment within the sample possesses 3'- and 5'-ends with known terminal subsequences, said method comprising: contacting said nucleic acid fragments in said sample in amplifying conditions with (i) a nucleic acid polymerase; (ii) "regular" primer oligonucleotides having sequences comprising hybridizable portions of said known terminal subsequences; and (iii) a "poisoning" oligonucleotide primer, said poisoning primer having a sequence comprising a first subsequence that is a portion of the sequence of one of said known terminal subsequences and a second subsequence that is a hybridizable portion of said putatively unidentified sequence which is adjacent to said one known terminal subsequence, wherein nucleic acids amplified with said poisoning primer are distinguishable upon detection from nucleic acids amplified with said nucleic acids amplified only with said regular primers; separating the products of the contacting step; and the detecting sequence is confirmed if the nucleic acids amplified with said poisoning primer are detected.
摘要翻译：本发明公开了一种旨在提供肯定确认的方法，核酸具有预测产生观察到的GeneCalling TM信号的推定鉴定序列实际上存在于最初得到信号的样本内。所述样品中的推测鉴定的核酸片段具有已知末端亚序列的3'和5'末端，所述方法包括：使扩增条件下的所述样品中的所述核酸片段与（i）核酸聚合酶; （ii）具有包含所述已知末端子序列的可杂交部分的序列的“规则”引物寡核苷酸; 所述中毒引物具有包含作为所述已知末端子序列之一序列的一部分的第一子序列和作为所述假定未鉴定序列的可杂交部分的第二子序列的序列，与所述一个已知末端子序列相邻，其中用所述中毒引物扩增的核酸在从用所述常规引物扩增的所述核酸扩增的核酸检测时是可区分的; 分离接触步骤的产物; 如果检测到用所述中毒引物扩增的核酸，则确认检测序列。

2. 发明申请

WO0120039A3 METHOD OF SEQUENCING A NUCLEIC ACID 审中-公开
标题翻译：测序核酸的方法
公开(公告)号：WO0120039A3
公开(公告)日：2002-03-21
申请号：PCT/US0025290
申请日：2000-09-15
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , BADER JOEL S , DEWELL SCOTT B , MCDADE KEITH , SIMPSON JOHN W , BERKA JAN , COLANGELO CHRISTOPHER M
发明人： ROTHBERG JONATHAN M , BADER JOEL S , DEWELL SCOTT B , MCDADE KEITH , SIMPSON JOHN W , BERKA JAN , COLANGELO CHRISTOPHER M
IPC分类号： G01N33/50 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N21/05 , G01N21/17 , G01N33/15 , G01N33/53 , G01N33/566 , H04N5/225 , B01J19/00
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q1/6869 , C12Q1/6874 , C12Q2531/125 , C12Q2535/101 , C12Q2565/301
摘要： Disclosed herein are methods and apparatuses for sequencing a nucleic acid. In one aspect, the method includes annealing a population of circular nucleic acid molecules to a plurality of anchor primers linked to a solid support, and amplifying those members of the population of circular nucleic acid molecules which anneal to the target nucleic acid, and then sequencing the amplified molecules by detecting the presence of a sequence by-product such as pyrophosphate.
摘要翻译：本文公开了用于测序核酸的方法和装置。一方面，该方法包括将多个环状核酸分子退火至与固体支持物连接的多个锚定引物，并扩增与靶核酸退火的环状核酸分子群体的那些成员，然后测序通过检测序列副产物如焦磷酸盐的存在来扩增分子。

3. 发明申请

WO0007018A3 THREE-HYBRID SCREENING METHOD FOR LIGAND-PROTEIN INTERACTIONS 审中-公开
标题翻译：用于配体蛋白相互作用的三种混合筛选方法
公开(公告)号：WO0007018A3
公开(公告)日：2001-10-04
申请号：PCT/US9917055
申请日：1999-07-28
申请人： CURAGEN CORP , MEHTA VIMAL D , JARVIE TOMAS P , ROTHBERG JONATHAN M
发明人： MEHTA VIMAL D , JARVIE TOMAS P , ROTHBERG JONATHAN M
IPC分类号： G01N33/53 , C12N1/19 , C12N5/10 , C12N15/09 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/50 , G01N33/542 , G01N33/566 , G01N33/68
CPC分类号： G01N33/542 , C12Q1/6897
摘要： A rapid method and kit is provided for identifying the targets of biologically active small molecules to identify new drugs that are capable of specific therapeutic effects as well as to identify novel small molecules including agonists and antagonists that may bind selected targets.
摘要翻译：提供了一种快速方法和试剂盒，用于鉴定生物活性小分子的靶标，以鉴定能够具有特定治疗效果的新药物，以及鉴定可能结合所选靶标的新型小分子，包括激动剂和拮抗剂。

4. 发明申请

WO0218661A2 METHODS FOR IDENTIFYING NOVEL THERAPEUTIC AGENTS 审中-公开
标题翻译：识别新型治疗药物的方法
公开(公告)号：WO0218661A2
公开(公告)日：2002-03-07
申请号：PCT/US0141982
申请日：2001-09-04
申请人： CURAGEN CORP , HERRMANN JOHN L , RASTELLI LUCA , BURGESS CATHERINE E , GOULD ROTHBERG BONNIE E , ROTHBERG JONATHAN M , SKIMKETS RICHARD A
发明人： HERRMANN JOHN L , RASTELLI LUCA , BURGESS CATHERINE E , GOULD-ROTHBERG BONNIE E , ROTHBERG JONATHAN M , SKIMKETS RICHARD A
IPC分类号： C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/18 , G06F19/24 , G01N33/53 , G06F17/00
CPC分类号： G06F19/18 , C12Q2600/158 , G06F19/24
摘要： The invention provides a method for identifying a therapeutic agent. The method includes detecting a nucleic acid in a test sample, e.g. cells, cell lines or tissue, which contains a plurality of nucleic acid species, determining if the detected nucleic acid contributes to a disease state and is thus a qualified therapeutic target, and establishing if the qualified therapeutic target plays a role in disease progress and is thus a verified therapeutic candidate that can function as a therapeutic agent.
摘要翻译：本发明提供了用于鉴定治疗剂的方法。该方法包括检测测试样品中的核酸，例如，包含多个核酸物质的细胞，细胞系或组织，确定所检测的核酸是否有助于疾病状态，因此是合格的治疗靶标，并确定合格的治疗靶标是否在疾病进展中起作用，并且是因此可以用作治疗剂的已验证的治疗候选物。

5. 发明申请

WO0040757A9 METHOD OF IDENTIFYING NUCLEIC ACIDS 审中-公开
标题翻译：鉴定核酸的方法
公开(公告)号：WO0040757A9
公开(公告)日：2001-09-20
申请号：PCT/US0000402
申请日：2000-01-07
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , MCKENNA MICHAEL , PREDKI PAUL , WINDEMUTH ANDREAS , SHIMKETS RICHARD A
发明人： ROTHBERG JONATHAN M , MCKENNA MICHAEL , PREDKI PAUL , WINDEMUTH ANDREAS , SHIMKETS RICHARD A
IPC分类号： G01N33/50 , C12N15/09 , C12N15/10 , C12Q1/68 , G01N33/53 , G01N33/566
CPC分类号： C12N15/1096 , C12N15/1034 , C12N15/1093
摘要： Disclosed are methods for identifying nucleic acids in a sample of nucleic acids in which nucleic acids are initially present in unequal amounts. The methods include partitioning the starting population of nucleic acids to form one or more subpopulations, and then identifying nucleic acids that are present in different amounts in the partitioned nucleic acid sample as compared to the starting population.
摘要翻译：公开了用于鉴定核酸样品中核酸最初以不等量存在的核酸的方法。所述方法包括将起始核酸群体分配以形成一个或多个亚群体，然后鉴定与起始群体相比在分配的核酸样品中以不同的量存在的核酸。

6. 发明申请

WO0138580A9 NUCLEIC ACID PROBE ARRAYS 审中-公开
标题翻译：核酸探针阵列
公开(公告)号：WO0138580A9
公开(公告)日：2002-12-05
申请号：PCT/US0032131
申请日：2000-11-27
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , BADER JOEL S
发明人： ROTHBERG JONATHAN M , BADER JOEL S
IPC分类号： G01N33/53 , C12M1/00 , C12N15/09 , C12Q1/48 , C12Q1/68 , G01N33/566 , G01N37/00
CPC分类号： B82Y30/00 , C12Q1/682 , C12Q1/6853 , C12Q2600/156 , C12Q2565/519 , C12Q2531/125 , C12Q2521/501
摘要： Disclosed are nucleic acid probe arrays and methods of identifying and sequencing nucleic acids in a population of nucleic acids using the arrays. The method is preferably performed by annealing a nucleic acid template to an anchor primer attached to a durface of the array. At least one anchor in the array has a sequence complementary to sequences at the 5' and 3' termini of a target nucleic acid.The annealed linear target nucleic acid is circularized using one or two ligation reactions. In one embodiment, one liggation is issued. Annealing of of the linear nucleic acid results in juxtaposition of the 5' and 3' termini of the target nucleic acid on the anchor primer. Addition of a ligase results in circulization of the target nucleic acid. This circularized nucleic acid is a template for extension of the anchor primer in a rolling circle amplification reaction. An extended anchor primer containing multiple copies of a sequence complementary to the circular mucleic acid is also referred to herein as a anchor primer nucleid acid-nucleic acid concatamer. The presence of multiple copies of the complementary sequence facilitates detection of the nucleic acid. Thus, the method provides for a highly sensitive method of detecting a desired nucleic acid attached at a discrete location on the array.
摘要翻译：公开了核酸探针阵列和使用阵列鉴定和测序核酸群体中的核酸的方法。该方法优选通过将核酸模板退火至连接到阵列的表面的锚定引物进行。阵列中的至少一个锚具有与靶核酸的5'和3'末端的序列互补的序列。退火的线性靶核酸使用一个或两个连接反应进行环化。在一个实施例中，发出一次结扎。线性核酸的退火导致靶核酸的5'和3'末端在锚定引物上并列。连接酶的加入导致靶核酸的循环。该循环核酸是用于在滚环扩增反应中延伸锚定引物的模板。包含与环状核酸互补的多个拷贝的扩增的锚定引物在本文中也称为锚定引物核酸 - 核酸连接体。互补序列的多拷贝的存在便于检测核酸。因此，该方法提供了检测在阵列上离散位置附着的所需核酸的高灵敏度方法。

7. 发明申请

WO0138580A2 NUCLEIC ACID PROBE ARRAYS 审中-公开
标题翻译：核酸探针阵列
公开(公告)号：WO0138580A2
公开(公告)日：2001-05-31
申请号：PCT/US0032131
申请日：2000-11-27
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , BADER JOEL S
发明人： ROTHBERG JONATHAN M , BADER JOEL S
IPC分类号： G01N33/53 , C12M1/00 , C12N15/09 , C12Q1/48 , C12Q1/68 , G01N33/566 , G01N37/00
CPC分类号： B82Y30/00 , C12Q1/682 , C12Q1/6853 , C12Q2600/156 , C12Q2565/519 , C12Q2531/125 , C12Q2521/501
摘要： Disclosed are nucleic acid probe arrays and methods of identifying and sequencing nucleic acids in a population of nucleic acids using the arrays.
摘要翻译：公开了核酸探针阵列和使用阵列鉴定和测序核酸群体中的核酸的方法。

8. 发明申请

WO2007081386A2 MICROFLUIDIC DEVICES AND METHODS OF USE 审中-公开
标题翻译：微流体装置及其使用方法
公开(公告)号：WO2007081386A2
公开(公告)日：2007-07-19
申请号：PCT/US2006021286
申请日：2006-06-01
申请人： RAINDANCE TECHNOLOGIES INC , LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
发明人： LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
IPC分类号： B01L3/00 , B01F13/00 , G01N15/14
CPC分类号： C12N15/1075 , B01F3/0807 , B01F13/0071 , B01F13/0076 , B01J19/0046 , B01J2219/00286 , B01J2219/00459 , B01J2219/00466 , B01J2219/00468 , B01J2219/00479 , B01J2219/005 , B01J2219/00576 , B01J2219/00599 , B01J2219/00702 , B01J2219/0072 , B01J2219/00743 , B01L3/5027 , B01L3/502715 , B01L3/50273 , B01L3/502746 , B01L3/502761 , B01L3/502784 , B01L3/502792 , B01L3/565 , B01L7/52 , B01L2200/027 , B01L2200/0621 , B01L2200/0647 , B01L2200/0652 , B01L2200/0673 , B01L2300/0816 , B01L2300/0864 , B01L2300/0867 , B01L2300/0896 , B01L2400/0415 , B01L2400/0424 , B01L2400/0487 , B01L2400/084 , B82Y5/00 , B82Y30/00 , C07K1/047 , C12Q1/6804 , C12Q1/6816 , C12Q1/6825 , C12Q1/6834 , C12Q1/686 , C12Q1/6869 , C12Q1/6874 , C12Q1/6876 , C12Q2525/161 , C12Q2561/119 , C12Q2563/103 , C12Q2563/107 , C12Q2563/159 , C12Q2565/537 , C12Q2565/629 , C12Q2600/16 , C40B30/04 , C40B40/04 , C40B50/08 , C40B60/08 , C40B60/12 , C40B70/00 , G01N21/6428 , G01N21/6445 , G01N21/6458 , G01N33/536 , G01N33/542 , G01N33/543 , G01N33/6845 , G01N33/6854 , G01N2500/10
摘要： The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The device can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged on a microfabricated substrate such that a continuous channel is provided for flow of immiscible fluids.
摘要翻译：本发明提供了可用于进行高通量筛选测定和组合化学的新型微流体装置和方法。该装置可以包括多个可电寻址的通道支承流体模块，其一体地布置在微加工基板上，使得提供用于不混溶流体流动的连续通道。

9. 发明申请

WO2007081385A2 MICROFLUIDIC DEVICES AND METHODS OF USE IN THE FORMATION AND CONTROL OF NANOREACTORS 审中-公开
标题翻译：微流体装置和用于形成和控制纳米反应器的方法
公开(公告)号：WO2007081385A2
公开(公告)日：2007-07-19
申请号：PCT/US2006021280
申请日：2006-06-01
申请人： RAINDANCE TECHNOLOGIES INC , LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
发明人： LINK DARREN R , BOITARD LAURENT , BRANCIFORTE JEFFREY , CHARLES YVES , FEKE GILBERT , LU JOHN Q , MARRAN DAVID , TABATABAI AHMADALI , WEINER MICHAEL , HINZ WOLFGANG , ROTHBERG JONATHAN M
IPC分类号： G01N33/536 , B01J19/00 , C07B61/00 , C07K1/04 , C12Q1/68 , G01N33/68
CPC分类号： C12N15/1075 , B01F3/0807 , B01F13/0071 , B01F13/0076 , B01J19/0046 , B01J2219/00286 , B01J2219/00459 , B01J2219/00466 , B01J2219/00468 , B01J2219/00479 , B01J2219/005 , B01J2219/00576 , B01J2219/00599 , B01J2219/00702 , B01J2219/0072 , B01J2219/00743 , B01L3/5027 , B01L3/502715 , B01L3/50273 , B01L3/502746 , B01L3/502761 , B01L3/502784 , B01L3/502792 , B01L3/565 , B01L7/52 , B01L2200/027 , B01L2200/0621 , B01L2200/0647 , B01L2200/0652 , B01L2200/0673 , B01L2300/0816 , B01L2300/0864 , B01L2300/0867 , B01L2300/0896 , B01L2400/0415 , B01L2400/0424 , B01L2400/0487 , B01L2400/084 , B82Y5/00 , B82Y30/00 , C07K1/047 , C12Q1/6804 , C12Q1/6816 , C12Q1/6825 , C12Q1/6834 , C12Q1/686 , C12Q1/6869 , C12Q1/6874 , C12Q1/6876 , C12Q2525/161 , C12Q2561/119 , C12Q2563/103 , C12Q2563/107 , C12Q2563/159 , C12Q2565/537 , C12Q2565/629 , C12Q2600/16 , C40B30/04 , C40B40/04 , C40B50/08 , C40B60/08 , C40B60/12 , C40B70/00 , G01N21/6428 , G01N21/6445 , G01N21/6458 , G01N33/536 , G01N33/542 , G01N33/543 , G01N33/6845 , G01N33/6854 , G01N2500/10
摘要： The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. Such methods can include labeling a library of compounds by emulsifying aqueous solutions of the compounds and aqueous solutions of unique liquid labels on a microfluidic device, which includes a plurality of electrically addressable, channel bearing fluidic modules integrally arranged on a microfabricated substrate such that a continuous channel is provided for flow of immiscible fluids, whereby each compound is labeled with a unique liquid label, pooling the labeled emulsions, coalescing the labeled emulsions with emulsions containing a specific cell or enzyme, thereby forming a nanoreactor, screening the nanoreactors for a desirable reaction between the contents of the nanoreactor, and decoding the liquid label, thereby identifying a single compound from a library of compounds.
摘要翻译：本发明提供了用于进行高通量筛选测定和组合化学的新型微流体装置和方法。这样的方法可以包括通过乳化化合物的水溶液和独特液体标签的水溶液在微流体装置上标记化合物文库，所述微流体装置包括整体地布置在微制造基底上的多个可电寻址的流道承载流体模块，通道用于不混溶流体的流动，由此每种化合物用独特的液体标签标记，汇集标记的乳液，使标记的乳液与含有特定细胞或酶的乳液聚结，由此形成纳米反应器，筛选纳米反应器以获得期望的反应在纳米反应器的内容物之间，以及解码液体标签，从而从化合物文库中鉴定单一化合物。

10. 发明申请

WO2011106629A3 MODIFIED PROTEINS AND METHODS OF MAKING AND USING SAME 审中-公开
标题翻译：改良蛋白质及其制备方法和使用方法
公开(公告)号：WO2011106629A3
公开(公告)日：2012-01-19
申请号：PCT/US2011026219
申请日：2011-02-25
申请人： LIFE TECHNOLOGIES CORP , DAVIDSON JOHN F , HINZ WOLFGANG , ROTHBERG JONATHAN M , WHITAKER RICHARD
发明人： DAVIDSON JOHN F , HINZ WOLFGANG , ROTHBERG JONATHAN M , WHITAKER RICHARD
IPC分类号： C12Q1/68 , C12N9/12 , C12Q1/48
CPC分类号： C12N9/1252
摘要： Methods, compositions, systems, apparatuses and kits comprising modified proteins, particularly modified nucleic acid-binding proteins with altered buffering properties are provided. For example, in some embodiments, methods of forming modified proteins including one or more amino acid modifications to achieve desired pKa values are described. Furthermore, the invention provides methods for using such modified proteins in ion-producing reactions, such as ion-based nucleic acid sequencing reactions.
摘要翻译：提供了包含修饰的蛋白质，特别是具有改变的缓冲性质的经修饰的核酸结合蛋白质的方法，组合物，系统，装置和试剂盒。例如，在一些实施方案中，描述了形成包含一个或多个氨基酸修饰以获得所需pKa值的修饰蛋白质的方法。此外，本发明提供了在离子产生反应中使用这些修饰蛋白质的方法，例如基于离子的核酸测序反应。

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