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1. 发明授权

US08906626B2 Multiplex nucleic acid reactions 有权
标题翻译：多重核酸反应
公开(公告)号：US08906626B2
公开(公告)日：2014-12-09
申请号：US13604872
申请日：2012-09-06
申请人： Arnold Oliphant , John R. Stuelpnagel , Mark S. Chee , Scott L. Butler , Jian-Bing Fan , Min-Jui Richard Shen
发明人： Arnold Oliphant , John R. Stuelpnagel , Mark S. Chee , Scott L. Butler , Jian-Bing Fan , Min-Jui Richard Shen
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6876 , C12Q1/6834 , C12Q1/6837 , C12Q2600/16 , Y10T436/143333 , C12Q2525/155 , C12Q2563/131 , C12Q2563/179
摘要： A method for detecting nucleic acids by (a) providing a sample having target nucleic acids, each nucleic acid having contiguous first, second, and third domains; (b) contacting the sample with probe sets to form hybridization complexes, wherein each probe set includes (i) a first probe having a sequence that is complementary to the first domain; and (ii) a second probe having a sequence substantially complementary to the third domain; (c) extending the first probes along the second domains of the complexes while the complexes are immobilized on a solid support; (d) ligating the extended first probes to the second probes to form templates; (e) amplifying the templates with primers that are complementary to the first and second priming sequences to produce amplicons; and (f) detecting the amplicons on the surface of a nucleic acid array.
摘要翻译：一种用于通过（a）提供具有靶核酸的样品来检测核酸的方法，每个核酸具有连续的第一，第二和第三结构域; （b）使样品与探针组接触以形成杂交复合物，其中每个探针组包括（i）具有与第一结构域互补的序列的第一探针; 和（ii）具有与第三结构域基本上互补的序列的第二探针; （c）沿络合物的第二结构域扩展第一探针，同时将复合物固定在固体支持物上; （d）将扩展的第一探针连接到第二探针以形成模板; （e）用与第一和第二引物序列互补的引物扩增模板以产生扩增子; 和（f）检测核酸阵列表面上的扩增子。

2. 发明授权

US08440407B2 Gene expression profiles to predict relapse of prostate cancer 有权
标题翻译：基因表达谱预测前列腺癌的复发
公开(公告)号：US08440407B2
公开(公告)日：2013-05-14
申请号：US13327496
申请日：2011-12-15
申请人： Eugene Chudin , Jean Lozach , Jian-Bing Fan , Marina Bibikova
发明人： Eugene Chudin , Jean Lozach , Jian-Bing Fan , Marina Bibikova
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/16 , G06F19/00
摘要： The present disclosure provides a method for cancer relapse prediction that provides higher resolution grading than Gleason score alone. In particular, the method provides for prediction of prostate cancer relapse that correlates gene expression of each individual signature gene and deriving a prostate cancer gene expression (GEX) score in the plurality of prostate cancer tissue samples; and correlating said GEX score with the clinical outcome for each prostate carcinoma tissue sample. A set of signature genes is provided that encompasses all or a sub-combination of GI_2094528, KIP2, NRG1, NBL1, Prostein, CCNE2, CDC6, FBP1, HOXC6, MKI67, MYBL2, PTTG1, RAMP, UBE2C, Wnt5A, MEMD, AZGP1, CCK, MLCK, PPAP2B, and PROK1.
摘要翻译：本公开提供了一种癌症复发预测的方法，其提供比单独的格列森评分更高的分辨率分级。特别地，该方法提供预测与多个前列腺癌组织样本中的每个个体签名基因的基因表达相关并导出前列腺癌基因表达（GEX）评分的前列腺癌复发; 并将所述GEX评分与每个前列腺癌组织样品的临床结果相关联。提供了一组签名基因，其包含GI_2094528，KIP2，NRG1，NBL1，Prostein，CCNE2，CDC6，FBP1，HOXC6，MKI67，MYBL2，PTTG1，RAMP，UBE2C，Wnt5A，MEMD，AZGP1的全部或亚组合， CCK，MLCK，PPAP2B和PROK1。

3. 发明授权

US08288103B2 Multiplex nucleic acid reactions 有权
标题翻译：多重核酸反应
公开(公告)号：US08288103B2
公开(公告)日：2012-10-16
申请号：US12790757
申请日：2010-05-28
申请人： Arnold Oliphant , John R. Stuelpnagel , Mark S. Chee , Scott L. Butler , Jian-Bing Fan , Min-Jui Richard Shen
发明人： Arnold Oliphant , John R. Stuelpnagel , Mark S. Chee , Scott L. Butler , Jian-Bing Fan , Min-Jui Richard Shen
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6876 , C12Q1/6834 , C12Q1/6837 , C12Q2600/16 , Y10T436/143333 , C12Q2525/155 , C12Q2563/131 , C12Q2563/179
摘要： The invention is directed to a variety of multiplexing methods used to amplify and/or genotype a variety of samples simultaneously.
摘要翻译：本发明涉及用于同时扩增和/或基因型多种样品的多种多样化方法。

4. 发明申请

US20120202704A1 MULTI-SAMPLE INDEXING FOR MULTIPLEX GENOTYPING 审中-公开
标题翻译：多重基因多样性指数
公开(公告)号：US20120202704A1
公开(公告)日：2012-08-09
申请号：US13501502
申请日：2010-12-07
申请人： Jian-Bing Fan , Kevin Gunderson
发明人： Jian-Bing Fan , Kevin Gunderson
IPC分类号： C40B30/04
CPC分类号： C12N15/1065 , C12Q1/6816 , C12Q1/6827 , C12Q2521/501 , C12Q2525/155 , C12Q2533/101 , C12Q2533/107 , C12Q2537/143 , C12Q2563/179 , C12Q2565/102 , C12Q2525/186
摘要： A method for determining the presence of multiple nucleotide sequences of interest in multiple samples while preserving the identity of each sample, by contacting the samples with a plurality of probe sets. The probes are designed to indicate the presence of the sequences of interest and the identity of the sample containing the sequence of interest in complex mixtures. Applications of the method include genotyping, expression analysis, and identification of individual species in complex samples. Kits of probe sets for use in the methods are also provided.
摘要翻译：通过使样本与多个探针组接触，确定多个样品中多个核苷酸序列的存在同时保持每个样品的身份的方法。探针被设计为指示感兴趣的序列的存在和在复杂混合物中含有感兴趣的序列的样品的身份。该方法的应用包括基因分型，表达分析和复杂样本中个体物种的鉴定。还提供了用于方法的探针组的套件。

5. 发明授权

US08003354B2 Multiplex nucleic acid reactions 有权
公开(公告)号：US08003354B2
公开(公告)日：2011-08-23
申请号：US12032581
申请日：2008-02-15
申请人： Min-Jui Richard Shen , Arnold Oliphant , Scott L. Butler , John R. Stuelpnagel , Mark S. Chee , Kenneth M. Kuhn , Jian-Bing Fan
发明人： Min-Jui Richard Shen , Arnold Oliphant , Scott L. Butler , John R. Stuelpnagel , Mark S. Chee , Kenneth M. Kuhn , Jian-Bing Fan
IPC分类号： C12P19/34 , C12Q1/68 , C12M1/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q2535/125 , C12Q2537/143 , C12Q2561/125 , C12Q2565/515
摘要： The invention is directed to a variety of multiplexing methods used to amplify and/or genotype a variety of samples simultaneously.

6. 发明授权

US07955794B2 Multiplex nucleic acid reactions 有权
标题翻译：多重核酸反应
公开(公告)号：US07955794B2
公开(公告)日：2011-06-07
申请号：US10177727
申请日：2002-06-20
申请人： Mun-Jui Richard Shen , Arnold Oliphant , Scott L. Butler , John E. Stuelpnagel , Mark S. Chee , Kenneth M. Kuhn , Jian-Bing Fan
发明人： Mun-Jui Richard Shen , Arnold Oliphant , Scott L. Butler , John E. Stuelpnagel , Mark S. Chee , Kenneth M. Kuhn , Jian-Bing Fan
IPC分类号： C12Q1/68 , C12P19/34 , C12M1/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q2535/125 , C12Q2537/143 , C12Q2561/125 , C12Q2565/515
摘要： The invention is directed to a variety of multiplexing methods used to amplify and/or genotype a variety of samples simultaneously.
摘要翻译：本发明涉及用于同时扩增和/或基因型多种样品的多种多样化方法。

7. 发明授权

US07803537B2 Parallel genotyping of multiple patient samples 有权
标题翻译：多个患者样本的并行基因分型
公开(公告)号：US07803537B2
公开(公告)日：2010-09-28
申请号：US10759576
申请日：2004-01-16
申请人： Jian-Bing Fan , Mark S Chee
发明人： Jian-Bing Fan , Mark S Chee
IPC分类号： C12Q1/68 , C12M1/36 , C07H21/04
CPC分类号： C12Q1/6883 , C12Q1/6837 , C12Q2565/501 , C12Q2563/149 , C12Q2537/143
摘要： The present invention relates to parallel genotyping (or other sample analysis) of multiple patients by direct sample immobilization onto microspheres of an array. The patient beads can then be used in a variety of target analyte analyses.
摘要翻译：本发明涉及通过直接样品固定在阵列的微球上的多个患者的平行基因分型（或其他样品分析）。然后将患者珠子用于各种目标分析物分析。

8. 发明申请

US20080182248A1 PARALLEL GENOTYPING OF MULTIPLE PATIENT SAMPLES 审中-公开
标题翻译：多个患者样本的并行遗传学
公开(公告)号：US20080182248A1
公开(公告)日：2008-07-31
申请号：US11873380
申请日：2007-10-16
申请人： Jian-Bing FAN , Mark S. Chee
发明人： Jian-Bing FAN , Mark S. Chee
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： C12Q1/6883 , C12Q1/6837 , C12Q2565/501 , C12Q2563/149 , C12Q2537/143
摘要： The present invention relates to parallel genotyping (or other sample analysis) of multiple patients by direct sample immobilization onto microspheres of an array. The patient beads can then be used in a variety of target analyte analyses.
摘要翻译：本发明涉及通过直接样品固定在阵列的微球上的多个患者的平行基因分型（或其他样品分析）。然后将患者珠子用于各种目标分析物分析。

9. 发明授权

US08150627B2 Methods and compositions for diagnosing lung cancer with specific DNA methylation patterns 有权
标题翻译：用特定DNA甲基化模式诊断肺癌的方法和组合物
公开(公告)号：US08150627B2
公开(公告)日：2012-04-03
申请号：US11259546
申请日：2005-10-25
申请人： Jian-Bing Fan , Marina Bibikova
发明人： Jian-Bing Fan , Marina Bibikova
IPC分类号： G01N33/48 , C12Q1/00
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/154 , C12Q2600/16 , C12Q2523/125
摘要： The present invention provides a method for identification of differentially methylated genomic CpG dinucleotide sequences within genomic target sequences that are associated with cancer in an individual by obtaining a biological sample comprising genomic DNA from the individual measuring the level or pattern of methylated genomic CpG dinucleotide sequences for two or more of the genomic targets in the sample, and comparing the level of methylated genomic CpG dinucleotide sequences in the sample to a reference level of methylated genomic CpG dinucleotide sequences, wherein a difference in the level or pattern of methylation of the genomic CpG dinucleotide sequences in the sample compared to the reference level identifies differentially methylated genomic CpG dinucleotide sequences associated with cancer. As disclosed herein, the methods of the invention have numerous diagnostic and prognostic applications. The methods of the invention can be combined with a miniaturized array platform that allows for a high level of assay multiplexing and scalable automation for sample handling and data processing. Also provided by the invention are genomic targets and corresponding nucleic acid probes that are useful in the methods of the invention as they enable detection of differentially methylated genomic CpG dinucleotide sequences associated with adenocarcinomas of the lung.
摘要翻译：本发明提供了通过获得包含来自个体的基因组DNA的生物样品来鉴定与个体癌症相关的基因组靶序列内的差异甲基化基因组CpG二核苷酸序列的方法，所述生物样品包含测量甲基化基因组CpG二核苷酸序列的水平或模式，样品中的两个或更多个基因组靶标，并将样品中甲基化的基因组CpG二核苷酸序列的水平与甲基化的基因组CpG二核苷酸序列的参考水平进行比较，其中基因组CpG二核苷酸的甲基化水平或模式的差异与参考水平相比，样品中的序列鉴定与癌症相关的差异甲基化的基因组CpG二核苷酸序列。如本文所公开的，本发明的方法具有许多诊断和预后应用。本发明的方法可以与微型阵列平台组合，其允许用于样品处理和数据处理的高水平的测定复用和可扩展的自动化。本发明还提供了可用于本发明方法的基因组靶标和相应的核酸探针，因为它们能够检测与肺腺癌相关的差异甲基化的基因组CpG二核苷酸序列。

10. 发明申请

US20110153534A1 Expression Profiles to Predict Relapse of Prostate Cancer 有权
标题翻译：表达谱预测前列腺癌复发
公开(公告)号：US20110153534A1
公开(公告)日：2011-06-23
申请号：US13035797
申请日：2011-02-25
申请人： Eugene Chudin , Jean Lozach , Jian-Bing Fan , Marina Bibikova
发明人： Eugene Chudin , Jean Lozach , Jian-Bing Fan , Marina Bibikova
IPC分类号： G06F19/00 , G06G7/60
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/16 , G06F19/00
摘要： The present invention provides a method for preparing a reference model for cancer relapse prediction that provides higher resolution grading than Gleason score alone. The method encompasses obtaining from different individuals a plurality of prostate carcinoma tissue samples of known clinical outcome representing different Gleason scores; selecting a set of signature genes having an expression pattern that correlates positively or negatively in a statistically significant manner with the Gleason scores; independently deriving a prediction score that correlates gene expression of each individual signature gene with Gleason score for each signature gene in said plurality of prostate carcinoma tissue samples; deriving a prostate cancer gene expression (GEX) score that correlates gene expression of said set of signature genes with the Gleason score based on the combination of independently derived prediction scores in the plurality of prostate cancer tissue samples; and correlating said GEX score with the clinical outcome for each prostate carcinoma tissue sample. A set of signature genes is provided that encompasses all or a sub-combination of GI_2094528, KIP2, NRG1, NBL1, Prostein, CCNE2, CDC6, FBP1, HOXC6, MKI67, MYBL2, PTTG1, RAMP, UBE2C, Wnt5A, MEMD, AZGP1, CCK, MLCK, PPAP2B, and PROK1. Also provided a methods for predicting the probability of relapse of cancer in an individual and methods for deriving a prostate cancer gene expression (GEX) score for a prostate carcinoma tissue sample obtained from an individual.
摘要翻译：本发明提供了一种制备癌症复发预测的参考模型的方法，其提供比单独的格列森评分更高的分辨率分级。该方法包括从不同个体获得表达不同格列森分数的已知临床结果的多个前列腺癌组织样品; 选择一组具有统计学显着的方式与Gleason评分正相关或负相关的表达模式的特征基因; 独立地导出将所述多个前列腺癌组织样品中每个特征基因的基因表达与每个特征基因的Gleason评分相关联的预测分数; 基于所述多个前列腺癌组织样本中独立衍生的预测分数的组合，得到使所述特征基因组的基因表达与格列森分数相关的前列腺癌基因表达（GEX）评分; 并将所述GEX评分与每个前列腺癌组织样品的临床结果相关联。提供了一组签名基因，其包含GI_2094528，KIP2，NRG1，NBL1，Prostein，CCNE2，CDC6，FBP1，HOXC6，MKI67，MYBL2，PTTG1，RAMP，UBE2C，Wnt5A，MEMD，AZGP1的全部或亚组合， CCK，MLCK，PPAP2B和PROK1。还提供了预测个体中癌症复发概率的方法以及从个体获得的前列腺癌组织样品的前列腺癌基因表达（GEX）得分的方法。

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