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31. 发明授权

US06171794B2 Methods for determining cross-hybridization 失效
标题翻译：确定交叉杂交的方法
公开(公告)号：US06171794B2
公开(公告)日：2001-01-09
申请号：US09335971
申请日：1999-06-18
申请人： Julja Burchard , Roland Stoughton , Stephen H. Friend
发明人： Julja Burchard , Roland Stoughton , Stephen H. Friend
IPC分类号： C12Q168
CPC分类号： C12Q1/6832 , C07B2200/11 , C12Q2527/107
摘要： The present invention provides methods for distinguishing the fractions of polynucleotide sequences which hybridize to any given probe, including probes on microarrays such as those described herein. In particular, the present invention enables users to identify the fraction of sequences which are perfectly complementary to a probe, thereby correcting for effects of cross hybridization in a hybridization assay. The methods of the invention work by monitoring the kinetics of dissociation of sequences from the probe so that a resulting “dissociation curve” may be compared to a combination of the individual “dissociation profiles” for each sequence which hybridizes. In alternative embodiments, the invention also provides computer systems for performing the present methods, as well as databases of the dissociation profiles.
摘要翻译：本发明提供了用于区分与任何给定探针杂交的多核苷酸序列的级分的方法，包括在诸如本文所述的微阵列之类的微阵列上的探针。特别地，本发明使得用户能够鉴定与探针完全互补的序列部分，从而在杂交测定中校正交叉杂交的作用。本发明的方法通过监测序列从探针中解离的动力学来起作用，从而可将所得到的“解离曲线”与杂交的每个序列的单独“解离曲线”的组合进行比较。在替代实施例中，本发明还提供用于执行本方法的计算机系统以及解离曲线的数据库。

32. 发明授权

US08019552B2 Classification of breast cancer patients using a combination of clinical criteria and informative genesets 失效
标题翻译：乳腺癌患者使用临床标准和信息基因组合的分类
公开(公告)号：US08019552B2
公开(公告)日：2011-09-13
申请号：US10591800
申请日：2005-03-07
申请人： Hongyue Dai , Laura J. Van't Veer , John Lamb , Roland Stoughton , Stephen H. Friend , Yudong He
发明人： Hongyue Dai , Laura J. Van't Veer , John Lamb , Roland Stoughton , Stephen H. Friend , Yudong He
IPC分类号： G01N33/48 , G01N33/50
CPC分类号： G01N33/57415 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , Y10T436/143333
摘要： The present invention provides prognostic methods for conditions such as cancer, for example, breast cancer, comprising classifying an individual by a plurality of phenotypic, genotypic or clinical characteristics of the condition into a plurality of patient subsets, and analyzing the pattern of expression of prognosis-informative genes identified for that subset in a sample from the individual. The present invention also provides methods for constructing such patient subsets and of identifying prognosis-informative genesets for such subsets. The invention further provides methods of assigning a therapeutic regimen to an individual, microarrays useful for performing prognosis, kits comprising these microarrays, and computer systems and programs for implementing the methods of the invention.
摘要翻译：本发明提供了诸如癌症例如乳腺癌的病症的预后方法，包括将个体的多个表型，基因型或临床特征分类为多个患者子集，并分析预后表达模式在来自个体的样品中识别该子集的信息基因。本发明还提供了用于构建这样的患者子集以及鉴定这样的子集的预后信息性基因组的方法。本发明进一步提供了将个体的治疗方案分配给用于进行预后的微阵列，包括这些微阵列的试剂盒以及用于实施本发明的方法的计算机系统和程序的方法。

33. 发明申请

US20080187909A1 Classification of Breast Cancer Patients Using a Combination of Clinical Criteria and Informative Genesets 失效
标题翻译：乳腺癌患者使用临床标准和信息基因组合的分类
公开(公告)号：US20080187909A1
公开(公告)日：2008-08-07
申请号：US10591800
申请日：2005-03-07
申请人： Hongyue Dai , Laura J. Van't Veer , John Lamb , Roland Stoughton , Stephen H. Friend , Yudong He
发明人： Hongyue Dai , Laura J. Van't Veer , John Lamb , Roland Stoughton , Stephen H. Friend , Yudong He
IPC分类号： C12Q1/68 , C40B40/06
CPC分类号： G01N33/57415 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , Y10T436/143333
摘要： The present invention provides prognostic methods for conditions such as cancer, for example, breast cancer, comprising classifying an individual by a plurality of phenotypic, genotypic or clinical characteristics of the condition into a plurality of patient subsets, and analyzing the pattern of expression of prognosis-informative genes identified for that subset in a sample from the individual. The present invention also provides methods for constructing such patient subsets and of identifying prognosis-informative genesets for such subsets. The invention further provides methods of assigning a therapeutic regimen to an individual, microarrays useful for performing prognosis, kits comprising these microarrays, and computer systems and programs for implementing the methods of the invention.
摘要翻译：本发明提供了诸如癌症例如乳腺癌的病症的预后方法，包括将个体的多个表型，基因型或临床特征分类为多个患者子集，并分析预后表达模式在来自个体的样品中识别该子集的信息基因。本发明还提供了用于构建这样的患者子集以及鉴定这样的子集的预后信息性基因组的方法。本发明进一步提供了将个体的治疗方案分配给用于进行预后的微阵列，包括这些微阵列的试剂盒以及用于实施本发明的方法的计算机系统和程序的方法。

34. 发明申请

US20070275407A1 Methods for determining therapeutic index from gene expression profiles 失效
公开(公告)号：US20070275407A1
公开(公告)日：2007-11-29
申请号：US11879161
申请日：2007-07-16
申请人： Matthew Marton , Roland Stoughton
发明人： Matthew Marton , Roland Stoughton
IPC分类号： C12Q1/68 , C12Q1/18 , G01N33/566
CPC分类号： C12Q1/6883 , C12Q1/025 , C12Q1/18 , C12Q2600/106 , C12Q2600/158 , G01N33/5005 , G01N33/5088 , G06F19/20 , G06F19/70
摘要： This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

35. 发明申请

US20060141501A1 Iterative probe design and detailed expression profiling with flexible in-situ synthesis arrays 审中-公开
标题翻译：迭代探针设计和具有灵活原位合成阵列的详细表达谱
公开(公告)号：US20060141501A1
公开(公告)日：2006-06-29
申请号：US11282025
申请日：2005-11-16
申请人： Stephen Friend , Roland Stoughton , Peter Linsley , Julia Burchard
发明人： Stephen Friend , Roland Stoughton , Peter Linsley , Julia Burchard
IPC分类号： C12Q1/68
CPC分类号： G16B25/00
摘要： Methods and compositions are provided that are useful for detecting and reporting a plurality of different target polynucleotide sequences in a sample, such as polynucleotides corresponding to a plurality of different genes expressed by a cell or cells. In particular, the invention provides methods for screening a plurality of candidate polynucleotide probes to evaluate both the sensitivity and the specificity with which each candidate probe hybridizes to a target polynucleoide sequence. Candidate polynucleotide probes can then be ranked according to both their sensitivity and specificity, and probes that have optimal sensitivity and specificity for a target polynucleotide sequence can be selected. In one embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “screening chips” wherein a large number of target polynucleotide sequences are detected using a single microarray have a few (e.g., 1-5) probes for each target polynucleotide sequence. In a particularly preferred embodiment, the invention provides a screening chip that can detect genetic transcripts from the entire genome of an organism. In an alternative embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “signature chips” to more accurately detect certain selected “signature genes” using several polynucleotide probes (e:g., 10-20) for each signature gene. The invention additionally provides microarrays containing polynucleotide probes for a large number of genes expressed by a cell or organism. Further, methods for detecting a plurality of polynucleotide molecules, including a large number of genes expressed by a cell or organism, are also provided.
摘要翻译：提供了可用于检测和报告样品中多个不同靶多核苷酸序列的方法和组合物，例如对应于由细胞或细胞表达的多种不同基因的多核苷酸。特别地，本发明提供了筛选多个候选多核苷酸探针以评估每个候选探针与目标多核苷酸序列杂交的灵敏度和特异性的方法。然后可以根据其灵敏度和特异性对候选多核苷酸探针进行排序，并且可以选择对靶多核苷酸序列具有最佳敏感性和特异性的探针。在一个实施方案中，可以根据本文所述的方法选择多核苷酸探针以制备“筛选芯片”，其中使用单个微阵列检测大量目标多核苷酸序列，其中每个靶多核苷酸具有少量（例如1-5）探针序列。在一个特别优选的实施方案中，本发明提供了可以检测来自生物体的整个基因组的遗传转录物的筛选芯片。在替代实施方案中，可以根据本文所述的方法选择多核苷酸探针，以制备“签名芯片”，以使用每个签名基因的多个多核苷酸探针（例如，10-20）更准确地检测某些所选择的“签名基因” 。本发明另外提供含有由细胞或生物表达的大量基因的多核苷酸探针的微阵列。此外，还提供了用于检测多个多核苷酸分子的方法，包括由细胞或生物体表达的大量基因。

36. 发明授权

US07013221B1 Iterative probe design and detailed expression profiling with flexible in-situ synthesis arrays 有权
标题翻译：迭代探针设计和具有灵活原位合成阵列的详细表达谱
公开(公告)号：US07013221B1
公开(公告)日：2006-03-14
申请号：US09561487
申请日：2000-04-28
申请人： Stephen H. Friend , Roland Stoughton , Peter S. Linsley , Julja Burchard
发明人： Stephen H. Friend , Roland Stoughton , Peter S. Linsley , Julja Burchard
IPC分类号： G01N33/48 , C12Q1/68
CPC分类号： G06F19/20
摘要： Methods and compositions are provided that are useful for detecting and reporting a plurality of different target polynucleotide sequences in a sample, such as polynucleotides corresponding to a plurality of different genes expressed by a cell or cells. In particular, the invention provides methods for screening a plurality of candidate polynucleotide probes to evaluate both the sensitivity and the specificity with which each candidate probe hybridizes to a target polynucleoide sequence. Candidate polynucleotide probes can then be ranked according to both their sensitivity and specificity, and probes that have optimal sensitivity and specificity for a target polynucleotide sequence can be selected. In one embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “screening chips” wherein a large number of target polynucleotide sequences are detected using a single microarray have a few (e.g., 1–5) probes for each target polynucleotide sequence. In a particularly preferred embodiment, the invention provides a screening chip that can detect genetic transcripts from the entire genome of an organism. In an alternative embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “signature chips” to more accurately detect certain selected “signature genes” using several polynucleotide probes (e.g., 10–20) for each signature gene. The invention additionally provides microarrays containing polynucleotide probes for a large number of genes expressed by a cell or organism. Further, methods for detecting a plurality of polynucleotide molecules, including a large number of genes expressed by a cell or organism, are also provided.
摘要翻译：提供了可用于检测和报告样品中多个不同靶多核苷酸序列的方法和组合物，例如对应于由细胞或细胞表达的多种不同基因的多核苷酸。特别地，本发明提供了筛选多个候选多核苷酸探针以评估每个候选探针与目标多核苷酸序列杂交的灵敏度和特异性的方法。然后可以根据其灵敏度和特异性对候选多核苷酸探针进行排序，并且可以选择对靶多核苷酸序列具有最佳敏感性和特异性的探针。在一个实施方案中，可以根据本文所述的方法选择多核苷酸探针以制备“筛选芯片”，其中使用单个微阵列检测大量目标多核苷酸序列，其中每个靶多核苷酸具有少量（例如1-5）探针序列。在一个特别优选的实施方案中，本发明提供了可以检测来自生物体的整个基因组的遗传转录物的筛选芯片。在替代实施方案中，可以根据本文所述的方法选择多核苷酸探针以通过使用每个特征基因的多个多核苷酸探针（例如10-20）来制备“签名芯片”以更精确地检测某些所选择的“特征基因”。本发明另外提供含有由细胞或生物表达的大量基因的多核苷酸探针的微阵列。此外，还提供了用于检测多个多核苷酸分子的方法，包括由细胞或生物体表达的大量基因。

37. 发明申请

US20050130215A1 Systems and methods for correcting error in biological response signal data 审中-公开
标题翻译：用于校正生物反应信号数据误差的系统和方法
公开(公告)号：US20050130215A1
公开(公告)日：2005-06-16
申请号：US11042653
申请日：2005-01-24
申请人： Roland Stoughton , Hongyue Dai
发明人： Roland Stoughton , Hongyue Dai
IPC分类号： G01N33/53 , C12N15/09 , C12Q1/68 , C12Q1/6837 , G01N33/48 , G01N33/566 , G01N33/58 , G01N37/00 , G06F17/18 , G06F19/20 , G06F19/00 , G01N33/50
CPC分类号： C12Q1/6837 , G16B25/00 , Y10T436/10
摘要： A method for fluorophore bias removal in microarray experiments in which the fluorophores used in microarray experiment pairs are reversed. Further, a method for calculating the individual errors associated with each measurement made in nominally repeated microarray experiments. This error measurement is optionally coupled with rank based methods in order to determine a probability that a cellular constituent is up or down regulated in response to a perturbation. Finally, a method for determining the confidence in the weighted average of the expression level of a cellular constituent in nominally repeated microarray experiments.
摘要翻译：用于微阵列实验对中的荧光团的微阵列实验中的荧光团偏置去除方法是相反的。此外，一种用于计算与名义上重复的微阵列实验中进行的每个测量相关联的各个错误的方法。该误差测量可选地与基于秩的方法耦合，以便确定响应于扰动的细胞成分向上或向下调节的概率。最后，在名义上重复的微阵列实验中确定细胞成分的表达水平的加权平均的置信度的方法。

38. 发明授权

US06370478B1 Methods for drug interaction prediction using biological response profiles 有权
标题翻译：使用生物反应曲线进行药物相互作用预测的方法
公开(公告)号：US06370478B1
公开(公告)日：2002-04-09
申请号：US09222595
申请日：1998-12-28
申请人： Roland Stoughton , Sergey Stepaniants
发明人： Roland Stoughton , Sergey Stepaniants
IPC分类号： G01N3348
CPC分类号： G06F19/20 , G06F19/00 , G06F19/18 , G06F19/24 , G16H50/50
摘要： This invention provides methods for detecting and predicting drug interaction. In one embodiment of the invention, a plurality of cellular constituents in a biological sample is monitored as the sample is subject to various drug treatments. The response of the cellular constituents are analyzed to detect interactions. This method is particularly useful for predicting drug interaction using a model organism. It is also useful for analyzing interaction between any perturbations to a biological system.
摘要翻译：本发明提供了检测和预测药物相互作用的方法。在本发明的一个实施方案中，当样品进行各种药物治疗时，监测生物样品中的多种细胞成分。分析细胞成分的反应以检测相互作用。该方法对于使用模型生物体预测药物相互作用特别有用。它也可用于分析与生物系统的任何扰动之间的相互作用。

39. 发明申请

US20100233693A1 METHODS FOR DIAGNOSING, PROGNOSING, OR THERANOSING A CONDITION USING RARE CELLS 审中-公开
标题翻译：用于诊断，预处理或治疗使用稀有细胞的条件的方法
公开(公告)号：US20100233693A1
公开(公告)日：2010-09-16
申请号：US12595949
申请日：2008-04-16
申请人： Anne R. Kopf-Sill , Lena Wu , Roland Stoughton
发明人： Anne R. Kopf-Sill , Lena Wu , Roland Stoughton
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： G01N33/57488 , C12Q1/6883 , C12Q1/6886 , C12Q2600/118 , C12Q2600/156 , G01N1/31 , G01N33/5091 , G01N33/57484 , G01N33/57492 , G01N2333/705 , G01N2333/71 , G01N2333/912 , G01N2333/96433
摘要： The invention encompasses methods for diagnosing, theranosing, or prognosing a condition in a patient based on the results of one or more analysis methods. The methods can comprise enriching a sample obtained from the patient for one or more rare cells. The analysis methods can include performing enumeration of the one or more rare cells or cell subtypes, performing nucleic acid analysis, or detecting a serum marker.
摘要翻译：本发明包括基于一种或多种分析方法的结果来诊断，鉴别或预测患者病症的方法。所述方法可以包括富集从患者获得的一种或多种稀有细胞的样品。分析方法可以包括执行一个或多个稀有细胞或细胞亚型的计数，进行核酸分析或检测血清标记。

40. 发明授权

US07254487B2 Methods for determining therapeutic index from gene expression profiles 失效
标题翻译：从基因表达谱确定治疗指数的方法
公开(公告)号：US07254487B2
公开(公告)日：2007-08-07
申请号：US09823322
申请日：2001-04-02
申请人： Matthew Marton , Roland Stoughton
发明人： Matthew Marton , Roland Stoughton
IPC分类号： G01N33/48 , G01N31/00 , A01N37/18 , A01N43/04 , C12Q1/00 , C12Q1/68 , C12Q1/70 , C12P21/06
CPC分类号： C12Q1/6883 , C12Q1/025 , C12Q1/18 , C12Q2600/106 , C12Q2600/158 , G01N33/5005 , G01N33/5088 , G06F19/20 , G06F19/70
摘要： This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.
摘要翻译：本发明提供用于确定个体患者的药物特异性，治疗指数和有效剂量的方法。根据本发明的方法，将分级药物施用于生物样品或患者。测量多个细胞成分以确定药物在靶途径和至少一个脱靶途径上的活性。通过比较药物的靶标和脱靶活性来确定药物特异性。治疗浓度（或剂量）被定义为在目标途径中诱导一定反应的药物的浓度（或剂量）。毒性浓度（或剂量）被定义为在脱靶途径中诱导某些反应的药物的浓度（或剂量）。治疗指标是毒性浓度与治疗浓度的比值。还提供了通过测量特定患者上的药物的活性来确定患者药物的有效剂量的方法。

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