公开(公告)号：US08753811B2

公开(公告)日：2014-06-17

申请号：US13398560

申请日：2012-02-16

申请人： Stephen H. Friend ,  Michele A. Cleary ,  Ernest M. Coffey ,  Kristopher A. Killian ,  Gregory J. Hannon ,  Patrick Paddison

发明人： Stephen H. Friend ,  Michele A. Cleary ,  Ernest M. Coffey ,  Kristopher A. Killian ,  Gregory J. Hannon ,  Patrick Paddison

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12Q1/6837 ,  Y10S977/792 ,  C12Q2565/513 ,  C12Q2531/113 ,  C12Q2525/161

摘要： The present invention provides methods of making a population of nucleic acid molecules, wherein each nucleic acid molecule comprises a predetermined nucleic acid sequence, each of said methods comprising the steps of: (a) synthesizing, on a substrate, a population of nucleic acid molecules wherein: i) each synthesized nucleic acid molecule comprises a predetermined nucleic acid sequence; and ii) each synthesized nucleic acid molecule is localized to a defined area of said substrate; (b) harvesting said population of synthesized nucleic acid molecules from said substrate to yield harvested nucleic acid molecules; and (c) introducing said harvested nucleic acid molecules into vector molecules.

摘要翻译： 本发明提供了制备核酸分子群体的方法，其中每个核酸分子包含预定的核酸序列，所述方法中的每一种包括以下步骤：（a）在底物上合成核酸分子群体 其中：i）每个合成的核酸分子包含预定的核酸序列; 和ii）每个合成的核酸分子定位于所述基质的限定区域; （b）从所述底物收获所述合成核酸分子群体以产生收获的核酸分子; 和（c）将所述收获的核酸分子引入载体分子。

公开(公告)号：US06801859B1

公开(公告)日：2004-10-05

申请号：US09220142

申请日：1998-12-23

申请人： Stephen H. Friend ,  Roland Stoughton ,  Yudong He

发明人： Stephen H. Friend ,  Roland Stoughton ,  Yudong He

IPC分类号： G01N3348

CPC分类号： G06F19/24 ,  G06F19/20

摘要： The present invention provides methods for enhanced detection of biological response profiles. In particular, the methods of this invention allow for the detection of biological response patterns, such as gene expression patterns, in response to different drug treatments. The methods of the invention also allow the determination of a “consensus profile” which describes a particular class or type of biological response. In certain embodiments the consensus profile may describe the biological response of a particular group or class of drugs. In other embodiments, the consensus profile may describe an “ideal” biological response such as one associated with a desired therapeutic effect. The methods of the present invention also allow for the comparison of different biological responses. Thus, the methods of the invention may be used, e.g., to identify and/or study new drugs.

摘要翻译： 本发明提供用于增强生物反应曲线检测的方法。 特别地，本发明的方法允许响应于不同的药物治疗来检测生物反应模式，如基因表达模式。 本发明的方法还允许确定描述特定类别或类型的生物反应的“共有概况”。 在某些实施方案中，共有概况可以描述特定组或一类药物的生物反应。 在其它实施方案中，共有概况可以描述“理想”生物反应，例如与期望的治疗效果相关联的生物反应。 本发明的方法还允许比较不同的生物反应。 因此，本发明的方法可以用于例如鉴定和/或研究新的药物。

公开(公告)号：US06673536B1

公开(公告)日：2004-01-06

申请号：US09408582

申请日：1999-09-29

申请人： Roland Stoughton ,  Julja Burchard ,  Stephen H. Friend

发明人： Roland Stoughton ,  Julja Burchard ,  Stephen H. Friend

IPC分类号： C12Q168

CPC分类号： G06F19/22 ,  C12Q1/6832 ,  C12Q2565/107

摘要： The present invention provides methods and systems, particularly computer systems, for determining the relative specificity with which a particular polynucleotide molecule hybridizes to a polynucleotide probe. For example, the methods and systems of the invention enable a user to compare the specificity with which different polynucleotides hybridize to a given probe and/or rank these polynucleotides according to their specificity to that probe. The methods and systems of the invention also enable a user to compare the specificity with which a particular polynucleotide hybridizes to different probes, and/or rank those different probes according to their specificity for that particular polynucleotide.

摘要翻译： 本发明提供了用于确定特定多核苷酸分子与多核苷酸探针杂交的相对特异性的方法和系统，特别是计算机系统。 例如，本发明的方法和系统使用户能够根据其对该探针的特异性，比较不同多核苷酸与给定探针杂交的特异性和/或对这些多核苷酸进行排序。 本发明的方法和系统还使用户能够根据其对特定多核苷酸的特异性，比较特定多核苷酸与不同探针杂交的特异性和/或对这些不同探针进行排序。

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。

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。

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。

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。

公开(公告)号：US07173063B1

公开(公告)日：2007-02-06

申请号：US10129936

申请日：2000-11-10

申请人： John R. Lamb ,  Julian Simon ,  Heather Dunstan ,  Stephen H. Friend

发明人： John R. Lamb ,  Julian Simon ,  Heather Dunstan ,  Stephen H. Friend

IPC分类号： A61K31/16 ,  A61K31/165 ,  C07C241/00 ,  C07C233/00

CPC分类号： C07C251/86 ,  A61K31/16 ,  A61K31/165

摘要： Methods for the treatment of a proliferative disorder are provided in which a subject in need of such treatment is administered an effective amount of a compound selected from: compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein X1 and X2 are independently H, Cl, F, Br, I, CN, CF3 or NO2, and Ar1 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and compounds of formula (II) wherein X3 and X4 are each independently H, Cl, F, Br, I, CN, CF3 or NO2; Y is (C2–C6)alkylene or (C2–C6)heteroalkylene; and Z is Cl, F, Br, I, CN, CF3 or NO2.

摘要翻译： 提供了治疗增殖性疾病的方法，其中需要这种治疗的受试者施用有效量的选自以下的化合物：式（I）化合物或其药学上可接受的盐，其中X 1， / O 2和X 2独立地为H，Cl，F，Br，I，CN，CF 3或NO 2， 取代或未取代的芳基或取代或未取代的杂芳基; 和其中X 3和X 4的式（II）化合物各自独立地为H，Cl，F，Br，I，CN，CF 3 >或NO <2>; Y是（C 2 -C 6 -C 6）亚烷基或（C 2 -C 6 -C 6）杂亚烷基; Z是Cl，F，Br，I，CN，CF 3或NO 2。

公开(公告)号：US07122312B1

公开(公告)日：2006-10-17

申请号：US10232211

申请日：2002-08-30

申请人： Stephen H. Friend ,  Leland Hartwell

发明人： Stephen H. Friend ,  Leland Hartwell

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6809 ,  C12Q1/025 ,  C12Q1/68 ,  C12Q2565/515

摘要： The present invention provides methods for identifying targets of a drug in a cell by comparing (i) the effects of the drug on a wild-type cell, (ii) the effects on a wild-type cell of modifications to a putative target of the drug, and (iii) the effects of the drug on a wild-type cell which has had the putative target modified of the drug. In various embodiments, the effects on the cell can be determined by measuring gene expression, protein abundances, protein activities, or a combination of such measurements. In various embodiments, modifications to a putative target in the cell can be made by modifications to the genes encoding the target, modification to abundances of RNAs encoding the target, modifications to abundances of target proteins, or modifications to activities of the target proteins. The present invention also provides methods for drug development based on the methods for identifying drug targets.

公开(公告)号：US06859735B1

公开(公告)日：2005-02-22

申请号：US09374565

申请日：1999-08-13

申请人： Roland Stoughton ,  Stephen H. Friend

发明人： Roland Stoughton ,  Stephen H. Friend

IPC分类号： G01N33/53 ,  C12N15/09 ,  C12Q1/02 ,  C12Q1/04 ,  C12Q1/68 ,  G06F19/12 ,  G01N33/48 ,  C12P21/06 ,  G06G7/48

CPC分类号： G06F19/12 ,  C12Q1/025 ,  G01N33/5041

摘要： The present invention provides methods and computer systems for identifying and representing the biological pathways of drug action on a cell The present invention also provides methods and computer systems for assessing the significance of the identified representation and for verifying that the identified pathways are actual pathway of drug action. The present invention also provides methods and computer systems for drug development based on the methods for identifying biological pathways of drug action, and methods and computer systems for representing the biological pathways involved in the effect of an environmental change upon a cell.

摘要翻译： 本发明提供用于鉴定和表示药物作用于细胞的生物学途径的方法和计算机系统本发明还提供了用于评估所鉴定的表现的重要性并用于验证所鉴定的途径是药物的实际途径的方法和计算机系统 行动。 本发明还提供了用于鉴定药物作用的生物学途径的方法的用于药物开发的方法和计算机系统，以及用于表示涉及环境变化对细胞的影响的生物学途径的方法和计算机系统。