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1. 发明申请

WO2005100609A3 METHODS FOR IDENTIFYING GENES THAT MEDIATE A RESPONSE OF A LIVING CELL TO AN AGENT 审中-公开
公开(公告)号：WO2005100609A3
公开(公告)日：2005-10-27
申请号：PCT/US2005/012452
申请日：2005-04-12
申请人： ROSETTA INPHARMATICS LLC , MAO, Mao , JACKSON, Aimee , LINSLEY, Peter, S. , DAI, Hongyue
发明人： MAO, Mao , JACKSON, Aimee , LINSLEY, Peter, S. , DAI, Hongyue
IPC分类号： C12Q1/68
摘要： In one aspect, the present invention provides methods for determining whether a gene mediates the response of a living cell to an agent. In another aspect, the present invention provides methods to identify a mammalian subject responsive to a KSP inhibitor.

2. 发明申请

WO2005042708A2 METHOD OF DESIGNING siRNAS FOR GENE SILENCING 审中-公开
标题翻译：设计用于基因沉默的siRNA的方法
公开(公告)号：WO2005042708A2
公开(公告)日：2005-05-12
申请号：PCT/US2004/035636
申请日：2004-10-27
申请人： ROSETTA INPHARMATICS LLC , JACKSON, Aimee, L. , BARTZ, Steven, R. , BURCHARD, Julja , LINSLEY, Peter, S. , GE, Wei , CAVET, Guy, L.
发明人： JACKSON, Aimee, L. , BARTZ, Steven, R. , BURCHARD, Julja , LINSLEY, Peter, S. , GE, Wei , CAVET, Guy, L.
IPC分类号： C12N
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/11 , C12N2330/31 , G06F19/18 , G06F19/22
摘要： The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.
摘要翻译：本发明提供使用位置特异性评分矩阵法来鉴定转录物中的siRNA靶基序的方法。本发明还提供了一种使用位置特异性评分矩阵方法鉴定siRNA的靶外基因的方法。本发明还提供了设计具有较高沉默功效和特异性的siRNA的方法。本发明还提供了包含具有高沉默功效和特异性的siRNA的siRNA文库。

3. 发明申请

WO2005018534A3 METHODS AND COMPOSITIONS FOR RNA INTERFERENCE 审中-公开
公开(公告)号：WO2005018534A3
公开(公告)日：2005-03-03
申请号：PCT/US2004/015439
申请日：2004-05-17
申请人： ROSETTA INPHARMATICS, LLC , JACKSON, Aimee, L. , BARTZ, Steven, R. , BURCHARD, Julia , SCHELTER, Janell, M. , LINSLEY, Peter, S.
发明人： JACKSON, Aimee, L. , BARTZ, Steven, R. , BURCHARD, Julia , SCHELTER, Janell, M. , LINSLEY, Peter, S.
IPC分类号： C07H21/04
摘要： The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.

4. 发明申请

WO2007041453A3 METHODS AND COMPOSITIONS FOR TREATING CANCER 审中-公开
标题翻译：用于治疗癌症的方法和组合物
公开(公告)号：WO2007041453A3
公开(公告)日：2009-05-07
申请号：PCT/US2006038350
申请日：2006-09-29
申请人： ROSETTA INPHARMATICS LLC , BARTZ STEVEN R , LINSLEY PETER S
发明人： BARTZ STEVEN R , LINSLEY PETER S
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C12Q1/485 , C12N15/1137 , C12N2310/11 , C12N2310/12 , C12N2310/14 , C12N2310/15
摘要： The present invention relates to methods and compositions for treating cancers by reducing the expression or activity of one or more of the genes encoding protein kinases ATR, MAST2, MAP3K6, TBKl, ADRBK2, CDKL2, LATS2, STK32B, STKIl, DDRl3 PSKH2, and NEK8, and/or the encoded kinases. The invention also relates to methods and compositions for determining the responsiveness of a cancer patient to anti-cancer drugs based on the status of one or more of such kinases. The invention further relates to methods and compositions for screening compounds that can be used to modulate the expression/activity of these kinases.
摘要翻译：本发明涉及通过降低一种或多种编码蛋白激酶ATR，MAST2，MAP3K6，TBK1，ADRBK2，CDKL2，LATS2，STK32B，STKI1，DDR13 PSKH2和NEK8的基因的表达或活性来治疗癌症的方法和组合物。，和/或编码的激酶。本发明还涉及用于基于一种或多种这样的激酶的状态确定癌症患者对抗癌药物的反应性的方法和组合物。本发明还涉及用于筛选可用于调节这些激酶的表达/活性的化合物的方法和组合物。

5. 发明申请

WO2005031002A3 SYNTHETIC LETHAL SCREEN USING RNA INTERFERENCE 审中-公开
标题翻译：使用RNA干扰的合成网页
公开(公告)号：WO2005031002A3
公开(公告)日：2005-10-13
申请号：PCT/US2004031629
申请日：2004-09-22
申请人： ROSETTA INPHARMATICS LLC , MERCK & CO INC , LINSLEY PETER S , MAO MAO , KIM ANNETTE S , FRIEND STEPHEN H , BARTZ STEVEN R , CLEARY MICHELE A
发明人： LINSLEY PETER S , MAO MAO , KIM ANNETTE S , FRIEND STEPHEN H , BARTZ STEVEN R , CLEARY MICHELE A
IPC分类号： C07H21/02 , C12N15/11 , C12N15/85 , C12Q1/68
CPC分类号： C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/12
摘要： The invention provides a method for identifying one or more genes in a cell of a cell type which interact with, e.g., modulate the effect of, an agent, e.g., a drug. For example, an identified gene may confer resistance or sensitivity to a drug, i.e., reduces or enhances the effect of the drug. The invention also provides STK6 and TPX2 as a gene that exhibits synthetic lethal interactions with KSP encoding a kinesin-like motor protein, and methods and compositions for treatment of diseases, e.g., cancers, by modulating the expression of STK6 or TPX2 gene and/or the activity of STK6 or TPX2 gene product. The invention also provides genes involved in cellular response to DNA damage, and their therapeutic uses.
摘要翻译：本发明提供了一种用于鉴定与例如药物的作用相互作用的细胞类型的细胞中的一种或多种基因的方法。例如，鉴定的基因可赋予药物抗药性或敏感性，即降低或增强药物的作用。本发明还提供STK6和TPX2作为与编码驱动蛋白样运动蛋白的KSP显示出合成的致死相互作用的基因，以及通过调节STK6或TPX2基因和/或的表达的治疗疾病例如癌症的方法和组合物 STK6或TPX2基因产物的活性。本发明还提供涉及对DNA损伤的细胞反应及其治疗用途的基因。

6. 发明申请

WO2004109290A3 METHODS FOR IDENTIFYING MODULATORS OF KINESIN ACTIVITY 审中-公开
标题翻译：用于鉴定金属蛋白酶活性调节剂的方法
公开(公告)号：WO2004109290A3
公开(公告)日：2005-03-24
申请号：PCT/US2004017234
申请日：2004-05-28
申请人： ROSETTA INPHARMATICS LLC , MERCK & CO INC , MAO MAO , LINSLEY PETER S , BUSER CAROLYN A , MARSHALL CHRISTOPHER GARY , KIM ANNETTE S
发明人： MAO MAO , LINSLEY PETER S , BUSER CAROLYN A , MARSHALL CHRISTOPHER GARY , KIM ANNETTE S
IPC分类号： A61K31/175 , A61K38/00 , C12Q1/34 , G01N33/573 , G01N33/574 , G01N33/50 , C12Q1/48
CPC分类号： G01N33/5011 , A61K31/175 , A61K38/00 , C12Q1/34 , G01N33/573 , G01N33/57415
摘要： In a first aspect, the invention provides methods for screening for modulators of a target protein, comprising the steps of contacting a target protein with a candidate agent and determining whether the candidate agent modulates the activity of the target protein, wherein the target protein comprises a sequence that has more than 80% amino acid sequence identity to KIF14 (SEQ ID NO:2) or the KIF14 motor domain (SEQ ID NO:3). In a second aspect, the invention provides methods for modulating cell proliferation comprising administering to a cell an effective amount of a modulator of the activity of a target protein. Some embodiments of this aspect provide methods for treating a subject with a cellular hyperproliferation disorder, such as cancer. In a third aspect, the invention provides methods for identifying candidate subjects for treatment with an inhibitor of the activity of a target protein.
摘要翻译：在第一方面，本发明提供了筛选靶蛋白的调节剂的方法，包括以下步骤：使靶蛋白与候选试剂接触并确定候选试剂是否调节靶蛋白的活性，其中靶蛋白包含与KIF14（SEQ ID NO：2）或KIF14运动结构域（SEQ ID NO：3）具有80％以上氨基酸序列同一性的序列。在第二方面，本发明提供了调节细胞增殖的方法，包括向细胞施用有效量的靶蛋白活性的调节剂。该方面的一些实施方案提供了用细胞过度增殖病症如癌症治疗受试者的方法。在第三方面，本发明提供用于鉴定候选受试者用靶蛋白活性抑制剂治疗的方法。

7. 发明申请

WO2004109290A2 METHODS FOR IDENTIFYING MODULATORS OF KINESIN ACTIVITY 审中-公开
标题翻译：用于鉴定金属蛋白酶活性调节剂的方法
公开(公告)号：WO2004109290A2
公开(公告)日：2004-12-16
申请号：PCT/US2004/017234
申请日：2004-05-28
申请人： ROSETTA INPHARMATICS LLC , MERCK & CO., INC. , MAO, Mao , LINSLEY, Peter, S. , BUSER, Carolyn, A. , MARSHALL, Christopher, Gary , KIM, Annette, S.
发明人： MAO, Mao , LINSLEY, Peter, S. , BUSER, Carolyn, A. , MARSHALL, Christopher, Gary , KIM, Annette, S.
IPC分类号： G01N33/68
CPC分类号： G01N33/5011 , A61K31/175 , A61K38/00 , C12Q1/34 , G01N33/573 , G01N33/57415
摘要： In a first aspect, the invention provides methods for screening for modulators of a target protein, comprising the steps of contacting a target protein with a candidate agent and determining whether the candidate agent modulates the activity of the target protein, wherein the target protein comprises a sequence that has more than 80% amino acid sequence identity to KIF14 (SEQ ID NO:2) or the KIF14 motor domain (SEQ ID NO:3). In a second aspect, the invention provides methods for modulating cell proliferation comprising administering to a cell an effective amount of a modulator of the activity of a target protein. Some embodiments of this aspect provide methods for treating a subject with a cellular hyperproliferation disorder, such as cancer. In a third aspect, the invention provides methods for identifying candidate subjects for treatment with an inhibitor of the activity of a target protein.
摘要翻译：在第一方面，本发明提供了筛选靶蛋白的调节剂的方法，包括以下步骤：使靶蛋白与候选试剂接触并确定候选试剂是否调节靶蛋白的活性，其中靶蛋白包含与KIF14（SEQ ID NO：2）或KIF14运动结构域（SEQ ID NO：3）具有80％以上氨基酸序列同一性的序列。在第二方面，本发明提供了调节细胞增殖的方法，包括向细胞施用有效量的靶蛋白活性的调节剂。该方面的一些实施方案提供了用细胞过度增殖病症如癌症治疗受试者的方法。在第三方面，本发明提供用于鉴定候选受试者用靶蛋白活性抑制剂治疗的方法。

8. 发明申请

WO2007147067A8 METHODS AND COMPOSITIONS FOR REGULATING CELL CYCLE PROGRESSION 审中-公开
标题翻译：用于调节细胞周期进程的方法和组合物
公开(公告)号：WO2007147067A8
公开(公告)日：2009-07-23
申请号：PCT/US2007071239
申请日：2007-06-14
申请人： ROSETTA INPHARMATICS LLC , KIBUKAWA MIHO , LIM LEE , LINSLEY PETER S , SCHELTER JANELL , BURCHARD JULJA
发明人： KIBUKAWA MIHO , LIM LEE , LINSLEY PETER S , SCHELTER JANELL , BURCHARD JULJA
IPC分类号： C07H21/02 , C07H21/04 , C12Q1/68
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/12 , C12N2330/10 , C12N2330/31
摘要： In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5' end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5' end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the method comprises introducing at least one iRNA that inhibits the expression of at least one miR-16 responsive gene selected from TABLE 5 into the mammalian cell.
摘要翻译：一方面，提供抑制哺乳动物细胞增殖的方法，包括向所述细胞中引入有效量的至少一种至少一种小干扰RNA试剂（iRNA），其中所述iRNA包含至少15个核苷酸的核苷酸序列，其中所述核苷酸序列包含由核苷酸位置1至12组成的种子区，其中位置1表示iRNA核苷酸序列的5'末端，并且其中所述种子区包含与六个互补的至少六个连续核苷酸的核苷酸序列核苷酸序列的第1至12位的连续核苷酸，其中位置1表示核苷酸序列的5'端，其中所述核苷酸序列选自SEQ ID NO：1，SEQ ID NO：2，SEQ ID NO： NO：3，SEQ ID NO：4，SEQ ID NO：5，SEQ ID NO：6，SEQ ID NO：7和SEQ ID NO：8。在一些实施方案中，所述方法包括将至少一种抑制至少一种选自表5的miR-16应答基因的表达的iRNA引入到哺乳动物细胞中。

9. 发明申请

WO2008137862A2 METHODS OF USING MIR34 AS A BIOMARKER FOR TP53 FUNCTIONAL STATUS 审中-公开
标题翻译：使用MIR34作为生物标记物用于TP53功能状态的方法
公开(公告)号：WO2008137862A2
公开(公告)日：2008-11-13
申请号：PCT/US2008062681
申请日：2008-05-05
申请人： ROSETTA INPHARMATICS LLC , COLD SPRING HARBOR LAB , LINSLEY PETER S , LIM LEE P , CLEARY MICHELE A , JACKSON AIMEE L , BURCHARD JULJA , MAGNUS JILL F , HANNON GREGORY J , HE LIN , LOWE SCOTT W , HE XINGYUE
发明人： LINSLEY PETER S , LIM LEE P , CLEARY MICHELE A , JACKSON AIMEE L , BURCHARD JULJA , MAGNUS JILL F , HANNON GREGORY J , HE LIN , LOWE SCOTT W , HE XINGYUE
IPC分类号： C12Q1/68 , G06F19/00
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/14 , C12N2310/141 , C12N2320/53 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178
摘要： In one aspect, the invention generally relates to use of miR-34 as a biomarker to estimate TP53 function in a cell. In another aspect, the invention generally relates to multiple uses of miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.
摘要翻译：一方面，本发明一般涉及miR-34作为生物标志物来估计细胞中TP53功能的用途。在另一方面，本发明一般涉及miR-34和siRNA在功能上和结构上与miR-34相关的多种用途，用于治疗癌症。

10. 发明申请

WO2008137867A2 COMPOSITIONS COMPRISING MIR34 THERAPEUTIC AGENTS FOR TREATING CANCER 审中-公开
标题翻译：包含MIR34治疗癌症治疗剂的组合物
公开(公告)号：WO2008137867A2
公开(公告)日：2008-11-13
申请号：PCT/US2008/062689
申请日：2008-05-05
申请人： ROSETTA INPHARMATICS LLC , CLEARY, Michele, A. , JACKSON, Aimee, L. , LINSLEY, Peter, S. , BURCHARD, Julja , LIM, Lee, P. , MAGNUS, Jill, F.
发明人： CLEARY, Michele, A. , JACKSON, Aimee, L. , LINSLEY, Peter, S. , BURCHARD, Julja , LIM, Lee, P. , MAGNUS, Jill, F.
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/14 , C12N2310/141 , C12N2320/53 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178
摘要： In one aspect, the invention generally relates to compositions comprising miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.
摘要翻译：一方面，本发明一般涉及包含miR-34和在功能上和结构上与用于治疗癌症的miR-34相关的siRNA的组合物。

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