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1. 发明申请

WO2015108175A1 GENE SIGNATURES ASSOCIATED WITH SENSITIVITY TO MDM2 INHIBITORS 审中-公开
标题翻译：与MDM2抑制剂相关的基因信号与敏感性相关
公开(公告)号：WO2015108175A1
公开(公告)日：2015-07-23
申请号：PCT/JP2015/051157
申请日：2015-01-13
申请人： DAIICHI SANKYO COMPANY, LIMITED
发明人： TSE, Ngai-chiu Archie , NAKAMARU, Kenji , TAZAKI, Koichi , WATANABE, Kenji , SEKI, Takahiko
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , A61K31/4439 , A61K31/496 , C12Q2600/106 , C12Q2600/158 , G01N33/57484
摘要： Provided are gene signatures that are predictive of the sensitivity of a cancer or tumor to an MDM2i or an antagonist of the MDM2-p53 interaction. Differentially expressed genes in the provided gene signatures serve as biomarkers for determining and assessing the sensitivity of cancer and tumor samples to treatment or therapy with an MDM2i. Also provided are methods of determining MDM2i sensitivity of different cancer and tumor types and subtypes, based on the expression of genes in the MDM2i sensitive gene signatures, and treating individuals with an MDM2i if their cancers are determined to be MDM2i-sensitive, based on the practice of the described methods. TP53 gene and p53 protein status can also be determined for the samples undergoing analysis for MDM2i sensitivity. Methods, platforms, kits, reagents, and compositions of the invention provide advantageous approaches and tools for personalized or individualized treatments of cancer patients whose cancers exhibit sensitivity to MDM2 inhibitors, as indicated by the differential expression of genes in the gene signatures relative to controls according to the described methods.
摘要翻译：提供了预测癌症或肿瘤对MDM2i或MDM2-p53相互作用的拮抗剂的敏感性的基因特征。提供的基因标签中的差异表达基因用作确定和评估癌症和肿瘤样品对于MDM2i治疗或治疗的敏感性的生物标志物。还提供了基于MDM2i敏感基因签名中基因表达来确定不同癌症和肿瘤类型和亚型的MDM2i敏感性的方法，并且如果将MDM2i的癌症确定为MDM2i敏感性，则基于MDM2i敏感性来治疗个体描述方法的实践。对于经历MDM2i敏感性分析的样品，也可以测定TP53基因和p53蛋白状态。本发明的方法，平台，试剂盒，试剂和组合物为癌症患者的个体化或个体化治疗提供了有利的方法和工具，其癌症对MDM2抑制剂表现出敏感性，如基因签名中基因的差异表达相对于对照，涉及到所描述的方法。

2. 发明申请

WO2016056673A1 ALGORITHMS FOR GENE SIGNATURE-BASED PREDICTOR OF SENSITIVITY TO MDM2 INHIBITORS 审中-公开
标题翻译：基于基因签名的MDM2抑制剂敏感性预测因子的算法
公开(公告)号：WO2016056673A1
公开(公告)日：2016-04-14
申请号：PCT/JP2015/079389
申请日：2015-10-09
申请人： DAIICHI SANKYO COMPANY, LIMITED
发明人： TSE, Ngai-chiu Archie , NAKAMARU, Kenji , TAZAKI, Koichi , WATANABE, Kenji , SEKI, Takahiko
IPC分类号： C12Q1/68 , A61K31/499
CPC分类号： C12Q1/6886 , A61K31/4439 , A61K31/499 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/574
摘要： Provided are gene signatures that are predictive of the sensitivity of a cancer or tumor to an MDM2i or an antagonist of the MDM2-p53 interaction. Differentially expressed genes in the provided gene signatures serve as biomarkers for determining and assessing the sensitivity of cancer and tumor samples to treatment or therapy with an MDM2i. Also provided are methods of determining MDM2i sensitivity of a test sample such as different cancer and tumor types and subtypes, based on the expression of genes in the MDM2i sensitive gene signatures in reference samples and the test sample even if all of the MDM2i sensitivities of the reference samples are unknown, and treating individuals with an MDM2i if their cancers are determined to be MDM2i-sensitive, based on the practice of the described methods. TP53 gene and p53 protein status can also be determined for the samples undergoing analysis for MDM2i sensitivity. Methods, platforms, kits, reagents, and compositions of the invention provide advantageous approaches and tools for personalized or individualized treatments of cancer patients whose cancers exhibit sensitivity to MDM2 inhibitors, as indicated by the differential expression of genes in the gene signatures relative to controls according to the described methods.
摘要翻译：提供了预测癌症或肿瘤对MDM2i或MDM2-p53相互作用的拮抗剂的敏感性的基因特征。提供的基因标签中的差异表达基因用作确定和评估癌症和肿瘤样品对于MDM2i治疗或治疗的敏感性的生物标志物。还提供了基于参考样品和测试样品中MDM2i敏感基因特征中的基因表达来测定诸如不同癌症和肿瘤类型和亚型的测试样品的MDM2i敏感性的方法，即使所有MDM2i灵敏度参考样品是未知的，并且基于所描述的方法的实践，如果他们的癌症被确定为MDM2i敏感性，则使用MDM2i治疗个体。对于经历MDM2i敏感性分析的样品，也可以测定TP53基因和p53蛋白状态。本发明的方法，平台，试剂盒，试剂和组合物为癌症患者的个体化或个体化治疗提供了有利的方法和工具，其癌症对MDM2抑制剂表现出敏感性，如基因签名中基因的差异表达相对于对照，涉及到所描述的方法。

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