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1. 发明申请

WO2011097333A1 IDENTIFICATION OF LKB1 MUTATION AS A PREDICTIVE BIOMARKER FOR SENSITIVITY TO TOR KINASE INHIBITORS 审中-公开
标题翻译：鉴定LKB1突变作为预测生物标志物，用于感应激酶激酶抑制剂
公开(公告)号：WO2011097333A1
公开(公告)日：2011-08-11
申请号：PCT/US2011/023524
申请日：2011-02-03
申请人： SIGNAL PHARMACEUTICALS, LLC , SANKAR, Sabita , CHOPRA, Rajesh , XU, Weiming , NING, Yuhong , XU, Shuichan
发明人： SANKAR, Sabita , CHOPRA, Rajesh , XU, Weiming , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/497
CPC分类号： A61K31/519 , A61K31/155 , A61K31/4985 , A61K31/7004 , A61K2300/00
摘要： Provided herein are methods for treating and/or preventing a cancer or a tumor syndrome in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having cancer or a tumor syndrome, characterized by a LKB 1 and/or AMPK gene or protein loss or mutation.
摘要翻译：本文提供了用于治疗和/或预防患者的癌症或肿瘤综合征的方法，包括向具有癌症或肿瘤综合征的患者施用有效量的TOR激酶抑制剂，其特征在于LKB 1和/或AMPK基因或蛋白质丢失或突变。

2. 发明申请

WO2014113429A2 SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH 审中-公开
标题翻译：取代的吡咯并嘧啶化合物，其组合物及其治疗方法
公开(公告)号：WO2014113429A2
公开(公告)日：2014-07-24
申请号：PCT/US2014/011612
申请日：2014-01-15
申请人： SIGNAL PHARMACEUTICALS, LLC
发明人： CALABRESE, Andrew, Antony , JEFFY, Brandon , ROBINSON, Dale , ZHU, Dan , HUANG, Dehua , ELSNER, Jan , BOYLAN, John , TEHRANI, Lida , NAGY, Mark, A. , RAHEJA, Raj, Kumar , ERDMAN, Paul , NARLA, Rama, K. , HARRIS, Roy, L. , TRAN, Tam, Minh , RIGGS, Jennifer , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/519
CPC分类号： A61K31/519 , A61K31/5377 , C07D471/04 , C07D487/04
摘要： Provided herein are Pyrrolopyrimidine Compounds having the following structure: wherein R 1 , R 2 , R 3 , and L are as defined herein, compositions comprising an effective amount of a Pyrrolopyrimidine Compound, and methods for treating or preventing breast cancer, more particularly triple negative breast cancer, comprising administering an effective amount of such Pyrrolopyrimidine Compounds to a subject in need thereof.
摘要翻译：本文提供了具有以下结构的吡咯并嘧啶化合物：其中R 1，R 2，R 3和 L如本文所定义，包含有效量的吡咯并嘧啶化合物的组合物，以及用于治疗或预防乳腺癌，更特别是三阴性乳腺癌的方法，所述方法包括向有需要的受试者施用有效量的所述吡咯并嘧啶化合物。 p>

3. 发明申请

WO2013019927A1 IDENTIFICATION OF GENE EXPRESSION PROFILE AS A PREDICTIVE BIOMARKER FOR LKB1 STATUS 审中-公开
标题翻译：基因表达谱的识别作为LKB1状态的预测生物标记
公开(公告)号：WO2013019927A1
公开(公告)日：2013-02-07
申请号：PCT/US2012/049281
申请日：2012-08-02
申请人： SIGNAL PHARMACEUTICALS, LLC , NING, Yuhong , XU, Weiming , CHOPRA, Rajesh , WORLAND, Peter , XU, Shuichan
发明人： NING, Yuhong , XU, Weiming , CHOPRA, Rajesh , WORLAND, Peter , XU, Shuichan
IPC分类号： C12Q1/68
CPC分类号： A61K31/5377 , A61K31/437 , A61K31/498 , A61K31/53 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： Provided herein are methods for predicting the LKBl status of a patient or a biological sample, comprising the measurement of particular gene expression levels relative to a set of reference levels that represent the gene expression level of a biological wild-type sample without LKBl gene or protein loss or mutation and the gene expression level of a reference sample with LKBl gene or protein loss or mutation. Further provided herein are methods for treating and/or preventing a cancer or a tumor syndrome in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having cancer or a tumor syndrome, characterized by particular gene expression levels.
摘要翻译：本文提供了用于预测患者或生物样品的LKB1状态的方法，其包括相对于代表没有LKB1基因或蛋白质的生物野生型样品的基因表达水平的一组参考水平的特定基因表达水平的测量损失或突变以及具有LKB1基因或蛋白质丢失或突变的参照样品的基因表达水平。本文还提供了用于治疗和/或预防患者的癌症或肿瘤综合征的方法，其包括以具有特定基因表达水平为特征的患有癌症或肿瘤综合征的患者施用有效量的TOR激酶抑制剂。

4. 发明授权

EP2945636B1 SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH 失效
标题翻译：取代的吡咯并嘧啶化合物，其组合物及其治疗方法
公开(公告)号：EP2945636B1
公开(公告)日：2017-06-28
申请号：EP14702393.1
申请日：2014-01-15
申请人： Signal Pharmaceuticals, LLC
发明人： CALABRESE, Andrew Antony , JEFFY, Brandon David , ROBINSON, Dale , ZHU, Dan , HUANG, Dehua , ELSNER, Jan , BOYLAN, John Frederick , TEHRANI, Lida , NAGY, Mark, A. , RAHEJA, Raj, Kumar , ERDMAN, Paul , NARLA, Rama, K. , HARRIS, Roy, L. , TRAN, Tam, Minh , RIGGS, Jennifer R. , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/519 , C07D487/00 , A61P35/00
CPC分类号： A61K31/519 , A61K31/5377 , C07D471/04 , C07D487/04
摘要： The present invention relates to a compound of formula (I): and pharmaceutically acceptable salts, tautomers, stereoisomers, enantiomers, and isotopologues thereof, wherein R 1 , R 2 , R 3 and L are as defined herein. Also provided is a compound or a pharmaceutical composition of the present invention for use in a method for treating or preventing breast cancer.
摘要翻译：本文提供具有以下结构的吡咯并嘧啶化合物：其中R 1，R 2，R 3和L如本文所定义，包含有效量的吡咯并嘧啶化合物的组合物，以及用于治疗或预防乳腺癌，更特别是三阴性乳腺癌的方法，包括给有此需要的受试者施用有效量的这种吡咯并嘧啶化合物。

5. 发明公开

EP2992878A1 IDENTIFICATION OF LKB1 MUTATION AS A PREDICTIVE BIOMARKER FOR SENSITIVITY TO TOR KINASE INHIBITORS 审中-公开
标题翻译： LKB1突变预测性生物标记的鉴定灵敏度TO TOR激酶抑制剂
公开(公告)号：EP2992878A1
公开(公告)日：2016-03-09
申请号：EP15180730.2
申请日：2011-02-03
申请人： Signal Pharmaceuticals, LLC
发明人： SANKAR, Sabita , CHOPRA, Rajesh , XU, Weiming , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/155 , A61K31/4985 , A61K31/519 , A61K31/7004 , A61P35/00
CPC分类号： A61K31/519 , A61K31/155 , A61K31/4985 , A61K31/7004 , A61K2300/00
摘要： The invention provides a TOR kinase inhibitor for use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the method comprises administering the TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a LKB1 gene or protein loss or mutation, relative to wild type, wherein the TOR kinase inhibitor is 1-ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one or a pharmaceutically acceptable salt, clathrate, solvate, stereoisomer, or tautomer thereof. The TOR kinase inhibitor can be used use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the the TOR kinase inhibitor is administered in combination with one or more agents selected from 2-deoxyglucose, metformin, phenformin and pemetrexed. The TOR kinase inhibitor can further be used for predicting the likelihood of a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy.
摘要翻译：本发明提供了使用TOR激酶抑制剂在制备用于治疗非小细胞肺癌，宫颈癌或黑斑息肉综合症的方法，worin该方法包括施用所述TOR激酶抑制剂具有非小细胞肺癌的患者，宫颈癌症或黑斑息肉综合症由LKB1基因或蛋白的缺失或突变，相对于野生型，worin TOR激酶抑制剂是1-乙基-7-（2-甲基-6-（4H-1,2,4-特点三唑-3-基）吡啶-3-基）-3,4-二氢吡嗪并[2,3-b]吡嗪-2） - 酮或其药学上可接受的盐，包合物，溶剂化物，立体异构体，或互变异构体（1H。 TOR激酶抑制剂可用于使用在一种用于治疗非小细胞肺癌，宫颈癌或黑斑息肉综合征，worin的TOR激酶抑制剂给予与选自2-脱氧葡萄糖，二甲双胍中选择的一种或多种试剂，苯乙双胍和培美曲塞。 TOR激酶抑制剂可用于进一步预测患有非小细胞肺癌，宫颈癌或黑斑息肉综合症响应于TOR激酶抑制剂治疗的患者的可能性。

6. 发明公开

EP2945636A2 SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH 失效
标题翻译：替代品吡咯并嘧啶，ZUSAMMENSETZUNGEN DAVON UND BEHANDLUNGSVERFAHREN DAMIT
公开(公告)号：EP2945636A2
公开(公告)日：2015-11-25
申请号：EP14702393.1
申请日：2014-01-15
申请人： Signal Pharmaceuticals, LLC
发明人： CALABRESE, Andrew Antony , JEFFY, Brandon David , ROBINSON, Dale , ZHU, Dan , HUANG, Dehua , ELSNER, Jan , BOYLAN, John Frederick , TEHRANI, Lida , NAGY, Mark, A. , RAHEJA, Raj, Kumar , ERDMAN, Paul , NARLA, Rama, K. , HARRIS, Roy, L. , TRAN, Tam, Minh , RIGGS, Jennifer R. , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/519 , C07D487/00 , A61P35/00
CPC分类号： A61K31/519 , A61K31/5377 , C07D471/04 , C07D487/04
摘要： The present invention relates to a compound of formula (I): and pharmaceutically acceptable salts, tautomers, stereoisomers, enantiomers, and isotopologues thereof, wherein R 1 , R 2 , R 3 and L are as defined herein. Also provided is a compound or a pharmaceutical composition of the present invention for use in a method for treating or preventing breast cancer.
摘要翻译：本文提供具有以下结构的吡咯并嘧啶化合物：其中R1，R2，R3和L如本文所定义，包含有效量的吡咯并嘧啶化合物的组合物，以及用于治疗或预防乳腺癌的方法，更特别是三阴性乳腺癌，包括向有需要的受试者施用有效量的这种吡咯并嘧啶化合物。

7. 发明公开

EP2739751A1 IDENTIFICATION OF GENE EXPRESSION PROFILE AS A PREDICTIVE BIOMARKER FOR LKB1 STATUS 审中-公开
标题翻译：基因表达资料的确认，作为LKB1状态的预测生物标志物
公开(公告)号：EP2739751A1
公开(公告)日：2014-06-11
申请号：EP12748616.5
申请日：2012-08-02
申请人： Signal Pharmaceuticals, LLC
发明人： NING, Yuhong , XU, Weiming , CHOPRA, Rajesh , WORLAND, Peter , XU, Shuichan
IPC分类号： C12Q1/68
CPC分类号： A61K31/5377 , A61K31/437 , A61K31/498 , A61K31/53 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： Provided herein are methods for predicting the LKBl status of a patient or a biological sample, comprising the measurement of particular gene expression levels relative to a set of reference levels that represent the gene expression level of a biological wild-type sample without LKBl gene or protein loss or mutation and the gene expression level of a reference sample with LKBl gene or protein loss or mutation. Further provided herein are methods for treating and/or preventing a cancer or a tumor syndrome in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having cancer or a tumor syndrome, characterized by particular gene expression levels.

8. 发明授权

EP2531194B1 IDENTIFICATION OF LKB1 MUTATION AS A PREDICTIVE BIOMARKER FOR SENSITIVITY TO TOR KINASE INHIBITORS 有权转让
标题翻译：鉴定LKB1突变对预测激酶抑制剂敏感性的预测生物标志物
公开(公告)号：EP2531194B1
公开(公告)日：2018-04-18
申请号：EP11740321.2
申请日：2011-02-03
申请人： Signal Pharmaceuticals, LLC
发明人： SANKAR, Sabita , CHOPRA, Rajesh , XU, Weiming , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/4985 , A61P35/00
CPC分类号： A61K31/519 , A61K31/155 , A61K31/4985 , A61K31/7004 , A61K2300/00
摘要： The invention provides a TOR kinase inhibitor for use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the method comprises administering the TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a LKB1 gene or protein loss or mutation, relative to wild type, wherein the TOR kinase inhibitor is 1-ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one or a pharmaceutically acceptable salt, clathrate, solvate, stereoisomer, or tautomer thereof. The TOR kinase inhibitor can be used use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the the TOR kinase inhibitor is administered in combination with one or more agents selected from 2-deoxyglucose, metformin, phenformin and pemetrexed. The TOR kinase inhibitor can further be used for predicting the likelihood of a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy.

9. 发明公开

EP3202403A1 SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH 审中-公开
标题翻译：取代的吡咯并嘧啶化合物，其组合物及其治疗方法
公开(公告)号：EP3202403A1
公开(公告)日：2017-08-09
申请号：EP17152166.9
申请日：2014-01-15
申请人： Signal Pharmaceuticals, LLC
发明人： CALABRESE, Andrew Antony , JEFFY, Brandon David , ROBINSON, Dale , ZHU, Dan , Huang, Dehua , Elsner, Jan , BOYLAN, John Frederick , Tehrani, Lida , NAGY, Mark A. , RAHEJA, Raj Kumar , ERDMAN, Paul , NARLA, Rama K. , Harris, Roy L. , TRAN, Tam Minh , Riggs, Jennifer R. , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/519 , C07D487/00 , A61P35/00 , A61K31/5377 , C07D487/04
CPC分类号： A61K31/519 , A61K31/5377 , C07D471/04 , C07D487/04
摘要： The present invention relates to a compound of formula (I):

and pharmaceutically acceptable salts, tautomers, stereoisomers, enantiomers, and isotopologues thereof, wherein R 1 , R 2 , R 3 and L are as defined herein. Also provided is a compound or a pharmaceutical composition of the present invention for use in a method for treating or preventing breast cancer.
摘要翻译：本发明涉及式（I）化合物及其药学上可接受的盐，互变异构体，立体异构体，对映异构体和同位素异构体，其中R 1，R 2，R 3和L如本文所定义。还提供了用于治疗或预防乳腺癌的方法中的本发明的化合物或药物组合物。

10. 发明公开

EP2531194A1 IDENTIFICATION OF LKB1 MUTATION AS A PREDICTIVE BIOMARKER FOR SENSITIVITY TO TOR KINASE INHIBITORS 有权转让
标题翻译： LKB1突变预测性生物标记的鉴定灵敏度TO TOR激酶抑制剂
公开(公告)号：EP2531194A1
公开(公告)日：2012-12-12
申请号：EP11740321.2
申请日：2011-02-03
申请人： Signal Pharmaceuticals, LLC
发明人： SANKAR, Sabita , CHOPRA, Rajesh , XU, Weiming , NING, Yuhong , XU, Shuichan
IPC分类号： A61K31/497
CPC分类号： A61K31/519 , A61K31/155 , A61K31/4985 , A61K31/7004 , A61K2300/00
摘要： The invention provides a TOR kinase inhibitor for use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the method comprises administering the TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a LKB1 gene or protein loss or mutation, relative to wild type, wherein the TOR kinase inhibitor is 1-ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one or a pharmaceutically acceptable salt, clathrate, solvate, stereoisomer, or tautomer thereof. The TOR kinase inhibitor can be used use in a method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, wherein the the TOR kinase inhibitor is administered in combination with one or more agents selected from 2-deoxyglucose, metformin, phenformin and pemetrexed. The TOR kinase inhibitor can further be used for predicting the likelihood of a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy.

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