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1. 发明申请

WO2012129145A8 NSCLC COMBINATION THERAPY 审中-公开
公开(公告)号：WO2012129145A8
公开(公告)日：2012-09-27
申请号：PCT/US2012/029598
申请日：2012-03-19
申请人： OSI PHARMACEUTICALS, LLC , THOMSON, Stuart , BROWN, Eric, N. , CHAU, Andrew , FRANKLIN, Maryland , IWATA, Kenneth, K.
发明人： THOMSON, Stuart , BROWN, Eric, N. , CHAU, Andrew , FRANKLIN, Maryland , IWATA, Kenneth, K.
IPC分类号： A61K31/4985 , A61K31/517 , A61K45/06 , A61P35/00
摘要： A method of treating NSCLC comprising in some aspects administering OSI-906 and an EGFR inhibitor to a patient having NSCLC having an activating EGFR mutation, as disclosed herein.

2. 发明申请

WO2009111067A2 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL -LIKE TUMOR CELLS OR THEIR FORMATION 审中-公开
公开(公告)号：WO2009111067A2
公开(公告)日：2009-09-11
申请号：PCT/US2009001456
申请日：2009-03-06
申请人： OSI PHARM INC , HALEY JOHN D , THOMSON STUART , KAN JULIE , SHAABAN SALAM A
发明人： HALEY JOHN D , THOMSON STUART , KAN JULIE , SHAABAN SALAM A
IPC分类号： G01N33/574
CPC分类号： G01N33/5011 , G01N2333/475 , G01N2333/485 , G01N2333/495 , G01N2333/525
摘要： The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-IR kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.

3. 发明申请

WO2008127718A2 BIOLOGICAL MARKERS PREDICTIVE OF ANTI-CANCER RESPONSE TO EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITORS 审中-公开
标题翻译：生物标志物对表皮生长因子受体激酶抑制剂的抗癌反应预测
公开(公告)号：WO2008127718A2
公开(公告)日：2008-10-23
申请号：PCT/US2008/004818
申请日：2008-04-14
申请人： OSI PHARMACEUTICALS, INC. , HALEY, John , THOMSON, Stuart , PETTI, Filippo
发明人： HALEY, John , THOMSON, Stuart , PETTI, Filippo
IPC分类号： G01N33/574 , C12Q1/68
CPC分类号： G01N33/6893 , G01N33/5011 , G01N33/57407 , G01N33/57484 , G01N2800/52
摘要： The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.
摘要翻译：本发明提供了用于预测用EGFR激酶抑制剂治疗癌症患者的有效性的诊断和预后方法。提供了用于预测肿瘤细胞生长对EGFR激酶抑制剂的抑制的敏感性的方法，包括通过确定上皮和/或间充质生物标志物的表达水平来评估肿瘤细胞是否已经经历上皮至间质转化（EMT），其中经历EMT的肿瘤细胞对EGFR激酶抑制剂的抑制作用明显较不敏感。还提供了包含上述方法的用EGFR激酶抑制剂治疗癌症患者的改进方法。另外，提供了用于鉴定预测肿瘤对EGFR激酶抑制剂的响应性的新生物标志物的方法。此外，还提供了用于鉴定恢复已经经历EMT的肿瘤细胞对EGFR激酶抑制剂的抑制的敏感性的试剂的方法。

4. 发明申请

WO2012149014A1 USE OF EMT GENE SIGNATURES IN CANCER DRUG DISCOVERY, DIAGNOSTICS, AND TREATMENT 审中-公开
标题翻译：在癌症药物发现，诊断和治疗中使用EMT基因标志
公开(公告)号：WO2012149014A1
公开(公告)日：2012-11-01
申请号：PCT/US2012/034989
申请日：2012-04-25
申请人： OSI PHARMACEUTICALS, LLC , AVEO PHARMACEUTICALS, INC. , KAN, Julie , THOMSON, Stuart , ARGAST, Gretchen M. , O'CONNOR, Matthew E. , ROBINSON, Murray , FENG, Bin , HEYER, Joerg , CHIU, Maria Isabel , NICOLETTI, Richard
发明人： KAN, Julie , THOMSON, Stuart , ARGAST, Gretchen M. , O'CONNOR, Matthew E. , ROBINSON, Murray , FENG, Bin , HEYER, Joerg , CHIU, Maria Isabel , NICOLETTI, Richard
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/158
摘要： The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.
摘要翻译：本发明提供用于评估肿瘤细胞的EMT状态的诊断方法，并且利用EMT基因特征指数评分来预测用EGFR或IGF-1R激酶抑制剂治疗癌症患者的有效性。本发明还提供了用于治疗纳入这些方法的癌症患者的方法。

5. 发明申请

WO2009111067A3 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL -LIKE TUMOR CELLS OR THEIR FORMATION 审中-公开
公开(公告)号：WO2009111067A3
公开(公告)日：2009-09-11
申请号：PCT/US2009/001456
申请日：2009-03-06
申请人： OSI PHARMACEUTICALS, INC. , HALEY, John, D. , THOMSON, Stuart , KAN, Julie , SHAABAN, Salam, A.
发明人： HALEY, John, D. , THOMSON, Stuart , KAN, Julie , SHAABAN, Salam, A.
IPC分类号： G01N33/574
摘要： The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-IR kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.

6. 发明申请

WO2008127718A3 BIOLOGICAL MARKERS PREDICTIVE OF ANTI-CANCER RESPONSE TO EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITORS 审中-公开
标题翻译：生物标志物预防抗癌生长因子受体激酶激酶抑制剂
公开(公告)号：WO2008127718A3
公开(公告)日：2008-12-04
申请号：PCT/US2008004818
申请日：2008-04-14
申请人： OSI PHARM INC , HALEY JOHN , THOMSON STUART , PETTI FILIPPO
发明人： HALEY JOHN , THOMSON STUART , PETTI FILIPPO
IPC分类号： G01N33/574 , C12Q1/68
CPC分类号： G01N33/6893 , G01N33/5011 , G01N33/57407 , G01N33/57484 , G01N2800/52
摘要： The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.
摘要翻译：本发明提供用于预测EGFR激酶抑制剂治疗癌症患者的有效性的诊断和预后方法。提供了用于预测肿瘤细胞生长对EGFR激酶抑制剂抑制的敏感性的方法，包括通过测定上皮和/或间质生物标志物的表达水平来评估肿瘤细胞是否经历了上皮间质转化（EMT），其中已经经历EMT的肿瘤细胞对EGFR激酶抑制剂的抑制基本上较不敏感。还提供了用于治疗结合上述方法的EGFR激酶抑制剂的癌症患者的改进方法。另外，提供了用于鉴定预测肿瘤对EGFR激酶抑制剂的反应性的新生物标志物的方法。此外，还提供了用于鉴定恢复已经经历EMT的肿瘤细胞对EGFR激酶抑制剂抑制的敏感性的药剂的方法。

7. 发明申请

WO2005032955A3 CORNER AND BULKHEAD PROTECTOR 审中-公开
标题翻译：角落和BULKHEAD保护者
公开(公告)号：WO2005032955A3
公开(公告)日：2005-07-14
申请号：PCT/US2004032565
申请日：2004-09-30
申请人： HOLLAND LP , THOMSON STUART H , O'NEILL BRIAN E
发明人： THOMSON STUART H , O'NEILL BRIAN E
IPC分类号： B60P7/06 , B60P7/08 , B65D20060101
CPC分类号： B60P7/0823 , B60P7/0869 , B61D45/00 , B65D81/055 , B65D2581/055
摘要： A corner protector and bulkhead protector for a cargo carrying vehicle such as a rail car are formed to have deep channels or corrugations that provide for both. increased strength and rigidity while also providing support for load restraining web straps.
摘要翻译：用于诸如轨道车的货物运载工具的角保护器和隔板保护器形成为具有提供这两者的深通道或波纹。增加强度和刚性，同时还提供对限制载荷的腹板带的支撑。

8. 发明申请

WO2005032955A2 CORNER AND BULKHEAD PROTECTOR 审中-公开
标题翻译：拐角和大型保护器
公开(公告)号：WO2005032955A2
公开(公告)日：2005-04-14
申请号：PCT/US2004/032565
申请日：2004-09-30
申请人： HOLLAND L.P. , THOMSON, Stuart, H. , O'NEILL, Brian, E.
发明人： THOMSON, Stuart, H. , O'NEILL, Brian, E.
IPC分类号： B65D
CPC分类号： B60P7/0823 , B60P7/0869 , B61D45/00 , B65D81/055 , B65D2581/055
摘要： A corner protector and bulkhead protector for a cargo carrying vehicle such as a rail car are formed to have deep channels or corrugations that provide for both. increased strength and rigidity while also providing support for load restraining web straps.
摘要翻译：形成用于载货车辆如轨道车的角保护器和隔舱保护器，以具有提供两者的深通道或波纹。提高强度和刚性，同时也为负载限制网带提供支持。

9. 发明申请

WO2012129145A1 NSCLE COMBINATION THERAPY 审中-公开
标题翻译： NSCLE组合治疗
公开(公告)号：WO2012129145A1
公开(公告)日：2012-09-27
申请号：PCT/US2012029598
申请日：2012-03-19
申请人： OSI PHARMACEUTICALS LLC , THOMSON STUART , BROWN ERIC N , CHAU ANDREW , FRANKLIN MARYLAND , IWATA KENNETH K
发明人： THOMSON STUART , BROWN ERIC N , CHAU ANDREW , FRANKLIN MARYLAND , IWATA KENNETH K
IPC分类号： A61K31/4985 , A61K31/517 , A61K45/06 , A61P35/00
CPC分类号： A61K31/4985 , A61K31/517 , A61K45/06 , A61K2300/00
摘要： A method of treating NSCLC comprising in some aspects administering OSI-906 and an EGFR inhibitor to a patient having NSCLC having an activating EGFR mutation, as disclosed herein.
摘要翻译：本文公开的治疗NSCLC的方法，其包括在某些方面对具有激活性EGFR突变的NSCLC的患者施用OSI-906和EGFR抑制剂。

10. 发明申请

WO2009111067A9 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL -LIKE TUMOR CELLS OR THEIR FORMATION 审中-公开
标题翻译：鉴定抑制MESENCHYMAL-LUM肿瘤细胞或其形成的药物的方法
公开(公告)号：WO2009111067A9
公开(公告)日：2009-12-23
申请号：PCT/US2009001456
申请日：2009-03-06
申请人： OSI PHARM INC , HALEY JOHN D , THOMSON STUART , KAN JULIE , SHAABAN SALAM A
发明人： HALEY JOHN D , THOMSON STUART , KAN JULIE , SHAABAN SALAM A
IPC分类号： G01N33/574
CPC分类号： G01N33/5011 , G01N2333/475 , G01N2333/485 , G01N2333/495 , G01N2333/525
摘要： The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-IR kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.
摘要翻译：本发明提供用作鉴定抗癌剂的EMT方法的模型的肿瘤细胞制剂，其中所述肿瘤细胞制剂包含受体配体刺激以诱导EMT的上皮肿瘤细胞系H358的细胞，或已被设计成可诱导地表达刺激EMT的蛋白质。本发明还提供了通过使用这样的肿瘤细胞制剂鉴定潜在的抗癌剂的方法来鉴定抑制EMT，刺激MET或抑制间充质细胞生长的药剂。当与其它抗癌药物如EGFR和IGF-1R激酶抑制剂联合使用时，这些药剂应该特别有用，这对于抑制已经经历EMT的肿瘤细胞来说效果较差。

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