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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

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。

3. 发明申请

WO2013152252A1 COMBINATION ANTI-CANCER THERAPY 审中-公开
标题翻译：组合抗癌治疗
公开(公告)号：WO2013152252A1
公开(公告)日：2013-10-10
申请号：PCT/US2013/035358
申请日：2013-04-05
申请人： OSI PHARMACEUTICALS, LLC
发明人： BUCK, Elizabeth, A. , HALEY, John, D. , THOMSON, Stuart , MULVIHILL, Mark, J. , EPSTEIN, David, M. , MIGLARESE, Mark, R.
IPC分类号： A61K38/00 , A61K39/00 , A61K45/06 , A61K31/404 , A61K31/4985 , A61K31/517 , A61K31/713 , A61P35/00 , A61P35/04 , A61K31/53
CPC分类号： A61K31/404 , A61K31/4985 , A61K31/517 , A61K31/53 , A61K31/713 , A61K45/06 , A61K2300/00
摘要： The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an inhibitor of MET kinase signaling (e.g. a small molecule MET kinase inhibitor, an anti-MET antibody, or an HGF binding protein) and an inhibitor of IGF-1R signaling (e.g. a small molecule IGF-1R kinase inhibitor (e.g. OSI-906), an anti-IGF-1R antibody, or one or more IGF binding proteins (e.g. IGFBP3)). The present invention also provides a pharmaceutical composition comprising a combination of an inhibitor of MET kinase signaling and an inhibitor of IGF-1R signaling, with a pharmaceutically acceptable carrier. The present invention also provides such methods or compositions where the inhibitory activities of MET kinase signaling and IGF-1R kinase signaling reside in the same molecule.
摘要翻译：本发明提供了一种治疗患者肿瘤或肿瘤转移的方法，其包括向所述患者同时或依次施用治疗有效量的MET激酶信号传导抑制剂（例如小分子MET激酶抑制剂， MET抗体或HGF结合蛋白）和IGF-1R信号传导抑制剂（例如小分子IGF-1R激酶抑制剂（例如OSI-906），抗IGF-1R抗体或一种或多种IGF结合蛋白（例如IGFBP3））。本发明还提供了包含MET激酶信号传导抑制剂和IGF-1R信号传导抑制剂的组合的药物组合物与药学上可接受的载体。本发明还提供了这样的方法或组合物，其中MET激酶信号传导和IGF-1R激酶信号传导的抑制活性位于同一分子中。

4. 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。

5. 发明申请

WO2008127719A1 BIOLOGICAL MARKERS PREDICTIVE OF ANTI-CANCER RESPONSE TO KINASE INHIBITORS 审中-公开
标题翻译：生物标志物预防抗癌剂对激酶抑制剂的反应
公开(公告)号：WO2008127719A1
公开(公告)日：2008-10-23
申请号：PCT/US2008/004819
申请日：2008-04-14
申请人： OSI PHARMACEUTICALS, INC. , HALEY, John , THOMSON, Stuart
发明人： HALEY, John , THOMSON, Stuart
IPC分类号： C12Q1/48 , G01N33/574 , G01N33/74
CPC分类号： G01N33/6893 , G01N33/5011 , G01N2333/4712 , G01N2333/4742 , G01N2333/91215
摘要： The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Based on the surprising discovery that tumors cells after having undergone an EMT, while being mesenchymal-like, still express characteristics of both epithelial and mesenchymal cells, and that such cells have altered sensitivity to inhibition by receptor protein-tyrosine kinase inhibitors, in that they have become relatively insensitive to EGFR kinase inhibitors, but have frequently aquired sensitivity to inhibitors of other receptor protein-tyrosine kinases such as PDGFR or FGFR, methods have been devised for determining levels of specific epithelial and mesenchymal biomarkers that identify such "hybrid" tumor cells (e.g. determination of co-expression of vimentin and epithelial keratins), and thus predict the tumor's likely sensitivity to inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Improved methods for treating cancer patients with EGFR, PDGFR or FGFR kinase inhibitors that incorporate such methodology are also provided.
摘要翻译：本发明提供用于预测具有EGFR激酶，PDGFR激酶或FGFR激酶抑制剂的癌症患者治疗有效性的诊断和预后方法。基于令人惊讶的发现，肿瘤细胞在经历EMT之后，同时是间充质的，仍然表现出上皮细胞和间充质细胞的特征，并且这种细胞对受体蛋白 - 酪氨酸激酶抑制剂的抑制具有改变的敏感性，因为它们已经对EGFR激酶抑制剂变得相对不敏感，但是经常对其他受体蛋白酪氨酸激酶（例如PDGFR或FGFR）的抑制剂具有敏感性，已经设计出用于确定鉴定这种“杂合”肿瘤细胞的特异性上皮和间充质生物标志物的水平的方法（例如测定波形蛋白和上皮角蛋白的共表达），从而预测肿瘤对EGFR激酶，PDGFR激酶或FGFR激酶抑制剂的敏感性。还提供了用于治疗结合这种方法的EGFR，PDGFR或FGFR激酶抑制剂的癌症患者的改进方法。

6. 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.

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