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1. 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.

2. 发明申请

WO2010099363A1 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL-LIKE TUMOR CELLS OR THEIR FORMATION 审中-公开
标题翻译：鉴别抑制类似肿瘤细胞或其形成的药物的方法
公开(公告)号：WO2010099363A1
公开(公告)日：2010-09-02
申请号：PCT/US2010/025473
申请日：2010-02-26
申请人： OSI PHARMACEUTICALS, INC. , FRANKLIN, Maryland , KAN, Julie , KRUEGER, Joseph, S. , SHAABAN, Salam, A. , WILD, Robert, C.
发明人： FRANKLIN, Maryland , KAN, Julie , KRUEGER, Joseph, S. , SHAABAN, Salam, A. , WILD, Robert, C.
IPC分类号： G01N33/50
CPC分类号： G01N33/5017 , G01N33/5011 , G01N33/5044
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 CFPAC-I, 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上皮肿瘤细胞系CFPAC-1的细胞，其被受体配体刺激诱导EMT，或已被设计成可诱导表达刺激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。

3. 发明申请

WO2009099982A1 2-AMINOPYRIDINE KINASE INHIBITORS 审中-公开
标题翻译： 2-氨基吡啶激酶抑制剂
公开(公告)号：WO2009099982A1
公开(公告)日：2009-08-13
申请号：PCT/US2009/032791
申请日：2009-02-02
申请人： OSI PHARMACEUTICALS, INC. , STEINIG, Arno, G. , MULVIHILL, Mark, J. , WANG, Jing , WERNER, Douglas, S. , WENG, Qinghua , KAN, Julie , COATE, Heather , CHEN, Xin
发明人： STEINIG, Arno, G. , MULVIHILL, Mark, J. , WANG, Jing , WERNER, Douglas, S. , WENG, Qinghua , KAN, Julie , COATE, Heather , CHEN, Xin
IPC分类号： A61K31/4427 , C07D401/04 , C07D401/14 , A61P35/00 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04 , C07D513/04 , C07D491/04
CPC分类号： C07D417/14 , C07D401/04 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/04 , C07D451/04
摘要： 2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, F1t3, FGFR3, Ab1, Aurora A, c-Src, IGF- IR, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.
摘要翻译：具有式I结构的2-氨基吡啶化合物和这些化合物的药学上可接受的盐。式I的化合物抑制动物（包括人）中酪氨酸激酶的活性，并且可用于治疗和/或预防各种疾病和病症。特别地，本文公开的化合物是激酶抑制剂，特别是但不限于KDR，Tie-2，F1t3，FGFR3，Ab1，Aurora A，c-Src，IGF-1R，ALK，c-MET，RON， PAK1，PAK2和TAK1，并且可用于治疗增殖性疾病，例如但不限于癌症。本发明还涉及包含治疗有效量的式I化合物或其药学上可接受的盐和药学上可接受的载体的药物组合物。本发明还涉及通过向患者施用治疗有效量的上述药物组合物来治疗具有由蛋白激酶活性介导的病症的患者的方法。

4. 发明申请

WO2010099138A2 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL-LIKE TUMOR CELLS OR THEIR FORMATION 审中-公开
标题翻译：鉴别抑制类似肿瘤细胞或其形成的药物的方法
公开(公告)号：WO2010099138A2
公开(公告)日：2010-09-02
申请号：PCT/US2010/025137
申请日：2010-02-24
申请人： OSI PHARMACEUTICALS, INC. , KAN, Julie
发明人： KAN, Julie
IPC分类号： G01N33/50
CPC分类号： G01N33/5017
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 H292, 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：本发明提供用作识别抗癌剂的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H292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。

5. 发明申请

WO2010099364A2 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL-LIKE TUMOR CELLS OR THEIR FORMATION 审中-公开
标题翻译：鉴别抑制类似肿瘤细胞或其形成的药物的方法
公开(公告)号：WO2010099364A2
公开(公告)日：2010-09-02
申请号：PCT/US2010/025475
申请日：2010-02-26
申请人： OSI PHARMACEUTICALS, INC. , KAN, Julie
发明人： KAN, Julie
IPC分类号： G01N33/50
CPC分类号： C12N5/0693 , G01N33/5011
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 H1650, 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-1R 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上皮细胞系H1650的细胞，其被受体配体刺激以诱导EMT ，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。

6. 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。

7. 发明公开

EP2265270A1 2-AMINOPYRIDINE KINASE INHIBITORS 审中-公开
标题翻译： 2-氨基吡啶激酶抑制剂
公开(公告)号：EP2265270A1
公开(公告)日：2010-12-29
申请号：EP09708329.9
申请日：2009-02-02
申请人： OSI Pharmaceuticals, Inc.
发明人： STEINIG, Arno, G. , MULVIHILL, Mark, J. , WANG, Jing , WERNER, Douglas, S. , WENG, Qinghua , KAN, Julie , COATE, Heather , CHEN, Xin
IPC分类号： A61K31/4427 , C07D401/04 , C07D401/14 , A61P35/00 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04 , C07D513/04 , C07D491/04
CPC分类号： C07D417/14 , C07D401/04 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/04 , C07D451/04
摘要： 2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, F1t3, FGFR3, Ab1, Aurora A, c-Src, IGF- IR, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.

8. 发明授权

EP2271941B1 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL-LIKE TUMOR CELLS OR THEIR FORMATION 有权
标题翻译：一种用于识别MESENCHYMÄHNLICHE肿瘤细胞或他们的教育炎性物质
公开(公告)号：EP2271941B1
公开(公告)日：2012-08-08
申请号：EP09716601.1
申请日：2009-03-06
申请人： OSI Pharmaceuticals, Inc.
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.

9. 发明公开

EP2271941A2 METHODS FOR THE IDENTIFICATION OF AGENTS THAT INHIBIT MESENCHYMAL-LIKE TUMOR CELLS OR THEIR FORMATION 有权
标题翻译：一种用于识别MESENCHYMÄHNLICHE肿瘤细胞或他们的教育炎性物质
公开(公告)号：EP2271941A2
公开(公告)日：2011-01-12
申请号：EP09716601.1
申请日：2009-03-06
申请人： OSI Pharmaceuticals, Inc.
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.

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