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1. 发明申请

US20170007605A1 Method of Optimizing the Treatment of Philadelphia-positive Leukemia with Abl Tyrosine Kinase Inhibitors 审中-公开
标题翻译：用Abl酪氨酸激酶抑制剂优化费城阳性白血病治疗的方法
公开(公告)号：US20170007605A1
公开(公告)日：2017-01-12
申请号：US15272576
申请日：2016-09-22
申请人： Insa Gathmann , Francois-Xavier Mahon , Mathieu Molimard , Stephane Picard , Yanfeng Wang
发明人： Insa Gathmann , Francois-Xavier Mahon , Mathieu Molimard , Stephane Picard , Yanfeng Wang
IPC分类号： A61K31/506 , G01N33/49
CPC分类号： A61K31/506 , A61K31/00 , G01N33/49 , G01N2800/52
摘要： The present invention provides a method of treating Philadelphia positive (Ph+) leukemia, such as Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (CML), in a human patient population comprising the steps of (a) administering a predetermined fixed therapeutically effective amount of an Bcr-Abl tyrosine kinase inhibitor, such as Imatinib, or a pharmaceutically acceptable salt thereof to human patients suffering from a Ph+ leukemia, (b) collecting at least one blood sample from said patients, (c) determining the plasma trough level (Cmin) of the Bcr-Abl tyrosine kinase inhibitor or of a metabolite thereof as well as the MMR rates, (d) assessing a discrimination potential of trough plasma concentrations for MMR and identifying a Cmin threshold for optimal sensitivity and specificity and (e) adjusting the dose of the inhibitor of the Bcr-Abl tyrosine kinase or a pharmaceutically acceptable salt thereof applied to the individual patients from said patient population and, optionally, future patients suffering from a Ph+ leukemia in a manner that a Cmin is achieved in each single patient equal to or higher than the Cmin threshold obtained under step (d).
摘要翻译：本发明提供了一种在人类患者群体中治疗费城阳性（Ph +）白血病如费城染色体阳性急性淋巴细胞白血病（Ph + ALL）或慢性骨髓性白血病（CML）的方法，包括以下步骤：（a）将固定量的Bcr-Abl酪氨酸激酶抑制剂（例如伊马替尼）或其药学上可接受的盐给予患有Ph +白血病的人类患者，（b）从所述患者收集至少一种血液样品，（c）测定血浆槽 Bcr-Abl酪氨酸激酶抑制剂或其代谢物的水平（Cmin）以及MMR率，（d）评估MMR的谷浆浓度的鉴别潜力，并鉴定最佳灵敏度和特异性的Cmin阈值，（e ）调节从所述患者群体应用于个体患者的Bcr-Abl酪氨酸激酶抑制剂或其药学上可接受的盐的剂量以及任选地，患有Ph +白血病的未来患者以等于或高于步骤（d）获得的Cmin阈值的每个单个患者中实现Cmin的方式。

2. 发明申请

US20090281113A1 METHOD OF OPTIMIZING THE TREATMENT OF PHILADELPHIA-POSITIVE LEUKEMIA WITH ABL TYROSINE KINASE INHIBITORS 审中-公开
标题翻译：用ABL酪氨酸激酶抑制剂优化治疗菲律宾阳性白血病的方法
公开(公告)号：US20090281113A1
公开(公告)日：2009-11-12
申请号：US12442126
申请日：2007-09-20
申请人： Insa Gathmann , Francois-Xavier Mahon , Mathieu Molimard , Stephane Picard , Yanfeng Wang
发明人： Insa Gathmann , Francois-Xavier Mahon , Mathieu Molimard , Stephane Picard , Yanfeng Wang
IPC分类号： A61K31/506 , A61P35/02
CPC分类号： A61K31/506 , A61K31/00 , G01N33/49 , G01N2800/52
摘要： The present invention provides a method of treating Philadelphia positive (Ph+) leukemia, such as Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (CML), in a human patient population comprising the steps of (a) administering a predetermined fixed amount of a Bcr-Abl tyrosine kinase inhibitor, such as Imatinib, or a pharmaceutically acceptable salt thereof to human patients suffering from a Ph+ leukemia, (b) collecting at least one blood sample from said patients, (c) determining the plasma trough level (Cmin) of the Bcr-Abl tyrosine kinase inhibitor or of a metabolite thereof as well as the MMR rates, (d) assessing a discrimination potential of trough plasma concentrations for MMR and identifying a Cmin threshold for optimal sensitivity and specificity and (e) adjusting the dose of the inhibitor of the Bcr-Abl tyrosine kinase or a pharmaceutically acceptable salt thereof applied to the individual patients from said patient population and, optionally, future patients suffering from a Ph+ leukemia in a manner that a Cmin is achieved in each single patient equal to or higher than the Cmin threshold obtained under step (d).
摘要翻译：本发明提供了一种在人类患者群体中治疗费城阳性（Ph +）白血病如费城染色体阳性急性淋巴细胞白血病（Ph + ALL）或慢性骨髓性白血病（CML）的方法，包括以下步骤：（a）将固定量的Bcr-Abl酪氨酸激酶抑制剂（例如伊马替尼）或其药学上可接受的盐给予患有Ph +白血病的人类患者，（b）从所述患者收集至少一种血液样品，（c）测定血浆槽 Bcr-Abl酪氨酸激酶抑制剂或其代谢物的水平（Cmin）以及MMR率，（d）评估MMR的谷浆浓度的鉴别潜力，并鉴定最佳灵敏度和特异性的Cmin阈值，（e ）调节从所述患者群体应用于个体患者的Bcr-Abl酪氨酸激酶抑制剂或其药学上可接受的盐的剂量以及任选地，患有Ph +白血病的未来患者以等于或高于步骤（d）获得的Cmin阈值的每个单个患者中实现Cmin的方式。

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