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    Camptothecin drug combinations and methods with reduced side effects
    1.
    发明授权
    Camptothecin drug combinations and methods with reduced side effects 失效
    喜树碱药物的组合和方法具有减少的副作用

    公开(公告)号：US5786344A

    公开(公告)日：1998-07-28

    申请号：US423641

    申请日：1995-04-17

    申请人： Mark J. Ratain ,  Elora Gupta

    发明人： Mark J. Ratain ,  Elora Gupta

    IPC分类号： A61K45/00 ,  A61K31/47 ,  A61K45/06 ,  A61K31/545

    CPC分类号： A61K31/47 ,  A61K45/06 ,  Y10S514/01

    摘要： This invention provides methods and combination formulations and kits to reduce the toxicity of camptothecin drugs, such as irinotecan (CPT-11). Disclosed are therapeutics and treatment methods employing such drugs in combination with agents that increase conjugative enzyme activity or glucuronosyltransferase activity, and agents that decrease biliary transport protein activity, such as cyclosporine A, the resultant effects of which are to decrease the significant side effects previously associated with treatment using these drugs.

    摘要翻译： 本发明提供了减少喜树碱药物如伊立替康（CPT-11）的毒性的方法和组合制剂和试剂盒。 公开了使用这些药物与增加共轭酶活性或葡糖醛酸基转移酶活性的试剂组合的治疗和治疗方法，以及降低胆道转运蛋白活性的试剂，例如环孢菌素A，其结果是减少先前相关的显着副作用 用这些药物治疗。

    METHODS AND COMPOSITIONS RELATING TO PHARMACOGENETICS OF DIFFERENT GENE VARIANTS IN THE CONTEXT OF IRINOTECAN-BASED THERAPIES
    3.
    发明申请
    METHODS AND COMPOSITIONS RELATING TO PHARMACOGENETICS OF DIFFERENT GENE VARIANTS IN THE CONTEXT OF IRINOTECAN-BASED THERAPIES 审中-公开
    不同基因组变异基因在不同基因型治疗中的药代动力学方法与组成

    公开(公告)号：US20090247475A1

    公开(公告)日：2009-10-01

    申请号：US11913150

    申请日：2006-05-12

    申请人： Mark J. Ratain ,  Federico Innocenti ,  Deanna L. Kroetz ,  Samir Undevia ,  Tan D. Nguyen ,  Wanqing Liu

    发明人： Mark J. Ratain ,  Federico Innocenti ,  Deanna L. Kroetz ,  Samir Undevia ,  Tan D. Nguyen ,  Wanqing Liu

    IPC分类号： C12Q1/68 ,  A61K31/4545

    CPC分类号： A61K31/4545 ,  C12Q1/6827

    摘要： The present invention is directed to methods and compositions for determining the presence or absence of polymorphisms within an ABCC2, UGT1A1, and/or SLCO1B1 gene and correlating these polymorphisms with activity levels of their gene products and making evaluations regarding the effect on their substrates, particularly those substrates that are drugs. In addition, there are methods and compositions of evaluating the risk of an individual for developing toxicity or adverse event(s) to an ABCC2, UGT1A1, and/or SLCO1B1 substrate. In some embodiments, the invention concerns methods and compositions for determining the presence or absence of ABCC2 3972C>T variant and predicting or anticipating the level of activity of ABCC2 and determining dosages of an ABCC2 drug substrate, such as irinotecan, in a patient. Such methods and compositions can be used to evaluate whether irinotecan-based therapy, or therapy involving other ABCC2 substrates, may pose toxicity problems if given to a particular patient or predicting their efficacy. Alterations in suggested therapy may ensue based on genotyping results.

    摘要翻译： 本发明涉及用于确定ABCC2，UGT1A1和/或SLCO1B1基因内存在或不存在多态性的方法和组合物，并将这些多态性与其基因产物的活性水平相关联并且对其底物的影响进行评估，特别是 那些底物是药物。 此外，还有一些方法和组成来评估个体对ABCC2，UGT1A1和/或SLCO1B1底物的毒性或不良事件的风险。 在一些实施方案中，本发明涉及用于确定ABCC23972C> T变体的存在或不存在以及预测或预测ABCC2的活性水平并确定患者体内ABCC2药物底物（例如伊立替康）的剂量的方法和组合物。 这样的方法和组合物可用于评估依托替替治疗或涉及其他ABCC2底物的治疗如果给予特定患者或预测其功效，可能引起毒性问题。 建议治疗的改变可能是基于基因分型结果。

    Methods for detection of promoter polymorphism in a UGT gene promoter
    4.
    发明授权
    Methods for detection of promoter polymorphism in a UGT gene promoter 有权
    检测UGT基因启动子启动子多态性的方法

    公开(公告)号：US06395481B1

    公开(公告)日：2002-05-28

    申请号：US09251274

    申请日：1999-02-16

    申请人： Anna Di Rienzo ,  Lalitha Iyer ,  Mark J. Ratain

    发明人： Anna Di Rienzo ,  Lalitha Iyer ,  Mark J. Ratain

    IPC分类号： C12Q168

    CPC分类号： A61K31/55 ,  C12N9/1051 ,  C12Q1/6844 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Y204/01017

    摘要： The present invention is, directed to methods for detecting the presence of genetic polymorphisms that correlate with altered gene expression. More specifically, the present invention is directed to methods for detecting the genetic polymorphisms located in the UGT1A1 promoter. The invention also provides methods for optimizing drug dosages based upon the presence of the polymorphisms. The invention further provides methods of predicting sensitivity to xenobiotics and diagnostic kits for detecting genetic polymorphisms.

    摘要翻译： 本发明涉及用于检测与改变的基因表达相关的遗传多态性的存在的方法。 更具体地，本发明涉及用于检测位于UGT1A1启动子中的遗传多态性的方法。 本发明还提供了基于多态性存在来优化药物剂量的方法。 本发明还提供了预测对异生物的敏感性的方法和用于检测遗传多态性的诊断试剂盒。

    METHODS AND COMPOSITIONS RELATING TO THE PHARMACOGENETICS OF DIFFERENT GENE VARIANTS
    9.
    发明申请
    METHODS AND COMPOSITIONS RELATING TO THE PHARMACOGENETICS OF DIFFERENT GENE VARIANTS 审中-公开
    与不同基因变异体药物相关的方法和组合物

    公开(公告)号：US20090017452A1

    公开(公告)日：2009-01-15

    申请号：US10591484

    申请日：2005-03-07

    申请人： Mark J. Ratain ,  Federico Innoceti ,  Deanna L. Kroetz ,  Samir Undevia ,  Tan D. Nguyen ,  Wanqing Liu

    发明人： Mark J. Ratain ,  Federico Innoceti ,  Deanna L. Kroetz ,  Samir Undevia ,  Tan D. Nguyen ,  Wanqing Liu

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/142 ,  C12Q2600/172

    摘要： The present invention is directed to methods and compositions for determining the presence or absence of polymorphisms within an ABCC2, UGT1A1, and/or SLCO1B1 gene and correlating these polymorphisms with activity levels of their gene products and making evaluations regarding the effect on their substrates, particularly those substrates that are drugs. In addition, there are methods and compositions of evaluating the risk of an individual for developing toxicity or adverse event(s) to an ABCC2, UGT1A1, and/or SLCO1B1 substrate. In some embodiments, the invention concerns methods and compositions for determining the presence or absence of ABCC2 3972C>T variant and predicting or anticipating the level of activity of ABCC2 and determining dosages of an ABCC2 drug substrate, such as irinotecan, in a patient. Such methods and compositions can be used to evaluate whether irinotecan-based therapy, or therapy involving other ABCC2 substrates, may pose toxicity problems if given to a particular patient or predicting their efficacy. Alterations in suggested therapy may ensue based on genotyping results.

    摘要翻译： 本发明涉及用于确定ABCC2，UGT1A1和/或SLCO1B1基因内存在或不存在多态性的方法和组合物，并将这些多态性与其基因产物的活性水平相关联并且对其底物的影响进行评估，特别是 那些底物是药物。 此外，还有一些方法和组成来评估个体对ABCC2，UGT1A1和/或SLCO1B1底物的毒性或不良事件的风险。 在一些实施方案中，本发明涉及用于确定ABCC23972C> T变体的存在或不存在以及预测或预测ABCC2的活性水平并确定患者体内ABCC2药物底物（例如伊立替康）的剂量的方法和组合物。 这样的方法和组合物可用于评估依托替替治疗或涉及其他ABCC2底物的治疗如果给予特定患者或预测其功效，可能引起毒性问题。 建议治疗的改变可能是基于基因分型结果。