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1. 发明申请

US20090247475A1 METHODS AND COMPOSITIONS RELATING TO PHARMACOGENETICS OF DIFFERENT GENE VARIANTS IN THE CONTEXT OF IRINOTECAN-BASED THERAPIES 审中-公开
标题翻译：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。

2. 发明申请

US20090017452A1 METHODS AND COMPOSITIONS RELATING TO THE PHARMACOGENETICS OF DIFFERENT GENE VARIANTS 审中-公开
标题翻译：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。

3. 发明授权

US06693130B2 Inhibitors of epoxide hydrolases for the treatment of hypertension 失效
标题翻译：环氧化物水解酶抑制剂治疗高血压
公开(公告)号：US06693130B2
公开(公告)日：2004-02-17
申请号：US10328495
申请日：2002-12-23
申请人： Deanna L. Kroetz , Darryl C. Zeldin , Bruce D. Hammock , Christophe Morisseau
发明人： Deanna L. Kroetz , Darryl C. Zeldin , Bruce D. Hammock , Christophe Morisseau
IPC分类号： A61K31335
CPC分类号： A61K31/325 , A61K31/00 , A61K31/336
摘要： The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by wherein R is alkyl or aryl, the compound is trans-across the epoxide ring, OX is a carbonyl (═O) or hydroxy group (OH) and R′ is a H, alkyl or aryl group. The invention further provides methods of identifying patients at increased risk for hypertension, comprising assaying for epoxide hydrolase activity in a urine sample from the patient. In particular, the assays comprise determining the amount of dihydroxyeicosatrienoic acids (DHETs), determining the amount of epoxyeicosatrienoic acids (EETs) in said sample, or determining the amount of both DHETs and EETs in said sample.
摘要翻译：本发明提供在治疗高血压的治疗应用中抑制环氧化物水解酶的化合物。用于实施本发明的一类优选的化合物具有其中R为烷基或芳基的化合物，该化合物跨环氧环，OX为羰基（= O）或羟基（OH），R'为H ，烷基或芳基。本发明还提供了鉴定患有高血压风险增加的患者的方法，包括测定来自患者的尿液样品中的环氧化物水解酶活性。特别地，测定法包括确定二羟基二十碳三烯酸（DHET）的量，确定所述样品中环氧二十碳三烯酸（EET）的量，或确定所述样品中DHET和EET两者的量。

4. 发明授权

US06531506B1 Inhibitors of epoxide hydrolases for the treatment of hypertension 失效
标题翻译：环氧化物水解酶抑制剂治疗高血压
公开(公告)号：US06531506B1
公开(公告)日：2003-03-11
申请号：US09721261
申请日：2000-11-21
申请人： Deanna L. Kroetz , Darryl C. Zeldin , Bruce D. Hammock , Christophe Morisseau
发明人： Deanna L. Kroetz , Darryl C. Zeldin , Bruce D. Hammock , Christophe Morisseau
IPC分类号： A61K31335
CPC分类号： A61K31/7088 , A61K31/00 , A61K31/155 , A61K31/20 , A61K31/336 , G01N2500/10
摘要： The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by Formula I wherein Z is oxygen or sulfur, W is carbon phosphorous or sulfur, X and Y is each independently nitrogen, oxygen, or sulfur, and X can further be carbon, at least one of R1-R4 is hydrogen, R2 is hydrogen when X is nitrogen but is not present when X is sulfur or oxygen, R4 is hydrogen when Y is nitrogen but is not present when Y is sulfur or oxygen, R1 and R3 is each independently C1-C20 substituted or unsubstituted alkyl, cycloalkyl, aryl, acyl, or heterocyclic.
摘要翻译：本发明提供在治疗高血压的治疗应用中抑制环氧化物水解酶的化合物。用于实施本发明的一类优选的化合物具有式I所示的结构，其中Z是氧或硫，W是碳磷或硫，X和Y各自独立地是氮，氧或硫，X可以进一步为碳，当X为氮时，R 2为氢，当X为硫或氧时不存在，当Y为氮时，R4为氢，Y为硫或氧时不存在，R 1和R 3为独立地是C 1 -C 20取代或未取代的烷基，环烷基，芳基，酰基或杂环。

5. 发明申请

US20110245331A1 INHIBITORS OF EPOXIDE HYDROLASES FOR THE TREATMENT OF HYPERTENSION 审中-公开
标题翻译：用于治疗高血压的环氧化物水解物的抑制剂
公开(公告)号：US20110245331A1
公开(公告)日：2011-10-06
申请号：US13113028
申请日：2011-05-20
申请人： Deanna L. Kroetz , Darryl C. Zeldin , Bruce D. Hammock , Christophe Morisseau
发明人： Deanna L. Kroetz , Darryl C. Zeldin , Bruce D. Hammock , Christophe Morisseau
IPC分类号： A61K31/7088 , A61P9/12 , C12N9/96 , C12Q1/34
CPC分类号： A61K31/325 , A61K31/00 , A61K31/336
摘要： The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by Formula 1 wherein Z is oxygen or sulfur, W is carbon phosphorous or sulfur, X and Y is each independently nitrogen, oxygen, or sulfur, and X can further be carbon, at least one of R1-R4 is hydrogen, R2 is hydrogen when X is nitrogen but is not present when X is sulfur or oxygen, R4 is hydrogen when Y is nitrogen but is not present when Y is sulfur or oxygen, R1 and R3 is each independently C1-C20 substituted or unsubstituted alkyl, cycloalkyl, aryl, acyl, or heterocyclic.
摘要翻译：本发明提供在治疗高血压的治疗应用中抑制环氧化物水解酶的化合物。用于实施本发明的一类优选的化合物具有式1所示的结构，其中Z是氧或硫，W是碳磷或硫，X和Y各自独立地是氮，氧或硫，并且X还可以是碳，当X为氮时，R 1为R 4为氢，R 2为氢时，当X为硫或氧时不存在，当Y为氮时为R4，当Y为硫或氧时不存在，R 1和R 3为各自独立地为C1-C20取代或未取代的烷基，环烷基，芳基，酰基或杂环。

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