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1. 发明申请

US20080319025A1 Therapeutic and Diagnostic Methods Dependent on CYP2A Enzymes 审中-公开
标题翻译：依赖于CYP2A酶的治疗和诊断方法
公开(公告)号：US20080319025A1
公开(公告)日：2008-12-25
申请号：US12106402
申请日：2008-04-21
申请人： Edward M. Sellers , Rachel F. Tyndale
发明人： Edward M. Sellers , Rachel F. Tyndale
IPC分类号： A61K31/465 , A61P25/34
CPC分类号： A61K31/135 , A61K31/465 , A61K2300/00
摘要： A method of regulating the activity of human cytochrome P450 isozyme CYP2A6 to control nicotine metabolism or decrease to production of carcinogens from procarcinogens, such as those present in tobacco smoke, in an individual by selectively inhibiting CYP2A6. Various prophylactic (i.e., prevention and treatment) compositions and methods are also described, including an improved oral nicotine composition and method comprising the use of nicotine together with an inhibitor of the CYP2A6 enzyme.Furthermore, it has been discovered that the presence in an individual of a mutant allele of human cytochrome P450 enzyme CYP2A6 (referred to throughout this specification as “CYP2A6” for brevity) is predictive of an individual who: (i) has a decreased risk of becoming a smoker, (ii) will smoke less if he/she becomes dependent, and/or (iii) may be at relatively lower risk for cancer due to both decreased smoke exposure and decreased CYP2A6-mediated activation of tobacco smoke and other procarcinogenic substrates. This invention provides diagnostic methods for predicting tobacco dependence risk and risk for cancers related to CYP2A6 substrates in an individual by analysing for the presence of a mutant genotype for human cytochrome P450 enzyme CYP2A6 in an individual, ranging from gene duplication (multiple copies of CYP2A6) to single or even no copies due to null alleles or gene deletion.
摘要翻译：调节人细胞色素P450同功酶CYP2A6的活性以通过选择性抑制CYP2A6调节个体中烟碱代谢或降低至产生致癌物质（如烟草烟雾中的致癌物质）的活性的方法。还描述了各种预防（即预防和治疗）组合物和方法，包括改进的口服尼古丁组合物和包括将尼古丁与CYP2A6酶抑制剂一起使用的方法。此外，已经发现，人细胞色素P450酶CYP2A6的突变等位基因（简称为“CYP2A6”）在个体中的存在是预测个体的：（i）具有降低的成为吸烟者，（ii）如果他/她变得依赖，则会吸烟较少，和/或（iii）由于烟雾暴露减少和CYP2A6介导的烟草烟雾和其他致癌基质活化降低，癌症风险相对较低。本发明提供诊断方法，用于通过分析个体中针对人细胞色素P450酶CYP2A6的突变基因型的存在，从基因复制（CYP2A6的多个拷贝）中预测个体中与CYP2A6底物相关的癌症的烟草依赖性风险和风险。由于无效等位基因或基因缺失而单拷贝或甚至无拷贝。

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