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1.发明授权Mutational profiles in HIV-1 reverse transcriptase correlated with phenotypic drug resistance 失效HIV-1逆转录酶的突变特征与表型耐药性相关公开(公告)号：US08574831B2
公开(公告)日：2013-11-05
申请号：US11933747
申请日：2007-11-01
摘要： The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.
摘要翻译： 本发明提供与HIV药物的表型抗性相关的HIV-1逆转录酶和/或蛋白酶基因的新突变，突变组合或突变分布。 更具体地，本发明涉及HIV的目标群体的基因型表征的使用以及该信息随后与表型解释的相关性，以将病毒突变特征与耐药性相关联。 本发明还涉及在数据库，药物开发，即药物设计，药物修饰，治疗和治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。
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2.发明申请Mutational profiles in HIV-1 reverse transcriptase correlated with phenotypic drug resistance 失效HIV-1逆转录酶的突变特征与表型耐药性相关公开(公告)号：US20080286754A1
公开(公告)日：2008-11-20
申请号：US11933747
申请日：2007-11-01
IPC分类号： C12Q1/70
摘要： The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.
摘要翻译： 本发明提供与HIV药物的表型抗性相关的HIV-1逆转录酶和/或蛋白酶基因的新突变，突变组合或突变分布。 更具体地，本发明涉及HIV的目标群体的基因型表征的使用以及该信息随后与表型解释的相关性，以将病毒突变特征与耐药性相关联。 本发明还涉及在数据库，药物开发，即药物设计，药物修饰，治疗和治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。
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公开(公告)号：US07206699B2
公开(公告)日：2007-04-17
申请号：US09836477
申请日：2001-04-18
申请人： Brendan Larder , Stuart Bloor , Kurt Hertogs , Pascale Alfons Rosa Dehertogh , Rudy Jean Marc Mortier
发明人： Brendan Larder , Stuart Bloor , Kurt Hertogs , Pascale Alfons Rosa Dehertogh , Rudy Jean Marc Mortier
IPC分类号： G06F19/00
CPC分类号： C12Q1/6876 , C12Q1/703 , C12Q1/707 , C12Q2600/156 , G06F19/18 , G06F19/22 , G06F19/24 , G06F19/28
摘要： The present invention concerns methods for measuring drug resistance by correlating genotypic information with phenotypic profiles. In one embodiment, a method for interpreting genotypic information is described wherein a genetic code is generated from a patient sample, a list of mutations known or suspect to play a role in the development of resistance to one or more drugs is obtained from the generated genetic code, a genotype database is interrogated for previous samples with similar mutations relating to said one or more drugs, a phenotype for said sample is located in a phenotype database, the mean change in inhibition is determined based on all the examples located in said phenotype database, a distribution of sensitivities of one or more drugs suitable for treating a specific indication is determined.
摘要翻译： 本发明涉及通过将基因型信息与表型谱相关联来测量耐药性的方法。 在一个实施方案中，描述了一种用于解释基因型信息的方法，其中从患者样品产生遗传密码，从产生的遗传基因获得已知或怀疑在发展对一种或多种药物的抗性发展中起作用的突变的列表 对于先前具有与所述一种或多种药物相似的突变的样品，询问基因型数据库，所述样品的表型位于表型数据库中，基于位于所述表型数据库中的所有实施例确定抑制的平均变化 确定一种或多种适合于治疗特定指征的药物的灵敏度分布。
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4.发明授权公开(公告)号：US07292944B2
公开(公告)日：2007-11-06
申请号：US10399412
申请日：2001-10-22
IPC分类号： G06F19/00
CPC分类号： G01N33/5091 , G01N2800/52
摘要： The present invention concerns methods and systems for improving the accuracy of predicting resistance of a disease to a therapy. In one embodiment of the invention, mean and standard deviation (SD) values of fold change in normalized sensitivity, relative to a laboratory wild type standard pathogen or malignant cell are calculated to demonstrate that the patient samples display inherently different degrees of variation in susceptibility to each therapy. In another embodiment, the 2×SD value for each therapy is used as the cut-off between sensitive (within normal susceptible range) and resistant (above normal susceptible range).
摘要翻译： 本发明涉及用于提高预测疾病对治疗的抵抗力的准确性的方法和系统。 在本发明的一个实施方案中，计算相对于实验室野生型标准病原体或恶性细胞的归一化灵敏度的折叠变化的平均值和标准偏差（SD）值，以证明患者样品显示出对 每次治疗 在另一个实施方案中，每次治疗的2xSD值用作敏感（在正常敏感范围内）和抗性（高于正常敏感范围）之间的截止值。
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5.发明授权Mutational profiles in HIV-1 protease and reverse transcriptase correlated with phenotypic drug resistance 有权HIV-1蛋白酶和逆转录酶的突变特征与表型耐药性相关公开(公告)号：US07494768B1
公开(公告)日：2009-02-24
申请号：US09580491
申请日：2000-05-30
申请人： Kurt Hertogs , Brendan Larder , Rudi Pauwels
发明人： Kurt Hertogs , Brendan Larder , Rudi Pauwels
CPC分类号： C12Q1/703 , Y10S435/911 , Y10S435/912
摘要： The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.
摘要翻译： 本发明提供与HIV药物的表型抗性相关的HIV-1逆转录酶和/或蛋白酶基因的新突变，突变组合或突变分布。 更具体地，本发明涉及HIV的目标群体的基因型表征的使用以及该信息随后与表型解释的相关性，以将病毒突变特征与耐药性相关联。 本发明还涉及在数据库，药物开发，即药物设计，药物修饰，治疗和治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。
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6.发明授权公开(公告)号：US08563236B2
公开(公告)日：2013-10-22
申请号：US12352626
申请日：2009-01-13
申请人： Kurt Hertogs , Brendan Larder , Rudi Pauwels
发明人： Kurt Hertogs , Brendan Larder , Rudi Pauwels
CPC分类号： C12Q1/703 , Y10S435/911 , Y10S435/912
摘要： The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.
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7.发明申请MUTATIONAL PROFILES IN HIV-1 REVERSE TRANSCRIPTASE CORRELATED WITH PHENOTYPIC DRUG RESISTANCE 有权HIV-1逆转录酶的突变型与相应药物耐药性相关公开(公告)号：US20090162867A1
公开(公告)日：2009-06-25
申请号：US12352626
申请日：2009-01-13
申请人： Kurt Hertogs , Brendan Larder , Rudl Pauwels
发明人： Kurt Hertogs , Brendan Larder , Rudl Pauwels
IPC分类号： C12Q1/68
CPC分类号： C12Q1/703 , Y10S435/911 , Y10S435/912
摘要： The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.
摘要翻译： 本发明提供与HIV药物的表型抗性相关的HIV-1逆转录酶和/或蛋白酶基因的新突变，突变组合或突变分布。 更具体地，本发明涉及HIV的目标群体的基因型表征的使用以及该信息随后与表型解释的相关性，以将病毒突变特征与耐药性相关联。 本发明还涉及在数据库，药物开发，即药物设计，药物修饰，治疗和治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。
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公开(公告)号：US20070166747A1
公开(公告)日：2007-07-19
申请号：US11682749
申请日：2007-03-06
申请人： Brendan Larder , Stuart Bloor , Kurt Hertogs , Pascale Dehertogh , Rudy Mortier
发明人： Brendan Larder , Stuart Bloor , Kurt Hertogs , Pascale Dehertogh , Rudy Mortier
CPC分类号： C12Q1/6876 , C12Q1/703 , C12Q1/707 , C12Q2600/156 , G16B20/00 , G16B30/00 , G16B40/00 , G16B50/00
摘要： The present invention concerns methods for measuring drug resistance by correlating genotypic information with phenotypic profiles. In one embodiment, a method for interpreting genotypic information is described wherein a genetic code is generated from a patient sample, a list of mutations known or suspect to play a role in the development of resistance to one or more drugs is obtained from the generated genetic code, a genotype database is interrogated for previous samples with similar mutations relating to said one or more drugs, a phenotype for said sample is located in a phenotype database, the mean change in inhibition is determined based on all the examples located in said phenotype database, a distribution of sensitivities of one or more drugs suitable for treating a specific indication is determined.
摘要翻译： 本发明涉及通过将基因型信息与表型谱相关联来测量耐药性的方法。 在一个实施方案中，描述了一种用于解释基因型信息的方法，其中从患者样品产生遗传密码，从产生的遗传基因获得已知或怀疑在发展对一种或多种药物的抗性发展中起作用的突变的列表 对于先前具有与所述一种或多种药物相似的突变的样品，询问基因型数据库，所述样品的表型位于表型数据库中，基于位于所述表型数据库中的所有实施例确定抑制的平均变化 确定一种或多种适合于治疗特定指征的药物的灵敏度分布。
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9.发明授权Method and system for predicting resistance of a disease to a therapeutic agent using a neural network 失效使用神经网络预测疾病对治疗剂的抵抗力的方法和系统公开(公告)号：US07058616B1
公开(公告)日：2006-06-06
申请号：US09589167
申请日：2000-06-08
申请人： Brendan Larder , Dechao Wang
发明人： Brendan Larder , Dechao Wang
摘要： A method and system for predicting the resistance of a disease to a therapeutic agent is provided. Further provided is a method and system for designing a therapeutic treatment agent for a patient afflicted with a disease. Specifically, the methods use a trained neural network to interpret genotypic information obtained from the disease. The trained neural network is trained using a database of known or determined genotypic mutations that are correlated with phenotypic therapeutic agent resistance. The present invention also provides methods and systems for predicting the probability of a patient developing a genetic disease. A trained neural network for making such predictions is also provided.
摘要翻译： 提供了一种用于预测疾病对治疗剂的抵抗力的方法和系统。 还提供了设计用于患有疾病的患者的治疗剂的方法和系统。 具体来说，该方法使用训练有素的神经网络来解释从疾病获得的基因型信息。 训练有素的神经网络使用与表型治疗剂抗性相关的已知或确定的基因型突变的数据库进行训练。 本发明还提供了用于预测患者发展遗传性疾病的可能性的方法和系统。 还提供了用于进行这种预测的经过训练的神经网络。
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公开(公告)号：US07087375B1
公开(公告)日：2006-08-08
申请号：US09599877
申请日：2000-06-23
申请人： Johan Lennerstrand , Brendan Larder
发明人： Johan Lennerstrand , Brendan Larder
IPC分类号： C12Q1/70
CPC分类号： C12Q1/48 , G01N2333/16 , G01N2333/9125
摘要： The present invention is directed to the field of HIV resistance to RT inhibitors and methods of determining the levels and mechanisms of action of HIV resistance. The methods of the present invention may be accomplished using a novel in vitro assay that provides a reaction well comprising a template for an HIV RT enzyme, a primer, a detectable dNTP substrate, an HIV RT inhibitor, and a ribonucleotide chosen from ATP and GTP or a pyrophosphate. The RT activity is determined by measuring the amount of the detectable dNTP substrate that is incorporated into the template, and the level and/or mechanism of resistance of HIV to the HIV RT inhibitor is determined using the RT activity. The methods may also be used for designing new therapies, screening for new drugs and treatments, and determining the role of mutations in observed resistance.
摘要翻译： 本发明涉及抗RT抑制剂的HIV抗性领域和确定HIV抗性作用的水平和机制的方法。 本发明的方法可以使用提供包含HIV RT酶，引物，可检测的dNTP底物，HIV RT抑制剂和选自ATP和GTP的核糖核苷酸的模板的反应孔的新颖的体外测定来完成 或焦磷酸盐。 通过测量掺入到模板中的可检测的dNTP底物的量来确定RT活性，并且使用RT活性确定HIV对HIV RT抑制剂的抗性的水平和/或机制。 该方法还可用于设计新疗法，筛选新药和治疗，以及确定突变在观察抵抗中的作用。
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