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。

公开(公告)号：US08574831B2

公开(公告)日：2013-11-05

申请号：US11933747

申请日：2007-11-01

申请人： Pascale Alfons Rosa Dehertogh ,  Kurt Hertogs ,  Brendan Larder ,  Dechao Wang

发明人： Pascale Alfons Rosa Dehertogh ,  Kurt Hertogs ,  Brendan Larder ,  Dechao Wang

IPC分类号： C12Q1/70 ,  C12Q1/68

CPC分类号： G06F19/18 ,  G06F19/28

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。

公开(公告)号：US20080286754A1

公开(公告)日：2008-11-20

申请号：US11933747

申请日：2007-11-01

申请人： Pascale Alfons Rosa DEHERTOGH ,  Kurt Hertogs ,  Brendan Larder ,  Dechao Wang

发明人： Pascale Alfons Rosa DEHERTOGH ,  Kurt Hertogs ,  Brendan Larder ,  Dechao Wang

IPC分类号： C12Q1/70

CPC分类号： G06F19/18 ,  G06F19/28

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。

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

IPC分类号： C12Q1/68 ,  G06F19/00

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。

公开(公告)号：US07292944B2

公开(公告)日：2007-11-06

申请号：US10399412

申请日：2001-10-22

申请人： Brendan Larder ,  Richard P. Harrigan ,  Kurt Hertogs

发明人： Brendan Larder ,  Richard P. Harrigan ,  Kurt Hertogs

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。

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

IPC分类号： C12Q1/70 ,  C12Q1/68 ,  C12P19/34

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。

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

IPC分类号： C12Q1/70 ,  C12Q1/69 ,  C12P19/34

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.

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。

公开(公告)号：US20100048563A1

公开(公告)日：2010-02-25

申请号：US12547151

申请日：2009-08-25

申请人： Bart Rudolf Romanie KESTELEYN ,  Wim Van De Vreken ,  Natalie Maria Francisca Kindermans ,  Maxime Francis Jean-Marie Ghislain Canard ,  Kurt Hertogs ,  Eva Bettens ,  Veronique Corine Paul De Vroey ,  Dirk Edward Désiré Jochmans

发明人： Bart Rudolf Romanie KESTELEYN ,  Wim Van De Vreken ,  Natalie Maria Francisca Kindermans ,  Maxime Francis Jean-Marie Ghislain Canard ,  Kurt Hertogs ,  Eva Bettens ,  Veronique Corine Paul De Vroey ,  Dirk Edward Désiré Jochmans

IPC分类号： A61K31/5377 ,  A61K31/437 ,  A61P31/04 ,  A61P31/12

CPC分类号： C07D471/04

摘要： The present invention concerns the compounds of formula (I) their N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites, wherein n is 1, 2 or 3; R1 is H, CN, halo, aminoC(═O), C(═O)OH, C1-4alkyloxyC(═O), C1-4alkylC(═O), mono- or di(C1-4alkyl)aminoC(═O), arylaminoC(═O), N-(aryl)-N—(C1-4alkyl)aminoC(═O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; R2 is H, C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, wherein said C1-10alkyl, C2-10alkenyl and C3-7cycloalkyl may be optionally substituted; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxyC(═O), aminoC(═O), C1-4alkyloxyC(═O), mono- or di(C1-4alkyl)aminoC(═O), C1-4alkylC(═O), methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1; for use as a medicine. The invention further relates to a novel subgroup of the compounds of formula (I), and to compositions comprising compounds of formula (I).

摘要翻译： 本发明涉及式（I）化合物的N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物，其中n为1,2或3; R 1是H，CN，卤素，氨基C（= O），C（= O）OH，C 1-4烷氧基C（= O），C 1-4烷基C（= O），单或二（C 1-4烷基）氨基C ），芳基氨基C（= O），N-（芳基）-N-（C 1-4烷基）氨基C（= O），甲亚氨基亚氨基，N-羟基 - 甲亚磺酰氨基，单或二（C 1-4烷基）甲酰亚胺基，Het1或Het2; R 2是H，C 1-10烷基，C 2-10烯基，C 3-7环烷基，其中所述C 1-10烷基，C 2-10烯基和C 3-7环烷基可以任选被取代; R3是硝基，氰基，氨基，卤素，羟基，C1-4烷氧基，羟基C（= O），氨基C（= O），C1-4烷氧基C（= O），单或二（C1-4烷基）氨基C（= ，C 1-4烷基C（= O），甲亚氨基酰胺基，单或二（C 1-4烷基）甲亚氨基酰胺基，N-羟基 - 甲酰亚胺基或Het1; 用作药物。 本发明还涉及式（I）化合物的新亚组和包含式（I）化合物的组合物。

公开(公告)号：US20060286547A1

公开(公告)日：2006-12-21

申请号：US10570358

申请日：2004-09-20

申请人： Koenraad Van Acker ,  Lieve Bunkens ,  Gery Dams ,  Kurt Hertogs ,  Tania Ivens ,  Erik Nijs

发明人： Koenraad Van Acker ,  Lieve Bunkens ,  Gery Dams ,  Kurt Hertogs ,  Tania Ivens ,  Erik Nijs

IPC分类号： A61K38/00 ,  C12M1/34 ,  C12Q1/70

CPC分类号： C12Q1/701 ,  C12Q1/18 ,  G01N33/56988 ,  G01N2500/10

摘要： The present invention relates to a multi-well assay for identifying a compound inhibiting the replication cycle of a micro-organism, for example, HIV, and to an apparatus for carrying out an assay according to the present invention. The invention further relates to compounds identifiable with an assay according to the invention and pharmaceutical compositions comprising a therapeutically effective amount of such compounds. The identified compounds may be used as medicaments, and in particular for the manufacture of a medicament for treating infectious diseases and in method for treating infectious diseases including AIDS.

摘要翻译： 本发明涉及用于鉴定抑制微生物（例如HIV）的复制周期的化合物的多孔测定法和用于进行根据本发明的测定的装置。 本发明还涉及可根据本发明的测定法鉴定的化合物和包含治疗有效量的这些化合物的药物组合物。 所鉴定的化合物可以用作药物，特别是用于制备用于治疗感染性疾病的药物和用于治疗包括AIDS的感染性疾病的方法。