公开(公告)号：US07384734B2

公开(公告)日：2008-06-10

申请号：US10367223

申请日：2003-02-13

申请人： Neil T. Parkin ,  Colombe Chappey ,  Christos J. Petropoulos

发明人： Neil T. Parkin ,  Colombe Chappey ,  Christos J. Petropoulos

IPC分类号： C12Q1/70

CPC分类号： C12Q1/703 ,  C12Q2600/156

摘要： The present invention provides an approach for developing an algorithm for determining the effectiveness of anti-viral drugs based on a comprehensive analysis of paired phenotypic and genotypic data guided by phenotypic clinical cut-offs. In one aspect, the algorithm allows one to provide a patient with effective treatment. It helps predict whether an infected individual will respond to treatment with an anti-viral compound, thereby allowing an effective treatment regimen to be designed without subjecting the patient to unnecessary side effects. Also, by avoiding the administration of ineffective drugs, considerable time and money is saved.

摘要翻译： 本发明提供了一种基于通过表型临床切片指导的成对表型和基因型数据的综合分析来开发用于确定抗病毒药物有效性的算法的方法。 在一个方面，算法允许给患者提供有效的治疗。 它有助于预测受感染的个体是否会对抗病毒化合物进行治疗反应，从而允许设计有效的治疗方案，而不会对患者造成不必要的副作用。 此外，通过避免无效药物的管理，节省了大量的时间和金钱。

公开(公告)号：US20110033836A1

公开(公告)日：2011-02-10

申请号：US12635539

申请日：2009-12-10

申请人： DOUGLAS RICHMAN ,  MARY T. WRIN ,  SUSAN LITTLE ,  CHRISTOS J. PETROPOULOS ,  NEIL T. PARKIN ,  JEANNETTE WHITCOMB ,  WEI HUANG

发明人： DOUGLAS RICHMAN ,  MARY T. WRIN ,  SUSAN LITTLE ,  CHRISTOS J. PETROPOULOS ,  NEIL T. PARKIN ,  JEANNETTE WHITCOMB ,  WEI HUANG

IPC分类号： C12Q1/70

CPC分类号： G01N33/56988 ,  C07K14/005 ,  C07K14/16 ,  C07K14/162 ,  C07K16/08 ,  C07K16/10 ,  C12Q1/6897 ,  C12Q1/703 ,  G01N33/5044 ,  G01N33/5091 ,  G01N33/56983 ,  G01N2333/16

摘要： The present invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced in the absence of the compound, wherein a reduced amount of signal measured in the presence of the compound indicates that the compound inhibits entry of the virus into the second cell.

摘要翻译： 本发明提供了鉴定化合物是否抑制病毒进入细胞的方法，该方法包括：（a）从病毒感染的患者获得编码病毒包膜蛋白的核酸; （b）共转染入第一细胞（i）步骤（a）的核酸，和（ii）缺乏编码包膜蛋白的核酸的病毒表达载体，其包含指示核酸，其产生 使得第一细胞产生包含由患者获得的核酸编码的包膜蛋白的病毒颗粒; （c）在化合物存在下使步骤（b）中产生的病毒颗粒与第二细胞接触，其中第二细胞表达病毒结合的细胞表面受体; （d）测量由第二细胞产生的信号量以确定病毒颗粒的感染性; 和（e）将步骤（d）中测量的信号量与在不存在化合物时产生的信号量进行比较，其中在化合物存在下测量的信号量减少表明化合物抑制病毒进入 进入第二个细胞。

公开(公告)号：US07553618B2

公开(公告)日：2009-06-30

申请号：US10612600

申请日：2003-07-01

申请人： Neil T. Parkin ,  Ellen Paxinos ,  Colombe Chappey ,  Mary T. Wrin ,  Andrea Gamarnik ,  Christos J. Petropoulos

发明人： Neil T. Parkin ,  Ellen Paxinos ,  Colombe Chappey ,  Mary T. Wrin ,  Andrea Gamarnik ,  Christos J. Petropoulos

IPC分类号： C12Q1/70 ,  A61K39/21

CPC分类号： C12Q1/703 ,  C12Q1/37 ,  G01N33/56988

摘要： The present invention provides an approach for developing an algorithm for determining the effectiveness of anti-viral drugs based on a comprehensive analysis of paired phenotypic and genotypic data guided by phenotypic clinical cut-offs. In one aspect, the algorithm allows one to provide a patient with effective treatment. It helps predict whether an infected individual will respond to treatment with an anti-viral compound, thereby allowing an effective treatment regimen to be designed without subjecting the patient to unnecessary side effects. Also, by avoiding the administration of ineffective drugs, considerable time and money is saved.

摘要翻译： 本发明提供了一种基于通过表型临床切片指导的成对表型和基因型数据的综合分析来开发用于确定抗病毒药物有效性的算法的方法。 在一个方面，算法允许给患者提供有效的治疗。 它有助于预测受感染的个体是否会对抗病毒化合物进行治疗反应，从而允许设计有效的治疗方案，而不会对患者造成不必要的副作用。 此外，通过避免无效药物的管理，节省了大量的时间和金钱。

公开(公告)号：US06489098B1

公开(公告)日：2002-12-03

申请号：US09339357

申请日：1999-06-23

申请人： Christos J. Petropoulos ,  Jeannette Whitcomb

发明人： Christos J. Petropoulos ,  Jeannette Whitcomb

IPC分类号： C12Q170

CPC分类号： C12Q1/703 ,  C12Q2600/156

摘要： This invention relates to antiviral drug susceptibility and resistance tests to be used in identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and further relates to the means and methods of monitoring the clinical progression of HIV infection and its response to antiretroviral therapy, particularly nucleoside reverse transcriptase inhibitor therapy using phenotypic susceptibility assays or genotypic assays.

摘要翻译： 本发明涉及用于鉴定用于治疗人类免疫缺陷病毒（HIV）感染和获得性免疫缺陷综合征（AIDS）的有效药物方案的抗病毒药物敏感性和抗性测试，并且还涉及监测临床进展的手段和方法 艾滋病毒感染及其对抗逆转录病毒治疗的反应，特别是使用表型易感性测定或基因型测定的核苷逆转录酶抑制剂治疗。

公开(公告)号：US08603736B2

公开(公告)日：2013-12-10

申请号：US11146879

申请日：2005-06-06

申请人： Christos J. Petropoulos

发明人： Christos J. Petropoulos

IPC分类号： C12Q1/70

CPC分类号： C12Q1/703 ,  C07K14/005 ,  C12N7/00 ,  C12N2740/16062 ,  C12N2740/16122 ,  C12N2800/107 ,  C12N2800/40 ,  C12Q1/04 ,  C12Q1/66 ,  G01N33/5008 ,  G01N2333/16 ,  G01N2333/162

摘要： The invention provides a method for determining whether a human immunodeficiency virus is resistance to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

摘要翻译： 本发明提供了一种用于确定人类免疫缺陷病毒是否对病毒进入抑制剂的抗性的方法。 该方法对于确定通过非竞争性机制起作用的抑制剂的抗性特别有用。 在某些方面，所述方法包括确定HIV群体对HIV入侵抑制剂是否具有抗性，包括确定在存在不同浓度的HIV入侵抑制剂的情况下包括HIV群体进入的数据点的对数乙状结肠抑制曲线，其中 如果艾滋病毒携带者的输入不能完全被艾滋病毒入侵者抑制，艾滋病毒携带者就能抵抗艾滋病毒入侵者。

公开(公告)号：US07097970B2

公开(公告)日：2006-08-29

申请号：US09874475

申请日：2001-06-04

申请人： Christos J. Petropoulos ,  Neil T. Parkin ,  Jeanette M. Whitcomb ,  Wei Huang

发明人： Christos J. Petropoulos ,  Neil T. Parkin ,  Jeanette M. Whitcomb ,  Wei Huang

IPC分类号： C12Q1/70

CPC分类号： G01N33/5044 ,  C12Q1/703 ,  G01N33/5008 ,  G01N33/502

摘要： The invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced in the absence of the compound, wherein a reduced amount of signal measured in the presence of the compound indicates that the compound inhibits entry of the virus into the second cell.

摘要翻译： 本发明提供了一种用于鉴定化合物是否抑制病毒进入细胞的方法，其包括：（a）从感染病毒的患者获得编码病毒包膜蛋白的核酸; （b）共转染入第一细胞（i）步骤（a）的核酸，和（ii）缺乏编码包膜蛋白的核酸的病毒表达载体，其包含指示核酸，其产生 使得第一细胞产生包含由患者获得的核酸编码的包膜蛋白的病毒颗粒; （c）在化合物存在下使步骤（b）中产生的病毒颗粒与第二细胞接触，其中第二细胞表达病毒结合的细胞表面受体; （d）测量由第二细胞产生的信号量以确定病毒颗粒的感染性; 和（e）将步骤（d）中测量的信号量与在不存在化合物时产生的信号量进行比较，其中在化合物存在下测量的信号量减少表明化合物抑制病毒进入 进入第二个细胞。

公开(公告)号：US06942969B2

公开(公告)日：2005-09-13

申请号：US09875082

申请日：2001-06-05

申请人： Daniel J. Capon ,  Christos J. Petropoulos

发明人： Daniel J. Capon ,  Christos J. Petropoulos

IPC分类号： C12N15/867 ,  C12Q1/18 ,  C12Q1/68 ,  C12Q1/70 ,  G01N33/50

CPC分类号： C12N15/86 ,  C12N2740/16043 ,  C12N2830/00 ,  C12N2830/15 ,  C12N2830/60 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/206 ,  C12N2840/44 ,  C12Q1/18 ,  C12Q1/6881 ,  C12Q1/6897 ,  C12Q1/701 ,  C12Q1/703 ,  C12Q1/707 ,  C12Q2600/158 ,  G01N33/5023 ,  G01N2333/16 ,  G01N2800/52 ,  C12Q2545/113

摘要： This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c). This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time; (b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient. This invention also provides a method for evaluating the biological effectiveness of a candidate anti-viral drug compound. Compositions including resistance test vectors comprising a patient-derived segment and an indicator gene and host cells transformed with the resistance test vectors are provided.

摘要翻译： 本发明提供了一种用于确定抗病毒药物敏感性的方法，包括：（a）将包含患者来源区段和指示基因的抗性测试载体导入宿主细胞; （b）从（a）培养宿主细胞; （c）测量靶宿主细胞中指示基因的表达; 和（d）比较来自（c）的指示基因的表达与在不存在抗病毒药物的情况下进行步骤（a） - （c）时测量的指示基因的表达，其中测试浓度 在步骤（a） - （c）中存在抗病毒药物; 在步骤（b） - （c）; 或在步骤（c）。 本发明还提供了一种用于测定患者抗病毒药物耐药性的方法，包括：（a）使用上述敏感性试验在第一时间确定患者的抗病毒药物敏感性，其中所述患者衍生部分获自 病人约在上述时间; （b）以后确定同一病人的抗病毒药物敏感性; 和（c）比较步骤（a）和（b）中确定的抗病毒药物敏感性，其中与第一次相比后来的抗病毒药物敏感性的降低表明抗病毒药物耐药性的发展或进展 在病人身上 本发明还提供了评估候选抗病毒药物化合物的生物学效力的方法。 提供了包含抗性测试载体的组合物，其包含患者来源的区段和指示基因以及用抗性测试载体转化的宿主细胞。

公开(公告)号：US06242187B1

公开(公告)日：2001-06-05

申请号：US09371774

申请日：1999-08-10

申请人： Daniel J. Capon ,  Christos J. Petropoulos

发明人： Daniel J. Capon ,  Christos J. Petropoulos

IPC分类号： C12Q168

CPC分类号： C12N15/86 ,  C12N2740/16043 ,  C12N2830/00 ,  C12N2830/15 ,  C12N2830/60 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/206 ,  C12N2840/44 ,  C12Q1/18 ,  C12Q1/6881 ,  C12Q1/6897 ,  C12Q1/701 ,  C12Q1/703 ,  C12Q1/707 ,  C12Q2600/158 ,  G01N33/5023 ,  G01N2333/16 ,  G01N2800/52 ,  C12Q2545/113

摘要： This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c) This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time;(b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient. This invention also provides a method for evaluating the biological effectiveness of a candidate anti-viral drug compound. Compositions including resistance test vectors comprising a patient-derived segment and an indicator gene and host cells transformed with the resistance test vectors are provided.

摘要翻译： 本发明提供了一种用于确定抗病毒药物敏感性的方法，包括：（a）将包含患者来源区段和指示基因的抗性测试载体导入宿主细胞; （b）从（a）培养宿主细胞; （c）测量靶宿主细胞中指示基因的表达; 和（d）比较来自（c）的指示基因的表达与在不存在抗病毒药物的情况下进行步骤（a） - （c）时测量的指示基因的表达，其中测试浓度 在步骤（a） - （c）中存在抗病毒药物; 在步骤（b） - （c）; 或在步骤（c）本发明还提供了一种用于测定患者抗病毒耐药性的方法，包括：（a）使用上述敏感性试验在第一时间确定患者的抗病毒药物敏感性，其中患者 （b）在以后的时间内测定同一患者的抗病毒药物敏感性; 和（c）比较步骤（a）和（b）中确定的抗病毒药物敏感性，其中与第一次相比后来的抗病毒药物敏感性的降低表明抗病毒药物耐药性的发展或进展 在病人身上 本发明还提供了评估候选抗病毒药物化合物的生物学效力的方法。 提供了包含抗性测试载体的组合物，其包含患者来源的区段和指示基因以及用抗性测试载体转化的宿主细胞。

公开(公告)号：US5837464A

公开(公告)日：1998-11-17

申请号：US790963

申请日：1997-01-29

申请人： Daniel Capon ,  Christos J. Petropoulos

发明人： Daniel Capon ,  Christos J. Petropoulos

IPC分类号： C12N15/867 ,  C12Q1/68

CPC分类号： C12N15/86 ,  C12Q1/6897 ,  C12N2740/16043 ,  C12N2830/00 ,  C12N2830/15 ,  C12N2830/60 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44 ,  G01N2333/16 ,  Y10S977/804 ,  Y10S977/923 ,  Y10S977/927 ,  Y10S977/958

摘要： This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c). This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time; (b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient. This invention also provides a method for evaluating the biological effectiveness of a candidate anti-viral drug compound. Compositions including resistance test vectors comprising a patient-derived segment and an indicator gene and host cells transformed with the resistance test vectors are provided.

摘要翻译： 本发明提供了一种用于确定抗病毒药物敏感性的方法，包括：（a）将包含患者来源区段和指示基因的抗性测试载体导入宿主细胞; （b）从（a）培养宿主细胞; （c）测量靶宿主细胞中指示基因的表达; 和（d）比较来自（c）的指示基因的表达与在不存在抗病毒药物的情况下进行步骤（a） - （c）时测量的指示基因的表达，其中测试浓度 在步骤（a） - （c）中存在抗病毒药物; 在步骤（b） - （c）; 或在步骤（c）。 本发明还提供了一种用于测定患者抗病毒药物耐药性的方法，包括：（a）使用上述敏感性试验在第一时间确定患者的抗病毒药物敏感性，其中所述患者衍生部分获自 病人约在上述时间; （b）以后确定同一病人的抗病毒药物敏感性; 和（c）比较步骤（a）和（b）中确定的抗病毒药物敏感性，其中与第一次相比后来的抗病毒药物敏感性的降低表明抗病毒药物耐药性的发展或进展 在病人身上 本发明还提供了评估候选抗病毒药物化合物的生物学效力的方法。 提供了包含抗性测试载体的组合物，其包含患者来源的区段和指示基因以及用抗性测试载体转化的宿主细胞。

公开(公告)号：US09175355B2

公开(公告)日：2015-11-03

申请号：US12635539

申请日：2009-12-10

申请人： Douglas Richman ,  Mary T. Wrin ,  Susan Little ,  Christos J. Petropoulos ,  Neil T. Parkin ,  Jeannette Whitcomb ,  Wei Huang

发明人： Douglas Richman ,  Mary T. Wrin ,  Susan Little ,  Christos J. Petropoulos ,  Neil T. Parkin ,  Jeannette Whitcomb ,  Wei Huang

IPC分类号： C12Q1/70 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/569 ,  C07K14/16 ,  C07K16/08 ,  C07K14/005 ,  C07K16/10

CPC分类号： G01N33/56988 ,  C07K14/005 ,  C07K14/16 ,  C07K14/162 ,  C07K16/08 ,  C07K16/10 ,  C12Q1/6897 ,  C12Q1/703 ,  G01N33/5044 ,  G01N33/5091 ,  G01N33/56983 ,  G01N2333/16

摘要： The present invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced in the absence of the compound, wherein a reduced amount of signal measured in the presence of the compound indicates that the compound inhibits entry of the virus into the second cell.

摘要翻译： 本发明提供了鉴定化合物是否抑制病毒进入细胞的方法，该方法包括：（a）从病毒感染的患者获得编码病毒包膜蛋白的核酸; （b）共转染入第一细胞（i）步骤（a）的核酸，和（ii）缺乏编码包膜蛋白的核酸的病毒表达载体，其包含指示核酸，其产生 使得第一细胞产生包含由患者获得的核酸编码的包膜蛋白的病毒颗粒; （c）在化合物存在下使步骤（b）中产生的病毒颗粒与第二细胞接触，其中第二细胞表达病毒结合的细胞表面受体; （d）测量由第二细胞产生的信号量以确定病毒颗粒的感染性; 和（e）将步骤（d）中测量的信号量与在不存在化合物时产生的信号量进行比较，其中在化合物存在下测量的信号量减少表明化合物抑制病毒进入 进入第二个细胞。