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1. 发明申请

US20100203498A1 METHODS AND COMPOSITIONS FOR IDENTIFYING ANTI-HCV AGENTS 审中-公开
标题翻译：鉴定抗HCV药物的方法和组合物
公开(公告)号：US20100203498A1
公开(公告)日：2010-08-12
申请号：US12510150
申请日：2009-07-27
申请人： JEFFREY S. GLENN , SHIRIT EINAV , MENASHE ELAZAR
发明人： JEFFREY S. GLENN , SHIRIT EINAV , MENASHE ELAZAR
IPC分类号： C12Q1/70 , C12Q1/68 , C12Q1/34
CPC分类号： G01N33/5767 , C12Q1/707 , G01N33/56983 , G01N33/6875 , G01N2333/18 , G01N2500/04
摘要： The invention provides methods and compositions for identifying agents for treating infection by viruses that encode a nucleotide-binding NS4B protein, or functional equivalent thereof, e.g., hepatitis C virus (HCV) or other members of the family Flaviviridae. In general, the methods involve contacting an NS4B nucleotide binding motif (NBM)-containing polypeptide with a candidate agent, and determining the effect of the candidate agent on nucleotide binding activity, a nucleotide hydrolyzing activity, or a nucleotide-dependent RNA binding activity of the polypeptide. A candidate agent that inhibits NS4B polypeptide binding to a nucleotide is an anti-viral agent, e.g., an anti-HCV agent. The invention also features a polynucleotide encoding a NS4B polypeptide having a modified NBM (e.g., which is impaired in NTP binding). The subject methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：本发明提供用于鉴定用于治疗编码与核苷酸结合的NS4B蛋白或其功能等同物如丙型肝炎病毒（HCV）或黄病毒科的其他成员的病毒感染的药剂的方法和组合物。通常，所述方法包括将含NS4B核苷酸结合基序（NBM）的多肽与候选试剂接触，并确定候选试剂对核苷酸结合活性，核苷酸水解活性或核苷酸依赖性RNA结合活性的影响多肽。抑制NS4B多肽与核苷酸结合的候选试剂是抗病毒剂，例如抗HCV剂。本发明还特征在于编码具有修饰的NBM（例如其在NTP结合中受损的）的NS4B多肽的多核苷酸。主题方法和组合物可用于各种治疗和筛选应用。

2. 发明申请

US20090083869A1 METHODS AND COMPOSITIONS FOR IDENTIFYING AGENTS THAT INHIBIT AN NS4B-MEDIATED NEOPLASTIC CELLULAR PHENOTYPE OF HCV INFECTED CELLS 有权
标题翻译：用于鉴定抑制NS4B介导的HCV感染细胞的神经细胞细胞的方法和组合物
公开(公告)号：US20090083869A1
公开(公告)日：2009-03-26
申请号：US12143630
申请日：2008-06-20
申请人： Jeffrey S. Glenn , Shirit Einav
发明人： Jeffrey S. Glenn , Shirit Einav
IPC分类号： A01K67/00 , C12Q1/02 , C12Q1/70 , C40B40/02 , C12N5/00
CPC分类号： G01N33/5011 , A61K49/0008
摘要： The disclosure provides methods and compositions for identifying agents that inhibit a neoplastic cellular phenotype mediated by the NS4B protein nucleotide binding motif (NBM) of hepatitis C virus (HCV). In general, the methods involve contacting a candidate agent with a mammalian cell expressing an NS4B NBM polypeptide of an HCV virus, wherein expression of the NS4B NBM polypeptide in the absence of candidate agent promotes a neoplastic cellular phenotype, and detecting the presence or absence of an effect of said candidate agent on NS4B-mediated promotion of a neoplastic cellular phenotype. The disclosed methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：本公开提供用于鉴定抑制由丙型肝炎病毒（HCV）的NS4B蛋白核苷酸结合基序（NBM）介导的肿瘤细胞表型的药剂的方法和组合物。通常，所述方法包括使候选试剂与表达HCV病毒的NS4B NBM多肽的哺乳动物细胞接触，其中NS4B NBM多肽在不存在候选试剂的情况下的表达促进肿瘤细胞表型，并检测是否存在所述候选试剂对NS4B介导的肿瘤细胞表型的促进的作用。所公开的方法和组合物可用于各种治疗和筛选应用。

3. 发明授权

US09149463B2 Methods and compositions of treating a Flaviviridae family viral infection 有权
标题翻译：治疗黄病毒科病毒感染的方法和组成
公开(公告)号：US09149463B2
公开(公告)日：2015-10-06
申请号：US12383071
申请日：2009-03-18
申请人： Shirit Einav , Jeffrey S. Glenn , Wenjin Yang , Hadas Dvory-Sobol , Ingrid C. Choong , Robert McDowell
发明人： Shirit Einav , Jeffrey S. Glenn , Wenjin Yang , Hadas Dvory-Sobol , Ingrid C. Choong , Robert McDowell
IPC分类号： A61K31/535 , A61K31/416 , A61K31/4439 , A61K31/454 , A61K31/7056 , A61K38/21 , A61K45/06 , C07D231/56 , C07D401/06 , C07D401/12 , C07K14/005
CPC分类号： A61K31/416 , A61K31/426 , A61K31/4439 , A61K31/454 , A61K31/7056 , A61K38/212 , A61K45/06 , C07D231/56 , C07D401/06 , C07D401/12 , C07K14/005 , C12N2770/24122 , C12N2770/24222 , G01N2333/186 , G01N2500/02 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395 , A61K2300/00
摘要： Briefly described, embodiments of this disclosure include compounds (e.g., such as Formula II, Formula II-a, and specific compounds shown in Table 1), pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of inhibiting HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3′UTR of HCV negative strand RNA in a host, methods of treating liver fibrosis in a host, and the like.
摘要翻译：简要描述，本公开的实施方案包括化合物（例如，式II，式II-a和表1所示的具体化合物），药物组合物，用于从病毒的黄病毒科病毒感染病毒的宿主的方法，抑制宿主中HCV复制的方法，抑制NS4B多肽与宿主中HCV负链RNA 3'UTR结合的方法，宿主中肝纤维化的治疗方法等。

4. 发明授权

US07582428B2 Methods and compositions for identifying anti-HCV agents 失效
标题翻译：用于鉴定抗HCV药物的方法和组合物
公开(公告)号：US07582428B2
公开(公告)日：2009-09-01
申请号：US10528377
申请日：2004-08-18
申请人： Jeffrey S. Glenn , Shirit Einav , Menashe Elazar
发明人： Jeffrey S. Glenn , Shirit Einav , Menashe Elazar
IPC分类号： C12Q1/68 , C12Q1/00
CPC分类号： G01N33/5767 , C12Q1/707 , G01N33/56983 , G01N33/6875 , G01N2333/18 , G01N2500/04
摘要： The invention provides methods and compositions for identifying agents for treating infection by viruses that encode a nucleotide-binding NS4B protein, or functional equivalent thereof, e.g., hepatitis C virus (HCV) or other members of the family Flaviviridae. In general, the methods involve contacting an NS4B nucleotide binding motif (NBM)-containing polypeptide with a candidate agent, and determining the effect of the candidate agent on nucleotide binding activity, a nucleotide hydrolyzing activity, or a nucleotide-dependent RNA binding activity of the polypeptide. A candidate agent that inhibits NS4B polypeptide binding to a nucleotide is an anti-viral agent, e.g., an anti-HCV agent. The invention also features a polynucleotide encoding a NS4B polypeptide having a modified NBM (e.g., which is impaired in NTP binding). The subject methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：本发明提供用于鉴定用于治疗编码与核苷酸结合的NS4B蛋白或其功能等同物如丙型肝炎病毒（HCV）或黄病毒科的其他成员的病毒感染的药剂的方法和组合物。通常，所述方法包括将含NS4B核苷酸结合基序（NBM）的多肽与候选试剂接触，并确定候选试剂对核苷酸结合活性，核苷酸水解活性或核苷酸依赖性RNA结合活性的影响多肽。抑制NS4B多肽与核苷酸结合的候选试剂是抗病毒剂，例如抗HCV剂。本发明还特征在于编码具有修饰的NBM（例如其在NTP结合中受损的）的NS4B多肽的多核苷酸。主题方法和组合物可用于各种治疗和筛选应用。

5. 发明申请

US20060199174A1 Methods and compositions for identifying anti-hcv agents 失效
标题翻译：用于鉴定抗hcv药物的方法和组合物
公开(公告)号：US20060199174A1
公开(公告)日：2006-09-07
申请号：US10528377
申请日：2004-08-18
申请人： Jeffrey Glenn , Shirit Einav , Menashe Elazar
发明人： Jeffrey Glenn , Shirit Einav , Menashe Elazar
IPC分类号： C12Q1/70
CPC分类号： G01N33/5767 , C12Q1/707 , G01N33/56983 , G01N33/6875 , G01N2333/18 , G01N2500/04
摘要： The invention provides methods and compositions for identifying agents for treating infection by viruses that encode a nucleotide-binding NS4B protein, or functional equivalent thereof, e.g., hepatitis C virus (HCV) or other members of the family Flaviviridae. In general, the methods involve contacting an NS4B nucleotide binding motif (NBM)-containing polypeptide with a candidate agent, and determining the effect of the candidate agent on nucleotide binding activity, a nucleotide hydrolyzing activity, or a nucleotide-dependent RNA binding activity of the polypeptide. A candidate agent that inhibits NS4B polypeptide binding to a nucleotide is an anti-viral agent, e.g., an anti-HCV agent. The invention also features a polynucleotide encoding a NS4B polypeptide having a modified NBM (e.g., which is impaired in NTP binding). The subject methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：本发明提供用于鉴定用于治疗编码与核苷酸结合的NS4B蛋白或其功能等同物如丙型肝炎病毒（HCV）或黄病毒科的其他成员的病毒感染的药剂的方法和组合物。通常，所述方法包括将含NS4B核苷酸结合基序（NBM）的多肽与候选试剂接触，并确定候选试剂对核苷酸结合活性，核苷酸水解活性或核苷酸依赖性RNA结合活性的影响多肽。抑制NS4B多肽与核苷酸结合的候选试剂是抗病毒剂，例如抗HCV剂。本发明还特征在于编码具有修饰的NBM（例如其在NTP结合中受损的）的NS4B多肽的多核苷酸。主题方法和组合物可用于各种治疗和筛选应用。

6. 发明授权

US09101628B2 Methods and composition of treating a flaviviridae family viral infection 有权
标题翻译：治疗黄病毒科病毒感染的方法和组成
公开(公告)号：US09101628B2
公开(公告)日：2015-08-11
申请号：US12383030
申请日：2009-03-18
申请人： Shirit Einav , Jeffrey S. Glenn , Wenjin Yang , Hadas Dvory-Sobol , Ingrid C. Choong , Robert McDowell
发明人： Shirit Einav , Jeffrey S. Glenn , Wenjin Yang , Hadas Dvory-Sobol , Ingrid C. Choong , Robert McDowell
IPC分类号： A01N43/00 , A61K31/33 , A61K38/21 , A61K31/497 , A61K31/4184 , A61K31/4439 , A61K31/708 , A61K45/06 , C07K14/005
CPC分类号： A61K31/497 , A61K31/4184 , A61K31/4439 , A61K31/708 , A61K45/06 , C07K14/005 , C12N2770/24222 , G01N2333/186 , G01N2500/02 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395 , A61K2300/00
摘要： Briefly described, embodiments of this disclosure include compounds, pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of inhibiting HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3′UTR of HCV negative strand RNA in a host, methods of treating liver fibrosis in a host, and the like. In an embodiment, the compounds can include clemizole or a clemizole analog, or a pharmaceutically acceptable salt, an isomer, a tautomer, or a prodrug thereof.
摘要翻译：简要描述，本公开的实施方案包括化合物，药物组合物，治疗感染病毒的病毒的病毒的病毒的方法，用于抑制宿主中HCV复制的方法，抑制NS4B多肽与3'端的结合的方法，宿主中HCV负链RNA的UTR，宿主中肝纤维化的治疗方法等。在一个实施方案中，化合物可以包括克立咪唑或克立姆唑类似物，或其药学上可接受的盐，异构体，互变异构体或其前药。

7. 发明申请

US20110052536A1 METHODS OF TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION AND COMPOSITIONS FOR TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION 有权
标题翻译：用于治疗弗氏病家族病毒感染的方法和用于治疗弗氏病家族病毒感染的组合物
公开(公告)号：US20110052536A1
公开(公告)日：2011-03-03
申请号：US12677989
申请日：2008-09-18
申请人： Shirit Einav , Jeffrey S. Glenn , Robert McDowell , Wenjin Yang , Hadas Dvory-Sobol
发明人： Shirit Einav , Jeffrey S. Glenn , Robert McDowell , Wenjin Yang , Hadas Dvory-Sobol
IPC分类号： A61K38/21 , A61K31/4184 , A61K31/7076 , A61K31/437 , A61K31/4985 , A61K31/52 , A61K31/415 , A61K31/404 , A61K31/55 , A61P31/14
CPC分类号： A61K31/4184 , A61K31/67 , A61K31/7056 , A61K38/212 , A61K45/06 , C07D235/08 , C07D235/12 , C07K14/005 , C12N2770/24222 , G01N2333/186 , G01N2500/02 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395 , A61K2300/00
摘要： Briefly described, embodiments of this disclosure include compositions, pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of treating HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3′UTR of HCV negative strand RNA in a host, methods of treating liver fibrosis in a host, and the like.
摘要翻译：简要描述，本公开的实施方案包括组合物，药物组合物，治疗感染来自病毒的病毒的宿主的病毒的方法，用于在宿主中治疗HCV复制的方法，抑制NS4B多肽与3'端的结合的方法，宿主中HCV负链RNA的UTR，宿主中肝纤维化的治疗方法等。

8. 发明授权

US09061010B2 Methods of treating a Flaviviridae family viral infection and compositions for treating a Flaviviridae family viral infection 有权
标题翻译：治疗黄病毒科家族病毒感染的方法和治疗黄病毒科病毒感染的组合物
公开(公告)号：US09061010B2
公开(公告)日：2015-06-23
申请号：US12677989
申请日：2008-09-18
申请人： Shirit Einav , Jeffrey S. Glenn , Robert McDowell , Wenjin Yang , Hadas Dvory-Sobol
发明人： Shirit Einav , Jeffrey S. Glenn , Robert McDowell , Wenjin Yang , Hadas Dvory-Sobol
IPC分类号： A61K31/415 , A61K31/4184 , A61K31/67 , A61K31/7056 , A61K45/06 , C07K14/005 , A61K38/21 , C07D235/08 , C07D235/12
CPC分类号： A61K31/4184 , A61K31/67 , A61K31/7056 , A61K38/212 , A61K45/06 , C07D235/08 , C07D235/12 , C07K14/005 , C12N2770/24222 , G01N2333/186 , G01N2500/02 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395 , A61K2300/00
摘要： Briefly described, embodiments of this disclosure include compositions, pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of treating HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3′UTR of HCV negative strand RNA in a host, methods of treating liver fibrosis in a host, and the like.
摘要翻译：简要描述，本公开的实施方案包括组合物，药物组合物，治疗感染来自病毒的病毒的宿主的病毒的方法，用于在宿主中治疗HCV复制的方法，抑制NS4B多肽与3'端的结合的方法，宿主中HCV负链RNA的UTR，宿主中肝纤维化的治疗方法等。

9. 发明授权

US08871435B2 Methods and compositions for identifying agents that inhibit an NS4B-mediated neoplastic cellular phenotype of HCV infected cells 有权
标题翻译：用于鉴定抑制NS4B介导的HCV感染细胞的肿瘤细胞表型的药剂的方法和组合物
公开(公告)号：US08871435B2
公开(公告)日：2014-10-28
申请号：US12143630
申请日：2008-06-20
申请人： Jeffrey S. Glenn , Shirit Einav
发明人： Jeffrey S. Glenn , Shirit Einav
IPC分类号： C12Q1/02 , C12Q1/18 , C12Q1/70 , C12N5/00 , G01N33/50 , A61K49/00
CPC分类号： G01N33/5011 , A61K49/0008
摘要： Methods and compositions for identifying agents that inhibit a neoplastic cellular phenotype mediated by the NS4B protein nucleotide binding motif (NBM) of hepatitis C virus (HCV) are provided. In general, the methods involve contacting a candidate agent with a mammalian cell expressing an NS4B NBM polypeptide of an HCV virus, wherein expression of the NS4B NBM polypeptide in the absence of candidate agent promotes a neoplastic cellular phenotype, and detecting the presence or absence of an effect of the candidate agent on NS4B-mediated promotion of a neoplastic cellular phenotype. The provided methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：提供了用于鉴定抑制由丙型肝炎病毒（HCV）的NS4B蛋白核苷酸结合基序（NBM）介导的肿瘤细胞表型的药剂的方法和组合物。通常，所述方法包括使候选试剂与表达HCV病毒的NS4B NBM多肽的哺乳动物细胞接触，其中NS4B NBM多肽在不存在候选试剂的情况下的表达促进肿瘤细胞表型，并检测是否存在候选药剂对NS4B介导的促进肿瘤细胞表型的作用。所提供的方法和组合物可用于各种治疗和筛选应用。

10. 发明申请

US20100028299A1 Methods and compositions of treating a flaviviridae family viral infection 有权
标题翻译：治疗黄病毒科病毒感染的方法和组成
公开(公告)号：US20100028299A1
公开(公告)日：2010-02-04
申请号：US12383030
申请日：2009-03-18
申请人： Shirit Einav , Jeffrey S. Glenn , Wenjin Yang , Hadas Dvory-Sobol , Ingrid C. Choong , Robert McDowell
发明人： Shirit Einav , Jeffrey S. Glenn , Wenjin Yang , Hadas Dvory-Sobol , Ingrid C. Choong , Robert McDowell
IPC分类号： A61K38/21 , A61K31/4184 , C07D403/02 , C07D403/12 , C07D471/04 , A61K31/497 , A61K31/4439 , A61K31/708 , A61P31/12
CPC分类号： A61K31/497 , A61K31/4184 , A61K31/4439 , A61K31/708 , A61K45/06 , C07K14/005 , C12N2770/24222 , G01N2333/186 , G01N2500/02 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395 , A61K2300/00
摘要： Briefly described, embodiments of this disclosure include compounds, pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of inhibiting HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3′UTR of HCV negative strand RNA in a host, methods of treating liver fibrosis in a host, and the like.
摘要翻译：简要描述，本公开的实施方案包括化合物，药物组合物，治疗感染病毒的病毒的病毒的病毒的方法，用于抑制宿主中HCV复制的方法，抑制NS4B多肽与3'端的结合的方法，宿主中HCV负链RNA的UTR，宿主中肝纤维化的治疗方法等。

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