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公开(公告)号：US08354518B2
公开(公告)日：2013-01-15
申请号：US10577893
申请日：2004-11-03
申请人： Steven W. Ludmerer , Donald J. Graham , Robert L. LaFemina , Osvaldo A. Flores , Maura Pizzuti , Cinzia Traboni
发明人： Steven W. Ludmerer , Donald J. Graham , Robert L. LaFemina , Osvaldo A. Flores , Maura Pizzuti , Cinzia Traboni
CPC分类号： C12Q1/707 , C07K14/005 , C12N7/00 , C12N2770/24221 , C12N2770/24222
摘要： The present invention features methods for enhancing the ability of a genotype 2b NS5B sequence to function in a replicon, for producing replicons containing a functional genotype 2b NS5B, and for using replicons to measure the ability of a compound to affect HCV replication that is sustained with the genotype 2b polymerase. Also featured is a genotype 1b NS4B adaptive mutation. The ability to produce replicons containing a functional genotype 2b NS5B is illustrated by the production of chimeric replicons based on HCV genotype 1b where substantially all the NS5B sequence is replaced with a genotype 2b NS5B.
摘要翻译： 本发明的特征在于增强基因型2b NS5B序列在复制子中起作用的能力的方法，用于产生含有功能性基因型2b NS5B的复制子，并且使用复制子来测量化合物影响HCV复制的能力 基因型2b聚合酶。 还有一个基因型1b NS4B自适应突变。 通过产生基于HCV基因型1b的嵌合复制子来说明产生含有功能性基因型2b NS5B的复制子的能力，其中基本上所有NS5B序列被基因型2b NS5B替代。
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公开(公告)号：US20110250628A1
公开(公告)日：2011-10-13
申请号：US10577893
申请日：2004-11-03
申请人： Steven W. Ludmerer , Donald J. Graham , Robert L. Lafemina , Osvaldo A. Flores , Maura Pizzuti , Cinzia Traboni
发明人： Steven W. Ludmerer , Donald J. Graham , Robert L. Lafemina , Osvaldo A. Flores , Maura Pizzuti , Cinzia Traboni
CPC分类号： C12Q1/707 , C07K14/005 , C12N7/00 , C12N2770/24221 , C12N2770/24222
摘要： The present invention features methods for enhancing the ability of a genotype 2b NS5B sequence to function in a replicon, for producing replicons containing a functional genotype 2b NS5B, and for using replicons to measure the ability of a compound to affect HCV replication that is sustained with the genotype 2b polymerase. Also featured is a genotype 1b NS4B adaptive mutation. The ability to produce replicons containing a functional genotype 2b NS5B is illustrated by the production of chimeric replicons based on HCV genotype 1b where substantially all the NS5B sequence is replaced with a genotype 2b NS5B.
摘要翻译： 本发明的特征在于增强基因型2b NS5B序列在复制子中起作用的能力的方法，用于产生含有功能性基因型2b NS5B的复制子，并且使用复制子来测量化合物影响HCV复制的能力 基因型2b聚合酶。 还有一个基因型1b NS4B自适应突变。 通过产生基于HCV基因型1b的嵌合复制子来说明产生含有功能性基因型2b NS5B的复制子的能力，其中基本上所有NS5B序列被基因型2b NS5B替代。
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公开(公告)号：US07569374B2
公开(公告)日：2009-08-04
申请号：US12002392
申请日：2007-12-17
CPC分类号： C07K14/005 , C07H21/00 , C07H21/04 , C12N9/127 , C12N2770/24222 , G01N2333/18 , G01N2333/9125 , G01N2500/04
摘要： The present invention features NS5B polypeptides from different clinically important HCV genotypes. The polypeptides can be used individually, or as part of a panel of RNA-dependent RNA polymerases, to evaluate the effectiveness of a compound to inhibit NS5B activity.
摘要翻译： 本发明特征来自不同临床重要HCV基因型的NS5B多肽。 多肽可以单独使用或作为一组RNA依赖性RNA聚合酶的一部分使用，以评估化合物抑制NS5B活性的有效性。
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公开(公告)号：US07329732B2
公开(公告)日：2008-02-12
申请号：US10584810
申请日：2005-01-06
CPC分类号： C07K14/005 , C07H21/00 , C07H21/04 , C12N9/127 , C12N2770/24222 , G01N2333/18 , G01N2333/9125 , G01N2500/04
摘要： The present invention features NS5B polypeptides from different clinically important HCV genotypes. The polypeptides can be used individually, or as part of a panel of RNA-dependent RNA polymerases, to evaluate the effectiveness of a compound to inhibit NS5B activity.
摘要翻译： 本发明特征来自不同临床重要HCV基因型的NS5B多肽。 多肽可以单独使用或作为一组RNA依赖性RNA聚合酶的一部分使用，以评估化合物抑制NS5B活性的有效性。
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公开(公告)号：US20080187903A1
公开(公告)日：2008-08-07
申请号：US12002392
申请日：2007-12-17
IPC分类号： C12Q1/00 , C07K14/005 , C07H21/04 , C12N15/63
CPC分类号： C07K14/005 , C07H21/00 , C07H21/04 , C12N9/127 , C12N2770/24222 , G01N2333/18 , G01N2333/9125 , G01N2500/04
摘要： The present invention features NS5B polypeptides from different clinically important HCV genotypes. The polypeptides can be used individually, or as part of a panel of RNA-dependent RNA polymerases, to evaluate the effectiveness of a compound to inhibit NS5B activity.
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6.发明申请Rapid method to determine inhibitor sensitivity of NS3/4A protease sequences cloned from clinical samples 审中-公开确定从临床样品克隆的NS3 / 4A蛋白酶序列的抑制剂敏感性的快速方法公开(公告)号：US20090203008A1
公开(公告)日：2009-08-13
申请号：US12308010
申请日：2007-06-04
IPC分类号： C12Q1/68
CPC分类号： C12N9/506
摘要： A method for measuring HCV NS3/4A activity from a HCV NS3/4A sequence, comprising obtaining and cloning the sequence into a mammalian expression vector, transiently transfecting a mammalian cell with the vector, which includes a reporter construct encoding a HCV NS3/4A cleavage site fused to a detectable label, measuring signal production from the label resulting from cleavage at the cleavage site, and measuring effects on signal production by addition of a test compound.
摘要翻译： 一种从HCV NS3 / 4A序列测量HCV NS3 / 4A活性的方法，包括获得并将该序列克隆到哺乳动物表达载体中，该载体用载体瞬时转染哺乳动物细胞，其包括编码HCV NS3 / 4A切割的报道构建体 与可检测标记融合的位点，测量从切割位点处切割得到的标记物的信号产生，以及通过添加测试化合物测量对信号产生的影响。
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公开(公告)号：US20100143886A1
公开(公告)日：2010-06-10
申请号：US12529785
申请日：2008-03-05
CPC分类号： C12Q1/707 , C12Q2535/125 , C12Q2535/131
摘要： HCV mutations emerged in chimpanzees treated with a N5B polymerase inhibitor (Compound A) or a NS3 protease inhibitor (Compound B). Short term treatment with Compound A was followed by the initial emergence of an HCV with a S282T polymerase mutation following treatment. Short term treatment with Compound B selected for HCV with a R155K or D168T protease mutation.
摘要翻译： HCV突变出现在用N5B聚合酶抑制剂（化合物A）或NS3蛋白酶抑制剂（化合物B）处理的黑猩猩中。 化合物A的短期治疗之后，治疗后首次出现HCV与S282T聚合酶突变。 使用化合物B进行短期治疗，选择具有R155K或D168T蛋白酶突变的HCV。
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8.发明授权Color screening assay for identifying inhibitor resistant HIV protease mutants 失效用于鉴定抑制剂的HIV蛋白酶突变体的彩色筛选测定
公开(公告)号：US5436131A
公开(公告)日：1995-07-25
申请号：US45264
申请日：1993-04-02
申请人： Jon H. Condra , Donald J. Graham , Leah Gotlib
发明人： Jon H. Condra , Donald J. Graham , Leah Gotlib
CPC分类号： C12N9/506
摘要： A chromogenic assay is described for the identification and isolation of drug-resistant HIV protease mutants. Coversely, the assay is useful to screen for new inhibitors of HIV protease, e.g., inhibitors not affected by drug-resistance of the HIV protease. This color screening assay contains a vector comprising a regulatable promoter which controls the transcription of two adjacent structural sequences, one sequence coding for HIV protease or mutant thereof, the other sequence coding for beta-galactosidase with an amino acid substrate insert cleavable by HIV protease. A library of HIV proteases is also described and is isolated in the form of a collection of such vectors, which is a color screen vector library.
摘要翻译： 描述了用于鉴定和分离耐药HIV蛋白酶突变体的显色测定法。 相反，该测定可用于筛选HIV蛋白酶的新抑制剂，例如不受HIV蛋白酶耐药性影响的抑制剂。 该彩色筛选测定法包含含有可调控启动子的载体，其控制两个相邻结构序列的转录，编码HIV蛋白酶或其突变体的一个序列，编码具有可被HIV蛋白酶切割的氨基酸底物插入物的β-半乳糖苷酶的其它序列。 还描述了HIV蛋白酶库，并以这样的载体的集合的形式分离，其为彩色荧光载体文库。
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公开(公告)号：US4892224A
公开(公告)日：1990-01-09
申请号：US190998
申请日：1988-05-06
申请人： Donald J. Graham
发明人： Donald J. Graham
IPC分类号： B65F1/06
CPC分类号： B65F1/06 , Y10S220/908
摘要： A trash entry chute device for mounting on a top-opening trash container, which device supports and holds open a limp plastic film bag for use as a disposable liner for the container. The device comprises a chute having a flange which supports the device on the container and diverts trash into the chute, and bag support means in opposite positions on the outside surface of the chute. When a bag is supported by the device, the chute fits into the mouth of the bag, holding it open to receive trash.
摘要翻译： 一种用于安装在顶部开口的垃圾容器上的垃圾入口斜槽装置，该装置支撑并保持打开用于容器的一次性衬垫的柔软塑料膜袋。 该装置包括具有凸缘的滑槽，该凸缘支撑容器上的装置并将垃圾转移到滑槽中，以及袋支撑装置，其位于滑槽的外表面上的相对位置。 当设备支持袋子时，滑槽装入袋的口中，将其打开以接收垃圾。
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