公开(公告)号：US08481050B2

公开(公告)日：2013-07-09

申请号：US12310309

申请日：2007-08-22

申请人： Qui-Lim Choo ,  Jang Han ,  Michael Houghton ,  Taewoo Kwon ,  Hyun Chul Song ,  Yifei Zhu

发明人： Qui-Lim Choo ,  Jang Han ,  Michael Houghton ,  Taewoo Kwon ,  Hyun Chul Song ,  Yifei Zhu

IPC分类号： A61K48/00 ,  A61K50/00

CPC分类号： C12N7/00 ,  A61K2039/525 ,  C07K14/005 ,  C07K2319/61 ,  C12N2760/16022 ,  C12N2770/24243 ,  G01N2333/186 ,  G01N2500/10

摘要： A tissue culture system for production of infectious hepatitis C virus is described. In particular, the invention provides recombinant monocistronic and bicistronic genomic constructs for production of virus, including constructs for production of wild-type HCV type 2a strain JFH1 and constructs for production of chimeric viruses comprising HCV proteins from strain JFH1 and a second HCV isolate. Constructs of the invention also include a reporter gene to facilitate measurement of RNA replication and viral infectivity in cultures. The cell culture system may also include various factors that improve viral replication or infectivity. In addition, a neutralization assay using HCV grown in cell culture is described.

摘要翻译： 描述了用于生产感染性丙型肝炎病毒的组织培养系统。 特别地，本发明提供了用于产生病毒的重组单顺反子和双顺反子基因组构建体，包括用于产生野生型HCV 2a型菌株JFH1的构建体和用于产生包含来自菌株JFH1的HCV蛋白质和第二HCV分离物的嵌合病毒的构建体。 本发明的构建体还包括有利于测量培养物中RNA复制和病毒感染性的报告基因。 细胞培养系统还可以包括改善病毒复制或感染性的各种因素。 此外，描述了使用在细胞培养物中生长的HCV的中和测定。

公开(公告)号：US08138161B2

公开(公告)日：2012-03-20

申请号：US11664008

申请日：2005-09-30

申请人： Jang Han ,  Michael Houghton

发明人： Jang Han ,  Michael Houghton

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/1131 ,  A61K38/00 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2310/334 ,  C12N2310/335 ,  C12N2310/3515 ,  Y02A50/463

摘要： The present invention provides double-stranded RNA molecules that mediate RNA interference in target cells, preferably hepatic cells. The invention also provides double-stranded RNA (dsRNA) molecules that are modified to be resistant to nuclease degradation, which inactivates a virus, and more specifically, hepatitis C virus (HCV). The invention also provides a method of using these modified RNA molecules to inactivate virus in mammalian cells and a method of making modified small interfering RNAs (siRNAs) using human Dicer. The invention provides modified RNA molecules that are modified to include a dsRNA or siRNA wherein one or more of the pyrimidines in the RNA molecule are modified to include 2′-Fluorine. The invention also provides dsRNA or siRNA in which all pyrimidines are modified to include a 2′-Fluorine. The invention provides that the 2′-Fluorine dsRNA or siRNA molecule is further modified to include a two base deoxynucleotide “TT” sequence at the 3′ end of the molecule.

摘要翻译： 本发明提供了介导靶细胞，优选肝细胞中的RNA干扰的双链RNA分子。 本发明还提供被修饰为对核酸酶降解具有抗性的双链RNA（dsRNA）分子，其使病毒失活，更具体地，丙型肝炎病毒（HCV）。 本发明还提供了使用这些修饰的RNA分子来灭活哺乳动物细胞中的病毒的方法和使用人Dicer制备修饰的小干扰RNA（siRNA）的方法。 本发明提供经修饰以包括dsRNA或siRNA的修饰的RNA分子，其中RNA分子中的一个或多个嘧啶被修饰为包括2'-氟。 本发明还提供dsRNA或siRNA，其中所有嘧啶被修饰以包括2'-氟。 本发明提供了2'-氟dsRNA或siRNA分子被进一步修饰，以在分子的3'端包括两碱基脱氧核苷酸“TT”序列。

公开(公告)号：US20080269148A1

公开(公告)日：2008-10-30

申请号：US11664008

申请日：2005-09-30

申请人： Jang Han ,  Michael Houghton

发明人： Jang Han ,  Michael Houghton

IPC分类号： A61K31/70 ,  C07H21/00 ,  A61P31/00

CPC分类号： C12N15/1131 ,  A61K38/00 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2310/334 ,  C12N2310/335 ,  C12N2310/3515 ,  Y02A50/463

摘要： The present invention provides double-stranded RNA molecules that mediate RNA interference in target cells, preferably hepatic cells. The invention also provides double-stranded RNA (dsRNA) molecules that are modified to be resistant to nuclease degradation, which inactivates a virus, and more specifically, hepatitis C virus (HCV). The invention also provides a method of using these modified RNA molecules to inactivate virus in mammalian cells and a method of making modified small interfering RNAs (siRNAs) using human Dicer. The invention provides modified RNA molecules that are modified to include a dsRNA or siRNA wherein one or more of the pyrimidines in the RNA molecule are modified to include 2′-Fluorine. The invention also provides dsRNA or siRNA in which all pyrimidines are modified to include a 2′-Fluorine. The invention provides that the 2′-Fluorine dsRNA or siRNA molecule is further modified to include a two base deoxynucleotide “TT” sequence at the 3′end of the molecule.

摘要翻译： 本发明提供了介导靶细胞，优选肝细胞中的RNA干扰的双链RNA分子。 本发明还提供被修饰为对核酸酶降解具有抗性的双链RNA（dsRNA）分子，其使病毒失活，更具体地，丙型肝炎病毒（HCV）。 本发明还提供了使用这些修饰的RNA分子来灭活哺乳动物细胞中的病毒的方法和使用人Dicer制备修饰的小干扰RNA（siRNA）的方法。 本发明提供经修饰以包括dsRNA或siRNA的修饰的RNA分子，其中RNA分子中的一个或多个嘧啶被修饰为包括2'-氟。 本发明还提供dsRNA或siRNA，其中所有嘧啶被修饰以包括2'-氟。 本发明提供了2'-氟dsRNA或siRNA分子进一步修饰，以在分子的3'末端包括两碱基脱氧核苷酸“TT”序列。

公开(公告)号：US07033805B2

公开(公告)日：2006-04-25

申请号：US10232643

申请日：2002-11-25

申请人： Michael Houghton ,  Qui-Lim Choo ,  Jang Han ,  Joonho Choe

发明人： Michael Houghton ,  Qui-Lim Choo ,  Jang Han ,  Joonho Choe

IPC分类号： C12N9/00 ,  C12N9/10 ,  C07H21/04

CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K14/00 ,  C07K2319/00 ,  C12N9/0089 ,  C12N9/506 ,  C12N9/90 ,  C12N2770/24222

摘要： The Hepatitis C Virus (HCV) NS3 protein contains amino acid motifs of a serine proteinase, a nucleotide triphosphatase (NTPase), and an RNA helicase. A carboxy fragment of the HCV NS3 protein was purified and possessed RNA helicase activity. Detections from the amino terminus resulted in the protein becoming soluble. Deletions from the carboxy terminus do not result in a loss of helicase activity until at least 50 amino acids are deleted. The helicase activity requires ATP and divalent cations such as Mg2+ and Mn2+. The helicase activity was blocked by monoclonal antibody specific to the HCV NS3 protein.

摘要翻译： 丙型肝炎病毒（HCV）NS3蛋白含有丝氨酸蛋白酶，核苷酸三磷酸酶（NTPase）和RNA解旋酶的氨基酸基序。 HCV NS3蛋白的羧基片段被纯化并具有RNA解旋酶活性。 氨基末端的检测导致蛋白质变得可溶。 从羧基末端的缺失不会导致直到至少50个氨基酸被缺失的解旋酶活性丧失。 解旋酶活性需要ATP和二价阳离子如Mg 2+和Mn 2+。 解旋酶活性被针对HCV NS3蛋白特异性的单克隆抗体阻断。

公开(公告)号：US20050058982A1

公开(公告)日：2005-03-17

申请号：US10626879

申请日：2003-07-25

申请人： Jang Han ,  Mi-Young Seo ,  Michael Houghton

发明人： Jang Han ,  Mi-Young Seo ,  Michael Houghton

IPC分类号： C12N15/09 ,  A61K31/7105 ,  A61K31/711 ,  A61K38/00 ,  A61P31/12 ,  A61P31/16 ,  A61P31/20 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/113 ,  A61K48/00 ,  C12Q1/70

CPC分类号： C12N15/1131 ,  A61K31/711 ,  A61K38/00 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/334 ,  C12N2310/335 ,  C12N2310/3515 ,  C12N2310/53 ,  C12N2320/30 ,  Y02A50/463 ,  Y02A50/465

摘要： The present invention provides double-stranded RNA molecules that mediate RNA interference in target cells, preferably hepatic cells. The invention also provides double-stranded RNA molecules that are modified to be resistant to nuclease degradation, which inactivates a virus, and more specifically, hepatitis C virus (HCV). The invention also provides a method of using these modified RNA molecules to inactivate virus in mammalian cells and a method of making modified small interfering RNAs (siRNAs) using human Dicer.

摘要翻译： 本发明提供了介导靶细胞，优选肝细胞中的RNA干扰的双链RNA分子。 本发明还提供被修饰为对核酸酶降解具有抗性的双链RNA分子，其使病毒失活，更具体地，丙型肝炎病毒（HCV）。 本发明还提供了使用这些修饰的RNA分子来灭活哺乳动物细胞中的病毒的方法和使用人Dicer制备修饰的小干扰RNA（siRNA）的方法。

公开(公告)号：US06194140B1

公开(公告)日：2001-02-27

申请号：US08529169

申请日：1995-09-15

申请人： Michael Houghton ,  Qui-Lim Choo ,  Jang Han ,  Joonho Choe

发明人： Michael Houghton ,  Qui-Lim Choo ,  Jang Han ,  Joonho Choe

IPC分类号： C12Q100

CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K14/00 ,  C07K2319/00 ,  C12N9/0089 ,  C12N9/506 ,  C12N9/90 ,  C12N2770/24222

摘要： The Hepatitis C Virus (HCV) NS3 protein contains amino acid motifs of a serine proteinase, a nucleotide triphosphatase (NTPase), and an RNA helicase. A carboxy fragment of the HCV NS3 protein was purified and possessed RNA helicase activity. Deletions from the amino terminus resulted in the protein becoming soluble. Deletions from the carboxy terminus do not result in a loss of helicase activity until at least 50 amino acids are deleted. The helicase activity requires ATP and divalent cations such as Mg2+ and Mn2+. The helicase activity was blocked by monoclonal antibody specific to the HCV NS3 protein.

摘要翻译： 丙型肝炎病毒（HCV）NS3蛋白含有丝氨酸蛋白酶，核苷酸三磷酸酶（NTPase）和RNA解旋酶的氨基酸基序。 HCV NS3蛋白的羧基片段被纯化并具有RNA解旋酶活性。 从氨基末端的缺失导致蛋白质变得可溶。 从羧基末端的缺失不会导致直到至少50个氨基酸被缺失的解旋酶活性丧失。 解旋酶活性需要ATP和二价阳离子如Mg2 +和Mn2 +。 解旋酶活性被HCV NS3蛋白特异性的单克隆抗体阻断。

公开(公告)号：US5712088A

公开(公告)日：1998-01-27

申请号：US440769

申请日：1995-05-15

申请人： Michael Houghton ,  Qui-Lim Choo ,  George Kuo ,  Amy J. Weiner ,  Jang Han ,  Michael Steven Urdea ,  Bruce Duncan Irvine ,  Janice A. Kolberg

发明人： Michael Houghton ,  Qui-Lim Choo ,  George Kuo ,  Amy J. Weiner ,  Jang Han ,  Michael Steven Urdea ,  Bruce Duncan Irvine ,  Janice A. Kolberg

IPC分类号： C07K14/18 ,  C07K16/10 ,  C12Q1/68 ,  C12Q1/70 ,  C07H21/02 ,  C12N15/00 ,  C12P19/34

CPC分类号： C07K14/005 ,  C07K16/109 ,  C12Q1/6853 ,  C12Q1/6858 ,  C12Q1/701 ,  C12Q1/707 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/40 ,  C12N2770/24222

摘要： A new virus, Hepatitis C virus (HCV), which has proven to be the major etiologic agent of blood-borne NANBH, was discovered by Applicant. Reagents for isolating, amplifying, and detecting HCV polynucleotides are provided. These reagents are oligomers containing polynucleotide sequences which are capable of forming hybrid structures with HCV target polynucleotide sequences.

摘要翻译： 被证明是血液传播的NANBH的主要病原体的新型病毒丙型肝炎病毒（HCV）被申请人发现。 提供了用于分离，扩增和检测HCV多核苷酸的试剂。 这些试剂是含有能够与HCV靶多核苷酸序列形成杂交结构的多核苷酸序列的寡聚物。

公开(公告)号：US20220239253A1

公开(公告)日：2022-07-28

申请号：US17596643

申请日：2020-12-21

申请人： Jang Han Engineers, Inc.

发明人： Kyung Ho RYU ,  Won Dae RYU ,  Bong Gyu KIM

IPC分类号： H02S40/42 ,  H01L31/052

摘要： According to one embodiment, a cooling plate for a solar panel for cooling a solar panel comprises: a planar body positioned on the rear surface of a solar panel; and a fluid guide part comprising a plurality of flow paths for guiding a fluid for cooling the solar panel, between inlets formed on one side of the planar body and outlets formed on the other side of the planar body, wherein the surface of the planar body that comes into direct contact with a back sheet of the solar panel may be flat.

公开(公告)号：US20130081036A1

公开(公告)日：2013-03-28

申请号：US13620037

申请日：2012-09-14

申请人： Peter D. Cohen ,  Daniel A. Sanderson ,  Mikhail Seregine ,  Brett Kiefer ,  Jang Han Goo ,  Jeffrey P. Bezos

发明人： Peter D. Cohen ,  Daniel A. Sanderson ,  Mikhail Seregine ,  Brett Kiefer ,  Jang Han Goo ,  Jeffrey P. Bezos

IPC分类号： G06F9/50

CPC分类号： G06F9/5005 ,  G06Q10/06 ,  G06Q10/06311 ,  G06Q10/063112 ,  G06Q30/0601 ,  G06Q30/08 ,  G06Q40/04

摘要： A method, system, and computer-readable medium is described for facilitating interactions between task requesters who have tasks that are available to be performed and task performers who are available to perform tasks. In some situations, the tasks to be performed are human performance tasks that use cognitive and other mental skills of human task performers, such as to employ judgment, perception and/or reasoning skills of the human task performers. In addition, in some situations the available tasks are submitted by human task requesters via application programs that programmatically invoke one or more application program interfaces of an electronic marketplace in order to request that the tasks be performed and to receive corresponding results of task performance in a programmatic manner, so that an ensemble of unrelated human agents can interact with the electronic marketplace to collectively perform a wide variety and large number of tasks.

公开(公告)号：US07945469B2

公开(公告)日：2011-05-17

申请号：US10990949

申请日：2004-11-16

申请人： Peter D. Cohen ,  Daniel A. Sanderson ,  Mikhail Seregine ,  Brett Kiefer ,  Jang Han Goo ,  Jeffrey P. Bezos

发明人： Peter D. Cohen ,  Daniel A. Sanderson ,  Mikhail Seregine ,  Brett Kiefer ,  Jang Han Goo ,  Jeffrey P. Bezos

IPC分类号： G06F9/46

CPC分类号： G06F9/5005 ,  G06Q10/06 ,  G06Q10/06311 ,  G06Q10/063112 ,  G06Q30/0601 ,  G06Q30/08 ,  G06Q40/04

摘要： A method, system, and computer-readable medium is described for facilitating interactions between task requesters who have tasks that are available to be performed and task performers who are available to perform tasks. In some situations, the tasks to be performed are human performance tasks that use cognitive and other mental skills of human task performers, such as to employ judgment, perception and/or reasoning skills of the human task performers. In addition, in some situations the available tasks are submitted by human task requesters via application programs that programmatically invoke one or more application program interfaces of an electronic marketplace in order to request that the tasks be performed and to receive corresponding results of task performance in a programmatic manner, so that an ensemble of unrelated human agents can interact with the electronic marketplace to collectively perform a wide variety and large number of tasks.

摘要翻译： 描述了一种方法，系统和计算机可读介质，用于促进具有可执行任务的任务请求者与可执行任务的任务执行者之间的交互。 在某些情况下，要执行的任务是使用人类任务执行者的认知和其他心理技能的人类执行任务，例如采用人类任务执行者的判断，感知和/或推理技能。 此外，在某些情况下，可用任务由人工任务请求者通过程序化地调用电子市场的一个或多个应用程序接口的应用程序提交，以便请求执行任务并且接收相应的任务执行结果 使得一系列无关的人类代理可以与电子市场相互作用，共同执行各种各样的大量任务。