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1. 发明申请

WO2006039656A3 MODIFIED SMALL INTERFERING RNA MOLECULES AND METHODS OF USE 审中-公开
标题翻译：改良的小干扰RNA分子及其使用方法
公开(公告)号：WO2006039656A3
公开(公告)日：2007-02-01
申请号：PCT/US2005035493
申请日：2005-09-30
申请人： CHIRON CORP , HAN JANG , HOUGHTON MICHAEL
发明人： HAN JANG , HOUGHTON MICHAEL
IPC分类号： A61K48/00 , A61K31/22 , A61K31/7105 , C12N15/113 , C12Q1/70
CPC分类号： C12N15/1131 , A61K38/00 , C12N2310/14 , C12N2310/322 , C12N2310/334 , C12N2310/335 , C12N2310/3515
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。

2. 发明专利

JPH1089A DIAGNOSIS OF NANBV: POLYNUCLEOTIDE USEFUL FOR SCREENING HEPATITIS C VIRUS 失效
公开(公告)号：JPH1089A
公开(公告)日：1998-01-06
申请号：JP30570796
申请日：1996-10-30
申请人： CHIRON CORP
发明人： HOUGHTON MICHAEL , QUI-LIM CHOO , KUO GEORGE , HAN JANG , URDEA MICHAEL S , WEINER AMY J
IPC分类号： C12N15/09 , A61K39/00 , C07K14/18 , C12N15/40 , C12N15/51 , C12Q1/68 , C12Q1/70 , C12R1/93 , G01N33/576
摘要： PROBLEM TO BE SOLVED: To obtain a new polynucleotide capable of selectively hybridizing with the polynucleotide sequence of hepatitis C virus (HCV), thus useful as e.g. a probe for detectting HCV polynucleotide, and to be used for e.g. diagnosing hepatitis non-A non-B virus (NANBV). SOLUTION: This new polynucleotide has a 10 or more nucleotides- consecutive sequence consisting of either chain of nucleotide sequences of formula I and formula II, being capable of selectively hybridizing with the polynucleotide sequence of HCV. This new polynucleotide is useful as a polynucleotide probe for detecting the polynucleotide of HCV, a PCR primer for amplifying the polynucleotide, etc., and enables infection diagnoses of NANBV. This new polynucleotide is obtained by preparing a cDNA library including a HCV cDNA sequence and by screening the library.

3. 发明申请

WO2004092360A3 THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 审中-公开
标题翻译：严重急性呼吸道综合症冠状病毒
公开(公告)号：WO2004092360A3
公开(公告)日：2005-08-04
申请号：PCT/US2004011710
申请日：2004-04-09
申请人： CHIRON CORP , RAPPUOLI RINO , MASIGNANI VEGA , STADLER KONRAD , GREGERSEN JENS-PETER , CHIEN DAVID , HAN JANG , POLO JOHN , WEINER AMY , HOUGHTON MICHAEL , SONG HYUN CHUL , SEO MI YOUNG , DONNELLY JOHN J , KLENK HANS DIETER , VALIANTE NICHOLAS
发明人： RAPPUOLI RINO , MASIGNANI VEGA , STADLER KONRAD , GREGERSEN JENS-PETER , CHIEN DAVID , HAN JANG , POLO JOHN , WEINER AMY , HOUGHTON MICHAEL , SONG HYUN CHUL , SEO MI YOUNG , DONNELLY JOHN J , KLENK HANS DIETER , VALIANTE NICHOLAS
IPC分类号： A61K35/76 , A61K38/16 , A61K39/00 , A61K39/215 , C07K14/165 , C07K16/10 , C12N7/06 , C12Q1/70
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/215 , A61K2039/5252 , A61K2039/545 , A61K2039/55505 , A61K2039/55511 , A61K2039/55566 , C07K16/10 , C07K2317/34 , C07K2317/76 , C07K2319/21 , C12N7/00 , C12N2770/20021 , C12N2770/20022 , C12N2770/20034 , C12N2770/20043 , C12N2770/20051 , C12N2770/20063 , C12Q1/701 , G01N2333/165 , G01N2469/20
摘要： An outbreak of a virulent respiratory virus, now known as Severe Acute Respiratory Syndrome (SARS), was identified in Hong Kong, China and a growing number of countries around the world in 2003. The invention relates to nucleic acids and proteins from the SARS coronavirus. These nucleic acids and proteins can be used in the preparation and manufacture of vaccine formulations, diagnostic reagents, kits, etc. The invention also provides methods for treating SARS by administering small molecule antiviral compounds, as well as methods of identifying potent small molecules for the treatment of SARS.
摘要翻译：在2003年，中国香港和世界各地越来越多的国家确定了现在称为严重急性呼吸综合征（SARS）的毒性呼吸道病毒的爆发。本发明涉及SARS冠状病毒的核酸和蛋白质。这些核酸和蛋白质可用于制备和制造疫苗制剂，诊断试剂，试剂盒等。本发明还提供了通过施用小分子抗病毒化合物治疗SARS的方法，以及鉴定用于治疗SARS的有效小分子的方法治疗SARS。

4. 发明申请

WO2006039656A9 MODIFIED SMALL INTERFERING RNA MOLECULES AND METHODS OF USE 审中-公开
标题翻译：改良的小干扰RNA分子及其使用方法
公开(公告)号：WO2006039656A9
公开(公告)日：2006-06-22
申请号：PCT/US2005035493
申请日：2005-09-30
申请人： CHIRON CORP , HAN JANG , HOUGHTON MICHAEL
发明人： HAN JANG , HOUGHTON MICHAEL
IPC分类号： C12N15/113
CPC分类号： C12N15/1131 , A61K38/00 , C12N2310/14 , C12N2310/322 , C12N2310/334 , C12N2310/335 , C12N2310/3515
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。

5. 发明申请

WO2004011647A8 MODIFIED SMALL INTERFERING RNA MOLECULES AND METHODS OF USE 审中-公开
标题翻译：修饰的小分子干扰RNA分子及其使用方法
公开(公告)号：WO2004011647A8
公开(公告)日：2004-06-10
申请号：PCT/US0323104
申请日：2003-07-25
申请人： CHIRON CORP , HAN JANG , SEO MI YOUNG , HOUGHTON MICHAEL
发明人： HAN JANG , SEO MI YOUNG , HOUGHTON MICHAEL
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 , C12N15/11
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
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 method of making modified small interfering RNAs (siRNAs) using human Dicer.
摘要翻译：本发明提供了在靶细胞，优选肝细胞中介导RNA干扰的双链RNA分子。本发明还提供经修饰以抵抗核酸酶降解的双链RNA分子，其使病毒失活，更具体而言，使丙型肝炎病毒（HCV）失活。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以及使用人类切丁酶制备修饰的小干扰RNA（siRNA）的方法。

6. 发明专利

JP2006320327A MODIFIED SMALL INTERFERING RNA MOLECULE AND METHOD OF USING THE SAME 审中-公开
公开(公告)号：JP2006320327A
公开(公告)日：2006-11-30
申请号：JP2006165652
申请日：2006-06-15
申请人： CHIRON CORP
发明人： HAN JANG , SEO MI-YOUNG , HOUGHTON MICHAEL
IPC分类号： C12N15/09 , A61K31/7105 , A61K31/711 , A61K31/713 , A61K38/00 , A61K48/00 , A61P1/16 , A61P11/00 , A61P31/12 , A61P31/14 , A61P31/16 , A61P31/20 , A61P43/00 , C07H21/02 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/113
摘要： PROBLEM TO BE SOLVED: To provide a modified small interfering RNA molecule, that is, to provide a double-stranded RNA(dsRNA) mediating RNA interference in a target cell, particularly to provide a small interfering RNA(siRNA) inhibiting the replication of virus in an infected cell. SOLUTION: A double-stranded RNA molecule mediating RNA interference in a target cell, preferably hepatocyte is provided. Another double-stranded RNA molecule deactivating a virus, more specifically, hepatitis C virus, and modified to be resistant to nuclease degradation. Besides, a method of using these modified RNA molecules for deactivating virus in mammalian cells and a method for making a small interfering RNA(siRNA) modified using human Dicer are also provided, respectively. COPYRIGHT: (C)2007,JPO&INPIT

7. 发明专利

JP2007300933A Hcv ns3 protein fragments having helicase activity and improved solubility 审中-公开
标题翻译：丙型肝炎病毒NS3蛋白质片段具有良好的抗凝活性和改善的溶解性
公开(公告)号：JP2007300933A
公开(公告)日：2007-11-22
申请号：JP2007164372
申请日：2007-06-21
申请人： Chiron Corp , カイロンコーポレイション
发明人： HAN JANG , CHOE JOONHO
IPC分类号： C12N9/00 , C12N15/09 , A61K38/00 , A61P31/20 , A61P43/00 , C07K14/00 , C07K14/18 , C07K19/00 , C12N1/21 , C12N9/02 , C12N9/22 , C12N9/50 , C12N9/90 , C12N15/00 , C12N15/57 , C12R1/19 , C12R1/92
CPC分类号： C07K14/005 , A61K38/00 , C07K14/00 , C07K2319/00 , C12N9/0089 , C12N9/506 , C12N9/90 , C12N2770/24222
摘要： PROBLEM TO BE SOLVED: To provide a recombinant hepatitis C virus (HCV) NS3 protein fragments having helicase activity and improved solubility, an HCV NS3 fusion protein fragment having helicase activity and improved solubility, a truncated and altered HCV NS3 protein fragment having helicase activity and improved solubility, a cloning and expression vector therefor, and a method for using these protein fragments in a screening assay to evaluate whether a compound inhibits RNA helicase activity and therefore can inhibit HCV duplication or not. SOLUTION: Disclosed is a truncated and purified HCV NS3 helicase fragment having a specific amino acid sequence or its mutants in which one or several amino acids are inserted, deleted or substituted, wherein the mutants retain helicase activity and are soluble. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：为了提供具有解旋酶活性和改善的溶解性的重组丙型肝炎病毒（HCV）NS3蛋白片段，具有解旋酶活性和改善的溶解性的HCV NS3融合蛋白片段，具有截短和改变的HCV NS3蛋白片段，其具有解旋酶活性和改善的溶解度，其克隆和表达载体，以及在筛选测定中使用这些蛋白质片段的方法来评估化合物是否抑制RNA解旋酶活性，因此可以抑制HCV复制。解决方案：公开了具有特定氨基酸序列的截短和纯化的HCV NS3解旋酶片段或其突变体，其中插入，缺失或取代一个或几个氨基酸，其中突变体保持解旋酶活性并且是可溶的。版权所有（C）2008，JPO＆INPIT

8. 发明专利

JP2006271388A Hcv ns3 protein fragment having helicase activity and improved solubility 审中-公开
标题翻译： HCV NS3蛋白质片段具有促凝活性和改善的溶解性
公开(公告)号：JP2006271388A
公开(公告)日：2006-10-12
申请号：JP2006129683
申请日：2006-05-08
申请人： Chiron Corp , カイロンコーポレイション
发明人： HAN JANG , CHOE JOONHO
IPC分类号： C12N9/00 , C12N15/09 , A61K38/00 , A61P31/20 , A61P43/00 , C07K14/00 , C07K14/18 , C07K19/00 , C12N1/21 , C12N9/02 , C12N9/22 , C12N9/50 , C12N9/90 , C12N15/00 , C12N15/57 , C12R1/19 , C12R1/92
CPC分类号： C07K14/005 , A61K38/00 , C07K14/00 , C07K2319/00 , C12N9/0089 , C12N9/506 , C12N9/90 , C12N2770/24222
摘要： PROBLEM TO BE SOLVED: To provide a recombinant HCV NS3 protein fragment having helicase activity and improved solubility, a fused HCV NS3 protein fragment having helicase activity and improved solubility and a truncated and modified HCV NS3 protein fragment having helicase activity and improved solubility. SOLUTION: The invention provides a truncated and refined hepatitis C virus (HCV) NS3 protein helicase fragment derived from HCV NS3 protein and having helicase activity and a specific amino acid sequence or its modified product obtained by the insertion, deletion or substitution of one or more amino acids. The modified product keeps the helicase activity and is soluble. COPYRIGHT: (C)2007,JPO&INPIT
摘要翻译：要解决的问题：为了提供具有解旋酶活性和改善溶解性的重组HCV NS3蛋白片段，具有解旋酶活性和改善溶解性的融合HCV NS3蛋白片段和具有解旋酶活性和改善的溶解度的截短和修饰的HCV NS3蛋白片段。解决方案：本发明提供了从HCV NS3蛋白衍生的具有解旋酶活性的截短和精制的丙型肝炎病毒（HCV）NS3蛋白解旋酶片段，以及通过插入，缺失或取代得到的特异性氨基酸序列或其修饰产物一个或多个氨基酸。经修饰的产品保持解旋酶的活性并可溶。版权所有（C）2007，JPO＆INPIT

9. 发明专利

JP2005143512A Novel hcv isolated strain 审中-公开
标题翻译：新型HCV分离菌株
公开(公告)号：JP2005143512A
公开(公告)日：2005-06-09
申请号：JP2005018955
申请日：2005-01-26
申请人： Chiron Corp , National Institute Of Infectious Diseases , カイロンコーポレイション , 国立感染症研究所長
发明人： MIYAMURA TATSUO , SAITO IZUMI , HOUGHTON MICHAEL , WEINER AMY J , HAN JANG , KOLBERG JANICE A , CHA TAI-AN , IRVINE BRUCE DUNCAN
IPC分类号： A61K38/00 , A61K39/00 , A61P31/12 , C07K14/00 , C07K14/02 , C07K14/10 , C07K14/18 , C07K16/00 , C12N1/21 , C12N15/09 , C12N15/40 , C12N15/51 , C12P21/02 , C12P21/08 , C12Q1/68 , C12R1/19 , G01N33/53 , G01N33/566 , G01N33/576 , G01N33/577
CPC分类号： C07K14/005 , A61K39/00 , C12N2770/24222
摘要： PROBLEM TO BE SOLVED: To provide a polynucleotide and polypeptide derived from a novel isolated strain and useful for diagnosis of Hepatitis C virus (HCV). SOLUTION: Disclosed are a probe and a primer for polynucleotide derived from an HCV isolated strain J1 or J7, and a polypeptide for detecting an antibody against J1 or J7. The probe and the primer contain a contiguous sequence comprising at least 8 nucleotides obtained from a polynucleotide sequence of J1 or J7 disclosed by the present invention, and are not homologous to the nucleotide sequence of isolated strain of HCV1. The polypeptide contains a contiguous sequence comprising at least 10 amino acids containing an antigenic determinant which may be bound by the antibody against J1 or J7, wherein the contiguous sequence is obtained from the amino acid sequence of J1 or J7 disclosed by the present invention, and comprises substitution of at least one amino acid in comparison with an amino acid sequence corresponding to the HCV1 sequence. COPYRIGHT: (C)2005,JPO&NCIPI
摘要翻译：待解决的问题：提供衍生自新型分离菌株并可用于诊断丙型肝炎病毒（HCV）的多核苷酸和多肽。解决方案：公开了衍生自HCV分离株J1或J7的多核苷酸的探针和引物，以及用于检测针对J1或J7的抗体的多肽。探针和引物含有包含从本发明公开的J1或J7的多核苷酸序列获得的至少8个核苷酸的连续序列，并且与HCV1的分离株的核苷酸序列不同源。该多肽含有包含至少10个氨基酸的连续序列，该氨基酸含抗原决定簇，该抗原决定簇可被针对J1或J7的抗体结合，其中连续序列由本发明公开的J1或J7的氨基酸序列获得，包括与对应于HCV1序列的氨基酸序列相比至少一个氨基酸的取代。版权所有（C）2005，JPO＆NCIPI

10. 发明专利

JP2004147661A Hcv ns3 protein fragment having helicase activity and improved solubility 审中-公开
标题翻译： HCV NS3蛋白质片段具有促凝活性和改善的溶解性
公开(公告)号：JP2004147661A
公开(公告)日：2004-05-27
申请号：JP2003418777
申请日：2003-12-16
申请人： Chiron Corp , カイロンコーポレイション
发明人： HAN JANG , CHOE JOONHO
IPC分类号： C12N15/09 , A61K38/00 , A61P31/20 , A61P43/00 , C07K14/00 , C07K14/18 , C07K19/00 , C12N1/21 , C12N9/00 , C12N9/02 , C12N9/22 , C12N9/50 , C12N9/90 , C12N15/00 , C12N15/57 , C12R1/19 , C12R1/92
CPC分类号： C07K14/005 , A61K38/00 , C07K14/00 , C07K2319/00 , C12N9/0089 , C12N9/506 , C12N9/90 , C12N2770/24222
摘要： PROBLEM TO BE SOLVED: To provide a recombinant HCV NS3 protein fragment having helicase activity and improved solubility, a fused HCV NS3 protein fragment having the helicase activity and the improved solubility, a truncated altered HCV NS3 protein fragment having the helicase activity and the improved solubility, cloning and expression vectors therefor and a method of using these protein fragments for screening assay to evaluate whether HCV replication can be inhibited by inhibition of RNA helicase activity through a compound. SOLUTION: Disclosed are a truncated purified hepatitis C virus (HCV) NS3 helicase fragment having a specific amino acid sequence and modifications thereof in which one or several amino acids are inserted, deleted or substituted, wherein the modifications retain the helicase activity and are soluble. COPYRIGHT: (C)2004,JPO
摘要翻译：待解决的问题：为了提供具有解旋酶活性和改善的溶解性的重组HCV NS3蛋白片段，具有解旋酶活性和改善的溶解性的融合HCV NS3蛋白片段，具有解旋酶活性的截短的改变的HCV NS3蛋白片段，以及改进的溶解度，克隆和表达载体以及使用这些蛋白质片段进行筛选测定以评估HCV复制是否可以通过化合物抑制RNA解旋酶活性而被抑制的方法。解决方案：公开了具有特定氨基酸序列及其修饰的截短的纯化丙型肝炎病毒（HCV）NS3解旋酶片段，其中插入，缺失或取代一个或几个氨基酸，其中所述修饰保留解旋酶活性，是可溶的。版权所有（C）2004，JPO

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