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1. 发明申请

WO2012078536A2 DOUBLE STRANDED OLIGONUCLEOTIDE COMPOUNDS COMPRISING POSITIONAL MODIFICATIONS 审中-公开
标题翻译：包含位置修饰的双重拉链寡核苷酸化合物
公开(公告)号：WO2012078536A2
公开(公告)日：2012-06-14
申请号：PCT/US2011063365
申请日：2011-12-06
申请人： QUARK PHARMACEUTICALS INC , AVKIN-NACHUM SHARON , FEINSTEIN ELENA , BEIGELMAN LEONID
发明人： AVKIN-NACHUM SHARON , FEINSTEIN ELENA , BEIGELMAN LEONID
IPC分类号： C12N15/11 , C07H21/00
CPC分类号： C12N15/1137 , C12N15/111 , C12N2310/14 , C12N2310/31 , C12N2310/314 , C12N2310/317 , C12N2310/319 , C12N2310/321 , C12N2310/323 , C12N2310/332 , C12N2310/335 , C12N2320/51 , C12N2310/3521
摘要： Disclosed herein are double stranded RNA molecules which have been modified to exhibit one of the following, increased activity, enhanced nuclease stability, reduced off target activity and or reduced immunogenicity, to pharmaceutical compositions comprising such compounds and to methods of use. Further disclosed is a method for the synthesis of threose nucleic acid phosphoramidites and methods of use thereof.
摘要翻译：本文公开了双链RNA分子，其被修饰以显示下列之一，增加的活性，增强的核酸酶稳定性，降低的靶活性和/或降低的免疫原性，包括这些化合物的药物组合物和使用方法。进一步公开了一种合成苏氨酸核酸亚磷酰胺的方法及其使用方法。

2. 发明申请

WO2009044392A3 NOVEL SIRNA STRUCTURES 审中-公开
标题翻译：新的SIRNA结构
公开(公告)号：WO2009044392A3
公开(公告)日：2010-03-04
申请号：PCT/IL2008001197
申请日：2008-09-04
申请人： QUARK PHARMACEUTICALS INC , FEINSTEIN ELENA , AYGUN HUSEYIN , SKALITER RAMI , KALINSKI HAGAR , METT IGOR , MCSWIGGEN JAMES , BEIGELMAN LEONID
发明人： FEINSTEIN ELENA , AYGUN HUSEYIN , SKALITER RAMI , KALINSKI HAGAR , METT IGOR , MCSWIGGEN JAMES , BEIGELMAN LEONID
IPC分类号： A61K31/7088 , C07H21/02
CPC分类号： C07H21/02 , C12N15/111 , C12N2310/14 , C12N2310/319 , C12N2310/321 , C12N2310/3231 , C12N2310/332 , C12N2310/346 , C12N2320/51 , C12N2310/3521
摘要： The invention relates to siRNA compounds possessing novel sequences and structural motifs which down-regulate the expression of specific human genes. The invention also relates to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The present invention also provides a method of treating and/or preventing the incidence or severity of various diseases or conditions associated with the genes and/or symptoms associated with such diseases or conditions comprising administering to a subject in need of treatment for such disease or condition and/or symptom the compound or the pharmaceutical composition in a therapeutically effective dose so as to thereby treat the subject.
摘要翻译：本发明涉及具有下调特定人基因表达的新型序列和结构基序的siRNA化合物。本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。本发明还提供了治疗和/或预防与这些疾病或病症相关的基因和/或症状相关的各种疾病或病症的发生率或严重性的方法，包括对需要治疗的疾病或病症和/或以治疗有效剂量症状化合物或药物组合物，从而治疗受试者。

3. 发明申请

WO2008005511A8 NOVEL INHIBITORS OF HEPATITIS C VIRUS REPLICATION 审中-公开
标题翻译： HEPATITIS C VIRUS REPLICATION的新型抑制剂
公开(公告)号：WO2008005511A8
公开(公告)日：2009-03-19
申请号：PCT/US2007015530
申请日：2007-07-05
申请人： INTERMUNE INC , ARRAY BIOPHARMA INC , BLATT LAWRENCE M , SEIWERT SCOTT , BEIGELMAN LEONID , KERCHER TIMOTHY , KENNEDY APRIL L , ANDREWS STEVEN W
发明人： BLATT LAWRENCE M , SEIWERT SCOTT , BEIGELMAN LEONID , KERCHER TIMOTHY , KENNEDY APRIL L , ANDREWS STEVEN W
IPC分类号： C07D231/56 , A61K31/4035 , A61K31/416 , A61K31/437 , A61P31/14 , C07D403/14 , C07D471/04
CPC分类号： C07D403/14 , C07D231/56 , C07D471/04
摘要： The embodiments provide compounds of the general Formula (I), as well as compositions, including pharmaceutical compositions, comprising a, subject compound. The embodiments provide compounds of the general Formula (II), as well as compositions, including pharmaceutical compositions, comprising a subject compound, The embodiments provide compounds of the general Formula (III), as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
摘要翻译：实施方案提供了通式（I）的化合物，以及包含主题化合物的组合物，包括药物组合物。实施方案提供了通式（II）的化合物，以及包含主题化合物的组合物，包括药物组合物。实施方案提供了通式（III）的化合物，以及包含药物组合物的组合物，其包含受试者复合。实施方案还提供治疗方法，包括治疗丙型肝炎病毒感染的方法和治疗肝纤维化的方法，所述方法通常涉及向有需要的个体施用有效量的主题化合物或组合物。

4. 发明申请

WO2007044893A3 COMPOUNDS AND METHODS FOR INHIBITING HEPATITIS C VIRAL REPLICATION 审中-公开
标题翻译：用于抑制乙型肝炎病毒复制的化合物和方法
公开(公告)号：WO2007044893A3
公开(公告)日：2008-10-02
申请号：PCT/US2006040049
申请日：2006-10-10
申请人： INTERMUNE INC , ARRAY BIOPHARMA INC , BEIGELMAN LEONID , SEIWERT SCOTT D , BLATT LAWRENCE M , ANDREWS STEVEN , HAAS JULIA
发明人： BEIGELMAN LEONID , SEIWERT SCOTT D , BLATT LAWRENCE M , ANDREWS STEVEN , HAAS JULIA
IPC分类号： C07D471/04 , A61K31/407 , A61P31/14 , C07D487/04
CPC分类号： C07D487/04 , C07D471/04
摘要： Macrocyclic compounds having the structures described herein arc useful for inhibiting replication of the hepatitis C virus (HCV). In preferred embodiments, the compounds are active against both the NS3 protease and the NS3 helicase of HCV. Formulae (I), (II), (III), (IV) and (V).
摘要翻译：具有本文所述结构的大环化合物可用于抑制丙型肝炎病毒（HCV）的复制。在优选的实施方案中，所述化合物对NS3蛋白酶和HCV的NS3解旋酶均有活性。式（I），（II），（III），（IV）和（V）。

5. 发明申请

WO2008005511A3 NOVEL INHIBITORS OF HEPATITIS C VIRUS REPLICATION 审中-公开
标题翻译： HEPATITIS C VIRUS REPLICATION的新型抑制剂
公开(公告)号：WO2008005511A3
公开(公告)日：2008-07-31
申请号：PCT/US2007015530
申请日：2007-07-05
申请人： INTERMUNE INC , ARRAY BIOPHARMA INC , BLATT LAWRENCE M , SEIWERT SCOTT , BEIGELMAN LEONID , KERCHER TIMOTHY , KENNEDY APRIL L , ANDREWS STEVEN W
发明人： BLATT LAWRENCE M , SEIWERT SCOTT , BEIGELMAN LEONID , KERCHER TIMOTHY , KENNEDY APRIL L , ANDREWS STEVEN W
IPC分类号： C07D231/56 , A61K31/4035 , A61K31/416 , A61K31/437 , A61P31/14 , C07D403/14 , C07D471/04
CPC分类号： C07D403/14 , C07D231/56 , C07D471/04
摘要： The embodiments provide compounds of the general Formula (I), as well as compositions, including pharmaceutical compositions, comprising a, subject compound. The embodiments provide compounds of the general Formula (II), as well as compositions, including pharmaceutical compositions, comprising a subject compound, The embodiments provide compounds of the general Formula (III), as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
摘要翻译：实施方案提供了通式（I）的化合物，以及包含主题化合物的组合物，包括药物组合物。实施方案提供了通式（II）的化合物，以及包含主题化合物的组合物，包括药物组合物。实施方案提供了通式（III）的化合物，以及包含药物组合物的组合物，其包含受试者复合。实施方案还提供治疗方法，包括治疗丙型肝炎病毒感染的方法和治疗肝纤维化的方法，所述方法通常涉及向有需要的个体施用有效量的主题化合物或组合物。

6. 发明申请

WO2007022369A3 CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID MOLECULES THAT MEDIATE RNA INTERFERENCE 审中-公开
标题翻译：化学修饰的短暂干扰RNA干扰的核酸分子
公开(公告)号：WO2007022369A3
公开(公告)日：2007-07-26
申请号：PCT/US2006032168
申请日：2006-08-17
申请人： SIRNA THERAPEUTICS INC , MORRISEY DAVID , MCSWIGGEN JAMES , BEIGELMAN LEONID
发明人： MORRISEY DAVID , MCSWIGGEN JAMES , BEIGELMAN LEONID
IPC分类号： C07K14/02 , C12N15/11 , C12N15/113
CPC分类号： C12N15/1131 , C12N15/111 , C12N2310/14 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/3521
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce diseases, traits and conditions that are associated with gene expression or activity in a subject or organism.
摘要翻译：本发明涉及用于研究，诊断和治疗对基因表达和/或活性调节作出反应的性状，疾病和病症的化合物，组合物和方法。本发明还涉及与涉及参与基因表达途径的基因的表达和/或活性的调节作用的性状，疾病和病症相关的化合物，组合物和方法，或调节其维持或发展的其他细胞过程性状，疾病和状况。具体地说，本发明涉及包括小核酸分子如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）和双链RNA 能够介导基因表达的RNA干扰（RNAi）的短发夹RNA（shRNA）分子，包括这种小核酸分子的这种小核酸分子的混合物和这种小核酸分子的脂质纳米颗粒（LNP）制剂。本发明还涉及可以抑制内源性微RNA（miRNA）（例如miRNA抑制剂）或内源性短干扰RNA（例如miRNA抑制剂）的内源性RNA分子的功能的小核酸分子，例如siNA，siRNA等， siRNA）（例如siRNA抑制剂）或可以通过干扰与这些内源性RNA（例如RISC）相关的内源性RNA或蛋白质的调节功能来调节基因表达来调节基因表达（例如，RISC抑制剂），包括这种小核酸分子的鸡尾酒和这种小核酸分子的脂质纳米颗粒（LNP）制剂。这样的小核酸分子并且可用于例如提供组合物以预防，抑制或减少与受试者或生物体中的基因表达或活性相关的疾病，性状和病症。

7. 发明申请

WO2006122154A3 PYRIDONE DERIVATIVES FOR MODULATING STRESS-ACTIVATED PROTEIN KINASE SYSTEM 审中-公开
标题翻译：用于调节应激激活蛋白激酶系统的吡啶酮衍生物
公开(公告)号：WO2006122154A3
公开(公告)日：2007-07-26
申请号：PCT/US2006017988
申请日：2006-05-09
申请人： INTERMUNE INC , BLATT LAWRENCE M , SEIWERT SCOTT D , BEIGELMAN LEONID , RADHAKRISHNAN RAMACHANDRAN
发明人： BLATT LAWRENCE M , SEIWERT SCOTT D , BEIGELMAN LEONID , RADHAKRISHNAN RAMACHANDRAN
IPC分类号： A61K31/44 , A61K31/4412 , A61K31/4704 , A61P9/00 , A61P11/00 , A61P13/12 , A61P29/00 , A61P43/00
CPC分类号： A61K31/4412 , A61K31/44 , A61K31/444 , A61K31/45 , A61K31/4704 , A61K31/7052 , C07D213/16 , C07D213/26 , C07D213/63 , C07D213/64 , C07D213/69 , C07D215/227 , C07H15/26
摘要： Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.
摘要翻译：公开了用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物表现出低的抑制至少一种p38MAPK的能力; 并且其中所述接触以对所述化合物抑制所述至少一种p38MAPK的低百分比抑制浓度的SAPK调节浓度进行。还公开了吡非尼酮的衍生物。这些衍生物可调节应激活化蛋白激酶（SAPK）系统。

8. 发明申请

WO2009142842A2 NOVEL MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS REPLICATION 审中-公开
标题翻译： HEPATITIS C病毒复制的新型MACROCYCLIC抑制剂
公开(公告)号：WO2009142842A2
公开(公告)日：2009-11-26
申请号：PCT/US2009040565
申请日：2009-04-14
申请人： INTERMUNE INC , SEIWERT SCOTT , BEIGELMAN LEONID , BUCKMAN BRAD , STOYCHEVA ANTITSA DIMITROVA , PORTER STEVEN B , BRADFORD WILLIAMSON ZIEGLER , SEREBRYANY VLADIMIR
发明人： SEIWERT SCOTT , BEIGELMAN LEONID , BUCKMAN BRAD , STOYCHEVA ANTITSA DIMITROVA , PORTER STEVEN B , BRADFORD WILLIAMSON ZIEGLER , SEREBRYANY VLADIMIR
IPC分类号： A61K38/21 , A61K31/407 , A61K31/4709 , A61K31/4725 , A61K31/4738 , A61K31/517 , A61K31/7056 , C07D245/04 , C12N9/99
CPC分类号： C07D471/04 , A61K31/407 , A61K31/4709 , A61K31/4725 , A61K31/4738 , A61K31/517 , A61K31/7056 , A61K38/212 , A61K38/217 , A61K45/06 , C07D487/04 , C07K5/123 , A61K2300/00
摘要： The embodiments provide compounds of the general Formulae I, II, EI, IV, V, VI, VII, and X, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods enerally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
摘要翻译：实施方案提供了通式I，II，EI，IV，V，VI，VII和X的化合物，以及包含主题化合物的组合物，包括药物组合物。实施方案进一步提供治疗方法，包括治疗丙型肝炎病毒感染的方法和治疗肝纤维化的方法，所述方法主要涉及向有需要的个体施用有效量的受试化合物或组合物。

9. 发明申请

WO03070972A2 RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) 审中-公开
标题翻译： RNA干扰介导的抑制染色体转录基因表达使用短暂的核酸（siNA）
公开(公告)号：WO03070972A2
公开(公告)日：2003-08-28
申请号：PCT/US0305234
申请日：2003-02-20
申请人： RIBOZYME PHARM INC , MCSWIGGEN JAMES , BEIGELMAN LEONID , CHOWRIRA BHARAT
发明人： MCSWIGGEN JAMES , BEIGELMAN LEONID , CHOWRIRA BHARAT
IPC分类号： A61K38/00 , C12N15/113 , C12Q
CPC分类号： C12N15/1135 , C12N2310/111 , C12N2310/14 , C12N2310/315 , C12N2310/317 , C12N2310/318 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/346 , C12N2310/53 , C12N2310/3521
摘要： The present invention concerns methods and reagents useful in modulating modulating chromosomal translocation gene expression gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against modulating chromosomal translocation gene expression and/or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of BCR-ABL, TEL-AML1, EWS-FLI1, TLS-FUS, PAX3-FKHR, and/or AML1-ETO fusion gene expression or activity.
摘要翻译：本发明涉及可用于调节在各种应用中调节染色体易位基因表达基因表达的方法和试剂，包括用于治疗，诊断，靶标验证和基因组发现应用。具体而言，本发明涉及小核酸分子，如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）和短发夹RNA（shRNA）能够介导RNA干扰（RNAi）以调节染色体易位基因表达和/或活性的分子。小核酸分子可用于诊断和治疗癌症，增殖性疾病以及响应BCR-ABL，TEL-AML1，EWS-FLI1，TLS-FUS，PAX3-FKHR的调节的任何其它疾病或病症，以及 /或AML1-ETO融合基因表达或活性。

10. 发明申请

WO03070914A2 RNA INTERFERENCE MEDIATED INHIBITION OF FOS GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID siNA 审中-公开
标题翻译： RNA干扰介导的抑制FOS基因表达使用短暂的干扰核酸siNA
公开(公告)号：WO03070914A2
公开(公告)日：2003-08-28
申请号：PCT/US0305162
申请日：2003-02-20
申请人： SIRNA THERAPEUTICS INC , MCSWIGGEN JAMES , BEIGELMAN LEONID
发明人： MCSWIGGEN JAMES , BEIGELMAN LEONID
IPC分类号： C12N15/09 , A61K31/7088 , A61K31/7105 , A61K31/711 , A61K31/7115 , A61K31/712 , A61K31/7125 , A61K31/713 , A61K38/00 , A61K47/48 , A61K48/00 , A61P1/00 , A61P1/04 , A61P1/16 , A61P3/00 , A61P3/10 , A61P11/06 , A61P13/08 , A61P13/10 , A61P13/12 , A61P17/00 , A61P17/02 , A61P19/00 , A61P19/02 , A61P21/00 , A61P25/00 , A61P25/02 , A61P25/28 , A61P27/02 , A61P27/16 , A61P29/00 , A61P31/00 , A61P31/04 , A61P31/10 , A61P31/12 , A61P31/14 , A61P31/16 , A61P31/18 , A61P31/20 , A61P31/22 , A61P35/00 , A61P35/02 , A61P37/00 , A61P37/04 , A61P37/06 , A61P37/08 , A61P43/00 , C07H21/02 , C07H21/04 , C12N15/11 , C12N15/113 , C12N15/82 , C12N
CPC分类号： C12N15/8218 , A61K38/00 , A61K47/54 , C07H21/02 , C12N15/111 , C12N15/1131 , C12N15/1138 , C12N2310/111 , C12N2310/14 , C12N2310/315 , C12N2310/317 , C12N2310/318 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/344 , C12N2310/346 , C12N2310/53 , C12N2320/51 , C12N2330/30 , C12N2310/3521
摘要： The present invention concerns methods and reagents useful in modulating c-fos gene expression in a variety of applications, including use of therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid siNA, short interfering RNA siRNA, double-stranded RNA dsRNA, micro-RNA miRNA, and short hairpin RNA shRNA molecules capable of mediating RNA interference RNAi against c-fos gene expression and/ activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of c-fos expression or activity.
摘要翻译：本发明涉及可用于调节各种应用中的c-fos基因表达的方法和试剂，包括使用治疗，诊断，靶标验证和基因组发现应用。具体地说，本发明涉及能够介导RNA干扰RNAi的小核酸分子，例如短干扰核酸siNA，短干扰RNA siRNA，双链RNA dsRNA，微RNA miRNA和短发夹RNA shRNA分子， fos基因表达和/活性。小核酸分子可用于诊断和治疗癌症，增殖性疾病以及对c-fos表达或活性调节作出反应的任何其它疾病或病症。

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