公开(公告)号：US08871737B2

公开(公告)日：2014-10-28

申请号：US13236435

申请日：2011-09-19

申请人： David Bernard Smith ,  Jerome Deval ,  Natalia Dyatkina ,  Leonid Beigelman ,  Guangyi Wang

发明人： David Bernard Smith ,  Jerome Deval ,  Natalia Dyatkina ,  Leonid Beigelman ,  Guangyi Wang

IPC分类号： A61K31/70 ,  C07H19/04 ,  C07H19/10 ,  C07H19/20 ,  C07H19/06 ,  A61K31/7072 ,  C07H19/16 ,  A61K45/06 ,  A61K31/7076

CPC分类号： C07H19/10 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61K45/06 ,  C07H19/06 ,  C07H19/16 ,  C07H19/20 ,  Y02A50/414 ,  Y02A50/465 ,  A61K2300/00

摘要： Disclosed herein are phosphorothioate nucleotide analogs, such as thiophosphoroamidate prodrugs and thiophosphates (including α-thiomonophosphates, α-thiodiphosphates, and α-thiotriphosphates), methods of synthesizing phosphorothioate nucleotide analogs, such as thiophosphoramidate prodrugs, and thiophosphates and methods of treating viral infections, such as HCV, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs, such as thiophosphoramidate prodrugs, and thiophosphates.

摘要翻译： 本文公开了硫代磷酸酯核苷酸类似物，例如硫代磷酰胺酸酯前药和硫代磷酸酯（包括α-硫代磷酸酯，α-硫代二磷酸酯和α-硫代三磷酸酯），合成硫代磷酸酯核苷酸类似物如硫代磷酰胺酸酯前药和硫代磷酸酯的方法和治疗病毒感染的方法， 例如具有硫代磷酸酯核苷酸类似物的HCV，癌症和/或寄生虫病，例如硫代磷酰胺酸酯前药和硫代磷酸酯。

公开(公告)号：US08772474B2

公开(公告)日：2014-07-08

申请号：US13332068

申请日：2011-12-20

申请人： Leonid Beigelman ,  David Bernard Smith ,  Jerome Deval ,  Vivek Kumar Rajwanshi

发明人： Leonid Beigelman ,  David Bernard Smith ,  Jerome Deval ,  Vivek Kumar Rajwanshi

IPC分类号： C07H19/00 ,  C07H19/20 ,  C07H19/04 ,  A01N43/04 ,  A61K31/70

CPC分类号： C07H19/20 ,  A61K31/14 ,  A61K31/513 ,  A61K31/52 ,  A61K31/685 ,  A61K31/7072 ,  A61K31/7076 ,  A61K45/06 ,  C07F9/65744 ,  C07H17/02 ,  C07H19/10 ,  C07H19/11 ,  C07H19/213 ,  Y02A50/414 ,  Y02A50/465 ,  A61K2300/00

摘要： Disclosed herein are cyclic nucleotide analogs, methods of synthesizing cyclic nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with cyclic nucleotide analogs.

摘要翻译： 本文公开了环状核苷酸类似物，合成环状核苷酸类似物的方法和用环状核苷酸类似物治疗疾病和/或病症如病毒感染，癌症和/或寄生虫病的方法。

公开(公告)号：US20130123334A1

公开(公告)日：2013-05-16

申请号：US13595519

申请日：2012-08-27

申请人： Elena Feinstein ,  Husevin Aygun ,  Rami Skaliter ,  Hagar Kalinski ,  Igor Mett ,  James McSwiggen ,  Leonid Beigelman

发明人： Elena Feinstein ,  Husevin Aygun ,  Rami Skaliter ,  Hagar Kalinski ,  Igor Mett ,  James McSwiggen ,  Leonid Beigelman

IPC分类号： 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程度的方法，包括向需要治疗的受试者施用此类疾病或病症 和/或治疗有效剂量的化合物或药物组合物的症状，从而治疗受试者。

公开(公告)号：US20130012567A1

公开(公告)日：2013-01-10

申请号：US13471857

申请日：2012-05-15

申请人： James McSwigen ,  Leonid Beigelman

发明人： James McSwigen ,  Leonid Beigelman

IPC分类号： A61K31/713 ,  A61P31/14 ,  A61P35/00 ,  A61P31/20 ,  C07H21/02 ,  A61P1/16

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 ,  Y02A50/393 ,  C12N2310/3521

摘要： The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified 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 target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

公开(公告)号：US08242257B2

公开(公告)日：2012-08-14

申请号：US13081362

申请日：2011-04-06

申请人： Leonid Beigelman ,  James McSwiggen

发明人： Leonid Beigelman ,  James McSwiggen

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

CPC分类号： C12N15/111 ,  A61K9/0019 ,  A61K9/0048 ,  A61K47/544 ,  A61K47/549 ,  A61K47/554 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/51 ,  C12N2310/3521

摘要： The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified 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 target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

公开(公告)号：US08119592B2

公开(公告)日：2012-02-21

申请号：US12089895

申请日：2006-10-10

申请人： Leonid Beigelman ,  Scott D. Seiwert ,  Lawrence Blatt ,  Steven Andrews ,  Julia Haas

发明人： Leonid Beigelman ,  Scott D. Seiwert ,  Lawrence Blatt ,  Steven Andrews ,  Julia Haas

IPC分类号： A61K38/12

CPC分类号： C07D487/04 ,  C07D471/04

摘要： Macrocyclic compounds having the structures described herein are 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.

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。

公开(公告)号：US08013143B2

公开(公告)日：2011-09-06

申请号：US12334163

申请日：2008-12-12

申请人： James McSwiggen ,  Leonid Beigelman

发明人： James McSwiggen ,  Leonid Beigelman

IPC分类号： C07H21/04

CPC分类号： C12N15/1138 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3521

摘要： This invention relates to compounds, compositions, and methods useful for modulating chemokine receptor (CXCR) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of CXCR gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features 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 and methods used to modulate the expression of CXCR genes such as CXCR4 and CXCR7A.

摘要翻译： 本发明涉及使用短干扰核酸（siNA）分子调节趋化因子受体（CXCR）基因表达的化合物，组合物和方法。 本发明还涉及可用于通过使用小核酸分子调节涉及CXCR基因表达和/或通过RNA干扰（RNAi）的活性的其它基因的其他基因的表达和活性的化合物，组合物和方法。 特别地，本发明的特征在于小核酸分子，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） ）分子和用于调节CXCR基因如CXCR4和CXCR7A的表达的方法。

公开(公告)号：US08008472B2

公开(公告)日：2011-08-30

申请号：US12777767

申请日：2010-05-11

申请人： James McSwiggen ,  Leonid Beigelman

发明人： James McSwiggen ,  Leonid Beigelman

IPC分类号： C07H21/02 ,  C07H21/04 ,  A61K31/70 ,  C12Q1/68

CPC分类号： C12N15/1132 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3521 ,  C12N2310/3533

摘要： This invention relates to compounds, compositions, and methods useful for modulating human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of human immunodeficiency virus (HIV) gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features 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 and methods used to modulate the expression of HIV genes. The small nucleic acid molecules are useful in the treatment of HIV infection, AIDS, and/or disease and conditions related to HIV infection and/or AIDS in a subject or organism.

摘要翻译： 本发明涉及可用于使用短干扰核酸（siNA）分子调节人免疫缺陷病毒（HIV）基因表达的化合物，组合物和方法。 本发明还涉及可用于通过使用小核酸分子调节涉及人免疫缺陷病毒（HIV）基因表达和/或通过RNA干扰（RNAi）的活性的其它基因的其他基因的表达和活性的化合物，组合物和方法。 特别地，本发明的特征在于小核酸分子，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） ）分子和用于调节HIV基因表达的方法。 小核酸分子可用于治疗受试者或生物体中的HIV感染，AIDS和/或与HIV感染和/或AIDS相关的疾病和病症。

公开(公告)号：US07985853B2

公开(公告)日：2011-07-26

申请号：US12777913

申请日：2010-05-11

申请人： James McSwiggen ,  Leonid Beigelman

发明人： James McSwiggen ,  Leonid Beigelman

IPC分类号： C07H21/04 ,  C07H21/02 ,  A61K31/70 ,  C12Q1/68

CPC分类号： C07H21/02 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/14

摘要： This invention relates to compounds, compositions, and methods useful for modulating platelet derived growth factor (PDGF) and/or platelet derived growth factor receptor (PDGFr) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of platelet derived growth factor (PDGF) and/or platelet derived growth factor receptor (PDGFr) gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features 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 and methods used to modulate the expression of platelet derived growth factor (PDGF) and/or platelet derived growth factor receptor (PDGFr) genes, such as PDGF and/or PDGFr.

摘要翻译： 本发明涉及使用短干扰核酸（siNA）分子调节血小板衍生生长因子（PDGF）和/或血小板衍生生长因子受体（PDGFr）基因表达的化合物，组合物和方法。 本发明还涉及可用于调节参与血小板衍生生长因子（PDGF）和/或血小板衍生生长因子受体（PDGFr）基因表达和/或活性的途径的其它基因的表达和活性的化合物，组合物和方法， 使用小核酸分子的RNA干扰（RNAi）。 特别地，本发明的特征在于小核酸分子，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） ）分子和用于调节血小板衍生生长因子（PDGF）和/或血小板衍生生长因子受体（PDGFr）基因如PDGF和/或PDGFr的表达的方法。

公开(公告)号：US07977472B2

公开(公告)日：2011-07-12

申请号：US12765450

申请日：2010-04-22

申请人： Leonid Beigelman ,  James McSwiggen

发明人： Leonid Beigelman ,  James McSwiggen

IPC分类号： C07H21/04

CPC分类号： C12N15/113 ,  A61K31/7105 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  C07H21/02 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3521

摘要： This invention relates to compounds, compositions, and methods useful for modulating myostatin (GDF8) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of myostatin gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features 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 and methods used to modulate the expression of myostatin genes.

摘要翻译： 本发明涉及使用短干扰核酸（siNA）分子调节肌生成抑制素（GDF8）基因表达的化合物，组合物和方法。 本发明还涉及可用于通过使用小核酸分子调节涉及肌肉生长抑制素基因表达和/或通过RNA干扰（RNAi）的活性的其它基因的其它基因的表达和活性的化合物，组合物和方法。 特别地，本发明具有小的核酸分子，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） 用于调节肌生成抑制素基因表达的分子和方法。