公开(公告)号：US20100093836A1

公开(公告)日：2010-04-15

申请号：US12524778

申请日：2008-01-29

申请人： Balkrishen Bhat ,  Eric E. Swayze ,  Walter F. Lima ,  Stanley T. Crooke

发明人： Balkrishen Bhat ,  Eric E. Swayze ,  Walter F. Lima ,  Stanley T. Crooke

IPC分类号： A61K31/7088 ,  C07H19/04 ,  C12N5/02

CPC分类号： C07H21/00 ,  C12N15/113 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2310/3533

摘要： The present invention includes compositions and methods useful for modulating protein expression. In certain embodiments, the present invention includes oligomeric compounds comprising modified nucleosides and modified internucleoside linkages.

摘要翻译： 本发明包括可用于调节蛋白质表达的组合物和方法。 在某些实施方案中，本发明包括包含修饰的核苷和经修饰的核苷间键的寡聚化合物。

公开(公告)号：US20090298174A1

公开(公告)日：2009-12-03

申请号：US12345780

申请日：2008-12-30

申请人： Christine Esau ,  Bridget Lollo ,  C. Frank Bennett ,  Susan M. Freier ,  Richard H. Griffey ,  Brenda F. Baker ,  Timothy A. Vickers ,  Eric G. Marcusson ,  Erich Koller ,  Eric E. Swayze ,  Ravi Jain ,  Balkrishen Bhat ,  Eigen Peralta

发明人： Christine Esau ,  Bridget Lollo ,  C. Frank Bennett ,  Susan M. Freier ,  Richard H. Griffey ,  Brenda F. Baker ,  Timothy A. Vickers ,  Eric G. Marcusson ,  Erich Koller ,  Eric E. Swayze ,  Ravi Jain ,  Balkrishen Bhat ,  Eigen Peralta

IPC分类号： C12N5/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/3181 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/11 ,  C12N2320/30 ,  C12N2320/50 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

公开(公告)号：US07547684B2

公开(公告)日：2009-06-16

申请号：US11747057

申请日：2007-05-10

申请人： Punit P. Seth ,  Eric E. Swayze ,  Balkrishen Bhat

发明人： Punit P. Seth ,  Eric E. Swayze ,  Balkrishen Bhat

IPC分类号： A01N43/04 ,  A61K31/70

CPC分类号： C07H19/04 ,  C07H21/00

摘要： The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.

摘要翻译： 本发明提供了包含这些核苷类似物中的至少一种的5'-修饰的双环核苷类似物和寡聚化合物。 在优选的实施方案中，核苷类似物在5'-碳上具有（R）或（S） - 亲和性。 这些双环核苷类似物可用于增强低聚化合物的性质，包括例如增强的核酸酶抗性。

公开(公告)号：US20090092981A1

公开(公告)日：2009-04-09

申请号：US12192847

申请日：2008-08-15

申请人： Eric E. Swayze ,  Andrew M. Siwkowski ,  Balkrishen Bhat ,  Thazha P. Prakash ,  Charles Allerson ,  Punit P. Seth

发明人： Eric E. Swayze ,  Andrew M. Siwkowski ,  Balkrishen Bhat ,  Thazha P. Prakash ,  Charles Allerson ,  Punit P. Seth

IPC分类号： A61K31/7105 ,  C07H19/06 ,  C12Q1/00 ,  C07H19/16

CPC分类号： C12N15/113 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  C12N15/111 ,  C12N2310/323 ,  C12N2320/51

摘要： The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

摘要翻译： 本公开描述了四氢吡喃核苷类似物，由其制备的低聚化合物和使用寡聚化合物的方法。 更具体地，提供四氢吡喃核苷类似物，其具有一个或多个手性取代基，其可用于增强低聚化合物的性质，包括核酸酶抗性和结合亲和力。 在一些实施方案中，本文提供的寡聚化合物与靶RNA的一部分杂交，导致靶RNA的正常功能丧失。

公开(公告)号：US20080207541A1

公开(公告)日：2008-08-28

申请号：US10592919

申请日：2005-03-15

申请人： Michael T. Migawa ,  Walter F. Lima ,  Eric E. Swayze ,  Joshua Nichols ,  Hongjiang Wu ,  Thazha P. Prakash ,  Tadeusz Krzysztof Wyrzykiewicz ,  Balkrishen Bhat ,  Stanley T. Crooke

发明人： Michael T. Migawa ,  Walter F. Lima ,  Eric E. Swayze ,  Joshua Nichols ,  Hongjiang Wu ,  Thazha P. Prakash ,  Tadeusz Krzysztof Wyrzykiewicz ,  Balkrishen Bhat ,  Stanley T. Crooke

IPC分类号： A61K31/70 ,  C12N15/87 ,  A61P43/00

CPC分类号： C12N15/85 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/321 ,  C12N2310/346 ,  C12N2310/3519 ,  C12N2310/3525

摘要： The present invention provides compositions and methods for the optimization of cleavage of RNA species by RNase H. In some embodiments, the invention provides oligonucleotides that possess two or more regions of differing conformation, and at least one transitional nucleobase positioned between the regions that is capable of modulating transfer of the helical conformation characteristic of the region bound to the 3′hydroxy thereof, to the region bound to the 5′ hydroxyl thereof.

摘要翻译： 本发明提供了通过RNA酶H优化RNA种类的切割的组合物和方法。在一些实施方案中，本发明提供具有不同构象的两个或更多个区域的寡核苷酸，以及位于能够区分的区域之间的至少一个过渡核碱基 调节与其3'-羟基结合的区域的螺旋构象特征转移到与其5'羟基结合的区域。

公开(公告)号：US07323449B2

公开(公告)日：2008-01-29

申请号：US10520925

申请日：2003-07-18

申请人： David B. Olsen ,  Balkrishen Bhat ,  Phillip Dan Cook

发明人： David B. Olsen ,  Balkrishen Bhat ,  Phillip Dan Cook

IPC分类号： C07D487/04 ,  A61K31/52 ,  A61K31/675 ,  C07F9/6561 ,  A61P31/14

CPC分类号： A61K45/06 ,  C07H19/14

摘要： The present invention provides thionucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such thionucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the thionucleoside compounds of the present invention.

摘要翻译： 本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷类化合物及其某些衍生物。 这些化合物是RNA依赖性RNA病毒复制的抑制剂，可用于治疗RNA依赖性RNA病毒感染。 它们特别可用作丙型肝炎病毒（HCV）NS5B聚合酶的抑制剂，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。 本发明还描述了单独或与其它对RNA依赖性RNA病毒感染（特别是HCV感染）有活性的试剂组合含有这样的硫代核苷化合物的药物组合物。 还公开了用本发明的硫代核苷化合物抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。

公开(公告)号：US20070179107A1

公开(公告)日：2007-08-02

申请号：US11565816

申请日：2006-12-01

申请人： Balkrishen Bhat ,  Thazha Parkash ,  Prasad Dande ,  Charles Allerson ,  Richard Griffey ,  Eric Swayze

发明人： Balkrishen Bhat ,  Thazha Parkash ,  Prasad Dande ,  Charles Allerson ,  Richard Griffey ,  Eric Swayze

IPC分类号： A61K48/00 ,  C12N15/09

CPC分类号： C12N15/113 ,  C07H21/02 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/30 ,  C12N2320/51 ,  C12N2310/3521

摘要： The present invention provides double stranded compositions wherein each strand is modified to have a motif defined by positioning of β-D-ribonucleosides and sugar modified nucleosides. More particularly, the present compositions comprise one strand having a gapped motif and another strand having a gapped motif, a hemimer motif, a blockmer motif, a fully modified motif, a positionally modified motif or an alternating motif. At least one of the strands has complementarity to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In some embodiments, the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

摘要翻译： 本发明提供双链组合物，其中每条链被修饰以具有通过定位β-D-核糖核苷和糖修饰核苷定义的基序。 更具体地，本发明的组合物包含一个具有间隙基序的链，另一个链具有间隙基序，半缩体基序，封闭基序，完全修饰的基序，位置修饰的基序或交替基序。 至少一条链与核酸靶具有互补性。 该组合物可用于靶向选定的核酸分子并调节一个或多个基因的表达。 在一些实施方案中，本发明的组合物与靶RNA的一部分杂交导致靶RNA的正常功能丧失。 本发明还提供了调节基因表达的方法。

公开(公告)号：US20070161547A1

公开(公告)日：2007-07-12

申请号：US10559636

申请日：2004-06-03

申请人： Balkrishen Bhat ,  Bharvin Patel ,  Eric Swayze

发明人： Balkrishen Bhat ,  Bharvin Patel ,  Eric Swayze

IPC分类号： A61K48/00 ,  C07H21/02

CPC分类号： C12N15/1135 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322

摘要： Compounds and compositions are provided for modulating the expression of survivin. The compounds, exemplified by those acting through an RNAi antisense mechanism of action, include double-stranded and single-stranded constructs, as well as siRNAs, canonical siRNAs, blunt-ended siRNAs and single-stranded antisense RNA compounds. Methods of using these compounds for modulation of survivin expression and for treatment of diseases associated with expression of survivin are provided.

摘要翻译： 提供化合物和组合物用于调节存活蛋白的表达。 由通过RNAi反义作用机制起作用的那些实例所列举的化合物包括双链和单链构建体，以及siRNA，典型siRNA，平端siRNA和单链反义RNA化合物。 提供了使用这些化合物调节存活蛋白表达和治疗与存活蛋白表达相关的疾病的方法。

公开(公告)号：US20060122154A1

公开(公告)日：2006-06-08

申请号：US10520925

申请日：2003-07-18

申请人： David Olsen ,  Balkrishen Bhat ,  Philip Cook

发明人： David Olsen ,  Balkrishen Bhat ,  Philip Cook

IPC分类号： A61K31/675 ,  A61K31/519 ,  C07D487/02 ,  C07F9/6512

CPC分类号： A61K45/06 ,  C07H19/14

摘要： The present invention provides thionucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such thionucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the thionucleoside compounds of the present invention.

摘要翻译： 本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷类化合物及其某些衍生物。 这些化合物是RNA依赖性RNA病毒复制的抑制剂，可用于治疗RNA依赖性RNA病毒感染。 它们特别可用作丙型肝炎病毒（HCV）NS5B聚合酶的抑制剂，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。 本发明还描述了单独或与其它对RNA依赖性RNA病毒感染（特别是HCV感染）有活性的试剂组合含有这样的硫代核苷化合物的药物组合物。 还公开了用本发明的硫代核苷化合物抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。

公开(公告)号：US09193752B2

公开(公告)日：2015-11-24

申请号：US13580218

申请日：2011-03-10

申请人： Michael T. Migawa ,  Thazha P. Prakash ,  Charles Allerson ,  Balkrishen Bhat ,  Punit P. Seth ,  Eric E. Swayze

发明人： Michael T. Migawa ,  Thazha P. Prakash ,  Charles Allerson ,  Balkrishen Bhat ,  Punit P. Seth ,  Eric E. Swayze

IPC分类号： C07H19/00 ,  C07H21/00 ,  C07H19/073 ,  C07H19/173 ,  C07H21/04 ,  C12N15/11

CPC分类号： C07H19/073 ,  C07H19/173 ,  C07H21/04 ,  C12N15/111 ,  C12N2310/3231

摘要： Provided herein are novel 5′-(S)—CH3 substituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5′-(S)—CH3 substituted bicyclic nucleosides includes a 2′ to 4′ bridging group. The 5′-(S)—CH3 substituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

摘要翻译： 本文提供了新的5' - （S）-CH 3取代的双环核苷，由其制备的低聚化合物和使用低聚化合物的方法。 更具体地，每个新的5' - （S）-CH 3取代的双环核苷的呋喃糖环包括2'至4'桥连基团。 预期5' - （S）-CH 3取代的双环核苷可用于增强所掺入的寡聚化合物的一种或多种性质，例如增加结合亲和力。 在某些实施方案中，本文提供的寡聚化合物与靶RNA的一部分杂交，导致靶RNA的正常功能丧失。