公开(公告)号：US20050272676A1

公开(公告)日：2005-12-08

申请号：US11200499

申请日：2005-08-09

申请人： Balkrishen Bhat ,  Anne Eldrup ,  Thazha Prakash ,  Phillip Cook ,  Robert LaFemina ,  Amy Simcoe ,  Carrie Rutkowski ,  Mario Valenciano

发明人： Balkrishen Bhat ,  Anne Eldrup ,  Thazha Prakash ,  Phillip Cook ,  Robert LaFemina ,  Amy Simcoe ,  Carrie Rutkowski ,  Mario Valenciano

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61K31/70 ,  A61K31/7052 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7076 ,  A61K31/708 ,  A61K31/7105 ,  A61K31/712 ,  A61K38/21 ,  A61K45/00 ,  A61K45/06 ,  A61P1/16 ,  A61P31/14 ,  A61P43/00 ,  C07D473/00 ,  C07D487/02 ,  C07H20060101 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048 ,  C07H19/06 ,  C07H19/067 ,  C07H19/09 ,  C07H19/10 ,  C07H19/14 ,  C07H19/16 ,  C07H19/167 ,  C07H19/173 ,  C07H19/19 ,  C07H19/20 ,  C12N20060101

CPC分类号： C07H19/16 ,  A61K9/4858 ,  A61K31/7056 ,  A61K31/7064 ,  A61K31/7076 ,  A61K38/21 ,  A61K45/06 ,  C07D473/00 ,  C07D487/04 ,  C07H19/00 ,  C07H19/06 ,  C07H19/10 ,  C07H19/12 ,  C07H19/14 ,  C07H19/20 ,  Y02P20/582 ,  A61K2300/00

摘要： The present invention provides nucleoside 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 nucleoside 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 nucleoside 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）有活性的试剂组合的药物组合物。 还公开了本发明的核苷化合物抑制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：US20060264389A1

公开(公告)日：2006-11-23

申请号：US10521006

申请日：2003-07-11

申请人： Balkrishen Bhat ,  Steven Carroll ,  Anne Eldrup ,  Malcolm MacCoss ,  David Olsen ,  Thazha Prakash

发明人： Balkrishen Bhat ,  Steven Carroll ,  Anne Eldrup ,  Malcolm MacCoss ,  David Olsen ,  Thazha Prakash

IPC分类号： A61K31/7076 ,  C07H19/22

CPC分类号： C07H19/14 ,  C07H19/22

摘要： Thee present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA via 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 nucleoside 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 creating RNA-dependent RNA viral infection with the nucleoside 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化合物及其某些衍生物。 这些化合物是通过复制的RNA依赖性RNA的抑制剂，并且可用于治疗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）有活性的试剂组合的药物组合物。 还公开了抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或用本发明的核苷化合物产生RNA依赖性RNA病毒感染的方法。

公开(公告)号：US20060205686A1

公开(公告)日：2006-09-14

申请号：US11236224

申请日：2005-09-27

申请人： Balkrishen Bhat ,  Anne Eldrup ,  Thazha Prakash ,  Phillip Cook ,  Steven Carroll ,  Malcolm MacCoss ,  David Olsen

发明人： Balkrishen Bhat ,  Anne Eldrup ,  Thazha Prakash ,  Phillip Cook ,  Steven Carroll ,  Malcolm MacCoss ,  David Olsen

IPC分类号： A61K31/7056 ,  A61K31/7076

CPC分类号： C07H19/16 ,  A61K9/4858 ,  A61K31/7056 ,  A61K31/7064 ,  A61K31/7076 ,  A61K38/21 ,  A61K45/06 ,  C07D473/00 ,  C07D487/04 ,  C07H19/00 ,  C07H19/06 ,  C07H19/10 ,  C07H19/12 ,  C07H19/14 ,  C07H19/20 ,  Y02P20/582 ,  A61K2300/00

摘要： The present invention provides nucleoside 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 nucleoside 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 nucleoside compounds of the present invention.

公开(公告)号：US08604183B2

公开(公告)日：2013-12-10

申请号：US10701007

申请日：2003-11-04

申请人： Charles Allerson ,  Balkrishen Bhat ,  Anne B. Eldrup ,  Muthiah Manoharan ,  Richard H. Griffey ,  Brenda F. Baker ,  Eric E. Swayze

发明人： Charles Allerson ,  Balkrishen Bhat ,  Anne B. Eldrup ,  Muthiah Manoharan ,  Richard H. Griffey ,  Brenda F. Baker ,  Eric E. Swayze

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68 ,  C12P19/34

CPC分类号： C07H21/00 ,  C07H21/04 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/343 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2320/51

摘要： The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary 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 preferred 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.

公开(公告)号：US20130035369A1

公开(公告)日：2013-02-07

申请号：US13566864

申请日：2012-08-03

申请人： Balkrishen Bhat ,  Thazha P. Prakash ,  Charles Allerson ,  Garth A. Kinberger ,  Eric G. Marcusson ,  Eric E. Swayze

发明人： Balkrishen Bhat ,  Thazha P. Prakash ,  Charles Allerson ,  Garth A. Kinberger ,  Eric G. Marcusson ,  Eric E. Swayze

IPC分类号： A61K31/7125 ,  A61P35/00 ,  A61P29/00 ,  C12N5/07 ,  A61K31/7088

CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3515 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2320/51 ,  C12Y301/03048 ,  C12N2310/3521

摘要： The present invention provides double stranded compositions wherein the first strand is modified to have a particular motif and the second strand is modified a selected motif. More particularly, the present compositions comprise an antisense strand that is modified to have a positional/full motif and the sense strand is modified to have an alternating motif, a hemimer motif, a blockmer motif, a gapped motif, a positional motif, a positional/full motif or a fully modified motif. Each strand further comprises one or more phosphorothioate internucleoside linkage. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes.

摘要翻译： 本发明提供双链组合物，其中第一链被修饰成具有特定的基序，第二链被修饰为选定的基序。 更具体地，本发明的组合物包含被修饰为具有位置/完整基序的反义链，并且有义链被修饰为具有交替基序，半缩氨酸基序，阻断基序，间隙基序，位置基序，位置 /完整的图案或完全修饰的图案。 每条链还包含一个或多个硫代磷酸酯核苷间键。 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。

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：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。

公开(公告)号：US08440803B2

公开(公告)日：2013-05-14

申请号：US13308750

申请日：2011-12-01

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： C07H21/00 ,  C07H21/02 ,  C07G3/00 ,  C12Q1/68

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.

公开(公告)号：US08124745B2

公开(公告)日：2012-02-28

申请号：US12774566

申请日：2010-05-05

申请人： Charles Allerson ,  Balkrishen Bhat ,  Eric E. Swayze ,  Thazha P. Prakash

发明人： Charles Allerson ,  Balkrishen Bhat ,  Eric E. Swayze ,  Thazha P. Prakash

IPC分类号： C07H19/00 ,  C07H21/04

CPC分类号： C07H21/00 ,  C07H21/04 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/343 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2320/51

摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modification comprising a polycyclic sugar surrogate. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a polycyclic sugar surrogate modification.

摘要翻译： 提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶 核酸，并且第一或第二寡聚体中的至少一种包括包含多环糖替代物的修饰物。 还提供寡聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一种核苷 低聚物具有多环糖替代物修饰。

公开(公告)号：US20110046206A1

公开(公告)日：2011-02-24

申请号：US12666042

申请日：2008-06-23

申请人： Balkrishen Bhat ,  Thazha P. Prakash ,  Charles Allerson ,  Garth A. Kinberger ,  Eric G. Marcusson ,  Eric E. Swayze

发明人： Balkrishen Bhat ,  Thazha P. Prakash ,  Charles Allerson ,  Garth A. Kinberger ,  Eric G. Marcusson ,  Eric E. Swayze

IPC分类号： A61K31/711 ,  C12N5/071 ,  A61P43/00

CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3515 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2320/51 ,  C12Y301/03048 ,  C12N2310/3521

摘要： The present invention provides double stranded compositions wherein the first strand is modified to have a particular motif and the second strand is modified a selected motif. The motifs are defined by positioning of differentially modified nucleosides wherein at least the sugar moieties are different. More particularly, the present compositions comprise an antisense strand that is modified to have a positional/full motif and the sense strand is modified to have an alternating motif, a hemimer motif, a blockmer motif, a gapped motif, a positional motif, a positional/full motif or a fully modified motif. Each strand further comprises one or more phosphorothioate internucleoside linkage. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred 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，其中第一链被修饰成具有特定的基序，第二链被修饰为选定的基序。 通过定位差异修饰的核苷定义基序，其中至少糖部分不同。 更具体地，本发明的组合物包含被修饰为具有位置/完整基序的反义链，并且有义链被修饰为具有交替基序，半缩氨酸基序，阻断基序，间隙基序，位置基序，位置 /完整的图案或完全修饰的图案。 每条链还包含一个或多个硫代磷酸酯核苷间键。 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。 在优选的实施方案中，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。