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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
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.
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2.发明授权2′-substituted oligomeric compounds and compositions for use in gene modulations 有权2'-取代的寡聚化合物和用于基因调节的组合物公开(公告)号：US07919612B2
公开(公告)日：2011-04-05
申请号：US10701316
申请日：2003-11-04
申请人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
发明人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
CPC分类号： C12N15/113 , A61K38/00 , C07H21/00 , C12N9/22 , C12N15/1135 , C12N2310/311 , C12N2310/312 , C12N2310/314 , C12N2310/315 , C12N2310/316 , C12N2310/318 , C12N2310/3181 , C12N2310/321 , C12N2310/322 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , C12N2310/346 , Y02A50/395 , Y02P20/582 , C12N2310/3527 , C12N2310/3525 , C12N2310/3521
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 modified sugar and/or backbone modification. In some embodiments the modification is a 2′ substituent group on a sugar moiety that is not H or OH. 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 nucleotide of the oligomer has a modified sugar and/or backbone 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修饰的糖和/或骨架修饰。 在一些实施方案中，修饰是糖部分上不是H或OH的2'取代基。 还提供低聚物/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，其中至少一个核苷酸 低聚物具有修饰的糖和/或骨架修饰。
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3.发明授权Compositions comprising alternating 2′-modified nucleosides for use in gene modulation 有权包含交替的2'-修饰核苷的组合物用于基因调控公开(公告)号：US09150605B2
公开(公告)日：2015-10-06
申请号：US10860265
申请日：2004-06-03
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 , C07H21/00 , C07H21/04 , C12N15/11 , C12N15/113
CPC分类号： C12N15/113 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/111 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2320/30 , 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.
摘要翻译： 本发明提供包含至少一种包含交替基序的低聚化合物并且还包括与核酸靶互补的区域的组合物。 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。
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4.发明申请Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权核苷衍生物作为RNA依赖性RNA病毒聚合酶的抑制剂公开(公告)号：US20120165515A1
公开(公告)日：2012-06-28
申请号：US11701682
申请日：2007-02-02
申请人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
发明人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
IPC分类号： C07H19/20
CPC分类号： C07H19/10 , A61K9/4858 , C07D471/04 , C07D473/34 , C07D487/04 , C07H17/02 , C07H19/06 , C07H19/16 , C07H19/207 , Y02P20/582
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。
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公开(公告)号：US08481712B2
公开(公告)日：2013-07-09
申请号：US11701682
申请日：2007-02-02
申请人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
发明人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
CPC分类号： C07H19/10 , A61K9/4858 , C07D471/04 , C07D473/34 , C07D487/04 , C07H17/02 , C07H19/06 , C07H19/16 , C07H19/207 , Y02P20/582
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.
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6.发明授权C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase 有权C-嘌呤核苷类似物作为RNA依赖性RNA病毒聚合酶的抑制剂公开(公告)号：US07534767B2
公开(公告)日：2009-05-19
申请号：US11628513
申请日：2005-06-10
申请人： Gabor Butora , Malcolm MacCoss , Balkrishen Bhat , Anne B. Eldrup
发明人： Gabor Butora , Malcolm MacCoss , Balkrishen Bhat , Anne B. Eldrup
IPC分类号： A01N43/04
CPC分类号： C07D491/04 , C07D487/04 , C07H19/16 , C07H19/20
摘要： The present invention provides C-purine nucleoside analogs and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors 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 C-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 C-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C-嘌呤核苷类似物及其某些衍生物。 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含有这种C-核苷化合物的药物组合物。 还公开了本发明的C-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。
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公开(公告)号：US07125855B2
公开(公告)日：2006-10-24
申请号：US10688691
申请日：2003-10-17
申请人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
发明人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
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.
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8.发明授权Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权核苷衍生物作为RNA依赖性RNA病毒聚合酶的抑制剂公开(公告)号：US07105499B2
公开(公告)日：2006-09-12
申请号：US10250873
申请日：2002-01-18
申请人： Steven S. Carroll , David B. Olsen , Malcolm MacCoss , Balkrishen Bhat , Phillip Dan Cook , Anne B. Eldrup , Thazha P. Prakash
发明人： Steven S. Carroll , David B. Olsen , Malcolm MacCoss , Balkrishen Bhat , Phillip Dan Cook , Anne B. Eldrup , Thazha P. Prakash
IPC分类号： A61K31/7052 , A61K31/7042 , A61K31/7068 , C07H19/04 , C07H19/06
CPC分类号： A61K45/06 , A61K9/4858 , A61K31/7056 , A61K31/7064 , A61K31/7068 , A61K31/7076 , A61K38/212 , A61K38/2292 , C07H19/10 , C07H19/14 , C07H19/20 , Y02P20/582 , A61K2300/00
摘要： The present invention provides nucleoside derivatives 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 derivatives 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 derivatives 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衍生物抑制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。
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9.发明授权2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations 有权2'-氟取代低聚化合物和用于基因调控的组合物公开(公告)号：US07812149B2
公开(公告)日：2010-10-12
申请号：US10700689
申请日：2003-11-04
申请人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
发明人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/346 , C12N2310/3521 , C12N2310/3533 , C12N2310/531 , 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 modified sugar and/or backbone modification. In some embodiments the modification is a 2′-F substituent group on a sugar moiety. 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 modified sugar and/or backbone 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修饰的糖和/或骨架修饰。 在一些实施方案中，修饰是糖部分上的2'-F取代基。 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 低聚物具有修饰的糖和/或骨架修饰。
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10.发明授权公开(公告)号：US07323453B2
公开(公告)日：2008-01-29
申请号：US10504445
申请日：2003-02-07
CPC分类号： A61K31/7064 , A61K31/519 , A61K31/52 , A61K31/522 , A61K31/655 , A61K31/7068 , A61K31/7076 , A61K31/708 , A61K45/06
摘要： The present invention provides methods of inhibiting orthopoxvirus replication and/or treating orthopoxvirus infection with certain nucleoside compounds and derivatives thereof. These compounds are particularly useful as inhibitors of vaccinia virus and variola virus replication and/or for the treatment of vaccinia virus and variola virus infection. The nucleoside compounds may be administered alone or in combination with other agents active against orthopoxvirus infection, in particular against vaccinia virus or variola virus infection. Another aspect of the present invention provides for the use of such nucleoside compounds in the manufacture of a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection. Yet a further aspect of the present invention provides such nucleoside compounds for use as a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection.
摘要翻译： 本发明提供了用某些核苷化合物及其衍生物抑制正痘病毒复制和/或治疗正痘病毒感染的方法。 这些化合物特别可用作痘苗病毒和天花病毒复制的抑制剂和/或用于治疗痘苗病毒和天花病毒感染。 核苷化合物可以单独施用或与其它对抗正痘病毒感染，特别是针对痘苗病毒或天花病毒感染的试剂组合施用。 本发明的另一方面提供了这样的核苷化合物在制备用于抑制正痘病毒复制和/或治疗正痘病毒感染的药物中的用途。 本发明的另一方面提供了用作抑制正痘病毒复制和/或治疗正痘病毒感染的药物的这种核苷化合物。
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