公开(公告)号：EP1355916B1

公开(公告)日：2007-01-10

申请号：EP02709299.8

申请日：2002-01-18

申请人： Merck & Co., Inc. ,  ISIS PHARMACEUTICALS, INC.

发明人： CARROLL, Steven, S. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  BHAT, Balkrishen ,  BHAT, Neelima ,  COOK, Phillip Dan ,  ELDRUP, Anne, B. ,  PRAKASH, Thazha, P. ,  PRHAVC, Marija ,  SONG, Quanlai

IPC分类号： C07H19/14 ,  A61K31/7064 ,  A61P31/14

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： 本发明提供了核苷化合物，其是RNA依赖性RNA病毒聚合酶的抑制剂，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，可用于治疗HCV感染。

公开(公告)号：EP1556399A2

公开(公告)日：2005-07-27

申请号：EP03751791.9

申请日：2003-07-11

申请人： Merck & Co., Inc. ,  Isis Pharmaceuticals, Inc.

发明人： BHAT, Balkrishen ,  CARROLL, Steven, S. ,  ELDRUP, Anne, B. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  PRAKASH, Thazha, P.

IPC分类号： C07H19/14 ,  A61K31/70

CPC分类号： C07H19/14 ,  C07H19/22

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：EP1539188A2

公开(公告)日：2005-06-15

申请号：EP02709095.0

申请日：2002-01-18

申请人： Merck & Co., Inc. ,  ISIS PHARMACEUTICALS, INC.

发明人： CARROLL, Steven, S. ,  LAFEMINA, Robert, L. ,  HALL, Dawn, L. ,  HIMMELBERGER, Amy, L. ,  KUO, Lawrence, C. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  RUTKOWSKI, Carrie, A. ,  TOMASSINI, Joanne, E. ,  AN, Haoyun ,  BHAT, Balkrishen ,  BHAT, Neelima ,  COOK, Phillip, Dan ,  ELDRUP, Anne, B. ,  GUINOSSO, Charles, J. ,  PRHAVC, Marija ,  PRAKASH, Thazha, P.

IPC分类号： A61K31/70 ,  A61K31/712 ,  A61K31/7105

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 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.

公开(公告)号：EP1355916A2

公开(公告)日：2003-10-29

申请号：EP02709299.8

申请日：2002-01-18

申请人： Merck & Co., Inc. ,  ISIS PHARMACEUTICALS, INC.

发明人： CARROLL, Steven, S. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  BHAT, Balkrishen ,  BHAT, Neelima ,  COOK, Phillip Dan ,  ELDRUP, Anne, B. ,  PRAKASH, Thazha, P. ,  PRHAVC, Marija ,  SONG, Quanlai

IPC分类号： C07H19/14 ,  A61K31/7064 ,  A61P31/14

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：EP2173358B1

公开(公告)日：2015-10-21

申请号：EP08771759.1

申请日：2008-06-23

申请人： Isis Pharmaceuticals, Inc.

发明人： BHAT, Balkrishen ,  PRAKASH, Thazha, P. ,  ALLERSON, Charles ,  KINBERGER, Garth, A. ,  MARCUSSON, Eric, G. ,  SWAYZE, Eric, E.

IPC分类号： C12N15/113 ,  C12N15/11

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

公开(公告)号：EP1765416A2

公开(公告)日：2007-03-28

申请号：EP05757632.4

申请日：2005-06-02

申请人： ISIS PHARMACEUTICALS, INC.

发明人： BHAT, Balkrishen ,  PRAKASH, Thazha, P. ,  DANDE, Prasad ,  ALLERSON, Charles ,  GRIFFEY, Richard, H. ,  SWAYZE, Eric, E.

IPC分类号： A61K48/00 ,  C07H21/04 ,  C12Q1/68

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 an alternating motif and another strand having a hemimer motif, a blockmer motif, a fully modified motif or a positionally modified 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 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： 本发明提供了双链组合物，其中每条链被修饰成具有通过定位β-D-核糖核苷和糖修饰的核苷确定的基序。 更具体地说，本发明的组合物包含具有交替基序的一条链和具有半色体基序，封闭剂基序，完全修饰的基序或位置修饰的基序的另一条链。 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种或多种基因的表达。 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。

公开(公告)号：EP1765074A2

公开(公告)日：2007-03-28

申请号：EP04754153.7

申请日：2004-06-03

申请人： ISIS PHARMACEUTICALS, INC.

发明人： BHAT, Balkrishen ,  SWAYZE, Eric ,  PRAKASH, Thazha, P. ,  ALLERSON, Charles ,  DANDE, Prasad ,  GRIFFEY, Richard, H.

IPC分类号： A01N43/04

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2320/50 ,  C12Y301/03048 ,  C12N2310/3525 ,  C12N2310/3521

摘要： The present invention provides oligomeric compounds having sufficient complementarity to hybridize to a nucleic acid target and methods for their use in modulating gene expression. In one embodiment the oligomeric compounds comprise double stranded constructs wherein one of the strands capable of hybridizing to a nucleic acid target, and has a plurality of modified ribofuranosyl nucleosides at defined locations. The presense of modifications at such defined positions greatly enhances the properties of the corresponding compositions.

公开(公告)号：EP1499627A2

公开(公告)日：2005-01-26

申请号：EP02746811.5

申请日：2002-07-01

申请人： ISIS Pharmaceuticals, Inc.

发明人： MANOHARAN, Muthiah ,  MAIER, Martin, A. ,  PRAKASH, Thazha, P. ,  RAJEEV, Kallanthottathil, Gopalan

IPC分类号： C07H21/02 ,  C07H21/04 ,  A61K48/00 ,  C12Q1/68 ,  C12N15/85 ,  C12N15/86

CPC分类号： C07H21/00

摘要： The present invention relates to novel nuclease-resistant oligomeric compounds and to novel methods for increasing resistance of oligomeric compounds. In preferred embodiments of the invention, the oligomeric compounds comprise at least one modified nucleoside containing a modified sugar moiety at either the 3' or 5' terminus of the oligomeric compound, and further comprise at least one internucleoside linking group that is other than phosphodiester. Other preferred embodiments of the invention include methods of enhancing the nuclease resistance of oligomeric compounds comprising incorporating at least one modified nucleoside containing a modified sugar moiety at either the 3' or 5' terminus of an oligomeric compound.

公开(公告)号：EP1765074B1

公开(公告)日：2012-10-03

申请号：EP04754153.7

申请日：2004-06-03

申请人： Isis Pharmaceuticals, Inc.

发明人： BHAT, Balkrishen ,  SWAYZE, Eric ,  PRAKASH, Thazha, P. ,  ALLERSON, Charles ,  DANDE, Prasad ,  GRIFFEY, Richard, H.

IPC分类号： C07H21/04 ,  C12N15/11

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2320/50 ,  C12Y301/03048 ,  C12N2310/3525 ,  C12N2310/3521

公开(公告)号：EP1765415A2

公开(公告)日：2007-03-28

申请号：EP05756325.6

申请日：2005-06-02

申请人： ISIS PHARMACEUTICALS, INC.

发明人： SWAYZE, Eric, E. ,  BHAT, Balkrishen ,  GRIFFEY, Richard, H. ,  PRAKASH, Thazha, P. ,  ALLERSON, Charles

IPC分类号： A61K48/00 ,  C12Q1/68 ,  C07H21/04

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 one of the strands is useful in, for example, influencing the preferential loading the opposite strand into the RISC (or cleavage) complex. In particular, the present invention provides oligomeric compounds that comprise chemical modifications in at least one of the strands to drive loading of the opposite strand into the RISC (or cleavage) complex. Such modifications can be used to increase potency of duplex constructs that have been modified to enhance stability. Examples of chemical modifications that drive loading of the second strand include, but are not limited to, MOE (2'-O(CH2)2OCH3), 2'-O-methyl, -ethyl, -propyl, and -N-methylacetamide. Such modifications can be distributed throughout the strand, or placed at the 5' and/or 3' ends to make a gapmer motif on the sense strand. The activity of the 4'-thio gapmer RNA antisense strand can be improved by incorporating alternating MOE or MOE gapmer motif into the sense strand.