公开(公告)号：EP1539188B1

公开(公告)日：2015-01-07

申请号：EP02709095.0

申请日：2002-01-18

申请人： Merck Sharp & Dohme Corp. ,  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： C07H19/14 ,  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

公开(公告)号：EP1758453B1

公开(公告)日：2014-07-16

申请号：EP05785614.8

申请日：2005-06-10

申请人： Merck Sharp & Dohme Corp. ,  Isis Pharmaceuticals, Inc.

发明人： BUTORA, Gabor ,  MACCOSS, Malcolm ,  BHAT, Balkrishen ,  ELDRUP, Anne, B.

IPC分类号： C07D498/04 ,  A01N43/04 ,  A61K31/70 ,  A61P35/00 ,  C07D487/04 ,  C07D491/04

CPC分类号： C07D491/04 ,  C07D487/04 ,  C07H19/16 ,  C07H19/20

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：EP2188298B1

公开(公告)日：2013-09-18

申请号：EP08798023.1

申请日：2008-08-15

申请人： Isis Pharmaceuticals, Inc.

发明人： ALLERSON, Charles ,  BHAT, Balkrishen ,  PRAKASH, Thazha, P. ,  SWAYZE, Eric, E. ,  SIWKOWSKI, Andrew, M. ,  SETH, Punit, P.

IPC分类号： C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  C12N15/11

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

公开(公告)号：EP2393825A2

公开(公告)日：2011-12-14

申请号：EP10704867.0

申请日：2010-02-05

申请人： Isis Pharmaceuticals, Inc.

发明人： SWAYZE, Eric, E. ,  SIWKOWSKI, Andrew, M. ,  BHAT, Balkrishen ,  PRAKASH, Thazha, P. ,  ALLERSON, Charles ,  SETH, Punit, P.

IPC分类号： C07H21/00 ,  A61K31/712

CPC分类号： C07H21/00

摘要： The present invention provides oligomeric compounds and uses thereof. In certain embodiments, such oligomeric compounds are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds, as RNAi compounds, and/or as modulators of splicing.

公开(公告)号：EP2173358A1

公开(公告)日：2010-04-14

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： A61K31/70 ,  C12N15/00

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： 本发明提供了双链组合物，其中第一条链被修饰成具有特定基序并且第二条链被修饰成选定基序。 基序是通过定位差异修饰的核苷定义的，其中至少糖部分是不同的。 更特别地，本发明的组合物包含经修饰以具有位置/完整基序并且有义链经修饰以具有交替基序，半个体基元，封闭剂基序，缺口基序，位置基序，位置 /完整主题或完全修改的主题。 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：EP1668130A2

公开(公告)日：2006-06-14

申请号：EP04784326.3

申请日：2004-09-17

申请人： ISIS PHARMACEUTICALS, INC. ,  ELI LILLY AND COMPANY

发明人： FREIER, Susan, M. ,  DOBIE, Kenneth, W. ,  MARCUSSON, Eric, G. ,  SWAYZE, Eric, E. ,  BHAT, Balkrishen ,  GRAFF, Jeremy, R. ,  KONICEK, Bruce, W.

IPC分类号： C12N15/11 ,  A61K31/7088 ,  A61K31/713 ,  A61P35/00 ,  A61P9/00

CPC分类号： C07H21/00 ,  A61K38/00 ,  C12N15/113 ,  C12N2310/13 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/53 ,  C12N2310/3525 ,  C12N2310/3521 ,  C12N2310/3533

摘要： Oligomeric compounds, compositions and methods are provided for modulating the expression of eIF4E. The antisense compounds may be single- or double-stranded and are targeted to nucleic acid encoding eIF4E. Methods of using these compounds for modulation of eIF4E expression and for diagnosis and treatment of diseases and conditions associated with expression of eIF4E are provided.

公开(公告)号：EP1633307A2

公开(公告)日：2006-03-15

申请号：EP04754158.6

申请日：2004-06-03

申请人： ISIS PHARMACEUTICALS, INC. ,  ELI LILLY AND COMPANY

发明人： BHAT, Balkrishen ,  PATET, Bharvin, Kumar ,  SWAYZE, Eric

IPC分类号： A61K6/00

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.