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.

公开(公告)号：EP1562971A2

公开(公告)日：2005-08-17

申请号：EP03768647.4

申请日：2003-11-04

申请人： Isis Pharmaceuticals, Inc.

发明人： ALLERSON, Charles ,  BHAT, Balkrishen ,  ELDRUP, Ann, B. ,  MANOHARAN, Muthiah ,  GRIFFEY, Richard ,  BAKER, Brenda, F. ,  SWAYZE, Eric, E.

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

CPC分类号： C12N15/1135 ,  C07H21/04 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/53

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.

公开(公告)号：EP1677822B1

公开(公告)日：2014-04-23

申请号：EP04816222.6

申请日：2004-09-20

申请人： Isis Pharmaceuticals, Inc.

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

IPC分类号： A01N43/00 ,  A01N43/04 ,  A61K31/33 ,  A61K31/70 ,  C07H19/00 ,  C07D333/02 ,  C07D333/32 ,  C07D333/34 ,  C07D333/42

CPC分类号： C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/32

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：EP1984499A2

公开(公告)日：2008-10-29

申请号：EP07710352.1

申请日：2007-01-27

申请人： Isis Pharmaceuticals, Inc.

发明人： ESAU, Christine ,  SWAYZE, Eric, E. ,  BHAT, Balkrishen ,  KINBERGER, Garth, A.

IPC分类号： C12N15/11 ,  C07H21/00

CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/51 ,  C12N2310/3527 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapuetic index. Further provided are methods for selectively modulating miRNA activity in a cell.

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.