公开(公告)号：EP2356129A1

公开(公告)日：2011-08-17

申请号：EP09792892.3

申请日：2009-09-23

申请人： ISIS PHARMACEUTICALS, INC.

发明人： SETH, Punit, P. ,  SWAYZE, Eric, E.

IPC分类号： C07H21/00 ,  C07H19/04 ,  A61K31/712

CPC分类号： C07H21/00 ,  C07H19/04

摘要： The present disclosure describes substituted α-L-bicyclic nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, substituted α-L-bicyclic nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including 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：EP2274423A2

公开(公告)日：2011-01-19

申请号：EP09728284.2

申请日：2009-04-03

申请人： Isis Pharmaceuticals, Inc.

发明人： SWAYZE, Eric, E. ,  SIWKOWSKI, Andrew, M.

IPC分类号： C12N15/11 ,  C07H21/00 ,  A61K31/713

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/53

摘要： In certain embodiments, the present invention provides oligomeric compounds having favorable toxicity profiles and therapeutic indexes. Compounds of the present invention comprise bicyclic nucleosides. Certain such bicyclic nucleosides are pyrimidines that do not include a methyl group at the 5-carbon. Oligomeric compounds comprising such nucleosides are less toxic than compounds comprising bicyclic nucleosides that do include a methyl group at the 5-carbon. In certain embodiments, the present invention provides methods of preparing and using such compounds.

公开(公告)号：EP2265627A2

公开(公告)日：2010-12-29

申请号：EP09707464.5

申请日：2009-02-06

申请人： Isis Pharmaceuticals, Inc.

发明人： SETH, Punit, P. ,  MIGAWA, Michael, T. ,  SWAYZE, Eric, E. ,  SONG, Quanlai ,  HAN, Mingming ,  ROSS, Bruce

IPC分类号： C07H21/00

CPC分类号： C07H21/00

摘要： The present disclosure provides bicyclic cyclohexitol nucleoside analogs of formula I and oligomeric compounds comprising these nucleoside analogs. These bicyclic nucleoside analogs are expected to be useful for enhancing properties of oligomeric compounds including for example nuclease resistance.

摘要翻译： 本公开提供了式I的双环环己醇核苷类似物和包含这些核苷类似物的低聚化合物。 预期这些双环核苷类似物可用于增强寡聚化合物的性质，包括例如核酸酶抗性。

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：EP1984381A2

公开(公告)日：2008-10-29

申请号：EP07762892.3

申请日：2007-01-27

申请人： Isis Pharmaceuticals, Inc.

发明人： SWAYZE, Eric, E. ,  SETH, Punit, P.

IPC分类号： C07H19/04 ,  C07H21/00

CPC分类号： C07H21/00 ,  C07H19/00 ,  C07H19/04 ,  Y02P20/55

摘要： The present invention provides 6-modified bicyclic nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 6-position. These bicyclicnucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.

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.

公开(公告)号：EP1730309A2

公开(公告)日：2006-12-13

申请号：EP05725530.9

申请日：2005-03-15

申请人： Isis Pharmaceuticals, Inc.

发明人： MIGAWA, Michael, T. ,  LIMA, Walter, F. ,  SWAYZE, Eric, E. ,  NICHOLS, Joshua ,  WU, Hongjiang ,  PRAKASH, Thazha, P. ,  WYRZYKIEWICZ, Tadeusz, Krzysztof ,  BHAT, Balkrishen ,  CROOKE, Stanley, T.

IPC分类号： C12Q1/68 ,  C12N15/85 ,  A61K48/00 ,  C12N15/11 ,  C07H21/04

CPC分类号： C12N15/85 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/321 ,  C12N2310/346 ,  C12N2310/3519 ,  C12N2310/3525

摘要： The present invention provides compositions and methods for the optimization of cleavage of RNA species by RNase H. In some emboediments, the invention provides oligonucleotides that possess two or more regions of differing conformation, and at least one transitional nucleobase positioned between the regions that is capable of modulating transfer of the helical conformation characteristic of the region bound to the 3'hydroxy thereof, to the region bound to the 5' hydroxyl thereof.

公开(公告)号：EP1648914A2

公开(公告)日：2006-04-26

申请号：EP04780181.6

申请日：2004-07-30

申请人： ISIS PHARMACEUTICALS, INC.

发明人： ESAU, Christine ,  LOLLO, Bridget ,  BENNETT, C., Frank ,  FREIER, Susan, M. ,  GRIFFEY, Richard, H. ,  BAKER, Brenda, F. ,  VICKERS, Timothy ,  MARCUSSON, Eric, G. ,  KOLLER, Erich ,  SWAYZE, Eric, E. ,  JAIN, Ravi ,  BHAT, Balkrishen ,  PERALTA, Eigen

IPC分类号： C07H21/04 ,  A61K48/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/3181 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/11 ,  C12N2320/30 ,  C12N2320/50 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

摘要翻译： 化合物，组合物和方法提供了用于调节的小非编码RNA的表达和功能。 所述组合物包含低聚化合物，有针对性的小非编码RNA。 因此，提供了使用这些化合物用于小非编码RNA的调制以及合成的RNA和用于诊断和治疗与小的非编码RNA相关的疾病的下游靶的方法。

公开(公告)号：EP1578765A2

公开(公告)日：2005-09-28

申请号：EP03783131.0

申请日：2003-11-04

申请人： ISIS PHARMACEUTICALS, INC.

发明人： BAKER, Brenda, F. ,  ELDRUP, Anne, B. ,  MANOHARAN, Muthiah ,  BHAT, Balkrishen ,  GRIFFEY, Richard ,  SWAYZE, Eric, E. ,  CROOKE, Stanley, T.

IPC分类号： 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 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 sugar surrogate modification.

公开(公告)号：EP1563070A2

公开(公告)日：2005-08-17

申请号：EP03786574.8

申请日：2003-11-04

申请人： Isis Pharmaceuticals, Inc.

发明人： BAKER, Brenda ,  ELDRUP, Anne B. ,  MANOHARAN, Muthiah ,  BHAT, Balkrishen ,  GRIFFEY, Richard ,  SWAYZE, Eric, E. ,  CROOKE, Stanely, T. ,  PRAKASH, Thazha, P.

IPC分类号： C12N15/11 ,  C12Q1/68 ,  A61K48/00

CPC分类号： C12N15/1135 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/345 ,  C12N2310/346 ,  C12N2310/53 ,  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.