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31. 发明申请

US20070275921A1 Oligomeric Compounds That Facilitate Risc Loading 审中-公开
标题翻译：促进Risc加载的低分子化合物
公开(公告)号：US20070275921A1
公开(公告)日：2007-11-29
申请号：US11569929
申请日：2005-06-02
申请人： Eric Swayze , Balkrishen Bhat , Richard Griffey , Thazha Prakash , Charles Allerson
发明人： Eric Swayze , Balkrishen Bhat , Richard Griffey , Thazha Prakash , Charles Allerson
IPC分类号： A61K31/7052 , A61P43/00 , C07H21/00
CPC分类号： A61K31/7052
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.
摘要翻译：本发明提供双链组合物，其中一条链可用于例如影响相对链优先加载到RISC（或切割）复合物中。特别地，本发明提供了在至少一个链中包含化学修饰以驱动相反链加载到RISC（或切割）复合物中的低聚化合物。可以使用这些修饰来增加经修饰以增强稳定性的双链构建体的效力。驱动第二链的负载的化学修饰的实例包括但不限于MOE（2'-O（CH 2）2 OCH 3），2'-O-甲基， - 乙基， - 丙基和-N-甲基乙酰胺。这样的修饰可以分布在整个链上，或者放置在5'和/或3'末端以在有义链上形成gapmer基序。通过将交替的MOE或MOE gapmer基序并入有义链中，可以改善4'-硫代间隔RNA反义链的活性。

32. 发明申请

US20070185047A1 DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION 审中-公开
公开(公告)号：US20070185047A1
公开(公告)日：2007-08-09
申请号：US11565785
申请日：2006-12-01
申请人： Balkrishen Bhat , Thazha Prakash , Prasad Dande , Charles Allerson , Richard Griffey , Eric Swayze
发明人： Balkrishen Bhat , Thazha Prakash , Prasad Dande , Charles Allerson , Richard Griffey , Eric Swayze
IPC分类号： A61K48/00
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.

33. 发明申请

US20070179107A1 DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION 审中-公开
标题翻译：包含用于基因调控的差异化修饰条纹的双重条纹组合
公开(公告)号：US20070179107A1
公开(公告)日：2007-08-02
申请号：US11565816
申请日：2006-12-01
申请人： Balkrishen Bhat , Thazha Parkash , Prasad Dande , Charles Allerson , Richard Griffey , Eric Swayze
发明人： Balkrishen Bhat , Thazha Parkash , Prasad Dande , Charles Allerson , Richard Griffey , Eric Swayze
IPC分类号： A61K48/00 , C12N15/09
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 a gapped motif and another strand having a gapped motif, a hemimer motif, a blockmer motif, a fully modified motif, a positionally modified motif or an alternating 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 some 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：本发明提供双链组合物，其中每条链被修饰以具有通过定位β-D-核糖核苷和糖修饰核苷定义的基序。更具体地，本发明的组合物包含一个具有间隙基序的链，另一个链具有间隙基序，半缩体基序，封闭基序，完全修饰的基序，位置修饰的基序或交替基序。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个或多个基因的表达。在一些实施方案中，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。

34. 发明申请

US20070166734A1 DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION 审中-公开
标题翻译：包含用于基因调控的差异化修饰条纹的双重条纹组合
公开(公告)号：US20070166734A1
公开(公告)日：2007-07-19
申请号：US11565770
申请日：2006-12-01
申请人： Balkrishen Bhat , Thazha Prakash , Charles Allerson , Richard Griffey , Eric Swayze
发明人： Balkrishen Bhat , Thazha Prakash , Charles Allerson , Richard Griffey , Eric Swayze
IPC分类号： A61K48/00 , C12Q1/68 , C07H21/02
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：本发明提供双链组合物，其中每条链被修饰以具有通过定位β-D-核糖核苷和糖修饰核苷定义的基序。更具体地说，本发明组合物包含一条具有交替基序的链，另一条链具有半缩体基序，封闭基序，完全修饰的基序或位置修饰的基序。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。

35. 发明申请

US20050165007A1 Benzimidazoles and analogs thereof as antivirals 失效
公开(公告)号：US20050165007A1
公开(公告)日：2005-07-28
申请号：US10946757
申请日：2004-09-22
申请人： Punit Seth , Elizabeth Jefferson , Richard Griffey , Eric Swayze
发明人： Punit Seth , Elizabeth Jefferson , Richard Griffey , Eric Swayze
IPC分类号： A61K31/4184 , A61K31/519 , A61K31/551 , A61P31/14 , C07D235/30 , C07D401/04 , C07D401/12 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/12 , C07D405/14 , C07D409/14 , C07D417/04 , C07D417/12 , C07D417/14 , C07D471/04 , C07D473/00 , C07D487/04 , C07D491/04 , C07D491/14
CPC分类号： C07D401/04 , C04B35/632 , C07B2200/11 , C07D235/30 , C07D401/12 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/12 , C07D405/14 , C07D409/14 , C07D417/04 , C07D417/12 , C07D417/14 , C07D471/04 , C07D473/00 , C07D487/04 , C07D491/04 , C07D491/14
摘要： Provided are compounds of the formula: wherein RN1 is a substituent of formula G1-NX1X2, wherein G1 is an optionally further substituted alkylene, which optionally forms, together with RN2, a cyclic group, and each of X1 and X2 is independently H or an N-substituent, or X1 and X2 together form a heterocyclic ring, or X1 together with G1 forms a cyclic group and X2 is H or an N-substituent; and each of Z1, Z2, Z3 and Z4 is H or a substituent, or two of Z1, Z2, Z3 and Z4 together form an optionally substituted ring, and further wherein at least one of Z1, Z2, Z3 and Z4 is other than H, and salts thereof, pharmaceutical compositions and methods of using the compounds. The compounds have antiviral activity.

36. 发明申请

US20050142581A1 Microrna as ligands and target molecules 审中-公开
标题翻译： Microrna作为配体和靶分子
公开(公告)号：US20050142581A1
公开(公告)日：2005-06-30
申请号：US10934798
申请日：2004-09-03
申请人： Richard Griffey , C. Bennett , David Ecker , Donna Ward , Susan Freier
发明人： Richard Griffey , C. Bennett , David Ecker , Donna Ward , Susan Freier
IPC分类号： C12N20060101 , C12N15/11 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/111 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2320/11 , C12N2330/10 , C12N2310/3525
摘要： The present invention provides methods for the identification of target molecules that bind to ligands, particularly microRNA ligands and mimics thereof and/or microRNA target molecules and mimics thereof, with as little as millimolar (mM) affinity using mass spectrometry. The methods may be used to determine the mode of binding interaction between two or more of these target molecules to the ligand as well as their relative affinities. Also provided are methods for designing compounds having greater affinity to a ligand by identifying two or more target molecules using mass spectrometry methods of the invention and linking the target molecules together to form a novel compound.
摘要翻译：本发明提供用于使用质谱法以少至毫摩尔（mM）亲和力鉴定结合配体，特别是微小RNA配体及其模拟物和/或微小RNA靶分子及其模拟物的靶分子的方法。该方法可用于确定这些靶分子中两个或更多个与配体之间的结合相互作用的模式以及它们的相对亲和力。还提供了通过使用本发明的质谱方法鉴定两个或更多个靶分子并将靶分子连接在一起以形成新化合物来设计对配体具有更大亲和力的化合物的方法。

37. 发明申请

US20050130924A1 Antisense inhibition via RNAse H-independent reduction in mRNA 审中-公开
标题翻译：通过RNA酶的反义抑制通过mRNA的H独立还原
公开(公告)号：US20050130924A1
公开(公告)日：2005-06-16
申请号：US10948947
申请日：2004-09-24
申请人： Brett Monia , Susan Freier , Muthiah Manoharan , William Gaarde , Richard Griffey , Eric Swayze , C. Bennett
发明人： Brett Monia , Susan Freier , Muthiah Manoharan , William Gaarde , Richard Griffey , Eric Swayze , C. Bennett
IPC分类号： A61K38/00 , C12N15/113 , A61K48/00 , A61K31/675
CPC分类号： C12N15/113 , A61K38/00 , C12N15/1137 , C12N2310/315 , C12N2310/318 , C12N2310/3181 , C12N2310/321 , C12N2310/322 , C12N2310/3233 , C12N2310/334 , C12N2310/3341 , C12N2310/345
摘要： The present invention provides compositions and methods for reducing levels of a preselected mRNA, using antisense compounds targeted to a splice site or a region up to 50 nucleobases upstream of an exon/intron junction on said mRNA. Preferably, said antisense compounds do not elicit RNAse H cleavage of the mRNA.
摘要翻译：本发明提供了使用靶向剪接位点的反义化合物或在所述mRNA上的外显子/内含子结上游多达50个核碱基的区域来降低预选mRNA水平的组合物和方法。优选地，所述反义化合物不引起mRNA的RNA酶H切割。

38. 发明申请

US20050080246A1 Compositions comprising alternating 2'-modified nucleosides for use in gene modulation 有权
标题翻译：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：US20050080246A1
公开(公告)日：2005-04-14
申请号：US10860265
申请日：2004-06-03
申请人： Charles Allerson , Balkrishen Bhat , Anne Eldrup , Muthiah Manoharan , Richard Griffey , Brenda Baker , Eric Swayze
发明人： Charles Allerson , Balkrishen Bhat , Anne Eldrup , Muthiah Manoharan , Richard Griffey , Brenda Baker , Eric Swayze
IPC分类号： A61K48/00 , C07H21/02 , C07H21/04
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。

39. 发明申请

US20050026160A1 Compositions comprising alternating 2'-modified nucleosides for use in gene modulation 有权
公开(公告)号：US20050026160A1
公开(公告)日：2005-02-03
申请号：US10701007
申请日：2003-11-04
申请人： Charles Allerson , Balkrishen Bhat , Anne Eldrup , Muthiah Manoharan , Richard Griffey , Brenda Baker , Eric Swayze
发明人： Charles Allerson , Balkrishen Bhat , Anne Eldrup , Muthiah Manoharan , Richard Griffey , Brenda Baker , Eric Swayze
IPC分类号： C07H21/00 , C07H21/04 , C12N15/113 , C12Q1/68
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.

40. 发明授权

US06358931B1 Compositions and methods for modulating RNA 失效
标题翻译：用于调节RNA的组合物和方法
公开(公告)号：US06358931B1
公开(公告)日：2002-03-19
申请号：US08295744
申请日：1994-08-30
申请人： Phillip Dan Cook , Thomas Bruice , Charles John Guinosso , Andrew Mamoru Kawasaki , Richard Griffey
发明人： Phillip Dan Cook , Thomas Bruice , Charles John Guinosso , Andrew Mamoru Kawasaki , Richard Griffey
IPC分类号： C07H2107
CPC分类号： C12N15/113 , A61K38/00 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C07K14/005 , C12N9/0069 , C12N15/1137 , C12N2310/3125 , C12N2310/315 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/336 , C12N2310/3511 , C12N2310/3521 , C12N2310/3523 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533 , C12N2740/16322 , C12Q1/68 , C12Q1/6813 , C12Y113/11012
摘要： Compositions and methods for modulating the activity of RNA are disclosed, In accordance with preferred embodiments, antisense compositions are prepared targeting reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.
摘要翻译：公开了调节RNA活性的组合物和方法。根据优选实施方案，制备靶向反应部分的反义组合物。反应性部分优选包含通过具有或不具有插入插入部分的接头与靶向寡核苷酸缀合的一个或两个咪唑官能团。还公开了治疗学，诊断和研究方法，合成核苷和可以被制成寡核苷酸的核苷片段也是公开的。

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