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公开(公告)号：US10023861B2
公开(公告)日：2018-07-17
申请号：US14342196
申请日：2012-08-29
IPC分类号： C07H21/04 , C12N15/113 , C12N15/11 , C07H21/00
摘要： Oligonucleotides, chemically-modified oligonucleotides, and oligonucleotide-conjugate complexes for use in research, diagnostics, and/or therapeutics are described herein. In some embodiments, oligonucleotides comprising a stabilized phosphate moiety covalently attached to the 5′-terminal nucleoside are provided.
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公开(公告)号：US10017764B2
公开(公告)日：2018-07-10
申请号：US13984260
申请日：2012-02-08
申请人： Susan M. Freier , Eric E. Swayze
发明人： Susan M. Freier , Eric E. Swayze
IPC分类号： A61K48/00 , C12N15/11 , C07H21/02 , C07H21/04 , C12N15/113
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/341 , C12N2310/345 , C12N2310/346 , C12N2310/3525 , C12N2320/50 , C12N2310/322 , C12N2310/3531 , C12N2310/3533 , C12N2310/321 , C12N2310/3521
摘要： The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.
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公开(公告)号：US09006198B2
公开(公告)日：2015-04-14
申请号：US13577622
申请日：2011-02-08
申请人： C. Frank Bennett , Michael Hayden , Susan M. Freier , Sarah Greenlee , Jeffrey Carroll , Simon Warby , Eric E. Swayze
发明人： C. Frank Bennett , Michael Hayden , Susan M. Freier , Sarah Greenlee , Jeffrey Carroll , Simon Warby , Eric E. Swayze
IPC分类号： C12N15/11 , C12Q1/68 , C12N15/113
CPC分类号： C12Q1/6883 , C12N15/113 , C12N2310/11 , C12N2320/34 , C12Q1/6811 , C12Q1/6897 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , C12Q2525/207 , C12Q2535/131 , C12Q2539/107 , C12Q2521/327 , C12Q2525/121 , C12Q2525/185
摘要： Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).
摘要翻译： 本文公开了用于选择性降低含有单核苷酸多态性（SNP）的亨廷顿氏基因的等位变体的表达的反义化合物和方法。 这些方法，化合物和组合物可用于治疗，预防或改善亨廷顿病（HD）。
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公开(公告)号：US08957040B2
公开(公告)日：2015-02-17
申请号：US13577616
申请日：2011-02-08
IPC分类号： C12N15/11 , C12Q1/68 , C12N15/113
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2320/34
摘要： Disclosed herein are antisense compounds and methods for selectively of reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative, such as Huntington's Disease (HD).
摘要翻译： 本文公开了用于选择性降低含有单核苷酸多态性（SNP）的基因的等位变体的表达的反义化合物和方法。 这些方法，化合物和组合物可用于治疗，预防或改善疾病，包括神经变性如亨廷顿病（HD）。
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5.发明授权Modulation of signal transducer and activator of transcription 3 (STAT3)expression 有权信号转导和转录激活因子3（STAT3）表达的调控公开(公告)号：US08816056B2
公开(公告)日：2014-08-26
申请号：US13436558
申请日：2012-03-30
IPC分类号： C07H21/02 , C07H21/04 , C12N15/11 , C12N15/113 , C12N15/00
CPC分类号： C12N15/113 , C07H21/00 , C07H21/04 , C12N15/00 , C12N15/11 , C12N15/1135 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2320/30 , C12N2310/321 , C12N2310/3521 , C12N2310/3525
摘要： Disclosed herein are antisense compounds and methods for decreasing STAT3 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate hyperproliferative diseases.
摘要翻译： 本文公开了用于降低STAT3 mRNA和蛋白质表达的反义化合物和方法。 这些方法，化合物和组合物可用于治疗，预防或改善过度增殖性疾病。
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公开(公告)号：US08673871B2
公开(公告)日：2014-03-18
申请号：US12299764
申请日：2007-05-07
申请人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric E. Swayze , Edward Wancewicz
发明人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric E. Swayze , Edward Wancewicz
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/3515 , C12Y203/0102 , C12N2310/3521
摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。
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公开(公告)号：US08586554B2
公开(公告)日：2013-11-19
申请号：US12299607
申请日：2007-05-07
申请人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric E. Swayze , Edward Wancewicz
发明人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric E. Swayze , Edward Wancewicz
IPC分类号： C12N15/11
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/3515 , C12Y203/0102 , C12N2310/3521
摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。
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8.发明申请公开(公告)号：US20130260460A1
公开(公告)日：2013-10-03
申请号：US13643062
申请日：2011-04-22
申请人： Jeremy Lackey , Muthiah Manoharan , Kallanthottathil Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash
发明人： Jeremy Lackey , Muthiah Manoharan , Kallanthottathil Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash
IPC分类号： C12N15/113 , C07H21/00
CPC分类号： C12N15/113 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00
摘要： This invention relates to conformationally locked dinucleotide motifs for exo- and phosphate stabilization. For instance, oligonucleotides can be prepared having one or more of the following formulas (IV-IX).
摘要翻译： 本发明涉及用于外切和磷酸酯稳定化的构象锁定二核苷酸基序。 例如，可以制备具有一个或多个下式（IV-IX）的寡核苷酸。
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9.发明申请5'-SUBSTITUTED BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM 有权5'-取代的双环核苷酸和其制备的低聚物公开(公告)号：US20130041144A1
公开(公告)日：2013-02-14
申请号：US13580218
申请日：2011-03-10
申请人： Michael T. Migawa , Thazha P. Prakash , Charles Allerson , Balkrishen Bhat , Punit P. Seth , Eric E. Swayze
发明人： Michael T. Migawa , Thazha P. Prakash , Charles Allerson , Balkrishen Bhat , Punit P. Seth , Eric E. Swayze
IPC分类号： C07H19/02 , C07H19/06 , C07H21/04 , C07H19/16 , C07H19/20 , C07H19/24 , C07H23/00 , C07H19/10
CPC分类号： C07H19/073 , C07H19/173 , C07H21/04 , C12N15/111 , C12N2310/3231
摘要： Provided herein are novel 5′-(S)—CH3 substituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5′-(S)—CH3 substituted bicyclic nucleosides includes a 2′ to 4′ bridging group. The 5′-(S)—CH3 substituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
摘要翻译： 本文提供了新的5' - （S）-CH 3取代的双环核苷，由其制备的低聚化合物和使用低聚化合物的方法。 更具体地，每个新的5' - （S）-CH 3取代的双环核苷的呋喃糖环包括2'至4'桥连基团。 预期5' - （S）-CH 3取代的双环核苷可用于增强所掺入的寡聚化合物的一种或多种性质，例如增加结合亲和力。 在某些实施方案中，本文提供的寡聚化合物与靶RNA的一部分杂交，导致靶RNA的正常功能丧失。
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公开(公告)号：US08362232B2
公开(公告)日：2013-01-29
申请号：US12883049
申请日：2010-09-15
申请人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric E. Swayze , Edward Wancewicz
发明人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric E. Swayze , Edward Wancewicz
IPC分类号： C07H21/04
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/3515 , C12Y203/0102 , C12N2310/3521
摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。
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