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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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3.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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公开(公告)号：US08088904B2
公开(公告)日：2012-01-03
申请号：US12192847
申请日：2008-08-15
申请人： Eric E. Swayze , Andrew M. Siwkowski , Balkrishen Bhat , Thazha P. Prakash , Charles Allerson , Punit P. Seth
发明人： Eric E. Swayze , Andrew M. Siwkowski , Balkrishen Bhat , Thazha P. Prakash , Charles Allerson , Punit P. Seth
CPC分类号： C12N15/113 , C07H19/10 , C07H19/20 , C07H21/00 , C12N15/111 , C12N2310/323 , C12N2320/51
摘要： The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and 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.
摘要翻译： 本公开描述了四氢吡喃核苷类似物，由其制备的低聚化合物和使用寡聚化合物的方法。 更具体地，提供四氢吡喃核苷类似物，其具有一个或多个手性取代基，其可用于增强低聚化合物的性质，包括核酸酶抗性和结合亲和力。 在一些实施方案中，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：US08022193B2
公开(公告)日：2011-09-20
申请号：US12774527
申请日：2010-05-05
申请人： Punit P. Seth , Eric E. Swayze
发明人： Punit P. Seth , Eric E. Swayze
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.
摘要翻译： 本发明提供了包含这些核苷类似物的6-修饰的双环核苷类似物和寡聚化合物。 在优选的实施方案中，核苷类似物在6-位具有（R）或（S） - 双键。 这些双环核苷类似物可用于增强包括核酸酶抗性的寡聚化合物的性质。
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公开(公告)号：US20110166205A1
公开(公告)日：2011-07-07
申请号：US13063921
申请日：2009-09-23
申请人： Punit P. Seth , Eric E. Swayze
发明人： Punit P. Seth , Eric E. Swayze
IPC分类号： A61K31/7088 , C07H21/00 , C12N5/02 , C12Q1/68 , C12Q1/02
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.
摘要翻译： 本公开描述了取代的α-L-双环核苷类似物，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，提供具有一个或多个手性取代基的取代的α-L-双环核苷类似物，其可用于增强包括结合亲和力的寡聚化合物的性质。 在一些实施方案中，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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8.发明申请OLIGOMERIC COMPOUNDS HAVING AT LEAST ONE NEUTRALLY LINKED TERMINAL BICYCLIC NUCLEOSIDES 有权具有至少一个中性连接终端双相核苷酸的低分子化合物公开(公告)号：US20110130441A1
公开(公告)日：2011-06-02
申请号：US12934498
申请日：2009-04-03
申请人： Punit P. Seth , Eric E. Swayze
发明人： Punit P. Seth , Eric E. Swayze
CPC分类号： C07H21/00
摘要： The present disclosure describes oligomeric compounds having at least one bicyclic nucleoside attached to the 3′ or 5′ termini by a neutral internucleoside linkage and methods of using the oligomeric compounds. 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.
摘要翻译： 本公开内容描述了通过中性核苷间键连接至3'或5'末端的至少一个双环核苷的低聚化合物和使用寡聚化合物的方法。 在一些实施方案中，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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9.发明申请OLIGOMERIC COMPOUNDS COMPRISING TRICYCLIC NUCELOSIDES AND METHODS FOR THEIR USE 有权包含三聚核苷酸的低分子化合物及其使用方法公开(公告)号：US20110092570A1
公开(公告)日：2011-04-21
申请号：US12922832
申请日：2009-03-19
IPC分类号： A61K31/712 , C07H21/04 , C07H19/10
CPC分类号： C12N15/113 , A61K31/7042 , A61K31/7052 , A61K31/7088 , A61K31/712 , A61K31/7125 , C07H19/10 , C07H21/04 , C12N2310/11 , C12N2310/3125 , C12N2310/314 , C12N2310/316 , C12N2310/3231
摘要： The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
摘要翻译： 本公开提供三环核苷，包含至少一种三环核苷的寡聚化合物和使用寡聚化合物的方法。 本文提供的方法包括使细胞接触或向动物施用至少一种低聚化合物。 在某些实施方案中，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：US07666854B2
公开(公告)日：2010-02-23
申请号：US12331226
申请日：2008-12-09
申请人： Punit P. Seth , Eric E. Swayze
发明人： Punit P. Seth , Eric E. Swayze
CPC分类号： C07H21/00 , C07H7/02 , C07H9/04 , C07H13/04 , C07H15/18 , C07H17/02 , C07H19/04 , C07H19/06 , C07H19/16 , C07H23/00
摘要： The present disclosure describes bis-modified bicyclic nucleosides and oligomeric compounds that can be prepared comprising at least one of these bis-modified bicyclic nucleosides. More particularly, the bis-modified bicyclic nucleosides have at least one substituent group at the 5′-methylene and on the bridge methylene and can be chiral. These bis-modified bicyclic nucleosides are expected to be useful for enhancing one or more property of oligomeric compounds including for example enhancing nuclease resistance.
摘要翻译： 本公开描述了可以制备的双改性双环核苷和寡聚化合物，其包含这些双改性双环核苷中的至少一种。 更具体地，双改性双环核苷在5'-亚甲基和亚甲基桥上具有至少一个取代基，并且可以是手性的。 预期这些双改性双环核苷可用于增强寡聚化合物的一种或多种性质，包括例如增强核酸酶抗性。
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