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公开(公告)号:US09011919B2
公开(公告)日:2015-04-21
申请号:US13615938
申请日:2012-09-14
申请人: David B. Rozema , David L. Lewis , Darren H. Wakefield , Torsten Hoffmann , Eric Kitas , Peter Mohr , Philipp Hadwiger , Wilma Thuer , Linda Valis
发明人: David B. Rozema , David L. Lewis , Darren H. Wakefield , Torsten Hoffmann , Eric Kitas , Peter Mohr , Philipp Hadwiger , Wilma Thuer , Linda Valis
IPC分类号: A61K9/14 , C07H21/02 , C07K1/00 , A61K47/32 , A61K9/08 , A61K48/00 , C12N15/11 , C12N15/87 , A61K47/48
CPC分类号: C12N15/113 , A61K9/08 , A61K31/713 , A61K47/32 , A61K47/549 , A61K47/60 , A61K47/65 , A61K48/0041 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2310/141 , C12N2310/3515 , C12N2320/32
摘要: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.
摘要翻译: 本发明涉及用于将体内RNA干扰(RNAi)多核苷酸靶向递送至肝细胞的组合物。 靶向RNAi多核苷酸与共靶向递送聚合物一起施用。 递送聚合物提供膜穿透功能,用于将RNAi多核苷酸从细胞外部移动到细胞内。 可逆修饰提供对递送聚合物的生理反应性。
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公开(公告)号:US20110207799A1
公开(公告)日:2011-08-25
申请号:US13032029
申请日:2011-02-22
申请人: David B. Rozema , David L. Lewis , Darren H. Wakefield , Torsten Hoffmann , Erik Kitas , Peter Mohr , Philipp Hadwiger , Wilma Thuer , Linda Valis
发明人: David B. Rozema , David L. Lewis , Darren H. Wakefield , Torsten Hoffmann , Erik Kitas , Peter Mohr , Philipp Hadwiger , Wilma Thuer , Linda Valis
IPC分类号: A61K31/7105 , A61K31/711 , A61K31/713 , A61P1/16 , A61P35/00 , A61P31/12 , A61P3/00 , A61P3/10 , A61P3/06
CPC分类号: C12N15/113 , A61K9/08 , A61K31/713 , A61K47/32 , A61K47/549 , A61K47/60 , A61K47/65 , A61K48/0041 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2310/141 , C12N2310/3515 , C12N2320/32
摘要: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.
摘要翻译: 本发明涉及用于将体内RNA干扰(RNAi)多核苷酸靶向递送至肝细胞的组合物。 靶向RNAi多核苷酸与共靶向递送聚合物一起施用。 递送聚合物提供膜穿透功能,用于将RNAi多核苷酸从细胞外部移动到细胞内。 可逆修饰提供对递送聚合物的生理反应性。
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公开(公告)号:US20130245091A1
公开(公告)日:2013-09-19
申请号:US13615938
申请日:2012-09-14
申请人: David B. Rozema , David L. Lewis , Darren H. Wakefield , Torsten Hoffmann , Eric A. Kitas , Peter Mohr , Philipp Hadwiger , Wilma Thuer , Linda Valis
发明人: David B. Rozema , David L. Lewis , Darren H. Wakefield , Torsten Hoffmann , Eric A. Kitas , Peter Mohr , Philipp Hadwiger , Wilma Thuer , Linda Valis
CPC分类号: C12N15/113 , A61K9/08 , A61K31/713 , A61K47/32 , A61K47/549 , A61K47/60 , A61K47/65 , A61K48/0041 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2310/141 , C12N2310/3515 , C12N2320/32
摘要: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.
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公开(公告)号:US08569515B2
公开(公告)日:2013-10-29
申请号:US13099630
申请日:2011-05-03
申请人: Dieter Heindl , Dirk Kessler , Angelika Roesler , Christoph Seidel , Wilma Thuer
发明人: Dieter Heindl , Dirk Kessler , Angelika Roesler , Christoph Seidel , Wilma Thuer
IPC分类号: C07F9/24
CPC分类号: G01N33/5308 , C07F9/6552 , C07F9/65586 , Y02P20/55
摘要: The trivalent phosphorous atom of a compound is reacted with a reagent in such a manner that a stable phosphate mimetic or a specifier is formed. Phosphoramidites with a phosphorous atom containing at least one hydroxyl residue which is provided with a protective group are reacted for this purpose with a free hydroxyl group: In the first synthesis cycle the hydroxyl group is linked to a solid support via a cleavable or non-cleavable linker. In further synthesis cycles the hydroxyl group is created by cleavage of the protective group from the growing oligomer. This results in formation of a phosphorous acid triester which is reacted with azides. By selecting suitable monomers for the synthesis which have a defined stereoconformation compounds of Formula 1 are produced in a stereocontrolled manner.
摘要翻译: 使化合物的三价磷原子与试剂反应,形成稳定的磷酸酯模拟物或说明物。 具有至少一个含有保护基团的羟基残基的磷原子的亚磷酰胺与该游离羟基反应:在第一个合成循环中,羟基通过可裂解或不可裂解的方式与固体支持物连接 接头。 在进一步的合成循环中,通过从生长的低聚物中切割保护基而产生羟基。 这导致形成与叠氮化物反应的亚磷酸三酯。 通过选择具有定义的立体定构的合成合成单体,以立体控制的方式制备式1的化合物。
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公开(公告)号:US20110212861A1
公开(公告)日:2011-09-01
申请号:US13099630
申请日:2011-05-03
申请人: Dieter Heindl , Dirk Kessler , Angelika Roesler , Christoph Seidel , Wilma Thuer
发明人: Dieter Heindl , Dirk Kessler , Angelika Roesler , Christoph Seidel , Wilma Thuer
CPC分类号: G01N33/5308 , C07F9/6552 , C07F9/65586 , Y02P20/55
摘要: The trivalent phosphorous atom of a compound is reacted with a reagent in such a manner that a stable phosphate mimetic or a specifier is formed. Phosphoramidites with a phosphorous atom containing at least one hydroxyl residue which is provided with a protective group are reacted for this purpose with a free hydroxyl group: In the first synthesis cycle the hydroxyl group is linked to a solid support via a cleavable or non-cleavable linker. In further synthesis cycles the hydroxyl group is created by cleavage of the protective group from the growing oligomer. This results in formation of a phosphorous acid triester which is reacted with azides. By selecting suitable monomers for the synthesis which have a defined stereoconformation compounds of Formula 1 are produced in a stereocontrolled manner.
摘要翻译: 使化合物的三价磷原子与试剂反应,形成稳定的磷酸酯模拟物或说明物。 具有至少一个含有保护基团的羟基残基的磷原子的亚磷酰胺与该游离羟基反应:在第一个合成循环中,羟基通过可裂解或不可切割的方式与固体支持物连接 接头。 在进一步的合成循环中,通过从生长的低聚物中切割保护基而产生羟基。 这导致形成与叠氮化物反应的亚磷酸三酯。 通过选择具有定义的立体定构的合成合成单体,以立体控制的方式制备式1的化合物。
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