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1.发明申请公开(公告)号：US20120172412A1
公开(公告)日：2012-07-05
申请号：US13336028
申请日：2011-12-23
申请人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffmann , Kerstin Jahn-Hofmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
发明人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffmann , Kerstin Jahn-Hofmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
CPC分类号： A61K38/00 , A61K31/7088 , A61K47/60 , A61K47/65 , A61K48/00 , C07C69/96 , C07C271/20 , C07H15/04 , C07H15/20 , C07H15/26 , C07K7/02 , C07K2317/77 , C12N15/1138 , C12N15/87 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/351 , C12N2320/30
摘要： The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.
摘要翻译： 本发明涉及用于将RNA干扰（RNAi）多核苷酸递送至细胞体内的组合物。 组合物包含用酶切割二肽 - 氨基苄基 - 碳酸酯掩蔽剂可逆地修饰的两亲膜活性多胺。 改性掩盖聚合物的膜活性，而可逆性提供生理反应性。 可逆修饰的多胺（动态多偶联物或DPC）进一步共价连接到RNAi多核苷酸或与靶向RNAi多核苷酸靶向分子缀合物共同施用。
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公开(公告)号：US08501930B2
公开(公告)日：2013-08-06
申请号：US13326433
申请日：2011-12-15
申请人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffmann , Kerstin Jahn-Hofmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
发明人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffmann , Kerstin Jahn-Hofmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
CPC分类号： A61K47/48261 , A61K47/549 , A61K47/64 , A61K47/6415 , C12N15/111 , C12N2310/14 , C12N2310/351 , 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 melittin delivery peptides. Delivery peptides 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 peptides.
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公开(公告)号：US20120165393A1
公开(公告)日：2012-06-28
申请号：US13326433
申请日：2011-12-15
申请人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffman , Kerstin Jahn-Hofmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
发明人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffman , Kerstin Jahn-Hofmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
CPC分类号： A61K47/48261 , A61K47/549 , A61K47/64 , A61K47/6415 , C12N15/111 , C12N2310/14 , C12N2310/351 , 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 melittin delivery peptides. Delivery peptides 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 peptides.
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。 靶向的RNAi多核苷酸与共靶向的蜂毒肽递送肽一起施用。 递送肽提供膜穿透功能，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肽的生理反应性。
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4.发明授权公开(公告)号：US08426554B2
公开(公告)日：2013-04-23
申请号：US13336028
申请日：2011-12-23
申请人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffmann , Kerstin Jahn-Hoffmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
发明人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jon A. Wolff , Andrei V. Blokhin , Jonathan D. Benson , Jeffrey C. Carlson , Philipp Hadwiger , Eric A. Kitas , Torsten Hoffmann , Kerstin Jahn-Hoffmann , Peter Mohr , Hans Martin Mueller , Guenther Ott , Ingo Roehl
IPC分类号： C07K16/00
CPC分类号： A61K38/00 , A61K31/7088 , A61K47/60 , A61K47/65 , A61K48/00 , C07C69/96 , C07C271/20 , C07H15/04 , C07H15/20 , C07H15/26 , C07K7/02 , C07K2317/77 , C12N15/1138 , C12N15/87 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/351 , C12N2320/30
摘要： The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.
摘要翻译： 本发明涉及用于将RNA干扰（RNAi）多核苷酸递送至细胞体内的组合物。 组合物包含用酶切割二肽 - 氨基苄基 - 碳酸酯掩蔽剂可逆地修饰的两亲膜活性多胺。 改性掩盖聚合物的膜活性，而可逆性提供生理反应性。 可逆修饰的多胺（动态多偶联物或DPC）进一步与RNAi多核苷酸共价连接，或与靶向RNAi多核苷酸靶向分子缀合物共同施用。
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公开(公告)号：US20080152661A1
公开(公告)日：2008-06-26
申请号：US11840468
申请日：2007-08-17
申请人： David B. Rozema , Darren H. Wakefield , Jason Klein , So Wong , Jon A. Wolff , David L. Lewis , James E. Hagstrom , Andrei Blokhin , Vladimir Trubetskoy , Hans Herweijer
发明人： David B. Rozema , Darren H. Wakefield , Jason Klein , So Wong , Jon A. Wolff , David L. Lewis , James E. Hagstrom , Andrei Blokhin , Vladimir Trubetskoy , Hans Herweijer
IPC分类号： A61K31/70 , A61K39/395 , C12N5/00 , A61K38/00
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58 , A61K48/0041
摘要： The present invention is directed to compounds, compositions, and methods useful for delivering polynucleotides or other cell-impermeable molecules to mammalian cells. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery vehicles. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.
摘要翻译： 本发明涉及可用于将多核苷酸或其它细胞不可渗透分子递送至哺乳动物细胞的化合物，组合物和方法。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送载体中的多偶联体系。 连接组成部分的多个可逆连接的使用提供了生理响应活性调节。
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公开(公告)号：US08137695B2
公开(公告)日：2012-03-20
申请号：US11840468
申请日：2007-08-17
申请人： David B. Rozema , James E. Hagstrom , Jason Klein , David L. Lewis , Sean D. Monahan , Darren H. Wakefield , Jon A. Wolff , So Wong
发明人： David B. Rozema , James E. Hagstrom , Jason Klein , David L. Lewis , Sean D. Monahan , Darren H. Wakefield , Jon A. Wolff , So Wong
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58 , A61K48/0041
摘要： The present invention is directed to compounds, compositions, and methods useful for delivering polynucleotides or other cell-impermeable molecules to mammalian cells. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery vehicles. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.
摘要翻译： 本发明涉及可用于将多核苷酸或其它细胞不可渗透分子递送至哺乳动物细胞的化合物，组合物和方法。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送载体中的多偶联体系。 连接组成部分的多个可逆连接的使用提供了生理响应活性调节。
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公开(公告)号：US08658211B2
公开(公告)日：2014-02-25
申请号：US13368796
申请日：2012-02-08
申请人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jason Klein , So Wong , Jon A. Wolff , James E. Hagstrom
发明人： David B. Rozema , Darren H. Wakefield , David L. Lewis , Jason Klein , So Wong , Jon A. Wolff , James E. Hagstrom
IPC分类号： A61K9/14 , C07D207/444 , C07H21/02 , C12N15/00 , C12N15/11
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58 , A61K48/0041 , C12N15/111 , C12N2310/14 , C12N2310/351 , C12N2320/32 , C12N2800/95 , C12N2810/10
摘要： The present invention is directed to compounds, compositions, and methods useful for delivering polynucleotides or other cell-impermeable molecules to mammalian cells. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery vehicles. The use of multiple reversible or labile linkages connecting component parts provides for physiologically responsive activity modulation.
摘要翻译： 本发明涉及可用于将多核苷酸或其它细胞不可渗透分子递送至哺乳动物细胞的化合物，组合物和方法。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送载体中的多偶联体系。 使用连接组成部分的多个可逆或不稳定的连接提供了生理响应活性调节。
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公开(公告)号：US08017109B2
公开(公告)日：2011-09-13
申请号：US12140703
申请日：2008-06-17
申请人： Darren H. Wakefield , David B. Rozema , Sean D. Monahan , Lori Higgs , Jon A. Wolff , James E. Hagstrom
发明人： Darren H. Wakefield , David B. Rozema , Sean D. Monahan , Lori Higgs , Jon A. Wolff , James E. Hagstrom
IPC分类号： A61K31/74
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58
摘要： The present invention is directed to membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.
摘要翻译： 本发明涉及可用于细胞递送化合物的膜活性聚合物。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送缀合物中的多偶联体系。 使用可逆修饰提供了生理反应活性调节。
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公开(公告)号：US20090048410A1
公开(公告)日：2009-02-19
申请号：US12123104
申请日：2008-05-19
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58 , A61K48/0008 , A61K48/0025 , A61K48/0041
摘要： The present invention is directed to a class of membrane active polymers useful for cellular delivery of compounds. Conjugation of the described membrane active polymers to targeting, anti-opsonization, and anti-aggregation agents provides polymers suitable for in vivo delivery. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.
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公开(公告)号：US20080287630A1
公开(公告)日：2008-11-20
申请号：US12140703
申请日：2008-06-17
申请人： Darren H. Wakefield , David B. Rozema , Sean D. Monahan , Lori Higgs , Jon A. Wolff , James E. Hagstrom
发明人： Darren H. Wakefield , David B. Rozema , Sean D. Monahan , Lori Higgs , Jon A. Wolff , James E. Hagstrom
IPC分类号： C08F220/52
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58
摘要： The present invention is directed to membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.
摘要翻译： 本发明涉及可用于细胞递送化合物的膜活性聚合物。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送缀合物中的多偶联体系。 使用可逆修饰提供了生理反应活性调节。
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