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1.发明申请公开(公告)号：US20120157509A1
公开(公告)日：2012-06-21
申请号：US13327271
申请日：2011-12-15
申请人： Philipp Hadwiger , Torsten Hoffmann , Eric A. Kitas , Peter Mohr , Ingo Roehl , Linda Valis , David B. Rozema , David L. Lewis , Darren H. Wakefield
发明人： Philipp Hadwiger , Torsten Hoffmann , Eric A. Kitas , Peter Mohr , Ingo Roehl , Linda Valis , David B. Rozema , David L. Lewis , Darren H. Wakefield
IPC分类号： A61K31/7088 , C07K14/00 , C07H21/02
CPC分类号： C07K5/1021 , C07H21/02
摘要： The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.
摘要翻译： 本发明涉及用于靶向将RNA干扰（RNAi）多核苷酸递送至细胞体内的组合物。 与单独的靶向配体相比，药代动力学调节剂改善体内靶向。 靶向配体 - 药代动力学调节剂靶向部分靶向的RNAi多核苷酸可以单独施用或与共靶向递送聚合物一起施用。
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2.发明授权Galactose cluster-pharmacokinetic modulator targeting moiety for siRNA 有权用于siRNA的半乳糖簇 - 药代动力学调节剂靶向部分公开(公告)号：US09249179B2
公开(公告)日：2016-02-02
申请号：US13327271
申请日：2011-12-15
申请人： Philipp Hadwiger , Torsten Hoffmann , Eric A. Kitas , Peter Mohr , Ingo Roehl , Linda Valis , David B. Rozema , David L. Lewis , Darren H. Wakefield
发明人： Philipp Hadwiger , Torsten Hoffmann , Eric A. Kitas , Peter Mohr , Ingo Roehl , Linda Valis , David B. Rozema , David L. Lewis , Darren H. Wakefield
IPC分类号： A61K31/7088 , C07H21/02
CPC分类号： C07K5/1021 , C07H21/02
摘要： The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.
摘要翻译： 本发明涉及用于靶向将RNA干扰（RNAi）多核苷酸递送至细胞体内的组合物。 与单独的靶向配体相比，药代动力学调节剂改善体内靶向。 靶向配体 - 药代动力学调节剂靶向部分靶向的RNAi多核苷酸可以单独施用或与共靶向递送聚合物一起施用。
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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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4.发明授权公开(公告)号：US08802773B2
公开(公告)日：2014-08-12
申请号：US13833814
申请日：2013-03-15
申请人： David B Rozema , David L Lewis , Darren H Wakefield , Eric A Kitas , Philipp Hadwiger , Jon A Wolff , Ingo Roehl , Peter Mohr , Torsten Hoffmann , Kerstin Jahn-Hofmann , Hans Martin Mueller , Guenther Ott , Andrei V Blokhin , Jeffrey C Carlson , Jonathan D Benson
发明人： David B Rozema , David L Lewis , Darren H Wakefield , Eric A Kitas , Philipp Hadwiger , Jon A Wolff , Ingo Roehl , Peter Mohr , Torsten Hoffmann , Kerstin Jahn-Hofmann , Hans Martin Mueller , Guenther Ott , Andrei V Blokhin , Jeffrey C Carlson , Jonathan D Benson
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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6.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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7.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：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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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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