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1.发明授权Compounds and methods for reversible modification of biologically active molecules 有权用于可逆修饰生物活性分子的化合物和方法公开(公告)号：US08541548B2
公开(公告)日：2013-09-24
申请号：US12140751
申请日：2008-06-17
申请人： David B. Rozema
发明人： David B. Rozema
CPC分类号： C07D495/04 , A01K2217/058 , A01K2267/0362 , A61K48/0041 , C07C233/21 , C07C233/31 , C07C233/39 , C07D307/60 , C07D475/00 , C12N15/87
摘要： The present invention is directed compounds for reversibly modification of biologically active molecules. 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： 本发明涉及可逆地修饰生物活性分子的化合物。 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：US09107957B2
公开(公告)日：2015-08-18
申请号：US13926380
申请日：2013-06-25
发明人： David B Rozema , David L Lewis , Darren Wakefield , Eric Kitas , Philipp Hadwiger , Jon Wolff , Ingo Röhl , Peter Mohr , Torsten Hoffmann , Kerstin Jahn-Hofmann , Hans Martin Mueller , Günther Ott , Andrei V Blokhin , Jonathan D Benson , Jeffrey C Carlson
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： 本发明涉及用于在体内向肝细胞靶向递送RNA干扰（RNAi）多核苷酸的组合物。 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：US08933047B2
公开(公告)日：2015-01-13
申请号：US13592403
申请日：2012-08-23
申请人： Darren H. Wakefield , David B. Rozema , Nicholas Rossi , Lauren Almeida , Anthony L. Perillo-Nicholas
发明人： Darren H. Wakefield , David B. Rozema , Nicholas Rossi , Lauren Almeida , Anthony L. Perillo-Nicholas
IPC分类号： C12N15/11 , C08F20/10 , C08F120/10 , C08F220/10 , A61K47/32 , C08F220/00 , C08F220/36
CPC分类号： B25F5/02 , A61K47/32 , A61K47/58 , B23D45/16 , B23Q13/00 , B27B5/29 , B27B9/00 , C08F220/00 , C08F220/34 , C08F220/36 , C08F220/18
摘要： The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.
摘要翻译： 本发明涉及膜活性聚（丙烯酸酯）聚合物和用于在体内靶向递送RNA干扰（RNAi）多核苷酸细胞的组合物。 RNAi多核苷酸与聚（丙烯酸酯）聚合物缀合，并且可逆地修饰聚合物以实现体内靶向递送。 聚（丙烯酸酯）的膜活性提供了从细胞外部到细胞内的RNAi多核苷酸的移动。 可逆修饰提供生理反应。
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公开(公告)号：US08313772B2
公开(公告)日：2012-11-20
申请号：US13032029
申请日：2011-02-22
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： 本发明涉及用于在体内向肝细胞靶向递送RNA干扰（RNAi）多核苷酸的组合物。 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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5.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：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：US20150104408A1
公开(公告)日：2015-04-16
申请号：US14552664
申请日：2014-11-25
发明人： Darren H. Wakefield , Nicholas A. Rossi , David B. Rozema , Lauren J. Almeida , Anthony L. Perillo-Nicholas
IPC分类号： A61K47/48 , C08F220/34 , A61K47/32
CPC分类号： B25F5/02 , A61K47/32 , A61K47/58 , B23D45/16 , B23Q13/00 , B27B5/29 , B27B9/00 , C08F220/00 , C08F220/34 , C08F220/36 , C08F220/18
摘要： The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.
摘要翻译： 本发明涉及膜活性聚（丙烯酸酯）聚合物和用于在体内靶向递送RNA干扰（RNAi）多核苷酸细胞的组合物。 RNAi多核苷酸与聚（丙烯酸酯）聚合物缀合，并且可逆地修饰聚合物以实现体内靶向递送。 聚（丙烯酸酯）的膜活性提供了从细胞外部到细胞内的RNAi多核苷酸的移动。 可逆修饰提供生理反应。
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8.发明授权公开(公告)号：US08809293B2
公开(公告)日：2014-08-19
申请号：US13535454
申请日：2012-06-28
申请人： Daniel Chin , Jochen Deckert , Markus Hossbach , Matthias John
发明人： Daniel Chin , Jochen Deckert , Markus Hossbach , Matthias John
CPC分类号： A61K31/713 , C12N15/1131 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/335 , C12N2310/3521 , A61K2300/00
摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a Hepatitis B Virus gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Hepatitis B Virus infection using said pharmaceutical composition; and methods for inhibiting the expression of a Hepatitis B Virus gene in a cell.
摘要翻译： 本发明涉及用于抑制乙型肝炎病毒基因表达的双链核糖核酸（dsRNA）。 本发明还涉及包含dsRNA或核酸分子的药物组合物或其编码与其药学上可接受的载体的载体; 使用所述药物组合物治疗由乙型肝炎病毒感染引起的疾病的方法; 以及抑制细胞中乙型肝炎病毒基因表达的方法。
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公开(公告)号：US20140128584A1
公开(公告)日：2014-05-08
申请号：US14119074
申请日：2012-05-31
IPC分类号： C07D307/89 , C07D307/60 , C07H15/26
CPC分类号： C07D307/89 , C07D307/60 , C07D307/66 , C07D307/88 , C07H15/08 , C07H15/26
摘要： We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.
摘要翻译： 我们描述适用于含胺分子的生理不稳定修饰的酸酐化合物。 所述的酸酐形成具有用于体内递送生物活性分子的所需动力学的可逆连接。 还描述了通过用所述酸酐修饰膜活性多胺而形成的内体分解聚合物。
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公开(公告)号：US20130121954A1
公开(公告)日：2013-05-16
申请号：US13592393
申请日：2012-08-23
IPC分类号： A61K47/48
CPC分类号： A61K47/48176 , A61K31/7105 , A61K47/58 , C08F218/04 , C08F218/10 , C08F2218/22 , C12N15/113 , C12N2310/14 , C12N2310/351 , C12N2320/30
摘要： The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.
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