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公开(公告)号：US20060122096A1
公开(公告)日：2006-06-08
申请号：US11312319
申请日：2005-12-20
申请人： David Rozema , Darren Wakefield , Jon Wolff , Kirk Ekena , James Hagstrom
发明人： David Rozema , Darren Wakefield , Jon Wolff , Kirk Ekena , James Hagstrom
IPC分类号： A61K48/00 , A61K38/17 , C07K14/47 , C07D475/10
CPC分类号： A61K47/60
摘要： An process for the reversible modification of an amine-containing compound is described. Modification of the compound can be used to facilitate delivery of molecules to cells in vitro and in vivo or to alter interactions or activities the compounds. The described modifiers can also be utilized as cross-linkers.
摘要翻译： 描述了含胺化合物的可逆修饰的方法。 化合物的修饰可用于促进分子在体外和体内递送至细胞，或改变化合物的相互作用或活性。 所描述的改性剂也可以用作交联剂。
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公开(公告)号：US20050250683A9
公开(公告)日：2005-11-10
申请号：US10444662
申请日：2003-05-23
申请人： David Rozema , Darren Wakefield , Jon Wolff , Kirk Ekena , James Hagstrom
发明人： David Rozema , Darren Wakefield , Jon Wolff , Kirk Ekena , James Hagstrom
CPC分类号： C12N15/87 , A61K38/00 , A61K47/60 , A61K48/00 , A61K48/0008 , A61K48/0041 , C07H21/00 , C07H21/04 , C07K7/06
摘要： An process for the reversible modification of membrane interaction of a compound is described. Modification of membrane interaction can be used to facilitate delivery of molecules to cells in vitro and in vivo. The described modifiers, which are used to reversibly inactivate the membrane active compounds, can also be utilized as cross-linkers or to reverse the charge of a molecule.
摘要翻译： 描述了化合物的膜相互作用的可逆修饰的方法。 膜相互作用的改变可用于促进分子在体外和体内传递给细胞。 用于可逆灭活膜活性化合物的所述改性剂也可用作交联剂或逆转分子的电荷。
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公开(公告)号：US20070036865A1
公开(公告)日：2007-02-15
申请号：US11533115
申请日：2006-09-19
申请人： David Rozema , Darren Wakefield , Jon Wolff , Vladimir Budker , Tatyana Budker , Sean Monahan , Vladimir Trubetskoy , James Hagstrom , Aaton Loomis , Paul Slattum
发明人： David Rozema , Darren Wakefield , Jon Wolff , Vladimir Budker , Tatyana Budker , Sean Monahan , Vladimir Trubetskoy , James Hagstrom , Aaton Loomis , Paul Slattum
摘要： We describe pH-sensitive endosomolytic polymers, delivery particles containing pH-sensitive endosomolytic polymers. The described particles are capable of delivering polynucleotides to cells from the peripheral circulation with subsequent release from endosomes. The endosomolytic polymers are inactive outside the cell but disrupt membranes upon exposure to an acidified endosomal compartment.
摘要翻译： 我们描述了pH敏感的内分泌溶解聚合物，包含pH敏感的内分解溶解聚合物的递送颗粒。 所述的颗粒能够将多核苷酸递送至来自外周循环的细胞，随后从内体释放。 内细胞分解的聚合物在细胞外是无活性的，但在暴露于酸化的内体室时破坏膜。
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公开(公告)号：US20060063257A1
公开(公告)日：2006-03-23
申请号：US11256322
申请日：2005-10-21
申请人： Darren Wakefield , David Rozema , Jon Wolff , Vladimir Trubetskoy , James Hagstrom , Vladimir Budker , Jason Klein , So Wong
发明人： Darren Wakefield , David Rozema , Jon Wolff , Vladimir Trubetskoy , James Hagstrom , Vladimir Budker , Jason Klein , So Wong
IPC分类号： C12N15/87
CPC分类号： C12N15/87 , A61K47/6455 , C12N15/88
摘要： Polyampholyte are able to condense nucleic acid to form small complexes which can be utilized in the delivery of nucleic acid to mammalian cells. The polyampholytes can be formed prior to interaction with nucleic acid or they can be formed in the presence of nucleic acid. Stabilized polycation/nucleic acid complexes can be modified to reduce the positive charge of the polycation and add targeting ligands without destabilizing the complex. The resultant particles retain their small size and are more effective in delivery of nucleic acid to cells in vivo.
摘要翻译： 聚阴离子能够冷凝核酸以形成可用于将核酸递送至哺乳动物细胞的小复合物。 聚阴离子可以在与核酸相互作用之前形成，或者可以在核酸存在下形成。 可以修饰稳定的聚阳离子/核酸复合物以减少聚阳离子的正电荷并添加靶向配体而不使复合物失稳。 所得颗粒保留其小尺寸并且在体内将核酸递送至细胞更有效。
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公开(公告)号：US20050170505A1
公开(公告)日：2005-08-04
申请号：US11046598
申请日：2005-01-28
申请人： Darren Wakefield , David Rozema , Jon Wolff , Vladimir Trubetskoy , James Hagstrom , Vladimir Budker , Jason Klein , So Wong
发明人： Darren Wakefield , David Rozema , Jon Wolff , Vladimir Trubetskoy , James Hagstrom , Vladimir Budker , Jason Klein , So Wong
CPC分类号： C12N15/87 , A61K47/6455 , C12N15/88
摘要： Polyampholyte are able to condense nucleic acid to form small complexes which can be utilized in the delivery of nucleic acid to mammalian cells. The polyampholytes can be formed prior to interaction with nucleic acid or they can be formed in the presence of nucleic acid. Stabilized polycation/nucleic acid complexes can be modified to reduce the positive charge of the polycation and add targeting ligands without destabilizing the complex. The resultant particles retain their small size and are more effective in delivery of nucleic acid to cells in vivo.
摘要翻译： 聚阴离子能够冷凝核酸以形成可用于将核酸递送至哺乳动物细胞的小复合物。 聚阴离子可以在与核酸相互作用之前形成，或者可以在核酸存在下形成。 可以修饰稳定的聚阳离子/核酸复合物以减少聚阳离子的正电荷并添加靶向配体而不使复合物不稳定。 所得颗粒保留其小尺寸并且在体内将核酸递送至细胞更有效。
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6.发明申请公开(公告)号：US20130190484A1
公开(公告)日：2013-07-25
申请号：US13833814
申请日：2013-03-15
申请人： David Rozema , David Lewis , Darren Wakefield , Eric Kitas , Philipp Hadwiger , Jon Wolff , Ingo Roehl , Peter Mohr , Torsten Hoffmann , Kerstin Jahn-Hofmann , Hans Martin Mueller , Guenther Ott , Andrei Blokhin , Jeffrey Carlson , Jonathan Benson
发明人： David Rozema , David Lewis , Darren Wakefield , Eric Kitas , Philipp Hadwiger , Jon Wolff , Ingo Roehl , Peter Mohr , Torsten Hoffmann , Kerstin Jahn-Hofmann , Hans Martin Mueller , Guenther Ott , Andrei Blokhin , Jeffrey Carlson , Jonathan Benson
IPC分类号： C12N15/113 , C07C271/20 , C07C69/96
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：US20050037496A1
公开(公告)日：2005-02-17
申请号：US10899509
申请日：2004-07-26
申请人： David Rozema , Vladimir Budker , James Hagstrom , Vladimir Trubetskoy , Jon Wolff , Sean Monahan , Paul Slattum
发明人： David Rozema , Vladimir Budker , James Hagstrom , Vladimir Trubetskoy , Jon Wolff , Sean Monahan , Paul Slattum
CPC分类号： C12N15/88 , A61K47/58 , A61K47/59 , A61K47/645
摘要： An polyampholyte is utilized in a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The complex can be formed with an appropriate amount of positive and/or negative charge such that the resulting complex can be delivered to the extravascular space and may be further delivered to a cell.
摘要翻译： 为了向细胞递送核酸，将聚二聚物用于缩合的多核苷酸复合物中。 络合物可以用适量的正电荷和/或负电荷形成，使得所得复合物可以递送到血管外空间并且可以进一步递送至细胞。
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公开(公告)号：US20060159764A1
公开(公告)日：2006-07-20
申请号：US11322419
申请日：2005-12-30
申请人： Sean Monahan , David Rozema , Vladimir Trubetskoy , Paul Slattum , Jon Wolff , Vladimir Budker , James Hagstrom , Lisa Hanson
发明人： Sean Monahan , David Rozema , Vladimir Trubetskoy , Paul Slattum , Jon Wolff , Vladimir Budker , James Hagstrom , Lisa Hanson
CPC分类号： C12N15/87 , A61K47/59 , A61K47/60 , A61K47/645 , A61K48/00 , A61K48/0008 , A61K48/0025 , A61K48/0041
摘要： A method of forming polymers in the presence of nucleic acid using template polymerization. These methods can be used for the delivery of nucleic acids, for condensing the nucleic acid, for forming nucleic acid binding polymers, for forming supramolecular complexes containing nucleic acid and polymer, and for forming an interpolyelectrolyte complex.
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公开(公告)号：US20050123600A1
公开(公告)日：2005-06-09
申请号：US11046590
申请日：2005-01-28
申请人： Vladimir Trubetskoy , James Hagstrom , Vladimir Budker , Jon Wolff , David Rozema , Sean Monahan
发明人： Vladimir Trubetskoy , James Hagstrom , Vladimir Budker , Jon Wolff , David Rozema , Sean Monahan
CPC分类号： C12N15/88 , A61K47/60 , A61K47/645
摘要： An polyampholyte is utilized in a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The complex can be formed with an appropriate amount of positive and/or negative charge such that the resulting complex can be delivered to the extravascular space and may be further delivered to a cell.
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公开(公告)号：US20050153451A1
公开(公告)日：2005-07-14
申请号：US10977025
申请日：2004-10-28
申请人： Jon Wolff , Vladimir Budker , James Hagstrom , Hans Herweijer , Julia Hegge , Paul Slattum , Sean Monahan , David Rozema
发明人： Jon Wolff , Vladimir Budker , James Hagstrom , Hans Herweijer , Julia Hegge , Paul Slattum , Sean Monahan , David Rozema
CPC分类号： A61K48/0083 , A61K38/00 , A61K48/00 , A61K48/0008 , A61K48/0016 , A61K48/0041 , A61K48/0075 , C12N15/87
摘要： Disclosed is a process for providing for expression of an exogenous nucleic acid in an extravascular parenchymal cell of a mammal. The nucleic acid is inserted into a vessel of a mammal and the permeability of the vessel is increased. Increasing permeability of the vessel allows delivery of the nucleic acid to an extravascular parenchymal cell.
摘要翻译： 公开了一种提供外源核酸在哺乳动物血管外实质细胞中表达的方法。 将核酸插入哺乳动物的容器中并增加血管的渗透性。 增加容器的渗透性允许将核酸递送至血管外实质细胞。
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