公开(公告)号：US08450282B2

公开(公告)日：2013-05-28

申请号：US13386554

申请日：2010-07-23

申请人： Kazunori Kataoka ,  Atsushi Ishii ,  Hiroyasu Takemoto ,  Masataka Nakanishi ,  Nobuhiro Nishiyama ,  Kanjiro Miyata

发明人： Kazunori Kataoka ,  Atsushi Ishii ,  Hiroyasu Takemoto ,  Masataka Nakanishi ,  Nobuhiro Nishiyama ,  Kanjiro Miyata

IPC分类号： A61K38/00 ,  C07K14/72 ,  C07K14/705

CPC分类号： C08L79/02 ,  C08G69/10 ,  C08G73/0206 ,  C08G73/028 ,  C08L77/04

摘要： There are provided an anionic polymer, a polyion complex, and a ternary polymer composite, each of which is stable in a biological environment and is capable of realizing small RNA delivery without causing any undesired immune response. An anionic polymer according to an embodiment of the invention includes: a main chain which includes repeating units having carboxyl groups; and a side chain which is linked with part of the carboxyl groups in the main chain and is represented by the following formula: -A-B—X where: A represents a residue having one or more aminoethyl bonds; B represents an in vivo cleavable bond; and X represents a small RNA. A polyion complex according to an embodiment of the invention includes the anionic polymer as described above and a cationic polymer. A ternary polymer composite according to an embodiment of the invention includes the polyion complex as described above and a charge conversional polymer.

摘要翻译： 提供阴离子聚合物，聚离子络合物和三元聚合物复合材料，其中每一种在生物环境中都是稳定的并且能够实现小的RNA递送而不引起任何不期望的免疫应答。 根据本发明实施方案的阴离子聚合物包括：主链，其包含具有羧基的重复单元; 和与主链中部分羧基连接并由下式表示的侧链：-A-B-X其中：A表示具有一个或多个氨基乙基的残基; B代表体内可剪切键; X表示小RNA。 根据本发明实施方案的聚离子络合物包括如上所述的阴离子聚合物和阳离子聚合物。 根据本发明实施方案的三元聚合物复合物包括如上所述的聚离子络合物和电荷转移聚合物。

公开(公告)号：US20120196810A1

公开(公告)日：2012-08-02

申请号：US13386554

申请日：2010-07-23

申请人： Kazunori Kataoka ,  Atsushi Ishii ,  Hiroyasu Takemoto ,  Masataka Nakanishi ,  Nobuhiro Nishiyama ,  Kanjiro Miyata

发明人： Kazunori Kataoka ,  Atsushi Ishii ,  Hiroyasu Takemoto ,  Masataka Nakanishi ,  Nobuhiro Nishiyama ,  Kanjiro Miyata

IPC分类号： A61K38/14 ,  C07K2/00

CPC分类号： C08L79/02 ,  C08G69/10 ,  C08G73/0206 ,  C08G73/028 ,  C08L77/04

摘要： There are provided an anionic polymer, a polyion complex, and a ternary polymer composite, each of which is stable in a biological environment and is capable of realizing small RNA delivery without causing any undesired immune response. An anionic polymer according to an embodiment of the invention includes: a main chain which includes repeating units having carboxyl groups; and a side chain which is linked with part of the carboxyl groups in the main chain and is represented by the following formula: -A-B—X where : A represents a residue having one or more aminoethyl bonds; B represents an in vivo cleavable bond; and X represents a small RNA. A polyion complex according to an embodiment of the invention includes the anionic polymer as described above and a cationic polymer. A ternary polymer composite according to an embodiment of the invention includes the polyion complex as described above and a charge conversional polymer.

摘要翻译： 提供阴离子聚合物，聚离子络合物和三元聚合物复合材料，其中每一种在生物环境中都是稳定的并且能够实现小的RNA递送而不引起任何不期望的免疫应答。 根据本发明实施方案的阴离子聚合物包括：主链，其包含具有羧基的重复单元; 和与主链中部分羧基连接并由下式表示的侧链：-A-B-X其中：A表示具有一个或多个氨基乙基的残基; B代表体内可剪切键; X表示小RNA。 根据本发明实施方案的聚离子络合物包括如上所述的阴离子聚合物和阳离子聚合物。 根据本发明实施方案的三元聚合物复合物包括如上所述的聚离子络合物和电荷转移聚合物。

公开(公告)号：US08431545B2

公开(公告)日：2013-04-30

申请号：US12922116

申请日：2009-03-06

申请人： Kazunori Kataoka ,  Nobuhiro Nishiyama ,  Atsushi Ishii ,  Yasuki Kato ,  Kanjiro Miyata ,  Hyunjin Kim ,  Hiroyasu Takemoto

发明人： Kazunori Kataoka ,  Nobuhiro Nishiyama ,  Atsushi Ishii ,  Yasuki Kato ,  Kanjiro Miyata ,  Hyunjin Kim ,  Hiroyasu Takemoto

IPC分类号： A61K48/00 ,  A61K38/00 ,  A61K47/00 ,  A61K9/127 ,  A61K9/14 ,  A61P35/00 ,  A01N25/00

CPC分类号： C08G69/10 ,  C08G81/00 ,  Y10T428/2982

摘要： The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.

摘要翻译： 本发明涉及含有不带电荷的亲水性聚合物链段和阳离子聚氨基酸链嵌段的嵌段共聚物，其中亲水性聚合物链嵌段共价键合到聚氨基酸链嵌段的主链的一端，疏水基 与聚氨基酸链嵌段中氨基酸重复单元的侧链共价结合不少于10％且不大于70％。 该嵌段共聚物在生理条件下与siRNA（小分子核酸）形成稳定的聚集体。

公开(公告)号：US20110052917A1

公开(公告)日：2011-03-03

申请号：US12922116

申请日：2009-03-06

申请人： Kazunori Kataoka ,  Nobuhiro Nishiyama ,  Atsushi Ishii ,  Yasuki Kato ,  Kanjiro Miyata ,  Hyunjin Kim ,  Hiroyasu Takemoto

发明人： Kazunori Kataoka ,  Nobuhiro Nishiyama ,  Atsushi Ishii ,  Yasuki Kato ,  Kanjiro Miyata ,  Hyunjin Kim ,  Hiroyasu Takemoto

IPC分类号： B32B27/00 ,  C08G69/48 ,  B82Y5/00

CPC分类号： C08G69/10 ,  C08G81/00 ,  Y10T428/2982

摘要： The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.

摘要翻译： 本发明涉及含有不带电荷的亲水性聚合物链段和阳离子聚氨基酸链嵌段的嵌段共聚物，其中亲水性聚合物链嵌段共价键合到聚氨基酸链嵌段的主链的一端，疏水基 与聚氨基酸链嵌段中氨基酸重复单元的侧链共价结合不少于10％且不大于70％。 该嵌段共聚物在生理条件下与siRNA（小分子核酸）形成稳定的聚集体。

公开(公告)号：US07829657B2

公开(公告)日：2010-11-09

申请号：US11884146

申请日：2006-02-08

申请人： Kazunori Kataoka ,  Keiji Itaka ,  Nobuhiro Nishiyama ,  Shigeto Fukushima ,  Woo-Dong Jang ,  Kanjiro Miyata ,  Masataka Nakanishi ,  Shunsaku Asano ,  Naoki Kanayama

发明人： Kazunori Kataoka ,  Keiji Itaka ,  Nobuhiro Nishiyama ,  Shigeto Fukushima ,  Woo-Dong Jang ,  Kanjiro Miyata ,  Masataka Nakanishi ,  Shunsaku Asano ,  Naoki Kanayama

IPC分类号： C08G69/08

CPC分类号： A61K48/0041 ,  A61K47/60 ,  A61K47/6455 ,  C08G18/0814 ,  C08G63/6854 ,  C08G69/10 ,  C08G73/028 ,  C08G73/0293 ,  C12N15/88

摘要： Disclosed is a composition for the delivery of nucleic acid to target cells or tissues, which comprises a polycationically charged polymer as a carrier of nucleic acid. The polycationically charged polymer is a polymer which may comprise a charged polymer segment having a main chain based on poly(amino acid), polysaccharide, polyester, polyether, polyurethane or vinyl polymer and having, as a side chain, a group of formula —NH—(CH2)a—(NH(CH2)2)e—NH2 (wherein a and e independently denote an integer of 1 to 5) which is connected to the main chain either directly or via a linker. The disclosed composition has low toxicity, and has a high efficiency in introducing nucleic acid into cells.

摘要翻译： 公开了用于将核酸递送至靶细胞或组织的组合物，其包含作为核酸载体的聚阳离子带电聚合物。 聚阳离子带电聚合物是聚合物，其可以包含具有基于聚（氨基酸），多糖，聚酯，聚醚，聚氨酯或乙烯基聚合物的主链的带电聚合物链段，并且具有作为侧链的式-NH基团 - （CH 2）a - （NH（CH 2）2）e-NH 2（其中a和e独立地表示1至5的整数），其直接或通过连接体与主链连接。 所公开的组合物具有低毒性，并且在将核酸引入细胞中具有高效率。

公开(公告)号：US20080249049A1

公开(公告)日：2008-10-09

申请号：US11884146

申请日：2006-02-08

申请人： Kazunori Kataoka ,  Keiji Itaka ,  Nobuhiro Nishiyama ,  Shigeto Fukushima ,  Woo-Dong Jang ,  Kanjiro Miyata ,  Masataka Nakanishi ,  Shunsaku Asano ,  Naoki Kanayama

发明人： Kazunori Kataoka ,  Keiji Itaka ,  Nobuhiro Nishiyama ,  Shigeto Fukushima ,  Woo-Dong Jang ,  Kanjiro Miyata ,  Masataka Nakanishi ,  Shunsaku Asano ,  Naoki Kanayama

IPC分类号： A61K48/00 ,  C12N5/00 ,  C08G12/00 ,  A61P43/00

CPC分类号： A61K48/0041 ,  A61K47/60 ,  A61K47/6455 ,  C08G18/0814 ,  C08G63/6854 ,  C08G69/10 ,  C08G73/028 ,  C08G73/0293 ,  C12N15/88

摘要： A composition for the delivery of nucleic acid to target cells or tissues, which comprises polycationically charged polymer as a carrier of nucleic acid is provided. Said polycationically charged polymer is a polymer which may comprise a charged polymer segment having a main chain based on poly(amino acid), polysaccharide, polyester, polyether, polyurethane or vinyl polymer and having, as a side chain, a group of formula —NH—(CH2)a—(NH(CH2)2)e—NH2 (wherein a and e independently denote an integer of 1 to 5) which is connected to said main chain either directly or via a linker. This composition is low-toxic, and has a high efficiency in introducing nucleic acid into cells.

摘要翻译： 提供了用于将核酸递送至靶细胞或组织的组合物，其包含作为核酸载体的聚阳离子带电聚合物。 所述聚阳离子带电聚合物是聚合物，其可以包含带有聚合物链段，该聚合物链段具有基于聚（氨基酸），多糖，聚酯，聚醚，聚氨酯或乙烯基聚合物的主链，并且具有作为侧链的式-NH - （CH 2）2 - （NH（CH 2）2） - （CH 2） 其中a和e独立地表示1〜5的整数），其直接或通过连接体与所述主链连接。 该组合物是低毒的，并且在将核酸引入细胞中具有高效率。

公开(公告)号：US20120149649A1

公开(公告)日：2012-06-14

申请号：US13258663

申请日：2011-02-23

申请人： Yasuki Kato ,  Atsushi Ishii ,  Naoya Shibata ,  Tatsuyuki Hayashi ,  Kazunori Kataoka ,  Kanjiro Miyata ,  Nobuhiro Nishiyama

发明人： Yasuki Kato ,  Atsushi Ishii ,  Naoya Shibata ,  Tatsuyuki Hayashi ,  Kazunori Kataoka ,  Kanjiro Miyata ,  Nobuhiro Nishiyama

IPC分类号： A61K38/16 ,  C07K7/08 ,  A61P43/00 ,  A61K38/08 ,  A61K38/10 ,  C07K7/06 ,  C07K14/00

CPC分类号： C08G69/10 ,  A61K47/60 ,  A61K47/6455 ,  C12N15/111 ,  C12N2310/14 ,  C12N2320/32

摘要： The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.

摘要翻译： 本发明提供一种适用于可在生理条件下与核酸形成稳定复合物的载体的阳离子聚氨基酸，并适当地释放细胞中的核酸。 阳离子聚氨基酸可以与核酸结合，并且包括在侧链中具有阳离子基团的阳离子氨基酸残基和在侧链中具有疏水基团的疏水性氨基酸残基。 阳离子聚氨基酸包含1〜20个单元的阳离子氨基酸残基，由下式（1）表示。 公式中每个符号的含义如说明书所示。

公开(公告)号：US08853167B2

公开(公告)日：2014-10-07

申请号：US13258663

申请日：2011-02-23

申请人： Yasuki Kato ,  Atsushi Ishii ,  Naoya Shibata ,  Tatsuyuki Hayashi ,  Kazunori Kataoka ,  Kanjiro Miyata ,  Nobuhiro Nishiyama

发明人： Yasuki Kato ,  Atsushi Ishii ,  Naoya Shibata ,  Tatsuyuki Hayashi ,  Kazunori Kataoka ,  Kanjiro Miyata ,  Nobuhiro Nishiyama

IPC分类号： A61K47/48 ,  C08G69/10 ,  C12N15/11

CPC分类号： C08G69/10 ,  A61K47/60 ,  A61K47/6455 ,  C12N15/111 ,  C12N2310/14 ,  C12N2320/32

摘要： The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.

摘要翻译： 本发明提供一种适用于可在生理条件下与核酸形成稳定复合物的载体的阳离子聚氨基酸，并适当地释放细胞中的核酸。 阳离子聚氨基酸可以与核酸结合，并且包括在侧链中具有阳离子基团的阳离子氨基酸残基和在侧链中具有疏水基团的疏水性氨基酸残基。 阳离子聚氨基酸包含1〜20个单元的阳离子氨基酸残基，由下式（1）表示。 公式中每个符号的含义如说明书所示。

公开(公告)号：US08546487B2

公开(公告)日：2013-10-01

申请号：US13147319

申请日：2010-02-15

申请人： Kazunori Kataoka ,  Shourong Wu ,  Takehiko Ishii ,  HyunJin Kim ,  Kanjiro Miyata ,  Nobuhiro Nishiyama

发明人： Kazunori Kataoka ,  Shourong Wu ,  Takehiko Ishii ,  HyunJin Kim ,  Kanjiro Miyata ,  Nobuhiro Nishiyama

IPC分类号： A61K47/48 ,  C08F283/04 ,  A01N25/26

CPC分类号： A61K48/0041 ,  A61K9/5192 ,  A61K31/7088 ,  A61K47/6455 ,  C07K14/001 ,  C07K14/003 ,  C08G69/08 ,  C08G69/10 ,  C08G69/48 ,  C12N15/111 ,  C12N2310/3181 ,  C12N2310/3513 ,  C12N2320/32

摘要： The present invention provides an efficient delivery system for a nucleic acid, more specifically, a cationic poly(amino acid) that has a side chain having a plurality of different amine functional groups in a moiety including a cationic group and that has a hydrophobic group introduced into part of the side chain, and a polyion complex (PIC) of the poly(amino acid) and an oligo- or polynucleotide.

摘要翻译： 本发明提供了一种用于核酸的有效递送系统，更具体地说，一种阳离子聚（氨基酸），该阳离子聚（氨基酸）在包括阳离子基团的部分中具有多个不同胺官能团的侧链，并且具有引入疏水基团 成为侧链的一部分，以及聚（氨基酸）的聚离子复合物（PIC）和寡核苷酸或多核苷酸。

公开(公告)号：US20110060123A1

公开(公告)日：2011-03-10

申请号：US12990386

申请日：2009-04-30

申请人： Kazunori Kataoka ,  Yan Lee ,  Nobuhiro Nishiyama ,  Kanjiro Miyata ,  Makoto Oba ,  Shigehiro Hiki ,  Mai Sanjo ,  HyunJin Kim

发明人： Kazunori Kataoka ,  Yan Lee ,  Nobuhiro Nishiyama ,  Kanjiro Miyata ,  Makoto Oba ,  Shigehiro Hiki ,  Mai Sanjo ,  HyunJin Kim

IPC分类号： C07K14/00

CPC分类号： C08G69/48 ,  A61K31/7084 ,  A61K31/785 ,  A61K48/0041 ,  C08G69/10 ,  C08G69/40 ,  C12N15/111 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32

摘要： Disclosed is a polymer composite (polyplex) that contains nucleic acid, a cationic polymer, and an anionic polymer. The anionic polymer covers the surface of the composite comprising the cationic polymer and nucleic acid, has a negative charge at neutral pH, and can change so as to have a positive charge at mildly acidic pH.

摘要翻译： 公开了含有核酸，阳离子聚合物和阴离子聚合物的聚合物复合物（polyplex）。 阴离子聚合物覆盖包含阳离子聚合物和核酸的复合物的表面，在中性pH下具有负电荷，并且可以改变以在弱酸性pH下具有正电荷。