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    PRODUCTION OF A COMPOSITION CONTAINING A COMPLEX BETWEEN A MEMBRANE COMPOSED OF A LIPID MONOLAYER AND A NUCLEIC ACID, AND, A LIPID MEMBRANE FOR ENCAPSULATING THE COMPLEX THEREIN
    4.
    发明公开
    PRODUCTION OF A COMPOSITION CONTAINING A COMPLEX BETWEEN A MEMBRANE COMPOSED OF A LIPID MONOLAYER AND A NUCLEIC ACID, AND, A LIPID MEMBRANE FOR ENCAPSULATING THE COMPLEX THEREIN 审中-公开
    含脂质单层膜与核酸组成的膜之间含有复合物的组合物的制备及用于包封其复合物的脂质膜的制备

    公开(公告)号：EP3301086A1

    公开(公告)日：2018-04-04

    申请号：EP17191653.9

    申请日：2012-11-02

    申请人： Kyowa Hakko Kirin Co., Ltd.

    发明人： KUBOYAMA, Takeshi ,  ERA, Tomohiro ,  NAOI, Tomoyuki ,  YAGI, Nobuhiro

    IPC分类号： C07C217/08 ,  A61K31/231 ,  A61K31/24 ,  A61K31/40 ,  A61P29/00 ,  A61P35/00 ,  C07C219/08 ,  C07C237/06 ,  C07C271/20 ,  C07D207/08 ,  C07D207/12 ,  C07D491/056 ,  C12N15/09 ,  A61K47/16 ,  A61K48/00

    CPC分类号： C07C217/06 ,  A61K9/0019 ,  A61K9/1272 ,  C07C217/08 ,  C07C219/08 ,  C07C237/06 ,  C07C237/08 ,  C07C271/16 ,  C07D207/08 ,  C07D207/12 ,  C07D295/08 ,  C07D317/28 ,  C07D401/04 ,  C07D491/04 ,  C07D491/056 ,  C12N15/88

    摘要： The present invention relates to a method for producing a composition containing a complex between a membrane composed of a lipid monolayer (reversed micelle) and a nucleic acid, and a lipid membrane for encapsulating the complex therein, comprising the following steps A to D:
    Step A: preparing a complex between the nucleic acid and a liposome comprising a cationic lipid represented by the formula (I) and/or a cationic lipid other than cationic lipid represented by the formula (I);
    Step B: preparing a dispersion liquid by dispersing the complex in water or ethanol aqueous solution;
    Step C: preparing a solution by dissolving the formula (I) and/or the cationic lipid other than cationic lipid represented by the formula (I) in ethanol or an ethanol aqueous solution; and
    Step D: mixing the dispersion liquid and the solution, and optionally adding water;
    wherein the formula (I) is

    (wherein:
    R 1 and R 2 are, the same or different, each linear or branched alkyl, alkenyl or alkynyl having 12 to 24 carbon atoms,
    X 1 and X 2 are hydrogen atoms, or are combined together to form a single bond or alkylene,
    X 3 is absent or is alkyl having 1 to 6 carbon atoms, or alkenyl having 3 to 6 carbon atoms,
    when X 3 is absent,
    Y is absent, a and b are 0, L 3 is a single bond, R 3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, and L 1 and L 2 are -O-,
    Y is absent, a and b are, the same or different, 0 to 3, and are not 0 at the same time, L 3 is a single bond, R 3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, L 1 and L 2 are, the same or different, -O-, -CO-O- or -O-CO-,
    Y is absent, a and b are, the same or different, 0 to 3, L 3 is a single bond, R 3 is a hydrogen atom, and L 1 and L 2 are, the same or different, -O-, -CO-O- or -O-CO-, or
    Y is absent, a and b are, the same or different, 0 to 3, L 3 is -CO- or -CO-O-, R 3 is alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, wherein at least one of the substituents is amino, monoalkylamino, dialkylamino, or trialkylammonio, and L 1 and L 2 are , the same or different, -O-, -CO-O- or -O-CO-, and
    when X 3 is alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms, Y is a pharmaceutically acceptable anion, a and b are, the same or different, 0 to 3, L 3 is a single bond, R 3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, L 1 and L 2 are, the same or different, -O-, -CO-O- or -O-CO-).

    摘要翻译： 本发明涉及含有由脂质单层（反胶束）构成的膜与核酸之间的复合体的组合物的制造方法，以及将该复合体封入其中的脂质膜，其包括以下工序A〜D：工序 A：制备核酸与包含由式（I）表示的阳离子脂质和/或由式（I）表示的阳离子脂质以外的阳离子脂质的脂质体之间的复合物; 步骤B：通过将复合物分散在水或乙醇水溶液中制备分散液; 步骤C：将式（I）和/或式（I）代表的阳离子脂质以外的阳离子脂质溶解在乙醇或乙醇水溶液中制备溶液; 步骤D：将分散液和溶液混合，并任选加入水; 其中式（I）是（其中：R 1和R 2相同或不同，各自具有12-24个碳原子的直链或支链烷基，烯基或炔基，X 1和X 2是氢原子，或者结合在一起形成 当X 3不存在时，Y不存在，a和b为0，L 3为单键，R 3为单键或亚烷基，X 3不存在或为具有1至6个碳原子的烷基或具有3至6个碳原子的烯基 具有1至6个碳原子的烷基，具有3至6个碳原子的烯基或具有1至6个碳原子的烷基，或具有1至3个取代基取代的具有3至6个碳原子的烯基， 或者不同的氨基，一烷基氨基，二烷基氨基，三烷基氨基，羟基，烷氧基，氨基甲酰基，单烷基氨基甲酰基或二烷基氨基甲酰基，并且L 1和L 2为-O-，Y不存在，a和b相同或不同， 不同时为0，L 3为单键，R 3为碳原子数1〜6的烷基，碳原子数3〜6的烯基或碳原子数1〜6的烷基 或被1至3个相同或不同的取代基取代的具有3至6个碳原子的链烯基，所述取代基相同或不同，为氨基，单烷基氨基，二烷基氨基，三烷基氨基，羟基，烷氧基，氨基甲酰基，单烷基氨基甲酰基或二烷基氨基甲酰基， L2相同或不同，为-O - ， - CO-O-或-O-CO-，Y不存在，a和b相同或不同，为0至3，L3为单键，R3为 氢原子，并且L 1和L 2相同或不同，为-O - ， - CO-O-或-O-CO-或Y不存在，a和b相同或不同，为0至3， L3是-CO-或-CO-O-，R3是具有1至6个碳原子的烷基或被1至3个相同或不同的取代基取代的具有3至6个碳原子的烯基， 氨基甲酰基，单烷基氨基甲酰基或二烷基氨基甲酰基，其中至少一个取代基是氨基，一烷基氨基，二烷基氨基或三烷基氨基，并且L 1和L 2相同或不同，为-O- ，-CO-O-或-O-CO-，以及wh X 3为具有1至6个碳原子的烷基或具有3至6个碳原子的烯基，Y为药学上可接受的阴离子，a和b相同或不同，为0至3，L 3为单键，R 3为具有 1至6个碳原子的链烯基，具有3至6个碳原子的链烯基，L 1和L 2相同或不同，为-O - ， - CO-O-或-O-CO-）。

    COMPOSITION FOR INHIBITING EXPRESSION OF TARGET GENE
    5.
    发明公开
    COMPOSITION FOR INHIBITING EXPRESSION OF TARGET GENE 有权
    ZUSAMMENSETZUNG ZUR HEMMUNG VON ZIELGENEXPRESSION

    公开(公告)号：EP2319519A1

    公开(公告)日：2011-05-11

    申请号：EP09803053.9

    申请日：2009-07-31

    申请人： Kyowa Hakko Kirin Co., Ltd.

    发明人： YAGI, Nobuhiro ,  ENOKIZONO, Junichi

    IPC分类号： A61K31/712 ,  A61K9/127 ,  A61K31/7105 ,  A61K31/713 ,  A61K47/10 ,  A61K47/18 ,  A61K47/24 ,  A61K47/28 ,  A61K47/34 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00

    CPC分类号： A61K31/7105 ,  A61K9/0019 ,  A61K9/1271 ,  A61K31/712 ,  A61K31/713 ,  C12N15/1135 ,  C12N2310/14 ,  Y10T436/143333

    摘要： An object of the present invention is to provide a composition for suppressing expression of a target gene, and the like. A composition comprising an RNA-encapsulated liposome, wherein the RNA contains a sequence consisting of 15 to 30 contiguous bases of a target gene mRNA (hereinafter, sequence X) and a base sequence (hereinafter, complementary sequence X') complementary to the sequence X, 1 to 90% of all sugars binding to the bases of the sequence X and the complementary sequence X' being ribose substituted by a modifying group at 2' position, and the liposome being capable of reaching a tissue or an organ containing an expression site of the target gene is provide.

    摘要翻译： 本发明的目的是提供抑制靶基因表达的组合物等。 包含RNA包封的脂质体的组合物，其中RNA含有由靶基因mRNA（以下称为序列X）的15〜30个连续碱基和与序列X互补的碱基序列（以下称为互补序列X'）组成的序列 ，与所述序列X的碱基结合的所有糖的1至90％，并且所述互补序列X'为在2'位置上被修饰基团取代的核糖，并且所述脂质体能够到达包含表达位点的组织或器官 的目标基因。