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    HETEROBIFUNCTIONAL MONODISPERSED POLYETHYLENE GLYCOL HAVING PEPTIDE LINKER
    5.
    发明申请
    HETEROBIFUNCTIONAL MONODISPERSED POLYETHYLENE GLYCOL HAVING PEPTIDE LINKER 有权

    公开(公告)号：US20220362397A1

    公开(公告)日：2022-11-17

    申请号：US17762719

    申请日：2020-09-25

    申请人： NOF CORPORATION

    发明人： Yuki MATSUNO ,  Hiroki YOSHIOKA ,  Akira SUZUKI

    IPC分类号： A61K47/68 ,  A61K47/60 ,  C07K5/06

    摘要： A heterobifunctional monodisperse polyethylene glycol with two adjacent monodisperse polyethylene glycol side chains, in which a peptide linker is degraded by intracellular enzymes to release a drug slowly and effectively mask the hydrophobicity of the drug, and an antibody-drug conjugate in which the antibody and the drug are bound using same is provided. A heterobifunctional monodisperse polyethylene glycol represented by the formula (1): wherein each symbol in the formula (1) is as defined in the DESCRIPTION.

    PRODUCTION METHOD OF POLYOXYETHYLENE DERIVATIVE HAVING PLURALITY OF HYDROXYL GROUPS AT TERMINAL
    6.
    发明申请
    PRODUCTION METHOD OF POLYOXYETHYLENE DERIVATIVE HAVING PLURALITY OF HYDROXYL GROUPS AT TERMINAL 审中-公开

    公开(公告)号：US20200079903A1

    公开(公告)日：2020-03-12

    申请号：US16492883

    申请日：2018-03-22

    申请人： NOF CORPORATION

    发明人： Hiroki YOSHIOKA ,  Yuji YAMAMOTO

    IPC分类号： C08G65/26 ,  C08G65/331

    摘要： A method of producing a polyoxyethylene derivative (1): where L1 is a divalent linker, X is a functional group capable of reacting with a physiologically active substance, a is 1 or 2, and n is from 11 to 3,650. The method includes Step (A): protecting 4 or 6 hydroxyl groups in a polyhydric alcohol having 5 or 7 hydroxyl groups by cyclic benzylidene acetalization to obtain a compound having a hydroxyl group at a 1-position and a protective group of a cyclic benzylidene acetal structure; Step (B): polymerizing from 11 to 3,650 moles of ethylene oxide to the compound obtained in the step (A) to obtain a polyoxyethylene derivative; Step (C): converting the hydroxyl group at a terminal of the polyoxyethylene derivative to a functional group capable of reacting with a physiologically active substance; and Step (D): deprotecting the protective group of the polyoxyethylene derivative.

    MULTI-ARM POLYETHYLENE GLYCOL DERIVATIVE, INTERMEDIATE THEREOF, AND METHOD FOR PRODUCING SAME
    9.
    发明申请
    MULTI-ARM POLYETHYLENE GLYCOL DERIVATIVE, INTERMEDIATE THEREOF, AND METHOD FOR PRODUCING SAME 审中-公开
    多臂聚乙烯衍生物，其中间体及其生产方法

    公开(公告)号：US20160326317A1

    公开(公告)日：2016-11-10

    申请号：US15216573

    申请日：2016-07-21

    申请人： NOF CORPORATION

    发明人： Hiroki YOSHIOKA ,  Midori HIRAI ,  Hitoshi NAKATSUHARA ,  Yuji YAMAMOTO

    IPC分类号： C08G65/26

    CPC分类号： C08G65/2609 ,  C08G65/2696 ,  C08G65/329 ,  C08G65/3322 ,  C08G65/33306 ,  C08G65/33337 ,  C08G65/33368 ,  C08G65/33389 ,  C08G2650/30

    摘要： A multi-arm polyethylene glycol derivative having a narrow molecular weight distribution represented by the formula (1): wherein, L represents a group selected from a linear or branched alkylene, arylene, or cycloalkylene group having two or more carbon atoms and combinations thereof, which may have an ether bond in a chain; X represents a dehydroxylation residue of a linear sugar alcohol having 5 or 7 carbon atoms; m is the number of polyethylene glycol chains bonded to X and represents 4 or 6; n is the average addition molar number of oxyethylene groups and represents an integer of 3 to 600; Y represents a single bond or an alkylene group as further defined herein; and Z represents a chemically reactive functional group.

    摘要翻译： 其中，L表示选自具有两个或更多个碳原子的直链或支链亚烷基，亚芳基或亚环烷基及其组合，其可以在链中具有醚键; X表示具有5或7个碳原子的直链糖醇的脱羟基残基; m是与X键合的聚乙二醇链的数目，代表4或6; n是氧乙烯基的平均加成摩尔数，为3〜600的整数。 Y代表本文进一步定义的单键或亚烷基; Z表示化学反应性官能团。

    METHOD FOR PRODUCING MULTI-ARM TYPE POLYETHYLENE GLYCOL DERIVATIVE
    10.
    发明申请
    METHOD FOR PRODUCING MULTI-ARM TYPE POLYETHYLENE GLYCOL DERIVATIVE 有权

    公开(公告)号：US20210024692A1

    公开(公告)日：2021-01-28

    申请号：US17041102

    申请日：2019-03-27

    申请人： NOF CORPORATION

    发明人： Akihide ONOZAWA ,  Hiroki YOSHIOKA ,  Masaki KAMIYA

    IPC分类号： C08G65/324 ,  C08G65/325 ,  C08G65/326 ,  C08G65/331 ,  C08G65/333 ,  C08G65/334 ,  A61K47/60

    摘要： A method for producing a multi-arm type polyethylene glycol derivative, which includes carrying out the following in order: Step (A): protecting an even number of hydroxyl groups, while leaving only the hydroxyl group at the 1-position of a polyhydric alcohol having an odd number of hydroxyl groups, other than the hydroxyl group at the 1-position by cyclic benzylidene acetalization, Step (B): linking two molecules of the compound obtained in step (A) to a compound for introducing a specific linker by etherification reaction, Step (C): deprotecting the cyclic benzylidene acetal structure at the terminal of the compound obtained in step (B), Step (D): polymerizing 3 to 600 mol of ethylene oxide to each hydroxyl group of the compound obtained in step (C) to obtain a multi-arm type polyethylene glycol derivative, and Step (E): functionalizing the hydroxyl group at the terminal of the multi-arm type polyethylene glycol derivative obtained in step (D).