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    METHODS FOR MAKING SACCHARIDE-PROTEIN GLYCOCONJUGATES
    1.
    发明申请
    METHODS FOR MAKING SACCHARIDE-PROTEIN GLYCOCONJUGATES 审中-公开
    制备海草蛋白糖蛋白的方法

    公开(公告)号：US20160297895A1

    公开(公告)日：2016-10-13

    申请号：US15150302

    申请日：2016-05-09

    Applicant: GlaxoSmithKline Biologicals SA

    Inventor： Allan James SAUL ,  Francesca MICOLI

    IPC: C08B37/00

    CPC classification number: C08B37/0006 ,  A61K39/02 ,  A61K39/0275 ,  A61K39/095 ,  A61K39/385 ,  A61K47/6415 ,  A61K47/646 ,  A61K2039/6037 ,  C07K14/34 ,  C07K16/1285 ,  C07K16/44 ,  C07K2317/734 ,  C08B37/0003 ,  C08B37/006 ,  C08B37/0063 ,  C08B37/0081 ,  Y02A50/482

    Abstract: The invention provides a process for the reductive amination of a carbonyl group at the reducing terminus of a polysaccharide, wherein the reductive amination is carried out at a pH between 4 and 5. The invention also provides a process for preparing a conjugate of a polysaccharide and a carrier molecule, comprising the steps of: (a) coupling the polysaccharide to a linker, to form a polysaccharide-linker compound in which the free terminus of the linker is an ester group; and (b) reacting the ester group with a primary amine group in the carrier molecule, to form a polysaccharide-linker-carrier molecule conjugate in which the linker is coupled to the carrier molecule via an amide linkage. The invention also provides a process for reducing contamination of a polysaccharide-linker compound with unreacted linker, comprising a step of precipitating unreacted linker under aqueous conditions at a pH of less than 5. The invention also provides polysaccharide-linker-carrier molecule conjugates and intermediate compounds obtained or obtainable by these processes.

    Abstract translation: 本发明提供了在多糖的还原末端还原胺化羰基的方法，其中还原胺化在pH4至5之间进行。本发明还提供了制备多糖和 载体分子，其包括以下步骤：（a）将多糖偶联至接头，以形成其中接头的游离末端为酯基的多糖 - 接头化合物; 和（b）在载体分子中使酯基与伯胺基反应，以形成多糖 - 连接体 - 载体分子缀合物，其中连接体经由酰胺键与载体分子偶联。 本发明还提供了一种减少多糖 - 接头化合物与未反应接头的污染的方法，包括在pH小于5的水性条件下沉淀未反应的接头的步骤。本发明还提供多糖 - 接头 - 载体分子缀合物和中间体 通过这些方法获得或可获得的化合物。

    METHODS FOR MAKING SACCHARIDE-PROTEIN GLYCOCONJUGATES
    4.
    发明申请
    METHODS FOR MAKING SACCHARIDE-PROTEIN GLYCOCONJUGATES 审中-公开

    公开(公告)号：US20180334515A1

    公开(公告)日：2018-11-22

    申请号：US15977754

    申请日：2018-05-11

    Applicant: GlaxoSmithKline Biologicals SA

    Inventor： Allan James SAUL ,  Francesca MICOLI

    IPC: C08B37/00 ,  A61K47/64 ,  C07K16/44 ,  C07K16/12 ,  C07K14/34 ,  A61K39/385 ,  A61K39/095 ,  A61K39/112 ,  A61K39/02 ,  A61K39/00

    Abstract: The invention provides a process for the reductive amination of a carbonyl group at the reducing terminus of a polysaccharide, wherein the reductive amination is carried out at a pH between 4 and 5. The invention also provides a process for preparing a conjugate of a polysaccharide and a carrier molecule, comprising the steps of: (a) coupling the polysaccharide to a linker, to form a polysaccharide-linker compound in which the free terminus of the linker is an ester group; and (b) reacting the ester group with a primary amine group in the carrier molecule, to form a polysaccharide-linker-carrier molecule conjugate in which the linker is coupled to the carrier molecule via an amide linkage. The invention also provides a process for reducing contamination of a polysaccharide-linker compound with unreacted linker, comprising a step of precipitating unreacted linker under aqueous conditions at a pH of less than 5. The invention also provides polysaccharide-linker-carrier molecule conjugates and intermediate compounds obtained or obtainable by these processes.

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