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    • 1. 发明申请
    • WHOLE CELL-PROTEIN CONJUGATES AND METHODS OF MAKING THE SAME
    • 全细胞蛋白质缀合物及其制备方法
    • WO2018009906A1
    • 2018-01-11
    • PCT/US2017/041258
    • 2017-07-07
    • PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    • MEKALANOS, John, J.IWASHKIW, Jeremy, Andrew
    • A61K39/00A61K39/02A61K39/116A61K39/385A61K39/395A61P31/04
    • A61P31/04A61K39/092A61K39/116A61K39/385A61K2039/55505A61K2039/6037
    • Disclosed are immunogenic whole cell-protein conjugates containing a carrier protein and a whole cell having an exterior surface including a polyol antigen that is linked to the carrier protein through a linker. The linker can be covalent, or the linker can include an affinity pair. The covalent linker may be of formula: Z 1 -C(Z 3 )-N(H)-N(H)-(-C(O)-(L-C(O)) n -N(H)-N(H)-) m -Z 2 , where Z 1 is a bond to an oxygen atom in the polyol antigen, Z 2 is a bond to a carbonyl group in the carrier protein, Z 3 is O or NH, each of n and m is 0 or 1, and L, when present, is C 2-6 alkanediyl or C 6-10 arenediyl. Also disclosed are immunogenic whole-cell protein conjugates containing a carrier protein and a whole cell having an exterior surface including a polyol antigen that is covalently linked to the carrier protein through a linker formed by a reaction between a cyanate group bonded to the polyol antigen and a hydrazine-activated carrier protein. Further disclosed are pharmaceutical compositions containing the immunogenic whole cell-protein conjugates, methods of preparing immunogenic whole cell-protein conjugates, methods of preparing polyol antigen-protein conjugates via whole cell-protein conjugates, and methods of generating an immune response in a subject using the disclosed pharmaceutical compositions.
    • 公开了包含载体蛋白的免疫原性全细胞 - 蛋白质偶联物和具有包括通过接头连接至载体蛋白的多元醇抗原的外表面的全细胞。 接头可以是共价键,或者接头可以包含亲和对。 共价连接基可以具有下式:Z 1 -C(Z 3)-N(H)-N(H) - ( - C(O) - (LC (O))n -N(H)-N(H) - )m -Z 2,其中Z 1, 是与多元醇抗原中的氧原子的键,Z 2是与载体蛋白中羰基的键,Z 3是O或NH, n和m中的每一个为0或1,且当存在时,L为C 2-6链烷二基或C 6-10芳烯基。 还公开了包含载体蛋白和全细胞的免疫原性全细胞蛋白缀合物,所述全细胞具有包括多元醇抗原的外表面,所述多元醇抗原通过连接基团共价连接至载体蛋白,所述连接基团通过连接至多元醇抗原的氰酸酯基团与 肼活化的载体蛋白。 还公开了含有免疫原性全细胞 - 蛋白质偶联物的药物组合物,制备免疫原性全细胞 - 蛋白质偶联物的方法,通过全细胞 - 蛋白质偶联物制备多元醇抗原 - 蛋白质偶联物的方法,以及在受试者体内产生免疫应答的方法 公开的药物组合物。