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    • 103. 发明专利
    • Method for selective and quantitative functionalization of immunoglobulin fab fragment
    • 免疫球蛋白FAB片段的选择性和定量功能化方法
    • JP2011148820A
    • 2011-08-04
    • JP2011089945
    • 2011-04-14
    • Bracco Imaging Spaブラッコ イメージング ソチエタ ペル アチオニBracco Imaging S.P.A.
    • DE HAEN CHRISTOPHMAISANO FEDERICO
    • C07K16/00A61K39/395A61K47/48A61K51/10C07K1/06
    • B82Y5/00A61K47/6887A61K47/6897A61K51/1093
    • PROBLEM TO BE SOLVED: To solve such a problem that none gives useful suggestions for solving the problem represented by the need of administering to the patient pharmaceutical formulations containing, as active ingredients, Fab fragments which are selectively and quantitatively functionalized only at desired specific sites of the molecule, thus showing a predefined precise substitution stoichiometry. SOLUTION: The invention provides chemical conjugates between an immunoglobulin Fab fragment and molecular compounds imparting diagnostic or therapeutic utility, whereby the only sites of conjugation on the Fab fragment are one or both of the sulfhydryl groups deriving from the selective and quantitative reduction of the inter-chain disulfide bond of the Fab fragment and whereby the molecular compounds imparting diagnostic or therapeutic utility have at least one free sulfhydryl-reactive group and are characterized in that the conjugation stoichiometric molar ratio of molecular compound to Fab fragment is in the range from 0.95 to 1.05 or in the range from 1.95 to 2.05. COPYRIGHT: (C)2011,JPO&INPIT
    • 要解决的问题:为了解决这样的问题,没有一个提出有用的建议来解决由对需要给予患者的药物制剂所需的问题,药物制剂含有作为活性成分的Fab片段,其仅在期望的情况下选择性和定量地官能化 因此显示了预定义的精确取代化学计量。 解决方案:本发明提供免疫球蛋白Fab片段和赋予诊断或治疗效用的分子化合物之间的化学共轭物,其中在Fab片段上缀合的唯一位点是衍生自选择和定量还原的巯基中的一个或两个 Fab片段的链间二硫键,由此赋予诊断或治疗效用的分子化合物具有至少一个游离巯基反应性基团,其特征在于分子化合物与Fab片段的共轭化学计量摩尔比在以下范围内 0.95至1.05或在1.95至2.05的范围内。 版权所有(C)2011,JPO&INPIT