Chemical compounds
    10.
    发明授权
    Chemical compounds 失效
    化合物

    公开(公告)号:US06436691B1

    公开(公告)日:2002-08-20

    申请号:US09011769

    申请日:1998-02-13

    IPC分类号: C12N964

    CPC分类号: B82Y5/00 A61K47/6899 C12N9/48

    摘要: Antibody Directed Enzyme Prodrug Therapy (ADEPT) systems for use in cancer based on mutated carboxypeptidase B (CPB) enzymes. Enzyme conjugates for ADEPT are substantially non-immunogenic in humans comprising a targeting moiety (for example an antibody) capable of binding with a tumor associated antigen, the targeting moiety being linked to a mutated form of a CPB enzyme capable of converting a prodrug into an antineoplastic drug wherein the prodrug is not significantly convertible into antineoplastic drug in humans by natural unmutated enzyme. A preferred enzyme mutant is human pancreatic CPB comprising a Lys or Arg residue at position 253. Suitable mustard prodrugs are disclosed in the specification.

    摘要翻译: 基于突变的羧肽酶B(CPB)酶的用于癌症的抗体定向酶前药治疗(ADEPT)系统。 用于ADEPT的酶缀合物在人中基本上是非免疫原性的,其包含能够与肿瘤相关抗原结合的靶向部分(例如抗体),所述靶向部分与能够将前药转化成为前体药物的CPB酶的突变形式连接 抗肿瘤药物,其中前药在天然未突变酶中不能显着转化成人类的抗肿瘤药物。 优选的酶突变体是人胰腺CPB,其包含位置253处的Lys或Arg残基。合适的芥子酰胺前药在说明书中公开。