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    Use of catalytic antibodies for synthesizing epothilone
    2.
    发明授权
    Use of catalytic antibodies for synthesizing epothilone 失效
    使用催化抗体合成埃坡霉素

    公开(公告)号：US06294374B1

    公开(公告)日：2001-09-25

    申请号：US09415453

    申请日：1999-10-08

    申请人： Subhash C. Sinha ,  Richard A. Lerner ,  Carlos F. Barbas, III

    发明人： Subhash C. Sinha ,  Richard A. Lerner ,  Carlos F. Barbas, III

    IPC分类号： C12S1300

    CPC分类号： C07D417/06 ,  C07B2200/07 ,  C07D277/24 ,  C07D277/34 ,  C07D277/36 ,  C07D493/04 ,  C12N9/0002 ,  C12P7/26 ,  C12P17/16 ,  C12P17/18 ,  C12P41/002

    摘要： Three monoclonal aldolase antibodies, generated against a &bgr;-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions providing ent-9a-k by kinetic resolution. Compounds 9a, 9g and 9k were resolved in multi-gram quantities using 0.005-0.0004 mol % antibody catalyst. Enantiomerically pure starting materials, 9a-k, are useful synthons for the construction of epothilones A-E (2-6) and their analogs including 13-alkyl derivatives. Previously, the use of compound 9a as a synthon was reported in the preparation of epothilones A-D, 2-5. To further expand this synthon-based strategy, syntheses of epothilone E, 6, 13-methyl epothilone C, 7, and their trans-isomers have been achieved starting from enantiomerically pure thiazole aldols 9g and 9a, respectively, prepared by large-scale antibody catalyzed resolutions.

    摘要翻译： 通过反应性免疫针对β-二酮半抗原产生的三种单克隆醛缩酶抗体催化快速和高度对映选择性的醛缩醇反应，通过动力学拆分提供ent-9a-k。 化合物9a，9g和9k用0.005-0.0004mol％抗体催化剂以多克量分离。 对映体纯原料9a-k是构建埃坡霉素A-E（2-6）及其类似物包括13-烷基衍生物的有用合成物。 以前，在制备埃坡霉素A-D，2-5中报道了使用化合物9a作为合成子。 为了进一步扩展这种基于合成子的策略，从分别由大规模抗体制备的对映体纯的噻唑醛醇9g和9a开始合成埃坡霉素E，6,13-​​甲基埃博霉素C 7及其反式异构体 催化分解。

    Use of Retro-Aldol Reaction to Generate Reactive Vinyl Ketone for Attachment to Antibody Molecules by Michael Addition Reaction for Use in Immunostaining and Immunotargeting
    3.
    发明申请
    Use of Retro-Aldol Reaction to Generate Reactive Vinyl Ketone for Attachment to Antibody Molecules by Michael Addition Reaction for Use in Immunostaining and Immunotargeting 审中-公开
    使用反 - 醛醇反应生成活性乙烯基酮以通过用于免疫染色和免疫靶向的迈克尔加成反应附着于抗体分子

    公开(公告)号：US20080213249A1

    公开(公告)日：2008-09-04

    申请号：US11774149

    申请日：2007-07-06

    申请人： Subhash C. Sinha ,  Carlos F. Barbas ,  Richard A. Lerner

    发明人： Subhash C. Sinha ,  Carlos F. Barbas ,  Richard A. Lerner

    IPC分类号： A61K39/395 ,  A61P35/00 ,  C07K16/00 ,  C07K1/00 ,  C07K5/10

    CPC分类号： B82Y5/00 ,  A61K47/6889 ,  A61K47/6891

    摘要： The present invention is directed to methods for formation of a chemically programmed antibody comprising the steps of: (1) reacting a conjugate comprising a signal module covalently linked to a proadapter with a catalytic moiety selected from the group consisting of a catalytic antibody and a Fab fragment of a catalytic antibody, wherein the proadapter includes therein a precursor to a reactive moiety activated to a reactive moiety by a reaction catalyzed by the catalytic moiety; and (2) crosslinking the reactive moiety to a side chain of an amino acid residue in the active site of the catalytic moiety to produce the chemically programmed antibody. The invention also encompasses chemically programmed antibodies formed by these methods, methods for their use, and pharmaceutical compositions, as well as proadaptors and conjugates including them. Chemically programmed antibodies are useful for the treatment of cancer, particularly in metastasis.

    摘要翻译： 本发明涉及形成化学程序性抗体的方法，其包括以下步骤：（1）使包含共价连接于前药的信号模块的缀合物与选自催化抗体和Fab的催化部分 催化抗体的片段，其中所述前药包括其中通过催化部分催化的反应活化至反应性部分的反应性部分的前体; 和（2）将反应性部分与催化部分的活性位点中的氨基酸残基的侧链交联以产生化学编程的抗体。 本发明还包括通过这些方法形成的化学程序性抗体，其使用方法和药物组合物，以及包括它们的前冲剂和共轭物。 化学编程抗体可用于治疗癌症，特别是转移癌症。