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    Resurfacing of rodent antibodies
    1.
    发明授权
    Resurfacing of rodent antibodies 失效
    表面抗啮齿动物抗体

    公开(公告)号：US5639641A

    公开(公告)日：1997-06-17

    申请号：US942245

    申请日：1992-09-09

    申请人： Jan T. Pedersen ,  Stephen M. J. Searle ,  Anthony R. Rees ,  Michael A. Roguska ,  Braydon C. Guild

    发明人： Jan T. Pedersen ,  Stephen M. J. Searle ,  Anthony R. Rees ,  Michael A. Roguska ,  Braydon C. Guild

    IPC分类号： C12N15/09 ,  A61K39/395 ,  C07K16/00 ,  C07K16/18 ,  C07K16/46 ,  C12N15/13 ,  C12P21/08 ,  G01N33/531 ,  C12N15/00

    CPC分类号： C07K16/467 ,  C07K2317/24

    摘要： The invention relates to a method for providing, via resurfacing, humanized rodent antibodies that have improved therapeutic efficacy due to the presentation of a human surface in the variable region. In the method, (1) position alignments of a pool of antibody heavy and light chain variable regions is generated to give a set of heavy and light chain variable region framework surface exposed positions wherein the alignment positions for all variable regions are at least about 98% identical; (2) a set of heavy and light chain variable region framework surface exposed amino acid residues is defined for a rodent antibody (or fragment thereof); (3) a set of heavy and light chain variable region framework surface exposed amino acid residues that is most closely identical to the set of rodent surface exposed amino acid residues is identified; (4) the set of heavy and light chain variable region framework surface exposed amino acid residues defined in step (2) is substituted with the set of heavy and light chain variable region framework surface exposed amino acid residues identified in step (3), except for those amino acid residues that are within 5 .ANG.ngstroms of any atom of any residue of the complementarity determining regions of the rodent antibody; and (5) the humanized rodent antibody having binding specificity is produced.

    摘要翻译： 本发明涉及通过表面重建提供由于在可变区中呈现人体表面而具有改善的治疗功效的人源化啮齿动物抗体的方法。 在该方法中，（1）产生抗体重链和轻链可变区池的位置比对，以产生一组重链和轻链可变区框架表面暴露位置，其中所有可变区的对准位置为至少约98 ％相同; （2）为啮齿动物抗体（或其片段）定义了一组重链和轻链可变区框架表面暴露的氨基酸残基; （3）鉴定了一组重链和轻链可变区框架表面暴露的氨基酸残基，其与啮齿动物表面暴露的氨基酸残基的集合最接近; （4）步骤（2）中定义的重链和轻链可变区框架表面暴露的氨基酸残基的集合被步骤（3）中鉴定的重链和轻链可变区框架表面暴露的氨基酸残基组所取代，除了 对于啮齿动物抗体互补决定区任何残基的任何原子的5个范围内的那些氨基酸残基; 和（5）产生具有结合特异性的人源化啮齿动物抗体。

    Modified carboxypeptidase enzymes and their use
    4.
    发明授权
    Modified carboxypeptidase enzymes and their use 失效
    改性羧肽酶及其用途

    公开(公告)号：US06656718B2

    公开(公告)日：2003-12-02

    申请号：US09898461

    申请日：2001-07-05

    申请人： Richard H. J. Begent ,  Kerry Chester ,  Nigel P. Minton ,  Anthony R. Rees ,  Surinder K. Sharma ,  Daniel I. R. Spencer

    发明人： Richard H. J. Begent ,  Kerry Chester ,  Nigel P. Minton ,  Anthony R. Rees ,  Surinder K. Sharma ,  Daniel I. R. Spencer

    IPC分类号： C12N948

    CPC分类号： C12N9/48 ,  C07K2319/00

    摘要： The invention relates to improvements relating to cancer therapy based on the identification of a number of regions of CPG2 which contain epitopes which appear to be involved in the production of a host immune response and which may be modified to alter the immunogenicity in patients. Production of fusions of CPG2 with an antibody, where the CPG2 protein has been tagged provides a CPG2 protein which has reduced immunogenicity. By using partially glycosylated enzyme obtainable by P. pastoris expression, the efficacy of antibody-CPG2 fusions is enhanced.

    摘要翻译： 本发明涉及基于鉴定多个CPG2区域的癌症治疗的改进，其包含似乎参与宿主免疫应答产生的表位，并且可以修饰以改变患者的免疫原性。 用已经标记了CPG2蛋白的抗体产生CPG2融合提供了具有降低的免疫原性的CPG2蛋白。 通过使用可由巴斯德毕赤酵母表达获得的部分糖基化酶，增强了抗体-CPG2融合的功效。