HUMAN ANTIBODIES THAT HAVE MN BINDING AND CELL ADHESION-NEUTRALIZING ACTIVITY
    2.
    发明申请
    HUMAN ANTIBODIES THAT HAVE MN BINDING AND CELL ADHESION-NEUTRALIZING ACTIVITY 审中-公开
    具有MN结合和细胞粘附中和活性的人抗体

    公开(公告)号:WO2003033674A2

    公开(公告)日:2003-04-24

    申请号:PCT/US2002/033470

    申请日:2002-10-18

    IPC: C12N

    Abstract: The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co-incubation with a peptide containing this repeat (PGEEDLPGEEDLP). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.

    Abstract translation: 本发明由针对蛋白多糖结构域内的GEEDLP重复的单克隆人MN抗体或MN抗体片段组成。 MN细胞表面蛋白的蛋白多糖结构域包含四个这些相同的GEEDLP重复序列。 通过竞争ELISA验证与所需表位的结合,其中ELISA信号可以通过与含有该重复的肽(PGEEDLPGEEDLP)共孵育来减毒。 还可以使用Biacore分析验证这种结合抑制,其中所需抗体与固定化的MN或蛋白聚糖肽的结合可被肽重复抑制。 除了结合肽重复之外,人抗MN抗体可以抑制CGL-1细胞对MN涂覆的塑料板的细胞粘附。 已经使用人抗MN抗体来诊断和定量癌细胞和肿瘤中的MN表达,使用FACS和免疫组织化学方法。 还提供了一种实例,其中人抗MN IgG1通过抗体依赖性细胞介导的细胞毒性介导肿瘤细胞裂解。 因此,这些抗体可用于治疗其中MN被上调的癌症或可用于诊断MN被上调的癌症。

    HUMAN ANTIBODIES THAT HAVE MN BINDING AND CELL ADHESION-NEUTRALIZING ACTIVITY
    3.
    发明申请
    HUMAN ANTIBODIES THAT HAVE MN BINDING AND CELL ADHESION-NEUTRALIZING ACTIVITY 审中-公开
    具有MN结合和细胞粘附 - 中和活性的人抗体

    公开(公告)号:WO03033674A3

    公开(公告)日:2003-08-21

    申请号:PCT/US0233470

    申请日:2002-10-18

    Abstract: The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co-incubation with a peptide containing this repeat (PGEEDLPGEEDLP). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.

    Abstract translation: 本发明由靶向蛋白聚糖结构域内的GEEDLP重复的单克隆人类MN抗体或MN抗体片段组成。 MN细胞表面蛋白的蛋白聚糖结构域含有四个这些相同的GEEDLP重复。 通过竞争ELISA验证与所需表位的结合,其中ELISA信号可通过与含有该重复的肽(PGEEDLPGEEDLP)共温育而减毒。 这种结合抑制作用也可以使用Biacore测定来验证,其中所需抗体与固定的MN或蛋白聚糖肽的结合可以被肽重复序列抑制。 除了与肽重复序列结合之外,人类抗MN抗体还可以抑制CGL-1细胞与MN包被塑料板的细胞粘附。 人类抗MN抗体已用于使用FACS和免疫组织化学方法诊断和量化癌细胞和肿瘤中的MN表达。 还提供了一个实例,其中人抗MN IgG1通过抗体依赖性细胞介导的细胞毒性介导肿瘤细胞裂解。 因此,这些抗体可用于治疗其中MN上调或可用于诊断MN上调的癌症的癌症。

    LIBRARIES, ARRAYS AND THEIR USES FOR TARGETED AFFINITY ENHANCEMENT
    8.
    发明申请
    LIBRARIES, ARRAYS AND THEIR USES FOR TARGETED AFFINITY ENHANCEMENT 审中-公开
    图书馆,阵列及其用于增强目标敏感度的用途

    公开(公告)号:WO2009088928A3

    公开(公告)日:2009-09-11

    申请号:PCT/US2008088639

    申请日:2008-12-31

    Abstract: The present disclosure relates to methods and materials for enhancing the binding affinity of an antibody by means of generating a library or an array of targeted amino acid changes (e.g., mutations) at one or more positions in an antibody variable domain. The present disclosure relates to libraries or arrays and their uses for enhancing antibody affinity. The present disclosure relates to methods and materials for mutagenesis, including for the generation of novel or improved antibody variable domains and libraries or arrays of mutant antibody variable domains or nucleic acids encoding such mutant or modified variable domains.

    Abstract translation: 本公开涉及通过在抗体可变结构域的一个或多个位置产生文库或一系列靶向氨基酸改变(例如,突变)来增强抗体的结合亲和力的方法和材料。 本公开涉及文库或阵列及其用于增强抗体亲和力的用途。 本公开涉及用于诱变的方法和材料,包括用于产生新的或改进的抗体可变结构域和文库或阵列的突变体抗体可变结构域或编码这种突变体或修饰的可变结构域的核酸。

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