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    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：US20100240100A1

    公开(公告)日：2010-09-23

    申请号：US12330504

    申请日：2008-12-08

    申请人： Toshihiko Takeuchi ,  Nathalie Dubois-Stringfellow ,  John E. Murphy ,  Julie Rinkenberger

    发明人： Toshihiko Takeuchi ,  Nathalie Dubois-Stringfellow ,  John E. Murphy ,  Julie Rinkenberger

    IPC分类号： C12P21/00 ,  C07H21/04 ,  C12N15/74 ,  C12N5/10

    CPC分类号： C07K16/3038 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/565 ,  C07K2317/732

    摘要： 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.

    摘要翻译： 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.
    发明授权
    Human antibodies that have MN binding and cell adhesion-neutralizing activity 有权
    具有MN结合和细胞粘附中和活性的人抗体

    公开(公告)号：US07462696B2

    公开(公告)日：2008-12-09

    申请号：US10273541

    申请日：2002-10-18

    申请人： Toshihiko Takeuchi ,  Nathalie Dubois-Stringfellow ,  John E. Murphy ,  Julie Rinkenberger

    发明人： Toshihiko Takeuchi ,  Nathalie Dubois-Stringfellow ,  John E. Murphy ,  Julie Rinkenberger

    IPC分类号： C07K16/46 ,  C07K16/24

    CPC分类号： C07K16/3038 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/565 ,  C07K2317/732

    摘要： The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP (SEQ ID NO: 118) repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP (SEQ ID NO: 118) 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 (SEQ ID NO: 119)). 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.

    摘要翻译： 本发明由针对蛋白多糖结构域内的GEEDLP（SEQ ID NO：118）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聚糖结构域包含四个这些相同的GEEDLP（SEQ ID NO：118）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（SEQ ID NO：119））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。