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    HUMAN ANTIBODIES THAT HAVE MN BINDING AND CELL ADHESION-NEUTRALIZING ACTIVITY
    1.
    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
    2.
    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。

    Bicycle shift control device
    3.
    发明授权
    Bicycle shift control device 有权
    自行车换档控制装置

    公开(公告)号：US08640568B2

    公开(公告)日：2014-02-04

    申请号：US12554065

    申请日：2009-09-04

    申请人： Toshihiko Takeuchi ,  Kazutaka Fukao ,  Yoshimitsu Miki

    发明人： Toshihiko Takeuchi ,  Kazutaka Fukao ,  Yoshimitsu Miki

    IPC分类号： F16C1/10

    CPC分类号： B62M25/04 ,  B62K23/06

    摘要： A bicycle shift control device is provided with a shifter housing, a gear shifting mechanism, a shift operating member, and a shift switching arrangement. The gear shifting mechanism is disposed in the shifter housing with the gear shifting mechanism having a plurality of operating positions. The shift operating member is movable with respect to the shifter housing to operate the gear shifting mechanism. The shift switching arrangement includes a restricting member movably mounted with respect to the shifter housing between a non-shift restricting position and a shift restricting position. The gear shifting mechanism moves in a first set of the operating positions when the restricting member is in the non-shift restricting position, and moves in a second set of the operating positions that are different from the first set of the operating positions when the restricting member is in the shift restricting position.

    摘要翻译： 一种自行车变速控制装置设置有变速器壳体，变速机构，变速操作构件和变速切换装置。 变速机构设置在变速器壳体中，变速机构具有多个操作位置。 变速操作构件可相对于换档器壳体移动以操作变速机构。 变速切换装置包括限制构件，其相对于变速器壳体可移动地安装在非换档限制位置和换档限制位置之间。 当限制构件处于非换档限制位置时，变速机构在第一组操作位置中移动，并且当限制构件处于非换挡限制位置时，在与第一组操作位置不同的第二组操作位置中移动 会员处于班次限制位置。

    BICYCLE SHIFT CONTROL DEVICE
    4.
    发明申请
    BICYCLE SHIFT CONTROL DEVICE 有权
    自行车移动控制装置

    公开(公告)号：US20110056319A1

    公开(公告)日：2011-03-10

    申请号：US12554065

    申请日：2009-09-04

    申请人： Toshihiko Takeuchi ,  Kazutaka Fukao ,  Yoshimitsu Miki

    发明人： Toshihiko Takeuchi ,  Kazutaka Fukao ,  Yoshimitsu Miki

    IPC分类号： B62M25/04 ,  B62M25/00

    CPC分类号： B62M25/04 ,  B62K23/06

    摘要： A bicycle shift control device is provided with a shifter housing, a gear shifting mechanism, a shift operating member, and a shift switching arrangement. The gear shifting mechanism is disposed in the shifter housing with the gear shifting mechanism having a plurality of operating positions. The shift operating member is movable with respect to the shifter housing to operate the gear shifting mechanism. The shift switching arrangement includes a restricting member movably mounted with respect to the shifter housing between a non-shift restricting position and a shift restricting position. The gear shifting mechanism moves in a first set of the operating positions when the restricting member is in the non-shift restricting position, and moves in a second set of the operating positions that are different from the first set of the operating positions when the restricting member is in the shift restricting position.

    摘要翻译： 一种自行车变速控制装置设置有变速器壳体，变速机构，变速操作构件和变速切换装置。 变速机构设置在变速器壳体中，变速机构具有多个操作位置。 变速操作构件可相对于换档器壳体移动以操作变速机构。 变速切换装置包括限制构件，其相对于变速器壳体可移动地安装在非换档限制位置和换档限制位置之间。 当限制构件处于非换档限制位置时，变速机构在第一组操作位置中移动，并且当限制构件处于非换挡限制位置时，在与第一组操作位置不同的第二组操作位置中移动 会员处于班次限制位置。

    MT-SP1 polynucleotides and polypeptides
    6.
    发明授权
    MT-SP1 polynucleotides and polypeptides 有权
    MT-SP1多核苷酸和多肽

    公开(公告)号：US07227009B2

    公开(公告)日：2007-06-05

    申请号：US11253869

    申请日：2005-10-18

    申请人： Charles S. Craik ,  Toshihiko Takeuchi ,  Marc Shuman

    发明人： Charles S. Craik ,  Toshihiko Takeuchi ,  Marc Shuman

    IPC分类号： C12N15/11

    CPC分类号： C12N9/6408

    摘要： This invention provides a novel membrane-type serine protease (designated MT-SP1) elevated expression of which is associated with cancer. In one embodiment, this invention provides a method obtaining a prognosis or of detecting or staging a cancer in an organism. The method involves providing a biological sample from the organism and detecting the level of a membrane type serine protease 1 (MT-SP1) in the sample, where an elevated level of the membrane-type serine protease, as compared to the level of the protease in a biological sample from a normal healthy organism indicates the presence or stage of the cancer.

    摘要翻译： 本发明提供了与癌症相关的新型膜型丝氨酸蛋白酶（称为MT-SP1），其表达升高。 在一个实施方案中，本发明提供了获得预后或在生物体中检测或分期癌症的方法。 该方法包括从生物体提供生物样品，并检测样品中膜型丝氨酸蛋白酶1（MT-SP1）的水平，其中与蛋白酶水平相比，膜型丝氨酸蛋白酶水平升高 来自正常健康生物体的生物样品表明癌症的存在或阶段。

    Membrane type serine protease 1 (MT-SP1) and uses thereof
    7.
    发明授权
    Membrane type serine protease 1 (MT-SP1) and uses thereof 失效
    膜型丝氨酸蛋白酶1（MT-SP1）及其用途

    公开(公告)号：US07030231B1

    公开(公告)日：2006-04-18

    申请号：US09410362

    申请日：1999-09-30

    申请人： Charles S. Craik ,  Toshihiko Takeuchi ,  Marc Shuman

    发明人： Charles S. Craik ,  Toshihiko Takeuchi ,  Marc Shuman

    IPC分类号： C12N15/11

    CPC分类号： C12N9/6408

    摘要： This invention provides a novel membrane-type serine protease (designated MT-SP1) elevated expression of which is associated with cancer. In one embodiment, this invention provides a method obtaining a prognosis or of detecting or staging a cancer in an organism. The method involves providing a biological sample from the organism and detecting the level of a membrane type serine protease 1 (MT-SP1) in the sample, where an elevated level of the membrane-type serine protease, as compared to the level of the protease in a biological sample from a normal healthy organism indicates the presence or stage of the cancer.

    摘要翻译： 本发明提供了与癌症相关的新型膜型丝氨酸蛋白酶（称为MT-SP1），其表达升高。 在一个实施方案中，本发明提供了获得预后或在生物体中检测或分期癌症的方法。 该方法包括从生物体提供生物样品，并检测样品中膜型丝氨酸蛋白酶1（MT-SP1）的水平，其中与蛋白酶水平相比，膜型丝氨酸蛋白酶水平升高 来自正常健康生物体的生物样品表明癌症的存在或阶段。