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公开(公告)号：US20140314675A1
公开(公告)日：2014-10-23
申请号：US14343364
申请日：2012-09-07
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Takeshi Watanabe , Koichi Matsubara , Atsuhiko Kato , Masami Suzuki
IPC分类号： G01N33/574 , A61K45/06 , A61K31/7088 , C07K16/18 , A61K39/395 , A61K39/00
CPC分类号： G01N33/574 , A61K31/4745 , A61K31/513 , A61K31/555 , A61K31/7088 , A61K31/7105 , A61K31/713 , A61K39/0011 , A61K39/3955 , A61K45/06 , C07K16/18 , C07K16/30 , C12N5/0695 , G01N33/5073 , G01N33/56966 , G01N2500/04
摘要： An objective of the present invention is to provide: a cancer stem cell isolated using a cell marker; a substantively homogeneous cancer stem cell population including said cancer stem cell; and a method of preparing said cancer stem cell population. Another objective of the present invention is to provide: a method for separating cancer stem cells with a high proliferative potential and those with a low proliferative potential; a method for inducing cancer stem cells to have a different proliferative potential; and cancer stem cells separated or induced by these separation or induction methods. A further objective of the present invention is to provide: a method of screening for pharmaceuticals using said cancer stem cell or cancer stem cell population; a method for detecting the presence of said cancer stem cell or cancer stem cell population and for identifying or quantifying the same. The present inventors discovered that highly pure colon cancer stem cells (CSC) can be obtained in a large quantity, and identified two types of states of colon CSCs distinguishable through Lgr5 expression.
摘要翻译： 本发明的目的是提供：使用细胞标记物分离的癌症干细胞; 包括所述癌干细胞的实质均匀的癌干细胞群; 以及制备所述癌症干细胞群体的方法。 本发明的另一目的是提供：分离具有高增殖潜力的癌干细胞和具有低增殖潜能的癌干细胞的方法; 诱导癌症干细胞具有不同增殖潜力的方法; 和通过这些分离或诱导方法分离或诱导的癌干细胞。 本发明的另一个目的是提供：使用所述癌症干细胞或癌症干细胞群体筛选药物的方法; 用于检测所述癌症干细胞或癌症干细胞群体的存在并用于鉴定或定量的方法。 本发明人发现可以大量获得高纯度的结肠癌干细胞（CSC），并鉴定出通过Lgr5表达可区分的结肠CSCs的两种状态。
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公开(公告)号：US20140302511A1
公开(公告)日：2014-10-09
申请号：US14354517
申请日：2012-10-26
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Takeshi Watanabe , Koichi Matsubara , Osamu Natori , Atsuhiko Kato , Masami Suzuki
IPC分类号： C07K16/18 , G01N33/574 , C12Q1/68
CPC分类号： C07K16/28 , A61K31/4745 , A61K39/0011 , A61K39/39558 , A61K2039/55566 , C07K14/51 , C07K16/18 , C07K16/3046 , C07K2317/41 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C12Q1/686 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N33/574 , G01N33/57419 , G01N33/57492 , G01N2333/726 , G01N2800/52
摘要： An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective of the present invention is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.
摘要翻译： 本发明的目的是获得可以使用细胞表面标志物Lgr5表征的两种类型的实质均匀的癌症干细胞群体，并且通过使用针对这些癌症干细胞特异性表达的细胞膜分子的抗体提供癌症治疗剂 识别所述细胞膜分子。 本发明的另一个目的是提供使用针对癌干细胞特异性表达的细胞膜分子的抗体，用于检测癌症干细胞的试剂，以及用于诊断和分选癌症患者的方法。 本发明人发现可以大量获得高纯度大肠癌干细胞（CSC），并且通过Lgr5表达鉴定了可以区分的大肠CSCs的两种状况。 此外，本发明人发现，针对在所述癌干细胞中特异性表达的细胞膜分子的抗体可以损伤所述细胞。
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公开(公告)号：US20150098941A1
公开(公告)日：2015-04-09
申请号：US14505932
申请日：2014-10-03
发明人： Gregory Alan Lazar , Bassil I. Dahiyat , Hisafumi Okabe , Masamichi Sugimoto , Shigeyuki Iijima , Izumi Sugo
IPC分类号： C07K16/18
CPC分类号： C07K16/18 , A61K2039/505 , C07K16/303 , C07K2317/24 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/732
摘要： An anti-glypican-3 antibody comprising one or more amino acid substitutions introduced in the Fc region is disclosed. Preferably, in the anti-glypican-3 antibody, one or more of the amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues. Since the Fc-modified anti-glypican-3 antibody of the invention exhibit enhanced ADCC activity, it is useful in treating cancers, such as hepatic cancer. Also disclosed are an anticancer agent comprising the anti-glypican-3 antibody of the invention and a pharmaceutically acceptable carrier, as well as a method of treating a patient with cancer comprising administering to the patient the anticancer agent of the invention.
摘要翻译： 公开了包含在Fc区中引入的一个或多个氨基酸取代的抗磷脂酰肌醇蛋白聚糖-3抗体。 优选地，在抗磷脂酰肌醇蛋白聚糖-3抗体中，Fc区中位置239,298,326,330和332处的一个或多个氨基酸残基被其它氨基酸残基取代。 由于本发明的Fc修饰的抗磷脂酰肌醇蛋白聚糖-3抗体表现出增强的ADCC活性，因此可用于治疗诸如肝癌的癌症。 还公开了包含本发明的抗磷脂酰肌醇蛋白聚糖-3抗体和药学上可接受的载体的抗癌剂，以及治疗患有癌症的患者的方法，包括向患者施用本发明的抗癌剂。
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公开(公告)号：US20200325222A1
公开(公告)日：2020-10-15
申请号：US16913341
申请日：2020-06-26
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Takeshi Watanabe , Koichi Matsubara , Osamu Natori , Atsuhiko Kato , Masami Suzuki
IPC分类号： C07K16/28 , C07K16/30 , C07K14/51 , G01N33/574 , A61K39/00 , C12Q1/6886 , C07K16/18 , C12Q1/686 , A61K31/4745 , A61K39/395
摘要： An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.
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公开(公告)号：US10118959B2
公开(公告)日：2018-11-06
申请号：US14505932
申请日：2014-10-03
发明人： Gregory Alan Lazar , Bassil I. Dahiyat , Hisafumi Okabe , Masamichi Sugimoto , Shigeyuki Iijima , Izumi Sugo
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395 , A61K39/40 , C07K16/18 , C07K16/30 , C07K1/00 , A61K39/00
摘要： An anti-glypican-3 antibody comprising one or more amino acid substitutions introduced in the Fc region is disclosed. Preferably, in the anti-glypican-3 antibody, one or more of the amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues. Since the Fc-modified anti-glypican-3 antibody of the invention exhibit enhanced ADCC activity, it is useful in treating cancers, such as hepatic cancer. Also disclosed are an anticancer agent comprising the anti-glypican-3 antibody of the invention and a pharmaceutically acceptable carrier, as well as a method of treating a patient with cancer comprising administering to the patient the anticancer agent of the invention.
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公开(公告)号：US11965180B2
公开(公告)日：2024-04-23
申请号：US16994388
申请日：2020-08-14
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Yu Jau Chen , Atsuhiko Kato , Masami Suzuki , Koichi Matsubara
CPC分类号： C12N5/0695 , G01N33/5011 , G01N33/5073
摘要： Provided is a cancer stem cell mass from which cells incapable of forming cancer are substantially removed and which has a characteristic property of reproducing a layered structure of a cancer tissue; a process for producing the cancer stem cell mass; and use of the cancer stem cell mass. A human cancer tissue was repeatedly grown in a NOG mouse, separated cancer cells from the grown cancer tissue, and tested and compared various cancer cell culture processes. As a result, a cancer stem cell composition which is homogeneous and is substantially free of the coexistence of cells capable of forming cancer and cells incapable of forming cancer in a mixed state can be produced successively by employing an attached culture process using a serum-free stem cell culture medium rather than a generally employed floating culture process.
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公开(公告)号：US11858987B2
公开(公告)日：2024-01-02
申请号：US16913341
申请日：2020-06-26
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Takeshi Watanabe , Koichi Matsubara , Osamu Natori , Atsuhiko Kato , Masami Suzuki
IPC分类号： C07K16/28 , C07K16/30 , C07K14/51 , G01N33/574 , C12Q1/6886 , A61K39/00 , C07K16/18 , C12Q1/686 , A61K31/4745 , A61K39/395
CPC分类号： C07K16/28 , A61K31/4745 , A61K39/001102 , A61K39/39558 , C07K14/51 , C07K16/18 , C07K16/3046 , C12Q1/686 , C12Q1/6886 , G01N33/574 , G01N33/57419 , G01N33/57492 , A61K2039/55566 , C07K2317/41 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C12Q2600/106 , C12Q2600/158 , G01N2333/726 , G01N2800/52
摘要： An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.
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公开(公告)号：US10934351B2
公开(公告)日：2021-03-02
申请号：US15042548
申请日：2016-02-12
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Takeshi Watanabe , Koichi Matsubara , Osamu Natori , Atsuhiko Kato , Masami Suzuki
IPC分类号： C07K16/28 , C07K16/30 , C07K14/51 , A61K39/00 , C07K16/18 , A61K31/4745 , A61K39/395 , G01N33/574 , C12Q1/6886 , C12Q1/686
摘要： An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.
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公开(公告)号：US20160159904A1
公开(公告)日：2016-06-09
申请号：US15042548
申请日：2016-02-12
发明人： Tatsumi Yamazaki , Hisafumi Okabe , Shinta Kobayashi , Takeshi Watanabe , Koichi Matsubara , Osamu Natori , Atsuhiko Kato , Masami Suzuki
IPC分类号： C07K16/28 , A61K31/4745 , A61K39/395 , C07K16/30
CPC分类号： C07K16/28 , A61K31/4745 , A61K39/0011 , A61K39/39558 , A61K2039/55566 , C07K14/51 , C07K16/18 , C07K16/3046 , C07K2317/41 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C12Q1/686 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N33/574 , G01N33/57419 , G01N33/57492 , G01N2333/726 , G01N2800/52
摘要： An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.
摘要翻译： 本发明的目的是获得可以使用细胞表面标志物Lgr5表征的两种类型的实质均匀的癌症干细胞群体，并且通过使用针对这些癌症干细胞特异性表达的细胞膜分子的抗体提供癌症治疗剂 识别所述细胞膜分子。 另一个目的是提供使用针对癌干细胞特异性表达的细胞膜分子的抗体，用于检测癌症干细胞的试剂，以及用于诊断和分选癌症患者的方法。 本发明人发现可以大量获得高纯度大肠癌干细胞（CSC），并且通过Lgr5表达鉴定了可以区分的大肠CSCs的两种状况。 此外，本发明人发现，针对在所述癌干细胞中特异性表达的细胞膜分子的抗体可以损伤所述细胞。
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