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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：US20230085803A1
公开(公告)日：2023-03-23
申请号：US17992032
申请日：2022-11-22
发明人： Masami Suzuki , Koichi Matsubara , Atsuhiko Kato , Chie Kato , Shinta Kobayashi , Yu Jau Chen , Masaki Yamazaki
IPC分类号： G01N33/50 , A01K67/027
摘要： An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.
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公开(公告)号：US11053308B2
公开(公告)日：2021-07-06
申请号：US16323142
申请日：2017-08-04
申请人： CHUGAI SEIYAKU KABUSHIKI KAISHA , JICHI MEDICAL UNIVERSITY , NATIONAL INSTITUTES OF BIOMEDICAL INNOVATION, HEALTH AND NUTRITION
发明人： Ayako Kakiuchi , Atsuhiko Kato , Shuji Hayashi , Izumi Yanagisawa , Ryo Konno , Sachiho Netsu , Tadashi Sankai
IPC分类号： A61K39/395 , C07K16/24 , A61P15/00 , A61P29/00 , A61P11/00 , A61K45/00 , A61P1/16 , A61P13/12 , A61P43/00 , A61P17/06 , A61P15/08 , C07K16/28 , A61K39/00
摘要： For example, therapeutic methods and the like for novel IL-8-related diseases using an IL-8 signal inhibitor are provided. Alternatively, for example, therapeutic methods and the like for known or novel IL-8-related diseases using a novel anti-IL-8 antibody are provided.
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公开(公告)号：US20240083996A1
公开(公告)日：2024-03-14
申请号：US18450863
申请日：2023-08-16
申请人： Chugai Seiyaku Kabushiki Kaisha , Jichi Medical University , National Institutes of Biomedical Innovation, Health and Nutrition
发明人： Ayako KAKIUCHI , Atsuhiko Kato , Shuji Hayashi , Izumi Yanagisawa , Ryo Konno , Sachiho Netsu , Tadashi Sankai
IPC分类号： C07K16/24 , A61K39/395 , A61K45/00 , A61P1/16 , A61P11/00 , A61P13/12 , A61P15/00 , A61P15/08 , A61P17/06 , A61P29/00 , A61P43/00 , C07K16/28
CPC分类号： C07K16/244 , A61K39/395 , A61K45/00 , A61P1/16 , A61P11/00 , A61P13/12 , A61P15/00 , A61P15/08 , A61P17/06 , A61P29/00 , A61P43/00 , C07K16/2866 , A61K2039/505 , C07K16/24
摘要： For example, therapeutic methods and the like for novel IL-8-related diseases using an IL-8 signal inhibitor are provided. Alternatively, for example, therapeutic methods and the like for known or novel IL-8-related diseases using a novel anti-IL-8 antibody are provided.
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5.发明申请公开(公告)号：US20170129950A1
公开(公告)日：2017-05-11
申请号：US15266829
申请日：2016-09-15
发明人： Hirotake SHIRAIWA , Keiko Esaki , Tomoyuki Igawa , Taichi Kuramochi , Atsuhiko Maeda , Shigero Tamba , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Yasuko Kinoshita , Masami Suzuki , Atsuhiko Kato , Etsuko Takeiri , Eri Hashimoto , Yoshinori Watanabe
IPC分类号： C07K16/22
CPC分类号： C07K16/22 , A61K2039/505 , C07K2317/24 , C07K2317/33 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94
摘要： The inventors successfully produced anti-Epiregulin antibodies showing cross-species reactivity between cynomolgus monkey (non-human animals) and human, anti-Epiregulin antibodies with suppressed chemical degradation, anti-Epiregulin antibodies with lowered isoelectric point, anti-Epiregulin antibodies with increased thermal denaturation midpoint temperature, and anti-Epiregulin antibodies with reduced amount of aggregate by performing appropriate amino acid residue substitutions in the variable-region sequences of the humanized EP27 antibody which inhibits growth of cancer cells by exhibiting cytotoxic activity and neutralizing activity against human Epiregulin-expressing cells.
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6.发明申请Humanized Anti-Epiregulin Antibody, and Cancer Therapeutic Agent Comprising Said Antibody as Active Ingredient 有权人源化抗前列腺素抗体和包含所述抗体作为活性成分的癌症治疗剂公开(公告)号：US20150110793A1
公开(公告)日：2015-04-23
申请号：US14369539
申请日：2012-12-28
发明人： Hirotake Shiraiwa , Keiko Esaki , Tomoyuki Igawa , Taichi Kuramochi , Atsuhiko Maeda , Shigero Tamba , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Yasuko Kinoshita , Masami Suzuki , Atsuhiko Kato , Etsuko Takeiri , Eri Hashimoto , Yoshinori Watanabe
IPC分类号： C07K16/22
CPC分类号： C07K16/22 , A61K2039/505 , C07K2317/24 , C07K2317/33 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94
摘要： The inventors successfully produced anti-Epiregulin antibodies showing cross-species reactivity between cynomolgus monkey (non-human animals) and human, anti-Epiregulin antibodies with suppressed chemical degradation, anti-Epiregulin antibodies with lowered isoelectric point, anti-Epiregulin antibodies with increased thermal denaturation midpoint temperature, and anti-Epiregulin antibodies with reduced amount of aggregate by performing appropriate amino acid residue substitutions in the variable-region sequences of the humanized EP27 antibody which inhibits growth of cancer cells by exhibiting cytotoxic activity and neutralizing activity against human Epiregulin-expressing cancer cells.
摘要翻译： 本发明人成功地生产出显示食蟹猴（非人动物）与抑制化学降解的人抗anti-epiregulin抗体之间的跨物种反应性的抗上游抗原蛋白抗体，具有降低的等电点的抗上皮蛋白抗体，具有增加的热量的抗上皮蛋白抗体 通过在人源化EP27抗体的可变区序列中进行适当的氨基酸残基置换，通过显示出细胞毒性活性和中和人类表达后代孕激素的活性来抑制癌细胞的生长，从而减少聚集体的量，使抗变性中点温度降低， 癌细胞。
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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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