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公开(公告)号：US11667713B2
公开(公告)日：2023-06-06
申请号：US16957837
申请日：2018-12-28
发明人： Shogo Kamikawaji , Yasuko Kinoshita , Shinya Ishii
CPC分类号： C07K16/2809 , A61P35/00 , C07K16/28 , C07K2317/52 , C07K2317/56
摘要： The present inventors discovered novel multispecific antigen-binding molecules with excellent cellular cytotoxicity, which comprise a first domain comprising a first antigen variable region which binds to DLL3 and a second domain comprising a second antigen variable region which binds to T cell receptor complex. The present inventors prepared further bispecific antibodies, and assessed their T cell-dependent cell cytotoxicity (TDCC), and found that they also show strong TDCC activity. Since the molecules/antibodies of the present invention show a strong cytotoxicity against cells expressing DLL3, novel pharmaceutical compositions comprising the molecules/antibodies for treating or preventing various cancers associated with DLL3 can be provided.
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公开(公告)号：US11612149B2
公开(公告)日：2023-03-28
申请号：US15743248
申请日：2016-07-08
发明人： Koichi Jishage , Otoya Ueda , Naoko Wada , Takahiro Ishiguro , Yasuko Kinoshita
IPC分类号： A01K67/027 , C07K16/28 , C07K14/725 , C12N15/85 , C12N15/09 , G01N33/50 , G01N33/15
摘要： The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3ε, CD3δ, and CD3γ in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3ε, CD3δ, and CD3γ. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.
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3.发明申请公开(公告)号：US20150291694A1
公开(公告)日：2015-10-15
申请号：US14567653
申请日：2014-12-11
发明人： Hiroyuki ABURATANI , Yoshitaka Hippo , Akira Watanabe , Masashi Fukayama , Yukio Ito , Masahiro Arai , Hirotaka Ito , Toshihiko Ohtomo , Shin-ichi Funahashi , Yasuko Kinoshita
IPC分类号： C07K16/28
CPC分类号： C07K16/2803 , A61K2039/505 , C07K16/30 , C07K16/303 , C07K2317/73 , C07K2317/732 , C07K2317/734 , G01N33/57438 , G01N33/57488 , G01N33/576
摘要： A method for diagnosing cancer comprising detecting ROBO1 protein is disclosed. In addition, a method for treating a disease caused by abnormal cell growth comprising administrating an antibody that binds to ROBO1, as well as a pharmaceutical composition, a cell growth inhibitor and an anticancer agent comprising an antibody that binds to ROBO1 as an active ingredient are disclosed. Further, a method for inducing cell damages in a ROBO1 expressing cell and a method for inhibiting the growth of a ROBO1 expressing cell by bringing a ROBO1 expressing cell into contact with an antibody that binds to ROBO1, are disclosed. Furthermore, a method for monitoring progression of hepatitis by detecting ROBO1 protein is disclosed.
摘要翻译： 公开了一种诊断癌症的方法，包括检测ROBO1蛋白。 另外，用于治疗由异常细胞生长引起的疾病的方法包括施用与ROBO1结合的抗体，以及药物组合物，细胞生长抑制剂和抗癌剂，其包含结合ROBO1作为有效成分的抗体的方法， 披露 此外，公开了通过使ROBO1表达细胞与与ROBO1结合的抗体接触来抑制ROBO1表达细胞中的细胞损伤的方法和抑制ROBO1表达细胞的生长的方法。 此外，公开了通过检测ROBO1蛋白来监测肝炎进展的方法。
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公开(公告)号：US11767362B1
公开(公告)日：2023-09-26
申请号：US16084346
申请日：2017-03-14
发明人： Mika Endo , Atsuhiko Kato , Toshihiko Ohtomo , Kenji Adachi , Yasuko Kinoshita , Yoshinori Narita
CPC分类号： C07K16/2827 , A61P35/00 , C07K16/303 , C07K2317/24 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/76
摘要： The invention provides compositions and methods for treating cancers. The methods comprising administering a PD-1 axis binding antagonist and an anti-GPC3 antibody. The compositions comprising a pharmaceutical composition for treating cancer which comprises a PD-1 axis binding antagonist and an anti-GPC3 antibody. Also disclosed are a pharmaceutical composition to be used in combination with a PD-1 axis binding antagonist for treating cancer which comprises an anti-GPC3 antibody as the active ingredient; and a pharmaceutical composition to be used in combination with an anti-GPC3 antibody for treating cancer which comprises as the active ingredient a PD-1 axis binding antagonist.
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5.发明授权Humanized anti-epiregulin antibody, and cancer therapeutic agent comprising said antibody as active ingredient 有权人源化抗上皮蛋白抗体，以及包含所述抗体作为活性成分的癌症治疗剂公开(公告)号：US09556264B2
公开(公告)日：2017-01-31
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
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：US11793180B2
公开(公告)日：2023-10-24
申请号：US16327218
申请日：2017-08-21
IPC分类号： A01K67/027 , C12N15/85 , G01N33/50 , C07K16/28 , C07K16/30 , C12N5/10 , C07K14/705 , A61K39/00
CPC分类号： A01K67/0278 , C07K14/705 , C07K16/2809 , C07K16/303 , C12N5/10 , C12N15/85 , G01N33/5041 , G01N33/5088 , A01K2217/052 , A01K2217/072 , A01K2217/206 , A01K2227/105 , A61K2039/505 , C07K2317/31 , C12N2015/8518
摘要： Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.
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公开(公告)号：US09644029B2
公开(公告)日：2017-05-09
申请号：US14567653
申请日：2014-12-11
发明人： Hiroyuki Aburatani , Yoshitaka Hippo , Akira Watanabe , Masashi Fukayama , Yukio Ito , Masahiro Arai , Hirotaka Ito , Toshihiko Ohtomo , Shin-ichi Funahashi , Yasuko Kinoshita
IPC分类号： C07K16/28 , C07K16/30 , A61K39/00 , G01N33/574 , G01N33/576
CPC分类号： C07K16/2803 , A61K2039/505 , C07K16/30 , C07K16/303 , C07K2317/73 , C07K2317/732 , C07K2317/734 , G01N33/57438 , G01N33/57488 , G01N33/576
摘要： A method for diagnosing cancer comprising detecting ROBO1 protein is disclosed. In addition, a method for treating a disease caused by abnormal cell growth comprising administrating an antibody that binds to ROBO1, as well as a pharmaceutical composition, a cell growth inhibitor and an anticancer agent comprising an antibody that binds to ROBO1 as an active ingredient are disclosed. Further, a method for inducing cell damages in a ROBO1 expressing cell and a method for inhibiting the growth of a ROBO1 expressing cell by bringing a ROBO1 expressing cell into contact with an antibody that binds to ROBO1, are disclosed. Furthermore, a method for monitoring progression of hepatitis by detecting ROBO1 protein is disclosed.
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公开(公告)号：US11072666B2
公开(公告)日：2021-07-27
申请号：US16083975
申请日：2017-02-24
发明人： Yasuko Kinoshita , Yumiko Kawai , Toshiaki Tsunenari , Takahiro Ishiguro , Mika Endo , Yuji Sano
摘要： The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.
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9.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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公开(公告)号：US20150259417A1
公开(公告)日：2015-09-17
申请号：US14713416
申请日：2015-05-15
发明人： Kiyotaka Nakano , Takeshi Yoshino , Jun-Ichi Nezu , Hiroyuki Tsunoda , Tomoyuki Igawa , Hiroko Konishi , Megumi Tanaka , Izumi Sugo , Shigeto Kawai , Takahiro Ishiguro , Yasuko Kinoshita
CPC分类号： C07K16/28 , C07K7/06 , C07K14/47 , C07K16/303 , C07K2317/24 , C07K2317/34 , C07K2317/565 , C07K2317/732 , C07K2317/734 , C07K2317/92
摘要： An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.
摘要翻译： 公开了能够结合磷脂酰肌醇蛋白聚糖3的特定区域的抗体以及基于该抗体产生的人源化抗体。 本发明的抗GPC3抗体与常规抗体相比具有较高的ADCC活性和CDC活性。 本发明的抗体可用作细胞生长抑制剂，抗癌剂和癌症诊断剂。
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