公开(公告)号：EP2842417B1

公开(公告)日：2018-03-14

申请号：EP13780731.9

申请日：2013-04-25

申请人： Tokyo Metropolitan Institute of Medical Science ,  Chugai Seiyaku Kabushiki Kaisha ,  Phoenixbio Co., Ltd.

发明人： KOHARA, Michinori ,  JISHAGE, Koichi ,  KAWASE, Yosuke ,  MUKAIDANI, Chise ,  OSHITA, Hiroki ,  HAMAMURA, Satoko

IPC分类号： C12N9/72 ,  C12N15/85 ,  A01K67/027 ,  G01N33/50

CPC分类号： A01K67/0275 ,  A01K67/0271 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2217/15 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2267/0337 ,  A01K2267/035 ,  C12N9/6462 ,  C12N15/8509 ,  C12N15/8775 ,  C12N2015/8581 ,  G01N33/5067 ,  G01N33/5088 ,  Y10T436/146666

摘要： The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

公开(公告)号：EP3502250A1

公开(公告)日：2019-06-26

申请号：EP17843526.9

申请日：2017-08-21

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： JISHAGE, Koichi ,  HINO, Hiroshi ,  ISHIGURO, Takahiro ,  KINOSHITA, Yasuko

IPC分类号： C12N15/09 ,  A01K67/027 ,  C07K16/28 ,  C12N5/10 ,  C12P21/08 ,  G01N33/15 ,  G01N33/50

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.

公开(公告)号：EP3320773A1

公开(公告)日：2018-05-16

申请号：EP16824403.6

申请日：2016-07-08

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： JISHAGE, Koichi ,  UEDA, Otoya ,  WADA, Naoko ,  ISHIGURO, Takahiro ,  KINOSHITA, Yasuko

IPC分类号： A01K67/027 ,  G01N33/15 ,  G01N33/50 ,  C12N15/09

CPC分类号： A01K67/0278 ,  A01K2207/12 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0325 ,  A01K2267/0331 ,  C07K14/7051 ,  C07K16/2809 ,  C12N15/09 ,  C12N15/8509 ,  C12N2015/8518 ,  G01N33/15 ,  G01N33/5008

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.

摘要翻译： 本发明提供遗传修饰的非人动物，其缺失至少一种或多种类型的CD3基因，所述基因选自由其基因组中的内源性CD3ε，CD3δ和CD3γ组成的组，并且其功能性表达至少一种或多种类型的人 选自人CD3ε，CD3δ和CD3γ的CD3基因。 在本发明的基因修饰的非人动物中，可以发生成熟的T细胞分化和产生，并且包括T细胞的免疫活性细胞可以发挥其功能。 本发明的基因修饰的非人动物能够有效评估和筛选开发使用人CD3介导的靶向药物的治疗剂和治疗方法。

公开(公告)号：EP2842417A1

公开(公告)日：2015-03-04

申请号：EP13780731.9

申请日：2013-04-25

申请人： Tokyo Metropolitan Institute of Medical Science ,  Chugai Seiyaku Kabushiki Kaisha ,  Phoenixbio Co., Ltd.

发明人： KOHARA, Michinori ,  JISHAGE, Koichi ,  KAWASE, Yosuke ,  MUKAIDANI, Chise ,  OSHITA, Hiroki ,  HAMAMURA, Satoko

IPC分类号： A01K67/027 ,  G01N33/15 ,  G01N33/50 ,  C12N15/09

CPC分类号： A01K67/0275 ,  A01K67/0271 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2217/15 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2267/0337 ,  A01K2267/035 ,  C12N9/6462 ,  C12N15/8509 ,  C12N15/8775 ,  C12N2015/8581 ,  G01N33/5067 ,  G01N33/5088 ,  Y10T436/146666

摘要： The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of:
(i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof;
(ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo;
(iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and
(iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.