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    Method for Producing Cell Aggregate Including Glial Progenitor Cells
    1.
    发明申请
    Method for Producing Cell Aggregate Including Glial Progenitor Cells 有权

    公开(公告)号：US20220323507A1

    公开(公告)日：2022-10-13

    申请号：US17639767

    申请日：2020-09-04

    申请人： Keio University ,  Sumitomo Dainippon Pharma Co., Ltd.

    发明人： Jun Kohyama ,  Yasuhiro Kamata ,  Masaya Nakamura ,  Hideyuki Okano ,  Miho Saito ,  Mitsuhiro Inoue

    IPC分类号： A61K35/30 ,  C12N5/079 ,  A61P25/28

    摘要： The method for producing a cell aggregate including glial progenitor cells according to the present invention comprises: (1) a step of subjecting pluripotent stem cells to suspension culture in an embryoid-body-forming culture medium containing one or more SMAD signaling inhibitors and one or more Wnt signaling activators in the absence of feeder cells for 5 days to 10 days, to form a cell aggregate; (2) a step of subjecting the cell aggregate obtained in (1) to suspension culture in an embryoid-body-forming culture medium containing retinoic acid; (3) a step of subjecting the cell aggregate obtained in (2) to suspension culture in an embryoid-body-forming culture medium or neuron-and-glia-proliferating culture medium containing retinoic acid and one or more SHH signaling activators; and (4) a step of subjecting the cell aggregate obtained in (3) to suspension culture in a neuron-and-glia-proliferating culture medium containing no retinoic acid and one or more SHH signaling activators.

    METHOD FOR PRODUCING PARVALBUMIN-POSITIVE NERVE CELLS, CELL, AND DIFFERENTIATION INDUCER
    2.
    发明申请
    METHOD FOR PRODUCING PARVALBUMIN-POSITIVE NERVE CELLS, CELL, AND DIFFERENTIATION INDUCER 有权

    公开(公告)号：US20220282210A1

    公开(公告)日：2022-09-08

    申请号：US17637862

    申请日：2020-08-28

    申请人： Keio University

    发明人： Mitsuru Ishikawa ,  Hideyuki Okano

    IPC分类号： C12N5/0793 ,  C12N15/113 ,  C07K14/47

    摘要： A production method for parvalbumin-positive nerve cells includes: an expression induction step of inducing expression of Ascl1 gene, Dlx2 gene, and MEF2C gene in a cell, and a differentiation step of culturing the cell after the expression induction to differentiate the cells into parvalbumin-positive nerve cell; a cell into which Ascl1 gene, Dlx2 gene, and MEF2C gene are introduced in an expressible manner; and a differentiation inducer for inducing differentiation of a cell into a parvalbumin-positive nerve cell, including Ascl1 gene, Dlx2 gene, and MEF2C gene, or gene products thereof, as an active ingredient.

    Therapeutic agents for inner ear hearing impairment
    4.
    发明授权
    Therapeutic agents for inner ear hearing impairment 有权

    公开(公告)号：US11058669B2

    公开(公告)日：2021-07-13

    申请号：US15544419

    申请日：2016-01-13

    申请人： Keio University

    发明人： Makoto Hosoya ,  Masato Fujioka ,  Hideyuki Okano ,  Kaoru Ogawa ,  Tatsuo Matsunaga

    IPC分类号： A61K31/155 ,  A61K31/436 ,  A61P27/16 ,  A61K31/439 ,  G01N33/50

    摘要： An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided: wherein R1 to R7 are each independently selected from a hydrogen atom, a halogen atom, or a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkoxy carbonyl group, a C3-8 cycloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, and a phenyl group; wherein R1 is a C1-6 alkyl or a C3-6 alkynyl, R2 is H, —CH2-OH or —CH2—CH2OH, and X is ═O, (H, H) or (H, OH).

    Therapeutic agents for inner ear hearing impairment
    5.
    发明授权
    Therapeutic agents for inner ear hearing impairment 有权

    公开(公告)号：US11013725B2

    公开(公告)日：2021-05-25

    申请号：US15654267

    申请日：2017-07-19

    申请人： Keio University

    发明人： Makoto Hosoya ,  Masato Fujioka ,  Hideyuki Okano ,  Kaoru Ogawa ,  Tatsuo Matsunaga

    IPC分类号： A61K31/436 ,  A61P27/16 ,  A61K31/155 ,  A61K31/439 ,  G01N33/50

    摘要： An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided: wherein R1 to R7 are each independently selected from a hydrogen atom, a halogen atom, or a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkoxy carbonyl group, a C3-8 cycloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, and a phenyl group; wherein R1 is a C1-6 alkyl or a C3-6 alkynyl, R2 is H, —CH2-OH or —CH2—CH2—OH, and X is ═O, (H, H) or (H, OH).

    MOUSE MODEL OF AMYOTROPHIC LATERAL SCLEROSIS AND/OR FRONTOTEMPORAL LOBAR DEGENERATION
    6.
    发明申请
    MOUSE MODEL OF AMYOTROPHIC LATERAL SCLEROSIS AND/OR FRONTOTEMPORAL LOBAR DEGENERATION 审中-公开
    淋巴结转移灶和/或冠状动脉狭窄的小鼠模型

    公开(公告)号：US20150173330A1

    公开(公告)日：2015-06-25

    申请号：US14404570

    申请日：2013-05-30

    申请人： Keio University

    发明人： Hideyuki Okano ,  Hirotaka James Okano ,  Chikako Miyauchi

    IPC分类号： A01K67/027

    CPC分类号： A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0318

    摘要： To generate an animal model exhibiting symptoms similar to those of human amyotrophic lateral sclerosis and/or human frontotemporal lobar degeneration. An animal model exhibiting symptoms similar to those of human amyotrophic lateral sclerosis and/or human frontotemporal lobar degeneration can be produced by means of generating a mutation in a vertebrate so that expression of a mutant protein with a substitution of tyrosine for alanine at a position corresponding to position 382 of SEQ ID NO. 1 or a mutant protein with a substitution of cysteine for glycine at a position corresponding to position 348 of SEQ ID NO. 1 is regulated by an endogenous TDP-43 gene promoter in at least one allele of an endogenous TDP-43 gene of the vertebrate.

    摘要翻译： 产生表现出类似于人肌萎缩性侧索硬化和/或人额颞叶变性的症状的动物模型。 可以通过在脊椎动物中产生突变来产生表现出与人肌萎缩性侧索硬化和/或人额颞叶变性相似的症状的动物模型，使得在对应位置处表达具有丙氨酸酪氨酸酪氨酸的突变蛋白 到SEQ ID NO的位置382。 1或在对应于SEQ ID NO的位置348的位置具有半胱氨酸取代甘氨酸的突变蛋白。 1在脊椎动物的内源性TDP-43基因的至少一个等位基因中由内源性TDP-43基因启动子调节。

    Method for producing naïve pluripotent stem cells
    10.
    发明授权
    Method for producing naïve pluripotent stem cells 有权

    公开(公告)号：US10738280B2

    公开(公告)日：2020-08-11

    申请号：US15558473

    申请日：2016-03-17

    申请人： ONO PHARMACEUTICAL CO., LTD. ,  KEIO UNIVERSITY

    发明人： Hideyuki Okano ,  Seiji Shiozawa ,  Fumihiko Kisa

    IPC分类号： C12N5/00 ,  C12N5/02 ,  C12N5/074 ,  C12N5/10 ,  C12N15/09

    摘要： To produce and/or maintain naïve pluripotent stem cells capable of highly expressing genes important for maintaining an undifferentiated state, which could not be achieved by known methods for producing pluripotent stem cells. The present invention can produce naïve pluripotent stem cells capable of maintaining an undifferentiated state by introducing and allowing transient expression of six genes (Oct3/4, Klf4, c-Myc, Sox2, Nanog, and Klf2) among the so-called initializing factors, and further performing culturing in a medium containing LIF, an MEK inhibitor, a GSK3 inhibitor, a cAMP production promoter, a TGF-β inhibitor and a PKC inhibitor. Thus, the problem of the present invention can be solved.