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.

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.

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.

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).

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).

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。

公开(公告)号：US20150104870A1

公开(公告)日：2015-04-16

申请号：US14397376

申请日：2013-04-26

申请人： KEIO UNIVERSITY

发明人： Hayato Kaneda ,  Hideyuki Okano ,  Takuya Shimazaki

IPC分类号： C12N5/0797 ,  A61K31/4439 ,  C12N5/0793 ,  C12N15/113

CPC分类号： C12N5/0623 ,  A61K31/4439 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  A61K35/30 ,  C12N5/0619 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2501/65 ,  C12N2501/727 ,  C12N2501/999 ,  C12N2506/08 ,  C12Y207/11024

摘要： The present invention provides an agent for promoting neuronal differentiation of neural stem cells, which contains a p38 inhibitor. In addition, the present invention provides a method of promoting neuronal differentiation of neural stem cells, which includes cultivating neural stem cells in the presence of a p38 inhibitor. Neural stem cells are gliogenic or neurogenic. The p38 inhibitor is a nucleic acid which hybridizes to DNA or mRNA encoding p38 under physiological conditions, thereby inhibiting the transcription and/or translation thereof, an expression vector of the nucleic acid, a low molecular p38 inhibitor and the like.

摘要翻译： 本发明提供了用于促进含有p38抑制剂的神经干细胞的神经元分化的药剂。 此外，本发明提供了促进神经干细胞的神经元分化的方法，其包括在p38抑制剂存在下培养神经干细胞。 神经干细胞是神经源性的或神经源性的。 p38抑制剂是在生理条件下与编码p38的DNA或mRNA杂交的核酸，从而抑制其转录和/或翻译，核酸表达载体，低分子p38抑制剂等。

公开(公告)号：US20220235331A1

公开(公告)日：2022-07-28

申请号：US17603645

申请日：2020-04-17

申请人： Keio University ,  Nihon University

发明人： Hideyuki Okano ,  Seiji Shiozawa ,  Sho Yoshimatsu ,  Kazuya Edamura ,  Aozora Iguchi

IPC分类号： C12N5/074

摘要： A method of producing induced pluripotent stem cells including a step for introducing an initialization factor into somatic cells of a mammal, and culturing in a neural stem cell culture medium to obtain induced neural stem cell-like cells, and a step for cultivating said induced neural stem cell-like cells in a growth medium to obtain induced pluripotent stem cells, wherein the initialization factor contains an OCT family, a SOX family, a KLF family, a MYC family, a LIN28 family and a P53 function inhibitor.