公开(公告)号：EP3957722A1

公开(公告)日：2022-02-23

申请号：EP20792193.3

申请日：2020-04-17

申请人： Keio University ,  Nihon University

发明人： OKANO, Hideyuki ,  SHIOZAWA, Seiji ,  YOSHIMATSU, Sho ,  EDAMURA, Kazuya ,  IGUCHI, Aozora

IPC分类号： C12N5/10 ,  C12N15/12 ,  C12N9/99

摘要： This method of producing induced pluripotent stem cells involves 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.

公开(公告)号：EP4349970A1

公开(公告)日：2024-04-10

申请号：EP22811395.7

申请日：2022-05-27

申请人： Keio University

发明人： OKANO, Hideyuki ,  KASE, Yoshitaka

IPC分类号： C12N5/079 ,  A61K35/30 ,  A61L27/38 ,  C12N15/63 ,  C12Q1/02

摘要： There are provided a neurite outgrowth promotion kit containing a γ-secretase inhibitor or a GADD45G expression vector, in which the neurite outgrowth promotion kit is used for significantly promoting neurite outgrowth of nerve cells as compared with a control, by acting on a neurosphere to induce differentiation of the neurosphere into nerve cells; a method for producing a neurosphere for treatment of spinal cord injury, which includes a step of using the above-described neurite outgrowth promotion kit on a neurosphere derived from a pluripotent stem cell; a neurosphere for treatment of spinal cord injury; and a method for selecting a neurosphere for treatment of spinal cord injury and a method for screening a neurite outgrowth-promoting agent.

公开(公告)号：EP4206320A1

公开(公告)日：2023-07-05

申请号：EP21858393.8

申请日：2021-08-20

申请人： JSR Corporation ,  Keio University

发明人： HIRAMINE, Hayato ,  SHIOZAWA, Seiji ,  OKANO, Hideyuki ,  ISHIKAWA, Mitsuru

IPC分类号： C12N5/074 ,  C12M3/00 ,  C12N5/079 ,  C12P7/44 ,  C12P13/08 ,  C12P13/24 ,  C12P17/10 ,  C12P19/32

摘要： A method of culturing human induced pluripotent stem cells includes a step of inoculating human induced pluripotent stem cells in a culture medium at an inoculation density of 1.0 × 10 4 to 1.0 × 10 6 cells/cm 2 in a culture vessel and subjecting the human induced pluripotent stem cells to two-dimensional culturing. A method of producing cerebral organoids includes a step 1 of culturing a culture of the human induced pluripotent stem cells obtained by the method of culturing human induced pluripotent stem cells in a culture medium containing a BMP inhibitor and a transforming growth factor β (TGFβ) inhibitor to form cell aggregates, a step 2 of culturing the cell aggregates in a culture medium containing a Wnt signal transduction pathway potentiator and an extracellular matrix, and a step 3 of subjecting the culturing obtained in the step 2 to spinner culturing.

公开(公告)号：EP3272858A1

公开(公告)日：2018-01-24

申请号：EP16765082.9

申请日：2016-03-17

申请人： ONO Pharmaceutical Co., Ltd. ,  Keio University

发明人： OKANO, Hideyuki ,  SHIOZAWA, Seiji ,  KISA, Fumihiko

IPC分类号： C12N5/10 ,  C12N5/0735 ,  C12N15/09

CPC分类号： C12N5/0696 ,  C12N5/10 ,  C12N15/09 ,  C12N2501/01 ,  C12N2501/20 ,  C12N2501/60 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/605 ,  C12N2501/606

摘要： To produce and/or maintain naive 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 naive 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.

摘要翻译： 为了产生和/或维持能够高度表达对维持未分化状态重要的基因的幼稚多能干细胞，这是通过用于产生多能干细胞的已知方法不能实现的。 本发明可通过在所谓的初始化因子中导入并允许六种基因（Oct3 / 4，Klf4，c-Myc，Sox2，Nanog和Klf2）的瞬时表达来产生能够维持未分化状态的幼稚多能干细胞， 并进一步在含有LIF，MEK抑制剂，GSK3抑制剂，cAMP产生促进剂，TGF-β抑制剂和PKC抑制剂的培养基中进行培养。 因此，可以解决本发明的问题。

公开(公告)号：EP2679226A1

公开(公告)日：2014-01-01

申请号：EP12749626.3

申请日：2012-02-23

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

发明人： OKANO, Hideyuki ,  TSUBOTA, Kazuo ,  SHIMMURA, Shigeto ,  OMOTO, Masahiro ,  KISHINO, Akiyoshi ,  MAEDA, Miho

IPC分类号： A61K31/352 ,  A61P27/02 ,  A61P27/04 ,  A61P43/00 ,  C07D311/86

CPC分类号： C07D311/86 ,  A61K31/352

摘要： A compound represented by formula (1), or a pharmaceutically acceptable salt thereof is effective as a therapeutic agent or a prophylactic agent for a corneal disease or sensory nerve damage due to corneal surgery, and as a regeneration accelerator for corneal sensory nerves:

wherein R 1 represents a hydrogen atom or a carboxyl group, R 2 represents a hydrogen atom or a hydroxy group, R 3 represents a hydrogen atom or a carboxyl group, and R 4 represents a hydrogen atom or a hydroxy group.

摘要翻译： 由式（1）表示的化合物或其药学上可接受的盐作为角膜疾病或由角膜手术引起的感觉神经损伤的治疗剂或预防剂是有效的，并且作为用于角膜感觉神经的再生促进剂：其中R1 表示氢原子或羧基，R 2表示氢原子或羟基，R 3表示氢原子或羧基，并且R 4表示氢原子或羟基。

公开(公告)号：EP2321406A1

公开(公告)日：2011-05-18

申请号：EP09804740.0

申请日：2009-08-05

申请人： Keio University ,  Kyoto University

发明人： OKANO, Hideyuki ,  TSUJI, Osahiko ,  NAKAMURA, Masaya ,  YAMANAKA, Shinya ,  MIURA, Kyoko

IPC分类号： C12N5/00 ,  G01N33/48

CPC分类号： C12N5/0618 ,  A61K35/12 ,  C12N2501/385 ,  C12N2501/60 ,  C12N2506/45 ,  C12N2510/00 ,  C12Q1/6886 ,  C12Q2600/158

摘要： In order to provide a therapeutic agent for nerve injury which contains iPS-derived neural stem cells and has low or no risk of side effects, as well as a method for treating a nerve injury using the iPS cells, by efficiently establishing in vivo the iPS-derived neural stem having low or no risk of tumor formation, neurospheres are formed following formation of embryoid bodies from the iPS cells, and a clone whose ratio of cells in which the promoter of Nanog gene is activated is 0.01% or less is selected, and the clone is administered to a patient suffering from the nerve injury.

公开(公告)号：EP2246423A1

公开(公告)日：2010-11-03

申请号：EP08871871.3

申请日：2008-12-09

申请人： Central Institute For Experimental Animals ,  Keio University

发明人： SASAKI, Erika ,  OKANO, Hideyuki

IPC分类号： C12N15/09 ,  A01K67/027

CPC分类号： A01K67/0275 ,  A01K2217/052 ,  A01K2227/106 ,  A01K2267/0318 ,  A01K2267/0356 ,  A01K2267/0393 ,  C07K14/43595 ,  C07K14/47 ,  C12N15/8509 ,  C12N2740/15043 ,  C12N2799/027 ,  C12N2999/007

摘要： An object of the present invention is to provide a method for introducing a gene into an embryo for production of a human disease model primate animal using a non-human primate animal such as a marmoset. The present invention relates to a method for introducing a foreign gene into an early embryo of a non-human primate animal, which comprises placing early embryos of a non-human primate in a 0.2 M to 0.3 M sucrose solution, so as to increase the volume of the perivitelline spaces, and then injecting a viral vector containing a human foreign gene operably linked to a promoter into the perivitelline spaces of the early embryos.

摘要翻译： 本发明的一个目的是提供一种用于将基因导入胚胎生产使用非人类灵长类动物中的人类疾病模型灵长类动物的提供一种方法：如狨猴。 本发明涉及一种方法用于将外源基因导入早期胚胎中的非人灵长类动物的方法，其包括将非人类灵长类动物的早期胚胎在0.2M至0.3M的蔗糖溶液，以增加 围卵腔的体积，然后将含有可操作地连接到启动子进早期胚胎的围卵腔人类外源基因的病毒载体。

公开(公告)号：EP4310178A1

公开(公告)日：2024-01-24

申请号：EP22771538.0

申请日：2022-03-18

申请人： Keio University

发明人： ISHII, Hiroko ,  OKANO, Hideyuki ,  KONDO, Takahiro ,  SATO, Yuta

IPC分类号： C12N5/079 ,  C12N15/12 ,  C12N15/864 ,  C12Q1/06 ,  G01N33/15

摘要： A method for producing a brain organoid having an aggregated tau protein including a step (a) of culturing pluripotent stem cells in the presence of a SMAD inhibitor to form an embryoid body, a step (b) of embedding the embryoid body in an extracellular matrix and three-dimensionally culturing the embryoid body in the presence of a SMAD inhibitor and a GSK3β inhibitor to form an organoid that includes neural precursor cells, a step (c) of extracting the organoid from the extracellular matrix and suspension-culturing the organoid in the presence of LIF to form a brain organoid, a step (d) of forcing the brain organoid to express a mutant MAPT gene, and a step (e) of further suspension-culturing the brain organoid after step (d) to obtain a brain organoid having an aggregated tau protein.

公开(公告)号：EP4001401A1

公开(公告)日：2022-05-25

申请号：EP20836508.0

申请日：2020-06-30

申请人： Keio University

发明人： ISHII, Hiroko ,  OKANO, Hideyuki

IPC分类号： C12N5/079 ,  C12N5/10 ,  C12Q1/06

摘要： A production method for a cerebral organoid having amyloid plaques is provided, the method including a step (a) of forming, in the presence of a SMAD inhibitor, an embryoid body from a pluripotent stem cell having a mutation in an Alzheimer's disease-related gene; a step (b) of embedding the embryoid body after the step (a) in an extracellular matrix and three-dimensionally culturing the embedded embryoid body in the presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor to form an organoid; and a step (c) of removing the organoid after the step (b) from the extracellular matrix and subjecting the removed organoid to stirring culture in a medium, where at least a part of the step (c) is carried out in the presence of leukemia inhibitory factor (LIF).

公开(公告)号：EP3904858A1

公开(公告)日：2021-11-03

申请号：EP19903278.0

申请日：2019-12-26

申请人： Sanyu Electron Co., Ltd. ,  Keio University

发明人： SHIBATA, Shinsuke ,  SHINDO, Tomoko ,  OKANO, Hideyuki ,  GOTO, Shuichi

IPC分类号： G01N1/28

摘要： Sample preparation system and method which enable electron microscope observation of a sample slice with simple structure and process are provided. The sample preparation system includes at least one of a plasma treatment apparatus and a sputtering apparatus, as well as a slice collecting apparatus. The plasma treatment apparatus is configured to feed a resin tape in a plasma irradiation area to irradiate the resin tape with plasma, thereby continuously hydrophilizing the resin tape. The sputtering apparatus is configured to feed the resin tape in a sputtering area to continuously perform sputtering on the resin tape, thereby imparting conductivity to the resin tape. The slice collecting apparatus is configured to serially collect slices cut out from a sample onto the resin tape having been subjected to plasma treatment or sputtering.