公开(公告)号：EP3312270A1

公开(公告)日：2018-04-25

申请号：EP16811730.7

申请日：2016-06-16

申请人： Kyoto University ,  Megakaryon Corporation

发明人： ETO, Koji ,  NAKAMURA, Sou ,  ITO, Yukitaka ,  SHIGEMORI, Tomohiro ,  DOHDA, Takeaki

IPC分类号： C12N5/078 ,  A61K35/19 ,  A61P7/04 ,  C12N15/09 ,  C12N15/113

摘要： The present invention provides a highly functional platelet production promoting agent which comprises one or a plurality of aryl hydrocarbon receptor (AhR) antagonists and one or a plurality of Rho-associated coiled-coil forming kinase (ROCK) inhibitors.

摘要翻译： 本发明提供高功能血小板产生促进剂，其包含一种或多种芳基烃受体（AhR）拮抗剂和一种或多种Rho相关卷曲螺旋形成激酶（ROCK）抑制剂。

公开(公告)号：EP4342982A1

公开(公告)日：2024-03-27

申请号：EP22825104.7

申请日：2022-06-17

申请人： Megakaryon Corporation

发明人： ITO, Yukitaka ,  MISUMI, Sachiyo

IPC分类号： C12N5/078 ,  A61K35/19 ,  A61P7/04 ,  C12N5/10 ,  C12N15/09

摘要： A method for improving the amount of platelets produced. The production method is a method for producing multinucleated megakaryocyte cells with enhanced platelet production capability, the method including a multinucleation step of inducing multinucleated megakaryocyte cells through multinucleation of pre-multinucleated megakaryocyte cells in the presence of a growth factor of the pre-multinucleated megakaryocyte cells. In the multinucleation step, the multinucleated megakaryocyte cells are induced by suppressing the activity of at least one protein selected from the group consisting of an aryl hydrocarbon receptor (AhR), a Rho-associated kinase (ROCK), dual-specificity tyrosine phosphorylation-regulated kinases (DYRK), and myosin 2, and multinucleating the pre-multinucleated megakaryocyte cells in the presence of harmine.

公开(公告)号：EP3650535A1

公开(公告)日：2020-05-13

申请号：EP18828313.9

申请日：2018-07-05

申请人： Kyoto University ,  Megakaryon Corporation ,  Satake Chemical Equipment Mfg.,Ltd.

发明人： ETO, Koji ,  NAKAMURA, Sou ,  ITO, Yukitaka ,  SHIGEMORI, Tomohiro ,  KATO, Yoshikazu

IPC分类号： C12N5/078 ,  B01F7/16 ,  B01F7/18 ,  B01F11/00 ,  C12M1/02 ,  C12M3/00 ,  C12N5/10

摘要： Methods of production and apparatuses for production for stably producing healthy and functional platelets, and methods for determining operating conditions of an apparatus for producing platelets are provided. The present invention relates to methods of production comprising a step of culturing megakaryocytes in a platelet production medium C, wherein the step of culturing comprises a step of stirring a medium C in containers 1, 4 using stirring mechanisms 2, 5. In one method of production, the step of stirring comprises reciprocating stirring blades 21, 24 in the stirring mechanisms 2, 24 such that any of predetermined turbulent energy, shearing stresses, or Kolmogorov scale is produced, in the medium C. In another method of production, the step of stirring comprises pivoting a stirring blade 51 in the stirring mechanism 5 wherein a plurality of stationary members 53 is placed therearound in a bottom region 4e of the container 4 such that the step of stirring produces turbulence in the medium C. The present invention also relates to apparatuses for production for carrying out the method of production. The present invention also relates to a method for determining operating conditions of an apparatus for producing platelets.

公开(公告)号：EP3312270B1

公开(公告)日：2020-09-30

申请号：EP16811730.7

申请日：2016-06-16

申请人： Kyoto University ,  Megakaryon Corporation

发明人： ETO, Koji ,  NAKAMURA, Sou ,  ITO, Yukitaka ,  SHIGEMORI, Tomohiro ,  DOHDA, Takeaki

IPC分类号： C12N5/078 ,  A61K35/19 ,  A61P7/04 ,  C12N15/09 ,  C12N15/113

公开(公告)号：EP3594325A1

公开(公告)日：2020-01-15

申请号：EP18763555.2

申请日：2018-03-05

申请人： Kyoto University ,  Megakaryon Corporation

发明人： ETO, Koji ,  NAKAMURA, Sou ,  ITO, Yukitaka

IPC分类号： C12N5/078 ,  C07K14/52 ,  C12N5/10

摘要： Healthy functional platelets are mass produced. A method for producing platelets, comprising: (1) a culture step of culturing megakaryocytes in a platelet producing medium in the presence of mechanical stress and platelet production promoting factors including MIF, NRDc, IGFBP2, TSP-1, PAI-1, and CCL5, and (2) a harvest step of harvesting the platelets obtained by the culture step; wherein the culture step comprises: (a) a step of promoting a release of the platelet production promoting factors from megakaryocytes by mechanical stress; and/or (b) a step of externally adding platelet production promoting factors including MIF, NRDc, and IGFBP2.

公开(公告)号：EP3453759A1

公开(公告)日：2019-03-13

申请号：EP17744459.3

申请日：2017-01-30

申请人： Kyoto University ,  Megakaryon Corporation

发明人： ETO, Koji ,  SEO, Hideya ,  OTA, Akira ,  ITO, Yukitaka ,  HAZAMA, Yasuko

IPC分类号： C12N15/09 ,  A61K35/19 ,  C12N5/10

摘要： The present invention provides: a platelet production promoter that contains one or more substances selected from the group consisting of Wnt inhibitors and FMS-like tyrosine kinase (FLT) inhibitors; and a platelet production method that uses this platelet production promoter.

公开(公告)号：EP3434761A1

公开(公告)日：2019-01-30

申请号：EP17770297.4

申请日：2017-03-22

申请人： Kyoto University ,  Megakaryon Corporation

发明人： ETO, Koji ,  ENDO, Hiroshi ,  ITO, Yukitaka ,  FUKUNAGA, Junichi

IPC分类号： C12N5/0735 ,  A61K35/19 ,  A61P7/08 ,  C12N5/078 ,  C12N5/10 ,  C12N15/09

摘要： Provided is a method for inducing mesoderm, comprising a step of bringing pluripotent stem cells into contact with bone morphogenetic protein 4 (BMP4) or CHIR for at least 3 days.

公开(公告)号：EP3409774A1

公开(公告)日：2018-12-05

申请号：EP17744457.7

申请日：2017-01-30

申请人： Kyoto University ,  Megakaryon Corporation

发明人： ETO, Koji ,  SEO, Hideya ,  OTA, Akira ,  ITO, Yukitaka ,  HAZAMA, Yasuko

IPC分类号： C12N15/09 ,  C12N5/078 ,  C12Q1/02 ,  C12Q1/68

CPC分类号： C12N15/09 ,  C12Q1/02 ,  C12Q1/68

摘要： The present invention provides a method for screening for platelet production promoters, the method including a step for selecting a candidate substance that significantly increases expression of TUBB1 as a platelet production promoter.