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公开(公告)号：EP3029140A1
公开(公告)日：2016-06-08
申请号：EP14831264.8
申请日：2014-07-28
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
IPC分类号： C12N15/09 , A61K35/12 , A61L27/00 , A61P27/02 , C12N5/071 , C12N5/10 , C12Q1/02 , C12Q1/68 , G01N33/53
CPC分类号： G01N33/56966 , A61K35/30 , C12N5/0621 , G01N2333/705 , G01N2333/70596
摘要： The purpose of the present invention is to provide a method of purification and preparation of cultured corneal endothelial cells, and in particular, to provide cell surface markers for use in corneal endothelial cells not including transformed cells. Provided are cell markers for distinguishing normal cells and transformed cells, in particular normal and transformed corneal endothelium cells. These cell markers relate to specific cell surface markers, for example, to a normal corneal endothelial surface marker such as CD166, and a transformed cell surface marker such as CD73. By using the transformed cell surface marker such as CD73 to remove transformed cells by sorting, it becomes possible to improve purity of a normal cultured corneal endothelium. By using normal corneal endothelial surface marker such as CD166, or by combined use with the transformed cell surface marker, it becomes possible to provide a means for verifying the purity of a prepared corneal endothelium.
摘要翻译： 本发明的目的是提供一种纯化和制备角膜内皮细胞的方法，特别是提供用于不包括转化细胞的角膜内皮细胞的细胞表面标志物。 提供用于区分正常细胞和转化细胞，特别是正常和转化的角膜内皮细胞的细胞标志物。 这些细胞标志物涉及特定细胞表面标志物，例如与正常角膜内皮表面标志物如CD166和转化的细胞表面标志物如CD73相关。 通过使用转化的细胞表面标志物如CD73通过分选来除去转化的细胞，可以提高正常培养的角膜内皮的纯度。 通过使用正常的角膜内皮表面标志物如CD166，或通过与转化的细胞表面标记物的组合使用，可以提供一种验证制备的角膜内皮的纯度的方法。
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公开(公告)号：EP3416658A1
公开(公告)日：2018-12-26
申请号：EP17709487.7
申请日：2017-02-14
发明人： KINOSHITA, Shigeru , HAMURO, Junji , SOTOZONO, Chie , UENO, Morio
CPC分类号： A61K35/00 , C12N5/0621
摘要： The present invention complete a technique of treating a corneal disorder or disease by infusion into an anterior chamber of human eyes. Specifically, the present invention based on the findings discovered that cultured human corneal endothelial cells are comprised of a plurality of subpopulations, most of them are not suitable for infusion into patients. The above-described subject was overcome by providing, as a medicament, functionally high grade quality of cells having the function of mature differentiated human corneal endothelial cells which is a specific subpopulation and characterized by their biochemical and functional phenotypes. The present invention provides such a functional mature differentiated corneal endothelial cells, medicament comprising the same, and manufacturing method, quality control and techniques related thereto.
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3.发明公开
公开(公告)号：EP4234682A1
公开(公告)日：2023-08-30
申请号：EP21882821.8
申请日：2021-10-19
摘要： Human corneal endothelial cells and/or human corneal endothelial precursor cells are preserved with a high survival rate of these cells being maintained, and the occurrence rate of contaminated cells in post-preservation culturing is suppressed. A storage method of human corneal endothelial cells and/or human corneal endothelial precursor cells is characterized in that human corneal endothelial cells and/or human corneal endothelial precursor cells that have been cultured using a culture medium that contains a ROCK inhibitor, and in which the content of epidermal growth factor (EGF) is less than a concentration that will cause a transformation are harvested at a timing when any one of or a plurality of the conditions (a) ~ (d) given below have been met, and are placed in a suspension state and then preserved.
(a) During a period from immediately after a morphology of the human corneal endothelial cells and/or human corneal endothelial precursor cells has shifted from a spindle-shaped to a polygonal shape or an elliptical shape whose major axis-minor axis ratio is close to 1, until immediately before boundaries between the cells become indistinct.
(b) During a period from when an expression level of CD44 becomes equal to or less than half a maximum value observed after the most recent subculturing until this expression level reaches a plateau.
(c) When the cell density of the human corneal endothelial cells and/or human corneal endothelial precursor cells is not less than 900 cells/mm 2 and not more than 2500 cells/mm 2 .
(d) When the number of culturing days since the most recent subculturing is not less than 4 days and not more than 14 days.-
公开(公告)号：EP4218773A1
公开(公告)日：2023-08-02
申请号：EP23160003.2
申请日：2017-02-14
发明人： KINOSHITA, Shigeru , HAMURO, Junji , SOTOZONO, Chie , UENO, Morio
摘要： The present invention complete a technique of treating a corneal disorder or disease by infusion into an anterior chamber of human eyes. Specifically, the present invention based on the findings discovered that cultured human corneal endothelial cells are comprised of a plurality of subpopulations, most of them are not suitable for infusion into patients. The above-described subject was overcome by providing, as a medicament, functionally high grade quality of cells having the function of mature differentiated human corneal endothelial cells which is a specific subpopulation and characterized by their biochemical and functional phenotypes. The present invention provides such a functional mature differentiated corneal endothelial cells, medicament comprising the same, and manufacturing method, quality control and techniques related thereto.
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公开(公告)号：EP4116411A1
公开(公告)日：2023-01-11
申请号：EP21761596.2
申请日：2021-02-26
摘要： To provide a cell trait assay technique for identifying cultured human corneal endothelium cells of which early clinical effect manifestation and a long-term stable clinical effect are confirmed, in clinical trials. Provided is a method of manufacturing a functional human corneal endothelial cell capable of eliciting a human corneal function when infused into an anterior chamber of a human eye, the method comprising the step of proliferating and/or differentiating or maturing a corneal endothelial progenitor cell under a culture condition capable of minimizing culture stress, such as proliferation stress. Further, provided is a functional human corneal endothelial cell in which expression of a functional protein leading to a corneal endothelial (cell) functional property leading to improvement on corneal opacity and hydrous edema, resulting in continuous and long-term retention of corneal endothelial tissue cell density and improvement on visual acuity is recognized or in which a protein that inhibits the corneal endothelial (cell) functional property is not elicited or is reduced.
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公开(公告)号：EP2193806A1
公开(公告)日：2010-06-09
申请号：EP08828145.6
申请日：2008-08-28
发明人： KINOSHITA, Shigeru , KOIZUMI, Noriko , UENO, Morio
IPC分类号： A61K45/00 , A61K31/4409 , A61K31/496 , A61P27/02 , A61P43/00
CPC分类号： A61K31/551 , A61K9/0048 , A61K31/4409 , A61K31/496 , C07D213/81 , C07D401/12 , C12N5/0621 , C12N2501/70
摘要： Provided is a means capable of efficiently growing corneal endothelial cells and a means of stably supplying a corneal endothelial preparation.
An agent for promoting adhesion of a corneal endothelial cell, containing a Rho kinase inhibitor, a culture medium for a corneal endothelial cell, containing a Rho kinase inhibitor, a solution for preservation of cornea, containing a Rho kinase inhibitor, and a method of producing a corneal endothelial preparation, including a step of culturing the corneal endothelial cell using the above culture medium.-
公开(公告)号：EP2193806B1
公开(公告)日：2017-12-06
申请号：EP08828145.6
申请日：2008-08-28
发明人： KINOSHITA, Shigeru , KOIZUMI, Noriko , UENO, Morio
IPC分类号： A61K45/00 , A61K31/4409 , A61K31/496 , A61P27/02 , A61P43/00 , A61K31/551 , A61K9/00 , C07D401/12 , C12N5/079 , C07D213/81
CPC分类号： A61K31/551 , A61K9/0048 , A61K31/4409 , A61K31/496 , C07D213/81 , C07D401/12 , C12N5/0621 , C12N2501/70
摘要： Provided is a means capable of efficiently growing corneal endothelial cells and a means of stably supplying a corneal endothelial preparation. An agent for promoting adhesion of a corneal endothelial cell, containing a Rho kinase inhibitor, a culture medium for a corneal endothelial cell, containing a Rho kinase inhibitor, a solution for preservation of cornea, containing a Rho kinase inhibitor, and a method of producing a corneal endothelial preparation, including a step of culturing the corneal endothelial cell using the above culture medium.
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