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11. 发明公开

EP4234682A1 PRESERVATION METHOD OF HUMAN CORNEAL ENDOTHELIAL CELLS AND/OR HUMAN CORNEAL ENDOTHELIAL PROGENITOR CELLS 审中-实审
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
申请人： Kyoto Prefectural Public University Corporation
发明人： KINOSHITA, Shigeru , TODA, Munetoyo , SOTOZONO, Chie , UENO, Morio
IPC分类号： C12N5/071 , C12N1/04
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.

12. 发明公开

EP3213762A1 NOVEL TREATMENT OF CORNEA USING LAMININ 有权转让
标题翻译：新型层粘连蛋白治疗角膜病
公开(公告)号：EP3213762A1
公开(公告)日：2017-09-06
申请号：EP15854129.2
申请日：2015-10-30
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
发明人： KOIZUMI, Noriko , OKUMURA, Naoki , KINOSHITA, Shigeru
IPC分类号： A61K38/00 , A61K31/4409 , A61K35/30 , A61K45/00 , A61P27/02
CPC分类号： A61K45/05 , A61K31/137 , A61K31/4409 , A61K35/30 , A61K35/44 , A61K38/39 , A61K45/00
摘要： The present invention provides a technique for treating the cornea. More specifically, the present invention is an agent for the treatment or prevention of a state of corneal endothelial disease, the agent including at least one factor selected from the group consisting of laminin and fragments thereof, wherein the problem is solved by also providing a technique characterized in that this agent is administered together with corneal endothelial cells. Specifically, the present invention can include laminin 511 (α5β1γ1), laminin 521 (α5β2γ1), or a fragment of these.
摘要翻译：本发明提供了一种治疗角膜的技术。更具体地说，本发明是用于治疗或预防角膜内皮疾病状态的药剂，该药剂包括至少一种选自层粘连蛋白及其片段的因子，其中该问题也通过提供一种技术来解决其特征在于该药剂与角膜内皮细胞一起施用。具体而言，本发明可以包括层粘连蛋白511（α5β1γ1），层粘连蛋白521（α5β2γ1）或它们的片段。

13. 发明公开

EP3064222A1 THERAPEUTIC DRUG FOR DISEASES RELATED TO ENDOPLASMIC RETICULUM CELL DEATH IN CORNEAL ENDOTHELIUM 有权转让
标题翻译：治疗方法ERKRANKUNGEN IM ZUSAMMENHANG MIT ENDOPLASMATISCHEM RETIKULUMSZELLTOD IM HORNHAUTENDOTHEL
公开(公告)号：EP3064222A1
公开(公告)日：2016-09-07
申请号：EP14857909.7
申请日：2014-10-30
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
发明人： KOIZUMI, Noriko , OKUMURA, Naoki , KINOSHITA, Shigeru
IPC分类号： A61K45/00 , A61K31/437 , A61K31/4439 , A61K31/444 , A61K31/4709 , A61K31/519 , A61K31/713 , A61K48/00 , A61P27/02 , A61P43/00
摘要： The present invention provides a treatment drug or prophylactic drug for diseases, disorders, or conditions related to endoplasmic reticulum (ER) stress. Specifically, the present invention provides a treatment drug or prophylactic drug for diseases, disorders, or conditions related to endoplasmic reticulum (ER) stress in the corneal epithelium, the drug containing a TGFβ-signal inhibitor. As a preferred TGFβ-signal inhibitor, the drug contains 4-[4-(1,3-benzodioxole-5-yl)-5-(2-pyridinyl)-1H-imidazole-2-yl]benzamide.
摘要翻译：本发明提供了与内质网（ER）应激相关的疾病，病症或病症的治疗药物或预防药物。具体地说，本发明提供了在角膜上皮细胞内涉及内质网（ER）应激的疾病，病症或病症的治疗药物或预防药物，该药物含有TGFβ信号抑制剂。作为优选的TGFβ信号抑制剂，该药物含有4- [4-（1,3-苯并间二氧杂环戊烯-5-基）-5-（2-吡啶基）-1H-咪唑-2-基]苯甲酰胺。

14. 发明公开

EP3804760A1 THERAPEUTIC DRUG FOR DISEASES RELATED TO ENDOPLASMIC RETICULUM CELL DEATH IN CORNEAL ENDOTHELIUM 审中-公开
公开(公告)号：EP3804760A1
公开(公告)日：2021-04-14
申请号：EP20195546.5
申请日：2014-10-30
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
发明人： KOIZUMI, Noriko , OKUMURA, Naoki , KINOSHITA, Shigeru
IPC分类号： A61K45/00 , A61K31/437 , A61K31/4439 , A61K31/444 , A61K31/4709 , A61K31/519 , A61K31/713 , A61K48/00 , A61P27/02 , A61P43/00 , A61K38/00 , A61K39/395 , A61K9/00 , C07K16/22 , A61P3/00 , A61P29/00
摘要： The present invention provides a treatment drug or prophylactic drug for diseases, disorders, or conditions related to endoplasmic reticulum (ER) stress. Specifically, the present invention provides a treatment drug or prophylactic drug for diseases, disorders, or conditions related to endoplasmic reticulum (ER) stress in the corneal epithelium, the drug containing a TGFβ-signal inhibitor. As a preferred TGFβ-signal inhibitor, the drug contains 4-[4-(1,3-benzodioxole-5-yl)-5-(2-pyridinyl)-1H-imidazole-2-yl]benzamide.

15. 发明公开

EP3733177A1 COMPOSITION FOR CORNEAL PROTECTION 有权转让
公开(公告)号：EP3733177A1
公开(公告)日：2020-11-04
申请号：EP18893697.5
申请日：2018-12-26
申请人： Kyoto University , Kyoto Prefectural Public University Corporation , The Doshisha
发明人： IKEDA, Hanako , KAKIZUKA, Akira , KINOSHITA, Shigeru , NAKAMURA, Takahiro , NAGATA, Maho , KOIZUMI, Noriko , OKUMURA, Naoki
IPC分类号： A61K31/4418 , A61P27/02 , A61P27/04 , A61P43/00
摘要： The inventors have found that VCP inhibitors protect corneal endothelial cells and corneal epithelial cells. Accordingly, the disclosure provides a composition for protecting a cornea comprising a compound of formula (I) or an ester, oxide, pharmaceutically acceptable salt or solvate thereof. In another aspect the disclosure provides a composition for treating and/or preventing a corneal disease comprising a compound of formula (I). In a further aspect the disclosure provides a composition for ocular irrigation comprising a compound of formula (I). In a still further aspect the disclosure provides a composition for preserving a corneal graft comprising a compound of formula (I).

16. 发明授权

EP2876160B1 DIFFERENTIATION MARKER FOR AND DIFFERENTIATION CONTROL FOR OCULAR CELLS 有权转让
公开(公告)号：EP2876160B1
公开(公告)日：2020-05-13
申请号：EP13812481.3
申请日：2013-07-03
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
发明人： NAKAMURA, Takahiro , KOIZUMI, Noriko , OKUMURA, Naoki , KINOSHITA, Shigeru , TOMINAGA, Kana , KAWASAKI, Satoshi
IPC分类号： A61K35/30

17. 发明公开

EP3074508A1 APPLICATION OF LAMININ TO CORNEAL ENDOTHELIAL CELL CULTURE 有权转让
标题翻译： VERWENDUNG VON LAMININ ZUR HORNHAUTENDOTHEL-ZELLKULTUR
公开(公告)号：EP3074508A1
公开(公告)日：2016-10-05
申请号：EP14831100.4
申请日：2014-11-26
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
发明人： KOIZUMI, Noriko , OKUMURA, Naoki , KINOSHITA, Shigeru , KRUSE, Friedrich E. , SCHLOETZER-SCHREHARDT, Ursula
IPC分类号： C12N5/079
CPC分类号： C12N5/0621 , A61K35/30 , C12N2533/52
摘要： The present invention provides a method of culturing corneal endothelial cells. More specifically, the present invention provides a composition for culturing or growing corneal endothelial cells, comprising at least one agent consisting of laminins and fragments thereof which express in corneal endothelial cells. Specifically, the present invention can comprise laminin 511 (alpha5 beta1 gamma1) and laminin 512 (alpha5 beta2 gamma 1). The present invention further provides a culture container for corneal endothelial cells, which is coated with the composition of the present invention. Furthermore, the present invention provides a method for culturing corneal endothelial cells comprising the step of using the composition or the container of the present invention to culture the corneal endothelial cells.
摘要翻译：本发明提供了培养角膜内皮细胞的方法。更具体地，本发明提供了用于培养或生长角膜内皮细胞的组合物，其包含至少一种由角质内皮细胞中表达的层粘连蛋白及其片段组成的试剂。具体地，本发明可以包含层粘连蛋白511（α5β1γ1）和层粘连蛋白512（α5β2γ1）。本发明还提供了用本发明的组合物涂覆的角膜内皮细胞的培养容器。此外，本发明提供了一种培养角膜内皮细胞的方法，包括使用本发明的组合物或容器培养角膜内皮细胞的步骤。

18. 发明公开

EP2876160A1 DIFFERENTIATION MARKER FOR AND DIFFERENTIATION CONTROL FOR OCULAR CELLS 有权转让
标题翻译：分化标记和微分控制眼部细胞
公开(公告)号：EP2876160A1
公开(公告)日：2015-05-27
申请号：EP13812481.3
申请日：2013-07-03
申请人： Kyoto Prefectural Public University Corporation , The Doshisha , Senju Pharmaceutical Co., Ltd.
发明人： NAKAMURA, Takahiro , KOIZUMI, Noriko , OKUMURA, Naoki , KINOSHITA, Shigeru , TOMINAGA, Kana , KAWASAKI, Satoshi
IPC分类号： C12N15/09 , A61K31/7088 , A61K35/12 , A61K35/44 , A61K38/00 , A61K48/00 , A61P27/02 , C07K14/705 , C12N5/071 , C12Q1/02 , C12Q1/68 , G01N33/53
CPC分类号： A61K38/1709 , A61K35/30 , A61K38/00 , A61K48/00 , C07K14/705 , C12N5/0621 , C12N2501/40 , C12N2501/415 , C12Q1/6881 , C12Q2600/158 , G01N33/56966 , G01N2333/726 , G01N2800/16
摘要： The present invention relates to a differentiation marker and a differentiation controlling technique for an eye cell. More particularly, the present invention has attained an object of providing a differentiation marker for an eye cell among the aforementioned problems, by providing a marker for identifying a cell having a high proliferation ability among corneal endothelial cells and/or the differentiation ability of a corneal endothelial cell, the marker comprising GPR49/LGR5, as well as a detection agent or detection method for identifying a cell having a high proliferation ability among corneal endothelial cells and/or the differentiation ability of a corneal endothelial cell, comprising a substance binding to GPR49/LGR5. In addition, the present invention has attained an object of providing a differentiation controlling technique for an eye cell, by providing an agent for suppressing differentiation and/or promoting proliferation of an eye cell, comprising R-spondins.

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