公开(公告)号：US20140087459A1

公开(公告)日：2014-03-27

申请号：US14024067

申请日：2013-09-11

申请人： Apceth GmbH & Co. KG

发明人： Elena Meurer ,  Christine GÜNTHER

IPC分类号： C12N5/0775

CPC分类号： C12N5/0665 ,  C12N5/0662 ,  C12N5/0663 ,  C12N5/0664 ,  C12N5/0666 ,  C12N5/0667 ,  C12N5/0668 ,  C12N2500/84 ,  C12N2500/90 ,  C12N2501/91 ,  C12N2502/115

摘要： This invention provides a cell growth medium comprising (a) a human platelet lysate free of solid matter greater than 0.22 μm in diameter; (b) a human fresh frozen plasma (FFP) filtrate free of solid matter greater than 0.22 μm in diameter; (c) heparin; (d) L-glutamine; and (e) a serum-free, low glucose medium suitable for mammalian cell growth, wherein the cell growth medium permits the expansion of human CD34− stem cells and wherein the resulting expanded CD34− stem cells retain the ability to differentiate. This invention also provides related cell growth medium supplements, a sterile human platelet lysate and human fresh frozen plasma (FFP) filtrate, kits, CD34− stem cell-containing compositions, and related production and cell expansion methods.

摘要翻译： 本发明提供一种细胞生长培养基，其包含（a）直径大于0.22μm的不含固体物质的人血小板裂解物; （b）不含直径大于0.22μm的固体物质的人新鲜冷冻血浆（FFP）滤液; （c）肝素; （d）L-谷氨酰胺; 和（e）适合于哺乳动物细胞生长的无血清低葡萄糖培养基，其中所述细胞生长培养基允许人CD34-干细胞的扩增，并且其中所产生的扩增的CD34-干细胞保留分化能力。 本发明还提供相关的细胞生长培养基补充剂，无菌人血小板裂解物和人新鲜冷冻血浆（FFP）滤液，试剂盒，含有CD34-干细胞的组合物以及相关的生产和细胞扩增方法。

公开(公告)号：US20180037868A1

公开(公告)日：2018-02-08

申请号：US15553954

申请日：2016-02-26

申请人： apceth GmbH & Co. KG

发明人： Christine Günther ,  Manfred Stangl ,  Felix Hermann

IPC分类号： C12N5/0775 ,  A61K48/00 ,  A61K38/47 ,  C12N9/24 ,  A61K35/28

CPC分类号： C12N5/0663 ,  A61K35/28 ,  A61K38/00 ,  A61K38/47 ,  A61K48/00 ,  A61K2035/124 ,  C07K14/435 ,  C12N9/2402 ,  C12N2501/73 ,  C12N2510/00 ,  C12Y302/01031

摘要： A genetically modified mesenchymal stem cell (MSC) includes an exogenous nucleic acid that includes a Klotho encoding region operably linked to a promoter or promoter/enhancer combination. The MSCs can be used for the treatment of cancer, organ fibrosis, renal failure, age-related changes of organs or organ systems, arteriosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), Multiple sclerosis (MS), Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, and Schizophrenia, as well as dementia, diabetes mellitus, sepsis and autoimmune diseases and autoimmune-related diseases.

公开(公告)号：US20160008401A1

公开(公告)日：2016-01-14

申请号：US14771714

申请日：2014-02-28

申请人： apceth GmbH & Co. KG

发明人： Günther Eissner ,  Christine Guenther ,  Ralf Huss

IPC分类号： A61K35/28 ,  G01N33/50 ,  A61K45/06 ,  A61K35/51 ,  A61K35/50

CPC分类号： A61K35/28 ,  A61K35/44 ,  A61K35/50 ,  A61K35/51 ,  A61K45/06 ,  A61K2035/122 ,  C12N5/0663 ,  C12N5/0665 ,  C12N5/0668 ,  G01N33/5073 ,  A61K2300/00

摘要： The present invention provides human CD34-negative progenitor cells for the use in protecting the vascular endothelium from immunologically mediated cytotoxic reactions of a subject at risk of, or afflicted with, vascular inflammatory disease. Also provided are a method for producing the human CD34-negative progenitor cells and a method for determining the ability of CD34-negative progenitor cells to protect the vascular endothelium from immunologically mediated cytotoxic reactions.

摘要翻译： 本发明提供用于保护血管内皮的人类CD34阴性祖细胞免受由于血管炎症性疾病危害或患有血管炎症性疾病的受试者的免疫介导的细胞毒性反应。 还提供了用于产生人CD34阴性祖细胞的方法和用于测定CD34阴性祖细胞保护血管内皮免受免疫介导的细胞毒性反应的能力的方法。

公开(公告)号：US20220033779A1

公开(公告)日：2022-02-03

申请号：US17447975

申请日：2021-09-17

申请人： apceth GmbH & Co. KG

发明人： Christine Günther ,  Manfred Stangl ,  Felix Hermann

IPC分类号： C12N5/0775 ,  C12N9/24 ,  A61K48/00 ,  A61K35/28 ,  C07K14/435 ,  A61K38/47

摘要： A genetically modified mesenchymal stem cell including an exogenous nucleic acid including a Klotho encoding region operably linked to a promoter or promoter/enhancer combination, wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell. Also disclosed are methods of treating a patient including administering a therapeutically effective number of the genetically modified mesenchymal stem cells to the patient. The methods of treatment include treating the patient for a neurodegenerative disease; cancer; organ fibrosis; renal disease; age-related changes of organs or organ systems; to slow, reverse and/or inhibit aging; arteriosclerosis; dementia; diabetes mellitus; erectile dysfunction; autoimmune diseases or autoimmune-related diseases; an inflammatory disease of the lung and sepsis.

公开(公告)号：US20170015976A1

公开(公告)日：2017-01-19

申请号：US15253353

申请日：2016-08-31

申请人： APCETH GMBH & CO. KG

发明人： Peter J. NELSON

IPC分类号： C12N5/0775 ,  A61K35/28 ,  C12N15/86

CPC分类号： C12N5/0663 ,  A61K35/28 ,  A61K2035/124 ,  C12N15/86 ,  C12N2510/00 ,  C12N2740/15043 ,  C12N2830/002

摘要： This invention provides a method for treating a subject afflicted with a tumor using genetically modified mesenchymal stem cells, wherein each genetically modified mesenchymal stem cell contains an exogenous nucleic acid comprising (i) a cytotoxic protein-encoding region operably linked to (ii) a promoter or promoter/enhancer combination, whereby the cytotoxic protein is selectively expressed when the genetically modified mesenchymal stem cells come into proximity with the tumor's stromal tissue. This invention further provides genetically modified mesenchymal stem cells for use in this method.

摘要翻译： 本发明提供了使用遗传修饰的间充质干细胞治疗患有肿瘤的受试者的方法，其中每个经遗传修饰的间充质干细胞含有外源核酸，其包含（i）与（ii）启动子有效连接的细胞毒性蛋白质编码区 或启动子/增强子组合，由此当遗传修饰的间充质干细胞与肿瘤的基质组织接近时，细胞毒性蛋白质被选择性地表达。 本发明进一步提供用于该方法的遗传修饰的间充质干细胞。

公开(公告)号：US20140322786A1

公开(公告)日：2014-10-30

申请号：US14358430

申请日：2012-11-13

申请人： APCETH GMBH & CO. KG

发明人： Frank Deubel ,  Bernhard Rieger ,  Stephan Salzinger ,  Ning Zhang

IPC分类号： C08F265/06 ,  C08F265/04 ,  B05D3/00

CPC分类号： C08F265/04 ,  B05D1/185 ,  B05D3/007 ,  B05D2203/30 ,  B05D2350/60 ,  B05D2502/00 ,  B05D2502/005 ,  B05D2507/00 ,  B82Y30/00 ,  B82Y40/00 ,  C08F265/06 ,  C08F293/005 ,  C09K21/14 ,  C12M23/20 ,  C12M25/02

摘要： Provided are polymer modified substrates which comprise a) a substrate, b) a binding layer covalently attached to the surface of the substrate and covering at least a part of this surface; and c) a polymer brush formed by a plurality of polymer chains, each of which is covalently attached at one of its terminals to the binding layer. Moreover, methods are provided, for the preparation of the polymer modified substrates by polymerizing vinyl group containing monomers, such as vinylphosphonates, on a binding layer provided on a substrate.

摘要翻译： 提供聚合物改性的基材，其包含a）基材，b）共价连接到基材表面并覆盖该表面的至少一部分的粘合层; 和c）由多个聚合物链形成的聚合物刷，每个聚合物链在其一个端子上共价连接到结合层。 此外，提供了通过在设置在基底上的结合层上聚合含乙烯基膦酸单体如乙烯基膦酸酯来制备聚合物改性底物的方法。

公开(公告)号：US20190030152A1

公开(公告)日：2019-01-31

申请号：US16081010

申请日：2017-03-31

申请人： apceth GmbH & Co. KG

发明人： Felix Hermann ,  Christine Günther ,  Ulf Geumann

IPC分类号： A61K39/00 ,  A61K35/28 ,  A61P35/00

摘要： A tumor or a malignant disease can be treated by the combined administration of mesenchymal stem cells (MSCs) with an anti-tumor immunotherapy. The MSCs need not be genetically modified, and do not include exogenous nucleic acids that encode immune response-stimulating cytokines. The anti-tumor immunotherapy can be a cellular immunotherapy, such as administration of chimeric antigen receptor (CAR) T cells, in which the T cell receptor binds specifically to a tumor-associated antigen.

公开(公告)号：US20180000969A1

公开(公告)日：2018-01-04

申请号：US15542031

申请日：2016-01-08

申请人： APCETH GMBH & CO. KG

发明人： Christine GÜNTHER ,  Sabine GEIGER-SCHREDELSEKER ,  Felix HERMANN ,  Ralf HUSS ,  Daria Larissa FORSTER

IPC分类号： A61K48/00 ,  A61K38/57 ,  A61K35/28 ,  C12N15/86 ,  A61K9/00

CPC分类号： A61K48/0058 ,  A61K9/0019 ,  A61K9/0073 ,  A61K35/28 ,  A61K38/57 ,  A61K2035/124 ,  C12N5/0663 ,  C12N15/86 ,  C12N2501/734 ,  C12N2510/00 ,  C12N2740/10043 ,  C12N2830/002 ,  C12N2830/008

摘要： Genetically modified mesenchymal stem cells can be used as a medicament in the treatment of medical conditions associated with inflammation and/or an unwanted immune response in subjects without an alpha1-antitrypsin (AAT) deficiency. The stem cells include an exogenous nucleic acid, which includes (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.

公开(公告)号：US20170239297A1

公开(公告)日：2017-08-24

申请号：US15504554

申请日：2015-08-18

申请人： apceth GmbH & Co. KG

发明人： Christine Günther ,  Stefanos Theoharis ,  Felix Hermann ,  Ralf Huss

IPC分类号： A61K35/28 ,  C07K16/30 ,  C07K14/705 ,  A61K35/17 ,  C07K14/54 ,  C07K14/555

CPC分类号： A61K35/28 ,  A61K35/17 ,  A61K38/00 ,  A61K2035/124 ,  C07K14/52 ,  C07K14/54 ,  C07K14/555 ,  C07K14/70521 ,  C07K16/30 ,  C12N5/0663 ,  C12N2510/02

摘要： A genetically modified mesenchymal stem cell (MSC) and medical use thereof in the treatment of tumors, the MSC including one or more exogenous nucleic acid molecule(s), wherein the exogenous nucleic acid molecule(s) include a region encoding one or more immune response-stimulating or immune response-modulating cytokine(s) operably linked to a promoter or promoter/enhancer combination. The invention encompasses the use of the cells in modulating the tumor microenvironment in order to attract immune effector cells and facilitate their activation and/or adoption of a memory phenotype. One aspect of the invention relates to the use of the cells in anti-tumor treatment including combined administration of the mesenchymal stem cells with anti-tumor immunotherapies, such as checkpoint inhibitors, immune cells, for example T cells, such as T cells with artificial T cell receptors, for example a chimeric antigen receptor (CAR-Ts) or exogenous T-Cell Receptor (TCR) transduced cells, NK cells or macrophages/monocytes, or a cancer vaccine.