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1. 发明申请

WO2008150368A1 CD34 STEM CELL-RELATED METHODS AND COMPOSITIONS 审中-公开
标题翻译： CD34干细胞相关方法和组合物
公开(公告)号：WO2008150368A1
公开(公告)日：2008-12-11
申请号：PCT/US2008/006434
申请日：2008-05-20
申请人： APCETH GMBH & CO. KG , HUSS, Ralf , NELSON, Peter , RAGGI, Matthias , STANGL, Manfred
发明人： HUSS, Ralf , NELSON, Peter , RAGGI, Matthias , STANGL, Manfred
IPC分类号： C12N5/08 , A61K45/00
CPC分类号： A61K35/545 , A61K35/12 , A61K35/28 , A61K38/1709 , A61K38/18 , A61K38/1866 , A61K48/00 , A61K2035/122 , A61K2035/124 , C07K14/49 , C12N5/0663
摘要： This invention provides novel stem cell-based methods for treating a number of conditions. These methods employ CD34 - stem cells, and have a tremendous advantage in that they do not require myeloablation in the subject being treated. The CD34 - stem cells used in the instant methods can be genetically modified or not, depending on the disorder treated.
摘要翻译：本发明提供了用于治疗许多病症的新型基于干细胞的方法。这些方法使用CD34-干细胞，并且具有巨大的优点，因为它们不需要在被治疗的受试者中进行myeloablation。本方法中使用的CD34-干细胞可以进行遗传修饰，取决于所治疗的病症。

2. 发明申请

WO2007039109A1 TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP) LINKED TO GLYCOSYLPHOSPHATIDYLINOSITOL (GPI) -ANCHORS FOR TREATMENT OF CANCER AND SKIN LESIONS 审中-公开
标题翻译：金属蛋白酶组织组织（TIMP）与谷氨酸磷脂酰胆碱（GPI）联用，用于治疗癌症和皮肤损伤
公开(公告)号：WO2007039109A1
公开(公告)日：2007-04-12
申请号：PCT/EP2006/009145
申请日：2006-09-20
申请人： HUSS, Ralf , NELSON, Peter, Jon
发明人： HUSS, Ralf , NELSON, Peter, Jon
IPC分类号： C07K19/00 , C07K14/81 , C12N15/62 , A61K38/57
CPC分类号： A61K38/57 , A61K38/1709 , A61K47/544 , A61K47/549 , A61K47/62 , C07K14/8146
摘要： The present invention relates to fusion constructs of glycosylphosphatidylinositol (GPI)- anchored tissue inhibitors of metalloproteinases (TIMPs) and their use for the treatment of cancer and in regenerative medicine. By this approach, the GPI-anchored TIMP proteins are incorporated into the surface membrane of tumor cells and render tumor cells sensitive to FAS-induced apoptosis. Furthermore, the fusion constructs of the present invention are effective agents useful in wound healing applications. In one embodiment, the TIMP is linked to mucin followed by GPI in order to enhance surface presentation. The use of GPI to link TIMP renders the resulting fusion protein particularly useful as an anti-cancer agent for the treatment of cancer, and, in particular, any residual cancer following an incomplete surgical resection of primary tumors in an individual.
摘要翻译：本发明涉及糖基磷脂酰肌醇（GPI） - 金属蛋白酶（TIMPs）的锚定组织抑制剂及其在再生医学中的治疗用途的融合构建体。通过这种方法，GPI锚定的TIMP蛋白被并入肿瘤细胞的表面膜，并使肿瘤细胞对FAS诱导的细胞凋亡敏感。此外，本发明的融合构建体是可用于伤口愈合应用的有效试剂。在一个实施方案中，TIMP与粘蛋白连接，然后与GPI连接，以增强表面表达。使用GPI连接TIMP使所得到的融合蛋白特别可用作治疗癌症的抗癌剂，特别是在个体不完全手术切除原发性肿瘤后的任何残留癌症。

3. 发明申请

WO2007062844A1 CHEMOKINE-MUCIN FUSIONS LINKED TO GLYCOSYLPHOSPHATIDYLINOSITOL (GPI)-ANCHORS IN TISSUE REGENERATION AND AS TUMOUR IMMUNE ADJUVANTS 审中-公开
标题翻译：连接到糖皮质激素（GPI） - 组织再生和肿瘤免疫调节剂中的CHEMOKINE-MUCIN FUSION
公开(公告)号：WO2007062844A1
公开(公告)日：2007-06-07
申请号：PCT/EP2006/011508
申请日：2006-11-30
申请人： LMU MÜNCHEN , DKFZ DEUTSCHES KREBSFORSCHUNGSZENTRUM , HUSS, Ralf , NELSON, Peter , GRÖNE, Hermann-Josef
发明人： HUSS, Ralf , NELSON, Peter , GRÖNE, Hermann-Josef
IPC分类号： C07K14/52 , C07K14/47 , A61K38/19 , C12N15/62
CPC分类号： C07K14/524 , A61K38/00 , C07K14/4727 , C07K2319/00
摘要： The present invention relates to chemokine-mucin fusions linked to glycosylphosphatidylinositol (GPI)-anchors and their use as anti-cancer adjuvants and as agents in tissue regeneration and suppression of vascular damage. GPI-linked chemokines are incorporated in the surface membrane of tumour cells and effect a recruitment of cytotoxic immune cells to the tumour site following injection in vivo. Leukocytes, cytotoxic T-cells and NK cells target the chemokine-GPI-anchored tumour cells and modulate cell-mediated lysis of the tumour cells. The efficiency of GPI-anchoring and modulation of immune cells can be further enhanced by linking the chemokine to a mucin domain followed by the GPI-anchor. The GPI-anchored chemokines, with or without mucin domain, are remarkably useful for the inhibition of tumour growth, tissue regeneration, and suppression of acute vascular damage to allografts.
摘要翻译：本发明涉及与糖基磷脂酰肌醇（GPI） - 锚定相关的趋化因子 - 粘蛋白融合物，以及它们作为抗癌辅助剂的用途，以及作为组织再生和抑制血管损伤的药剂。将GPI连接的趋化因子并入肿瘤细胞的表面膜中，并且在体内注射后可以诱导细胞毒性免疫细胞到肿瘤部位。白细胞，细胞毒性T细胞和NK细胞靶向趋化因子-GPI锚定的肿瘤细胞并调节细胞介导的肿瘤细胞裂解。 GPI锚定和调节免疫细胞的效率可以通过将趋化因子连接到粘蛋白结构域，然后连接GPI锚点来进一步增强。具有或不具有粘蛋白结构域的GPI锚定趋化因子对于抑制肿瘤生长，组织再生和抑制同种异体移植物的急性血管损伤是非常有用的。

4. 发明申请

WO2016146819A1 HYPOXIA-INDUCED EXPRESSION OF THERAPEUTIC PROTEINS IN MESENCHYMAL STEM CELLS 审中-公开
标题翻译：治疗性蛋白质在卵巢干细胞中的高磷诱导表达
公开(公告)号：WO2016146819A1
公开(公告)日：2016-09-22
申请号：PCT/EP2016/055979
申请日：2016-03-18
申请人： APCETH GMBH & CO. KG
发明人： NELSON, Peter Jon , HUSS, Ralf , SPITZWEG, Christine
IPC分类号： C12N5/0775 , C12N5/10 , A61K35/28
CPC分类号： C12N5/0663 , A61K35/28 , A61K38/18 , A61K38/212 , A61K38/45 , A61K38/55 , A61K45/06 , A61K2035/124 , C07K14/00 , C07K14/4702 , C07K16/00 , C07K2317/14 , C12N2510/00
摘要： The invention relates to genetically modified mesenchymal stem cells (MSCs) comprising one or more exogenous nucleic acid molecules, wherein said exogenous nucleic acid molecules comprise a therapeutic protein-encoding region operably linked to a hypoxia-induced promoter. The invention further relates to their use in the treatment of medical conditions associated with hypoxia or hypoxic tissue, such as tumour diseases, lung diseases, gastrointestinal diseases, ischemic diseases and infectious diseases.
摘要翻译：本发明涉及包含一种或多种外源核酸分子的遗传修饰的间充质干细胞（MSC），其中所述外源性核酸分子包含与低氧诱导的启动子可操作地连接的治疗性蛋白质编码区。本发明还涉及其用于治疗与缺氧或缺氧组织相关的医学病症，例如肿瘤疾病，肺部疾病，胃肠道疾病，缺血性疾病和感染性疾病。

5. 发明申请

WO2014131877A1 PROTECTION OF THE VASCULAR ENDOTHELIUM FROM IMMUNOLOGICALLY MEDIATED CYTOTOXIC REACTIONS WITH HUMAN CD34-NEGATIVE PROGENITOR CELLS 审中-公开
标题翻译：用人CD34阴性原核细胞从免疫介导的细胞毒性反应中保护血管内皮细胞
公开(公告)号：WO2014131877A1
公开(公告)日：2014-09-04
申请号：PCT/EP2014/053923
申请日：2014-02-28
申请人： APCETH GMBH & CO. KG
发明人： EISSNER, Günther , GUENTHER, Christine , HUSS, Ralf
IPC分类号： A61K45/00 , A61K35/00 , A61K38/17 , A61K35/28 , C12N5/071 , G01N33/00 , C12N5/0775
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确定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。

6. 发明申请

WO2016110565A1 GENETICALLY MODIFIED MESENCHYMAL STEM CELLS EXPRESSING ALPHA-1 ANTITRYPSIN (AAT) 审中-公开
标题翻译：表达ALPHA-1抗体（AAT）的遗传修饰的中胚层干细胞
公开(公告)号：WO2016110565A1
公开(公告)日：2016-07-14
申请号：PCT/EP2016/050271
申请日：2016-01-08
申请人： APCETH GMBH & CO. KG
发明人： GÜNTHER, Christine , GEIGER-SCHREDELSEKER, Sabine , HERMANN, Felix , HUSS, Ralf , FORSTER, Daria Larissa
IPC分类号： C12N5/0775 , A61K35/12
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： The invention relates to genetically modified mesenchymal stem cell for use 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, wherein said stem cells comprise an exogenous nucleic acid comprising (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.
摘要翻译：本发明涉及用作治疗与没有α1-抗胰蛋白酶（AAT）缺陷的受试者相关的炎症和/或不需要的免疫应答的医学病症的药物的遗传修饰的间充质干细胞，其中所述干细胞包含外源性核酸其包含（i）与（ii）启动子或启动子/增强子组合可操作地连接的α-1抗胰蛋白酶（AAT）编码区。

7. 发明申请

WO2016026854A2 GENETICALLY MODIFIED MESENCHYMAL STEM CELLS EXPRESSING AN IMMUNE RESPONSE-STIMULATING CYTOKINE TO ATTRACT AND/OR ACTIVATE IMMUNE CELLS 审中-公开
标题翻译：表达免疫应答 - 刺激细胞因子以吸引和/或激活免疫细胞的基因修饰的间质干细胞
公开(公告)号：WO2016026854A2
公开(公告)日：2016-02-25
申请号：PCT/EP2015/068942
申请日：2015-08-18
申请人： APCETH GMBH & CO. KG
发明人： GÜNTHER, Christine , THEOHARIS, Stefanos , HERMANN, Felix , HUSS, Ralf
IPC分类号： A61K35/28
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： The invention relates to a genetically modified mesenchymal stem cell (MSC) and medical use thereof in the treatment of tumours, said MSC comprising one or more exogenous nucleic acid molecule(s), wherein said exogenous nucleic acid molecule(s) comprise 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 said cells in modulating the tumour 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 said cells in anti-tumour treatment comprising the combined administration of said mesenchymal stem cells with anti-tumour 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.
摘要翻译：本发明涉及基因修饰的间充质干细胞（MSC）及其在治疗肿瘤中的医学用途，所述MSC包含一种或多种外源性核酸分子，其中所述外源性核酸分子包含编码与启动子或启动子/增强子组合可操作连接的一种或多种免疫应答刺激或免疫应答调节细胞因子的区域。本发明包括所述细胞在调节肿瘤微环境中的用途，以吸引免疫效应细胞并促进其激活和/或采用记忆表型。本发明的一个方面涉及所述细胞在抗肿瘤治疗中的用途，其包括将所述间充质干细胞与抗肿瘤免疫疗法例如检查点抑制剂，免疫细胞例如T细胞例如T细胞与人造T细胞受体，例如嵌合抗原受体（CAR-Ts）或外源T细胞受体（TCR）转导的细胞，NK细胞或巨噬细胞/单核细胞，或癌症疫苗。

8. 发明授权

EP2961430B1 PROTECTION OF THE VASCULAR ENDOTHELIUM FROM IMMUNOLOGICALLY MEDIATED CYTOTOXIC REACTIONS WITH HUMAN CD34-NEGATIVE PROGENITOR CELLS 失效转让
标题翻译：免疫介导细胞毒性反应与人CD34阴性祖细胞的血管内皮保护作用
公开(公告)号：EP2961430B1
公开(公告)日：2017-08-16
申请号：EP14707170.8
申请日：2014-02-28
申请人： Apceth GmbH & Co. KG
发明人： EISSNER, Günther , GUENTHER, Christine , HUSS, Ralf
IPC分类号： A61K35/00 , A61K35/28 , G01N33/00 , A61P37/00 , A61P29/00
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

9. 发明授权

EP2162534B1 Genetically modified CD34 negative mesenchymal stem cells for tumour treatment 有权
标题翻译：遗传修饰的CD34阴性间充质干细胞用于治疗肿瘤的
公开(公告)号：EP2162534B1
公开(公告)日：2014-07-23
申请号：EP08754569.5
申请日：2008-05-20
申请人： Apceth GmbH & Co. KG
发明人： HUSS, Ralf , NELSON, Peter , RAGGI, Matthias , STANGL, Manfred
IPC分类号： A61P35/04 , C12N5/0775 , A61K48/00 , A61K35/28 , A61K38/17 , A61K38/18
CPC分类号： A61K35/545 , A61K35/12 , A61K35/28 , A61K38/1709 , A61K38/18 , A61K38/1866 , A61K48/00 , A61K2035/122 , A61K2035/124 , C07K14/49 , C12N5/0663
摘要： This invention provides novel stem cell-based methods for treating a number of conditions. These methods employ CD34 - stem cells, and have a tremendous advantage in that they do not require myeloablation in the subject being treated. The CD34 - stem cells used in the instant methods can be genetically modified or not, depending on the disorder treated.

10. 发明公开

EP2961430A1 PROTECTION OF THE VASCULAR ENDOTHELIUM FROM IMMUNOLOGICALLY MEDIATED CYTOTOXIC REACTIONS WITH HUMAN CD34-NEGATIVE PROGENITOR CELLS 失效转让
标题翻译：血管内皮的保护之前免疫介导的与人群CD34阴性祖细胞细胞毒反应
公开(公告)号：EP2961430A1
公开(公告)日：2016-01-06
申请号：EP14707170.8
申请日：2014-02-28
申请人： Apceth GmbH & Co. KG
发明人： EISSNER, Günther , GUENTHER, Christine , HUSS, Ralf
IPC分类号： A61K45/00 , A61K35/00 , A61K38/17 , A61K35/28 , C12N5/071 , G01N33/00 , C12N5/0775
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：本发明提供了在保护来自受试者的免疫介导的细胞毒性反应的血管内皮处于危险的使用人CD34阴性的祖细胞，或与血管炎性疾病折磨。这样提供了用于生产人类CD34阴性的祖细胞的方法和用于确定性采矿CD34阴性的祖细胞的保护从免疫介导的细胞毒性反应的血管内皮的能力的方法。

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