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1. 发明申请

WO2014074695A1 RETINOIC ACID ENHANCED HUMAN STEM CELL DERIVED BLOOD BRAIN BARRIER MODEL 审中-公开
标题翻译：反义酸增强人类干细胞衍生的血液脑屏障模型
公开(公告)号：WO2014074695A1
公开(公告)日：2014-05-15
申请号：PCT/US2013/068914
申请日：2013-11-07
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , SHUSTA, Eric, V. , PALECEK, Sean, P. , LIPPMANN, Ethan, S. , AZARIN, Samira, M.
发明人： SHUSTA, Eric, V. , PALECEK, Sean, P. , LIPPMANN, Ethan, S. , AZARIN, Samira, M.
IPC分类号： C12N5/0797 , C12N5/071
CPC分类号： C12N5/0697 , C12N5/0623 , C12N5/069 , C12N5/0692 , C12N2500/90 , C12N2501/115 , C12N2501/385 , C12N2502/08 , C12N2502/088 , C12N2506/02 , C12N2506/45
摘要： In one embodiment, the present invention is a method of creating a fully-human blood-brain barrier (BBB) model, comprising the steps of (a) obtaining a mixture of neural cells and brain microvascular endothelial cells (BMECs), wherein the neural cells and BMECs that comprise the mixture were produced from the differentiation of human pluripotent stem cells (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs of step (a); and (c) co-cuituring the purified BMECs with a ceil type selected from the group consisting of pericytes, astrocytes and differentiated neural progenitor ceils (NPCs), wherein a blood brain barrier model is created. In another embodiment the present invention is a method of creating a retinoic acid (RA)-enhanced or RA-like compound-enhanced mammalian blood-brain barrier (BBB) model, comprising the steps of: (a) obtaining a mixture of neural cells and brain microvascular endothelial ceils (BMECs) in the presence of RA or RA-like compound, wherein the mixture of neural ceils and BMECs was produced from the differentiation of human pluripotent stem ceils (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs; and co- cuituring the purified BMECs with a cell type selected from the group consisting of astrocytes, pericytes and differentiated neural progenitor ceils (NPCs), wherein a BBB model is created.
摘要翻译：在一个实施方案中，本发明是一种产生完全人血脑屏障（BBB）模型的方法，其包括以下步骤：（a）获得神经细胞和脑微血管内皮细胞（BMEC）的混合物，其中神经构成混合物的细胞和BMECs由人多能干细胞（hPSC）的分化产生; （b）从步骤（a）的神经细胞和BMECs的混合物中纯化BMEC; 和（c）用选自周细胞，星形胶质细胞和分化的神经祖细胞（NPC））的细胞型共培养纯化的BMEC，其中产生血脑屏障模型。在另一个实施方案中，本发明是产生视黄酸（RA）增强或RA样化合物增强的哺乳动物血脑屏障（BBB）模型的方法，其包括以下步骤：（a）获得神经细胞在RA或RA样化合物存在下，脑微血管内皮细胞（BMECs），其中神经细胞和BMECs的混合物是由人多能干细胞（hPSC）的分化产生的; （b）从神经细胞和BMECs的混合物中纯化BMEC; 并用选自星形胶质细胞，周细胞和分化的神经祖细胞（NPC））的细胞类型共同测试纯化的BMEC，其中产生BBB模型。

2. 发明申请

WO2011159572A2 HUMAN BLOOD-BRAIN ENDOTHELIAL CELLS DERIVED FROM PLURIPOTENT STEM CELLS AND BLOOD-BRAIN BARRIER MODEL THEREOF 审中-公开
标题翻译：来自PLUIPOTETIC STEM CELLS的人血脑屏障内皮细胞及其血脑屏障模型
公开(公告)号：WO2011159572A2
公开(公告)日：2011-12-22
申请号：PCT/US2011/039998
申请日：2011-06-10
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , SHUSTA, Eric, V. , LIPPMANN, Ethan , AZARIN, Samira , PALECEK, Sean
发明人： SHUSTA, Eric, V. , LIPPMANN, Ethan , AZARIN, Samira , PALECEK, Sean
IPC分类号： C12N5/00
CPC分类号： C12N5/069 , C12N5/0697 , C12N2502/086 , C12N2502/28 , C12N2506/45 , C12N2533/90
摘要： A model blood brain barrier obtained from hPSCs is disclosed.
摘要翻译：公开了从hPSC获得的模型血脑屏障。

3. 发明申请

WO2011159572A3 HUMAN BLOOD-BRAIN ENDOTHELIAL CELLS DERIVED FROM PLURIPOTENT STEM CELLS AND BLOOD-BRAIN BARRIER MODEL THEREOF 审中-公开
标题翻译：来自PLUIPOTETIC STEM CELLS的人血脑屏障内皮细胞及其血脑屏障模型
公开(公告)号：WO2011159572A3
公开(公告)日：2012-04-12
申请号：PCT/US2011039998
申请日：2011-06-10
申请人： WISCONSIN ALUMNI RES FOUND , SHUSTA ERIC V , LIPPMANN ETHAN , AZARIN SAMIRA , PALECEK SEAN
发明人： SHUSTA ERIC V , LIPPMANN ETHAN , AZARIN SAMIRA , PALECEK SEAN
IPC分类号： C12N5/071 , G01N33/50
CPC分类号： C12N5/069 , C12N5/0697 , C12N2502/086 , C12N2502/28 , C12N2506/45 , C12N2533/90
摘要： A model blood brain barrier obtained from hPSCs is disclosed.
摘要翻译：公开了从hPSC获得的模型血脑屏障。

4. 发明申请

WO2007143711A3 BLOOD-BRAIN BARRIER TARGETING ANTIBODIES 审中-公开
标题翻译：血脑屏障定位抗体
公开(公告)号：WO2007143711A3
公开(公告)日：2008-03-06
申请号：PCT/US2007070587
申请日：2007-06-07
申请人： WISCONSIN ALUMNI RES FOUND , SHUSTA ERIC V , WANG XIN X , CHO YONGKU P
发明人： SHUSTA ERIC V , WANG XIN X , CHO YONGKU P
IPC分类号： C07K14/05 , A61K39/395 , C07K16/28 , G01N33/53
CPC分类号： C07K16/28 , A61K47/6849 , C07K2317/21 , C07K2317/622 , C07K2317/77 , G01N33/6854
摘要： This invention provides antibodies that bind brain endothelial cell receptors resulting in endocytosis/transcytosis of the receptor and bound ligands. In some embodiments, the ligand comprises the antibody in combination with a pharmaceutically active compound and the antibody directs delivery of the compound across the blood brain barrier (BBB). The invention also provides methods of identifying endothelial cell specific antibodies by panning the library against cultured cell monolayers. The invention further allows for identifying endothelial cell receptors that bind the antibody thereby providing target receptors against which to isolate further cognate ligands and their associated transport systems and by which to identify transcytosis transporters targeted by the antibodies.
摘要翻译：本发明提供了结合脑内皮细胞受体的抗体，导致受体和结合配体的内吞作用/胞吞作用。在一些实施方案中，配体包含与药物活性化合物组合的抗体，抗体指导化合物通过血脑屏障（BBB）的递送。本发明还提供了通过将文库缓冲培养的细胞单层来鉴定内皮细胞特异性抗体的方法。本发明还允许鉴定结合抗体的内皮细胞受体，从而提供靶细胞受体，以分离进一步的同源配体及其相关的转运系统，并通过其识别抗体靶向的转胞吞素转运蛋白。

5. 发明申请

WO2007143711A2 BLOOD-BRAIN BARRIER TARGETING ANTIBODIES 审中-公开
标题翻译：血脑屏障定位抗体
公开(公告)号：WO2007143711A2
公开(公告)日：2007-12-13
申请号：PCT/US2007/070587
申请日：2007-06-07
申请人： WISCONSIN ALUMNI RESEARCH FOUNDATION , SHUSTA, Eric, V. , WANG, Xin, X. , CHO, Yongku, P.
发明人： SHUSTA, Eric, V. , WANG, Xin, X. , CHO, Yongku, P.
CPC分类号： C07K16/28 , A61K47/6849 , C07K2317/21 , C07K2317/622 , C07K2317/77 , G01N33/6854
摘要： This invention provides antibodies that bind brain endothelial cell receptors resulting in endocytosis/transcytosis of the receptor and bound ligands. In some embodiments, the ligand comprises the antibody in combination with a pharmaceutically active compound and the antibody directs delivery of the compound across the blood brain barrier (BBB). The invention also provides methods of identifying endothelial cell specific antibodies by panning the library against cultured cell monolayers. The invention further allows for identifying endothelial cell receptors that bind the antibody thereby providing target receptors against which to isolate further cognate ligands and their associated transport systems and by which to identify transcytosis transporters targeted by the antibodies.
摘要翻译：本发明提供了结合脑内皮细胞受体的抗体，导致受体和结合配体的内吞作用/胞吞作用。在一些实施方案中，配体包含与药物活性化合物组合的抗体，抗体指导化合物通过血脑屏障（BBB）的递送。本发明还提供了通过将文库缓冲培养的细胞单层来鉴定内皮细胞特异性抗体的方法。本发明还允许鉴定结合抗体的内皮细胞受体，从而提供靶细胞受体，以分离进一步的同源配体及其相关的转运系统，并通过其识别抗体靶向的转胞吞素转运蛋白。

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