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1. 发明授权

US06872699B2 Truncated Flk-1 receptor protein, methods of use and a recombinant vector containing a nucleotide encoding the truncated Flk-1 protein 失效
标题翻译：截短的Flk-1受体蛋白，使用方法和含有编码截短的Flk-1蛋白的核苷酸的重组载体
公开(公告)号：US06872699B2
公开(公告)日：2005-03-29
申请号：US09766678
申请日：2001-01-23
申请人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
发明人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
IPC分类号： A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07D487/04 , C07D498/04 , C07K14/71 , C07K16/28 , G01N33/50 , G01N33/68
CPC分类号： G01N33/502 , A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07D487/04 , C07K14/71 , C07K16/2863 , C07K2319/00 , G01N33/5008 , G01N33/5011 , G01N33/5041 , G01N33/5064 , G01N33/6893 , G01N2333/71 , G01N2500/04
摘要： The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and truncated Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.
摘要翻译：本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。描述了表达Flk-1和截短的Flk-1的宿主细胞的工程和表达的Flk-1用于通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物的用途。本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

2. 发明授权

US5286716A Inhibitor of the proliferation of endothelial cells 失效
标题翻译：抑制内皮细胞增殖
公开(公告)号：US5286716A
公开(公告)日：1994-02-15
申请号：US920467
申请日：1992-08-25
申请人： Werner Risau , Hannes Drexler
发明人： Werner Risau , Hannes Drexler
IPC分类号： A61K38/00 , A61P3/08 , A61P9/00 , A61P9/06 , A61P27/02 , A61P29/00 , A61P35/00 , A61P43/00 , C07K1/14 , C07K1/20 , C07K1/22 , C07K14/435 , C07K14/47 , C07K14/515 , A61K37/00
CPC分类号： C07K14/515 , C07K14/4703
摘要： Protein which acts as an inhibitor of the proliferation of endothelial ce which is obtainable from baby hamster kidney cells (ATCC CCL 10) and has a molecular weight between 60 and 100 kD in gel filtration under native conditions and is thermally stable at 60.degree. C., as well as a process for its isolation and its use in the treatment of diseases.
摘要翻译：抑制内皮细胞增殖的蛋白质，其可从婴儿仓鼠肾细胞（ATCC CCL 10）获得，其在天然条件下凝胶过滤具有60至100kD的分子量，并且在60℃下加热稳定。富集过程它及其在治疗疾病中的应用。

3. 发明授权

US07964399B2 Cell line comprising vector encoding truncated FLK-1 receptor 失效
标题翻译：包含编码截短的FLK-1受体的载体的细胞系
公开(公告)号：US07964399B2
公开(公告)日：2011-06-21
申请号：US10799782
申请日：2004-03-15
申请人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
发明人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
IPC分类号： C12N5/10 , C07K14/71
CPC分类号： G01N33/502 , A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07D487/04 , C07K14/71 , C07K16/2863 , C07K2319/00 , G01N33/5008 , G01N33/5011 , G01N33/5041 , G01N33/5064 , G01N33/6893 , G01N2333/71 , G01N2500/04
摘要： The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention s based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.
摘要翻译：本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。本发明部分地基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。描述表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物。本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

4. 发明申请

US20050107321A1 FLK-1 is a receptor for vascular endothelial growth factor 失效
标题翻译： FLK-1是血管内皮生长因子受体
公开(公告)号：US20050107321A1
公开(公告)日：2005-05-19
申请号：US10799782
申请日：2004-03-15
申请人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
发明人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
IPC分类号： A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07D487/04 , C07D498/04 , C07K14/71 , C07K16/28 , G01N33/50 , G01N33/68 , A61K48/00 , C07H21/04 , C07K14/705 , C12N15/867
CPC分类号： G01N33/502 , A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07D487/04 , C07K14/71 , C07K16/2863 , C07K2319/00 , G01N33/5008 , G01N33/5011 , G01N33/5041 , G01N33/5064 , G01N33/6893 , G01N2333/71 , G01N2500/04
摘要： The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.
摘要翻译：本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。描述表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物。本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

5. 发明授权

US5851999A FLK-1 is a receptor for vascular endothelial growth factor 失效
标题翻译： FLK-1是血管内皮生长因子受体
公开(公告)号：US5851999A
公开(公告)日：1998-12-22
申请号：US443861
申请日：1995-05-22
申请人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
发明人： Axel Ullrich , Werner Risau , Birgit Millauer , Aviv Gazit , Alex Levitzki
IPC分类号： G01N33/53 , A61K31/047 , A61K31/235 , A61K31/245 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/381 , A61K31/40 , A61K31/403 , A61K31/404 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/496 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , A61K39/395 , A61P1/00 , A61P3/08 , A61P3/10 , A61P9/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P17/00 , A61P27/02 , A61P35/00 , C07C229/60 , C07C255/34 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/44 , C07C317/46 , C07C327/44 , C07D209/18 , C07D209/20 , C07D231/38 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07D261/08 , C07D333/42 , C07D403/06 , C07D487/04 , C07D491/052 , C07D498/04 , C07H21/04 , C07K14/71 , C07K16/28 , C12N5/10 , C12N15/09 , C12N15/12 , C12P21/02 , C12P21/08 , C12R1/91 , G01N33/50 , G01N33/566 , G01N33/577 , G01N33/68 , A61K48/00 , C12N5/00 , C12N15/00
CPC分类号： C07D487/04 , A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07K14/71 , C07K16/2863 , G01N33/5008 , G01N33/5011 , G01N33/502 , G01N33/5064 , G01N33/5091 , G01N33/6893 , A61K38/00 , C07K2319/32 , G01N2333/71 , G01N2500/04
摘要： The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.
摘要翻译：本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。描述表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物。本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

6. 发明授权

US5529792A Inhibitors of endothelial cell proliferation 失效
标题翻译：抑制内皮细胞增殖
公开(公告)号：US5529792A
公开(公告)日：1996-06-25
申请号：US108573
申请日：1993-11-10
申请人： Werner Risau , Hannes Drexler
发明人： Werner Risau , Hannes Drexler
IPC分类号： A61K35/30 , A61K35/48 , A61K38/00 , A61P27/02 , A61P29/00 , A61P35/00 , A61P43/00 , C07K1/16 , C07K1/18 , C07K1/20 , C07K14/435 , C07K14/47
CPC分类号： C07K14/4703 , A61K38/00
摘要： In order to isolate an inhibitor of the proliferation of endothelial cells from the tissue of vertebrates the tissue selected as the starting material e.g. embryonic tissue or adult brain tissue from birds or mammals, is centrifuged, homogenized and subsequently the tissue extract is applied to a cation exchanger and the substances which bind to the cation exchanger are subjected to a fractionation, the active fractions are separated by gel filtration chromatography and they are purified by reverse phase HPLC. The new inhibitor obtained in this way is suitable for treating disease states in which an inhibition of capillary growth is necessary such as for the treatment of tumors, rheumatoid arthritis, diabetic retinopathy and retrolental fibroplasia and for treating wounds in order to regulate the regeneration of blood vessels.
摘要翻译： PCT No.PCT / EP92 / 00419 Sec。 371日期：1993年11月10日 102（e）日期1993年11月10日PCT提交1992年2月27日PCT公布。 WO92 / 15606 PCT公开号日期为1992年9月17日。为了从脊椎动物组织中分离内皮细胞增殖的抑制剂，选择作为起始材料的组织。将来自鸟类或哺乳动物的胚胎组织或成体脑组织离心，均质化，随后将组织提取物施用于阳离子交换剂，并将结合阳离子交换剂的物质进行分级分离，通过凝胶过滤色谱法分离活性级分并通过反相HPLC纯化。以这种方式获得的新抑制剂适用于治疗需要抑制毛细血管生长的疾病状态，例如用于治疗肿瘤，类风湿性关节炎，糖尿病性视网膜病变和复发性纤维增生症以及治疗创伤以调节血液再生船只。

7. 发明申请

US20050235367A1 Regulatory sequences capable of conferring expression of a heterologous DNA sequence in endothelial cells and uses thereof 审中-公开
标题翻译：能够赋予异源DNA序列在内皮细胞中表达的调节序列及其用途
公开(公告)号：US20050235367A1
公开(公告)日：2005-10-20
申请号：US11015329
申请日：2004-12-17
申请人： Georg Breier , Werner Risau , Volker Ronicke , Andreas Kappel , Barbara Risau
发明人： Georg Breier , Werner Risau , Volker Ronicke , Andreas Kappel , Barbara Risau
IPC分类号： A01K67/027 , A61K31/7105 , A61K38/00 , A61K38/21 , A61K38/22 , A61K38/43 , A61K38/48 , A61K45/00 , A61K48/00 , A61P9/00 , A61P9/10 , A61P25/00 , A61P35/00 , C07K14/47 , C07K14/52 , C07K14/57 , C07K14/58 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/02 , C12N9/72 , C12N15/09 , C12N15/12 , C12N15/16 , C12N15/19 , C12N15/23 , C12N15/53 , C12N15/58 , C12N15/85 , C12Q1/00 , A01K67/00 , C07H21/04 , C07K14/71
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/05 , A01K2217/072 , A01K2267/0375 , A01K2267/0393 , A61K48/00 , C07K14/4702 , C12N15/85 , C12N2830/008 , C12N2830/42 , C12N2830/85
摘要： Described are recombinant DNA molecules comprising the regulatory sequence(s) of an intron of the Endothelial Growth Factor (VEGF) receptor-2 gene (Flk-1) or of a gene homologous to the Flk-1 gene, being capable of conferring expression of a heterologous DNA sequence in endothelial cells, preferably in vivo. Vectors comprising said DNA molecules as well as host cells containing the same are provided. Also provided are pharmaceutical and diagnostic compositions comprising such recombinant DNA molecules and vectors. Furthermore, cells and transgenic non-human animals, comprising the aforementioned recombinant DNA molecules or vectors stably integrated into their genome and their use for the identification of substances capable of suppressing or activating transcription of a gene in endothelial cells are described. Described is further the use of the before described recombinant DNA molecules and vectors for the preparation of pharmaceutical compositions for treating, preventing, and/or delaying a vascular or tumorous disease in a subject. Furthermore, uses of the recombinant DNA molecules and vectors of the invention for the preparation of pharmaceutical compositions for inducing a vascular or tumorous disease in a non-human animal are provided.
摘要翻译：描述了包含内皮生长因子（VEGF）受体-2基因（Flk-1）的内含子的调节序列或与Flk-1基因同源的基因的重组DNA分子，其能够赋予内皮细胞中的异源DNA序列，优选在体内。提供了包含所述DNA分子的载体以及含有该DNA分子的宿主细胞。还提供包含这样的重组DNA分子和载体的药物和诊断组合物。此外，描述了包含上述重组DNA分子或稳定整合到其基因组中的载体的细胞和转基因非人动物及其用于鉴定能够抑制或激活内皮细胞中基因转录的物质的用途。还描述了前述重组DNA分子和载体用于制备用于治疗，预防和/或延缓受试者的血管或肿瘤疾病的药物组合物的用途。此外，提供了本发明的重组DNA分子和载体用于制备用于在非人动物中诱导血管或肿瘤疾病的药物组合物的用途。

8. 发明授权

US06177401B1 Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis 失效
标题翻译：使用有机化合物抑制Flk-1介导的血管发生和血管生成
公开(公告)号：US06177401B1
公开(公告)日：2001-01-23
申请号：US08193829
申请日：1994-02-09
申请人： Axel Ullrich , Werner Risau , Birgit Millauer
发明人： Axel Ullrich , Werner Risau , Birgit Millauer
IPC分类号： A61K3100
CPC分类号： C07D487/04 , A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07K14/71 , C07K16/2863 , C07K2319/32 , G01N33/5008 , G01N33/5011 , G01N33/502 , G01N33/5064 , G01N33/5091 , G01N33/6893 , G01N2333/71 , G01N2500/04
摘要： The present invention relates to the use of proteins, peptides and organic molecules capable of modulating Flk-1 receptor signal transduction in order to inhibit or promote angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.
摘要翻译：本发明涉及能够调节Flk-1受体信号转导以抑制或促进血管生成和血管发生的蛋白质，肽和有机分子的用途。本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。描述了表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF和类似物的用途。本发明还涉及使用 FLK-1配体，包括VEGF激动剂和拮抗剂，通过调节血管发生和血管生成来治疗病症，包括癌症。

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