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2. 发明授权

US06375929B1 Gene therapy for inhibition of angiogenesis 失效
标题翻译：用于抑制血管生成的基因治疗
公开(公告)号：US06375929B1
公开(公告)日：2002-04-23
申请号：US09427353
申请日：1999-10-26
申请人： Kenneth A. Thomas, Jr. , Richard L. Kendall , Corey K. Goldman , William R. Huckle , Andrew J. Bett
发明人： Kenneth A. Thomas, Jr. , Richard L. Kendall , Corey K. Goldman , William R. Huckle , Andrew J. Bett
IPC分类号： A61K4900
CPC分类号： C07K14/71 , A61K38/00 , A61K48/00 , A61K49/0004 , C12N2799/022
摘要： The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with solid tumor growth, tumor metastasis, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration Gene therapy methodology is disclosed for inhibition of primary tumor growth and metastasis by gene transfer of a nucleotide sequence encoding a soluble form of a VEGF tyrosine kinase receptor to a mammalian host. The transferred nucleotide sequence transcribes mRNA and a soluble receptor protein which binds to VEGF in extracellular regions adjacent to the primary tumor and vascular endothelial cells. Formation of a sVEGF-R/VEGF complex will prevent binding of VEGF to the KDR and FLT-1 tyrosine kinase receptors, antagonizing transduction of the normal intracellular signals associated with vascular endothelial cell-induced tumor angiogenesis. In addition, expression of a soluble receptor tyrosine kinase may also impart a therapeutic effect by binding either with or without VEGFs to form non-functional heterodimers with full-length VEGF-specific tyrosine kinase receptors and thereby inhibiting the mitogenic and angiogenic activities of VEGFs.
摘要翻译：本发明涉及用于抑制与实体瘤生长，肿瘤转移，炎症，牛皮癣，类风湿性关节炎，血管瘤，糖尿病性视网膜病，血管纤维瘤和黄斑变性相关的血管生成的基因治疗方法，用于抑制原发性肿瘤生长和通过将编码可溶形式的VEGF酪氨酸激酶受体的核苷酸序列的基因转移到哺乳动物宿主的转移。转移的核苷酸序列转录mRNA和可溶性受体蛋白，其在与原发性肿瘤和血管内皮细胞相邻的细胞外区域中结合VEGF。 sVEGF-R / VEGF复合物的形成将阻止VEGF与KDR和FLT-1酪氨酸激酶受体的结合，拮抗与血管内皮细胞诱导的肿瘤血管生成相关的正常细胞内信号的转导。此外，可溶性受体酪氨酸激酶的表达还可以通过与或不与VEGF结合来赋予治疗效果，以形成具有全长VEGF特异性酪氨酸激酶受体的非功能异二聚体，从而抑制VEGF的促有丝分裂和血管生成活性。

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