专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明申请

WO1997039028A1 MUTANT PLASMINOGEN ACTIVATOR-INHIBITOR TYPE 1 (PAI-1) AND USES THEREOF 审中-公开
标题翻译：突变型PLASMINOGEN激活剂抑制剂1型（PAI-1）及其用途
公开(公告)号：WO1997039028A1
公开(公告)日：1997-10-23
申请号：PCT/US1997006071
申请日：1997-04-11
申请人： AMERICAN NATIONAL RED CROSS
发明人： AMERICAN NATIONAL RED CROSS , LAWRENCE, Daniel, A. , STEFANSSON, Steingrimur, P.
IPC分类号： C07K14/00
CPC分类号： C07K16/28 , A61K38/00 , C07K14/8132 , C07K2317/77
摘要： Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells. Such conditions include atherosclerosis, post angioplasty restenosis, fibrosis associated with chronic inflammation or chemotherapy, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. Also disclosed are peptides of such mutant proteins, mutant-specific antibodies, nucleic acid molecules, particularly DNA, encoding the mutant protein and host cells transformed by such nucleic acids.
摘要翻译：描述了人PAI-1蛋白的突变体，其是嗜中性粒细胞弹性蛋白酶抑制剂或玻连蛋白（Vn）依赖性细胞迁移的抑制剂。这些突变体优选在PAI-1的反应中心环中，特别是成熟蛋白的位置331和346处包含一个或两个氨基酸取代。这些突变体在抵抗对Vn具有高亲和力的弹性蛋白酶的失活或两种性质方面是显着的。这些作为药物组合物的突变蛋白质用于抑制受试者中的弹性蛋白酶，从而治疗与弹性蛋白酶活性相关的许多障碍，特别是肺气肿，ARDS，炎症性肺损伤和囊性纤维化。与Vn相互作用的突变体用于抑制受试者中的细胞迁移，从而治疗与不期望的细胞迁移和增殖相关的疾病或病症，特别是平滑肌细胞的增殖。这些病症包括动脉粥样硬化，血管成形术后再狭窄，与慢性炎症或化学疗法相关的纤维化，肿瘤浸润和转移以及血管发生是致病性的病症。还公开了这样的突变蛋白质，突变体特异性抗体，核酸分子，特别是DNA，编码由这种核酸转化的突变蛋白质和宿主细胞的肽。

2. 发明申请

WO2004103313A2 METHODS OF REDUCING VASCULAR PERMEABILITY IN TISSUE BY INHIBITION OF TISSUE PLASMINOGEN ACTIVATOR (TPA) AND TPA INHIBITORS USEFUL THEREIN 审中-公开
标题翻译：通过抑制组织培养基激活剂（TPA）和有用的TPA抑制剂来减少组织中血管渗透性的方法
公开(公告)号：WO2004103313A2
公开(公告)日：2004-12-02
申请号：PCT/US2004/015873
申请日：2004-05-20
申请人： THE AMERICAN NATIONAL RED CROSS , LAWRENCE, Daniel, A. , YEPES, Manuel, S. , STRICKLAND, Dudley
发明人： LAWRENCE, Daniel, A. , YEPES, Manuel, S. , STRICKLAND, Dudley
IPC分类号： A61K
CPC分类号： G01N33/5088 , G01N2333/9726 , G01N2800/2871
摘要： The present invention is a method of reducing vascular permeability in tissue of a subject comprising inhibiting the activity of serine proteinase tissue-type plasminogen activator (tPA). This tPA activity which increases permeability of the tissue in a subject results in edema in the tissue is separate from tPA's thrombolytic activity. The present invention more specifically relates to administering an amount of a tPA inhibitor sufficient to reduce the vascular permeability increasing activity of tPA in a subject. Useful tPA inhibitors for the present method are neuroserpin, mutant neuroserpin, wild-type PAI- 1, mutant PAI- 1, an antibody that binds to tPA, an antibody that binds to the low-density lipoprotein (LDL) receptor or a low-density lipoprotein (LDL) receptor family antagonist.
摘要翻译：本发明是减少受试者组织中血管通透性的方法，包括抑制丝氨酸蛋白酶组织型纤溶酶原激活物（tPA）的活性。增加受试者组织渗透性的这种tPA活性导致组织水肿与tPA的溶栓活性分开。本发明更具体地涉及给予一定量的足以降低受试者中tPA的血管通透性增加活性的量的tPA抑制剂。用于本方法的有用的tPA抑制剂是神经丝氨酸蛋白酶抑制剂，突变型神经丝氨酸蛋白酶抑制剂，野生型PAI-1，突变型PAI-1，结合tPA的抗体，结合低密度脂蛋白（LDL）受体的抗体或低密度脂蛋白密度脂蛋白（LDL）受体家族拮抗剂。

你已经成功收藏专利！

检索式保存成功!

IPRDB

热门服务

关于我们

友情链接

联系方式