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1. 发明申请

WO2003071267A1 THERAPEUTIC METHODS EMPLOYING PAI-1 INHIBITORS AND TRANSGENIC NON-HUMAN ANIMAL FOR SCREENING CANDIDATE PAI-1 INHIBITORS 审中-公开
标题翻译：使用PAI-1抑制剂和转基因非人动物筛选候选PAI-1抑制剂的治疗方法
公开(公告)号：WO2003071267A1
公开(公告)日：2003-08-28
申请号：PCT/US2003/005008
申请日：2003-02-19
申请人： VANDERBILT UNIVERSITY , DECLERCK, Paul, J. , VAUGHAN, Douglas, E. , EREN, Mesut
发明人： DECLERCK, Paul, J. , VAUGHAN, Douglas, E. , EREN, Mesut
IPC分类号： G01N33/00
CPC分类号： C12N15/873 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0312 , C07K14/8132 , C12N15/8509 , C12Q1/56 , G01N33/566 , G01N33/68 , G01N33/6893 , G01N33/6896 , G01N33/86 , G01N2333/8132 , G01N2500/00
摘要： A method of treating a warm-blooded vertebrate animal having a medical condition in need of treatment with a composition that exhibits PAI-1 inhibition activity is disclosed. The method includes the steps of administering a treatment effective amount of the composition to a warmblooded vertebrate animal having a medical condition selected from the group consisting of alopecia, undesired weight loss, Alzheimer's Disease, systemic amyloidosis, myelofibrosis, male pattern baldness, glomerulosclerosis, and combinations thereof; and observing an improvement in the medical condition in the warm-blooded vertebrate animal having the medical condition. A method of testing a candidate composition for PAI-1 inhibition activity is also disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer overexpression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful is such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.
摘要翻译：公开了一种治疗需要用表现出PAI-1抑制活性的组合物治疗的具有医学病症的温血脊椎动物的方法。该方法包括以下步骤：将治疗有效量的组合物施用于具有选自脱发，不希望的体重减轻，阿尔茨海默病，全身淀粉样变性，骨髓纤维化，男性型秃发，肾小球硬化和其组合; 并观察具有医疗状况的温血脊椎动物的医疗状况的改善。还公开了测试候选组合物用于PAI-1抑制活性的方法。该方法包括以下步骤：获得在其基因组中掺入了编码生物活性PAI-1多肽的PAI-1基因的转基因非人类温血脊椎动物，所述PAI-1基因以有效的拷贝数存在于基因组中以在PAI-1多肽的转基因非人动物中赋予过表达; 将所述组合物施用于所述转基因非人动物; 并观察转基因非人动物以测定表达PAI-1活性抑制的转基因非人动物的变化。还公开了一种有用的转基因非人动物，编码可用于制备转基因非人动物的生物活性PAI-1多肽的PAI-1转基因构建体也是公开的。

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