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POLYPEPTIDE INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY AND USES THEREOF
POLYPEPTIDE INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY AND USES THEREOF
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机译:中性粒细胞弹性蛋白酶活性的多肽抑制剂及其用途
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摘要
The invention features polypeptides that include variants of plasminogen activator inhibitor 1 (PAI-1) having a reduced ability to bind with vitronectin, having a reduced ability to interact with the PAI-1 clearance receptor LDL receptor-related protein 1 (LRP1), and having the ability to efficiently inhibit neutrophil elastase in the presence of neutrophil extracellular traps (NETs). In some embodiments, a polypeptide of the invention includes PAI-1 variants optionally fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions characterized with aberrant neutrophil elastase activity (e.g., Idiopathic Pulmonary Fibrosis).
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