Inventors:
Vladimir R. Muzykantov - Warwick PA, US
Douglas B. Cines - Wynnewood PA, US
Claudia Gottstein - Carpinteria CA, US
Steven M. Albelda - Philadelphia PA, US
Assignee:
The Trustees of the University of Pennsylvania - Philadelphia PA
International Classification:
A61K 39/395, A61P 7/02, A61P 7/10, A61P 29/00, A61P 9/10, C07K 19/00, A61P 11/00
Abstract:
Compositions are provided comprising a thrombomodulin domain linked to a targeting moiety that binds to a determinant on the surface of a target endothelial cell or red blood cell, wherein the thrombomodulin domain may be the extracellular domain, the N-terminal lectin-like domain, or an epidermal growth factor (EGF)-like domain. The targeting moiety may be a single chain antigen-binding domain (scFv), and the targeting moiety and thrombomodulin domain of the composition may be linked as a continuous polypeptide chain. Methods of delivery and use of a composition described herein are provided, as well as methods of treating or preventing thrombosis, inflammation, tissue ischemia, sepsis, acute lung injury (ALI), acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease is provided.