Targeted therapeutic or diagnostic agents and methods of making and using same

摘要

The present invention provides a targeted therapeutic or diagnostic agent comprising (a) a therapeutic or diagnostic functional entity linked to one of the following: (a) an isolated peptide mimetic that specifically binds a selected target; (b) an isolated, optimized, high-affinity polyamino acid that specifically binds a selected target; (c) an isolated protein surface loop that specifically binds a selected target, wherein the protein surface loop is not endogenous to the functional entity. The invention additionally provides methods of targeting therapeutic or diagnostic agents to a target. Additionally provided is a method of targeting a therapeutic agent to a platelet using the present agents, and methods of treating diseases and disorders associated with blood clots. Specifically provided is a recombinant targeting protein wherein the surface loop is the HCDR3 of monoclonal antibody Fab-9, the second protein is human tissue type plasminogen activator (t-PA), and the target is platelet glycoprotein GPIIb/IIIa (integrin alpha IIb beta I).