Patent ID: 8613929

Claim:
A method of delivering a therapeutic agent into and across an endothelial cell (EC) of a microvascular blood-central nervous system (CNS) barrier in a Diphtheria toxin (DT) sensitive subject in need thereof, comprising: (a) administering to the subject a moiety that increases binding of DT to DT receptors (DTR) selected from the group consisting of heparin, heparan sulfate, a heparan sulfate proteoglycan, a matrix metalloproteinase inhibitor, BB-94 (batimastat), an inhibitor of ADAM12 or ADAM10, or a MAP/ERK kinase inhibitor; followed by (b) administering to said subject a therapeutic agent with a pharmaceutically acceptable carrier, which therapeutic agent or carrier is conjugated to a DTR-binding targeting antibody molecule to constitute a conjugate that specifically binds to the DTR on target tissue cells, such that an effective barrier-entering, barrier-crossing amount of said therapeutic agent enters and crosses the EC microvascular barrier.