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US 5,759,542 AGranted
Compositions and methods for the delivery of drugs by platelets for the treatment of cardiovascular and other diseases
AssigneeNew England Deaconess Hospital Corporation
InventorVictor Gurewich
Life of this patent
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Abstract
A fusion drug including an isolated portion of the A-chain of a urokinase-type plasminogen activator linked to a drug, wherein the A-chain portion binds stably to an outer membrane of a platelet. The T.sub.1/2 of the fusion drug in plasma is thereby increased to about 4 to 5 days, and the fusion drug is automatically targeted to forming thrombi and sites of vascular injury. The fusion drug can thus be used to treat cardiovascular diseases, e.g., as adjunctive therapy to inhibit reocclusions in a patient after thrombolytic therapy or angioplasty.
Claims11
A fusion drug consisting of
- (a) a non-urokinase drug consisting of a peptide, protein, or polypeotide effective against a platelet-mediated thrombosis or stenosis;
- (b) a bvinding portion consisting of an isolated portion of at least amino acids 1 to 132 of the A-chain of a urokinase-type plasminogen activator (SEQ ID NO:18) that binds stably to an outer membrane of a platelet;
- and, optionally,
- (c) a linker region selected from the group of amino acid sequences consisting of amino acids 133 to 157, 133 to 158, 133 to 159, 133 to 160, 133 to 165, and 133 to 170, of a urokinase-type plasminogen activator (SEQ ID NO:18);
- wherein said binding portion is linked to the linker region, if present, or to the drug, and wherein said drug is linked to the carboxy terminal of said A-chain binding portion or to the linker region, if present.
2 more elements
Dependencies are inferred from the claim text.