Inhibition of heparin-binding
AssigneeGenentech, Inc.
InventorsSteven Chamow, Nishit Modi, Ralph Schwall, Thomas Zioncheck
Life of this patent
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Abstract
The invention provides a method for extending the plasma half-life of heparin-binding proteins by coadministering such proteins with a therapeutically acceptable compound capable of inhibiting their binding to a low affinity heparin-like binding site on the surface of cells. In one embodiment of the invention, the-heparin-binding protein is a selectin. The binding inhibitory compound can, for example, be a purified native heparin preparation, a heparin fragment, or another polyanionic compound, such as dextran sulfate, heparan sulfate, pentosan sulfate, or hyaluronate.
Claims27
A method of extending the plasma half-life of a selectin comprising coadministering a therapeutically effective amount of said selectin with a therapeutically acceptable compound capable of inhibiting the binding of said selectin to a low affinity heparin-like binding site on the surface of cells of an organ perfused with blood.
A method for improving the therapeutic potency of a selectin comprising coadministering a therapeutically effective amount of said selectin with a therapeutically acceptable polyanionic compound.
A method of improving the bioavailability of a subcutaneously or intraperitoneally administered selectin comprising coadministering said selectin with a therapeutically acceptable compound capable of inhibiting the interaction of said selectin with heparin or a substance which is a functional derivative of heparin in an extracellular matrix.
A method for preventing the inactivation of a selectin by a blood protein, which comprises coadministering an effective dose of said selectin with a polyanionic compound.
A pharmaceutical composition comprising a therapeutically effective amount of a selectin in association with a polyanionic compound.
A method for enhancing the sensitivity of an assay for the detection of a selectin in a test sample, comprising supplementing said test sample with a polyanionic compound selected from the group consisting of heparin, dextran, dextran sulfate, heparan sulfate, pentosan sulfate, and hyaluronate.
Dependencies are inferred from the claim text.