Method of extending the plasma half-life of deletion variants of hepatocyte growth factor
AssigneeGenentech, Inc.
InventorsSteven Chamow, Nishit Modi, Ralph Schwall, Thomas Zioncheck
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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 the cells. In one embodiment of the invention, the heparin-binding protein is a growth factor. 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.
Claims23
A method of extending the plasma half-life of hepatocyte growth factor (HGF)/NK1 comprising coadministering HGF/NK1 with an inhibitor of HGF binding to low affinity heparin-like binding sites.
A composition comprising HGF/NK1 in association with a polyanionic compound comprising dextran, dextran sulfate, heparin, or heparin sulfate.
A method for inducing hepatocyte growth comprising the intraperitoneal or subcutaneous administration to a patient a composition comprising HGF/NK1 and a polyanionic compound.
A method of extending the plasma half-life of a deletion variant of hepatocyte growth factor (HGF) comprising the n-terminal finger and first kringle domain of HGF, the method comprising:
- coadministering a therapeutically effective amount of said deletion variant with a composition comprising a polyanionic compound, which polyanionic compound inhibits binding of HGF to low affinity heparin-like binding sites.
A method for improving the therapeutic potency of a deletion variant of hepatocyte growth factor (HGF) comprising the n-terminal finger and first kringle domain of HGF, the method comprising:
- coadministering a therapeutically effective amount of said deletion variant with a composition comprising a polyanionic compound, which polyanionic compound inhibits binding of HGF to low affinity heparin-like binding sites.
A method for improving the therapeutic potency of a deletion variant of hepatocyte growth factor (HGF) comprising the n-terminal finger and first kringle domain of HGF, the method comprising:
- coadministering a therapeutically effective amount of said deletion variant with heparin, heparin sulfate, heparan sulfate, dextran sulfate, pentosan(poly)sulfate, or hyaluronate.
A method of improving the bioavailability of a subcutaneously or intraperitoneally administered deletion variant of hepatocyte growth factor (HGF) comprising the n-terminal finger and first kringle domain of HGF, the method comprising:
- coadministering said deletion variant with a compound which inhibits binding of said deletion variant to extracellular matrix.
A method for preventing the inactivation of a deletion variant of hepatocyte growth factor (HGF) comprising the n-terminal finger and first kringle domain of HGF, the method comprising:
- coadministering the deletion variant with a polyanionic compound which inhibits binding of said deletion variant to extracellular matrix.
Dependencies are inferred from the claim text.