Genentech, Inc.

Nishit B Modi

Thomas F Zioncheck

Ralph H Schwall

Steven M Chamow

Geralyn G DeGuzman

Rodney Gene Keck

Brigitte M Richard

Described herein are vascular endothelial cell growth factor (VEGF) variants having structural alterations in the C-terminus heparin binding domain and methods of use. The variants exhibit reduced clearance rates for systemic administration generally at lower doses compared with native VEGF thus providing variants having longer availability for therapeutic effect.

Methods of treatment utilizing variants of vascular endothelial cell growth factor

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 growth factor or 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.

Method of extending the plasma half-life of vascular endothelial cell

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.

Method of extending the plasma half-life of deletion variants of

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.

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San Bruno, CA, United States of America

Nishit B Modi