Genentech, Inc.

Thomas F Zioncheck

Nishit B Modi

Ralph H Schwall

Steven M Chamow

Rodney Gene Keck

Geralyn G DeGuzman

Ben-Quan Shen

Brigitte M Richard

Described herein are pharmaceutical compositions including vascular endothelial cell growth factor (VEGF) variants having modifications in the C-terminal heparin binding domain. 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.

Pharmaceutical compositions including variants of vascular endothelial cell growth factor having altered pharmacological properties

The present invention provides uses of VEGF or VEGF receptor agonists for the up-regulation of eNOS expression and activity. VEGF and VEGF receptor agonists are useful in the treatment of or prevention from hypertension, diabetes, angina, thrombosis, atherosclerosis, heart failure, and other conditions or disorders wherein nitric oxide is an important regulator.

Modulation of eNOS activity and therapeutic uses thereof

Described herein are vascular endothelial cell growth factor (VEGF) variants having modifications in the C-terminus heparin binding domain. 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.

Variants of vascular endothelial cell growth factor having altered pharmacological properties, and recombinant methods of production

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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Montara, CA, United States of America

Thomas F Zioncheck