University of California

Omniox, Inc.

Stephen P L Cary

Jonathan A Winger

Michael A Marletta

Natacha Le Moan

Elizabeth M Boon

Gregory Kapp

Laura Serwer

Emily Weinert

Kevin G Leong

Ana Krtolica

The invention provides methods to modulate hypoxia-mediated tumor immunity by administration of an Ocarrier polypeptide (e.g., an H-NOX protein). The methods of the invention target both hypoxia inducible factor 1 alpha (HIF-1α) pathways and non-HIF-1α pathways of tumor immunity. Such methods are useful in the treatment of a wide variety of cancers and may be used alone or in combination with other anti-cancer therapies.

Modulation of tumor immunity by protein-mediated Odelivery

The invention provides polymeric H-NOX proteins for the delivery of oxygen with longer circulation half-lives compared to monomeric H-NOX proteins. Polymeric H-NOX proteins extravasate into and preferentially accumulate in tumor tissue for sustained delivery of oxygen. The invention also provides the use of H-NOX proteins as radiosensitizers for the treatment of brain cancers.

Polymeric forms of H-NOX proteins

H&#x2014;NOX proteins are mutated to exhibit improved or optimal kinetic and thermodynamic properties for blood gas Odelivery. The engineered H&#x2014;NOX proteins comprise mutations that impart altered Oor NO ligand-binding relative to the corresponding wild-type H&#x2014;NOX domain, and are operative as physiologically compatible mammalian blood Ogas carriers. The invention also provides pharmaceutical compositions, kits, and methods that use wild-type or mutant H&#x2014;NOX proteins for the treatment of any condition for which delivery of Ois beneficial.

Compositions and methods for the delivery of oxygen

H-NOX proteins are mutated to exhibit improved or optimal kinetic and thermodynamic properties for blood gas NO delivery. The engineered H-NOX proteins comprise mutations that impart altered NO or Oligand-binding relative to the corresponding wild-type H-NOX domain, and are operative as physiologically compatible mammalian blood NO gas carriers. The invention also provides pharmaceutical compositions, kits, and methods that use wild-type or mutant H-NOX proteins for the treatment of any condition for which delivery of NO is beneficial.

Compositions and methods for the delivery of nitric oxide

H-NOX proteins are mutated to exhibit improved or optimal kinetic and thermodynamic properties for blood gas Odelivery. The engineered H-NOX proteins comprise mutations that impart altered Oor NO ligand-binding relative to the corresponding wild-type H-NOX domain, and are operative as physiologically compatible mammalian blood Ogas carriers. The invention also provides pharmaceutical compositions, kits, and methods that use wild-type or mutant H-NOX proteins for the treatment of any condition for which delivery of Ois beneficial.

Growing community of inventors

San Mateo, CA, United States of America

Stephen P L Cary