Oligoadenylate Synthetase (OAS)
The invention describes novel pharmaceutical compositions for the treatment of virus infections and cancer. The pharmaceutical compositions include mutant oligoadenylate synthetases (OAS) that have either enhanced cell permeability, reduced oxidative potential, improved antiviral activity, improved enzymatic activity, or absent enzymatic activity. The pharmaceutical compositions have improved drug properties and retain or have enhanced antiviral activity relative to their native forms. The pharmaceutical compositions further include chemically modified oligoadenylate synthetases, such chemical modifications being designed to increase serum stability and reduce immunogenicity in vivo. Such chemical modifications further increase drug stability and manufacturability in vitro. Compositions composed of more than ninety novel modifications are described. Also described are antibodies to polypeptides of the invention.
1. An isolated polypeptide consisting of an enzymatically inactive 2′,5′ oligoadenylate synthetase (OAS) of SEQ ID NO:1 except that alanine is at position 75 of SEQ ID NO:1 and/or position 77 of SEQ ID NO:1 wherein said polypeptide retains antiviral activity.
2. The isolated OAS polypeptide of claim 1 , wherein said polypeptide is modified with polyethylene glycol.
3. The polypeptide of claim 2 , wherein said polypeptide is covalently bonded to polyethylene glycol at one or more cysteine residues.
4. A pharmaceutical composition comprising a polypeptide of claim 1 or 2 .