Wisconsin Alumni Research Foundation

University of California

Quintessence Biosciences, Inc.

Thomas J Rutkoski

Ronald Thaddeus Raines

Julie C Mitchell

John A Kink

Laura Strong

Laura E Strong

This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.

Cytotoxic ribonuclease variants

The present invention relates generally to conjugates of human ribonucleases and water-soluble polymers, compositions comprising the conjugates and methods of using the same. In particular, the present invention provides conjugates of human ribonucleases and one or more water-soluble polymer compositions (e.g., to increase serum half-life and a pharmacokinetic profile, in vivo biological activity, stability, and/or reduce host immune response to the protein in vivo) as well as methods of using the conjugates in the therapy, treatment, and/or prevention of disease (e.g., cancer).

Compositions and methods for ribonuclease-based therapeutics

Method for delivering cytotoxic activity to cells

Nucleic acid constructs encoding cytotoxic ribonuclease variants

Growing community of inventors

Madison, WI, United States of America

Thomas J Rutkoski