Patent ID: 7655757

Claim:
An engineered human Ribonuclease (RNase 1) polypeptide differing in amino acid sequence from an RNase 1 protein comprising SEQ ID NO:2 by at least two amino acid substitutions, which electrostatically repel and/or sterically hinder binding by human Ribonuclease Inhibitor (hRI) to the engineered RNase 1, a first amino acid change located within residues 85 to 94 of SEQ ID NO:2, and a second amino acid change being at least one substitution of at least one amino acid residue wherein the at least one amino acid residue is selected from the group consisting of an amino acid residue located at position 7, 11, 31, 32, 38, 39, 41, 42, 66, 67, 71, 111, and 118 of SEQ ID NO:2, wherein the engineered RNase 1 has the following biological properties: (i) retains ribonucleolytic activity, (ii) exhibits enhanced cytotoxic activity relative to SEQ ID NO: 2, and (iii) has a lower binding affinity for hRI than SEQ ID NO:2.