Patent ID: 8293872
Filing Date: 2012-10-23
Classification: A61K,A61P,C12N

Abstract:
1. A method of modifying human Ribonuclease (RNase 1) to make an engineered cytotoxic RNase 1 polypeptide, the method comprising the steps of: (a) identifying electrostatic anchor amino acid residues in the three dimensional crystal structure of the human Ribonuclease Inhibitor•human Ribonuclease (hRI•RNase 1) complex defined by atomic coordinate data deposited in the Protein Data Bank (PDB) as PDB Accession No. 1Z7X and set forth in Appendix 1 of U.S. Pat. No. 7,655,757, wherein RNase 1 is defined by SEQ ID NO:2 and hRI is defined by SEQ ID NO: 4; and (b) modifying the anchor amino acid residues of RNase 1 identified in step (a) to make an engineered cytotoxic RNase 1 polypeptide, which inhibits binding to hRI through electrostatic repulsion and/or steric hindrance.