Patent ID: 9657066
Date: 2017-05-23
CPC Classifications: A61K,A61P,C07K

Claim:
1. A Pseudomonas exotoxin A (PE) comprising the amino acid sequence comprising Formula I: wherein: m, n, and p are, independently, 0 or 1; FCS comprises a furin cleavage sequence of amino acid residues, which sequence is cleavable by furin; R R R PE functional domain III comprises residues 395-613 of SEQ ID NO: 1 having a substitution of one or more of amino acid residues selected from the group consisting of E420, D463, Y481, L516, R563, and D581, as defined by reference to SEQ ID NO: 1, with the proviso that when the amino acid residue at position 516 is substituted with alanine, at least one of amino acid residues E420, D463, Y481, R563, and D581 is substituted, wherein the PE has a further substitution of one or more amino acid residues within one or more B cell epitopes, and the further substitution for an amino acid within one or more B-cell epitopes is a substitution of, independently, one or more of amino acid residues selected from the group consisting of E282, E285, P290, R313, N314, P319, D324, E327, E331, Q332, D403, D406, R412, R427, E431, R432, R458, D461, R467, R490, R505, R513, E522, R538, E548, R551, R576, Q592, and L597, as defined by reference to SEQ ID NO: 1, and wherein the PE optionally has a further substitution of one or more amino acid residues within one or more T-cell epitopes.