Patent ID: 8871906

Claim:
An isolated, mutated Pseudomonas exotoxin A (PE), comprising an amino acid sequence lacking all of domain II except for a furin cleavage sequence, and comprising an amino acid sequence of Formula I: R 1 n -FCS-R 2 n -R 3 n -PE functional domain III (Formula I) wherein: n=0 or 1, independently, for each of R 1 , R 2 and R 3 ; R 1 =1 to 10 amino acid residues; FCS=a furin cleavage sequence of 4 to 11 amino acid residues, which sequence is cleavable by furin and has an amino end and a carboxyl end, wherein the FCS: (a) comprises an amino acid sequence of P4-P3-P2-P1 (Formula II), wherein P4 is an amino acid residue at the amino end, P3 is an amino acid residue, P2 is an amino acid residue, P1 is an amino acid residue at the carboxyl end, P1 is an arginine or a lysine residue, and the amino acid sequence is cleavable at the carboxyl end of P1 by furin; or (b) is selected from SEQ ID NOs: 12-20; or (c) is SEQ ID NO: 10, or a truncated version thereof comprising RQPR (SEQ ID NO: 21); or (d) is SEQ ID NO: 11, or a truncated version thereof comprising RSKR (SEQ ID NO: 26); R 2 =1 to 10 amino acid residues; R 3 =1 or more contiguous amino acid residues of residues 365-394 of SEQ ID NO: 1; and PE functional domain III=residues 395-613 of SEQ ID NO: 1, optionally comprising: (i) a substitution of one or more of amino acid residues 609-613 as defined by reference to SEQ ID NO: 1; (ii) a substitution of amino acid residue R490, as defined by reference to SEQ ID NO: 1, with glycine, alanine, valine, leucine, or isoleucine; (iii) a substitution of one or more amino acid residues in an epitope or a subepitope of PE domain III; or (iv) a combination of any of (i)-(iii).