THE GOVERNMENT OF THE UNITED STATES OF AMERICA ASREPRESENTED BY THE SECRETARY OF THE DEPARTMENT OFHEALTH AND HUMAN SERVICES
发明人:
PASTAN IRA H.,WELDON JOHN,BEERS RICHARD
申请号：
NZ61738612
公开号：
NZ617386A
申请日:
2012.05.04
申请国别(地区):
NZ
年份:
2015
代理人:
摘要：
Discloses a chimeric molecule comprising a fusion polypeptide having the formula M-L1-FCS-FL-functional PE domain III characterised by an improved cytotoxicity for cells expressing mesothelin, wherein: M is an antibody which specifically binds to mesothelin, or a fragment thereof that specifically binds mesothelin； L1 consists of from 1 to 10 continuous amino acid residues； FCS is a furin cleavage site consisting of continuous amino acid residues capable of being cleaved by furin； FL consists of from 3 to 8 continuous amino acid residues selected independently from glycine and serine； Functional PE domain III consists of continuous amino acid residues identical in sequence to SEQ ID NO:1 from position 395 to 613, optionally comprising (i) a substitution of one or more residues corresponding to 609-613 of SEQ ID NO:1, (ii) a substitution of glycine, alanine, valine, leucine, or isoleucine for arginine at a position corresponding to position 490 of SEQ ID NO:1, (iii) a substitution of, independently, alanine, glycine, serine, or glutamine in place of one or more residues corresponding to residues D403, D406, R412, R427, E431, R432, R458, D461, R467, R490, R505, R513, E522, R538, E548, R551, R576, K590, Q592, and L597 of SEQ ID NO:1, which residues of SEQ ID NO:1 maintain immunogenicity of an epitope or subepitope of PE domain III, or (iv) a combination of any of (i)-(iii).
