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AssigneeThe Hong Kong Polytechnic University
InventorsYun Chung Leung, Wai-hung Lo
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Mono-pegylated arginase conjugate and method producing thereof. The mono-pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method of producing such arginase conjugate has a main step of genetically modifying the gene encoding an arginase so that the PEG moiety can attach to the enzyme at a predetermined, specific intended site. This is achieved by removing the PEG attaching amino acid residues at undesirable sites while keeping (or adding, if necessary) the one at the desirable site of the enzyme. Two exemplary mono-pegylated arginase conjugates so produced are human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.
A pharmaceutical composition for treating an arginine-dependent disease comprising a polyethylene glycol-arginase conjugate having a polyethylene glycol moiety covalently attached to a genetically-modified human arginase, wherein said genetically-modified human arginase has a single amino acid position for covalently attaching to the polyethylene glycol moiety, wherein said polyethylene glycol-arginase conjugate has a serum circulation half-life higher than the serum circulation half-life of pure, unmodified human arginase, wherein said polyethylene glycol-arginase conjugate has decreased immunogenicity compared to the immunogenicity of pure, unmodified human arginase, wherein said single amino acid position is sufficiently far from the active site of the genetically-modified human arginase such that the polyethylene glycol attachment does not interfere with the active site, wherein the genetically-modified human arginase comprises SEQ ID NO:
A pharmaceutical composition for treating an arginine-dependent disease comprising a polyethylene glycol-arginase conjugate having a polyethylene glycol moiety covalently attached to a genetically-modified Bacillus caldovelox arginase, wherein said genetically-modified Bacillus caldovelox arginase has a single amino acid position for covalently attaching to the polyethylene glycol moiety, wherein said polyethylene glycol-arginase conjugate has a serum circulation half-life higher than the serum circulation half-life of pure, unmodified Bacillus caldovelox arginase, wherein said polyethylene glycol-arginase conjugate has decreased immunogenicity compared to the immunogenicity of pure, unmodified Bacillus caldovelox arginase, wherein said single amino acid position is sufficiently far from the active site of the genetically-modified Bacillus caldovelox arginase such that the polyethylene glycol attachment does not interfere with the active site, wherein the genetically-modified Bacillus caldovelox arginase comprises SEQ ID NO:
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