Compositions of engineered human arginases and methods for treating cancer

Abstract

Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.

1 - 45 . (canceled) 
     
     
         46 . A pharmaceutical composition comprising an isolated human Arginase I and a non-native metal cofactor, wherein the non-native metal cofactor is cobalt, the composition being at physiological pH. 
     
     
         47 . The composition of  claim 46 , wherein the amino acid sequence lacks an N-terminal methionine. 
     
     
         48 . The composition of  claim 46 , wherein the human Arginase I is covalently linked to polyethylene glycol.