TH149173A - PEG-enriched L-asparaginase - Google Patents

Abstract

DC60 (06/01/55) Disclosed is a conjugate of a protein having substantially all L-asparagine aminohydrolase activity and polyethylene glycol. Specifically, the polyethylene glycol has a molecular mass less than or equal to approximately 5000 daltons and the protein is L-asparaginase from Erwinia. The conjugate of the invention exhibits superior properties such as maintenance of a high level of activity in vitro and an unexpected increase in half-life in vivo. Also disclosed are methods of producing the conjugate and therapeutic use of the conjugate. Specifically, methods are disclosed for the use of the conjugate in the treatment of cancer, more specifically acute lymphoblastic lymphoma (ALL). Methods are also disclosed for the use of the conjugate as a second-line therapy for patients who have developed hypersensitivity or relapsed following treatment with the prepared drug. Other L-asparaginases disclosed are protein conjugates containing substantially all L-asparagine aminohydrolase activity and polyethylene glycol. Specifically, the polyethylene glycol has a molecular mass less than or equal to approximately 5000 daltons and the protein is L-asparaginase from Erwinia. The conjugates of the invention exhibit superior properties such as maintenance of high levels of activity in vitro and an unexpected increase in half-life in vivo. Also disclosed are methods of producing the conjugates and therapeutic use of the conjugates. Specifically, methods are disclosed for the use of the conjugates in the treatment of cancer, more specifically acute lymphoblastic lymphoma (ALL). Methods are also disclosed for the use of the conjugates as second-line therapy for patients who have developed hypersensitivity or relapsed following treatment with other L-asparaginase preparations.