Method of treating AML with PEGylated l-asparaginase
AssigneeJazz Pharmaceuticals II SAS
InventorThierry Abribat
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Abstract
Disclosed is L-asparagine aminohydrolase and polyethylene glycol conjugate. The polyethylene glycol has a molecular weight less than or equal to about 5000 Da and the protein is an L-asparaginase from Erwinia. The conjugate has a high level of in vitro activity and an unexpected increase in half-life in vivo. Methods of producing the conjugate and methods of using the conjugate in therapy in treatment of cancer, particularly Acute Lymphoblastic Leukemia (ALL). The method is disclosed for use of the conjugate as a second line therapy for patients who have developed hypersensitivity or have had a disease relapse after treatment with other L-asparaginase preparations.
Claims44
A method of treating acute myelocytic leukemia (AML) in a human patient, comprising:
- administering to the human patient an effective amount of a conjugate comprising four L-asparaginase monomers, wherein each of the monomers has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:
- 1 and is conjugated to at least one polyethylene glycol (PEG) molecule,
- wherein each of the at least one PEG molecule has a molecular weight of about 2000 Da to about 5000 Da;
- wherein each of the monomers comprises accessible amino groups, wherein about 100% of the accessible amino groups in the monomers are covalently linked to the PEG molecule;
- and
- wherein the human patient had previous hypersensitivity to an Escherichia coli L-asparaginase or a PEGylated form of an Escherichia coli L-asparaginase.
A method of treating acute myelocytic leukemia (AML) in a human patient, comprising:
- administering to the human patient an effective amount of a conjugate comprising four L-asparaginase monomers, wherein each of the monomers has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:
- 1 and is conjugated to at least one polyethylene glycol (PEG) molecule,
- wherein each of the at least one PEG molecule has a molecular weight of about 2000 Da;
- wherein each of the monomers comprises accessible amino groups, and wherein about 100% of the accessible amino groups are covalently linked to the PEG molecule;
- and wherein the human patient had previous hypersensitivity to an Escherichia coli L-asparaginase or a PEGylated form of an Escherichia coli L-asparaginase.
A method of treating acute myelocytic leukemia (AML) in a human patient, comprising:
- administering to the human patient an effective amount of a conjugate comprising four L-asparaginase monomers, wherein each of the monomers has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:
- 1 and is conjugated to at least one polyethylene glycol (PEG) molecule,
- wherein each of the at least one PEG molecule has a molecular weight of about 5000 Da;
- wherein each of the monomers comprises accessible amino groups, and wherein about 100% of the accessible amino groups are covalently linked to the PEG molecule;
- and wherein the human patient had previous hypersensitivity to an Escherichia coli L-asparaginase or a PEGylated form of an Escherichia coli L-asparaginase.
Dependencies are inferred from the claim text.