L-asparaginase variants and fusion proteins with reduced L-glutaminase activity and enhanced stability
AssigneeThe Board of Trustees of the University of Illinois
InventorsArnon Lavie, Hien-Anh Nguyen
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Abstract
Variant Erwinia chrysanthemi L-asparaginases with reduced L-glutaminase activity and enhanced in vivo circulation are described as are fusion proteins containing an L-asparaginase and three tandem soluble domains of TRAIL for use in the treatment of cancers such as acute lymphoblastic leukemia and acute myeloid leukemia.
Claims69
An Erwinia chrysanthemi L-asparaginase (ErA) variant comprising an amino acid substitution at (i) position 31 of SEQ ID NO:1, and (ii) position 63 or 254 of SEQ ID NO:1.
An Erwinia chrysanthemi L-asparaginase (ErA) variant comprising an amino acid substitution at one or more of positions 31, 63 and 254 of SEQ ID NO:1, wherein the ErA variant is PEGylated and further comprises a cysteine residue at position 72, 76, 79, 84, 85, 206, 210, 215, 216, 235, 239, 240, 261, 264, 265, 268, 269, 318, 322, or a combination thereof.
An Erwinia chrysanthemi L-asparaginase (ErA) variant comprising an amino acid substitution at one or more of positions 31, 63 and 254 of SEQ ID NO:1, further comprising three tandem soluble domains of TRAIL.
A fusion protein comprising an L-asparaginase linked to three tandem soluble domains of TRAIL.
Dependencies are inferred from the claim text.