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AssigneesThe Governing Council of the University of Toronto, The Regents of the University of California, Yeda Research and Development Co. Ltd.
InventorsMolly S. SHOICHET, Marian H. HETTIARATCHI, Teresa R. O'MEARA, Matthew J. O'MEARA
Estimating the term…
The present application provides a Chondroitinase ABC (ChABC) mutants. ChABC stimulates axonal regeneration by degrading the inhibitory chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans in the glial scar that forms after traumatic injuries to the central nervous system (CNS). However, the therapeutic utility of this potent, fragile protein is severely limited by rapid aggregation at physiological temperature. To overcome this limitation, the ChABC mutants were engineered to at least 15 point mutations in domain 2 of the wild-type ChABC and/or at least 5 point mutations in domain 3 of the wild-type enzyme. These mutants exhibit improved stability over wild-type ChABC. The present application further provides method and compositions comprising the mutant ChABC for treating conditions associated with excess proteoglycan formation or conditions for which treatment is benefitted by degradation of proteoglycans, including CNS injuries, scarring and cancer.
A mutant of a wild-type chondroitinase ABC (ChABC) having ChABC activity, a melting temperature that is at least 4° C. higher than the melting temperature of the wild-type ChABC and a functional half-life that is at least 4 times longer than that of the wild-type ChABC.
A mutant of a wild-type ChABC said mutant having ChABC activity, a melting temperature that is at least 4° C. higher than the melting temperature of the wild-type ChABC and a functional half-life that is at least 4 times longer than that of the wild-type ChABC, wherein the mutant comprises at least 15 point mutations in domain 2 of the wild-type ChABC and/or at least 5 point mutations in domain 3 of the wild-type enzyme.
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Dependencies are inferred from the claim text.