β-hexosaminidase protein variants and associated methods for treating GM2 gangliosidoses

US10400227B2 · kind B2 · utility

Assignees

• University of Manitoba · CA
• The Hospital for Sick Children · CA

Inventors

• Don J. Mahuran · Toronto, CA
• Brian L. Mark · Princeton, US

Key dates

• Filing date: Mar 17, 2015
• Grant date: Sep 3, 2019
• Expiry date: Mar 17, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Y302/01052
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Embodiments herein include variants of β-hexosaminidase that are useful for hydrolyzing GM2 ganglioside, polynucleotides encoding the same, and related methods. In various embodiments, a variant β-hexosaminidase subunit is included wherein the variant β-hexosaminidase subunit forms a homodimer under physiological conditions and wherein the variant β-hexosaminidase subunit associates with GM2 activator protein to hydrolyze GM2 ganglioside. In some embodiments, an isolated or recombinant polynucleotide encoding such a variant β-hexosaminidase subunit is included. In some embodiments, a method of treating a subject exhibiting an abnormal cellular accumulation of GM2 ganglioside is included wherein the method includes administering a composition including a protein variant of β-hexosaminidase or a polynucleotide encoding the same. Other embodiments are included herein.