Engineered TGF-β monomers and their use for inhibiting TGF-β signaling

US11091523B2 · kind B2 · utility

Assignees

• University of Pittsburgh—Of the Commonwealth System of Higher Education · US
• National Research Council of Canada · CA

Inventors

• Andrew Peterson Hinck · Pittsburgh, US
• Traian Sulea · Kirkland, CA

Key dates

• Filing date: Nov 17, 2017
• Grant date: Aug 17, 2021
• Expiry date: Nov 17, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/31
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Recombinant transforming growth factor (TGF)-β monomers modified to inhibit dimerization and block TGF-β signaling are described. The recombinant TGF-β monomers lack the ability to bind and recruit TGF-β type I receptor (TβRI), but retain the capacity to bind the high affinity TGF-β type II receptor (TβRII), and in some instances, include mutations that increase their affinity for TβRII. Nucleic acid molecules and vectors encoding the recombinant TGF-β monomers are also described. Isolated cells, such as T cells, can be re-programmed with a TGF-β monomer-encoding nucleic acid or vector to secrete the monomer. Use of the recombinant TGF-β monomers and/or cells producing the recombinant TGF-β monomers, to inhibit TGF-β signaling, such as to treat disorders associated with aberrant TGF-β signaling, are also described.