Activatable cytokine polypeptides and methods of use thereof

US12076371B2 · kind B2 · utility

Assignee

• Werewolf Therapeutics, Inc. · US

Inventors

• William Winston · Marlborough, US
• Daniel Hicklin · Montclair, US
• Jose Andres Salemeron-Garcia · Acton, US
• Heather Brodkin · Newton, US
• Cynthia Seidel-Dugan · Belmont, US

Key dates

• Filing date: Feb 9, 2023
• Grant date: Sep 3, 2024
• Expiry date: Feb 9, 2043

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/50
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g., a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.