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AssigneeWerewolf Therapeutics, Inc.
InventorsWilliam WINSTON, Heather BRODKIN, Cynthia SEIDEL-DUGAN, Daniel HICKLIN, Jose Andres SALMERON-GARCIA
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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.
A fusion polypeptide comprising at least one of each of:
The fusion polypeptide of claim 8 wherein each protease-cleavable polypeptide independently comprises two or more cleavage sites for the same protease, or two or more cleavage sites that are cleaved by different proteases or at least one of the protease-cleavable polypeptides comprises a cleavage site for two or more different proteases.
A fusion polypeptide comprising at least one of each of:
The fusion polypeptide of any one of claims 31-0, wherein the interferon is free to dissociate from the interferon blocking moiety after the protease-cleavable polypeptide linker is cleaved by a protease.
The fusion polypeptide of claim-46, wherein the half-life extension element sterically inhibits or blocks activation and/or binding of the interferon polypeptide to its cognate receptor.
Dependencies are inferred from the claim text.