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US 10,704,038 B2Granted
Therapeutic fusion proteins
AssigneeIpsen Bioinnovation Limited
InventorsJohn Chaddock, Elaine Harper
Life of this patent
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Abstract
The present invention relates to the construction of a new class of Targeted Secretion Inhibitors (TSIs), which comprise a non-cytotoxic protease, translocation peptide and a targeting moiety peptide, wherein the targeting moiety peptide has a free N-terminal domain and a free C-terminal domain; to a single-chain fusion protein precursor thereof, and to a method of activating said single-chain fusion protein precursor.
Claims19
A nucleic acid encoding a single-chain polypeptide fusion protein comprising:
- (a) a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a target cell;
- (b) a targeting moiety capable of binding to a binding site on the target cell, which binding site is capable of undergoing endocytosis and being incorporated into an endosome within the target cell;
- (c) a translocation domain capable of translocating the protease from within an endosome, across the endosomal membrane, and into the cytosol of the target cell;
- (d) a first cleavage site that is cleavable by a protease, wherein the first cleavage site is located between the non-cytotoxic protease and the translocation domain;
- and
- (e) a second cleavage site that is cleavable by a protease, wherein the second cleavage site is located between the translocation domain and the targeting moiety and is not a destructive cleavage site;
- wherein the targeting moiety and the translocation domain are capable of forming a covalent linkage such that, following proteolytic cleavage at the second cleavage site, the targeting moiety remains linked to the translocation domain by the covalent linkage.
4 more elements
Dependencies are inferred from the claim text.