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AssigneeDana-Farber Cancer Institute, Inc.
InventorsLoren D. Walensky, Gregory Bird
Estimating the term…
The present invention provides stably cross-linked insulionotropic polypeptides having superior and un-expected benefits in the treatment of conditions involving abnormal glucose homeostasis, e.g., type 2 diabetes and conditions relating to type 2 diabetes. Such benefits include, but are not limited to, extended polypeptide half-life, enhanced alpha-helicity, improved thermal stability and protease resistance, increased functional activity and pharmacologic properties, improved bioavailability when administered by any route, and improved bioavailability and gastrointestinal absorption when delivered orally, as compared to the corresponding unmodified polypeptides. The invention also provides compositions for administering the polypeptides of the invention, as well as methods for pre-paring and evaluating the polypeptides of the invention.
A structurally-fortified insulinotropic polypeptide comprising an alpha helix and one or more molecular tethers, wherein each molecular tether covalently couples a single pair of residues residing on the alpha helix of said polypeptide, thereby structurally fortifying the insulinotropic polypeptide.
13-22. (canceled)
A method for treating or preventing diabetes comprising administering a therapeutically effective amount of a structurally-fortified insulinotropic polypeptide comprising an alpha helix and one or more molecular tethers, wherein each molecular tether covalently couples a single pair of non-natural amino acid residues residing on the alpha helix of said polypeptide.
32-34. (canceled)
Dependencies are inferred from the claim text.