Therapeutic agents comprising elastic peptides
AssigneeDuke University
InventorAshutosh Chilkoti
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Abstract
The present invention provides therapeutic agents and compositions comprising elastic peptides and therapeutic proteins. Such peptides exhibit a flexible, extended conformation. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist (e.g., GLP-1, exendin), insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.
Claims20
1-39. (canceled)
A therapeutic agent comprising a recombinant fusion between an elastic polypeptide and a therapeutic peptide, the therapeutic agent being formulated with a pharmaceutically acceptable carrier or excipient suitable for parenteral administration, and the therapeutic agent having an extended circulatory half-life when compared to the therapeutic peptide alone, wherein:
- the therapeutic peptide comprises insulin and is at the N-terminus of the therapeutic agent;
- and
- the elastic polypeptide is not less than 50 kDa and has a pattern of proline-containing beta-turns forming an extended, non-globular structure, with no tertiary structure.
A therapeutic agent comprising a recombinant fusion between an elastic polypeptide and a therapeutic peptide, the therapeutic agent being formulated with a pharmaceutically acceptable carrier or excipient suitable for parenteral administration, and the therapeutic agent having an extended circulatory half-life when compared to the therapeutic peptide alone, wherein:
- the therapeutic peptide comprises insulin and is at the N-terminus of the elastic polypeptide;
- the elastic polypeptide has a pattern of proline-containing beta-turns forming an extended, non-globular structure, with no tertiary structure,
- the elastic polypeptide consisting essentially of glycine and hydrophobic amino acids selected from alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, and methionine, and optionally serine, threonine, and glutamic acid, and
- the elastic polypeptide has a molecular weight of not less than 50 kDa.
Dependencies are inferred from the claim text.