Ligands modified by circular permutation as agonists and antagonists
AssigneeAlkermes, Inc.
InventorJuan Alvarez
Life of this patent
Estimating the term…
Abstract
The present invention provides fusion polypeptides comprising polypeptide ligands that are modified by circular permutation and fused to at least one polypeptide fusion partner wherein such fusion polypeptides have new, improved or enhanced biological functions or activities. Such improvements include, but are not limited to, increased binding affinity, increased activity, increased agonist activity (super agonist), antagonist activity, increased accessibility, increased flexibility of the active site, increased stability, broader and/or changed substrate specificity, and combinations thereof.
Claims5
A fusion polypeptide comprising a first polypeptide fusion partner linked to a modified ligand corresponding to all or a portion of a native ligand of a target receptor, wherein the modified ligand has been circularly permuted to create a new N-terminus and a new C-terminus as compared to the native ligand, wherein the new C-terminus and the new N-terminus of the modified ligand do not disrupt any binding domain of the modified ligand for the target receptor, wherein the modified ligand is circularly permuted IL-15, the fusion partner is IL-15Rα and the target receptor is IL-2Rβγ.
Dependencies are inferred from the claim text.