De novo design of potent and selective interleukin mimetics
AssigneesUniversity of Washington, The Board of Trustees of the Leland Stanford Junior University
InventorsDaniel Adriano Silva Manzano, Shawn Yu, Umut Ulge, David Baker, Kenan Christopher Garcia, Jamie Spangler, Carl Walkey
Life of this patent
Estimating the term…
Abstract
De novo designed polypeptides that bind to IL-2 receptor βγc heterodimer (IL-2Rβγc), IL-4 receptor αγc heterodimer (IL-4Rαγc), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.
Claims29
A non-naturally occurring polypeptide comprising domains X1, X2, X3, and X4, wherein:
- (a) X1 is a peptide comprising the amino acid sequence EHALYDAL (SEQ ID NO:1);
- (b) X2 is a helical-peptide of at least 8 amino acids in length;
- (c) X3 is a peptide comprising the amino acid sequence YAFNFELI (SEQ ID NO:2);
- and
- (d) X4 is a peptide comprising the amino acid sequence ITILQSWIF (SEQ ID NO:3);
- wherein X1, X2, X3, and X4 may be in any order in the polypeptide;
- wherein amino acid linkers may be present between any of the domains;
- and
- wherein the polypeptide binds to IL-2 receptor βγc heterodimer (IL-2Rβγc).
A non-naturally occurring polypeptide comprising domains X1, X2, X3, and X4, wherein:
- X1 is a peptide comprising an amino acid sequence at least 80% identical to the peptide PKKKIQLHAEHALYDALMILNI (SEQ ID NO:
- 4);
- X2 is a helical-peptide of at least 8 amino acids in length;
- X3 is a peptide comprising an amino acid sequence at least 80% identical to the peptide LEDYAFNFELILEEIARLFESG (SEQ ID NO:
- 5);
- and
- X4 is a peptide comprising an amino acid sequence at least 80% identical to the peptide EDEQEEMANAIITILQSWIFS (SEQ ID NO:
- 6);
- wherein X1, X2, X3, and X4 may be in any order in the polypeptide;
- wherein amino acid linkers may be present between any of the domains;
- and
- wherein the polypeptide binds to IL-2 receptor βγc heterodimer (IL-2Rβγc).
A non-naturally occurring polypeptide, wherein the polypeptide comprises a polypeptide at least 80% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS:
- 90 or 181, wherein the polypeptide binds to IL-2 receptor βγc heterodimer (IL-2Rβγc).
Dependencies are inferred from the claim text.