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, Alfredo Quijano Rubio, Brian Weitzner
Life of this patent
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Abstract
De novo designed polypeptides that bind to IL-2 receptor βγc heterodimer (IL-2Rβγc), IL-4 receptor αγcheterodimer (IL-4Rαγc), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.
Claims23
1-138. (canceled)
A nucleic acid encoding a non-naturally occurring polypeptide comprising domains X1, X2, X3, and X4, wherein:
- (a) X1 is a peptide comprising the amino acid sequence at least 25%, 27%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% identical to 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 at least 25%, 27%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% identical to YAFNFELI (SEQ ID NO:2);
- (d) X4 is a peptide comprising the amino acid sequence at least 25%, 27%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% identical to 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 βγβ heterodimer (IL-2Rβγc), IL-4 receptor αγcheterodimer (IL-4Rαγc), or IL-13 receptor α subunit (IL-13Rα).
The nucleic acid of claim 153, wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO:
- 181.
A method for treating cancer comprising administering to a subject having cancer a polypeptide comprising domains X1, X2, X3, and X4, wherein:
- (a) X1 is a peptide comprising the amino acid sequence at least 25%, 27%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% identical to 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 at least 25%, 27%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% identical to YAFNFELI (SEQ ID NO:2);
- (d) X4 is a peptide comprising the amino acid sequence at least 25%, 27%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 100% identical to 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), IL-4 receptor αγcheterodimer (IL-4Rαγc), or IL-13 receptor α subunit (IL-13Rα).
Dependencies are inferred from the claim text.