US 11,655,278 B2
De novo design of potent and selective interleukin mimetics
Daniel Adriano Silva Manzano, Seattle, WA (US); Shawn Yu, Seattle, WA (US); David Baker, Seattle, WA (US); Kenan Christopher Garcia, Stanford, CA (US); Jamie Spangler, Stanford, CA (US); Carl Walkey, Seattle, WA (US); and Umut Ulge, Seattle, WA (US)
Assigned to UNIVERSITY OF WASHINGTON, Seattle, WA (US); and THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
Filed by UNIVERSITY OF WASHINGTON, Seattle, WA (US); and THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
Filed on Sep. 13, 2021, as Appl. No. 17/473,731.
Application 17/473,731 is a continuation of application No. 16/905,669, filed on Jun. 18, 2020, granted, now 11,117,944, issued on Sep. 14, 2021.
Application 16/905,669 is a continuation of application No. 16/572,038, filed on Sep. 16, 2019, granted, now 10,703,791, issued on Jul. 7, 2021.
Application 16/572,038 is a continuation of application No. PCT/US2019/038703, filed on Jun. 24, 2019.
Claims priority of provisional application 62/689,769, filed on Jun. 25, 2018.
Claims priority of provisional application 62/768,733, filed on Nov. 16, 2018.
Prior Publication US 2022/0056095 A1, Feb. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/55 (2006.01); C07K 14/54 (2006.01); A61K 47/62 (2017.01); A61K 47/60 (2017.01); A61K 38/00 (2006.01)
CPC C07K 14/55 (2013.01) [A61K 47/60 (2017.08); A61K 47/62 (2017.08); C07K 14/5406 (2013.01); C07K 14/5437 (2013.01); C07K 14/5443 (2013.01); A61K 38/00 (2013.01); C07B 2200/13 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01); C07K 2319/74 (2013.01)] 20 Claims
 
1. A non-naturally occurring polypeptide comprising domains X1, X2, X3, and X4, wherein:
(a) X1 is a peptide comprising an amino acid sequence at least 80% identical to the amino acid sequence PKKKIQLHAEHALYDALMILNI (SEQ ID NO: 4);
(b) X2 is a helical-peptide of at least 8 amino acids in length that has no binding site for the IL-2 receptor α subunit (IL-2Rα);
(c) X3 is a peptide comprising an amino acid sequence at least 80% identical to the amino acid sequence LEDYAFNFELILEEIARLFESG (SEQ ID NO:5); and
(d) X4 is a peptide comprising an amino acid sequence at least 80% identical to the amino acid sequence EDEQEEMANAIITILQSWIFS (SEQ ID NO:6);
wherein the domains are arranged N-terminal to C-terminal in an arrangement X1-X3-X2-X4;
wherein amino acid linkers may be present between any of the domains; and
wherein the polypeptide binds to the IL-2 receptor βcustom characterc heterodimer (IL-2Rβcustom characterc).