US 12,343,379 B2
Interleukin-18 variants and methods of use
Aaron Ring, New Haven, CT (US); Ting Zhou, New Haven, CT (US); and Suzanne Fischer, New Haven, CT (US)
Assigned to YALE UNIVERSITY, New Haven, CT (US)
Filed by YALE UNIVERSITY, New Haven, CT (US)
Filed on Nov. 15, 2022, as Appl. No. 18/055,581.
Application 18/055,581 is a division of application No. 16/123,063, filed on Sep. 6, 2018, abandoned.
Claims priority of provisional application 62/554,605, filed on Sep. 6, 2017.
Claims priority of provisional application 62/652,279, filed on Apr. 3, 2018.
Prior Publication US 2023/0241172 A1, Aug. 3, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/20 (2006.01); C07K 14/54 (2006.01); A61K 35/17 (2025.01); A61K 35/768 (2015.01); A61K 38/17 (2006.01); A61K 47/64 (2017.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C12N 15/85 (2006.01)
CPC A61K 38/20 (2013.01) [C07K 14/54 (2013.01); A61K 35/17 (2013.01); A61K 35/768 (2013.01); A61K 38/1774 (2013.01); A61K 47/642 (2017.08); A61K 2300/00 (2013.01); A61P 35/00 (2018.01); C07K 14/70596 (2013.01); C07K 2319/02 (2013.01); C07K 2319/21 (2013.01); C07K 2319/35 (2013.01); C07K 2319/50 (2013.01); C12N 15/85 (2013.01)] 5 Claims
OG exemplary drawing
 
1. A method of promoting interleukin-18 (IL-18) signaling activity in a subject in need thereof, comprising administering to the subject a composition comprising a nucleic acid encoding a modified IL-18 polypeptide that specifically binds to the IL-18 receptor (IL-18R) and exhibits reduced binding to the IL-18 binding protein (IL-18BP) as compared to wild type (WT) IL-18 as set forth in SEQ ID NO: 30, wherein the modified IL-18 polypeptide comprises 90% or more sequence identity with WT IL-18 as set forth in SEQ ID NO:30 and at least four amino acid substitutions, relative to WT IL-18 as set forth in SEQ ID NO:30, at positions selected from: Methionine-51, Glutamine-56, Proline-57, Methionine-60, Glutamine-103, Serine-105, Aspartic acid-110, Asparagine-111, and Methionine-113.