Granted Patent
B1
US 12,286,463 · App. 18/948,648 · Granted Apr 29, 2025
Interleukin 18 (IL-18) variants and fusion proteins comprising same
Assignee:
SONNET BIOTHERAPEUTICS, INC.
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Abstract
Provided herein are variant human IL-18 (hIL-18) proteins and fusion proteins comprising the variant hIL-18 proteins. Such variant hIL-18 proteins exhibit biological IL-18 activity while having reduced or no detectable binding to inhibitory IL-18BP. Thus, in some embodiments, the variant hIL-18 proteins advantageously retain IL-18 biological activity in the presence of IL-18BP. Such variant hIL-18 and related fusion proteins find use, for example, in the treatment of cancer.
Claims (12)
1. A variant human IL-18 (hIL-18) protein comprising a substitution at amino acid positions Y1, M51, M60, S105, and D110, relative to human wild-type IL-18 (SEQ ID NO:2), wherein the substitutions are Y1W, Y1K, M51Y, M51S M60W, S105E, and D110Y.
2. The variant hIL-18 protein of claim 1 , wherein the variant hIL-18 protein further comprises one or more of the following amino acid substitutions: C38S, C68S, C76S, and/or C127S.
3. A variant hIL-18 protein comprising amino acid substitutions Y1W, C38S, M51Y, M60W, C68S, C76S, D110Y, and C127S, relative to human wild-type IL-18 (SEQ ID NO:2).
4. The variant hIL-18 protein of claim 3 comprising an amino acid sequence as set forth in SEQ ID NO:3.
5. A variant hIL-18 protein comprising amino acid substitutions Y1K, C38S, M51S, M60W, C68S, C76S, S105E, D110Y, and C127S, relative to human wild-type IL-18 (SEQ ID NO:2).
6. The variant hIL-18 protein of claim 5 comprising an amino acid sequence as set forth in SEQ ID NO:4.
7. The variant hIL-18 protein of claim 1 , wherein the variant hIL-18 protein exhibits reduced or no detectable binding to IL-18 binding protein as compared to wild-type hIL-18 (SEQ ID NO:2).
8. The variant hIL-18 protein of claim 1 , wherein the variant hIL-18 protein has increased IL-18 activity in the presence of IL-18 binding protein as compared to wild-type hIL-18 (SEQ ID NO:2).
9. A nucleic acid encoding the variant hIL-18 protein of claim 1 .
10. An expression vector comprising the nucleic acid of claim 9 .
11. A host cell comprising the expression vector of claim 10 .
12. A method of making a variant hIL-18 protein comprising culturing the host cell of claim 11 under conditions wherein the variant hIL-18 protein is expressed, and recovering the variant hIL-18 protein.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 1, 2026
From: SONNET BIOTHERAPEUTICS, INC.
To: GUIDANT BIOTHERAPEUTICS, INC.
Reel/Frame 074543/0675 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 20, 2024
From: CINI, JOHN K.; DEXTER, SUSAN J.
To: SONNET BIOTHERAPEUTICS, INC.
Reel/Frame 069649/0169 →
Continuity (3)
Continuation
18740390
· Jun 11, 2024
Provisional Application
63658322
· Jun 10, 2024
Provisional Application
63616148
· Dec 29, 2023
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