Granted Patent
B2
US 12,202,872 · App. 17/663,384 · Granted Jan 21, 2025
Interleukin-2/interleukin-2 receptor alpha fusion proteins and methods of use
Inventors:
Mary Struthers (Edison, NJ); Jonathan Harry Davis (Auburndale, MA); Michael Louis Doyle (Yardley, PA); Priyanka Apurva Madia (Franklin Park, NJ)
Assignee:
Bristol-Myers Squibb Company
C07K14/55A61K38/1793A61K38/2013A61K47/65A61P37/04C07K14/7155C07K16/2818C07K16/2827C12N15/62A61K38/00C07K2317/30C07K2319/00C07K2319/30C07K2319/31C07K2319/32C07K2319/75C07K2319/91
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Abstract
Disclosed herein are fusion proteins comprising: (a) a first polypeptide comprising Interleukin-2 (IL2); and (b) a second polypeptide, fused in frame to the first polypeptide, wherein the second polypeptide comprises an extracellular domain of Interleukin-2 Receptor alpha (IL2Rα), wherein IL2 or IL2Rα comprises at least one fewer glycosylation site compared to native IL2 or native IL2Rα. Methods of production and methods of therapeutic use of the fusion proteins are also disclosed.
Claims (19)
1. A nucleic acid that encodes a fusion protein, comprising:
(a) a first polypeptide comprising an Interleukin-2 (IL2) polypeptide, wherein the first polypeptide comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2; and
(b) a second polypeptide comprising an extracellular domain of an Interleukin-2 Receptor alpha (IL2Rα) polypeptide, wherein the second polypeptide comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 12;
wherein the extracellular domain of the IL2Rα polypeptide does not include the C-terminal portion corresponding to amino acids 192 to 219 of the extracellular domain of native IL2Rα (SEQ ID NO: 7); and
wherein the fusion protein has IL2 activity.
2. The nucleic acid of claim 1 , wherein the first polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 2.
3. The nucleic acid of claim 1 , wherein the second polypeptide comprises an amino acid sequence at least 96% identical to SEQ ID NO: 12.
4. The nucleic acid of claim 1 , wherein the first polypeptide comprises one or more substitutions at amino acids T3 and C125, compared to SEQ ID NO: 2.
5. The nucleic acid of claim 1 , wherein the second polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 12.
6. The nucleic acid of claim 1 , wherein the fusion protein further comprises a glycine/serine linker fused in frame between the first polypeptide and the second polypeptide.
7. The nucleic acid of claim 6 , wherein the glycine/serine linker comprises the amino acid sequence of (GGGS) 3 (SEQ ID NO: 71).
8. The nucleic acid of claim 1 , wherein the fusion protein comprises the amino acid sequence as set forth in any one of SEQ ID NO: 16, SEQ ID NO: 20, SEQ ID NO: 34, SEQ ID NOs: 39 to 41, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NOS: 49 to 53, SEQ ID NOs: 57 to 59, and SEQ ID NOs: 67 to 70.
9. The nucleic acid of claim 1 , wherein the fusion protein further comprises a heterologous moiety fused to the first polypeptide and/or the second polypeptide.
10. The nucleic acid of claim 9 , wherein the heterologous moiety is a half-life extending moiety.
11. The nucleic acid of claim 10 , wherein the half-life extending moiety comprises an Fc region.
12. The nucleic acid of claim 1 , wherein the fusion protein is a dimer.
13. A vector comprising the nucleic acid of claim 1 .
14. A host cell comprising the nucleic acid of claim 1 .
15. A method of producing a fusion protein, comprising: culturing the host cell of claim 14 under suitable conditions and recovering the fusion protein.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 16, 2022
From: DAVIS, JONATHAN HARRY; DOYLE, MICHAEL LOUIS; MADIA, PRIYANKA APURVA; STRUTHERS, MARY
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 060822/0045 →
Continuity (3)
Provisional Application
62649379
· Mar 28, 2018
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