IP Library › Granted Patent US 11,999,771
Granted Patent B2
US 11,999,771 · App. 18/061,567 · Granted Jun 4, 2024

IL-7Rαγc ligand immunoglobulin fusion proteins

Inventors: William J. Dower (Menlo Park, CA); Ronald W. Barrett (Menlo Park, CA); Michael C. Needels (Menlo Park, CA); Steven E. Cwirla (Menlo Park, CA); Alice V. Bakker (Menlo Park, CA); Inkyung Park (Menlo Park, CA)
Assignee: Medikine, Inc.
C07K14/5418A61K38/2046A61K38/00C07K7/08C07K14/7155C07K2319/30
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Quick Facts
Patent No.
US 11,999,771
App. No.
18/061,567
Granted
Jun 4, 2024
Kind
B2
Abstract

IL-7Rαγc ligands and IL-7Rαγc IgG-Fc fusion proteins are disclosed. The IL-7Rαγc ligands and IL-7Rαγc IgG-Fc fusion proteins are IL-7R agonists.

Claims (49)

1. An IL-7Rαγc ligand comprising:

an IL-7Rα ligand comprising an amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having greater than 70% sequence similarity to SEQ ID NO: 1; and

an Rγc ligand comprising an amino acid sequence of SEQ ID NO: 11 or an amino acid sequence having greater than 70% sequence similarity to SEQ ID NO: 11.

2. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises:

an IL-7Rα ligand comprising an amino acid sequence of SEQ ID NO: 1 and

an Rγc ligand comprising an amino acid sequence of SEQ ID NO: 11.

3. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises:

an IL-7Rα ligand comprising an amino acid sequence having greater than 70% sequence similarity to SEQ ID NO: 1; and

an Rγc ligand comprising an amino acid sequence having greater than 70% sequence similarity to SEQ ID NO: 11.

4. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises:

an IL-7Rα ligand comprising an amino acid sequence based on SEQ ID NO: 1 and having from 1 to 5 amino acid substitutions; and

an Rγc ligand comprising an amino acid sequence based on SEQ ID NO: 11 and having from 1 to 5 amino acid substitutions.

5. The IL-7Rαγc ligand of claim 1 , wherein each of the IL-7Rα ligand and the Rγc ligand independently comprises from 1 to 6 glycines (G) on the N-terminus, on the C-terminus, or on both the N-terminus and the C-terminus.

6. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rα ligand and the Rγc ligand are bound together through a ligand linker.

7. The IL-7Rαγc ligand of claim 6 , wherein the ligand linker comprises an amino acid sequence selected from any one of SEQ ID NO: 113-136.

8. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises:

an amino acid sequence of any one of SEQ ID NO: 21-26 or an amino acid sequence having greater than 70% sequence similarity to any one of SEQ ID NO: 21-26:

WGIPWCTLDPGSLQCAWLGKH-X 1 -VVCQDWEGVELCWQ (SEQ ID NO: 21)

GWGIPWCTLDPGSLQCAWLGKH-X 1 -VVCQDWEGVELCWQ (SEQ ID NO: 22)

WGIPWCTLDPGSLQCAWLGKH-X 1 -VVCQDWEGVELCWQGG (SEQ ID NO: 23)

GWGIPWCTLDPGSLQCAWLGKH-X 1 -VVCQDWEGVELCWQGG (SEQ ID NO: 24)

GGWGIPWCTLDPGSLQCAWLGKH-X 1 -VVCQDWEGVELCWQGG (SEQ ID NO: 25)

GGGWGIPWCTLDPGSLQCAWLGKH-X 1 -VVCQDWEGVELCWQGG (SEQ ID NO: 26);

and wherein X 1 is selected from an amino acid sequence of any one of SEQ ID NO: 101-143.

9. The IL-7Rαγc ligand of claim 8 , wherein X 1 is selected from of any one of SEQ ID NO: 137-143.

10. The IL-7Rαγc ligand of claim 8 , wherein X 1 has an amino acid sequence of SEQ ID NO: 139.

11. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises an amino acid sequence of any one of SEQ ID NO: 27-32, or an amino acid sequence having greater than 70% sequence similarity to any one of SEQ ID NO: 27-32.

12. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises an amino acid sequence of SEQ ID NO: 32 or an amino acid sequence having greater than 70% sequence similarity to SEQ ID NO: 32.

13. An IL-7Rαγc IgG-Fc fusion fragment comprising the IL-7Rαγc ligand of claim 1 bound to an IgG-Fc fragment.

14. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IgG-Fc fragment is selected from an IgG1-Fc fragment, an IgG2-Fc fragment, and an IgG4-Fc fragment.

15. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IgG-Fc fragment is an IgG2-Fc fragment.

16. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IL-7Rαγc ligand is bound to the IgG-Fc fragment through an IgG-Fc linker.

17. The IL-7Rαγc IgG-Fc fusion fragment of claim 16 , wherein the IgG-Fc linker comprises an amino acid sequence of any one of SEQ ID NO: 150-179.

18. The IL-7Rαγc IgG-Fc fusion fragment of claim 16 , wherein the IgG-Fc linker comprises an amino acid sequence of SEQ ID NO: 163.

19. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IL-7Rαγc IgG-Fc fusion fragment comprises an amino acid sequence having greater than 70% sequence similarity to any one of SEQ ID NO: 44-55.

20. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IL-7Rαγc IgG-Fc fusion fragment comprises an amino acid sequence of any one of SEQ ID NO: 44-55.

21. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IL-7Rαγc IgG-Fc fusion fragment comprises an amino acid sequence having greater than 70% sequence similarity to SEQ ID NO: 45.

22. The IL-7Rαγc IgG-Fc fusion fragment of claim 13 , wherein the IL-7Rαγc IgG-Fc fusion fragment comprises an amino acid sequence having SEQ ID NO: 45.

23. An IL-7Rαγc IgG-Fc fusion protein comprising:

a first IL-7Rαγc IgG-Fc fusion fragment of claim 13 ; and

a second IL-7Rαγc IgG-Fc fusion fragment of claim 13 ,

wherein the IgG-Fc of the first IL-7Rαγc IgG-Fc fusion fragment comprises a first hinge region; wherein the IgG-Fc of the second IL-7Rαγc IgG-Fc fusion fragment comprises a second hinge region; and

wherein the first IL-7Rαγc IgG-Fc fusion fragment and the second first IL-7Rαγc IgG-Fc fusion fragment are bound to each other at the first hinge region and the second hinge region through disulfide bonds.

24. The IL-7Rαγc IgG-Fc fusion protein of claim 23 , wherein the first IL-7Rαγc IgG-Fc fusion fragment and the second IL-7Rαγc IgG-Fc fusion fragment have the same amino acid sequence.

25. The IL-7Rαγc IgG-Fc fusion protein of claim 23 , wherein the first IL-7Rαγc IgG-Fc fusion fragment and the second IL-7Rαγc IgG-Fc fusion fragment comprise different amino acid sequences.

26. The IL-7Rαγc IgG-Fc fusion protein of claim 23 , wherein the first IL-7Rαγc IgG-Fc fusion fragment and the second IL-7Rαγc IgG-Fc fusion fragment comprise a different IL-7Rα ligand.

27. The IL-7Rαγc IgG-Fc fusion protein of claim 23 , wherein the first IL-7Rαγc IgG-Fc fusion fragment and the second IL-7Rαγc IgG-Fc fusion fragment comprise a different Rγc ligand.

28. A pharmaceutical composition comprising the IL-7Rαγc ligand of claim 1 .

29. A pharmaceutical composition comprising the IL-7Rαγc IgG-Fc fusion protein of claim 13 .

Assignments (2)
SECURITY INTEREST Recorded Oct 20, 2023
From: MEDIKINE, INC.
To: SAMSARA BIOCAPITAL, L.P.; LIGHTSPEED GENERAL PARTNER XIV-B (IGNITE), L.P.; BLUEBIRD VENTURES I, L.P.; JEFFREY W. AND CHRISTINA R. BIRD TRUST U/A/D; MCMEEKIN, DERMOT; WS INVESTMENT COMPANY, LLC (23A)
Reel/Frame 065303/0643 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2023
From: DOWER, WILLIAM J.; BARRETT, RONALD W.; NEEDELS, MICHAEL C.; CWIRLA, STEVEN E.; BAKKER, ALICE V.; PARK, INKYUNG
To: MEDIKINE, INC.
Reel/Frame 063249/0745 →
Continuity (2)
Provisional Application 63328700 · Apr 7, 2022
Related Publication 20230322880A1 · Oct 12, 2023