CD80 variant immunomodulatory proteins and uses thereof
Provided herein are variant CD80 polypeptides, immunomodulatory proteins comprising variant CD80 polypeptides, and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.
1. A pharmaceutical composition comprising a therapeutically effective amount of a homodimer of a fusion protein of the formula CD80-linker-Fc, wherein CD80 is a variant CD80 polypeptide comprising the amino acid substitutions H18Y, A26E, E35D, M47L, V68M, A71G and D90G in the amino acid sequence set forth in SEQ ID NO:2 or a portion thereof comprising the IgV domain, wherein the IgV domain is amino acids 35-141 of SEQ ID NO:1.
2. The pharmaceutical composition of claim 1 , wherein the variant CD80 polypeptide comprises the sequence set forth in SEQ ID NO: 2276.
3. The pharmaceutical composition of claim 1 , wherein the linker has 1-20 amino acid residues.
4. The pharmaceutical composition of claim 1 , wherein the linker is GSGGGS (SEQ ID NO: 1716).
5. The pharmaceutical composition of claim 1 , wherein the Fc is a variant human IgG1 Fc with reduced effector function.
6. The pharmaceutical composition of claim 2 , wherein the linker is GSGGGS (SEQ ID NO: 1716).
7. The pharmaceutical composition of claim 2 , wherein the Fc is a variant human IgG1 Fc with reduced effector function.
8. The pharmaceutical composition of claim 1 , wherein the Fc is set forth in SEQ ID NO:1712.
9. The pharmaceutical composition of claim 1 , wherein the Fc is set forth in SEQ ID NO:1713.
10. The pharmaceutical composition of claim 1 , wherein the Fc is set forth in SEQ ID NO:1714.
11. The pharmaceutical composition of claim 1 , wherein the Fc is set forth in SEQ ID NO:1715.
12. The pharmaceutical composition of claim 1 , wherein the variant CD80 polypeptide is set forth in SEQ ID NO:2276, the linker is set forth in SEQ ID NO: 1716 and the Fc is set forth in SEQ ID NO:1712.
13. The pharmaceutical composition of claim 1 , wherein the variant CD80 polypeptide is set forth in SEQ ID NO:2276, the linker is set forth in SEQ ID NO: 1716, and the Fc is set forth in SEQ ID NO:1713.
14. The pharmaceutical composition of claim 1 , wherein the variant CD80 polypeptide is set forth in SEQ ID NO:2276, the linker is set forth in SEQ ID NO: 1716, and the Fc is set forth in SEQ ID NO:1714.
15. The pharmaceutical composition of claim 1 , wherein the homodimer is a purified homodimer.
16. The pharmaceutical composition of claim 1 , wherein the homodimer is the only therapeutic agent in the composition.
17. A pharmaceutical composition comprising a therapeutically effective amount of a CD80-Fc fusion protein homodimer comprising two identical copies of a CD80-Fc fusion protein, wherein the CD80-Fc fusion protein consists of a variant CD80 polypeptide set forth in SEQ ID NO: 2276, an Fc domain and a linker, wherein the variant CD80 polypeptide is linked to the Fc domain via the linker.
18. The pharmaceutical composition of claim 17 , wherein the Fc domain is a variant human IgG1 Fc with reduced effector function.
19. The pharmaceutical composition of claim 17 , wherein the linker is GSGGGS (SEQ ID NO: 1716).
20. The pharmaceutical composition of claim 18 , wherein the linker is GSGGGS (SEQ ID NO: 1716).
21. The pharmaceutical composition of claim 17 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions L234A/L235E/G237A.
22. The pharmaceutical composition of claim 17 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions R292C/N297G/V302C.
23. The pharmaceutical composition of claim 17 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions E233P/L234V/L235A/G236del/S267K.
24. The pharmaceutical composition of claim 19 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions L234A/L235E/G237A.
25. The pharmaceutical composition of claim 19 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions R292C/N297G/V302C.
26. The pharmaceutical composition of claim 19 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions E233P/L234V/L235A/G236del/S267K.
27. The pharmaceutical composition of claim 20 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions L234A/L235E/G237A.
28. The pharmaceutical composition of claim 20 , wherein the Fc domain is a variant IgG1 Fc domain comprising the amino acid substitutions R292C/N297G/V302C.
29. The pharmaceutical composition of claim 17 , wherein the CD80-Fc fusion protein homodimer is a purified homodimer.
30. The pharmaceutical composition of claim 17 , wherein the homodimer is the only therapeutic agent in the composition.