IP Library › Granted Patent US 11,471,488
Granted Patent B2
US 11,471,488 · App. 16/320,981 · Granted Oct 18, 2022

CD155 variant immunomodulatory proteins and uses thereof

Inventors: Ryan Swanson (Seattle, WA); Michael Kornacker (Seattle, WA); Daniel William Demonte (Seattle, WA); Mark F. Maurer (Seattle, WA)
Assignee: ALPINE IMMUNE SCIENCES, INC.
A61K35/17A61P35/00C07K14/70532C07K14/70535C07K14/70596C07K16/28C12N15/62C12N15/85
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Quick Facts
Patent No.
US 11,471,488
App. No.
16/320,981
Granted
Oct 18, 2022
Kind
B2
Abstract

Provided herein are immunomodulatory proteins comprising variant CD155 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.

Claims (22)

1. A variant CD155 polypeptide comprising an amino acid sequence that exhibits at least 90% sequence identity to SEQ ID NO: 47 or amino acid residues 4-119 of SEQ ID NO: 47, wherein the variant CD155 polypeptide comprises the amino acid substitution L104M in the amino acid sequence of SEQ ID NO: 47, and wherein the variant CD155 polypeptide specifically binds to the ectodomain of TIGIT with increased affinity compared with the unmodified CD155 polypeptide to the same ectodomain.

2. The variant CD155 polypeptide of claim 1 , further comprising one or more amino acid substitutions selected from the group consisting of G7E, D8G, V9A, V9D, V91, V9L, V10F, V10G, V10I, V11A, V11E, V11M, Q12H, Q12K, Q12L, A13E, A13R, T15I, T15S, Q16H, P18C, P18F, P18H, P18L, P18S, P18T, P18Y, G19D, F20I, F20S, F20Y, L21S, L21M, G22S, D23A, D23G, D23N, D23Y, S24A, S24P, V25A, V25E, T26M, C29R, Y30C, Y30F, Y30H, Q32L, Q32R, V33M, P34S, N35D, N35F, N35S, M36I, M36R, M36T, E37G, E37P, E37S, E37V, V38A, V38G, T39A, T39S, H40Q, H40R, H40T, V41A, V41M, S42A, S42C, S42G, S42L, S42N, S42P, S42Q, S42T, S42V, S42W, L44P, L44V, T45A, T45G, T45I, T45S, T45Q, T45V, W46C, W46R, A47E, A47G, A47V, R48Q, H49L, H49Q, H49R, G50S, E51G, E51K, E51V, S52A, S52E, S52G, S52K, S52L, S52M, S52P, S52Q, S52R, S52T, S52W, G53R, S54C, S54G, S54H, S54N, S54R, M55I, M55L, M55V, A56V, V57A, V57L, V57T, F58L, F58Y, H59E, H59N, N59R, Q60H, Q60K, Q60P, Q60R, T61A, T61G, T61K, T61M, T61R, T61S, Q62F, Q62H, Q62K, Q62L, Q62M, Q62R, Q62Y, P64S, S65A, S65C, S65G, S65D, S65T, S65Y, S65H, S65N, S65T, S65W, S67A, S67E, S67G, S67H, S67L, S67T, S67V, S67W, E68D, E68G, S69L, S69P, K70E, K70R, K70Q, L72Q, E73D, E73G, E73R, V75A, V75L, A76E, A76G, A76T, A77T, A77V, R78G, R78K, R78S, L79P, L79Q, L79V, G80D, G80S, A81E, A81P, A81T, A81V, E82D, E82G, L83P, L83Q, R84W, N85D, N85Y, N87T, L88P, R89K, M90I, M90L, M90V, F91S, F91T, F91P, G92A, G92E, G92W, R94H, V95A, E96D, D97G, E98D, E98S, G99D, G99Y, N100Y, T102S, V106A, V1061, V106L, T107A, T107L, T107M, T107S, T107V, F108H, F108L, F108Y, Q110R, G111D, G111R, S112I, S112N, S112V, R113G, R113W, S114N, S114T, V115A, V115M, D116G, and D116N or a conservative amino acid substitution thereof.

3. The variant CD155 polypeptide of claim 1 , comprising one or more amino acid substitutions selected from the group consisting of P18S/L79P/L104M, P18S/L104M, L79P/L104M, P18S/H40T/V41M/A47V/S52Q/Q62L/S65T/E73R/L104M/V106A, P18F/T26M/L44V/Q62K/L79P/F91S/L104M/G111D, P18S/L79P/L104M/T107M, P18S/A47G/L79P/F91S/L104M/T107A/R113W, P18T/D23G/S24A/N35D/H49L/L79P/F91S/L104M/G111R, P18S/H49R/E73D/L79P/N85D/F91S/V95A/L104M/G111R, V11A/P18S/L79P/F91S/L104M/G111R, P18T/S52P/S65A/S67V/L79P/F91S/L104M/G111R, D8G/P18S/M36I/V38A/H49Q/A76E/F91S/L104M/T107A/R113W, P18S/S52P/S65A/S67V/L79P/F91S/L104M/T107 S/R113W, T15I/P18T/L79P/F91S/L104M/G111R, P18F/T26M/L44V/Q62K/L79P/E82D/F91S/L104M/G111D, P18T/E37G/G53R/Q62K/L79P/F91S/E98D/L104M/T107M, P18F/S65A/S67V/F91S/L104M/G111R, V9I/V10I/P18S/F20S/T45A/L79P/F91S/L104M/F108Y/G111R/S112V, V9L/P18L/L79P/M901/F91S/T102 S/L104M/G111R, P18C/T26M/L44V/M55I/Q62K/L79P/F91S/L104M/T107M, P18F/L79P/M90L/F91S/V95A/L104M/G111R, V9L/P18T/Q62R/L79P/F91S/L104M/G111R, P18F/H40Q/T61K/Q62K/L79P/F91S/L104M/T107V, P18T/W46C/H49R/S65A/S67V/A76T/L79P/S87T/L104M, P18S/H59N/V75A/L79P/A81T/F91S/L104M/T107M, P18S/D23G/C29R/N35D/E37G/M55I/Q62K/S65A/S67G/R78G/L79P/F91S/L104M/T107M/Q110R, P18S/V41A/H49R/S54C/L79/N85Y/L88P/F91S/L104M/T107M, V9L/V11M/P18S/N35S/S54G/Q62K/L79P/L104M/T107M/V115M, V9L/P18Y/V25A/V38G/M55V/A77T/L79P/M901/F91S/L104M, and V9D/V11M/Q12L/P18S/E37V/M55I/Q60R/K70Q/L79P/F91S/L104M/T107M.

4. The variant CD155 polypeptide of claim 1 , comprising an amino acid sequence set forth in any of SEQ ID NOs: 229-231, 267, 271, 273, 1230-1231, 1233-1234, 1236, 1238-1242, 1245-1248, 1250, 1252, 1612, 1616, 1629, 1637, 1642, 1646-1647, and 1654; or an amino acid sequence set forth in any of SEQ ID NOs: 326-328, 364, 368, 370, 423-425, 461, 465, 467, 1184-1185, 1187-1188, 1190, 1192-1196, 1199-1202, 1204, 1206-1208, 1210-1211, 1213, 1215-1219, 1222-1225, 1227, 1229, 1658, 1662, 1675, 1683, 1688, 1692-1693, 1700, 1704, 1708, 1721, 1729, 1734, 1738-1739, and 1746.

5. The variant CD155 polypeptide of claim 1 , wherein the variant CD155 polypeptide consists of an amino acid sequence that exhibits at least 90% sequence identity to amino acid residues 4-119 of SEQ ID NO: 47.

6. The variant CD155 polypeptide of claim 1 , wherein the variant CD155 polypeptide is soluble and lacks the CD155 transmembrane domain and intracellular domain.

7. A fusion protein comprising the variant CD155 polypeptide of claim 1 and a multimerization domain, wherein the variant CD155 polypeptide is linked to the multimerization domain.

8. The fusion protein of claim 7 , wherein the multimerization domain is an Fc domain or a variant Fc domain with reduced effector function.

9. The variant CD155 polypeptide of claim 1 , wherein the variant CD155 polypeptide is a transmembrane immunomodulatory protein further comprising a transmembrane domain.

10. The variant CD155 polypeptide of claim 9 , further comprising a cytoplasmic domain.

11. An immunomodulatory protein, comprising the variant CD155 of claim 1 linked to a second polypeptide comprising an immunoglobulin superfamily (IgSF) domain.

12. A conjugate, comprising a variant CD155 polypeptide of claim 1 linked to a targeting moiety that specifically binds to a molecule on the surface of a cell.

13. A conjugate, comprising a variant CD155 polypeptide of claim 1 linked to a targeting moiety that specifically binds to a molecule on the surface of a cell.

14. The conjugate of claim 13 , wherein the moiety is an antibody or antigen-binding fragment.

15. An infectious agent, comprising a variant CD155 polypeptide of claim 1 .

16. The infectious agent of claim 15 , wherein the infectious agent is a bacterium or a virus.

17. A pharmaceutical composition, comprising the variant CD155 polypeptide of claim 1 , an immunomodulatory protein comprising the variant CD155 polypeptide of claim 1 , an infectious agent comprising the variant CD155 polypeptide of claim 1 , or a conjugate comprising the variant CD155 polypeptide of claim 1 linked to a targeting moiety that specifically binds to a molecule on the surface of a cell.

18. A homodimer comprising the fusion protein of claim 7 .

19. The variant CD155 polypeptide of claim 1 , comprising the amino acid substitutions V9L/P18T/Q62R/L79P/F91S/L104M/G111R.

20. The variant CD155 polypeptide of claim 1 , comprising the sequence of amino acids set forth in SEQ ID NO:1229.

21. The fusion protein of claim 7 , wherein the variant CD155 polypeptide comprises the amino acid substitutions V9L/P18T/Q62R/L79P/F91S/L104M/G111R.

22. The fusion protein of claim 7 , wherein the variant CD155 polypeptide comprises the sequence of amino acids set forth in SEQ ID NO:1229.

Continuity (6)
Provisional Application 62367822 · Jul 28, 2016
Provisional Application 62394696 · Sep 14, 2016
Provisional Application 62410839 · Oct 20, 2016
Provisional Application 62472558 · Mar 16, 2017
Provisional Application 62475198 · Mar 22, 2017
Related Publication 20190175654A1 · Jun 13, 2019
Cited By (3)
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