US 11,732,022 B2
PD-L2 variant immunomodulatory proteins and uses thereof
Ryan Swanson, Seattle, WA (US); Michael Kornacker, Seattle, WA (US); Mark F. Maurer, Seattle, WA (US); Dan Ardourel, Seattle, WA (US); Daniel William Demonte, Seattle, WA (US); and Joseph L. Kuijper, Kenmore, WA (US)
Assigned to Alpine Immune Sciences, Inc., Seattle, WA (US)
Appl. No. 16/493,751
Filed by Alpine Immune Sciences, Inc., Seattle, WA (US)
PCT Filed Mar. 13, 2018, PCT No. PCT/US2018/022267
§ 371(c)(1), (2) Date Sep. 12, 2019,
PCT Pub. No. WO2018/170023, PCT Pub. Date Sep. 20, 2018.
Claims priority of provisional application 62/537,928, filed on Jul. 27, 2017.
Claims priority of provisional application 62/475,156, filed on Mar. 22, 2017.
Claims priority of provisional application 62/472,572, filed on Mar. 16, 2017.
Prior Publication US 2021/0130437 A1, May 6, 2021
Int. Cl. C07K 14/705 (2006.01); A61K 38/00 (2006.01)
CPC C07K 14/70532 (2013.01) [A61K 38/00 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/74 (2013.01)] 9 Claims
 
1. A variant PD-L2 polypeptide, comprising an IgV domain or both an IgV domain and an IgC domain, wherein the variant PD-L2 polypeptide comprises one or more amino acid substitutions in an unmodified PD-L2, with reference to numbering of SEQ ID NO:31;
wherein the one or more amino acid substitutions are selected from the group consisting of H15Q, H15Q/K65R, H15Q/Q72H/V89D, H15Q/S67L/R76G, H15Q/T47A/Q82R, H15Q/Q82R/V89D, H15Q/S67L/I86T, I13V/H15Q/S67L/I86T, I13V/H15Q/E44D/V89D, H15Q/T47A/Q72H/R76G/I86T, H15Q/T47A/Q72H/R76G, I13V/H15Q/T47A/Q72H/R76G, H15Q/S39I/S67L/V89D, H15Q/N32D/S67L/V89D, H15Q/S67L/Q72H/R76G/V89D, I13V/H15Q/S39I/E44D/S67L, H15Q/V89D, H15Q/T47A, I13V/H15Q/Q82R, I13V/H15Q/V89D, I13V/H15Q/Q82R/V89D, H15Q/V31M/S67L/Q82R/V89D, I13V/H15Q/T47A/Q82R, I13V/H15Q/V31A/N45S/Q82R/V89D, H15Q/T47A/H69L/Q82R/V89D, I13V/H15Q/T47A/H69L/R76G/V89D, I12V/I13V/H15Q/T47A/Q82R/V89D, I13V/H15Q/R76G/D77N/Q82R/V89D, I13V/H15Q/T47A/R76G/V89D, I13V/H15Q/T47A/Q82R/V89D, I13V/H15Q/I36V/T47A/S67L/V89D, H15Q/T47A/K65R/S67L/Q82R/V89D, H15Q/L33P/T47A/S67L/P71S/V89D, I13V/H15Q/Q72H/R76G/I86T, H15Q/T47A/S67L/Q82R/V89D, F2L/H15Q/D46E/T47A/Q72H/R76G/Q82R/V89D, I13V/H15Q/L33F/T47A/Q82R/V89D, H15Q/N24S/T47A/Q72H/R76G/V89D, I13V/H15Q/E44V/T47A/Q82R/V89D, H15Q/N18D/T47A/Q72H/V73A/R76G/I86T/V89D, I13V/H15Q/T37A/E44D/S48C/S67L/Q82R/V89D, H150/L33H/S67L/R76G/Q82R/V89D, I13V/H15Q/T47A/Q72H/R76G/I86T, H15Q/S39I/E44D/Q72H/V75G/R76G/Q82R/V89D, H15Q/T47A/S67L/R76G/Q82R/V89D, and I13V/H15Q/T47A/S67L/Q72H/R76G/Q82R/V89D;
wherein the unmodified PD-L2 comprises the sequence of amino acids set forth in SEQ ID NO:31, or a portion thereof comprising an IgV domain;
wherein the variant PD-L2 polypeptide comprises a sequence of amino acids that exhibits at least 90% sequence identity to SEQ ID NO:31 or the portion of SEQ ID NO:31 comprising the IgV domain; and
wherein the variant PD-L2 polypeptide specifically binds to the ectodomain of PD-1 with increased affinity compared to the binding of the unmodified PD-L2 to the ectodomain of PD-1.