	US 11,834,490 B2
	CD112 variant immunomodulatory proteins and uses thereof
Ryan Swanson, Seattle, WA (US); Michael Kornacker, Seattle, WA (US); Daniel William Demonte, Seattle, WA (US); Mark F. Maurer, Seattle, WA (US); Dan Ardourel, Woodinville, WA (US); and Joseph L. Kuijper, Kenmore, WA (US)
Assigned to ALPINE IMMUNE SCIENCES, INC., Seattle, WA (US)
Appl. No. 16/321,000
Filed by ALPINE IMMUNE SCIENCES, INC., Seattle, WA (US)
PCT Filed Jul. 27, 2017, PCT No. PCT/US2017/044260 § 371(c)(1), (2) Date Jan. 25, 2019, PCT Pub. No. WO2018/022945, PCT Pub. Date Feb. 1, 2018.
Claims priority of provisional application 62/475,130, filed on Mar. 22, 2017.
Claims priority of provisional application 62/472,569, filed on Mar. 16, 2017.
Claims priority of provisional application 62/410,840, filed on Oct. 20, 2016.
Claims priority of provisional application 62/394,698, filed on Sep. 14, 2016.
Claims priority of provisional application 62/367,819, filed on Jul. 28, 2016.
Prior Publication US 2021/0253668 A1, Aug. 19, 2021
Int. Cl. A61K 39/00 (2006.01); C07K 14/705 (2006.01); A61K 35/12 (2015.01); C07K 14/725 (2006.01); C12N 15/85 (2006.01); A61K 38/00 (2006.01)

CPC C07K 14/70596 (2013.01) [A61K 35/12 (2013.01); C07K 14/7051 (2013.01); C12N 15/85 (2013.01); A61K 38/00 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C12N 2510/00 (2013.01)]

35 Claims

1. A variant CD112 polypeptide, comprising an IgV domain or both an IgV domain and an IgC domain;

wherein the variant CD112 polypeptide comprises the amino acid substitution A112V or A112I in an unmodified CD112 with reference to positions set forth in SEQ ID NO:48, wherein the unmodified CD112 comprises the sequence of amino acids set forth in SEQ ID NO:48 or a portion thereof comprising an IgV domain;

wherein the variant CD112 polypeptide comprises a sequence of amino acids that exhibits at least 85% sequence identity to SEQ ID NO:48 or the portion thereof comprising the IgV domain; and

wherein the variant CD112 polypeptide specifically binds to the ectodomain of TIGIT with increased affinity compared to the binding of the unmodified CD112 to the same ectodomain of TIGIT.