US 12,065,476 B2
PD-1 variant immunomodulatory proteins and uses thereof
Ryan Swanson, Seattle, WA (US); and Daniel William Demonte, Seattle, WA (US)
Assigned to Alpine Immune Sciences, Inc., Seattle, WA (US)
Appl. No. 17/252,233
Filed by Alpine Immune Sciences, Inc., Seattle, WA (US)
PCT Filed Jun. 14, 2019, PCT No. PCT/US2019/037388
§ 371(c)(1), (2) Date Dec. 14, 2020,
PCT Pub. No. WO2019/241758, PCT Pub. Date Dec. 19, 2019.
Claims priority of provisional application 62/774,145, filed on Nov. 30, 2018.
Claims priority of provisional application 62/753,886, filed on Oct. 31, 2018.
Claims priority of provisional application 62/685,880, filed on Jun. 15, 2018.
Prior Publication US 2021/0363219 A1, Nov. 25, 2021
Int. Cl. C07K 14/00 (2006.01); C07K 14/705 (2006.01); C07K 16/28 (2006.01); C12N 15/86 (2006.01); A61K 38/00 (2006.01)
CPC C07K 14/70521 (2013.01) [C07K 16/2818 (2013.01); C12N 15/86 (2013.01); A61K 38/00 (2013.01); C07K 2317/53 (2013.01); C07K 2319/03 (2013.01)] 11 Claims
 
1. A variant PD-1 polypeptide comprising an IgV domain, wherein:
(a) the variant PD-1 polypeptide comprises one or more amino acid substitutions in an unmodified PD-1 polypeptide selected from the amino acid substitutions P8T, D9E, D9G, D9N, D9V, P11A, W12G, W12L, W12R, N13Y, P14H, P14L, P14S, T16A, T16I, T16S, F17I, F17V, F17Y, S18T, A20S, A20T, A20V, L21V, L22I, V23E, V23G, V24L, D28E, N29D, T31I, T31N, T31S, T33I, C34Y, S35N, F36I, F36L, F36Y, S37P, S37T, N38S, N38T, T39R, T39S, S40P, S40T, E41D, E41V, S42G, S42R, F43L, F43Y, V44M, Y48N, M50T, S51G, P52A, P52L, S53T, N54H, Q55R, T56M, T56P, T56S, K58R, L59M, L59R, L59V, E64D, E64K, R66H, R66S, S67C, S67I, S67N, S67R, P69H, G70C, G70E, G70S, Q71H, Q71K, Q71L, D72N, C73A, C73G, C73H, C73P, C73Y, F75Y, R76H, R76S, V77D, T78S, Q79P, L80Q, P81S, R84H, R84Q, D85G, D85N, F86Y, H87L, S89G, S89N, V90L, V90M, V91A, V91D, V91I, R92N, R92S, A93V, R94Q, R95L, N96T, T100A, T100I, T100S, L102F, G104A, G104T, G104V, A105C, A105G, A105L, I106L, L108T, A109G, K111M, K111N, Q113R, Q113W, I114T, K115D, K115E, K115I, K115N, K115Q, E116D, R119H, R119L, R119P, R119Q, R119W, T125K, T125S, R127S, R128M, A129S, E130K, V131A, V131E, P132H, P132R, P132S, P132T, T133A, T133R, T133S, A134D, A134V, H135N, H135R, H135Y, P136L, P136T, S137C, P138S, P138T, S139T, P140A, P140L, P140R, R141G, R141M, R141S, R141W, P142A, P142L, P142R, P142T, A143D, A143S, A143V, G144D, or G144S with reference to numbering of positions set forth in SEQ ID NO:37; or
(b) the variant PD-1 polypeptide comprises two or more amino acid substitutions in an unmodified PD-1 polypeptide selected from C73A, C73G, C73H, C73P, C73R, C73S, C73Y, F86Y, S107T, A112V, K115D, K115E, K115I, K115N, K115Q, R119H, R119L, R119P, R119Q, R119W or A120V, with reference to numbering of positions set forth in SEQ ID NO:37;
wherein the unmodified PD-1 polypeptide comprises (i) the sequence of amino acids set forth in any of SEQ ID NOS: 37, 244, or 392, (ii) a sequence of amino acids that has at least 95% sequence identity to any of SEQ ID NOS:37, 244, or 392; or (iii) is a portion of (i) or (ii) comprising an IgV domain.