US 12,240,902 B2
Anti-TREM2 antibodies and methods of use thereof
Mark S. Dennis, South San Francisco, CA (US); Sherie Duncan, South San Francisco, CA (US); Kathleen Lisaingo, South San Francisco, CA (US); Kathryn M. Monroe, South San Francisco, CA (US); Joshua I. Park, South San Francisco, CA (US); Rachel Prorok, South San Francisco, CA (US); Ju Shi, South San Francisco, CA (US); Ankita Srivastava, South San Francisco, CA (US); Bettina Van Lengerich, South San Francisco, CA (US); and Riley Walsh, South San Francisco, CA (US)
Assigned to Denali Therapeutics Inc., South San Francisco, CA (US)
Filed by Denali Therapeutics Inc., South San Francisco, CA (US)
Filed on Aug. 16, 2021, as Appl. No. 17/402,986.
Application 17/402,986 is a continuation of application No. PCT/US2020/019104, filed on Feb. 20, 2020.
Claims priority of provisional application 62/808,141, filed on Feb. 20, 2019.
Prior Publication US 2022/0119522 A1, Apr. 21, 2022
Int. Cl. A61K 39/00 (2006.01); C07K 16/28 (2006.01)
CPC C07K 16/2803 (2013.01) [A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/565 (2013.01); C07K 2317/75 (2013.01); C07K 2317/92 (2013.01)] 20 Claims
 
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to a human triggering receptor expressed on myeloid cells 2 (TREM2), wherein the antibody or antigen-binding fragment thereof comprises:
(a) a CDR-H1 sequence comprising the sequence of G-Y-T-F-T-α6-Y-α8-α9-α10 (SEQ ID NO:293), wherein α6 is N, S, or D; α8 is W or N; α9 is I or M; and α10 is S, T, M, or H;
(b) a CDR-H2 sequence comprising the sequence of β1-I-β3-P-β5-β6-β7-β8-β9-β10-Y-N-β13-β14-F-β16-β17 (SEQ ID NO:294), wherein β1 is D or Y; β3 is Y or F; β5 is H, G, S, N, or β6 is S or N; β7 is T or G; β8 is S, N, or G; β9 is T or N; β10 is N or G; β13 is E or Q; β14 is R or K; β16 is R or K; and β17 is S, G, or N;
(c) a CDR-H3 sequence comprising the sequence of γ1-R-γ3-G-γ5-G-γ7-γ8-γ9 (SEQ ID NO:295), wherein γ1 is A or S; γ3 is E or S; γ5 is F, Y, R, or T; γ7 is I or F; γ8 is S or A; and γ9 is A or Y;
(d) a CDR-L1 sequence comprising:
(i) the sequence of δ1-A-δ3-δ4-δ5-V-δ7-δ8-Y-δ10-δ11 (SEQ ID NO:296), wherein δ1 is S or K; δ3 is T or S; δ4 is S or E; δ5 is S or N; δ7 is absent or G; δ8 is S or T; δ10 is M or V; and δ11 is H or S; or
(ii) the sequence of δ1-S-S-δ4-S-L-L-δ8-S-δ10-N-δ12-δ13-δ14-Y-L-δ17 (SEQ ID NO:297), wherein δ1 is K or R; δ4 is Q or K; δ8 is N or H; δ10 is G or absent; δ12 is Q or G; δ13 is K or N; δ14 is N or T; and δ17 is T or Y;
(e) a CDR-L2 sequence comprising the sequence of ε1-ε2-S-ε4-ε5-ε6-ε7 (SEQ ID NO:298), wherein ε1 is S, G, W or Q; ε2 is T, A, or M; ε4 is N or T; ε5 is L or R; ε6 is A, Y, or E; and ε7 is S or T; and
(f) a CDR-L3 sequence comprising the sequence of ϕ1-ϕ2-ϕ3-ϕ4-ϕ5-ϕ6-P-ϕ8-T (SEQ ID NO:299), wherein ϕ1 is Q, G, or M; ϕ2 is Q or N; ϕ3 is R, S, D, or H; ϕ4 is S, Y, or L; ϕ5 is S or Q; ϕ6 is Y or F; and ϕ8 is L, F, or Y.