US 12,433,953 B2
Compositions and methods related to tumor activated antibodies targeting EGFR and effector cell antigens
David Campbell, San Diego, CA (US); Thomas R. Diraimondo, San Diego, CA (US); and Ramesh Bhatt, San Diego, CA (US)
Assigned to JANUX THERAPEUTICS, INC., San Diego, CA (US)
Filed by Janux Therapeutics, Inc., San Diego, CA (US)
Filed on Oct. 17, 2024, as Appl. No. 18/919,094.
Application 18/919,094 is a continuation of application No. 18/559,201, granted, now 12,161,724, previously published as PCT/US2022/027688, filed on May 4, 2022.
Claims priority of provisional application 63/327,317, filed on Apr. 4, 2022.
Claims priority of provisional application 63/187,690, filed on May 12, 2021.
Prior Publication US 2025/0177552 A1, Jun. 5, 2025
Int. Cl. A61K 47/68 (2017.01)
CPC A61K 47/6849 (2017.08) [A61K 47/6843 (2017.08); A61K 47/6851 (2017.08); A61K 47/6871 (2017.08); A61K 47/6889 (2017.08)] 31 Claims
 
1. A polypeptide or polypeptide complex according to Formula Ia:
P2-L2-A2-A1-L1-P1-H1  (Formula Ia)
wherein:
A1 comprises a first antigen recognizing molecule that binds to an effector cell antigen comprising cluster of differentiation 3 (CD3), wherein A1 comprises an anti-CD3 binding molecule comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, the HC-CDR2, and the HC-CDR3 of A1 comprise: HC-CDR1: SEQ ID NO: 4, HC-CDR2: SEQ ID NO: 5, and HC-CDR3: SEQ ID NO: 6; and A1 comprises CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, the LC-CDR2, and the LC-CDR3 of A1 comprise LC-CDR1: SEQ ID NO: 1, LC-CDR2: GTK, and LC-CDR3: SEQ ID NO: 3;
P1 comprises a peptide that binds to A1 according to the formula: U1-U2-C-U4-P-U6-U7-U8-U9-U10-U11-U12-C-U14, wherein U1 is selected from the group consisting of D, Y, F, I, N, V, H, L, A, T, S, and P; U2 is selected from the group consisting of D, Y, L, F, I, N, A, V, H, T, and S; U4 is selected from the group consisting of G and W; U6 is selected from the group consisting of E, D, V, and P; U7 is selected from the group consisting of W, L, F, V, G, M, I, and Y; U8 is selected from the group consisting of E, D, P, and Q; U9 is selected from the group consisting of E, D, Y, V, F, W, P, L, and Q; U10 is selected from the group consisting of S, D, Y, T, I, F, V, N, A, P, L, and H; U11 is selected from the group consisting of I, Y, F, V, L, T, N, S, D, A, and H; U12 is selected from the group consisting of F, D, Y, L, I, V, A, N, T, P, S, G, and H; and U14 is selected from the group consisting of D, Y, N, F, I, P, V, A, T, H, L, M, and S;
L1 comprises a linking moiety that connects A1 to P1 and is a substrate for a tumor specific protease;
H1 comprises a half-life extending molecule comprising serum albumin or an antibody or antibody fragment that binds to serum albumin;
A2 comprises a second antigen recognizing molecule that binds to epidermal growth factor receptor (EGFR), wherein A2 comprises an anti-EGFR binding domain that comprises heavy chain complementarity determining regions: HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, the HC-CDR2, and the HC-CDR3 comprise: HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR3: SEQ ID NO: 20; and the anti-EGFR binding domain comprises light chain complementarity determining regions: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, the LC-CDR2, and the LC-CDR3 comprise LC-CDR1: SEQ ID NO: 15, LC-CDR2: YAS, and LC-CDR3: SEQ ID NO: 17;
L2 comprises a linking moiety that connects A2 to P2 and is a substrate for a tumor specific protease; and
P2 comprises a peptide that binds to A2 according to the formula:
X1-C-X2-X3-X4-X5-D-X6-A-X7-P-X8-C-X9 (SEQ ID NO: 841),
wherein
X1 is selected from the group consisting of: P and L;
X2 is selected from the group consisting of: R, L, T, A, N, I, V, S, H, and P;
X3 is selected from the group consisting of: S, P, F, and Y;
X4 is selected from the group consisting of: H, L, Q, P, R, F, and N;
X5 is selected from the group consisting of: I, F, Y, H, N, T, S, D, A, L, and V;
X6 is selected from the group consisting of: T, P, N, L, I, V, S, D, H, A, and Y;
X7 is selected from the group consisting of K and Y;
X8 is selected from the group consisting of: I, P, L, and M; and
X9 is selected from the group consisting of: A, V, I, T, L, S, D, F, V, and H.