US 11,952,681 B2
Masked activatable CD137 antibodies
Peter Peizhi Luo, San Mateo, CA (US); and Fangyong Du, Jiangsu (CN)
Assigned to Adagene Inc., Grand Cayman (KY)
Appl. No. 16/966,848
Filed by Adagene Inc., Grand Cayman (KY)
PCT Filed Feb. 2, 2019, PCT No. PCT/CN2019/074581
§ 371(c)(1), (2) Date Jul. 31, 2020,
PCT Pub. No. WO2019/149282, PCT Pub. Date Aug. 8, 2019.
Claims priority of application No. PCT/CN2018075065 (WO), filed on Feb. 2, 2018.
Prior Publication US 2021/0207126 A1, Jul. 8, 2021
Int. Cl. C07K 16/46 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); C40B 40/08 (2006.01); C40B 40/10 (2006.01); A61K 39/00 (2006.01)
CPC C40B 40/08 (2013.01) [A61P 35/00 (2018.01); C07K 16/2818 (2013.01); C07K 16/2878 (2013.01); C40B 40/10 (2013.01); A61K 39/001117 (2018.08); A61K 2039/505 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01); C07K 2319/50 (2013.01); C07K 2319/74 (2013.01)] 43 Claims
OG exemplary drawing
 
1. An activatable antibody comprising:
a first polypeptide comprising, from N-terminus to C-terminus, a masking moiety (MM), a cleavable moiety (CM), and a target binding moiety (TBM),
wherein the MM comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 79-85;
wherein the CM comprises at least a first cleavage site and a first flexible linker (L1); and
wherein:
a) the TBM comprises an antibody light chain variable region (VL), and the activatable antibody further comprises a second polypeptide comprising an antibody heavy chain variable region (VH);
b) the TBM comprises an antibody heavy chain variable region (VH), and the activatable antibody further comprises a second polypeptide comprising an antibody light chain variable region (VL);
c) the TBM comprises from the N-terminus to the C-terminus, an antibody light chain variable region (VL) and an antibody heavy chain variable region (VH); or
d) the TBM comprises from the N-terminus to the C-terminus, an antibody heavy chain variable region (VH) and an antibody light chain variable region (VL);
wherein:
(i) the VH comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 65, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 66, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 67; and
(ii) the VL comprises an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 68, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 69, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 70; and
wherein the activatable antibody binds to human CD137 via the VH and the VL when the CM is cleaved.