	US 11,939,385 B2
	Activatable antibodies and methods of use thereof
Marija Vrljic, San Mateo, CA (US); and Jaume Pons, San Francisco, CA (US)
Assigned to ALX ONCOLOGY INC., South San Francisco, CA (US)
Appl. No. 16/613,774
Filed by ALX Oncology Inc., South San Francisco, CA (US)
PCT Filed May 15, 2018, PCT No. PCT/US2018/032806 § 371(c)(1), (2) Date Nov. 14, 2019, PCT Pub. No. WO2018/213335, PCT Pub. Date Nov. 22, 2018.
Claims priority of provisional application 62/507,129, filed on May 16, 2017.
Prior Publication US 2020/0062851 A1, Feb. 27, 2020
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 14/47 (2006.01); C07K 14/52 (2006.01); C07K 14/54 (2006.01); C07K 16/32 (2006.01)

CPC C07K 16/2863 (2013.01) [A61P 35/00 (2018.01); C07K 14/47 (2013.01); C07K 14/52 (2013.01); C07K 14/5428 (2013.01); C07K 14/5434 (2013.01); C07K 16/2818 (2013.01); C07K 16/32 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/41 (2013.01); C07K 2317/55 (2013.01); C07K 2317/62 (2013.01); C07K 2317/76 (2013.01); C07K 2319/01 (2013.01); C07K 2319/30 (2013.01); C07K 2319/50 (2013.01)]

9 Claims

1. An activatable antibody comprising an antigen-binding domain (ABD), wherein the ABD comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the N-terminus of the VH is fused to a first polypeptide shield moiety (S1), and the N-terminus of the VL is fused to a second polypeptide shield moiety (S2), wherein each of S1 and S2 is a polypeptide no more than about 50 amino acids long,

wherein association of S1 with S2 blocks binding of the ABD to its target,

wherein the ABD does not specifically bind to S1, S2, or association thereof,

wherein S1 comprises a first association moiety (B), and S2 comprises a second association moiety (C), wherein B and C are conjugated to each other by an isopeptide bond, and wherein S1 comprises the amino acid sequence of any one of SEQ ID NOs: 140, 142 and 227, and wherein S2 comprises the amino acid sequence of any one of SEQ ID NOs: 141 and 143; or wherein S1 comprises the amino acid sequence of any one of SEQ ID NOs: 141 and 143, and wherein S2 comprises the amino acid sequence of any one of SEQ ID NOs: 140, 142 and 227.