	US 12,110,332 B2
	Bifunctional fusion protein targeting CD47 and PD-L1
Yajun Guo, Shanghai (CN)
Assigned to Taizhou Mabtech Pharmaceutical Co., Ltd., Jiangsu (CN)
Appl. No. 16/765,008
Filed by Taizhou Mabtech Pharmaceutical Co., Ltd., Jiangsu (CN)
PCT Filed Nov. 20, 2017, PCT No. PCT/CN2017/111828 § 371(c)(1), (2) Date May 18, 2020, PCT Pub. No. WO2019/095358, PCT Pub. Date May 23, 2019.
Prior Publication US 2020/0354458 A1, Nov. 12, 2020
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); A61P 37/02 (2006.01); C07K 14/705 (2006.01)

CPC C07K 16/2827 (2013.01) [A61P 35/00 (2018.01); A61P 37/02 (2018.01); C07K 14/70503 (2013.01); C07K 16/2896 (2013.01); A61K 2039/505 (2013.01); C07K 16/2803 (2013.01); C07K 2317/31 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/52 (2013.01); C07K 2317/732 (2013.01); C07K 2319/70 (2013.01)]

2 Claims

1. A bifunctional protein, characterized in that the bifunctional protein consists of two moieties linked by disulfide bonds,

wherein one moiety is a CD47 binding moiety formed by linking SIRPα mutant to an antibody Fc, and the other moiety is a Programmed death-ligand 1 (PD-L1) binding moiety formed by linking a light chain and a heavy chain of anti-PD-L1 antibody by disulfide bond, the PD-L1 binding moiety having a Fc segment;

wherein the bifunctional protein has a Knob-in-Hole structure formed by the CD47 binding moiety and the PD-L1 binding moiety, the Fc of the CD47 binding moiety has four amino acid mutations of y349c, t366s, 1368a and y407v, and the Fc segment of the PD-L1 binding moiety has two amino acid mutations of t366w and s354c; and

wherein the CD47 binding moiety comprises SEQ ID NO: 1, the light chain of the PD-L1 binding moiety comprises SEQ ID NO: 2, and the heavy chain comprises in SEQ ID NO: 3.