US 12,473,337 B2
Homodimeric or heterodimeric interleukin 12 fusion proteins, and compositions and therapeutic methods thereof
Yang-Xin Fu, Dallas, TX (US); Hua Peng, Beijing (CN); and Diyuan Xue, Beijing (CN)
Assigned to Shanghai Kangabio Co., Limited, Shanghai (CN)
Appl. No. 17/049,021
Filed by Shanghai KangaBio Co., Ltd., Shanghai (CN)
PCT Filed Apr. 24, 2019, PCT No. PCT/US2019/028933
§ 371(c)(1), (2) Date Oct. 19, 2020,
PCT Pub. No. WO2019/209965, PCT Pub. Date Oct. 31, 2019.
Claims priority of application No. 201810376920.1 (CN), filed on Apr. 25, 2018.
Prior Publication US 2022/0162280 A1, May 26, 2022
Int. Cl. C07K 14/54 (2006.01); A61K 38/00 (2006.01); A61P 35/00 (2006.01)
CPC C07K 14/5434 (2013.01) [A61P 35/00 (2018.01); A61K 38/00 (2013.01); C07K 2319/02 (2013.01); C07K 2319/30 (2013.01)] 19 Claims
 
1. A homodimeric or heterodimeric protein, comprising:
a first structural unit: one or two subunits of interleukin 12 (IL12) selected from P35 and P40 subunits, having sequence identity to SEQ ID NOS: 1 to 4;
a second structural unit: an antibody Fc domain, wherein the second structural unit is located at the C-terminus of the fusion protein and having sequence identity to SEQ ID NOS: 5 to 7;
a first linker segment covalently linking the first structural unit and the second structural unit;
an interleukin 12 receptor (IL12R) linked to the N-terminus of the first structural unit and having an IL12 binding portion comprising IL12RB1 (Rβ1) and IL12Rβ2 (Rβ2) domains of SEQ ID NOS: 8 to 11; and
a second linker segment (L2) covalently linking the IL12R binding domain to the first structural unit, wherein
L2 is capable of being recognized and hydrolyzed by a proteolytic enzyme specifically expressed in a tumor microenvironment,
wherein the homodimeric or heterodimeric protein has an amino acid sequence of at least one of SEQ ID NO: 31, 32, 37, 38, 39, 41, 40, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52.