	US 11,787,863 B2
	Multi-specific antibodies and methods of making and using thereof
Yi Zhu, Chengdu (CN); Ole Olsen, Everett, WA (US); Dong Xia, Redmond, WA (US); David Jellyman, Duvall, WA (US); Katrina Bykova, Seattle, WA (US); Anne-Marie K. Rousseau, Seattle, WA (US); Bill Brady, Bothell, WA (US); Blair Renshaw, Renton, WA (US); Brian Kovacevich, Snohomish, WA (US); Yu Liang, Redmond, WA (US); and Zeren Gao, Redmond, WA (US)
Assigned to SYSTIMMUNE, INC.; and BAILI-BIO (CHENGDU) PHARMACEUTICAL CO., LTD., Chengdu (CN)
Appl. No. 16/615,122
Filed by SYSTIMMUNE, INC., Redmond, WA (US); and SICHUAN BAILI PHARMACEUTICAL CO. LTD., Chengdu (CN)
PCT Filed Jun. 22, 2018, PCT No. PCT/US2018/038156 § 371(c)(1), (2) Date Nov. 19, 2019, PCT Pub. No. WO2019/005639, PCT Pub. Date Jan. 3, 2019.
Claims priority of provisional application 62/524,557, filed on Jun. 25, 2017.
Prior Publication US 2022/0002406 A1, Jan. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61P 35/02 (2006.01)

CPC C07K 16/2809 (2013.01) [A61P 35/02 (2018.01); C07K 16/2803 (2013.01); C07K 16/2827 (2013.01); C07K 16/2863 (2013.01); C07K 16/2878 (2013.01); C07K 2317/31 (2013.01); C07K 2317/52 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01)]

16 Claims

1. A tetra-specific antibody monomer having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal,

a first scFv domain at the N-terminal,

a Fab domain, wherein the Fab domain comprises a CL having an amino acid SEQ ID NO. 64,

a Fc domain having an amino acid SEQ ID NO. 62,

a second scFv domain, and

a third scFv domain at the C-terminal, and

wherein the first scFv domain, the Fab domain, the second scFv domain and the third scFv domain have a combination of binding specificities selected from:

i) the first scFv domain having a specificity against CD3, the Fab domain having a specificity against EGFR VIII, the second scFv domain having a specificity against PD-L1, and the third scFv domain having a specificity against 4-1BB, wherein the tetra-specific anti-body monomer comprises 3 complementarity determining regions (CDRs) of SEQ ID NO. 2 and 3 CDRs of SEQ ID NO: 4, 3 CDRs of SEQ ID NO. 10 and 3 CDRs of SEQ ID NO. 12, 3 CDRs of SEQ ID NO. 30 and 3 CDRs of SEQ ID NO. 32, and 3 CDRs of SEQ ID NO. 38 and 3 CDRs of SEQ ID NO: 40,

ii) the first scFv domain having a binding specificity against CD3, the Fab domain having a binding affinity to CD19, the second scFv domain having a binding affinity to PD-L1, and the third scFv domain having a binding affinity to 4-1BB, wherein the tetra-specific anti-body monomer comprises 3 CDRs of SEQ ID NO. 2 and 3 CDRs of SEQ ID NO: 4, 3 CDRs of SEQ ID NO. 14 and 3 CDRs of SEQ ID NO. 16, 3 CDRs of SEQ ID NO: 26 and 3 CDRs of SEQ ID NO. 28, and 3 CDRs of SEQ ID NO: 54 and 3 CDRs of SEQ ID NO. 56, and

iii) the first scFv domain having a binding affinity to 4-1BB, the Fab domain having a binding affinity to PD-L1, the second scFv domain having a binding affinity to ROR1, and the third scFv domain having a binding affinity to CD3, wherein the tetra-specific anti-body monomer comprises,

a. 3 CDRs of SEQ ID NO. 2 and 3 CDRs of SEQ ID NO: 4, 3 CDRs of SEQ ID NO. 14 and 3 CDRs of SEQ ID NO. 16, 3 CDRs of SEQ ID NO: 26 and 3 CDRs of SEQ ID NO. 28, and 3 CDRs of SEQ ID NO: 54 and 3 CDRs of SEQ ID NO. 56; or

b. 3 CDRs of SEQ ID NO. 2 and 3 CDRs of SEQ ID NO: 4, 3 CDRs of SEQ ID NO. 14 and 3 CDRs of SEQ ID NO. 16, 3 CDRs of SEQ ID NO. 22 and 3 CDRs of SEQ ID NO. 24, and 3 CDRs of SEQ ID NO. 50 and 3 CDRs of SEQ ID NO. 52.