US 12,247,074 B2
Antibody molecules
Francisca Wollerton, Cambridge (GB); Matthew Lakins, Cambridge (GB); Mateusz Wydro, Cambridge (GB); Sachin Surade, Cambridge (GB); and Michael Dyson, Sawston Cambridgeshire (GB)
Assigned to INVOX PHARMA LIMITED, London (GB)
Appl. No. 17/259,642
Filed by F-star Beta Limited, Cambridge (GB)
PCT Filed Jul. 12, 2019, PCT No. PCT/EP2019/068804
§ 371(c)(1), (2) Date Jan. 12, 2021,
PCT Pub. No. WO2020/011973, PCT Pub. Date Jan. 16, 2020.
Claims priority of application No. 1811403 (GB), filed on Jul. 12, 2018.
Prior Publication US 2021/0301022 A1, Sep. 30, 2021
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2827 (2013.01) [A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/526 (2013.01); C07K 2317/565 (2013.01); C07K 2317/71 (2013.01)] 21 Claims
 
1. An antibody or antigen-binding fragment thereof, capable of binding specifically to PD-L1, comprising a variable heavy (VH) domain comprising heavy chain complementarity determining regions (CDRs) HCDR1, HCRD2 and HCDR3, and a variable light (VL) domain comprising light chain CDRs LCDR1, LCDR2 and LCDR3, wherein the antibody or antigen-binding fragment thereof comprises an antigen-binding site comprising HCDR1, HCRD2, HCDR3, LCDR1, LCDR2 and LCDR3;
wherein the antigen-binding site comprises HCDR1, HCRD2, HCDR3, LCDR1, LCDR2 and LCDR3 of antibody:
(a) G1AA/E12v2 of SEQ ID NO: 1, 18, 3, 15, 16 and 17;
(b) G1AA/G12v2 of SEQ ID NO: 1, 18, 3, 19, 20, and 21;
(c) G1AA/E05v2 of SEQ ID NO: 1, 18, 3, 19, 20 and 22;
(d) G1/887_04_E12 of SEQ ID NO: 1, 23, 3, 15, 16 and 17;
(c) G1/887_04_G12 of SEQ ID NO: 1, 23, 3, 19, 20 and 21;
(f) G1/894_08_E05 of SEQ ID NO: 1, 23, 3, 19, 20 and 22;
(g) G1/894_08_A05 of SEQ ID NO: 1, 23, 3, 19, 20 and 24;
(h) G1AA/lambdav3 of SEQ ID NO: 1, 18, 3, 25, 13 and 14;
(i) G1/280_02_G02_NS of SEQ ID NO: 1, 23, 3, 26, 13 and 14; or
(j) G1/280_02_G02 of SEQ ID NO: 1, 78, 3, 26, 13 and 14;
wherein the sequences are defined by Kabat nomenclature; and/or
wherein the antigen-binding site comprises HCDR1, HCRD2, HCDR3, LCDR1, LCDR2 and LCDR3 of antibody:
(a) G1AA/E12v2 of SEQ ID NO: 102, 111, 69, 103, 71 and 17;
(b) G1AA/G12v2 of SEQ ID NO: 94, 111, 69, 100, 71, and 21;
(c) G1AA/E05v2 of SEQ ID NO: 94, 111, 69, 100, 71 and 22;
(d) G1/887_04_E12 of SEQ ID NO: 102, 98, 69, 103, 71 and 17;
(c) G1/887_04_G12 of SEQ ID NO: 94, 98, 69, 100, 77 and 21;
(f) G1/894_08_E05 of SEQ ID NO: 94, 98, 69, 100, 71 and 22;
(g) G1/894_08_A05 of SEQ ID NO: 94, 98, 69, 100, 106 and 24;
(h) G1AA/lambdav3 of SEQ ID NO: 94, 111, 69, 132, 77 and 14;
(i) G1/280_02_G02 NS of SEQ ID NO: 94, 98, 69, 96, 77 and 14; or
(j) G1/280_02_G02 of SEQ ID NO: 94, 95, 69, 96, 77 and 14;
wherein the sequences are defined by ImMunoGeneTics (IMGT) nomenclature;
and wherein:
when the antigen-binding site of the antibody or antigen-binding fragment thereof comprises HCDR1, HCRD2, HCDR3, LCDR1, LCDR2 and LCDR3 of antibody G1AA/E12v2 of SEQ ID NO: 1, 18, 3, 15, 16 and 17, antibody G1AA/G12v2 of SEQ ID NO: 1, 18, 3, 19, 20, and 21, or antibody G1AA/E05v2 of SEQ ID NO: 1, 18, 3, 19, 20 and 22, and/or HCDR1, HCRD2, HCDR3, LCDR1, LCDR2 and LCDR3 of antibody G1AA/E12v2 of SEQ ID NO: 102, 111, 69, 103, 71 and 17, antibody G1AA/G12v2 of SEQ ID NO: 94, 111, 69, 100, 71, and 21, or antibody G1AA/E05v2 of SEQ ID NO: 94, 111, 69, 100, 71 and 22,
the antibody or antigen-binding fragment thereof does not comprise a CD137 antigen-binding site comprising a first amino acid sequence and a second amino acid sequence located in the AB structural loop and the EF structural loop, respectively, of a CH3 domain of the antibody or antigen-binding fragment thereof, wherein the first amino acid sequence and the second amino acid sequence are PYIIPPY and GADRWLE, NPPYLFS and DYWRWLE, or NPPYLFS and YHWRWLE, respectively.