	US 12,344,672 B2
	Antibody molecules that bind PD-L1 and CD137
Matthew Lakins, Cambridge (GB); Jose Munoz-Olaya, Cambridge (GB); Francisca Wollerton, Cambridge (GB); Sarah Batey, Cambridge (GB); Mihriban Tuna, Cambridge (GB); and Alexander Koers, Cambridge (GB)
Assigned to INVOX PHARMA LIMITED, London (GB)
Appl. No. 17/259,791
Filed by INVOX PHARMA LIMITED, London (GB)
PCT Filed Jul. 12, 2019, PCT No. PCT/EP2019/068793 § 371(c)(1), (2) Date Jan. 12, 2021, PCT Pub. No. WO2020/011964, PCT Pub. Date Jan. 16, 2020.
Claims priority of application No. 1811405 (GB), filed on Jul. 12, 2018; application No. 1818283 (GB), filed on Nov. 9, 2018; and application No. 1902594 (GB), filed on Feb. 26, 2019.
Prior Publication US 2022/0049007 A1, Feb. 17, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01)

CPC C07K 16/2878 (2013.01) [A61P 35/00 (2018.01); C07K 16/2827 (2013.01); A61K 2039/507 (2013.01); A61K 2039/545 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/526 (2013.01); C07K 2317/60 (2013.01); C07K 2317/75 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)]

25 Claims

1. An antibody molecule that binds to programmed death-ligand 1 (PD-L1) and CD137, comprising:

(a) a complementarity determining region (CDR)-based antigen-binding site for PD-L1; and

(b) a CD137 antigen-binding site located in a CH3 domain of the antibody molecule;

wherein the CDR-based antigen-binding site comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, defined according to the Kabat numbering scheme, set forth in:

(i) SEQ ID NOs: 1, 2, 3, 4, 5 and 6, respectively;

(ii) SEQ ID NOS: 1, 2, 3, 18, 19 and 20, respectively; or

(iii) SEQ ID NOs: 1, 2, 3, 18, 19 and 29, respectively; and/or

wherein the CDR-based antigen-binding site comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, defined according to the ImMunoGeneTics (IMGT) numbering scheme, set forth in:

(iv) SEQ ID NOs: 7, 8, 9, 10, 11 and 6, respectively;

(v) SEQ ID NOs: 21, 8, 9, 22, 11 and 20, respectively; or

(vi) SEQ ID NOs: 21, 8, 9, 22, 11 and 29, respectively; and

wherein the CD137 antigen-binding site comprises a first sequence and a second sequence located in the AB structural loop and the EF structural loop of the CH3 domain, respectively, wherein the first sequence and the second sequence are set forth in SEQ ID NOs: 113 and 114, SEQ ID NOs: 79 and 80, or SEQ ID NOs: 79 and 89, respectively.