	US 12,319,739 B2
	Mesothelin and CD137 binding molecules
Jose Munoz-Olaya, Cambridge (GB); Mihriban Tuna, Cambridge (GB); Remi Fertin, Cambridge (GB); Claire Reader, Cambridge (GB); Francisca Wollerton, Cambridge (GB); and Neil Brewis, Cambridge (GB)
Assigned to INVOX PHARMA LIMITED, London (GB)
Appl. No. 17/259,634
Filed by F-star Delta Limited, Cambridge (GB)
PCT Filed Jul. 12, 2019, PCT No. PCT/EP2019/068817 § 371(c)(1), (2) Date Jan. 12, 2021, PCT Pub. No. WO2020/011976, PCT Pub. Date Jan. 16, 2020.
Claims priority of application No. 1811450 (GB), filed on Jul. 12, 2018.
Prior Publication US 2021/0309753 A1, Oct. 7, 2021
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/2878 (2013.01) [A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/35 (2013.01); C07K 2317/40 (2013.01); C07K 2317/72 (2013.01); C07K 2317/75 (2013.01); C07K 2317/92 (2013.01)]

22 Claims

1. An antibody molecule that binds to mesothelin (MSLN) and CD137, comprising

(a) a complementarity determining region (CDR)-based antigen-binding site for MSLN;

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 numbering scheme, set forth in:

(i) SEQ ID NOs 42, 33, 44, 20, 22, and 80, respectively [FS28-256-271];

(ii) SEQ ID NOs 14, 16, 27, 20, 22 and 24, respectively [FS28-024-052];

(iii) SEQ ID NOs 42, 33, 44, 20, 22, and 40, respectively [FS28-256-021];

(iv) SEQ ID NOs 42, 33, 44, 20, 22, and 37, respectively [FS28-256-012];

(v) SEQ ID NOs 50, 33, 52, 20, 22 and 40, respectively [FS28-256-023];

(vi) SEQ ID NOs 42, 33, 44, 20, 22 and 41, respectively [FS28-256-024];

(vii) SEQ ID NOs 50, 33, 52, 20, 22 and 41, respectively [FS28-256-026];

(viii) SEQ ID NOs 42, 33, 44, 20, 22, and 80, respectively [FS28-256-027];

(ix) SEQ ID NOs 38, 33, 35, 20, 22, and 40, respectively [FS28-256-001];

(x) SEQ ID NOs 38, 33, 35, 20, 22, and 41 respectively [FS28-256-005];

(xi) SEQ ID NOs 46, 33, 48, 20, 22 and 37, respectively [FS28-256-014];

(xii) SEQ ID NOs 50, 33, 52, 20, 22 and 37, respectively [FS28-256-018];

(xiii) SEQ ID NOs 31, 33, 35, 20, 22 and 37, respectively [FS28-256];

(xiv) SEQ ID NOs 14, 16, 25, 20, 22 and 24, respectively [FS28-024-051];

(xv) SEQ ID NOs 14, 16, 29, 20, 22 and 24, respectively [FS28-024-053]; or

(xvi) SEQ ID NOs 14, 16, 18, 20, 22 and 24, respectively [FS28-024]; 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 Kabat numbering scheme set forth in:

(i) SEQ ID NOs 43, 5, 45, 21, 23, and 80, respectively [FS28-256-271];

(ii) SEQ ID NOs 15, 17, 28, 21, 23 and 24, respectively [FS28-024-052];

(iii) SEQ ID NOs 43, 34, 45, 21, 23 and 40, respectively [FS28-256-021];

(iv) SEQ ID NOs 43, 34, 45, 21, 23 and 37, respectively [FS28-256-012];

(v) SEQ ID NOs 51, 34, 53, 21, 23 and 40, respectively [FS28-256-023];

(vi) SEQ ID NOs 43, 34, 45, 21, 23 and 41, respectively [FS28-256-024];

(vii) SEQ ID NOs 51, 34, 53, 21, 23 and 41, respectively [FS28-256-026];

(viii) SEQ ID NOs 43, 34, 45, 21, 23 and 80, respectively [FS28-256-027];

(ix) SEQ ID NOs 39, 34, 36, 21, 23 and 40, respectively [FS28-256-001];

(x) SEQ ID NOs 39, 34, 36, 21, 23 and 41, respectively [FS28-256-005];

(xi) SEQ ID NOs 47, 34, 49, 21, 23 and 37, respectively [FS28-256-014];

(xii) SEQ ID NOs 51, 34, 53, 21, 23 and 37, respectively [FS28-256-018];

(xiii) SEQ ID NOs 32, 34, 36, 21, 23 and 37, respectively [FS28-256];

(xiv) SEQ ID NOs 15, 17, 26, 21, 23 and 24, respectively [FS28-024-051];

(xv) SEQ ID NOs 15, 17, 30, 21, 23 and 24, respectively [FS28-024-053]; or

(xvi) SEQ ID NOs 15, 17, 19, 21, 23 and 24, respectively [FS28-024]; and

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

wherein the CD137 antigen-binding site comprises a first sequence and a second sequence located in the AB and EF structural loops of the CH3 domain, respectively, wherein the first and second sequence have the sequence set forth in SEQ ID NOs 10 and 11 [FS22-172-003], respectively.