US 11,685,776 B2
Engineered heterodimeric proteins
Regis Cebe, Saint-Louis (FR); Sebastien Irigaray, Mulhouse (FR); and Darko Skegro, Grenchen (CH)
Assigned to Novartis AG, Basel (CH)
Appl. No. 16/483,185
Filed by Novartis AG, Basel (CH)
PCT Filed Mar. 1, 2018, PCT No. PCT/IB2018/051305
§ 371(c)(1), (2) Date Aug. 2, 2019,
PCT Pub. No. WO2018/158719, PCT Pub. Date Sep. 7, 2018.
Claims priority of provisional application 62/465,937, filed on Mar. 2, 2017.
Prior Publication US 2019/0382475 A1, Dec. 19, 2019
Int. Cl. C07K 16/00 (2006.01); C12P 21/08 (2006.01); C07K 16/24 (2006.01); C07K 16/28 (2006.01); C07K 1/00 (2006.01)
CPC C07K 16/244 (2013.01) [C07K 16/2863 (2013.01); C07K 2317/31 (2013.01); C07K 2317/50 (2013.01); C07K 2317/522 (2013.01); C07K 2317/55 (2013.01); C07K 2317/60 (2013.01); C07K 2317/66 (2013.01)] 16 Claims
 
1. A heterodimeric IgG antibody or fragment thereof comprising at least two Fabs, wherein at least one Fab comprises:
(a) an engineered heavy chain variable domain (VH) and constant domain 1 (CH1) comprising an acidic amino acid at position 39, a basic amino acid at position 147 and an acidic amino acid at position 165; and an engineered light chain variable domain (VL) and constant domain (CL) comprising a basic amino acid at position 38, an acidic amino acid at position 124 and a basic amino acid at position 169 or 170, or
(b) an engineered VH domain and CH1 domain comprising a basic amino acid at position 39, an acidic amino acid at position 147 and a basic amino acid at position 165 and an engineered VL domain and CL domain comprising an acidic amino acid at position 38, a basic amino acid at position 124 and an acidic amino acid at position 169 or 170,
wherein said amino acids in the VH and CH1 domains and in the VL and CL domains pairwise are of opposing charge, and correspond to form an interface that is electrostatically favourable to heterodimerization,
wherein the acid amino acid is aspartic acid (D) or glutamic acid (E), the basic amino acid is arginine (R), lysine (K) or histidine (H), and
wherein the numbers are according to EU numbering.