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US 11,685,776 B2Granted
Engineered heterodimeric proteins
AssigneeNovartis AG
InventorsRegis Cebe, Sebastien Irigaray, Darko Skegro
Life of this patent
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Abstract
The present invention provides heterodimeric antibodies and fragments thereof and methods for their preparation, wherein the pairing of heavy and light chains has been improved. Interface residues were mutated such that each light chain strongly favoured its cognate heavy chain when two different heavy chains and two different light chains were co-transfected and co-expressed in the same cell to assemble a functional, heterodimeric antibody or fragment thereof.
Claims16
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.
3 more elements
Dependencies are inferred from the claim text.