	US 12,071,486 B2
	Bispecific antigen binding construct
Sebastian Van Der Woning, Bachte-Maria-Leerne (BE); and Christophe Blanchetot, Destelbergen (BE)
Assigned to argenx BV, Ghent (BE)
Filed by argenx BV, Zwijnaarde (BE)
Filed on Dec. 21, 2018, as Appl. No. 16/230,326.
Claims priority of provisional application 62/609,523, filed on Dec. 22, 2017.
Prior Publication US 2019/0218310 A1, Jul. 18, 2019
Int. Cl. C07K 16/46 (2006.01); C07K 16/00 (2006.01)

CPC C07K 16/468 (2013.01) [C07K 2317/22 (2013.01); C07K 2317/31 (2013.01); C07K 2317/52 (2013.01); C07K 2317/526 (2013.01); C07K 2317/55 (2013.01); C07K 2317/569 (2013.01); C07K 2317/64 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)]

4 Claims

1. A bispecific antigen binding construct comprising

(a) a single VHH domain of a heavy-chain-only antibody (VHH antibody) which binds a first target antigen, wherein said VHH domain is fused to the N-terminus of a first human IgG₁Fc domain polypeptide; and

(b) a single Fab portion of a conventional IgG antibody which binds a second target antigen, wherein said Fab portion is fused to the N-terminus of a second human IgG₁Fc domain polypeptide;

wherein the first and second IgG₁Fc domain polypeptides dimerize by knobs-into-holes interactions to form the bispecific antigen binding construct, and wherein the first human IgG₁Fc domain polypeptide comprises tryptophan at EU position 366, and the second human IgG₁Fc domain polypeptide comprises serine, alanine, and valine at EU positions 366, 368, and 407, respectively; or the second human IgG₁Fc domain polypeptide comprises tryptophan at EU position 366, and the first human IgG₁Fc domain polypeptide comprises serine, alanine, and valine at EU positions 366, 368, and 407, respectively.