US 12,264,198 B2
Tandem diabody for CD16A-directed NK-cell engagement
Thorsten Ross, Edingen-Neckarhausen (DE); Ivica Fucek, Hattersheim (DE); Kristina Ellwanger, Heidelberg (DE); Michael Weichel, Bischofsheim (DE); Uwe Reusch, Maikammer (DE); Stefan Knackmuss, Planckstadt (DE); Erich Rajkovic, Schriessheim (DE); and Martin Treder, Heidelberg (DE)
Assigned to AFFIMED GMBH, Mannheim (DE)
Filed by Affimed GmbH, Heidelberg (DE)
Filed on Oct. 26, 2021, as Appl. No. 17/510,738.
Application 17/510,738 is a continuation of application No. 16/520,218, filed on Jul. 23, 2019, granted, now 11,180,558.
Application 16/520,218 is a continuation of application No. PCT/EP2018/054989, filed on Feb. 28, 2018.
Claims priority of application No. 17158566 (EP), filed on Feb. 28, 2017; and application No. 17174407 (EP), filed on Jun. 2, 2017.
Prior Publication US 2022/0041717 A1, Feb. 10, 2022
Int. Cl. C07K 16/28 (2006.01); A61P 35/00 (2006.01)
CPC C07K 16/283 (2013.01) [A61P 35/00 (2018.01); C07K 2317/31 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/626 (2013.01); C07K 2317/732 (2013.01); C07K 2317/92 (2013.01)] 11 Claims
 
1. A dimeric multispecific antigen-binding molecule specifically binding to CD16A and a target cell antigen different from CD16A consisting of two polypeptide chains, wherein each polypeptide chain comprises at least four variable domains selected from the group consisting of:
(i) a heavy chain variable domain specific for CD16A (VH_CD16A) comprising a heavy chain CDR1 comprising the amino acid sequence set forth in SEQ ID NO:1; a heavy chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO:7; a heavy chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO:3,
(ii) a light chain variable domain specific for CD16A (VL_CD16A) comprising a light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO:4; a light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO:5; and a light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO:6,
(iii) a heavy chain variable domain specific for the target cell antigen (VH_TA), and
(iv) a light chain variable domain specific for the target cell antigen (VL_TA),
wherein
these variable domains are linked one after another by peptide linkers L1, L2 and L3 consisting of 12 or less amino acid residues and positioned within each of the two polypeptide chains from the N-terminus to the C-terminus in the order:
VH TA-L1-VL_CD16A-L2-VH_CD16A-L3-VL TA.