Multispecific antigen binding proteins

A multispecific protein comprising a first and a second polypeptide chain each comprising a variable domain fused to a CH1 or Cκ domain (a V-(CH1/Cκ) unit), in turn fused at its C-terminus to a human Fc domain, wherein the V-(CH1/Cκ) unit of the first chain is bound, by CH1-Cκ dimerization, to the V-(CH1/Cκ) unit of the second chain thereby foaming a first antigen binding domain and a dimeric Fc domain, wherein one of the polypeptide chains further comprises an antigen binding domain that forms a second antigen binding domain, and wherein the Fc domain comprises N-linked glycosylation at residue N297 (Kabat EU numbering) and binds to a human CD16 polypeptide.

A multispecific protein comprising three polypeptide chains, each comprise a variable domain fused to a CH1 or Cκ domain (a V-(CH1/Cκ) unit), wherein a first (central) chain comprises two V-(CH1/Cκ) units and a human Fc domain interposed between the units, the second chain comprises one V-(CH1/Cκ) unit and a human Fc domain, and the third chain comprises one V-(CH1/Cκ) unit, wherein one of the V-(CH1/Cκ) units of the central chain is bound, by CH1-Cκ dimerization, to the V-(CH1/Cκ) unit of the second chain thereby forming a first antigen binding domain and a dimeric Fc domain, and wherein the other of the V-(CH1/Cκ) units of the central chain is bound, by CH1-Cκ dimerization, to the V-(CH1/Cκ) unit of the third chain thereby forming a second antigen binding domain, and wherein the Fc domain comprises N-linked glycosylation at residue N297 (Kabat EU numbering) and binds to a human CD16 polypeptide.

A multispecific protein that binds to three antigens of interest and to a human CD16 polypeptide, the protein comprising three polypeptide chains that each comprise a variable domain fused to a CH1 or Cκ domain (a V-(CH1/Cκ) unit), wherein a first (central) chain comprises, from N- to C-terminus, a first V-(CH1/Cκ) unit, a human Fc domain and a second V-(CH1/Cκ) unit, and a second chain comprise from N- to C-terminus a first V-(CH1/Cκ) unit and a human Fc domain, and a third chain comprises a V-(CH1/Cκ) unit, and wherein the first V-(CH1/Cκ) unit of the central chain is bound, by CH1-Cκ dimerization, to the V-(CH1/Cκ) unit of the second chain thereby forming a first antigen binding domain and a dimeric Fc domain, wherein the second V-(CH1/Cκ) unit of the central chain is bound, by CH1-Cκ dimerization, to the V-(CH1/Cκ) unit of the third chain thereby forming a second antigen binding domain, and wherein the third polypeptide chain further comprises an antigen binding domain that forms a third antigen binding domain.

The protein of claim 2, wherein the multispecific protein is a trimer with a dimeric Fc domain, having the domain arrangement:

• wherein one V1 is a light chain variable domain and the other VI is a heavy chain variable domain, wherein one V2 is a light chain variable domain and the other V2 is a heavy chain variable domain, wherein the V1 pair will form a first ABD, and the V2 pair will form a second ABD.