Patent ID: 11866507
Assignee: INHIBRX, INC.
Field: Biotechnology (Chemistry)
Classification: CPC C  A | IPC A  C

Claim 0:
1. A multispecific polypeptide construct, the multispecific polypeptide construct comprising a first component comprising a heterodimeric immunoglobulin Fc region and a second component comprising a CD3-binding region wherein:
the first and second components are coupled by a first linker that is a polypeptide of 2-18 amino acids in length composed of at least 50% Glycine residues, wherein the Fc region is amino-terminal to the CD3-binding region;
the CD3-binding region is an anti-CD3 disulfide stabilized Fv antibody fragment (dsFv) comprising a variable heavy chain (VH) and a variable light chain (VL), wherein the VH has the amino acid sequence of SEQ ID NO: 44 or a sequence that exhibits at least 90% sequence identity to SEQ ID NO: 44, and the VL has the amino acid sequence of SEQ ID NO: 72 or a sequence that exhibits at least 90% sequence identity to SEQ ID NO: 72, wherein the VH and VL are each linked to opposite polypeptides of the heterodimeric Fc by the first linker;
each of the Fc polypeptides of the heterodimeric Fc region comprises a knob-into-hole modification or a charge mutation to increase electrostatic complementarity of the Fc polypeptides;
the first component comprises at least one antigen binding domain that is a single domain antibody (sdAb) and binds a tumor associated antigen (TAA), wherein each of the at least one antigen binding domain of the first component is linked amino-terminal to the Fc region by a second linker that is a polypeptide of 2-6 amino acids in length composed of at least 50% Glycine residues; and
the second component further comprises at least one antigen binding domain that is a sdAb and binds to the same TAA as the first component, wherein each of the at least one antigen binding domain of the second component is linked carboxy-terminal to the CD3-binding region by a third linker that is a polypeptide of 2-6 amino acids in length composed of at least 50% Glycine residues,
wherein (i) each of the sdAbs is a camelid VHH or a humanized camelid VHH; and (ii) the CD3-binding region is not able to bind cell surface CD3 as determined by flow cytometry, unless the at least one antigen binding domain is bound to its TAA.