Anti-CD83 antibodies and use thereof

Inventors

Seldon, Therese Ann • Munster, David John • Hart, Derek Nigel John • Jones, Martina Louise • Munro, Trent Phillip • Mahler, Stephen Michael • Zhou, Yu • Marks, James D.

Assignees

Kira Biotech Pty Ltd • University of Queensland UQ • University of California • University of California San Diego UCSD

Abstract

The present disclosure relates to proteins that bind to CD83 and uses thereof, for example, in therapy, prophylaxis, diagnosis, or prognosis.

Core Innovation

The invention relates to a CD83 binding protein comprising an antigen binding domain that binds to CD83. The CD83 binding protein is defined by a heavy chain variable region (VH) and a light chain variable region (VL) that each include specific complementarity determining region (CDR) sets, including a VH comprising three CDRs of the amino acid sequence shown in SEQ ID NO: 1 and a VL comprising three CDRs selected from amino acid sequences shown in SEQ ID NO: 5, 6, 7, 8, or 9, or a consensus sequence shown in SEQ ID NO: 10.

The described embodiments include engineered CD83 binding antibodies derived from a human scFv phage display and reformatted to IgG1, including the antibody 3C12 and engineered variants. The document reports that 3C12 outcompetes RA83 in binding assays and delays xenogeneic GVHD in SCID mice with human PBMC, and it also addresses antibody format options such as scFv/di-scFv/Fc, Fab/F(ab')2/Fv, and separate or single-chain VH/VL arrangements.

Engineered improvements are also described, including light-chain affinity maturation variants such as 3C12.B–E with distinct VLs and improved binding kinetics, and a variant 3C12.C showing the best KD/KOFF. Glyco-engineering is described to generate a defucosylated antibody, such as 3C12.Kif, to increase Fc-mediated effector function including ADCC and to increase in vitro potency.

Claims Coverage

The independent claim in this document covers a CD83 binding protein defined by specific VH CDR sequences and allowable VL CDR sequence sets, including a consensus option and consensus-derived CDR selections. The independent claim includes one principal set of inventive features, with dependent claims refining the structural arrangement, antibody formats, functional Fc properties, and competitive epitope behavior.

Overall, the claim coverage centers on defining a CD83-binding antigen binding domain by a VH CDR set anchored to SEQ ID NO: 1 and a VL CDR set selected from specified options, including a consensus VL sequence and consensus-derived CDR combinations.

Stated Advantages

Documented Applications