Immunosuppresive agent

Inventors

Okazaki, Taku • SUGIURA, Daisuke • Maeda, Takeo • Shibayama, Shiro

Assignees

Ono Pharmaceutical Co Ltd • University of Tokushima NUC

Abstract

An immunosuppressive agent containing a substance that is selected from anti-CD80 antibodies and anti-PD-L1 antibodies and that promotes binding between PD-L1 and PD-1.

Core Innovation

The disclosure describes an immunosuppressive strategy using selected anti-CD80 or anti-PD-L1 antibodies to promote PD-L1 binding to PD-1. This is achieved by inhibiting the cis CD80–PD-L1 interaction on the same antigen-presenting cell. The approach restores or strengthens PD-1-mediated T-cell inhibition, including suppression of T-cell activation and IL-2 production.

The disclosure further specifies anti-CD80 antibody variants defined by heavy chain and light chain variable regions with defined CDR1, CDR2, and CDR3 amino acid sequences given by SEQ ID NOs 9–14 and 17–22. The described variants include conditions such as binding affinity (KD ≤ 10^-7 M), reduced interference with CD80–CTLA-4, and weak/non-strong inhibition of CD80–CD28. Functional rationale includes cis versus trans binding and PD-L1 pathway dependence.

Supporting discussion includes experiments and analysis of cis-interaction residue mapping using PD-L1 and CD80 mutants, including co-immunoprecipitation demonstrating CD80 with PD-L1, and T-cell IL-2 suppression assays. The disclosure also includes in vivo autoimmune and cancer model observations presented in support of the PD-1 pathway effects. Therapeutic and prophylactic embodiments are described for autoimmune, allergic, and graft-versus-host diseases, and pharmaceutical application embodiments are included.

Claims Coverage

The partial content includes two independent claims. Across these, the claims primarily cover two sets of defined anti-CD80 antibody CDR sequence combinations, and through dependent claims use of those antibodies as immunosuppressive and therapeutic agents for specified disease categories.

The claim coverage centers on two independent anti-CD80 antibody definitions specified by heavy- and light-chain CDR1–CDR3 amino acid sequences. Dependent claims further constrain variant identity using sequence identity thresholds relative to specified SEQ ID sequences and recast the antibodies as immunosuppressive and therapeutic agents for autoimmune disease, allergic disease, or graft-versus-host disease.

Stated Advantages

Documented Applications