Native human antibodies for immune checkpoint modulation targets TIM-3 and B7-H3

Inventors

Estelles, Angeles • Gishizky, Mikhail • RYSER, Stefan • Kauvar, Lawrence M.

Assignees

Trellis Bioscience Inc

Abstract

Novel monoclonal antibodies directed against immune checkpoint modulator (ICM) proteins TIM-3 and B7-H3 are useful in treating cancer and immune system disorders.

Core Innovation

The document describes native human monoclonal antibodies isolated using CellSpot2 technology that specifically bind an extracellular portion of immune checkpoint modulator (ICM) protein targets. The targets include TIM-3 (CD366) and B7-H3 (CD276), and the antibodies are directed to these extracellular domains as immune checkpoint modulators. The antibodies are presented as native human monoclonal antibodies and effective antigen-binding portions with binding specificity to TIM-3 or B7-H3.

The invention is centered on antibodies that bind extracellular TIM-3 or extracellular B7-H3 to modulate immune checkpoint pathways. The rationale presented in the background is the need to target TIM-3 as a negative regulator of T-cell responses and B7-H3 as tumor-restricted and associated with immune evasion. The disclosed binders are positioned for modulation relevant to cancer and immune system disorders.

The core invention includes defined antibody binding regions using CDRs from specific TRL antibody variable-region definitions. For TIM-3, the document reports anti-TIM-3 monoclonal antibodies TRL6042, TRL6061, TRL6099, and TRL6120, and for B7-H3 it reports anti-B7-H3 monoclonal antibody TRL4542. Experimental cloning results are summarized for these native human antibodies, including sub-nM affinity findings for selected anti-TIM-3 antibodies, and the disclosure includes representative variable-region sequence identifiers (SEQ ID NOs 1-10).

The document further describes recombinant production/formats and intended therapeutic and diagnostic uses for the antibodies and/or their effective antigen-binding portions. It also references antibody formats including bispecific/multispecific and chimeric antibody formats, and includes discussion of pharmaceutical compositions and related intended uses. The disclosed binders are positioned for applications including cancer treatment and diagnostic detection, as well as treatment of immune system disorders.

Claims Coverage

The independent claims cover two classes of immune-checkpoint-targeting monoclonal antibodies, with binding specificity defined by inventive CDR sets. One independent claim covers TIM-3-binding antibodies using CDRs from four TRL TIM-3 variable-region definitions, and the other independent claim covers B7-H3-binding antibodies using CDRs from a single TRL B7-H3 variable-region definition. Overall, the claims center on extracellular binding to the specified ICM proteins and define the antibody binding regions using the listed CDRs from the specified SEQ ID NOs.

The claim set provides coverage for extracellular TIM-3-binding antibodies defined by CDR sets from TRL6042, TRL6061, TRL6099, or TRL6120 heavy and light chain variable regions, and for B7-H3-binding antibodies defined by TRL4542 heavy and light chain variable-region CDRs. Dependent claim coverage further addresses permitted antibody/portion formats and adds contexts of pharmaceutical compositions and intended uses including cancer treatment, diagnostic detection, and immune system disorder treatment.

Stated Advantages

Documented Applications