Novel non-cleavable triorthogonal linker technology for targeted antibody and peptide drug conjugates

Overview

This solution offers a novel non-cleavable linker technology designed for antibody drug conjugates (ADCs) and peptide drug conjugates (PDCs) used in targeted therapy for autoimmune diseases and cancer. Existing linker technologies rely primarily on bio-orthogonal designs and attach to antibodies through thiol groups, which requires disrupting disulfide bridges and results in significant antibody loss. The proposed triorthogonal linker overcomes these limitations by attaching via amino groups, enabling a more efficient conjugation process and supporting double drug payloads for enhanced therapeutic effect. The technology is particularly relevant for antigen-specific autoimmune conditions where targets such as anti-CD20, anti-IL6, and anti-TNF are involved.

Technical specifications

Key features:

• Triorthogonal linker design that extends beyond conventional bio-orthogonal linker chemistry
• Amino-group attachment site that avoids disrupting antibody disulfide bridges, reducing antibody loss during bioconjugation
• Double drug payload capability, allowing two therapeutic agents per conjugate for improved efficacy
• Non-cleavable architecture designed for enhanced target specificity in autoimmune and oncology applications
• Applicable to both antibody-based and peptide-based drug conjugates
• Synthesis and biological evaluation workflows have been established, including comparison against standard unconjugated drugs

Technology readiness level

The linker technology has progressed through synthesis of the final conjugate and biological evaluation against multiple targets, with results benchmarked against standard drug-only controls. The work has contributed to several publications. Future validation steps include identifying gene and protein targets for immunomodulation, selecting peptides from those proteins, synthesizing and evaluating candidate peptides, bioconjugating peptides to commercial drugs via the linker, refining linker chemistry for protein and peptide compatibility, producing complete ADC molecules, and evaluating them against potential targets. The technology is positioned for further development through collaborative partnerships.