Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

The analytical strategy for characterizing post-translational modifications (PTMs) on monoclonal antibodies (mAbs) relies on liquid chromatography-mass spectrometry (LC-MS). Accurate PTM profiling is a required component of the data package for Investigational New Drug (IND) submissions, providing insight into product consistency, stability, and potential immunogenicity. Our approach provides the high-resolution data needed to support regulatory filings and minimize clinical risk for biologic programs.

Analytical Requirements for PTM Profiling

The biological activity and immunogenic potential of a monoclonal antibody are directly influenced by its structure. Post-translational modifications, which occur during cellular production, can introduce structural heterogeneity that impacts both efficacy and the patient’s immune response. A lack of precise characterization introduces significant risk into a therapeutic program.

Our >100,000 sq ft facility is equipped with advanced LC-MS instrumentation to provide definitive structural elucidation. By employing techniques like peptide mapping, we generate high-resolution data that forms a core component of the CMC section of an IND filing. This level of detail is necessary for establishing product specifications and ensuring batch-to-batch consistency.

Connecting Antibody Structure to Biological Function

A deep understanding of antibody structure is a core competency that extends across therapeutic modalities. Insights gained from characterizing human monoclonal antibodies that target viral vectors, for instance, inform how next-generation AAV capsids can be engineered to evade pre-existing immunity (PMID: 32733434). This same analytical rigor is applied to therapeutic mAbs, where the goal is to confirm the desired structure and minimize any modifications that could trigger an unwanted immune response.

This analytical foundation supports accelerated program timelines. Franklin Biolabs has maintained a 100% successful IND rate for client programs since 2019, with the Franklin Biolabs brand officially launching in 2024. Our integrated approach helps move candidates toward IND submission within an 18-24 month timeline.

Learn More: Watch the full video on process optimization.

A Phased Approach to mAb Characterization for IND

Every biologic requires a tailored preclinical strategy. Our analytical services follow a science-based, data-driven process tailored specifically to the attributes of your molecule.

• Initial Structural Confirmation: High-resolution mass spectrometry to confirm the primary sequence and intact mass of the mAb.

• Peptide Mapping for PTM Hotspot Identification: Enzymatic digestion followed by LC-MS/MS analysis to locate and identify specific PTMs across the entire molecule.

• Glycosylation Profiling: Specialized analysis to characterize the complex glycan structures attached to the antibody, as these heavily influence effector functions.

• Forced Degradation Studies: Exposing the mAb to stress conditions (e.g., heat, light, oxidation) to identify potential degradation pathways and inform stability studies.

This methodical approach provides the robust data package required by regulatory authorities, demonstrating a comprehensive understanding of the product substance. Accelerated characterization for rapid product validation is a key component of de-risking a program prior to clinical evaluation.