A novel screening method to assess developability of antibody-like molecules

Area of Science:

• Biochemistry
• Biotechnology
• Pharmaceutical Development

Background:

• Monoclonal antibodies are vital biotherapeutics, but many fail due to poor developability factors.
• Identifying antibodies with high affinity is routine, yet assessing expression, solubility, stability, and interactions remains challenging.

Purpose of the Study:

• To introduce a high-performance liquid chromatography (HPLC)-based method for early assessment of biotherapeutic developability.
• To enable earlier selection of drug candidates with superior developability characteristics.

Main Methods:

• A simple HPLC screening method using a Zenix column was developed.
• The method requires only microgram quantities of protein and assesses colloidal stability, solubility, and interactions.

Main Results:

• Antibody retention times on the HPLC column correlated inversely with colloidal stability; aggregation-prone antibodies eluted later with broader peaks.
• Varying buffer salt content allowed estimation of antibody-column interactions.

Conclusions:

• This HPLC method provides a robust and early assessment of critical developability factors for monoclonal antibodies.
• The approach is potentially applicable to other biotherapeutic molecules, aiding in the selection of more developable drug candidates.