Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody...

Area of Science:

• Biochemistry
• Protein Engineering
• Pharmaceutical Sciences

Background:

• Antibody aggregation is influenced by hydrophobicity.
• Charge calculations aid in predicting high-concentration viscosity and pharmacokinetic (PK) clearance.
• Understanding these factors is crucial for therapeutic antibody development.

Purpose of the Study:

• Evaluate structure-based charge descriptors for predicting antibody isoelectric point (pI), viscosity, and clearance.
• Develop rules for therapeutic antibody profiling to address developability challenges.
• Identify strategies for optimizing antibody solution behavior and formulation.

Main Methods:

• Utilized structure-based charge descriptors.
• Analyzed recently published antibody pI, viscosity, and clearance data.
• Devised four rules for therapeutic antibody profiling.

Main Results:

• Charge descriptors showed predictive performance for antibody pI, viscosity, and clearance.
• Four rules were established for profiling therapeutic antibodies.
• Differences in optimization strategies for IgG1, IgG2, and IgG4 isotypes were identified.

Conclusions:

• Structure-based charge calculations are valuable for predicting antibody developability.
• The devised rules aid in addressing hydrophobicity and charge-related issues in antibody design.
• Formulation pH and antibody isotype significantly impact solution behavior and require tailored optimization strategies.