Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions

Area of Science:

• Biophysical Chemistry
• Materials Science
• Pharmaceutical Formulation

Background:

• Monoclonal antibodies are crucial therapeutics but challenging to formulate at high concentrations due to viscosity.
• Understanding the molecular basis of antibody self-assembly is key to overcoming formulation hurdles.

Purpose of the Study:

• To establish a link between microscopic molecular details and macroscopic solution properties of monoclonal antibodies.
• To investigate the role of antibody clustering in solution viscosity.
• To guide the development of stable and effective antibody formulations.

Main Methods:

• Analysis of experimental small-angle X-ray scattering (SAXS) data.
• Application of analytical models used for polymers and colloids.
• Theoretical calculations and computer simulations of a coarse-grained antibody model.
• Characterization of antibody clusters and their size distributions.

Main Results:

• Experimental SAXS data were interpreted using models based on the presence of antibody clusters.
• Theoretical calculations and simulations predicted cluster size distributions.
• Predicted cluster distributions accurately described experimental structure factors across various conditions.
• Microscopic evidence was provided for clusters causing concentration-dependent viscosity increases.

Conclusions:

• Antibody clustering is the microscopic origin of increased solution viscosity.
• Findings offer insights into monoclonal antibody self-assembly.
• This understanding can inform the formulation of stable antibody therapeutics for patient self-administration.