Behavior of monoclonal antibodies: relation between the second virial coefficient (B (2)) at low concentrations and aggregation propensity and viscosity at high concentrations

Pharm Res. 2012 Feb;29(2):397-410. doi: 10.1007/s11095-011-0563-x. Epub 2011 Aug 19.


Purpose: To investigate relationship between second virial coefficient B (2) and viscosity and aggregation propensity of highly concentrated monoclonal antibody (MAbs) solutions.

Methods: Intermolecular interactions of 3 MAbs solutions with varying pH were characterized according to B (2) estimated by analytical ultracentrifugation sedimentation equilibrium with initial loading concentrations <10 mg/mL. Viscosity measurements and stability assessments of MAb solutions at concentrations higher than 100 mg/mL were conducted.

Results: B (2) of all MAb solutions depended on solution pH and have qualitative correlation with viscosity and aggregation propensity. The more negative the B (2) values, the more viscous the solution, acquiring increased propensity to aggregate. Solutions with B (2) values of ~2 × 10(-5) mL·mol/g(2) acquire similar viscosity and aggregation propensity regardless of amino acid sequences; for solutions with negative B (2) values, viscosity and aggregation propensity differed depending on sequences. Results suggest attractive intermolecular interactions represented by negative B (2) values are influenced by surface properties of individual MAbs.

Conclusions: B (2) can be used, within certain limitations, as an effective indicator of viscosity and aggregation propensity of highly concentrated MAb solutions.

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoglobulin G / chemistry*
  • Protein Stability
  • Solutions / chemistry
  • Temperature
  • Ultracentrifugation
  • Viscosity


  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Solutions