title: Behavior of monoclonal antibodies: relation between the second virial coefficient (B                      (2)) at low concentrations and aggregation propensity and viscosity at high concentrations.
abstract: OBJECTIVE
  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.
authors.affiliation: Analytical & Quality Evaluation Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo, 134-8630, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Saito
authors.forename: Jun
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kishi
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Kiichi
authors.initials: K
authors.lastname: Fukui
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry*; D055550:Protein Stability; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D014461:Ultracentrifugation; D014783:Viscosity
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D012996:Solutions