Viral clearance by low pH hold
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsJena Daya, Valerie Ann Cusick, John Mattila
Life of this patent
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Abstract
Methods for viral clearance using low pH hold based on a statistical design of experiment are provided. Several factors are evaluated to characterize the impacts of a low pH hold step for virus inactivation, including the factors of pH conditions, conductivity conditions, protein type, temperature, acid titrant, spike timing, and post-spike filtration. In addition to the effect of pH on virus inactivation, an increase in ionic strength through manipulating the conductivity can be a key component that influences virus inactivation kinetics.
Claims38
A method for purifying a peptide or protein from a sample, the method comprising:
- subjecting the sample to increasing ionic strength by addition of sodium chloride, wherein the concentration of the sodium chloride is from about 1 mM to about 100 mM;
- subjecting the sample to an acidic pH, and
- subsequently maintaining the sample at the ionic strength condition and the pH condition for at least about 15 minutes to inactivate a quantity of viral particles;
- wherein the sample comprises one or more impurities including the viral particles.
A method of producing a preparation comprising a protein of interest and a reduced amount of viral particles from a sample having the protein of interest and an viral particle, comprising:
- subjecting the sample to a pH of greater than about 3.6;
- subjecting the sample to an increase in ionic strength condition by addition of sodium chloride to the starting solution, wherein the concentration of sodium chloride is from about 1 mM to about 100 mM;
- and
- maintaining the sample at the pH and ionic strength condition for an appropriate amount of time to produce the preparation comprising the protein of interest and the reduced amount of viral particles.
A method for purifying a peptide or protein from a sample containing IgG1 or IgG4, the method comprising:
- subjecting the sample to increasing ionic strength by addition of a salt, wherein the concentration of the salt is from about 1 mM to about 100 mM;
- subjecting the sample to an acidic pH, and
- subsequently maintaining the sample at the ionic strength condition and the pH condition for at least about 15 minutes to inactivate a quantity of viral particles;
- wherein the sample comprises one or more impurities including the viral particles.
Dependencies are inferred from the claim text.