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Prediction of IgG1 aggregation in solution.

Ojala, Frida LU ; Degerman, Marcus LU ; Budde Hansen, Thomas; Broberg Hansen, Ernst and Nilsson, Bernt LU (2014) In Biotechnology Journal 9(6). p.800-804
Abstract
Interest in monoclonal antibody aggregation is increasing as aggregates of biopharma-ceuticals can cause an immunogenic response when injected into the body. In this work a stoichiometric reaction model from concentration-time data is developed to predict the dimer ratio in stored antibody solutions over time. IgG1 was incubated at pH from 4.5 to 5.5, salt concentrations from 100 to 600 mmol/kg and protein concentrations of 10.6 to 26.3 g/l; samples were taken at intervals of 20 minutes to five hours over time periods from 4 hours to 7.6 days, and analyzed with size-exclusion chromatography. The experiments showed the formation of dimers from monomers, but no higher order aggregates. Dilution of samples containing dimers led to the... (More)
Interest in monoclonal antibody aggregation is increasing as aggregates of biopharma-ceuticals can cause an immunogenic response when injected into the body. In this work a stoichiometric reaction model from concentration-time data is developed to predict the dimer ratio in stored antibody solutions over time. IgG1 was incubated at pH from 4.5 to 5.5, salt concentrations from 100 to 600 mmol/kg and protein concentrations of 10.6 to 26.3 g/l; samples were taken at intervals of 20 minutes to five hours over time periods from 4 hours to 7.6 days, and analyzed with size-exclusion chromatography. The experiments showed the formation of dimers from monomers, but no higher order aggregates. Dilution of samples containing dimers led to the reversal of the dimerization reaction. Measurements of the concentrations of each component were made by fitting exponentially modified Gaussian peaks to the chromatograms used to measure the concentrations of the different forms of protein. This stoichiometric reaction model was able to predict the formation of dimers by the antibody studied. The equilibrium constant was found to be dependent on the salt concentration, and the kinetic constant showed a dependence on the pH of the solution. The prediction of the aggregation leads to a possibility of optimizing the conditions in order to prevent the dimer formation and to maximize the monomer concentration. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biotechnology Journal
volume
9
issue
6
pages
800 - 804
publisher
John Wiley & Sons
external identifiers
  • pmid:24760776
  • wos:000337700000010
  • scopus:84901691457
ISSN
1860-6768
DOI
10.1002/biot.201400018
language
English
LU publication?
yes
id
6ce2a22a-9415-4fba-81a4-ebfb4f0b56bd (old id 4429533)
date added to LUP
2014-05-07 17:58:57
date last changed
2017-01-01 04:00:57
@article{6ce2a22a-9415-4fba-81a4-ebfb4f0b56bd,
  abstract     = {Interest in monoclonal antibody aggregation is increasing as aggregates of biopharma-ceuticals can cause an immunogenic response when injected into the body. In this work a stoichiometric reaction model from concentration-time data is developed to predict the dimer ratio in stored antibody solutions over time. IgG1 was incubated at pH from 4.5 to 5.5, salt concentrations from 100 to 600 mmol/kg and protein concentrations of 10.6 to 26.3 g/l; samples were taken at intervals of 20 minutes to five hours over time periods from 4 hours to 7.6 days, and analyzed with size-exclusion chromatography. The experiments showed the formation of dimers from monomers, but no higher order aggregates. Dilution of samples containing dimers led to the reversal of the dimerization reaction. Measurements of the concentrations of each component were made by fitting exponentially modified Gaussian peaks to the chromatograms used to measure the concentrations of the different forms of protein. This stoichiometric reaction model was able to predict the formation of dimers by the antibody studied. The equilibrium constant was found to be dependent on the salt concentration, and the kinetic constant showed a dependence on the pH of the solution. The prediction of the aggregation leads to a possibility of optimizing the conditions in order to prevent the dimer formation and to maximize the monomer concentration.},
  author       = {Ojala, Frida and Degerman, Marcus and Budde Hansen, Thomas and Broberg Hansen, Ernst and Nilsson, Bernt},
  issn         = {1860-6768},
  language     = {eng},
  number       = {6},
  pages        = {800--804},
  publisher    = {John Wiley & Sons},
  series       = {Biotechnology Journal},
  title        = {Prediction of IgG1 aggregation in solution.},
  url          = {http://dx.doi.org/10.1002/biot.201400018},
  volume       = {9},
  year         = {2014},
}