Cell culture media supplementation of bioflavonoids for the targeted reduction of acidic species charge variants on recombinant therapeutic proteins.
Charge variants in recombinant proteins are an important series of protein modifications, whose potential role on protein stability, activity, immunogenicity, and pharmacokinetics continues to be studied. Monoclonal antibodies in particular have been shown to have a wide range of acidic species variants, including those associated with the addition of covalent modifications as well as the chemical degradation at specific peptide regions on the antibody. These variants play a significant role toward the overall heterogeneity of recombinant therapeutic proteins and are typically monitored during manufacturing to ensure they lie within proven acceptable ranges. In this work, it has been found that the supplementation of members of the bioflavonoid chemical family into mammalian cell culture media was effective toward the reduction of acidic species charge variants on recombinant monoclonal antibodies and dual variable domain immunoglobulins. The demonstrated reduction in acidic species through the use of bioflavonoids facilitates the manufacturing of a less heterogeneous product with potential improvements in antibody structure and function.
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Patrick
P
Hossler
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Min
M
Wang
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Sean
S
McDermott
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Christopher
C
Racicot
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Kofi
K
Chemfe
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Yun
Y
Zhang
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Christopher
C
Chumsae
Process Sciences, Global Pharmaceutical Operations, AbbVie Bioresearch Center, Worcester, MA, 01605.
Anton
A
Manuilov
D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002392:Catechin / Q000031:analogs & derivatives; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry* / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism*; D012431:Rutin
D003470:Culture Media; D005419:Flavonoids; D011994:Recombinant Proteins; D012431:Rutin; D002392:Catechin; C045651:epigallocatechin gallate
EGCG; acidic species; bioflavonoids; charge heterogeneity; mammalian cell culture