An Improved Cell Culture Process for Production of Omalizumab
Abstract
The demand for biopharmaceutical products such as monoclonal antibodies (MAbs), fusion proteins, viral vaccines, and hormones is rapidly increasing. Mammalian cell cultures with ease of process operations are adopted to get the desired product. The challenges of low productivity and impurities in the desired product can be eliminated by optimizing the process parameters. The present study focuses on the optimization of temperature with other parameters to achieve improved titer and reduced heterogeneity in Omalizumab. An anti-IgE antibody expressed in mammalian cell culture. It is noticed that maintaining a specific temperature of 36.5° C ± 0.5 and pH 6.8± 0.1 during fed-batch cell culture provides improved quality (reduced galactosylation and reduced acidic variants) and quantity (improved titer) of the Omalizumab.
Keywords: antibody, omalizumab, mammalian cells, acidic variants
Downloads
References
Sharker SM, Rahman A. A Review on the Current Methods of Chinese Hamster Ovary (CHO) Cells Cultivation for the Production of Therapeutic Protein. Curr Drug Discov Technol. 2021; 18(3):354-364. https://doi.org/10.2174/1570163817666200312102137 PMid:32164511
https://www.bioreactors.net/bioreactor-operational-requirements (accessed 4 July 2023)
Radhakrishnan D et al. Strategies to enhance productivity and modify product quality in therapeutic proteins. Curr. Opin. Chem. Eng. (2018). https://doi.org/10.1016/j.coche.2018.09.005
Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, van As A, Gupta N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. (2001) Aug; 108(2):184-90. https://doi.org/10.1067/mai.2001.117880 PMid:11496232
Du Y, Walsh A, Ehrick R, Xu W, May K, Liu H. Chromatographic analysis of the acidic and basic species of recombinant monoclonal antibodies. MAbs. (2012) Sep-Oct; 4(5):578-85. https://doi.org/10.4161/mabs.21328 PMid:22820257 PMCid:PMC3499298
McDonald AG, Hayes JM, Bezak T, Głuchowska SA, Cosgrave EF, Struwe WB, Stroop CJ, Kok H, van de Laar T, Rudd PM, Tipton KF, Davey GP. Galactosyltransferase 4 is a major control point for glycan branching in N-linked glycosylation. J Cell Sci. 2014; 127(Pt 23):5014-26. https://doi.org/10.1242/jcs.151878 PMid:25271059 PMCid:PMC4248093
Hodoniczky J, Zheng YZ, James DC. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol Prog. (2005) Nov-Dec; 21(6):1644-52. https://doi.org/10.1021/bp050228w PMid:16321047
Szabo M, Filep C, Nagy M, Sarkozy D, Szigeti M, Sperling E, Csanky E, Guttman A, N-glycosylation structure - function characterization of Omalizumab, an anti-asthma biotherapeutic product. J. Pharm. Biomed. Anal., 209 (2022), Article 114483, https://doi.org/10.1016/j.jpba.2021.114483 PMid:34864596
Copyright (c) 2023 Kaumil Bhavsar, Kasuhal Joshi, Ghanshyam Patel, Parth Vaishnav, Om Narayan, Abhishek Sharma, Hetal Katrodiya, Vivek Dave, Chandramauli Rawal
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
. 