Biopharmaceutical benchmarks 2010

Walsh, Gary

doi:10.1038/nbt0910-917

Cited by 709 publications

(428 citation statements)

References 20 publications

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“…For example, in 2015 the world's top selling drug was AbbVie's monoclonal antibody Humira (adalimumab) 1. Biopharmaceuticals, including many antibody fragments that are currently in development,2, 3 are primarily produced in non‐human host cells, including Escherichia coli , rodent cell lines and yeast 4. During purification it is well established that small amounts of host cell protein (HCP), including intracellular proteins, will co‐purify with the production biopharmaceutical 5.…”

Section: Introductionmentioning

confidence: 99%

Influence of Escherichia coli chaperone DnaK on protein immunogenicity

et al. 2016

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SummaryThe production of anti‐drug antibodies can impact significantly upon the safety and efficacy of biotherapeutics. It is known that various factors, including aggregation and the presence of process‐related impurities, can modify and augment the immunogenic potential of proteins. The purpose of the investigations reported here was to characterize in mice the influence of aggregation and host cell protein impurities on the immunogenicity of a humanized single‐chain antibody variable fragment (scFv), and mouse albumin. Host cell protein impurities within an scFv preparation purified from Escherichia coli displayed adjuvant‐like activity for responses to the scFv in BALB/c strain mice. The 70 000 MW E. coli chaperone protein DnaK was identified as a key contaminant of scFv by mass spectrometric analysis. Preparations of scFv lacking detectable DnaK were spiked with recombinant E. coli DnaK to mimic the process‐related impurity. Mice were immunized with monomeric and aggregated preparations, with and without 0·1% DnaK by mass. Aggregation alone enhanced IgM and IgG2a antibody responses, but had no significant effect on total IgG or IgG1 responses. The addition of DnaK further enhanced IgG and IgG2a antibody responses, but only in the presence of aggregated protein. DnaK was shown to be associated with the aggregated scFv by Western blot analysis. Experiments with mouse albumin showed an overall increase in immunogenicity with protein aggregation alone, and the presence of DnaK increased the vigour of the IgG2a antibody response further. Collectively these data reveal that DnaK has the potential to modify and enhance immunogenicity when associated with aggregated protein.

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Section: Introductionmentioning

confidence: 99%

Influence of Escherichia coli chaperone DnaK on protein immunogenicity

et al. 2016

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“…This led to the worldwide regulatory approval of recombinant hGH. Recombinant hGH or somatropin is nowadays used for the treatment of GHD, as well as the treatment of Turner Syndrome and AIDS associated catabolism [13]. Recently, biosimilar somatropin formulations were also globally approved [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Analytical characterization of NOTA-modified somatropins

Bracke

Wynendaele

D׳Hondt

et al. 2014

Journal of Pharmaceutical and Biomedical Analysis

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Highlights• NOTA-labeled somatropins were synthesized using different NOTA:protein ratios.• Direct LC-MS and CE-MS approaches indicated multiple substitution degrees.• Bottom-up approaches gave structural insights and information on the labeling yield.• Lys-70 (in silico calculated pKa of 8.3) is the NOTA-modification hotspot.• We report a synthesis procedure for the production of target-specific radiopharmaceuticals.

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“…1). CHO cell lines are the preferred host expression system for many therapeutic proteins 2 , and the cells have been repeatedly approved by regulatory agencies. Moreover, they can be easily cultured in suspension and can produce high titers of human-compatible therapeutic proteins 3 .…”

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confidence: 99%

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome

Lewis¹,

et al. 2013

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Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.

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Biopharmaceutical benchmarks 2010

Cited by 709 publications

References 20 publications

Influence of Escherichia coli chaperone DnaK on protein immunogenicity

Influence of Escherichia coli chaperone DnaK on protein immunogenicity

Analytical characterization of NOTA-modified somatropins

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome

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