A global comparability approach for biosimilar monoclonal antibodies using LC-tandem MS based proteomics

Shun Li Chen, Shiaw Lin Wu, Li Juan Huang, Jia Bao Huang, Shu-Hui Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Liquid chromatography-tandem mass spectrometry-based proteomics for peptide mapping and sequencing was used to characterize the marketed monoclonal antibody trastuzumab and compare it with two biosimilar products, mAb A containing D359E and L361M variations at the Fc site and mAb B without variants. Complete sequence coverage (100%) including disulfide linkages, glycosylations and other commonly occurring modifications (i.e., deamidation, oxidation, dehydration and K-clipping) were identified using maps generated from multi-enzyme digestions. In addition to the targeted comparison for the relative populations of targeted modification forms, a non-targeted approach was used to globally compare ion intensities in tryptic maps. The non-targeted comparison provided an extra-dimensional view to examine any possible differences related to variants or modifications. A peptide containing the two variants in mAb A, D359E and L361M, was revealed using the non-targeted comparison of the tryptic maps. In contrast, no significant differences were observed when trastuzumab was self-compared or compared with mAb B. These results were consistent with the data derived from peptide sequencing via collision induced dissociation/electron transfer dissociation. Thus, combined targeted and non-targeted approaches using powerful mass spectrometry-based proteomic tools hold great promise for the structural characterization of biosimilar products.

Original languageEnglish
Pages (from-to)126-135
Number of pages10
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume80
DOIs
Publication statusPublished - 2013 Jun 1

Fingerprint

Biosimilar Pharmaceuticals
Proteomics
Monoclonal Antibodies
Peptides
Peptide Mapping
Mass spectrometry
Tandem Mass Spectrometry
Glycosylation
Dehydration
Liquid Chromatography
Disulfides
Digestion
Mass Spectrometry
Liquid chromatography
Electrons
Ions
Enzymes
Population
Oxidation
Trastuzumab

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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abstract = "Liquid chromatography-tandem mass spectrometry-based proteomics for peptide mapping and sequencing was used to characterize the marketed monoclonal antibody trastuzumab and compare it with two biosimilar products, mAb A containing D359E and L361M variations at the Fc site and mAb B without variants. Complete sequence coverage (100{\%}) including disulfide linkages, glycosylations and other commonly occurring modifications (i.e., deamidation, oxidation, dehydration and K-clipping) were identified using maps generated from multi-enzyme digestions. In addition to the targeted comparison for the relative populations of targeted modification forms, a non-targeted approach was used to globally compare ion intensities in tryptic maps. The non-targeted comparison provided an extra-dimensional view to examine any possible differences related to variants or modifications. A peptide containing the two variants in mAb A, D359E and L361M, was revealed using the non-targeted comparison of the tryptic maps. In contrast, no significant differences were observed when trastuzumab was self-compared or compared with mAb B. These results were consistent with the data derived from peptide sequencing via collision induced dissociation/electron transfer dissociation. Thus, combined targeted and non-targeted approaches using powerful mass spectrometry-based proteomic tools hold great promise for the structural characterization of biosimilar products.",
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A global comparability approach for biosimilar monoclonal antibodies using LC-tandem MS based proteomics. / Chen, Shun Li; Wu, Shiaw Lin; Huang, Li Juan; Huang, Jia Bao; Chen, Shu-Hui.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 80, 01.06.2013, p. 126-135.

Research output: Contribution to journalArticle

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