Evidence map›Paper›PMID 32614170›Full record

ArticleAnalytical chemistry2020

Raman Spectroscopy to Monitor Post-Translational Modifications and Degradation in Monoclonal Antibody Therapeutics.

Bethan S McAvan, Leo A Bowsher, Thomas Powell, John F O'Hara, Mariangela Spitali, Royston Goodacre, Andrew J Doig

Open access · hybridAbstract read
In one paragraph

Article in Analytical chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
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  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. [Latest Research Findings on Health Management Based on Saliva Testing].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2021
    Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Bethan S McAvanSchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
Leo A BowsherUCB Celltech, UCB Pharma, Limited, 208 Bath Road, Slough, Berkshire SL1 3WE, United Kingdom.
Thomas PowellUCB Celltech, UCB Pharma, Limited, 208 Bath Road, Slough, Berkshire SL1 3WE, United Kingdom.ORCID 0000-0002-8308-6510
John F O'HaraUCB Celltech, UCB Pharma, Limited, 208 Bath Road, Slough, Berkshire SL1 3WE, United Kingdom.
Mariangela SpitaliUCB Celltech, UCB Pharma, Limited, 208 Bath Road, Slough, Berkshire SL1 3WE, United Kingdom.
Royston GoodacreDepartment of Biochemistry, Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, United Kingdom.ORCID 0000-0003-2230-645X
Andrew J DoigDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.ORCID 0000-0003-0346-2270
UCB Pharma (United Kingdom) · GBUniversity of Manchester · GBUniversity of Liverpool · GB

Funding

Biotechnology and Biological Sciences Research Council
6 · The paper itself

Abstract

Monoclonal antibodies (mAbs) represent a rapidly expanding market for biotherapeutics. Structural changes in the mAb can lead to unwanted immunogenicity, reduced efficacy, and loss of material during production. The pharmaceutical sector requires new protein characterization tools that are fast, applicable in situ and to the manufacturing process. Raman has been highlighted as a technique to suit this application as it is information-rich, minimally invasive, insensitive to water background and requires little to no sample preparation. This study investigates the applicability of Raman to detect Post-Translational Modifications (PTMs) and degradation seen in mAbs. IgG4 molecules have been incubated under a range of conditions known to result in degradation of the therapeutic including varied pH, temperature, agitation, photo, and chemical stresses. Aggregation was measured using size-exclusion chromatography, and PTM levels were calculated using peptide mapping. By combining principal component analysis (PCA) with Raman spectroscopy and circular dichroism (CD) spectroscopy structural analysis we were able to separate proteins based on PTMs and degradation. Furthermore, by identifying key bands that lead to the PCA separation we could correlate spectral peaks to specific PTMs. In particular, we have identified a peak which exhibits a shift in samples with higher levels of Trp oxidation. Through separation of IgG4 aggregates, by size, we have shown a linear correlation between peak wavenumbers of specific functional groups and the amount of aggregate present. We therefore demonstrate the capability for Raman spectroscopy to be used as an analytical tool to measure degradation and PTMs in-line with therapeutic production.

Indexed as

Protein Processing, Post-TranslationalAntibodies, MonoclonalCircular DichroismHumansImmunoglobulin GPeptide MappingProtein ConformationSpectrum Analysis, RamanAntibodies, MonoclonalImmunoglobulin G

Identifiers

PMID32614170
PMCPMC7467412
OpenAlexW3038175287

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.