Evidence map›Paper›PMID 39144567›Full record

ArticleACS pharmacology & translational science2024

A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach.

Georgina B Armstrong, Alan Lewis, Vidhi Shah, Paul Taylor, Craig J Jamieson, Glenn A Burley, William Lewis, Zahra Rattray

Abstract read
In one paragraph

Article in ACS pharmacology & translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

8 authors.

Georgina B ArmstrongDrug Substance Development, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, U.K.ORCID https://orcid.org/0009-0007-3846-0554
Alan LewisComputational and Modelling Sciences, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
Vidhi ShahLarge Molecule Discovery, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
Paul TaylorDrug Substance Development, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
Craig J JamiesonDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K.ORCID https://orcid.org/0000-0002-6567-8272
Glenn A BurleyDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K.ORCID https://orcid.org/0000-0002-4896-113X
William LewisDrug Substance Development, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
Zahra RattrayStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, U.K.ORCID https://orcid.org/0000-0002-8371-8549

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high-value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterized. Protein-protein interactions elevate solution viscosity in high-concentration formulations, impacting physicochemical stability, manufacturability, and the injectability of mAbs. Therefore, in this manuscript, the key molecular descriptors and biophysical properties of a model anti-IL-8 IgG1 and its IgG3 ortholog are characterized. A computational and experimental framework was applied to measure molecular descriptors impacting their downstream developability. Findings from this approach underpin a detailed understanding of the molecular characteristics of IgG3 mAbs as potential therapeutic entities. This work is the first report examining the manufacturability of IgG3 for high-concentration mAb formulations. While poorer conformational and colloidal stability and elevated solution viscosity were observed for IgG3, future efforts controlling surface potential through sequence-engineering of solvent-accessible patches can be used to improve biophysical parameters that dictate mAb developability.

Identifiers

PMID39144567
PMCPMC11320737

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Read underepoch 390

Registered trials

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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.