Evidence map›Paper›PMID 24700358›Full record

ArticleJournal of pharmaceutical sciences2014

Small-angle x-ray scattering screening complements conventional biophysical analysis: comparative structural and biophysical analysis of monoclonal antibodies IgG1, IgG2, and IgG4.

Xinsheng Tian, Annette E Langkilde, Matthias Thorolfsson, Hanne B Rasmussen, Bente Vestergaard

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of pharmaceutical sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

36 citing papers in PubMed, 74 citations in OpenAlex.

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  11. Getting Smaller by Denaturation: Acid-Induced Compaction of Antibodies.The journal of physical chemistry letters · 2023
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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

5 authors at 2 institutions in 1 country.

Xinsheng TianDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Annette E Langkilde
Matthias Thorolfsson
Hanne B Rasmussen
Bente Vestergaard
University of Copenhagen · DKNovo Nordisk (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A crucial step in the development of therapeutic monoclonal antibodies is the selection of robust pharmaceutical candidates and screening of efficacious protein formulations to increase the resistance toward physicochemical degradation and aggregation during processing and storage. Here, we introduce small-angle X-ray scattering (SAXS) to characterize antibody solution behavior, which strongly complements conventional biophysical analysis. First, we apply a variety of conventional biophysical techniques for the evaluation of structural, conformational, and colloidal stability and report a systematic comparison between designed humanized IgG1, IgG2, and IgG4 with identical variable regions. Then, the high information content of SAXS data enables sensitive detection of structural differences between three IgG subclasses at neutral pH and rapid formation of dimers of IgG2 and IgG4 at low pH. We reveal subclass-specific variation in intermolecular repulsion already at low and medium protein concentrations, which explains the observed improved stability of IgG1 with respect to aggregation. We show how excipients dramatically influence such repulsive effects, hence demonstrating the potential application of extensive SAXS screening in antibody selection, eventual engineering, and formulation development.

Indexed as

Antibodies, MonoclonalBiophysicsChromatography, GelChromatography, High Pressure LiquidHumansImmunoglobulin GProtein ConformationScattering, Small AngleAntibodies, MonoclonalImmunoglobulin GanalysisIgG antibodyphysicochemical propertiesprotein aggregationprotein formulationsmall-angle X-ray scattering (SAXS)stability

Identifiers

PMID24700358
PMCPMC4298811
OpenAlexW2056925186

What OpenQuestion holds

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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.