Evidence map›Paper›PMID 34747330›Full record

ArticlemAbs

Differences in human IgG1 and IgG4 S228P monoclonal antibodies viscosity and self-interactions: Experimental assessment and computational predictions of domain interactions.

Pin-Kuang Lai, Gaurav Ghag, Yao Yu, Veronica Juan, Laurence Fayadat-Dilman, Bernhardt L Trout

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  5. Fab-Fc and Fab-Fab interactions of variable strength and valency contribute to the high concentration viscosity of IgGProceedings of the National Academy of Sciences of the United States of America · 2026
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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

6 authors at 2 institutions in 1 country.

Pin-Kuang LaiDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts USA.
Gaurav GhagMerck & Co, Discovery Biologics, Protein Sciences Department, South San Francisco, CA , USA.
Yao YuMerck & Co, Discovery Biologics, Protein Sciences Department, South San Francisco, CA , USA.
Veronica JuanMerck & Co, Discovery Biologics, Protein Sciences Department, South San Francisco, CA , USA.
Laurence Fayadat-DilmanMerck & Co, Discovery Biologics, Protein Sciences Department, South San Francisco, CA , USA.
Bernhardt L TroutDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts USA.
Massachusetts Institute of Technology · USStevens Institute of Technology · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human/humanized IgG4 antibodies have reduced effector function relative to IgG1 antibodies, which is desirable for certain therapeutic purposes. However, the developability and biophysical properties for IgG4 antibodies are not well understood. This work focuses on the head-to-head comparison of key biophysical properties, such as self-interaction and viscosity, for 14 human/humanized, and chimeric IgG1 and IgG4 S228P monoclonal antibody pairs that contain the identical variable regions. Experimental measurements showed that the IgG4 S228P antibodies have similar or higher self-interaction and viscosity than that of IgG1 antibodies in 20 mM sodium acetate, pH 5.5. We report sequence and structural drivers for the increased viscosity and self-interaction detected in IgG4 S228P antibodies through a combination of experimental data and computational models. Further, we applied and extended a previously established computational model for IgG1 antibodies to predict the self-interaction and viscosity behavior for each antibody pair, providing insight into the structural characteristics and differences of these two isotypes. Interestingly, we observed that the IgG4 S228P swapped variants, where the CH3 domain was swapped for that of an IgG1, showed reduced self-interaction behavior. These domain swapped IgG4 S228P molecules also showed reduced viscosity from experiment and coarse-grained simulations. We also observed that experimental diffusion interaction parameter (kD) values have a high correlation with computational diffusivity prediction for both IgG1 and IgG4 S228P isotypes.Abbreviations:

Indexed as

Antibodies, MonoclonalImmunoglobulin GAntibodies, Monoclonal, HumanizedComplementarity Determining RegionsHumansViscosityAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedComplementarity Determining RegionsImmunoglobulin Gcomputational modelsdevelopabilitydiffusion interaction parameterIgG1IgG4PIgG4 S228PMonoclonal antibody self-interactionmonoclonal antibody viscosity

Identifiers

PMID34747330
PMCPMC8583000
OpenAlexW3214625166

What OpenQuestion holds

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LicenceCC BY-NC
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.