Evidence map›Paper›PMID 38475982›Full record

ArticlemAbs

Reduction of monoclonal antibody viscosity using interpretable machine learning.

Emily K Makowski, Hsin-Ting Chen, Tiexin Wang, Lina Wu, Jie Huang, Marissa Mock, Patrick Underhill, Emma Pelegri-O'Day, Erick Maglalang, Dwight Winters and 1 more

Abstract 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 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

  1. Article
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  4. Article
  5. Article
  6. Review
  7. Review
  8. 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
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Viscosity of concentrated antibodies from a dynamic model of electrostatics.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Article
  16. Explainable Artificial Intelligence in the Field of Drug Research.Drug design, development and therapy · 2025
    Review
  17. Hybrid Mass Spectrometry Applied across the Production of Antibody Biotherapeutics.Journal of the American Society for Mass Spectrometry · 2025
    Article
  18. Article
  19. Article
  20. 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

11 authors.

Emily K MakowskiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
Hsin-Ting ChenBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Tiexin WangBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Lina WuBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Jie HuangDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
Marissa MockTherapeutic Discovery, Research, Amgen Inc, Thousand Oaks, CA, USA.
Patrick UnderhillDepartment of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
Emma Pelegri-O'DayTherapeutic Discovery, Research, Amgen Inc, Thousand Oaks, CA, USA.
Erick MaglalangDrug Product Technologies, Amgen Inc, Thousand Oaks, CA, USA.
Dwight WintersTherapeutic Discovery, Research, Amgen Inc, Thousand Oaks, CA, USA.
Peter M TessierDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3220-007X

Funding

Interdepartmental Training in Pharmacological SciencesT32GM140223 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Lori L. Isom · 2021 to 2026
$3.8M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
National Science Foundation CBET 1804313,CBET 1803497NIGMS NIH HHS T32 GM140223NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

Early identification of antibody candidates with drug-like properties is essential for simplifying the development of safe and effective antibody therapeutics. For subcutaneous administration, it is important to identify candidates with low self-association to enable their formulation at high concentration while maintaining low viscosity, opalescence, and aggregation. Here, we report an interpretable machine learning model for predicting antibody (IgG1) variants with low viscosity using only the sequences of their variable (Fv) regions. Our model was trained on antibody viscosity data (>100 mg/mL mAb concentration) obtained at a common formulation pH (pH 5.2), and it identifies three key Fv features of antibodies linked to viscosity, namely their isoelectric points, hydrophobic patch sizes, and numbers of negatively charged patches. Of the three features, most predicted antibodies at risk for high viscosity, including antibodies with diverse antibody germlines in our study (79 mAbs) as well as clinical-stage IgG1s (94 mAbs), are those with low Fv isoelectric points (Fv pIs < 6.3). Our model identifies viscous antibodies with relatively high accuracy not only in our training and test sets, but also for previously reported data. Importantly, we show that the interpretable nature of the model enables the design of mutations that significantly reduce antibody viscosity, which we confirmed experimentally. We expect that this approach can be readily integrated into the drug development process to reduce the need for experimental viscosity screening and improve the identification of antibody candidates with drug-like properties.

Indexed as

Antibodies, MonoclonalImmunoglobulin GIsoelectric PointMutationViscosityAntibodies, MonoclonalImmunoglobulin GAntibody engineeringchargecomputationdevelopabilityformulationFvhydrophobicityin silicoisoelectric pointmutation

Identifiers

PMID38475982
PMCPMC10939158

What OpenQuestion holds

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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.