Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
Open accessAbstract
The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.S. Food and Drug Administration. Differences in strategy for optimizing the solution behavior of human IgG1 antibodies versus the IgG2 and IgG4 isotypes and the impact of pH alterations in formulation are discussed.
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Labute et al. reported structure-based charge calculations to predict PK clearance rate.
“Also, Labute et al. [36] reported structure-based charge calculations to predict PK clearance rate.”
From Computational and artificial intelligence-based methods for antibody development (2023) · cites this paper as [36]
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Computational and artificial intelligence-based methods for antibody development
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- Authors
- Thorsteinson, N., Gunn, J. R., Kelly, K., Long, W., & Labute, P.
- Affiliations
- Research and Development, Chemical Computing Group ULC, Montreal, Quebec, Canada
- Corresponding author
- Thorsteinson, Nels
- ORCID
- Thorsteinson, Nels
- Venue
- mAbs
- Publisher
- Informa UK Limited
- Published
- 2021-01-01
- Volume
- 13
- Issue
- 1
- Pages
- 1981805-1981805
- ISSN
- 1942-0862 (ISSN-L)
- 1942-0870
- PMC
- PMC8510563
- OpenAlex
- W3206994980
- Cited by
- 42
- References
- 31
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 7
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mAbs (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- no funding
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- therapeutic antibodies, viscosity prediction, hydrophobicity, antibody aggregation, developability, IgG1, IgG2, IgG4
- MeSH terms
- Antibodies, Monoclonal, Humans, Immunoglobulin G, Isoelectric Point, Viscosity
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