ArticleProceedings of the National Academy of Sciences of the United States of America2021
Intrinsic physicochemical profile of marketed antibody-based biotherapeutics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
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- Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation.mAbs · 2026Article
- Humanized Anti-PD-1 Antibodies Generated Using The Conditional Kernel-Elastic Autoencoder.bioRxiv : the preprint server for biology · 2026Article
- An intrinsic sequence-structural profile for mRNA-delivered therapeutic antibodies.Briefings in bioinformatics · 2026Article
- Characterising nanobody developability to improve therapeutic design using the Therapeutic Nanobody Profiler.Communications biology · 2026Article
- Review
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- Article
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- Deep learning-based design and experimental validation of a medicine-like human antibody library.Briefings in bioinformatics · 2024Article
- Biophysical cartography of the native and human-engineered antibody landscapes quantifies the plasticity of antibody developability.Communications biology · 2024Article
- Contextualising the developability risk of antibodies with lambda light chains using enhanced therapeutic antibody profiling.Communications biology · 2024Article
- Human Dose and Pharmacokinetic Predictions for Biologics at Boehringer Ingelheim: A Retrospective Analysis.Advances in therapy · 2024Article
- Matrixed CDR grafting: A neoclassical framework for antibody humanization and developability.The Journal of biological chemistry · 2024Article
- NKp46-specific single domain antibodies enable facile engineering of various potent NK cell engager formats.Protein science : a publication of the Protein Society · 2023Article
- Embedding Dynamics in Intrinsic Physicochemical Profiles of Market-Stage Antibody-Based Biotherapeutics.Molecular pharmaceutics · 2023Article
- Accelerating therapeutic protein design with computational approaches toward the clinical stage.Computational and structural biotechnology journal · 2023Review
- How can we discover developable antibody-based biotherapeutics?Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Feeding biopharma pipelines with biotherapeutic candidates that possess desirable developability profiles can help improve the productivity of biologic drug discovery and development. Here, we have derived an in silico profile by analyzing computed physicochemical descriptors for the variable regions (Fv) found in 77 marketed antibody-based biotherapeutics. Fv regions of these biotherapeutics demonstrate significant diversities in their germlines, complementarity determining region loop lengths, hydrophobicity, and charge distributions. Furthermore, an analysis of 24 physicochemical descriptors, calculated using homology-based molecular models, has yielded five nonredundant descriptors whose distributions represent stability, isoelectric point, and molecular surface characteristics of their Fv regions. Fv regions of candidates from our internal discovery campaigns, human next-generation sequencing repertoires, and those in clinical-stages (CST) were assessed for similarity with the physicochemical profile derived here. The Fv regions in 33% of CST antibodies show physicochemical properties that are dissimilar to currently marketed biotherapeutics. In comparison, physicochemical characteristics of ∼29% of the Fv regions in human antibodies and ∼27% of our internal hits deviated significantly from those of marketed biotherapeutics. The early availability of this information can help guide hit selection, lead identification, and optimization of biotherapeutic candidates. Insights from this work can also help support portfolio risk assessment, in-licensing, and biopharma collaborations.
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