ArticlePloS one2020
Modeling and mitigation of high-concentration antibody viscosity through structure-based computer-aided protein design.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- 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 · 2026Article
- Article
- Review
- Article
- Article
- PROPERMAB: an integrative framework formAbs · 2025Article
- A framework for the biophysical screening of antibody mutations targeting solvent-accessible hydrophobic and electrostatic patches for enhanced viscosity profiles.Computational and structural biotechnology journal · 2024Article
- A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach.ACS pharmacology & translational science · 2024Article
- Biophysical cartography of the native and human-engineered antibody landscapes quantifies the plasticity of antibody developability.Communications biology · 2024Article
- Sequence-Based Viscosity Prediction for Rapid Antibody Engineering.Biomolecules · 2024Article
- Optimization of therapeutic antibodies for reduced self-association and non-specific binding via interpretable machine learning.Nature biomedical engineering · 2024Article
- Low-data interpretable deep learning prediction of antibody viscosity using a biophysically meaningful representation.Scientific reports · 2023Article
- Accelerating therapeutic protein design with computational approaches toward the clinical stage.Computational and structural biotechnology journal · 2023Review
- Structure-Based Optimization of Antibody-Based Biotherapeutics for Improved Developability: A Practical Guide for Molecular Modelers.Methods in molecular biology (Clifton, N.J.) · 2023Article
- How can we discover developable antibody-based biotherapeutics?Frontiers in molecular biosciences · 2023Review
- Non-specificity as the sticky problem in therapeutic antibody development.Nature reviews. Chemistry · 2022Review
- Antibodies with Weakly Basic Isoelectric Points Minimize Trade-offs between Formulation and Physiological Colloidal Properties.Molecular pharmaceutics · 2022Article
- Characterization and Modeling of Reversible Antibody Self-Association Provide Insights into Behavior, Prediction, and Correction.Antibodies (Basel, Switzerland) · 2021Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For an antibody to be a successful therapeutic many competing factors require optimization, including binding affinity, biophysical characteristics, and immunogenicity risk. Additional constraints may arise from the need to formulate antibodies at high concentrations (>150 mg/ml) to enable subcutaneous dosing with reasonable volume (ideally <1.0 mL). Unfortunately, antibodies at high concentrations may exhibit high viscosities that place impractical constraints (such as multiple injections or large needle diameters) on delivery and impede efficient manufacturing. Here we describe the optimization of an anti-PDGF-BB antibody to reduce viscosity, enabling an increase in the formulated concentration from 80 mg/ml to greater than 160 mg/ml, while maintaining the binding affinity. We performed two rounds of structure guided rational design to optimize the surface electrostatic properties. Analysis of this set demonstrated that a net-positive charge change, and disruption of negative charge patches were associated with decreased viscosity, but the effect was greatly dependent on the local surface environment. Our work here provides a comprehensive study exploring a wide sampling of charge-changes in the Fv and CDR regions along with targeting multiple negative charge patches. In total, we generated viscosity measurements for 40 unique antibody variants with full sequence information which provides a significantly larger and more complete dataset than has previously been reported.
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Registered trials
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.