ArticlemAbs2016
Mitigation of reversible self-association and viscosity in a human IgG1 monoclonal antibody by rational, structure-guided Fv engineering.
Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed.
- Article
- Article
- A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach.ACS pharmacology & translational science · 2024Article
- Sequence-Based Viscosity Prediction for Rapid Antibody Engineering.Biomolecules · 2024Article
- A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration.Bioengineering & translational medicine · 2024Article
- Comparative Thermodynamics of the Reversible Self-Association of Therapeutic mAbs Reveal Opposing Roles for Linked Proton- and Ion-Binding Events.Pharmaceutical research · 2023Article
- Low-data interpretable deep learning prediction of antibody viscosity using a biophysically meaningful representation.Scientific reports · 2023Article
- Utility of High Resolution 2D NMR Fingerprinting in Assessing Viscosity of Therapeutic Monoclonal Antibodies.Pharmaceutical research · 2022Article
- Assessment of Therapeutic Antibody Developability by Combinations of In Vitro and In Silico Methods.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Energetic Dissection of Mab-Specific Reversible Self-Association Reveals Unique Thermodynamic Signatures.Pharmaceutical research · 2021Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Strategies for Precise Engineering and Conjugation of Antibody Targeted-nanoparticles for Cancer Therapy.Current medical science · 2020Review
- Mitigation of liquid-liquid phase separation of a monoclonal antibody by mutations of negative charges on the Fab surface.PloS one · 2020Article
- Framework Mutations of the 10-1074 bnAb Increase Conformational Stability, Manufacturability, and Stability While Preserving Full Neutralization Activity.Journal of pharmaceutical sciences · 2020Article
- Modeling and mitigation of high-concentration antibody viscosity through structure-based computer-aided protein design.PloS one · 2020Article
- Selecting and engineering monoclonal antibodies with drug-like specificity.Current opinion in biotechnology · 2019Review
- Phase-Appropriate Application of Analytical Methods to Monitor Subvisible Particles Across the Biotherapeutic Drug Product Life Cycle.The AAPS journal · 2019Article
- Article
- Predicting B cell receptor substitution profiles using public repertoire data.PLoS computational biology · 2018Article
- In Silico Prediction of Diffusion Interaction Parameter (kPharmaceutical research · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Undesired solution behaviors such as reversible self-association (RSA), high viscosity, and liquid-liquid phase separation can introduce substantial challenges during development of monoclonal antibody formulations. Although a global mechanistic understanding of RSA (i.e., native and reversible protein-protein interactions) is sufficient to develop robust formulation controls, its mitigation via protein engineering requires knowledge of the sites of protein-protein interactions. In the study reported here, we coupled our previous hydrogen-deuterium exchange mass spectrometry findings with structural modeling and in vitro screening to identify the residues responsible for RSA of a model IgG1 monoclonal antibody (mAb-C), and rationally engineered variants with improved solution properties (i.e., reduced RSA and viscosity). Our data show that mutation of either solvent-exposed aromatic residues within the heavy and light chain variable regions or buried residues within the heavy chain/light chain interface can significantly mitigate RSA and viscosity by reducing the IgG's surface hydrophobicity. The engineering strategy described here highlights the utility of integrating complementary experimental and in silico methods to identify mutations that can improve developability, in particular, high concentration solution properties, of candidate therapeutic antibodies.
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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.