ArticlemAbs
Establishing in vitro in vivo correlations to screen monoclonal antibodies for physicochemical properties related to favorable human pharmacokinetics.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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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
68 citing papers in PubMed, 97 citations in OpenAlex.
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- Prediction of antibody non-specificity using protein language models and biophysical parameters.mAbs · 2026Article
- Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation.mAbs · 2026Article
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- Efficient inference of non-polyreactive antibody variants dependent on local fine-tuning.mAbs · 2026Article
- Ultra-Dilute Developability Analysis of Antibody Self-Association and Non-Specific Binding.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Pioneer: a synthetic human antibody phage display library for rapid therapeutic lead generation.mAbs · 2025Article
- A novelmAbs · 2025Article
- Using phage display for rational engineering of a higher-affinity humanized 3' phosphohistidine-specific antibody.Communications chemistry · 2025Article
- Development of an mPBPK machine learning framework for early target pharmacology assessment of biotherapeutics.Scientific reports · 2025Article
- Isoelectric point, net charge and amino acid analysis of experimentally validated therapeutic antibodies.In silico pharmacology · 2025Article
- Rat as a Predictive Model for Human Clearance and Bioavailability of Monoclonal Antibodies.Antibodies (Basel, Switzerland) · 2024Article
- A minimal physiologically based pharmacokinetic model to study the combined effect of antibody size, charge, and binding affinity to FcRn/antigen on antibody pharmacokinetics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Protein language models enable prediction of polyreactivity of monospecific, bispecific, and heavy-chain-only antibodies.Antibody therapeutics · 2024Article
- Nonspecificity fingerprints for clinical-stage antibodies in solution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- "Redirecting an anti-IL-1β antibody to bind a new, unrelated and computationally predicted epitope on hIL-17A".Communications biology · 2023Article
- Application of Modelling and Simulation Approaches to Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies in Pediatric Population.Pharmaceutics · 2023Review
- Physiologically Based Pharmacokinetic Modeling to Characterize the Effect of Molecular Charge on Whole-Body Disposition of Monoclonal Antibodies.The AAPS journal · 2023Article
- Surface patches induce nonspecific binding and phase separation of antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Implementation of in vitro assays that correlate with in vivo human pharmacokinetics (PK) would provide desirable preclinical tools for the early selection of therapeutic monoclonal antibody (mAb) candidates with minimal non-target-related PK risk. Use of these tools minimizes the likelihood that mAbs with unfavorable PK would be advanced into costly preclinical and clinical development. In total, 42 mAbs varying in isotype and soluble versus membrane targets were tested in in vitro and in vivo studies. MAb physicochemical properties were assessed by measuring non-specific interactions (DNA- and insulin-binding ELISA), self-association (affinity-capture self-interaction nanoparticle spectroscopy) and binding to matrix-immobilized human FcRn (surface plasmon resonance and column chromatography). The range of scores obtained from each in vitro assay trended well with in vivo clearance (CL) using both human FcRn transgenic (Tg32) mouse allometrically projected human CL and observed human CL, where mAbs with high in vitro scores resulted in rapid CL in vivo. Establishing a threshold value for mAb CL in human of 0.32 mL/hr/kg enabled refinement of thresholds for each in vitro assay parameter, and using a combinatorial triage approach enabled the successful differentiation of mAbs at high risk for rapid CL (unfavorable PK) from those with low risk (favorable PK), which allowed mAbs requiring further characterization to be identified. Correlating in vitro parameters with in vivo human CL resulted in a set of in vitro tools for use in early testing that would enable selection of mAbs with the greatest likelihood of success in the clinic, allowing costly late-stage failures related to an inadequate exposure profile, toxicity or lack of efficacy to be avoided.
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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.