ArticleJournal of pharmaceutical and biomedical analysis2016
Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure.
Article in Journal of pharmaceutical and biomedical analysis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
25 citing papers in PubMed, 47 citations in OpenAlex.
- Simple Hydrodynamic Molecular Weight Model for Rapid Assessment of Therapeutic Protein Oligomerization States in Formulation.The AAPS journal · 2026Article
- Recent Advances in Atomic-Resolution NMR Investigations of Monoclonal Antibodies.Biomolecules · 2026Review
- Integration of NMR Spectroscopy in an Analytical Workflow to Evaluate the Effects of Oxidative Stress on Abituzumab: Beyond the Fingerprint of mAbs.Analytical chemistry · 2023Article
- Analytical Techniques for the Characterization and Quantification of Monoclonal Antibodies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Best Practices for Submission of NMR Data to Support Higher Order Structure Assessment of Generic Peptide Drugs.The AAPS journal · 2023Article
- Site-selective oral delivery of therapeutic antibodies to the inflamed colonActa pharmaceutica Sinica. B · 2022Article
- Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.Bioactive materials · 2022Article
- Principal Component Analysis of 1D 1H Diffusion Edited NMR Spectra of Protein Therapeutics.Journal of pharmaceutical sciences · 2021Article
- NMR Spectroscopy for Protein Higher Order Structure Similarity Assessment in Formulated Drug Products.Molecules (Basel, Switzerland) · 2021Article
- Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies.International journal of molecular sciences · 2020Review
- Sedimentation Velocity Analytical Ultracentrifugation Analysis of Marketed Rituximab Drug Product Size Distribution.Pharmaceutical research · 2020Article
- Principal component analysis for automated classification of 2D spectra and interferograms of protein therapeutics: influence of noise, reconstruction details, and data preparation.Journal of biomolecular NMR · 2020Article
- Assessment of the Higher-Order Structure of Formulated Monoclonal Antibody Therapeutics by 2D Methyl Correlated NMR and Principal Component Analysis.Current protocols in protein science · 2020Article
- Comparative Analysis of One-Dimensional Protein Fingerprint by Line Shape Enhancement and Two-DimensionalAnalytical chemistry · 2020Article
- An NMR-Based Similarity Metric for Higher Order Structure Quality Assessment Among U.S. Marketed Insulin Therapeutics.Journal of pharmaceutical sciences · 2020Article
- Crystal Structures of PF-06438179/GP1111, an Infliximab Biosimilar.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Article
- Chemometric Outlier Classification of 2D-NMR Spectra to Enable Higher Order Structure Characterization of Protein Therapeutics.Chemometrics and intelligent laboratory systems : an international journal sponsored by the Chemometrics Society · 2020Article
- Chemical Structure and Composition of Major Glycans Covalently Linked to Therapeutic Monoclonal Antibodies by Middle-Down Nuclear Magnetic Resonance.Analytical chemistry · 2018Article
- Chemometric Methods to Quantify 1D and 2D NMR Spectral Differences Among Similar Protein Therapeutics.AAPS PharmSciTech · 2018Article
- Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis.International journal of molecular sciences · 2018Review
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 at 1 institution in 1 country.
Funding
Abstract
Monoclonal antibody (mAb) drugs constitute the largest class of protein therapeutics currently on the market. Correctly folded protein higher order structure (HOS), including quinary structure, is crucial for mAb drug quality. The quinary structure is defined as the association of quaternary structures (e.g., oligomerized mAb). Here, several commonly available analytical methods, i.e., size-exclusion-chromatography (SEC) FPLC, multi-angle light scattering (MALS), circular dichroism (CD), NMR and multivariate analysis, were combined and modified to yield a complete profile of HOS and comparable metrics. Rituximab and infliximab were chosen for method evaluation because both IgG1 molecules are known to be homologous in sequence, superimposable in Fab crystal structure and identical in Fc structure. However, herein the two are identified to be significantly different in quinary structure in addition to minor secondary structure differences. All data collectively showed rituximab was mostly monomeric while infliximab was in mono-oligomer equilibrium driven by its Fab fragment. The quinary structure differences were qualitatively inferred from the less used but more reproducible dilution-injection-SEC-FPLC curve method. Quantitative principal component analysis (PCA) was performed on NMR spectra of either the intact or the in-situ enzymatic-digested mAb samples. The cleavage reactions happened directly in NMR tubes without further separation, which greatly enhanced NMR spectra quality and resulted in larger inter- and intra-lot variations based on PCA. The new in-situ enzymatic digestion method holds potential in identifying structural differences on larger therapeutic molecules using NMR.
Indexed as
Identifiers
What OpenQuestion holds
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.