What should next-generation analytical platforms for biopharmaceutical production look like?

Trends in biotechnology, Journal Year: 2023, Volume and Issue: 42(3), P. 282 - 292

Published: Sept. 27, 2023

Language: Английский

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Mass Spectrometry Advancements and Applications for Biomarker Discovery, Diagnostic Innovations, and Personalized Medicine

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9880 - 9880

Published: Sept. 12, 2024

Mass spectrometry (MS) has revolutionized clinical chemistry, offering unparalleled capabilities for biomolecule analysis. This review explores the growing significance of mass (MS), particularly when coupled with liquid chromatography (LC), in identifying disease biomarkers and quantifying biomolecules diagnostic prognostic purposes. The unique advantages MS accurately diverse molecules have positioned it as a cornerstone personalized-medicine advancement. MS-based technologies transformed precision medicine, enabling comprehensive understanding mechanisms patient-specific treatment responses. LC-MS shown exceptional utility analyzing complex biological matrices, while high-resolution expanded analytical capabilities, allowing detection low-abundance elucidation pathways. integration other techniques, such ion mobility spectrometry, opened new avenues biomarker discovery validation. As we progress toward will be crucial addressing challenges individualized patient care, driving innovations diagnosis, prognosis, strategies.

Language: Английский

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Facilitating high throughput bispecific antibody production and potential applications within biopharmaceutical discovery workflows

mAbs, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 21, 2024

A major driver for the recent investment surge in bispecific antibody (bsAb) platforms and products is multitude of distinct mechanisms action that bsAbs offer compared to a combination two monoclonal antibodies. Four bsAb were granted first regulatory approvals US or EU during 2023 biopharmaceutical industry pipeline brimming with candidates across broad range therapeutic applications. In previously reported discovery campaigns, following hypothesis-based choice specific target proteins, selections screening activities have often been performed mono-specific formats. The conversion modalities has usually positioned toward end process involved small numbers lead molecules, largely due challenges expressing, purifying, analyzing large bsAbs. this review, we discuss emerging strategies facilitate production expanded panels, focusing particularly upon combinatorial methods generate matrices. Such technologies will enable in. formats at earlier stages not only widening accessible protein space maximize chances success, but also advancing empirical bi-target validation assess initial selection hypotheses.

Language: Английский

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Multilevel─Intact, Subunits, and Peptides─Characterization of Antibody-Based Therapeutics by a Single-Column LC–MS Setup

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

A comprehensive characterization of biotherapeutics, mandated by regulatory authorities, requires analyses a protein drug at multiple structure levels. Such multilevel can be performed mass spectrometry (MS), with established conventional MS-based assays product quality attributes (PQAs) comprising intact and subunit middle-up MS analytes resolved on C4 column, bottom-up peptide mapping C18 column. Recent advances in have facilitated the increasing use middle-down analysis, expanding qualitative analytical capability for characterization. studies using less-retentive reversed-phase LC also offer an opportunity streamlining equipment configuration to single-column LC–MS setup therapeutic proteins. In this study, we developed robust method ZenoTOF 7600 evaluated NISTmAb, RG7221 bispecific antibody (bsAb), Fc-fusion etanercept protein, middle-up/down, analyses. Successful was demonstrated; notably, high sequence coverage post-translational modification profiling, including all 13 O- 3 N-glycosylation sites single run, were obtained LC–MS. This is first report analysis major TNFR Fc glycoforms. streamlined will enable more efficient workflows PQA assessment simplify integration analyzer as process technology instrument biopharma applications.

Language: Английский

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Recent developments of imaged capillary isoelectric focusing technology for in-depth biopharmaceutical characterization

TrAC Trends in Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 118212 - 118212

Published: Feb. 1, 2025

Language: Английский

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Immunocapture LC–MS Methods for Pharmacokinetics of Large Molecule Drugs

Bioanalysis, Journal Year: 2024, Volume and Issue: 16(7), P. 165 - 177

Published: Feb. 13, 2024

Implementation of immunocapture LC–MS methods to characterize the pharmacokinetic profile large molecule drugs has become a widely used technique over past decade. As pharmaceutical industry strives for speediness into clinical development without jeopardizing quality, robust assays with generic application across pipeline are becoming instrumental in bioanalysis, especially early-stage development. This review highlights capabilities and challenges involved hybrid techniques its continued applications nonclinical assay design. includes comparison LC–MS-based approaches conventional ligand-binding driving demands drug portfolios including growing sensitivity requirements unique new modalities requiring innovation bioanalytical laboratory.

Language: Английский

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An Online Two-Dimensional Approach to Characterizing the Charge-Based Heterogeneity of Recombinant Monoclonal Antibodies Using a 2D-CEX–AEX–MS Workflow

Journal of the American Society for Mass Spectrometry, Journal Year: 2023, Volume and Issue: 34(12), P. 2801 - 2810

Published: Nov. 23, 2023

Assessment of product quality attributes such as charge heterogeneity is an upmost requisite for the release a monoclonal antibody (mAb). Analytical techniques, cation-exchange chromatography (CEX), accomplish this, causing mAb to separate into acidic, main species, and basic variants. Here, online volatile-salt-containing two-dimensional liquid (2D-LC) method coupled with mass spectrometry (MS) was performed characterize mAbs using CEX in first dimension (D1) anion-exchange (AEX) second (D2). The peak profile D1 transferred through 2D heart-cut D2 further analysis by AEX-MS method. In method, A showed 10 distinct variants, while AEX resulted eight However, total 13 variants were successfully resolved Similarly, B exhibited seven four but 2D-LC revealed nine B. Likewise, C displayed AEX, whereas unveiled 11 C. Additionally, native MS that identified amidation, oxidation, isomerization Asp peak, which not stand-alone methods. present study demonstrates how can assist identifying minor variations distribution or conformation would otherwise be picked up single analytical alone.

Language: Английский

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Mass Spectrometry in Clinical Chemistry: Advancing Biomarker Discovery and Personalized Medicine

Published: Aug. 12, 2024

Mass spectrometry (MS) has revolutionized clinical chemistry, offering unparalleled capabilities for biomolecule analysis. This review explores the growing significance of MS, particularly when coupled with liquid chromatography (LC-MS), in identifying disease biomarkers and quantifying biomolecules diagnostic prognostic purposes. The unique advantages MS accurately diverse molecules have positioned it as a cornerstone personalized medicine advancement. MS-based technologies transformed precision medicine, enabling comprehensive understanding mechanisms patient-specific treatment responses. LC-MS shown exceptional utility analyzing complex biological matrices, while high-resolution expanded analytical capabilities, allowing detection low-abundance elucidation pathways. integration other techniques, such ion mobility spectrometry, opened new avenues biomarker discovery validation. As we progress towards will be crucial addressing challenges individualized patient care, driving innovations diagnosis, prognosis, strategies.

Language: Английский

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Future Horizons

Advances in educational technologies and instructional design book series, Journal Year: 2024, Volume and Issue: unknown, P. 114 - 134

Published: April 19, 2024

This chapter explores the transformative impact of artificial intelligence (AI) on various research domains. The highlights leading role AI platforms in development practices. In addition, describes fundamental concepts powered tools such as generative and large language models. narrative extends to integration modern practices, spotlighting its use hypothesis formulation, generation questions, data analysis. AI's contributions analysis many fields are explored, particularly automating processes generating insights. discussion further several applications domains RPA, Semantic Scholar, DeepChem. However, potential bias transparency main challenges AI-powered applications. Therefore, it is imperative champion explainable human-in-the-loop approaches improve confidence. recommends interdisciplinary collaboration between researchers developers.

Language: Английский

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End-To-End Automated Intact Protein Mass Spectrometry for High-Throughput Screening and Characterization of Bispecific and Multispecific Antibodies

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(45), P. 18287 - 18300

Published: Oct. 31, 2024

Bispecific antibodies (bsAbs) and multispecific (msAbs) represent a promising frontier in therapeutic antibody development, offering unique capabilities not achievable with traditional monoclonal antibodies. Despite their potential, significant challenges remain due to increased molecular complexity. One prominent challenge is the correct assembly of light heavy chains, as improper pairing leads mispaired or incompletely assembled species that lack efficacy possess undesired properties, impairing developability, manufacturability, safety. There critical need for rapid, sensitive analytical tools monitor control these ensure quality assessment bsAbs msAbs. To address this need, we present novel high-throughput, format-agnostic intact mass workflow significantly enhances efficiency detecting quantifying biotherapeutic products related impurities. This integrates automated sample preparation, high-resolution rapid detection powered by SampleStream-MS, an advanced data analysis pipeline. It offers throughput while substantially reducing turnover time labor. was demonstrated pilot program where ∼800 were processed 10 working days. The article details evaluation validation our method, demonstrating its repeatability intermediate precision terms measurement accuracy relative quantification various product-related species. We underscore transformative potential end-to-end high-throughput expediting bispecific discovery, optimizing production processes, ensuring high-quality development manufacturing

Language: Английский

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