Evidence map›Paper›PMID 39479787›Full record

ArticleAnalytical chemistry2024

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

Ben Niu, Benjamin Lee, Wen Chen, Cristian Alberto, Karen Betancourt Moreira, Philip Compton, Kristoff Homan, Jason Pinckney, Yaxing Zhu, Michelle Vendel and 6 more

Abstract read
In one paragraph

Article in Analytical chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ben NiuDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.ORCID 0000-0002-6646-9085
Benjamin LeeDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Wen ChenDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Cristian AlbertoDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Karen Betancourt MoreiraDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Philip ComptonDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Kristoff HomanDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Jason PinckneyDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Yaxing ZhuDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Michelle VendelDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Karl WetterhornDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Shana WalrondDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Esrath SanthaDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Amanda HorowitzDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Nicole ZaubiDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.
Jeffrey JohnsonDepartment of Discovery Biotherapeutics, Bristol Myers Squibb, San Diego, California 92121, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific antibodies (bsAbs) and multispecific antibodies (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 their increased molecular complexity. One prominent challenge is the correct assembly of light and heavy chains, as improper pairing leads to mispaired or incompletely assembled species that lack therapeutic efficacy and possess undesired properties, impairing the developability, manufacturability, and safety. There is a critical need for rapid, sensitive analytical tools to monitor and control these undesired species and ensure the quality assessment of bsAbs and msAbs. To address this need, we present a novel high-throughput, format-agnostic intact mass workflow that significantly enhances the efficiency of detecting and quantifying biotherapeutic products and related impurities. This workflow integrates automated sample preparation, novel high-resolution rapid mass detection powered by SampleStream-MS, and an advanced data analysis pipeline. It offers increased throughput and data quality while substantially reducing analysis turnover time and labor. This was demonstrated in a pilot program where ∼800 multispecific antibodies were processed in 10 working days. The article details the evaluation and validation of our method, demonstrating its repeatability and intermediate precision in terms of measurement accuracy and relative quantification of various product-related species. We underscore the transformative potential of this end-to-end high-throughput workflow in expediting bispecific and multispecific antibody discovery, optimizing production processes, and ensuring high-quality development and manufacturing for therapeutic antibodies.

Indexed as

Antibodies, BispecificMass SpectrometryProteinsAutomationCell LineChromatography, LiquidHumansProtein EngineeringReproducibility of ResultsTime FactorsAntibodies, BispecificProteins

Identifiers

PMID39479787
PMCPMC11562946

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.