Evidence map›Paper›PMID 30153083›Full record

ArticlemAbs

A systematic approach for analysis and characterization of mispairing in bispecific antibodies with asymmetric architecture.

Chunlei Wang, Bhargavi Vemulapalli, Mingyan Cao, Dhanesh Gadre, Jihong Wang, Alan Hunter, Xiangyang Wang, Dengfeng Liu

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
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

16 citing papers in PubMed, 50 citations in OpenAlex.

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  13. High sensitivity glycomics in biomedicine.Mass spectrometry reviews · 2022
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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

8 authors.

Chunlei Wanga Department of Analytical Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.
Bhargavi Vemulapallia Department of Analytical Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.ORCID 0000-0002-1677-1198
Mingyan Caoa Department of Analytical Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.
Dhanesh Gadreb Department of Purification Process Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.
Jihong Wanga Department of Analytical Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.
Alan Hunterb Department of Purification Process Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.
Xiangyang Wanga Department of Analytical Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.
Dengfeng Liua Department of Analytical Sciences , MedImmune, One Medimmune Way , Gaithersburg , MD , USA.ORCID 0000-0002-5816-4994

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunoglobulin G-like bispecific antibodies with asymmetric architecture are among the most widely used bispecific antibody formats for diagnostic and therapeutic applications. The primary technical challenge for this format is how to achieve correctly paired assembly of four unique polypeptide chains. Advances in protein engineering and process development are being used to overcome these challenges and are driving a corresponding demand for sensitive analytical tools to monitor and control mispaired species. Here, we report a systematic approach for analysis and characterization of mispairing in asymmetric bispecific antibodies. This approach consists of three orthogonal components, the first of which is a liquid chromatography (LC)-mass spectrometry (MS)-based method to measure the mass of intact antibodies. This method is used for fast analysis of mispairing and requires minimal method development, which makes it an ideal choice for early-stage development. The second component is a hydrophobic interaction chromatography (HIC)-based mispairing method that is suitable for lot release testing. The HIC method is robust and quality control friendly, and offers great linearity, precision, and accuracy. The third component is a two-dimensional LC-MS method for on-line chromatographic peak identification, which not only expedites this task but also reduces the risk of undesirable modifications during conventional fraction collection. These three methods dovetail to form the foundation of a complementary toolbox for analysis and characterization of mispairing in asymmetric bispecific antibodies and provide guidance and support for process development throughout the drug development life cycle.

Indexed as

AnimalsAntibodies, BispecificCHO CellsChromatography, LiquidCricetinaeCricetulusHydrogen-Ion ConcentrationImmunoglobulin GMolecular WeightPeptidesProtein EngineeringProtein MultimerizationProtein SubunitsReproducibility of ResultsTandem Mass SpectrometryAntibodies, BispecificImmunoglobulin GPeptidesProtein SubunitsBispecific antibodyDuetMabhydrophobic interaction chromatographymispairingtwo-dimensional liquid chromatography

Identifiers

PMID30153083
PMCPMC6284573
OpenAlexW2888805472

What OpenQuestion 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 OpenQuestion graph.