Evidence map›Paper›PMID 30130444›Full record

ArticlemAbs2018

High-throughput screening of antibody variants for chemical stability: identification of deamidation-resistant mutants.

Danielle M DiCara, Nisana Andersen, Ruby Chan, James A Ernst, Gai Ayalon, Greg A Lazar, Nicholas J Agard, Amy Hilderbrand, Isidro Hötzel

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
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  4. Intrinsic physicochemical profile of marketed antibody-based biotherapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2021
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  6. Review
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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

9 authors.

Danielle M DiCaraa Department of Antibody Engineering , Genentech Inc ., South San Francisco , CA , USA.
Nisana Andersenb Protein Analytical Chemistry , Genentech Inc ., South San Francisco , CA , USA.
Ruby Chanc Department of Protein Chemistry , Genentech Inc ., South San Francisco , CA , USA.
James A Ernstc Department of Protein Chemistry , Genentech Inc ., South San Francisco , CA , USA.
Gai Ayalond Department of Neuroscience , Genentech Inc ., South San Francisco , CA , USA.
Greg A Lazara Department of Antibody Engineering , Genentech Inc ., South San Francisco , CA , USA.
Nicholas J Agarda Department of Antibody Engineering , Genentech Inc ., South San Francisco , CA , USA.
Amy Hilderbrandc Department of Protein Chemistry , Genentech Inc ., South San Francisco , CA , USA.
Isidro Hötzela Department of Antibody Engineering , Genentech Inc ., South San Francisco , CA , USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Developability assessment of therapeutic antibody candidates assists drug discovery by enabling early identification of undesirable instabilities. Rapid chemical stability screening of antibody variants can accelerate the identification of potential solutions. We describe here the development of a high-throughput assay to characterize asparagine deamidation. We applied the assay to identify a mutation that unexpectedly stabilizes a critical asparagine. Ninety antibody variants were incubated under thermal stress in order to induce deamidation and screened for both affinity and total binding capacity. Surprisingly, a mutation five residues downstream from the unstable asparagine greatly reduced deamidation. Detailed assessment by LC-MS analysis confirmed the predicted improvement. This work describes both a high-throughput method for antibody stability screening during the early stages of antibody discovery and highlights the value of broad searches of antibody sequence space.

Indexed as

AmidesAnimalsAntibodiesAntibodies, MonoclonalAntibody AffinityAsparagineChromatography, LiquidDrug DiscoveryHigh-Throughput Screening AssaysHumansMutationProtein BindingProtein StabilityTandem Mass SpectrometryAmidesAntibodiesAntibodies, MonoclonalAsparagineAntibodiesasparagine deamidationdevelopabilityHTP developability assessmentsurface plasmon resonancetherapeutic antibody development

Identifiers

PMID30130444
PMCPMC6204805
OpenAlexW2888560739

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.