Evidence map›Paper›PMID 30526254›Full record

ArticlemAbs2019

Deamidation and isomerization liability analysis of 131 clinical-stage antibodies.

Xiaojun Lu, R Paul Nobrega, Heather Lynaugh, Tushar Jain, Kyle Barlow, Todd Boland, Arvind Sivasubramanian, Maximiliano Vásquez, Yingda Xu

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

72 citing papers in PubMed, 142 citations in OpenAlex.

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  17. Heat-induced structural and chemical changes to a computationally designed miniprotein.Protein science : a publication of the Protein Society · 2024
    Article
  18. Article
  19. Good practices forEJNMMI radiopharmacy and chemistry · 2024
    Review
  20. Article

12 more citing papers are in PubMed but not listed here.

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 at 1 institution in 1 country.

Xiaojun Lua Protein Analytics , Adimab , Lebanon , NH , USA.
R Paul Nobregaa Protein Analytics , Adimab , Lebanon , NH , USA.
Heather Lynaugha Protein Analytics , Adimab , Lebanon , NH , USA.
Tushar Jainb Computational Biology , Adimab , Palo Alto , CA , USA.
Kyle Barlowb Computational Biology , Adimab , Palo Alto , CA , USA.ORCID 0000-0002-9787-0066
Todd Bolandb Computational Biology , Adimab , Palo Alto , CA , USA.
Arvind Sivasubramanianb Computational Biology , Adimab , Palo Alto , CA , USA.
Maximiliano Vásquezb Computational Biology , Adimab , Palo Alto , CA , USA.ORCID 0000-0002-8838-2298
Yingda Xua Protein Analytics , Adimab , Lebanon , NH , USA.
Adimab (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Contemporary in vivo and in vitro discovery platform technologies greatly increase the odds of identifying high-affinity monoclonal antibodies (mAbs) towards essentially any desired biologically relevant epitope. Lagging discovery throughput is the ability to select for highly developable mAbs with drug-like properties early in the process. Upstream consideration of developability metrics should reduce the frequency of failures in later development stages. As the field moves towards incorporating biophysical screening assays in parallel to discovery processes, similar approaches should also be used to ensure robust chemical stability. Optimization of chemical stability in the early stages of discovery has the potential to reduce complications in formulation development and improve the potential for successful liquid formulations. However, at present, our knowledge of the chemical stability characteristics of clinical-stage therapeutic mAbs is fragmented and lacks comprehensive comparative assessment. To address this knowledge gap, we produced 131 mAbs with amino acid sequences corresponding to the variable regions of clinical-stage mAbs, subjected these to low and high pH stresses and identified the resulting modifications at amino acid-level resolution via tryptic peptide mapping. Among this large set of mAbs, relatively high frequencies of asparagine deamidation events were observed in CDRs H2 and L1, while CDRs H3, H2 and L1 contained relatively high frequencies of instances of aspartate isomerization.

Indexed as

Antibodies, MonoclonalComplementarity Determining RegionsDrug DiscoveryHumansIsomerismProtein StabilityAntibodies, MonoclonalComplementarity Determining Regionsantibodyasparagine deamidationaspartic acid isomerizationchemical liabilitydevelopabilityforced degradationlow and high pH stresstryptic peptide mapping

Identifiers

PMID30526254
PMCPMC6343770
OpenAlexW2905282967

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.