PreprintCited by 29Monoclonal and Polyclonal Antibodies Researchvaccines and immunoinformatics approachesBiosimilars and Bioanalytical Methods

Looking for therapeutic antibodies in next generation sequencing repositories

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Krawczyk, Konrad, Raybould, Matthew, Kovaltsuk, Aleksandr, Deane, Charlotte M.·2019·mAbs

Abstract

Recently it has become possible to query the great diversity of natural antibody repertoires using Next Generation Sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare Clinical Stage Therapeutic antibodies to the ∼1b sequences from 60 independent sequencing studies in the Observed Antibody Space Database. Of the 242 post Phase I antibodies, we find 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the discovery of antibody therapeutics and the legal protection of commercial antibodies.

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  • Many therapeutic CDRH3 loops can be found in naturally sourced NGS datasets, indicating a certain degree of convergence between antibodies raised experimentally and naturally occurring ones.

    “Furthermore, many therapeutic CDRH3 loops can be found in naturally sourced NGS datasets, indicating a certain degree of convergence between antibodies raised experimentally and naturally occurring ones [225].”

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Authors
Krawczyk, K., Raybould, M., Kovaltsuk, A., & Deane, C. M.
Affiliations
University of Oxford (GB)
Corresponding author
Krawczyk, Konrad
Venue
mAbs
Publisher
openRxiv
Published
2019-03-09
Volume
11
Issue
7
Pages
1197-1205
ISSN
1942-0862 (ISSN-L)
OpenAlex
W2950135969
Cited by
29
References
40
Citations by year
2025: 3 · 2024: 2 · 2023: 3 · 2022: 9 · 2021: 5 · 2020: 5 · 2019: 2
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • mAbs (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Engineering and Physical Sciences Research Council (1795796)
  • Biotechnology and Biological Sciences Research Council (1801486, BB/M011224/1)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Keywords
therapeutic antibodies, immunoglobulin gene repertoire
MeSH terms
Humans, Immunoglobulins, Immunotherapy, Complementarity Determining Regions, Databases, Genetic, Immunity, Humoral, Data Mining, High-Throughput Nucleotide Sequencing

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