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An antibody developability triaging pipeline exploiting protein language models

Martin, Andrew; Sweet-Jones, James; (2025) An antibody developability triaging pipeline exploiting protein language models. mAbs , 17 (1) , Article 2472009. 10.1080/19420862.2025.2472009. Green open access

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Abstract

Therapeutic monoclonal antibodies (mAbs) are a successful class of biologic drugs that are frequently selected from phage display libraries and transgenic mice that produce fully human antibodies. However, binding affinity to the correct epitope is necessary, but not sufficient, for a mAb to have therapeutic potential. Sequence and structural features affect the developability of an antibody, which influences its ability to be produced at scale and enter trials, or can cause late-stage failures. Using data on paired human antibody sequences, we introduce a pipeline using a machine learning approach that exploits protein language models to identify antibodies which cluster with antibodies that have entered the clinic and are therefore expected to have developability features similar to clinically acceptable antibodies, and triage out those without these features. We propose this pipeline as a useful tool in candidate selection from large libraries, reducing the cost of exploration of the antibody space, and pursuing new therapeutics.

Type: Article
Title: An antibody developability triaging pipeline exploiting protein language models
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/19420862.2025.2472009
Publisher version: https://doi.org/10.1080/19420862.2025.2472009
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Antibodies; developability ;machine learning; prediction; protein language models
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10204889
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