Five computational developability guidelines for therapeutic antibody profiling
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- Matthew I. J. Raybould
- Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom;
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- Claire Marks
- Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom;
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- Konrad Krawczyk
- Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom;
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- Bruck Taddese
- Department of Antibody Discovery and Protein Engineering, MedImmune, Cambridge CB21 6GH, United Kingdom;
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- Jaroslaw Nowak
- Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom;
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- Alan P. Lewis
- Computational and Modelling Sciences, GlaxoSmithKline Research and Development, Stevenage SG1 2NY, United Kingdom;
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- Alexander Bujotzek
- Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, DE-82377 Penzberg, Germany;
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- Jiye Shi
- Chemistry Department, UCB Pharma, Slough SL1 3WE, United Kingdom
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- Charlotte M. Deane
- Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom;
書誌事項
- 公開日
- 2019-02-14
- 権利情報
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- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1073/pnas.1810576116
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>Immunogenicity, instability, self-association, high viscosity, polyspecificity, or poor expression can all preclude an antibody from becoming a therapeutic. Early identification of these negative characteristics is essential. Akin to the Lipinski guidelines, which measure druglikeness in small molecules, our Therapeutic Antibody Profiler highlights antibodies that possess characteristics that are rare/unseen in clinical-stage mAb therapeutics. The only required input is the variable domain sequence. We show examples where our approach would have advised against manufacturing antibodies that were found to aggregate or have poor expression.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 116 (10), 4025-4030, 2019-02-14
Proceedings of the National Academy of Sciences