1. Target occupancy biomarker assay development using a conformation-selective antibody against small-molecule-bound TNF.
- Author
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Hickford ES, O'Connell J, Maloney A, Florian P, Johnston GI, Rospo CC, Herrmann M, Wright S, and Bourne T
- Subjects
- Enzyme-Linked Immunosorbent Assay, Antibodies
- Abstract
Background: An antibody specific to small-molecule inhibitor-bound TNF has enabled the development of target occupancy biomarker assays to support the development of novel treatments for autoimmune disorders. Materials & methods: ELISAs were developed for inhibitor-bound and total TNF to determine the percentage of TNF occupancy in samples from stimulated blood. Inhibitor-saturated samples allowed measurement of total and inhibitor-bound TNF in a single electrochemiluminescence immunoassay. Results: TNF occupancy was proportional to inhibitor concentration in plasma samples. An electrochemiluminescence method for inhibitor-bound TNF was validated for use as a potential clinical occupancy biomarker assay. Conclusion: Development of these assays has allowed measurement of a target occupancy biomarker, which has supported progression of the first small-molecule inhibitors of TNF.
- Published
- 2023
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