Oral delivery of the anti-tumor necrosis factor α domain antibody, V565, results in high intestinal and fecal concentrations with minimal systemic exposure in cynomolgus monkeys

• Published in: Drug development and industrial pharmacy Vol. 45; no. 3; pp. 387 - 394
• Main Authors: Crowe, J. Scott, Roberts, Kevin J., Carlton, Timothy M., Maggiore, Luana, Cubitt, Marion F., Ray, Keith P., Donnelly, Mary C., Wahlich, John C., Humphreys, Jonathan I., Robinson, Jan R., Whale, Gary A., West, Michael R.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.03.2019
• Subjects: Administration, Oral; Animals; Anti-TNFα; Antibodies - administration & dosage; Antibodies - metabolism; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Chemistry, Pharmaceutical - methods; domain antibody; enteric; Eudragit; Feces; formulation; gastrointestinal; Hydrogen-Ion Concentration; Ileum - drug effects; Ileum - metabolism; Inflammatory Bowel Diseases - economics; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Jejunum - drug effects; Jejunum - metabolism; Macaca fascicularis; oral; pharmacokinetics; Solubility; Tablets, Enteric-Coated - administration & dosage; Tablets, Enteric-Coated - pharmacokinetics; Tumor Necrosis Factor-alpha - antagonists & inhibitors; gastrointestinal; Anti-TNFα; formulation; pharmacokinetics; domain antibody; oral; Eudragit; enteric

Objective: V565 is a novel oral anti-tumor necrosis factor (TNF)-α domain antibody being developed for topical treatment of inflammatory bowel disease (IBD) patients. Protein engineering rendered the molecule resistant to intestinal proteases. Here we investigate the formulation of V565 required to...