6A4

6A4 is a monoclonal antibody developed to combat synthetic opioid intoxication, specifically targeting fentanyl and its related analogues like carfentanil. It was generated from hybridomas derived from mice vaccinated with a fentanyl conjugate vaccine. The antibody demonstrates high binding affinity for fentanyl (10–11 M) and broad cross-reactivity with other fentanyl analogues. In preclinical mouse models, 6A4 has been shown to blunt the antinociceptive effects of both fentanyl and carfentanil in a dose-responsive manner, enhance survival after lethal fentanyl doses, and effectively reverse fentanyl/carfentanil-induced antinociception, similar to naloxone. Its mechanism involves sequestering these drugs in the blood, thereby reducing their biodistribution to the brain and other tissues. Notably, 6A4 exhibits a longer half-life (approximately 6 days in mice) compared to naloxone, suggesting its potential utility in preventing renarcotization events and possibly in the treatment of opioid use disorder. The Scripps Research Institute is involved in its development.