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Three businessmen - who each paid $55 million (£41 million) to take part in the trip - undocked from the ISS at 1:10 BST and are due to land off the coast of Florida at around 18:00 BST (13:00 ET).
Axiom Space's Ax-1 mission includes three businessmen each paying $55 million for the ten day trip, and a former NASA astronaut acting as commander for Axiom.
The first ever all-civilian crew to launch to the International Space Station (ISS) arrived safely at the orbiting research platform on Saturday to begin a week-long science mission.
Canadian investor and philanthropist Mark Pathy, US entrepreneur Larry Connor, and ex-Israeli Air Force pilot Eytan Stibbe blasted off from Florida's Kennedy Space Center at 11:17 ET (16:17 BST).
The first fully commercial crew of astronauts will fly to the International Space Station later today, with three businessmen each paying $55 million (£41