Kim Janda from Scripps recently discovered that the structure small molecule drug currently undergoing stage I/II clinical trials is incorrect. The drug, known as ONC201, selectively triggers apoptosis in tumor cells. Researchers from Penn State originally reported on the therapeutic potential ONC201 (called TIC10 in the paper), and they licensed the drug to Oncoceutics to begin human trials. The key to the molecule's selectivity is the TRAIL protein (Tumor necrosis factor [TNF]-related apoptosis-inducing ligand). TRAIL is present at high levels in cancerous tissues but not in healthy ones. ONC201 binds to TRAIL and triggers apoptosis.
While the biochemistry is certainly fascinating, and Janda's discovery of the structural oversight is sure to create some bickering across academy, the newsworthy part of the story stems from what Janda does after discovering the structural error. Since any intellectual property related to the ONC201 is ostensibly covering the wrong structure, Janda decides to take advantage of the 'unpatented' active drug, and he licenses the drug to another company to begin independent clinical trials.
Beyond the fact that Janda's licensing deal is not exactly gentlemanly, the move could have major implications for pharmaceutical patents moving forward. For a small molecule, the issue is relatively straightforward (though the lawyers from each side will surely have a fit over Janda's move and the fate of ONC201). The confusion arises with the progression to more advanced pharmaceuticals, such as antibody therapeutics, antibody-drug conjugates, and nanomedicines.
Further, as sophisticated delivery mechanisms (e.g., spherical nucleic acids, MOFs, nanoparticles, etc.) continue to enter the clinic, it seems that the levels of intellectual property involved in a single treatment regimen is becoming overwhelmingly jumbled. With the advent of paired therapies in which a diagnostic procedure is coupled to a personalized therapeutic, the situation is only going to get even messier. While patent lawyers salivate at the jumbling, it is important to remember that the patient must be the ultimate concern. The complexity will almost certainly increase cost, but, hopefully, the end result will be adequate financial rewards for novel solutions to healthcare challenges.