“Chematica Software Uses Algorithm to Circumvent Drug Patents”
In a groundbreaking development, Chematica, a software that can plan chemical syntheses, has been used to circumvent drug patents by avoiding protected pathways to target molecules. The new feature is based on an algorithm that can identify and preserve particularly important bonds in the target compound. Using this tool, the creators of the software could find new routes to several known pharmaceuticals. They believe their results could affect the way intellectual property (IP) is viewed in the future.
Patents are a cornerstone of the pharmaceutical industry. They protect the intellectual property rights of the creators and ensure that no existing patents are infringed. Mark Pohl, an attorney at LLC Pharmaceutical Life Cycle Management Solutions, US, explains, ‘One can patent anything which is new, and which you can touch. Researchers could also patent a process, for example, a synthetic route to a given compound. You can touch the reactants, the reaction vessel, intermediates and product. So, one can patent compound X, and also patent cooking reactant W at 100°C until it turns into X.’
However, the new algorithm used to upgrade Chematica could help chemists avoid such protected routes. Bartosz Grzybowski of the Polish Academy of Sciences and Ulsan National Institute of Science and Technology, South Korea, says, ‘We show that computers, being able to consider millions upon millions of synthetic pathways, can find solutions that circumvent approaches humans take. Even in the case of heavily patent-guarded routes to blockbuster drugs, the machine can find alternatives.’
The team demonstrated how the software works by circumventing patented pathways to three commercial drugs. They instructed Chematica to bypass known synthetic routes to the antibiotic linezolid. The program found that most protected syntheses relied on the formation of an oxazolidinone ring and marked this ring as the motif to be preserved. It then designed several new paths within five minutes. The computer also generated plausible patent-evading syntheses for Merck & Co’s diabetes drug Januvia (sitagliptin) and Novartis’s multiple myeloma drug Farydak (panobinostat).
Andrea Cavalli, a professor of medicinal chemistry at the University of Bologna, Italy, believes that the new results could have an impact on the workflows of pharmaceutical companies. ‘The algorithm can help identify the most suitable chemical routes for making a new molecule, with large freedom to operate in terms of IP,’ he says. Grzybowski points out that tools like this one could help pharma firms make their IP systems more airtight.
The researchers are now upgrading the program to consider environmental and safety issues and tackle the syntheses of very complex molecules. ‘The first paper describing a natural product synthesis planned by Chematica and executed in the lab is close to submission,’ Grzybowski says. ‘A few glitches here and there, but we see the light in the tunnel – and the completion of Chematica after more than 15 years of work.’
This development could potentially revolutionize the pharmaceutical industry, offering a new way to navigate the complex world of patents and drug development. It could also lead to a reevaluation of current IP schemes, as computers prove capable of finding alternative routes to patented drugs. As the software continues to evolve, it will be interesting to see how it shapes the future of pharmaceutical research and development.