In 2003 and again in 2014, the University of South Florida and the University of Michigan applied for a patent on the use of crystal engineering to create multicomponent solid drugs. The US Patent and Trademark Office issued a patent in April 2020.
The institutions have now jointly filed a lawsuit against Novartis, claiming that its blockbuster treatment for heart failure, Entresto, a cocrystal of sacubitril and valsartan, infringes on their patent.
At the heart of the patent is the technology for designing cocrystals, which are single-phase crystalline mixtures of multiple compounds at specific stoichiometric ratios. Forming cocrystals can modify the physical properties of the starting ingredients and, for example, confer solubility to the mixture. Improved solubility usually translates to higher bioavailability for pharmaceutical cocrystals, which makes them attractive as oral drugs.
The inventors on the patent, US 10,633,344 B2, are Michael Zaworotko, Naír Rodríguez-Hornedo, and Brian Moulton. Zawarotko was a chemistry professor at the University of South Florida who, along with his then–PhD student Moulton, participated in the collaboration that led to the filing of the patent. Zawarotko has since joined the faculty of the University of Limerick. Rodríguez-Hornedo has been a professor of pharmaceutical sciences at the University of Michigan since 1989. All three inventors signed their rights over to their respective universities.
Both the US Food and Drug Administration and the European Medicines Agency approved Entresto in 2015. In the first quarter of this year, Entresto posted double-digit growth in sales, raking in over $1 billion and ranking as the second-best seller in Novartis’s drug portfolio.
But the universities of Michigan and South Florida contend that it’s time for the pharma giant to pay the piper. In a complaint submitted to US District Court in San Jose, California, the institutions request a jury trial and compensation for damages. Novartis declined to comment on the suit.