Shoring up IP in drug polymorphisms
(sertraline HCl) reveals how early research on the different
crystal forms of a drug can avoid generic challenges later on.
TransForm Pharmaceuticals, which specialises in the often neglected art of form and formulation in pharmaceuticals, has identified a series of new salt forms of sertraline, the active ingredient in Pfizer's blockbuster antidepressant Zoloft.
Not only did the effort uncover three salt forms of sertraline that are less prone to polymorphism than the marketed version of the drug, but it also revealed a new crystalline form of sertraline hydrochloride - the salt used in Pfizer's $2 billion product - that is suitable for pharmaceutical development.
The ability of salts to exist in different crystalline forms (polymorphisms) has been behind a number of high-profile patent challenges in the drug industry, perhaps most notably that relating to the histamine H2 antagonist Zantac (ranitidine) originated by Glaxo (now GlaxoSmithKline). In this case, generics companies were able to overturn the originator's exclusivity by developing forms of the drug that got around Glaxo's patent estates.
TransForm is not suggesting that it would develop its own version of sertraline hydrochloride based upon the polymorphism it has discovered. Indeed, the company believes the fact that it has uncovered so much new information about the drug is a compelling advertisement for its technologies.
"These studies demonstrate the power of high-throughput experimentation in identifying the various forms the active pharmaceutical ingredient, which is crucial for comprehensive intellectual property to protect the investment of the innovator," commented Colin Gardner, TransForm's chief scientific officer.
He noted that Zoloft looks set to face generic competition in 2006, despite the fact that a patent covers the polymorphic crystal form in the marketed product until 2012. Use of TransForm's approach in the early stages of this drug's development could have avoided this situation, saving Pfizer millions of dollars in lost revenues at the end of Zoloft's patented life.
TransForm conducted more than 6,200 total crystallisation experiments on sertraline, in three separate studies, with each study conducted in less than six weeks and using less than 5g of material. The work appears in the November issue of Organic Process Research and Development and in the November/December edition of Crystal Growth and Design.
