Case report: Eli Lilly loses latest Alimta battle
In the latest instalment of the long-running patent dispute between Actavis and Eli Lilly in relation to anti-cancer drug Alimta (pemetrexed disodium), in February 2016 Mr Justice Arnold at the English High Court handed down his judgment on the issues remitted to him by the English Court of Appeal.
Actavis’s pemetrexed products (pemetrexed dipotassium, pemetrexed diacid and pemetrexed ditromethamine) when diluted in dextrose were granted declarations of non-infringement in the UK, France, Italy and Spain. The claims of the patent in suit (EP 1 313 508), owned by Eli Lilly, concern the use of pemetrexed disodium for inhibiting tumour growth. The supplementary protection certificate for the basic patent for pemetrexed expired on December 10, 2015.
Following an unsuccessful jurisdictional challenge by Eli Lilly, the High Court had held in 2014 that Actavis was entitled to declarations of non-infringement in the UK, France, Italy and Spain. However, this decision was overturned on appeal in June 2015.
The Court of Appeal reasoned that Actavis’s pemetrexed products are means relating to an essential element of the invention under section 60(2) of the UK’s Patents Act 1977. While the active ingredients would not directly infringe, the court said, when a pharmacist reconstituted or diluted the products in saline there would be a stage when pemetrexed disodium was present in the form of pemetrexed ions and sodium ions in a molar ratio of 2:1.
On receipt of the draft judgment, Actavis requested that declarations be made reflecting the Court of Appeal’s decision that there would only be infringement under section 60(2) if saline were used as a diluent for Actavis’s products and that issues relating to use of dextrose as a diluent be remitted to the High Court for further consideration. The Court of Appeal declined to make the declarations, but remitted the dextrose remission issue to the High Court.
Actavis asked the court to consider whether the supply of its pemetrexed products, if marketed with clear instructions to reconstitute and/or dilute these products with dextrose instead of saline, would constitute indirect infringement of Eli Lilly’s patent.
“In granting the declarations requested by Actavis, Arnold held that the supply of Actavis’s product would not indirectly infringe Eli Lilly’s patent in the immediate future.”
Actavis also stated that it would write to all medical centres stating that its products should be reconstituted and/or diluted only in dextrose and to the National Health Service (and other relevant competent authorities) requesting that it issue central guidance to this effect. Actavis sought declarations that if such steps were taken, there would be no patent infringement.
In December 2015, Actavis launched a pemetrexed diacid product in the UK and had plans to launch it in France, Italy and Spain later this year. The summary of product characteristics (SmPC) specifies that it is only to be diluted with dextrose solution.
Eli Lilly’s central argument was that Actavis knew (or it was obvious to a reasonable person in the circumstances) that some pharmacists would intentionally dilute Actavis’s product in saline, despite any directions to only use dextrose.
Dextrose only
Eli Lilly accepted that for the time being, at least, pharmacists would follow the SmPC for Actavis’s pemetrexed product and use dextrose as the diluent. Pharmacists would not do otherwise unless and until data had been published showing that Actavis’s product was stable in saline. Further, Actavis had taken steps to avoid saline stability data from being published for its product.
Arnold accepted that such steps meant that it was unlikely that stability data for the product in saline would be published for at least two-to three years and that it was also unlikely that pharmacists would rely on such data, bearing in mind any deviation from the SmPC would shift liability for the product from the manufacturer to the pharmacist.
It was accepted that in the event that saline stability data for Actavis’s product were published and that pharmacists were motivated to use saline as opposed to dextrose, the commercial steps being taken by Actavis would probably prevent its product from being misused and saline used as a diluent. Such steps included the threat of stopping the supply of the product to customers in the event that it was discovered that saline was being used as a diluent.
In granting the declarations requested by Actavis, Arnold held that the supply of Actavis’s product would not indirectly infringe Eli Lilly’s patent in the immediate future, but granted the parties permission to apply for appropriate relief should the circumstances materially change.
David Read is owner and director of Bartle Read. He can be contacted at: david.read@bartleread.co.uk
