On Apr. 23, 2021, UK high court found glaucoma use patent valid in a revocation proceeding.
Claimant (Alcon) owns EP 1920764 patent which covers travoprost (fluprostenol isopropyl ester/FIE) for use in the treatment of glaucoma. This patent normally expired on Aug. 03, 2014, with SPC, it expired on May 28, 2017. Defendants (Actavis /Accord /Pharmathen /Aspire pharma) agreed to the infringement, if patent is valid. Although the Patent and the SPC have both expired, the trial happened because interim injunctions were obtained on the basis of them in respect of which cross-undertakings in damages were given. Defendants argued that the patent is invalid under lack of novelty (over EP 0603800), obviousness (over Stjernschantz) and/or insufficiency.
Court said that the problem sought to be solved by the Patent was that while natural prostaglandins and the derivative PGF2a-IE had been found to be capable of lowering intraocular pressure (IOP), they had unacceptable side-effects that had brought a stop to efforts to use them. Synthetic analogues were needed to maintain the activity while avoiding the side effects.
With respect to the novelty, Court said that only at one instance in Example E of EP’800, fluprostenol isopropyl ester was mentioned but again it was in combination with another, E series prostaglandin. However, current claims are related to monotherapy. The Defendants argued that the skilled person would not see the reference to the isopropyl ester form of fluprostenol being disclosed only in combination with the other components, but that it “comprises part of the general teaching”. Court rejected this argument and said that Example E is very specific and not a general teaching, and if other parts of the general teaching mentioned FIE then the Defendants would have relied on them. Therefore, anticipation attack fails.
With respect to the obviousness, Court said that Stjernschantz disclosed the PGF2a (and its ester) had effect in lowering IOP, but with the side effects of irritation and hyperemia. It then discloses about general methods for synthesis of phenyl substituted PGF2a analogues, one of them was latanoprost as shown below.
Alcon characterised there as being three differences between latanoprost & FIE. The Defendants, on the other hand, expressed the difference as being merely the choice of a different selective FP receptor agonist, i.e. FIE. Court said that Alcon’s position had a much greater focus on the medicinal chemistry content of Stjernschantz and its SAR work, and that is why it described the differences in terms of structure. Court’s conclusion is that Alcon’s approach better reflects the contents and approach of Stjernschantz and the presence of a medicinal chemist as an active member of the skilled team. In any event, the task for the Defendants was to show that it was obvious to use FIE, instead of any of the analogues in Stjernschantz, to treat glaucoma. The Defendants’ argued that Stjernschantz showed that it was most probably FP receptor binding which was responsible for reduced IOP, it would be obvious to try FIE for treating glaucoma, because it was known from the CGK to be a potent and selective FP receptor agonist. Thus, they argued, FIE fit the profile of an efficacious, side-effect sparing prostaglandin analogue.
Court said that the natural way for the skilled team to approach obvious developments from Stjernschantz would be to consider further prostaglandin analogues, altered in ways concretely reasoned out from the structure activity work described. It was very clearly the Defendants’ case that FIE was obvious to try based on its affinity and selectivity for the FP receptor and not structure. Even had the skilled team thought of trying fluprostenol in animal models to assess its possible use to treat glaucoma, they would have regarded it as very uncertain what effect it would have on side effects. Even if they had thought that initial animal experiments with fluprostenol would have needed such low resources that it could be justified as a gamble, that would not make it obvious. In the context of the overall direction of Stjernschantz, the skilled team would without invention have not turned its mind to fluprostenol as a possible treatment in the first place. Even if it did, the prospects of success (having regard to efficacy and side effects) would be very uncertain. Much more attractive options consistent with the overall teaching and direction of Stjernschantz were available. Thus, Court rejected the obviousness attack over Stjernschantz.