In Glenmark Generics (Europe) Limited & others v The Wellcome Foundation Limited & Glaxo Group Ltd [2013] EWHC 148 (Pat) the High Court has held that a patent for the 5:2 ratio combination of two anti-malarial drugs—atovaquone and proguanil—was obvious, based on prior art that disclosed the two drugs in combination, but not at the claimed ratio.

BACKGROUND

The Claimants sought revocation of European Patent (UK) No. 0 670 719 (the patent). The Defendants are both part of the GlaxoSmithKline group of companies. The Wellcome Foundation Limited is the registered proprietor of the patent and Glaxo Group Ltd is the beneficial owner and the exclusive licensee of the patent.

The patent relates to an anti-malarial medication with a priority date of 26 November 1992, comprising a combination of atovaquone and proguanil in the ratio 5:2. The only ground on which the Claimants contended that the patent was invalid was that of obviousness in relation to two pieces of prior art: a presentation by Dr David Hutchinson, one of inventors named in the patent, and an abstract from a plenary lecture by Dr A T Hudson, who also worked for the Defendants.

The Defendants sell a pharmaceutical composition consisting of a 5:2 combination of atovaquone and proguanil under the trade mark Malarone. The Claimants each wanted to launch a generic version of Malarone, resulting in the Defendants counterclaiming against both for infringement. There was no dispute that the Claimants’ proposed products would infringe the patent if it was valid. It is of note that the Defendants made an unconditional application to amend the Patent by deleting Claim 1 (which is a claim to a method of treatment using a combination of atovaquone and proguanil in any ratio) as granted. The application was granted and the trial was heard on an expedited basis.

DECISION

There were certain areas of dispute as to what fell within the common general knowledge, the most interesting of which related to combinations. One of the Claimants’ experts, Professor Molyneux, gave evidence as to the benefit of additive combinations of drugs where there is some resistance to one or both drugs and an absence of any synergy, arguing that it is rational to use an additive combination in the appropriate circumstances. Arnold J agreed with this, and commented that he found a combination that was shown to be significantly synergistic in vitro would encourage the skilled team to go forward to in vivo trials.

Arnold J continued by setting out the law on obviousness by reference to the restatement of the “Windsurfing” test in Pozzoli v BDMA SA [2007] EWCA Civ 588 and by reference to the consideration of that test in MedImmune Ltd v Novartis Pharmaceuticals Ltd [2012] EWCA Civ 1234.

Arnold J then applied the test to the patent’s claims. He found that there was no technical significance in the 5:2 ratio set out in the claims. The correct question therefore was whether or not it would be obvious to proceed with the development of a medication consisting of atovaquone and proguanil in combination. As the prior art disclosed the combination for the treatment of malaria and set out promising clinical trials results, the Defendants needed to show that the skilled team would not proceed with the development of the combination of atovaquone and proguanil in order to be successful. Arnold J rejected the Defendants’ arguments that critical comments made about the findings would have deterred the team of skilled persons from investigating the combination further. He also rejected arguments claiming that the invention was not obvious because a commercial pharmaceutical company would not have supported this investigation as there was limited profit in anti-malarial drugs; he stated that commercial factors are irrelevant in determining obviousness. Arnold J concluded that against the backdrop of a pressing need for new anti-malarial drugs, the skilled team would have reached the conclusion that the combination merited further investigation and that this would, in turn, have led to a formulation based on suitable proportions of the two drugs. As such the claim was obvious.

COMMENT

This decision is another nail in the coffin for combination patents at the hand of the English courts. While this is not a welcome decision for pharmaceutical combination patent owners, the issue of a combination patent, where the patent discloses a synergy that was not disclosed in any prior art, remains to be tackled by the courts.