On 25 July 2023, the Court of Appeal handed down its decision in Teva & Sandoz v Astellas [2023] EWCA Civ 880 concerning the validity of EP(UK) 1 559 427 B1 (the “Patent”), which claims the compound mirabegron for use in the treatment of overactive bladder (“OAB”).

At first instance, Mr Justice Meade found the patent valid, (infringement not contested). On appeal, Teva and Sandoz argued that the judge had erred in the application of the law on obviousness. The Court of Appeal dismissed the appeal, with Lord Justice Arnold giving the leading judgment and Lord Justice Stuart-Smith and Lady Justice Falk agreeing.

First instance decision

Astellas markets mirabegron for the treatment of OAB under the names Betmiga® and Myrbetriq®. Teva and Sandoz wanted to clear the way for the launch of their generic products, and so issued proceedings to revoke the Patent and associated SPC. They argued that the Patent was obvious over Australian patent application 199889288 (“AU 228”).

AU 228 discloses a series of compounds for the treatment of diabetes due to stimulation of the β3-adrenoceptor (“β3-AR”). Six example compounds are disclosed, including mirabegron as compound 5. However, the only numerical data in AU 228 relate to compound 6 and there is no mention of OAB.

Teva and Sandoz argued that it was common general knowledge that selective β3-AR agonists had the potential to treat OAB. Therefore, the skilled team would take the β3-AR agonists disclosed in AU 228 and test them in an OAB model. Assuming positive results were observed in this model, the skilled team would progress to clinical trials with a reasonable expectation of success.

Astellas argued that i) targeting β3-AR was only one of a number of potential ways to treat OAB; ii) there was no clinical evidence that β3-AR agonism would work to treat OAB; iii) AU 228 contains no mention of OAB and no data on mirabegron’s activity (i.e. selectivity and potency); and iv) even if targeting β3-AR was pursued, there were many compounds to choose other than mirabegron.

Meade J found that whilst there was “momentum” in the idea of using β3-AR agonists to treat OAB, other approaches were being explored. Further, not all β3-AR agonists behaved in the same way as only a handful were selective and their potency varied. Further, a β3-AR agonist for the treatment of obesity had failed in the clinic. Given this common general knowledge and the absence of data in AU 228, the skilled team would have no reasonable expectation of successfully treating OAB with mirabegron. Therefore, the obviousness attack failed and the Patent was upheld.

Appeal

Arnold LJ first noted the difficulty that all appellants face when appealing findings of obviousness; the Court of Appeal can only interfere in the first instance decision if there is an error of law or principle. Teva and Sandoz’s argument therefore was that the judge had made an error in the application of the law as laid down in Pozzoli v BDMO [2007] EWCA Civ 588 and Philips v Asus [2019] EWCA Civ 2230.

The law in question relates to the issue of whether a prior prejudice amounts to a ‘lion in the path’ or merely a ‘paper tiger’. If a patent shows that a prejudice was misguided, it demonstrates that the lion in the path is in fact a paper tiger, and the solution in the patent is therefore non-obvious. However, if the perceived problem is not plausibly solved by the patent and so remains a ‘lion in the path’, then there is no invention.

The use of mirabegron suffered from two prior prejudices. First, there was no clinical evidence that β3-AR agonists could treat OAB. Second, there was no data on whether mirabegron was sufficiently selective or potent against human β3-AR. Sandoz and Teva argued that the Patent dispelled neither of these uncertainties as it only presented the results of experiments on rats, and even the in vitro experiments did not use human cells or tissue. Therefore, there remained a ‘lion in the path’.

Arnold LJ rejected this argument for two reasons. First, for such an argument to succeed, Meade J would have had to have made a finding that the Patent would have been obvious over AU 288 but for these two prior prejudices, but that was not part of Meade J’s reasoning. Instead, he found that the skilled person, having read AU 288 with their common general knowledge, would not have tried mirabegron as a treatment for OAB with a reasonable expectation of success. Indeed, in relation to the selectivity point, Meade J explicitly recognised that, given the lack of selectivity data in the Patent, this was not a technical effect that Astellas could rely on.

Second, Arnold LJ considered Sandoz and Teva’s argument to really be one that had already been advanced and rejected by the House of Lords in Conor v Angiotech [2008] UKHL 49. In Conor, Lord Hoffman explained that if a patent’s specification makes the invention plausible, then no further evidence is required. At first instance, Sandoz and Teva had accepted that the Patent made plausible the use of mirabegron to treat OAB, and therefore they could not now argue that further evidence was required.

Finally, Sandoz and Teva argued that Meade J had failed to recognise that the Patent did not make a technical contribution for two reasons. First, they said that the Patent did not identify a new β3-AR agonist, as AU 288 disclosed mirabegron. Second, that the Patent did not identify a new use for β3-AR agonists, as their potential to treat OAB was common general knowledge. Arnold LJ also rejected these points; Meade J had identified the technical contribution in his judgment where he found that the Patent focused on mirabegron, taught its use in treating OAB, and gave concrete results in identified assays.

A copy of the judgment can be read here.

Headnote and summary: Kate O’Sullivan and Jonathan Ross, Bristows LLP