Partijen zijn in het Verenigd Koninkrijk (hierna: VK) verwikkeld in een procedure over het VK-deel van EP 427. Bij beslissing van 2 juni 2022 heeft de Engelse rechter (High Court of Justice, Business and Property Courts of England and Wales, Intellectual Property, Meade J) de door Sandoz en Teva Pharmaceutical Industries Limited (hierna: Teva) bepleite nietigheid van (het VK-deel van) EP 427, afgewezen.2Daartoe heeft de rechter onder meer het volgende overwogen:
“192. Although there are important arguments in both directions, I have come to the conclusion that the obviousness attack over `288 fails. I will explain my reasons, without I hope unduly repeating what I have already said.
193. It is true that at the priority date the β3-AR agonism mechanism had “momentum” relevant to OAB arising from the recent advancements in understanding that I have identified in relation to the CGK, and hence β3-AR agonists had, in a general sense, potential as agents to treat OAB.
194. However, the Claimants’ case suffers from the two defects of overstating the confidence that that would give the skilled addressee, and of oversimplifying the situation, in particular to the effect that any β3-AR agonist would be likely to succeed as a treatment. One can see these two problems clearly in the formulation of the Claimants’ case that they put forward in their written opening and which I have quoted above.
195. As to overstating the skilled addressee’s confidence in β3-AR agonism for OAB, I bear in mind that the mechanism had not been used successfully in any drug for any condition, and it had failed for diabetes. While there were potential reasons for this that would leave open the possibility of success for OAB, this is not a good starting point for the Claimants.
196. As to the clinical prospects for OAB, the review papers, examples of which I have given above, certainly said that clinical trials were needed for β3-AR agonists for the condition, but my overall assessment of those, as I have touched on already, is that the authors were saying that clinical evidence was what was missing and should be looked for, not that it would necessarily fall into place. Doing those clinical trials would be an exercise in hoping to find something new and promising, not a routine matter with a strong or clear expectation of positive results.
197. I also think the appropriate caution as it would be seen by the skilled addressee is evidenced by the large number of possibilities in play to improve the existing treatments for OAB. Some companies were exploring β3-AR agonism (along with other mechanisms) but others were not.
198. So I thought that Dr [1] and Dr [2] gave a much fairer impression of the state of play in seeking to improve OAB treatments than did Dr [3] : it was possible that β3-AR agonists would work for OAB and it was possible that they would not. The same could be said for a number of the other mechanisms under consideration for OAB that I have touched on above.
199. As to oversimplification, the central problem facing the Claimants seemed to me to be the poor quality of the disclosure of `288 as it applied to mirabegron in particular and the Examples generally, with the very limited data given. It was because of that that the Claimants had to contend, effectively, that any selective β3-AR agonist would be seen as obvious to use for the treatment of OAB. My findings on the evidence as set out above are that that is not so and was not the perception of the skilled addressee. It could not be assumed that any β3-AR agonist would work and it could not be predicted that the results for one would necessarily apply to another. The Claimants put to Astellas’ witnesses, and argued, that no β3-AR agonist had ever failed to show activity in detrusor tissue, but I accept the answer given, that failures would not be published, and I have already said that Dr [2] gave evidence that at Pfizer some agonists found to be potent in cell assays did not work in detrusor muscle.
200. This does not mean that the skilled addressee would positively think that mirabegron or the other Examples in `288 would not work, but it does mean that there would be a substantial degree of uncertainty. Furthermore, `288 does not “show its working”; the choice of compounds and structures to explore and test is not explained. The reader would probably expect that the thinking was shaped by the application that the authors had in mind (diabetes), and I was not at all convinced by the Claimants’ response to that, which was that it did not matter what condition the authors were working on, provided that they came up with β3-AR agonists in the end.
201. The Claimants tried to bring some unity and reality to their arguments about β3-AR agonism on the one hand and `288 on the other by the contention that the mechanism had been seen as extremely attractive for some time by the priority date, but was held up by the lack of appropriate compounds. Then, it was said, `288 would provide a good way forward for the first time. I have rejected this on the facts in dealing with the CGK. At least some other suitable compounds were around, and the skilled addressee would not think that there was a limitation such that they would naturally decide to proceed with the ill-characterised compounds in `288. As I have said, the argument was also unconvincing because Dr [3] had not with any clarity spelled it out in his written evidence, and I accept Astellas’ contention that it only really surfaced in the Claimants’ opening oral submissions.
202. It is of some relevance that `288 does not mention OAB in the list of possible conditions to be treated, but I do not think that it is a critical point in isolation, mainly because of my view that there is force in the Claimants’ argument that the skilled addressee would think OAB’s omission might be explained by `288 having been written before the advances I have identified above. In the course of oral closing argument and in the context of this point, I asked Counsel for Astellas whether he would accept that if `288 disclosed mirabegron as an excellent, potent and specific β3-AR agonist, it would then be obvious to try it for OAB, despite the condition’s not being mentioned in the list. Initially he accepted that it “probably” would be (although he caveated this shortly afterwards) and Counsel for the Claimants understandably sought to leverage this so as to argue that all the Claimants had to show was that `288 in fact did disclose mirabegron as a good compound (in being selective). I certainly did not think that Counsel for Astellas was abandoning all its points about the general uncertainty around β3-AR agonism and OAB, and in my view the shortcomings of `288 and the art’s perception of β3-AR agonism have to be seen and assessed as a whole.
203. Finally, a point made by the Claimants was that the effort involved in making the six compounds exemplified in `288 would not be great. I accept that so far as it goes, and Dr [2] did accept that the effort in making 23 compounds in the context of a commercial research organisation would not be “unreasonable”, but it is a small part of the picture and one still has to inquire which 6 compounds (or 23) to make, for what purpose and with what confidence that they might succeed.”