Facts

Teva Pharmaceuticals Industries Ltd sought the revocation of a European Patent designating the UK owned by Astellas Pharma Inc (the Patent) on the ground of obviousness over a single piece of prior art, an Australian Patent Application (the Prior Art). Teva also ran insufficiency as a “squeeze” against obviousness. The Patent had a priority date of 7 November 2002.

The Patent protected the compound mirabegron, sold by Astellas under the name Betmiga. It is a treatment for overactive bladder (OAB). The compound is a β3 adrenoreceptor agonist.

Astellas counterclaimed for infringement, which was admitted by Teva if the Patent was valid.

Decision

The skilled team and common general knowledge (CGK)

Teva argued that the notional skilled team would be a team working on β3-AR agonists for OAB.

Meade J found, on the evidence, that teams working in the OAB field would choose several targets to work on to try and improve OAB treatments and while the choice of targets of some teams would include β3-AR agonism, others would not. Further, there was no evidence of teams who only worked on β3-AR agonism. Additionally, at the relevant time, β3-AR agonist work was in the early stages: there were no β3-AR agonist drugs and understanding of the possibilities and problems was still developing.

Accordingly, Meade J concluded that the established field was broader than β3-AR agonism for OAB. It was, rather, new or improved pharmacological treatments for OAB generally. This affected the CGK as well. In fact, regarding the CGK, Meade J found that this was a field where there was known to be a real problem with the existing treatments and in which there were a significant number of possibilities to be considered, none of which was the clear favourite and none of which had an overwhelmingly clear rationale or body of evidence. There was no established field of β3-AR agonists and drug companies in the field were typically trying multiple approaches. Some but not all the active research programmes included β3-AR agonists and some who started work on β3-AR agonists later gave up on it.

Obviousness over the Prior Art

The Prior Art title was “Amide derivatives or salts thereof”. It disclosed “[a] therapeutic agent for diabetes mellitus having both an insulin secretion promoting action and an insulin sensitivity potentiating action and also having anti-obesity and anti-hyperlipemia actions due to a selective stimulating action to β3 receptors …”. The technical field was described as relating to novel compounds and treatments for mellitus.

Using the Pozzoli analysis, Meade J noted that, as regards step 3 [the difference between the state ot the art and the alleged invention], the Prior Art identified mirabegron among other compounds. The steps to the claims of the Patent were the choice of mirabegron and its use to treat OAB as opposed to the medical conditions mentioned in the Prior Art.

Pozzoli step 4 [were the steps obvious] was the real area of contention. Teva submitted that by the priority date it was part of the CGK that β3 agonists had the potential to be used to treat OAB and that consequently it was obvious that compounds disclosed as β3 adrenoceptor agonists were potential therapeutics. Mirabegron had been disclosed in the Prior Art as a β3 adrenoceptor agonist and it followed that no technical contribution resided in identifying that it had potential for use in treating OAB.

Astellas argued that β3-AR agonism was just one of several possible ways of treating OAB under consideration by the art and there was no clinical evidence that it would work. β3-agonism had been unsuccessful in the obesity field. The Prior Art was not about OAB at all and gave no information about mirabegron’s activity. Further, if β3-AR agonism were to be pursued there were many more attractive compounds to choose from than mirabegron.

Meade J concluded that the obviousness attack over the Prior Art failed. While it was true that at the priority date the β3-AR agonism mechanism had “momentum” relevant to OAB arising from the recent advancements in understanding and that β3-AR agonists therefore had potential as agents to treat OAB, Teva had overstated the confidence that this would give the skilled addressee. Teva had also oversimplified the situation, in particular as to the effect that any β3-AR agonist would be likely to succeed as a treatment.

In terms of the skilled addressee’s confidence in β3-AR agonism for OAB, the evidence was that at the priority date, the mechanism had not been used successfully in any drug for any condition and it had failed for diabetes. As for the clinical prospects for OAB, the review papers said that clinical trials were needed for β3-AR agonists for OAB. In Meade J’s view, the authors of these papers were saying that clinical evidence was what was missing, 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.

Further, the appropriate caution, as it would be seen by the skilled addressee, was 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.

The fairer way of explaining it was, Meade J said, that it was possible that β3-AR agonists would work for OAB and it was possible that they would not.

As for oversimplification, Meade J found that on the evidence, Teva’s argument that any selective β3-AR agonist would be seen as obvious to use for the treatment of OAB was not correct 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 β3-AR agonist would necessarily apply to another.

This did not mean that the skilled addressee would positively think that mirabegron or the other examples in the Prior Art would not work, but it did mean that there would be a substantial degree of uncertainty. Further, the choice of compounds and structures to explore and test was not explained in the Prior Art. The reader would expect that the thinking behind the Prior Art was shaped by the application that the authors had in mind (diabetes). Meade J did not agree that it did not matter what condition the authors were working on, provided they came up with β3-AR agonists in the end, as Teva argued.

Insufficiency

In the end, Teva did not devote time to insufficiency in its closing submissions. In any event, Meade J said, the disclosure of the Patent was quite different from that of the Prior Art. It focussed specifically on mirabegron, taught its use in treating OAB, and gave specific, concrete results in identified assays, albeit not in humans or human tissue. He therefore rejected the insufficiency allegation.

Conclusion

Meade J therefore concluded that the obviousness attack over the Prior Art failed, as did the insufficiency allegation. Accordingly, the Patent was valid and would be infringed by Teva’s proposed acts. (Teva Pharmaceutical Industries Ltd v Astellas Pharma Inc [2022] EWHC 1316 (Pat) (1 June 2022) — to read the judgment in full, click here).