Patents - Teva Pharmaceutical Industries Ltd v Astellas Pharma Inc.

 

Jane Lambert

Court of Appeal (Lords Justices Arnold and Stuart-Smith and Lady Justice Falk) Teva Pharmaceutical Industries Ltd and another v Astellas Pharma Inc [2023] EWCA Civ 880 (25 July 2023)

This was an appeal against the dismissal of the claim by Teva Pharmaceutical Industries Ltd. and Teva UK Ltd. ("Teva") for revocation of European Patent (UK) 1 559 427 B1 for a "Remedy for overactive bladder comprising acetic acid anilide derivative as the active ingredient" and Supplementary Protection Certificate No. SPC/GB13/035 and judgment on a counterclaim by Astellas Pharma Inc. ("Astellas") for infringement (see Teva Pharmaceutical Industries Ltd v Astellas Pharma Inc. [2022] EWHC 1316 (Pat) (1 June 2022), It came on before Lords Justices Arnold and Sturt-Smith and Lady Justice Falk on 17 and 18 July 2023.  Judgment was handed down on 25 July 2023.  By a unanimous judgment the Court dismissed the appeal (see Teva Pharmaceutical Industries Ltd and another v Astellas Pharma Inc [2023] EWCA Civ 880 (25 July 2023)).

The Patent

Claim 1 of the patent claimed:

"A remedy for use in the treatment of overactive bladder comprising (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or a salt thereof as an active ingredient."

At para [16] of his judgment, Lord Justice Arnold described the overactive bladder ("OAB") condition as "a set of symptoms which are presumed (in the absence of indication to the contrary) to be caused by involuntary detrusor contractions that occur during the storage phase. The symptoms associated with OAB include urgency (having to rush to the toilet suddenly), frequency (having to urinate too often during the day), nocturia (getting up at night to urinate) and urge incontinence (associated with urgency)." He noted that antimuscarinics were the conventional treatment of OAB at the patent's priority date of 7 Nov 2002 which worked "by blocking muscarinic receptors, preventing binding of acetylcholine to the receptors and therefore impeding detrusor contraction." These produced side effects such as a dry mouth and interference with bladder emptying.  Steps were therefore taken to develop new therapies for treating OAB.

Lord Justice Arnold mentioned those steps in paras [19] to [21] of his judgment.  He referred to ß3 adrenoreceptors between [22] to [24].  The abstract described the invention as follows:

"(R)-2-(2-aminothiazol-4-yl)-4’-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or its salt shows a potent bladder relaxation effect in 'isolated rat bladder smooth muscle relaxation test', dose-dependently lowers the contraction frequency of rhythmic bladder contractions in 'rat rhythmic bladder contraction measurement test' and, moreover, prolongs the urination intervals in 'urination function measurement test on cyclophosphamide-induced overactive bladder model rat.' Owing to these effects, the above compound is useful as a remedy for overactive bladder."

His lordship considered the description of the invention in the patent's specification between para [29] and para [37] of his judgment.  At para [2] of his judgment, the trial judge said that the patent protects the compound mirabegron, which is sold by Astellas under the name Betmiga.

The Action

Teva sought the revocation of the patent because it had a competing product that it admitted would infringe the patent    It alleged that the claimed invention was obvious over Australian Patent Application AU 199889288.  

The Australian Application

Lord Justice Arnold discussed the application and the trial judge's findings on it between para [38] and para [60] of his judgment.

The Trial

The learned Lord Justice noted at para [61] that the trial judge had "applied the structured approach to the assessment of obviousness set out in Pozzoli SpA v BDMO SA"  [2007] 1 Bus LR D117, [2007] Bus LR D117, [2007] FSR 37, [2007] BusLR D117, [2007] EWCA Civ 588.  I discussed that test and the reason for it under the paragraph marked "Obviousness" in my case note Patents - Akebia Therapeutics Inc v Fibrogen, Inc. on 5 May 2020.  The trial judge said as follows between para [170] and para [173]@

"OBVIOUSNESS DISCUSSION

[170] I will use the Pozzoli analysis.

Pozzoli steps 1 and 2

[171]. I have identified the skilled team and the CGK above.

Pozzoli step 3

[172] '288 identifies mirabegron among other compounds. The steps to the claims of the Patent are the choice of mirabegron and its use to treat OAB as opposed to the conditions mentioned in `288.

Pozzoli step 4

[173] This is the real area of contention."

Lord Justice Arnold remarked at para [61] of his own judgment:

"[The trial judge] identified the steps from 288 to the claim as being the choice of mirabegron and its use to treat OAB as opposed to the conditions mentioned in 288."

He quoted Teva's argument:

"The Claimants' case is straightforward. They submit that by the priority date it was part of the common general knowledge that ß3-agonists had the potential to be used to treat OAB and that consequently it was obvious that compounds disclosed as ß3-adrenoceptor agonists were potential therapeutics. Mirabegron had been disclosed in the AU288 Application as a ß3-adrenoceptor agonist and it follows that no technical contribution resides in identifying that it has potential for use in treating OAB."

He summarized Astellas's response at [64]:

"i) ß3-AR agonism was just one of a number of possible ways of treating OAB under consideration by the art.
ii) There was no clinical evidence yet that ß3-AR agonism would work to treat OAB.
iii) ß3-AR agonism had been unsuccessful in the obesity field.
iv) `288 is not about OAB at all and does not even mention it.
v) `288 gives no information about mirabegron's activity.
…
vii) If ß3-AR agonism were to be pursued there were many more attractive compounds to choose from than mirabegron.
viii) Although it accepted that it cannot rely on concerns over possible side effects in general because of the fact that the Patent contains no information about selectivity, there would have been a concern about urine retention, which would not be a side effect arising from lack of selectivity, but rather from ß3-AR agonism itself. That, Astellas says, is addressed by the Patent."

He analysed the trial judge's reasoning that the invention was not obvious in the light of 288 between [65] and [69].

The Appeal

Lord Justice Arnold said that although the trial judge had been persuaded to grant permission to appeal on the basis that there was arguably a tension between the House of Lords' decision in Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] UKHL 49, [2008] RPC 28 and the Court of Appeal's decisions in Pozzoli and Koninklijke Philips NV v Asustek Computer Inc [2019] EWCA Civ 2230, [2020] RPC 1, the resolution of which could lead to a different view of what the technical contribution of the patent was and a different assessment of obviousness, Teva accepted that there was no conflict between Conor on the one hand and Pozzoli and Philips on the other hand on the hearing of the appeal. Instead, Teva contended that the trial judge had erred in principle in that he had not correctly applied the law as stated in Pozzoli and Philips.

Before considering the parties' submissions, the learned Lord Justice observed that obviousness involves a multi-factorial evaluation.  It follows that n appeal court is not justified in intervening in the absence of an error of law or principle on the part of the judge (see Actavis Group PTC EHF v ICOS Corp [2019] UKSC 15, [2019] RPC 9, [2020] 1 All ER 213, (2019) 167 BMLR 1, [2019] Bus LR 1318 at [78]-[81] (Lord Hodge). This accords with the general approach of the Court of Appeal to appeals against evaluative decisions (see Re Sprintroom Ltd [2019] EWCA Civ 932, [2019] BCC 1031 at [72]-[78] (Lords Justices McCombe, Leggatt and Rose).  He added that in the present case, Teva faced not only this obstacle, which confronts all appeals on obviousness but two more specific difficulties. The first was the judge's assessment of the expert witnesses, which Teva could not and did not challenge. The second was that, on its face, the judgment contained a very careful, detailed and nuanced consideration of the evidence and the issues.

Lord Justice Arnold referred to paras [25] to [28] of Lord Justice Jacob's judgment in Pozzoli:

"[25] … There is an intellectual oddity about anti-obviousness or anti-anticipation arguments based on 'technical prejudice.' It is this: a prejudice can only come into play once you have had the idea. You cannot reject an idea as technically unfeasible or impractical unless you have had it first. And if you have had it first, how can the idea be anything other than old or obvious? Yet when a patent demonstrates that an established prejudice is unfounded — that what was considered unfeasible does in fact work, it would be contrary to the point of the patent system to hold the disclosure unpatentable.
…
[27] Patentability is justified because the prior idea which was thought not to work must, as a piece of prior art, be taken as it would be understood by the person skilled in the art. He will read it with the prejudice of such a person. So that which forms part of the state of the art really consists of two things in combination, the idea and the prejudice that it would not work or be impractical. A patentee who contributes something new by showing that, contrary to the mistaken prejudice, the idea will work or is practical has shown something new. He has shown that an apparent 'lion in the path' is merely a paper tiger. Then his contribution is novel and non-obvious and he deserves his patent.
[28] Where, however, the patentee merely patents an old idea thought not to work or to be practical and does not explain how or why, contrary to the prejudice, that it does work or is practical, things are different. Then his patent contributes nothing to human knowledge. The lion remains at least apparent (it may even be real) and the patent cannot be justified."

He also quoted para [73] of Lord Justice Floyd's judgment in Phillips:

"… The principle is that you cannot have a patent for doing something which the skilled person would regard as old or obvious but difficult or impossible to do, if it remains equally difficult or impossible to do when you have read the patent. To put it another way, the perceived problem must be solved by the patent."

Lord Justice Arnold added that when Lord Justice Floyd said "must be solved", he must have meant "must plausibly be solved".

Teva had argued that the trial judge's reasoning depended upon two uncertainties, neither of which was dispelled by the patent: 

• first, there was uncertainty as to ß3-AR agonist therapy as an approach for treating OAB pending human clinical trials; and 
• secondly, there was uncertainty as to whether mirabegron was a human ß3 selective agonist, or at least a sufficiently potent one. 

Teva said that those uncertainties were not dispelled by the patent because all it presented were the results of experiments in rats. Not only were there no clinical results, but also there were no results of experiments on human tissue.

Lord Justice Arnold rejected those submissions for two reasons,   First, the judge's reasoning was not that the invention was prima facie obvious in the light of the Australian application but the skilled team would think that it would not work because of some technical prejudice or perceived problem. If that had been his reasoning, it would then have been necessary for the respondent to show that that prejudice or problem was plausibly dispelled or solved by the patent. The judge had recognized that point in his judgment because he said at [35] of his judgment:

" In the present case there is no doubt that the skilled team in this field would have a keen awareness of the likelihood and risks of side effects with any mechanism, including ß3-AR agonism. A main potential cause of side effects for a ß3-AR agonist under consideration would be off-target effects if the compound turned out to be an agonist of ß1 or ß2 as well and the skilled team might be deterred from proceeding with a compound whose selectivity was unknown. But since the Patent contains nothing to say whether or to what extent mirabegron was selective for ß3 over ß1 and ß2, Astellas cannot rely on this, as its Counsel accepted. … "

That passage showed that it was not obvious in the light of the Australian application read with the common general knowledge to try mirabegron as a treatment for OAB with a reasonable expectation of success,'

Secondly, Teva's argument is in reality a more subtle variant of the argument rejected by the House of Lords in Conor. As Lord Hoffmann explained at para [19= of his speech in that appeal:

"… the patentee is entitled to have the question of obviousness determined by reference to his claim and not to some vague paraphrase based upon the extent of his disclosure in the description. There is no requirement in the EPC or the statute that the specification must demonstrate by experiment that the invention will work …"

He added:

" … there is in my opinion no reason as a matter of principle why, if a specification passes the threshold test of disclosing enough to make the invention plausible, the question of obviousness should be subject to a different test according to the amount of evidence which the patentee presents to justify a conclusion that his patent will work."

He said that the invention claimed was a medical use, namely the use of mirabegron to treat OAB. It is an implicit requirement of the claim that mirabegron is efficacious for that purpose. Teva accepted that the patent made it plausible that mirabegron was effective for the treatment of OAB. The House of Lords made it clear in Conor that the question of obviousness does not depend on the amount of evidence presented in the patent to justify that conclusion. Thus the question was simply whether the Australian application read together with the common general knowledge made it obvious to try mirabegron as a treatment for OAB with a reasonable expectation of success. The trial judge held that it was not.  He had based his decision on his findings as to common general knowledge, the disclosure of the Australian application and a careful assessment of the expert evidence, none of which was, or could be, challenged.

Teva also argued that Astellas was not entitled to a monopoly because the patent had made no technical contribution to the art.  It argued that the patent had neither identified a new human ß3-AR agonist nor identified a new use for ß3-AR agonists. All it had done was to dispel the two uncertainties mentioned above. 

The Lord Justice rejected that contention.  The trial judge found that the patent did make a technical contribution to the art.  He was fully entitled to reach that conclusion on the evidence.   There had been no error in the judge's approach and there was no basis for the Court of Appeal to interfere with his evaluation. Lord Justice Stuart-Smith and Lady Justice Falk agreed.

Further Information

This appeal will be one of the cases that I will discuss in the context of obviousness and plausibility at the IP Update talks that my colleagues and I shall give in chambers on 18 Sept 2023 and at 2 Snow Hill Birmingham on 25 Sept 2023.   If you want to attend either of those talks please give my senior clerk Emily Martin a ring on 020 7404 5252.   If you want to discuss this article, you can also call me on that number during office hours or send me a message through my contact form.