Wednesday, November 8, 2017

Obvious-to-try in the EWCA

Actavis v ICOS [2017] EWCA Civ 1671 Kitchin LJ: Lewison, Floyd LLJ rev’g [2016] EWHC 1955 (Pat) Birss J
EP (UK) 1,173,181 / tadalafil dosage / CIALIS

I don’t usually blog on foreign cases, but the decision of the EWCA in relevant to the on-going confusion regarding the obvious-to-try test that I blogged about last month. The general question is whether, for the invention to be obvious, it must be more or less self-evident that the specific invention would succeed, or whether it is enough that the invention is self-evident to try, and it did in fact succeed when tried, even though success could not have been predicted in advance. So, in a routine salt-screen (and this is not to suggest that all salt screens are necessarily routine), it might be obvious to try the most common pharmaceutically acceptable salts, with a reasonable expectation that one of them would work, even though it could not be predicted in advance which particular one would be the best.

This was the key issue in Actavis v ICOS, and the EWCA gave a clear answer, reversing Birss J on this point. The invention disclosed in the 181 patent was the discovery that tadalafil can be administered at low doses of up to 5mg per day in a manner which is clinically effective but also has low adverse side effects [49]. The patent correspondingly claimed a low dosage form of tadalafil [43]. The main issue was obviousness over WO 97/03675 (“Daugan”), the application which matured to, inter alia, the Canadian 2,226,784 patent. As described by Kitchin LJ, in the lead judgment

[103] Daugan teaches the use of PDE5 inhibitors for the treatment of ED. Tadalafil (compound A) is specifically disclosed, its IC50 against PDE5 is given and examples of a tablet containing a 50mg dose are described. It explains that doses of tadalafil will generally be in the range of from 0.5 to 800mg daily for the average adult patient.

The difference between Daugan and the key claims of 181 patent is that Daugan did not specifically disclose a 5mg daily dose of tadalafil or that such a dose is an effective treatment for sexual dysfunction [105]. In effect, the patentee's argument was that the 181 patent was a valid low-dose selection patent over Daugan.

Given Daugan and the great commercial success of the related compound sildenafil, Birss J found that would be entirely obvious for a skilled team to take tadalafil forward into a routine pre-clinical and clinical trial programme as an oral treatment for male ED, including at least 25, 50 and 100mg doses [110]. This was not contentious. While the point was disputed, Birss J also found that the skilled team would have gone on to test lower doses, including a 5mg dose, would have discovered this dose was efficacious, and would have taken it on to Phase III trials and clinical approval [123]. Birss J also found – and this finding was not challenged on appeal – that prior to actual testing, the team would have no reasonable expectation that a 5mg dose would produce a clinically relevant effect [120], [146], [165]. In other words, on the facts it was obvious to try the 5mg dose, and when tried, there would have been no difficulty in establishing this dose was efficacious, but the success of the 5mg dose could not have been predicted, and indeed, would have been unexpected and surprising.

On these facts, Birss J held the key claims to be valid. The EWCA unanimously reversed, holding the claims to be invalid for obviousness. The concurring opinion of Floyd LJ sets out the Court’s reasoning most succinctly:

[155] If one notionally asks that question of the skilled team before it embarked on the investigations which Birss J chronicles in his judgment, the answer would be, of course, that it was not obvious. The skilled team would respond that it could not know without conducting appropriate tests what if any dose of tadalafil would achieve that goal.

[156] The law, as it has developed at least in this jurisdiction, does not halt its enquiry at this point, however. If it did, this would have been a very short issue to decide. It is recognised that a patent will not be granted for an invention which, though not obvious in this a priori sense, is nevertheless an invention which would be arrived at by a line of routine and uninventive enquiry which would be carried out by a skilled team.

See also [164]-[169]. The opinions of Kitchin LJ, at [145]-[152], and Lewison LJ [174]-[181], are to the same effect. The requirement of a reasonable expectation of success in English law, corresponding to the requirement in Canadian law that it be more or less self-evident that what is being tested ought to work, is directed to the research program, not to the specific outcome: see eg Floyd LJ at [165]. Kitchin LJ summarized by saying

[152] The judge has lost sight of the fact that, on his own findings, the claimed invention lies at the end of the familiar path through the routine pre-clinical and clinical trials’ process. The skilled but non-inventive team would embark on that process with a reasonable expectation of success and in the course of it they would carry out Phase IIb dose ranging studies with the aim of finding out, among other things, the dose response relationship. It is very likely that in so doing they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention. In my judgment claims 7 and 10 are therefore invalid.

In my view the reasoning of the EWCA in Actavis v ICOS is entirely sound. It is also consistent with the law set out in Sanofi 2008 SCC 61, though it clarifies some points that were left obscure in that decision, at least to me, and evidently to Birss J as well. (This consistency should not be too surprising, as the EWCA and the SCC were both approving the same line of cases.) The law set out in Actavis v ICOS is also consistent with the way the obvious-to-try test has actually been applied in the Federal Court (see my discussion last month and earlier); despite the lack of clarity in Sanofi and earlier cases, the Federal Court has generally done better than Birss J in applying the law correctly.

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