The Court of Appeal has declared obvious a patent claiming a particular dosage regimen of a known drug on the basis that the skilled team would have arrived at the alleged invention, inevitably, during routine dose-ranging steps in clinical trials (Actavis v ICOS  EWCA Civ 1671).
In what circumstances will routine investigations and tests yield patentable inventions?
This is the question that patent advisers are asking in the light of the outcome in Actavis v ICOS, in which the court revisited the "obvious to try" test in the context of clinical trials. This test involves asking the question whether the inventive step claimed in a patent, which although may not be obvious in the ordinary sense, would nevertheless have been “obvious to try” to a skilled person with access to the relevant prior art. The court considered, in particular, whether a claim of "obvious to try" will only succeed where the skilled team had a "reasonable expectation of success" in relation to the efficacy of the alleged invention at the priority date of the patent.
At first instance, Birss J rejected an obviousness challenge by the claimants against EP (UK) No. 1 173 181 ("the Patent"), owned by ICOS and exclusively licensed to Eli Lilly. The Patent claims the use of tadalafil (Cialis) in a dosage form for the treatment of erectile dysfunction (ED). The challenge was directed in particular to claims 1, 7 and 10, which claimed dosages of up to 5mg, and was based upon a piece of prior art (Daugan) which specifically disclosed examples of a tablet containing 50mg of tadalafil.
The claimants appealed against various aspects of Birss J's decision, including his finding on obviousness.
High Court decision
In the High Court, the claimants contended that it would have been obvious for the skilled team, in view of Daugan, to take tadalafil into a routine clinical trial programme to assess its use as treatment for ED, and that in the course of that programme, it would have been revealed that a 5mg daily dose was a safe and effective treatment.
Birss disagreed. The court found that although very likely, it was "not inevitable" that the skilled team would investigate lower doses after the initial stages of the clinical trial programme; such investigation would not be quite as routine as the preceding steps. The fact that it would have taken the skilled team three rounds of dose ranging to arrive at the 5mg dose meant that the claimant's obviousness claim was, in Birss's words, "beginning to look like hindsight". He considered that the skilled team – mindful of the 50mg dose in Daugan - would have been surprised to discover that a 5mg dose could be useful. Accordingly, the skilled team could not reasonably have expected a 5mg daily dose to work.
In Birss's view, a number of value judgments would have to be made to reach the claimed invention, such as defining the level of clinical effect to be regarded as relevant and deciding what to do when an unexpected plateau in the dose-response relationship was identified.
He therefore rejected the claimants' challenge that claims 1, 7 and 10 were obvious.
Court of Appeal decision
The Court of Appeal overturned Birss's decision. Although it would not have been obvious to the skilled team that a 5mg daily dose of tadalafil would be a safe and effective treatment, the skilled team would nevertheless have reached the invention by a line of "routine and uninventive enquiry", as it lay at the end of the familiar path through the routine pre-clinical and clinical trials process. The judges gave particular weight to the fact that there is a specific phase in clinical trials aimed at determining the dose-response relationship of the drug (Phase IIb). Completion of this phase would have led, inevitably, to a 5mg daily dose. As Floyd LJ put it, even though the skilled team would be surprised by the efficacy of this dosage, a "surprising result, once uncovered, does not make these routine enquiries inventive".
The judges differed in their conclusions as to whether success in an "obvious to try" claim requires proof that the skilled team would have a "reasonable prospect of success" as to efficacy. Kitchin LJ considered that the skilled team would embark on the routine pre-clinical and clinical trials process with a reasonable expectation of success. On the other hand, Floyd LJ considered that there are some steps which can be characterised as so routine that the skilled person would carry them out simply because they are routine, irrespective of any prospect of success. Similarly, Lewison LJ considered that while an expectation of success can be relevant to the question of whether the skilled team would undertake a particular test or experiment, it is not a necessary condition in all cases.
On the question of value judgments, the court considered that whilst the existence of such judgments on the road to the invention would be highly material, the judgments identified by Birss were either collateral ones which had no impact on the decision to complete the Phase IIb study, or were not true value judgments at all.
The court unanimously allowed the appeal and held that claims 1, 7, and 10 were invalid for lack of inventive step.
This case establishes that although the outcome of certain steps may appear to be "surprising" and therefore inventive before relevant investigations and tests are carried out, the enquiry does not always halt there. It was therefore irrelevant, in this case, that the skilled team would have been surprised to learn at the outset that the results achieved by a 50mg dose of taladafil could also be achieved by a 5mg dose.
The Court of Appeal emphasised that a patent will not be granted for an invention which, although not obvious on the face of it, 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.
While Floyd LJ said it is "important not to let this approach to obviousness extend beyond its proper bounds", the judgment does not provide any indication as to where these "bounds" might lie. No doubt, the answer will vary depending on the specific circumstances of each case but at what stage(s) of the inventive process should the question "was it obvious to try?" be asked?
Eli Lilly has applied to the Supreme Court for permission to appeal. If permission is granted, pharmaceutical companies will no doubt monitor the case closely, as the goalposts for the obvious to try test could yet shift further.
Postscript (May 2018)
Permission to appeal was subsequently granted and the Supreme Court is due to hear the case in November 2018.
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