Whether or not a distinct dosage regime of a known compound can be inventive is an important policy question. Accordingly, it is not surprising that a number of industry bodies intervened in the recent appeal to the Supreme Court concerning the validity of ICOS' patent (which is licensed to Eli Lilly) relating to the use of tadalafil, sold under the brand name Cialis, in a dosage form for the treatment of erectile dysfunction (ED) (EP (UK) 1 173 181).
In its decision in Actavis v ICOS, the Supreme Court upheld the Court of Appeal's finding that the Patent was invalid for lack of an inventive step over a prior art patent disclosing the use of the drug to treat ED. The skilled team had embarked on familiar and routine testing of tadalafil to establish the appropriate dosage regime in the light of the prior art teaching. It was obvious for them to embark on that testing and carry out routine tests until the appropriate dose was identified, including completing dose-ranging studies as part of Phase IIb testing, which led to the claimed dose range. The fact that the dose identified (5mg/daily) as effective for treatment of ED, whilst having reduced side effects, was a surprising outcome did not mean that identifying that dose was inventive.
However, the Supreme Court reiterated that it is not the law that investigations into appropriate dosage regimes cannot yield patentable inventions, or that there are policy reasons which would justify such a blanket approach. That said, the outcome in this case does demonstrate that intensive, and expensive research leading to an unexpected result may not, in all circumstances, justify a patent where the work carried out is routine and alongside other potentially relevant factors.
The central issue was whether the Patent was inventive over the prior art, a patent ('Daugan'), which disclosed the use of PDE inhibitors to treat ED, and specifically disclosed taladafil, giving an example of a 50mg dose. Daugan did not purport to set out an appropriate dosage regime as an oral treatment of ED. The claimed invention in the Patent was the discovery that ED could be treated by administering a low dose of 5mg and with minimal side effects – this means that the drug can be taken daily, rather than on demand.
The trial judge, Birss J, found it would have been "entirely obvious" for the skilled team, given Daugan, to take tadalafil into a routine pre-clinical and clinical trial programme as an oral treatment for ED, which would have involved investigations of on demand and chronic daily dosing. The discovery of a therapeutic plateau starting at 25mg or 10mg would have surprised the skilled team but Birss J also held it was "very likely" that they would research further by testing a lower dose of 5mg. Despite this, he concluded that a 5mg daily dose was not obvious in the light of the prior art.
The Court of Appeal overturned this decision finding there was no inventive step. The Court of Appeal identified an error of principle, given the Judge's findings before he reached his conclusion. Whilst recognising the danger of hindsight, the Court of Appeal also noted in particular that Birss J had placed too much emphasis on 5mg being substantially lower than 50mg. The invention lay at the end of "the familiar path through the routine pre-clinical and clinical trials' process".
Supreme Court decision
The Supreme Court rejected Lilly's suggestion that it should disregard the work a skilled person would carry out after the priority date to implement the teaching of the prior art, and agreed with the Court of Appeal's decision. Giving the judgment of the Court, Lord Hodge identified the following non-exhaustive factors as being potentially relevant in each case (the weight of each factor may vary depending upon the circumstances):
- Whether at the priority date something was 'obvious to try': was it obvious to undertake a specific piece of research which had a reasonable or fair prospect of success?
- The routine nature of the research and any established practice of following such research through to a particular point.
- The burden and cost of the research programme.
- The necessity for, and nature of, the value judgment the skilled team would have in the course of a testing programme.
- The existence of alternative or multiple paths of research.
- The motive of the skilled person: it is not enough that the skilled person could undertake a particular trial, but it could be asked whether in the circumstances they would have been motivated to do so.
- The fact that the results are unexpected or surprising.
- When addressing the statutory question of obviousness, hindsight, including knowledge of the invention, should be avoided.
- Whether a feature of a claimed invention is an added benefit in a context in which the claimed innovation is obvious for another purpose.
Some of the intervener industry associations had raised concerns that the Court of Appeal's decision might be taken to suggest a blanket approach that empirical bioscience research would not be seen as inventive where the methods of research were well-established, and that the results of routine investigations cannot lead to a valid patent claim. Particular anxiety was directed at Lewison LJ's comment in the Court of Appeal judgment that "in a case which involves routine pre-clinical and clinical trials, what would be undertaken as part of that routine is unlikely to be inventive". Lord Hodge, giving the Supreme Court judgment, rejected this characterisation of the Court of Appeal's decision: "efficacious drugs discovered by research involving standard pre-clinical and clinical tests should be rewarded with a patent if they meet the statutory tests".