It is established that an inventive new dosage regime can merit a patent, and such regimes may be the product of extensive and expensive research. However, as indicated by Lord Justice Jacob in the leading case of Actavis v Merck[i], in practice most dosage regimes will fail the test of inventive step as it is standard practice to investigate appropriate dosages. A recent Supreme Court decision[ii] in relation to Cialis drives home the point that patents for dosage regimes will only be available in unusual cases.
Tadalafil (marketed as Cialis) is a competitor to Viagra (sildenafil). Although patent protection for tadalafil itself expired in 2017, ICOS had a patent for a dosage regime of about 1-5mg daily. The essence of this invention was the discovery that tadalafil can treat erectile dysfunction at a low dose and without the side effects associated with sildenafil. This allowed it to be taken on a daily basis, the advantage for patients being that they did not have to anticipate when sexual activity is likely to occur.
Actavis and three other generic manufacturers wished to market a generic form of tadalafil and sought to revoke ICOS’s dosage patent, arguing that the invention was obvious based on the prior art. Originally, the High Court upheld the patent. However, first the Court of Appeal and then the Supreme Court disagreed, confirming that the patent was invalid for obviousness.
Routine or invention?
It was clear that it would not have been obvious to the researchers at the outset that a dosage of 1-5mg would have significant benefits. This was in fact a surprising result. The key question was, however, whether the researchers had happened upon it as a result of carrying out routine tests which inevitably led to its discovery or whether there had been genuine inventiveness. The Court held that the target of the skilled team in such a situation would be to find the appropriate dose, which would usually be the lowest effective dose, and that the pre-clinical and clinical tests carried out involved familiar routine procedures. The evidence showed that even in a situation such as arose in this case, where the research team had found a therapeutic plateau, it would be likely to continue and test lower dosages in order to establish the lowest dose at which the drug was effective. The fact that the 5mg per day dosage had the surprising benefit of minimum side effects was “simply a bonus and did not make the dosage regime an invention”.
Implications of the case
A major stumbling block in patenting dosages is the standard regulatory testing regime which applies to them - steps taken along this well-trodden path are likely to attract the objection that they are ‘obvious to try’, as was the case here. This does not mean that such patents are bound to fail, however. In response to concerns expressed by the interveners, the UK BioIndustry Association and the IP Federation, Lord Hodge was at pains to emphasise that there was no “general proposition” that the product of routine tests cannot be inventive. The Court indicated that factors to be taken into account include the nature of value judgments taken by the skilled team in the course of testing, whether there were alternative routes to choose from and the motives of the skilled team. The fact that the results of research are unexpected or surprising may also point to an inventive step (although it did not do so in this case). All will depend on the facts of the case and whether there is something that lifts it out of the routine, an example being the case of Actavis v Merck referred to above where there had previously been an assumption that the substance would not work with any dosage regime.
A final, frustrating point for stakeholders is that, as is unfortunately often the case, this patent has been held to be valid in some European countries but not in others leaving patentees and generic manufacturers potentially exposed to litigation in multiple European jurisdictions.