UK Supreme Court provides guidance on the assessment of obviousness with respect to dosage patents
Selecting the right dose for a new drug is an important step in drug development. This may take several years of clinical trials. Inventions for such dosage regimes often arise years after the active ingredient was first patented. However, securing patent protection for these types of inventions has proved difficult in recent years.
In a recent UK Supreme Court judgement, a patent (UK 1173 181) for the drug Tadalafil has been ruled as invalid, on the basis that it lacked an inventive step. The patent is owned by ICOS and exclusively licensed to Eli Lilly. Tadalafil (branded as CIALIS) is an orally administered drug for treating erectile dysfunction (ED). Tadalafil works in a similar way to Pfizer’s famous blockbuster drug Viagra, but with fewer side effects. UK 1 173 181 relates to a dosage regime for Tadalafil. The patent claims doses of 1-5 mg of Tadalafil up to a maximum total dose of 5mg per day.
In an attempt to clear the market for their own Tadalafil generic, Actavis and others (being generic companies) brought revocation proceedings against the ICOS/Lilly patent. The case concerns a principle question; how does the test of obviousness apply to a dosage patent? In clarifying the theory behind inventive step, the Supreme Court provides new guidance, in the form of a 10 step approach. In summary, the following list of factors have to be considered in an obviousness assessment. These are:
- was it “obvious to try”?
- was the research routine in nature?
- the burden and cost of the research programme?
- what value judgments would the research team have to make?
- were there alternative paths of research?
- the motivation of the skilled person to undertake certain technical trials;
- were the results unexpected or surprising? The court did however caution that the fact that routine tests have uncertain results does not turn those results into an invention;
- the need to avoid hindsight. In other words, was the combination of steps by which the inventor arrived at his invention ascertained by hindsight knowledge;
- whether the feature of the claimed invention is an added benefit in which the claimed innovation is obvious for another purpose;
- in the case of a dosage patent, there is no blanket prohibition on such patents when drafted in the corrected format.
In considering the factors, the Supreme Court found the patent obvious. The obviousness argument was based on a prior art patent application (WO 97/03675) known as "Daugan" which disclosed the use of Tadalafil for the treatment of ED, giving a 50mg dose as a formulation example. Daugan specified a Tadalafil dose in the range of 0.5 to 800 mg per day. Daugan also provided data for a 50 mg Tadalafil dose. Daugan did not disclose a dose of 1 to 5 mg per day of Tadalafil as an effective treatment of sexual dysfunction. The novelty of the subsequent Tadalafil patent in view of Daugan was therefore not at issue.
The Court confirmed that the skilled team would use routine, established practices involved in pharmaceutical research, and the Daugan patent would have motivated them to identify the low dose. The skilled person generally aims for a dose as low as possible consistent with effectiveness and having regard to safety and tolerability, via routine and familiar pre-clinical and clinical procedures. It would then have been “very likely” that the skilled research team would have conducted further testing at lower doses, including 5mg, which the experts suggested would have been a “no brainer”.
So, what does this decision mean for South Africa? The patent for Tadalafil has also been filed in South Africa and is set to expire in 2020. Whilst it is unlikely that the patent would now be challenged in South Africa, the stringent 10 step approach may certainly be used as a blueprint and influence our Courts in assessing inventive step for future dosage patent cases.
The judgement causes one to question: So when are dosage patents inventive?
Having regard to the long list of factors that a court might take into account, it appears that dosage patent may now be more vulnerable to an obviousness attack, not just in the UK but throughout the world. Dosage patents can still be valid and a worthwhile means of protecting continuing research on a known drug, however, patent applicants should focus on any unusual features in their research programme and emphasise these where possible. As a result of this judgment, multinational pharmaceutical companies will no doubt reconsider their future worldwide patent filing strategy, for dosage patent applications.