ICOS Corporation and Eli Lilly & Company appealed against a judgement from the Court of Appeal, which held that the patent was invalid. The recent UK Supreme Court judgement Actavis v ICOS Corporation dismissed the appeal and upheld that the patent was invalid for lacking an inventive step.
The patent related to the use of a new dosage regime of tadalafil (sold under the brand name CIALIS®) to treat sexual dysfunction. The claimed invention specifically related to the use of a unit dose containing 1 to 5 mg of tadalafil for administration up to a maximum total dose of 5 mg of tadalafil per day.
The closest prior art was taken to be a patent application ("Daugan") generally disclosing the use of tadalafil to treat sexual dysfunction. Daugan discloses tadalafil's potency against PDE5 (which was previously implicated in sexual dysfunction), and suggests that doses of tadalafil will generally be in the range of 0.5 mg to 800 mg daily, giving an example of a tablet containing 50 mg of the tadalafil.
The assessment of inventive step in the present case focused on what the hypothetical skilled team would have done in phase IIb clinical trials. Phase IIb clinical trials involve testing a range of doses with the aim of finding the optimum dose at which the drug shows biological activity with minimal sideeffects.
The respondents argued that it would have been obvious for a skilled team to take tadalafil forward into a routine pre-clinical and clinical trial programme in view of the disclosure of Daugan. In particular, standard dose-ranging studies, involving routine work and not involving inventive effort, would have led to the new dosage regime claimed in the patent.
It was not disputed that it would have been obvious to take tadalafil forward into a routine pre-clinical and clinical trial programme as an oral treatment for sexual dysfunction in view of the teachings in Daugan. It was also not disputed that the skilled team would have first tested higher doses of tadalafil during the phase IIb trials and would have found the discovery of a therapeutic plateau between 25 mg and 100 mg doses to be surprising.
The respondents argued that it would have been obvious to go on to test doses as low as 5 mg per day after the discovery of the therapeutic plateau between 25 mg and 100 mg.
The appellants argued that it would not have been obvious at the start of the programme to try a dosage as low as 5 mg per day as there was no reason to think that it would be effective at that dosage. Further, it was not obvious at the start of the programme that a dosage as low as 5 mg per day would be safe and effective and also have minimal side effects.
Lord Hodge was not persuaded that the law adopts the extreme position of either submission. The judgement provides a useful discussion of the assessment of inventive step and many factors that should be taken into account in the analysis. In the present case, Lord Hodge considered that the following factors were relevant considerations:
- whether it was "obvious to try" at the priority date;
- the routine nature of the research;
- the burden and cost of the research programme;
- the necessity for and the nature of the value judgements;
- the existence of alternative or multiple paths of research;
- the motive of the skilled person;
- the unexpected or surprising nature of the results;
- that hindsight must not be used in the assessment of inventive step;
- whether a feature of a claimed invention is an added benefit in a context in which the claimed innovation is obvious for another purpose.
In relation to the balance between whether something was "obvious to try" and the unexpected or surprising nature of the results, Lord Hodge stated that "...there is no requirement that it is manifest that a test ought to work; that would impose a straightjacket which would preclude a finding of obviousness in a case where the results of an entirely routine test are unpredictable. As Birss J observed in this case (para 276), some experiments which are undertaken without any particular expectation as to result are obvious. The relevance of the "obvious to try" consideration and its weight when balanced against other relevant considerations depend on the particular facts of the case" (paragraph 65 of the judgement). Further, it was stated that "the fact that the results of research which the inventor actually carried out are unexpected or surprising is a relevant consideration as it may point to an inventive step, at least in so far as it suggests that a test was not obvious to try or otherwise the absence of a known target of the research which would make it less likely that the skilled person would conduct a test" (paragraph 71 of the judgement).
Ultimately, it was decided in the present case that the skilled team would have obviously pursued the phase IIb tests in a routine way until the claimed dosage regime was ascertained, as this would have been the target of the phase IIb tests. The lack of an expectation of efficacy therefore provided little weight. This was supported by the experts of both parties who agreed that the skilled team would not stop the dose ranging studies when they had revealed the therapeutic plateau between 25 mg and 100 mg. The fact that the claimed dosage also provided minimal side effects was simply an added benefit that did not prevent the identification of the new dose.
Impact on Other Dosage Regime Patents
Although the decision may be disheartening for patent applicants and proprietors, it is important to note that Lord Hodge clearly stated that he does not consider that the product of well established or routine enquiries cannot be inventive. It therefore seems that additional factors, such as a teaching away from a particular treatment or dose, or an improvement or unexpected effect going beyond a bonus effect, will be important when assessing the inventive step of a new dosage regime.
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