Ascertaining inventive step in a dosage of tadalafil

Cialis® is a pharmaceutical product for the treatment of erectile dysfunction developed by Lilly ICOS, a joint venture of ICOS Corporation and Eli Lilly and Company. The active pharmaceutical ingredient (API) of Cialis®, tadalafil, inhibits the PDE5 enzyme, just like sildenafil in the better-known Viagra®. 

Recently, the District Court of The Hague had to decide whether a pharmaceutical unit dosage composition for a maximum daily dosage of 5 mg of tadalafil for the treatment of a sexual dysfunction, as claimed in ICOS’s patent EP1173181, involves an inventive step. Teva Pharmaceuticals Europe, claiming invalidity of the patent before the court, argued that this dosage composition is obvious in view of an earlier patent publication by ICOS (WO 97/03675). 

Contrary to ICOS’s submissions, by disclosing the use of tadalafil for sexual dysfunction, this earlier document incentivises the skilled person to develop a second in class drug for this indication and the skilled person would accordingly start clinical trials. As such, the court reasoned that the case comes down to the question of which dosages would be tested in a phase IIb clinical trial and whether 5 mg would be part of this trial. 

Following this reasoning, the court judged that the skilled person could then walk down 

two one-way streets, which would both inevitably lead to the dosage unit composition of 5 mg. Going down a first street, the skilled person would find pharmaceutical data in phase I clinical trial studies which would, together with known efficacy data for sildenafil in Viagra®, enable him to make the calculated estimation that a 5 mg daily dosage should be included in phase IIb clinical trial tests.

The court then further argued that, even if the skilled person would not take this street, but instead would turn into phase IIb clinical trial studies with daily dosages of 25, 50 and 100 mg, the skilled person would have found a constant efficacy of tadalafil at these dosages and would accordingly have lowered the dosage to reduce side effects. As such, either street would lead the skilled person to an effective daily dosage of 5 mg with minimal side effects.  

Therefore, in the Court’s decision, all roads obviously lead to Cialis®.