Supreme Court holds Dosage Regime Patent Obvious

The patent

EP 1 173 181 relates to a dosage regime for Tadalafil: a "second-in-class" treatment for erectile dysfunction (ED), which followed the blockbuster drug sildenafil (VIAGRA). The patent claims doses of 1-5 mg of Tadalafil up to a maximum total dose of 5mg per day and discloses that such doses exhibit fewer side effects than sildenafil whilst retaining efficacy.

Tadalafil is marketed for the treatment of ED in unit doses of 10mg and 20mg for on-demand administration and in unit doses of 2.5mg and 5mg for daily administration. Sildenafil is marketed on demand at doses of 25mg, 50mg and 100mg.

Actavis brought revocation proceedings in respect of the 181 patent in December 2014, which were later combined with related proceedings brought by Teva UK Limited and Teva Pharmaceutical Industries Limited and Generics (UK) Limited (trading as Mylan) (the Claimants/Respondents). ICOS and its exclusive licensee, Eli Lilly and Company, (together "Lilly") counterclaimed for infringement.

The decision

The Supreme Court decision focuses on the correct approach to assessing obviousness. 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.

Lilly argued that the correct question to be asked when assessing obviousness was whether at the priority date, before the skilled team embarked on any testing, it was obvious in the light of Daugan that a 5mg daily dose of Tadalafil would be safe and effective with minimal side effects for sexual dysfunction. That is, was it obvious to try a low dose of 5mg because there was a reasonable expectation of success at the outset, before any testing. Lilly argued that this was in line with the second of the Windsurfing/Pozzoli obviousness questions requiring one to "identify the inventive concept of the claim". This approach then excludes any consideration of whether the steps required to reach the invention were routine.

The Respondents (Actavis et al) argued that, on the basis of the fundamental principles of patent law, a patent should not cover subject matter which was already in the skilled person's "repertoire", i.e. products or processes which the skilled person was already able to make or do. The claimed low dose of Tadalafil was the result of a familiar and routine path of pre-clinical and clinical research, in which each step was likely to follow the outcome of the prior step.

Contrary to Lilly's submissions, the Court held that it is not necessary for the skilled team to identify in advance of the clinical testing the specific dose which is the subject of the claim. Instead the Court relied on the findings of the trial judge that the skilled team, having embarked on Phase IIb dose ranging studies and identified a therapeutic plateau at doses of 10mg and above, would very likely test a 5mg dose given that the aim of a dose ranging study is to identify a dose as low as possible consistent with effectiveness. The claim was therefore obvious.

The Court further dismissed Lilly's argument that daily administration was a technical effect of the patent, given the claims cover both on demand and daily dosing and any inventive concept must apply to all embodiments falling within the claims. Furthermore, the fact that the claimed dosing regime had an added benefit of reduced side effects was merely that, an added benefit, and did not preclude the claims from being obvious.

Comment

In considering the factors to be assessed following the Windsurfing/Pozzoli approach, the Court recognised the "nature of the invention" as the overriding factor. The Court acknowledged that although there is "…no policy reason why a novel non-obvious dosage regime, which was the product of expensive and unpredictable research, should not be rewarded with a patent of a Swiss-form claim" (as stated in Actavis v Merck [2009] 1 WLR 1186), with respect to a dosage regime patent "[t]he target of the skilled person's research is in large measure pre-determined". The Court also confirmed that the skilled person aims for a dose as low as possible consistent with effectiveness – this is normally the appropriate dosage regime and consequently is an obvious one.

Click here to view the full judgment

Case: Actavis Group PTC EHF and others v ICOS Corporation and another

[2019] UKSC 15

[2017] EWCA Civ 1671

[2016] EWHC 1955 (Pat)