Actavis & Ors v Eli Lilly And Company

In pharmaceutical patent cases, a dosage regime may be patentable subject matter, but its validity depends on whether the particular regime involves an inventive step. Obviousness is a single question of fact. A staged research programme may contain many routine tests, yet the result may remain non-obvious when the skilled team had no reasonable expectation that the claimed dose would provide a clinically relevant effect with reduced side effects. Priority depends on technical disclosure of the same invention, assessed from the priority document as a whole. A numerical sub-range is not automatically entitled to priority merely because it falls within a broader disclosed range. A claim limited by pharmacokinetic properties is insufficient if it extends beyond the technical contribution made by the patent. A particle-size claim is not ambiguous where the skilled reader would understand it to require the industry-standard volume distribution.

The claimants sought to clear the way in relation to two patents concerning tadalafil, the active ingredient in CIALIS and ADCIRCA. The patents concerned, respectively, low-dose administration for treating sexual dysfunction and free-drug particulate formulations with defined particle-size characteristics.

The proceedings raised issues of claim construction, priority, added matter, novelty, obviousness, insufficiency and threatened infringement. The court considered whether low-dose tadalafil and micronised tadalafil formulations were obvious in light of the Daugan prior art and whether later applications constituted novelty-only prior art. It also considered whether the claimants’ marketing authorisations and proposed market entry created a sufficient probability of infringement to support quia timet counterclaims.

1. 181 patent. The maximum-dose wording in the basic product claim had no limiting effect. In the purpose-limited and Swiss-form claims it meant administration of no more than 5 mg per day, while permitting higher approved doses for other uses. Use of 2.5 mg and 5 mg tablets in accordance with the relevant SmPC would infringe.
2. The priority document disclosed tadalafil, dosage forms containing 1–5 mg, and administration up to 5 mg per day. The disclosure of tadalafil did not depend on Example 5 being recognised as a tadalafil experiment. Claims 2 and 12 lacked priority because a 2.5 mg dosage form was not disclosed. The remaining relevant claims were not added matter.
3. Stoner had legal priority, but did not anticipate because it disclosed combination therapy and did not plausibly enable an efficacious combination involving tadalafil at the claimed doses. Claims 2 and 12 were invalid for lack of novelty over Anderson and Oren.
4. Following Pozzoli v BDMO [2007] EWCA Civ 588, obviousness remained a single question of fact. The skilled team would undertake a clinical programme, but would not reasonably expect a 5 mg daily dose to provide a clinically relevant effect with minimal PDE5-related side effects. The 5 mg dose was therefore inventive. A 25 mg dose was obvious.
5. 092 patent. Oren inevitably produced formulations within the pharmacokinetic claims, which consequently lacked novelty. Micronised tadalafil with a surfactant was the first and obvious formulation approach over Daugan. Claims 1 and the related use claims were obvious. Claims 8, 9, 16–18 and the dependent version of claim 19 were insufficient because their breadth was not commensurate with the technical contribution. Claim 12 was broad but not ambiguous. The particle-size claims required a volume distribution and were not insufficient.
6. There was a sufficiently strong probability of infringement to justify the quia timet counterclaims, viewed objectively and in light of the marketing authorisations and intended generic market entry.

At least claim 7 of the 181 patent was valid and infringed. All claims of the 092 patent were invalid.