Actavis Group PTC EHF & Anor v Teva UK Ltd & Ors

In assessing obviousness of a pharmaceutical dosage claim, the court must ask whether the skilled but unimaginative team would arrive at the claimed product or regimen in light of the prior art and common general knowledge, having regard to all relevant circumstances.

A dosage claim is not inventive merely because efficacy at the claimed dose was unforeseeable or because routine dose-ranging studies reveal a surprising therapeutic effect. Where such studies are undertaken to establish the dose-response relationship, a plateau at higher doses may make lower-dose testing the routine continuation of the programme. Priority requires direct and unambiguous derivability from an enabling disclosure.

Actavis, Teva and Mylan sought revocation of ICOS and Lilly’s patent concerning low-dose tadalafil for treating sexual dysfunction. They challenged construction, priority, added matter, novelty over Stoner and obviousness over Daugan. Lilly counterclaimed for threatened infringement.

Birss J held that claims 1, 7 and 10 were valid and that the intended products would infringe, although claims 2 and 12 lacked novelty. The appeals concerned whether the low-dose regimen and dosage composition were properly construed, entitled to priority, novel and inventive. The central issue was whether the claimed 5 mg daily dose was obvious in light of the routine clinical development programme for tadalafil.

1. Disposition. The Court of Appeal allowed the appeal. Claims 1, 7 and 10 of the patent were invalid for lack of inventive step.
2. Construction and infringement. The claims were to be construed purposively. In claim 1, the expression suitable for oral administration did not limit the dosage form to a particular use, and the stated maximum daily dose did not restrict the scope of that product claim. In claims 7 and 10, however, the maximum total dose qualified the therapeutic use. Claim 10 was a conventional Swiss-form claim covering both the indication and the dosing regimen. Marketing and packaging tablets for authorised administration of 2.5 mg or 5 mg per day would infringe, notwithstanding the availability of higher authorised doses.
3. Priority and added matter. The priority test required the claimed subject matter to be derivable directly and unambiguously, using common general knowledge, from an enabling priority disclosure. The document disclosed tadalafil, dosage forms within the claimed range and administration up to a maximum total dose of 5 mg per day. Its technical rationale and supporting data made the claimed efficacy sufficiently plausible. Claims 7 and 10 therefore retained priority. The application as filed contained the same relevant disclosure, so the added-matter objection failed.
4. Novelty. Under section 2(3) of the Patents Act 1977, Stoner could be relevant earlier prior art. The legal burden of proving its earlier priority remained on the claimants, but the documentary evidence raised a prima facie case and shifted the evidential burden. Stoner was entitled to the earlier priority date, but its broad combination therapy and speculative efficacy did not provide an enabling disclosure. It therefore did not anticipate the claims.
5. Obviousness. Applying the statutory question described in [2012] EWCA Civ 1234 and the structured approach in [2007] EWCA Civ 588, the court held that claim 1 was obvious because it covered a dosage composition without a therapeutic-use limitation. Claims 7 and 10 were also obvious. Daugan and sildenafil made it obvious to develop tadalafil through routine pre-clinical and clinical trials. Phase IIb dose-ranging studies were undertaken to establish the dose-response relationship. Once higher doses showed an efficacy plateau, lower-dose testing, including 5 mg, was the likely routine continuation. The absence of a prior expectation that 5 mg would be efficacious, and the surprising reduction in side effects, did not make that routine enquiry inventive. Floyd LJ and Lewison LJ added separate observations on the limits of hindsight and the non-essential nature of an expectation of success where routine testing would be undertaken.

• Court of Appeal (Civil Division) In [2017] EWCA Civ 1671, the court allowed the appeal and held claims 1, 7 and 10 invalid for lack of inventive step.
• High Court of Justice, Chancery Division (Patents Court) Birss J, in [2016] EWHC 1955 (Pat), upheld the validity of the relevant claims, rejected the obviousness challenge and held that the intended products would infringe.