ratiopharm (UK) Ltd v Alza Corp

A patent claim for a fentanyl patch is construed through the eyes of the skilled person and given a practical meaning. A monolithic patch has one functional drug-delivery layer; binary and multilaminate systems fall outside that meaning. A requirement that the patch contain enough fentanyl to induce and maintain analgesia for three days is satisfied if it works for some humans, assessed by appropriate in vivo or validated in vitro testing. Broad claims may remain sufficient where the skilled person can determine their scope without undue burden. Novelty requires clear and unmistakable directions to perform the claimed invention. Obviousness is assessed without hindsight, including in an obvious-to-try case, but a fair expectation of success is required.

Alza Corporation and its exclusive licensee Janssen-Cilag Limited brought infringement proceedings concerning a patent for subsaturated, non-rate-controlled monolithic fentanyl patches. ratiopharm and Sandoz denied infringement and sought revocation on grounds of anticipation, obviousness and insufficiency. The allegedly infringing patches had obtained marketing approval on the basis of bioequivalence to Durogesic. The principal issues were the meaning of monolithic, the three-day analgesia requirement, sufficiency, novelty over Samyang and Roy, and obviousness in light of common general knowledge and several publications.

1. Construction. A monolithic patch meant a patch with one functional layer controlling drug delivery. It excluded multilaminates and binary systems, although a thin additional adhesive coating could be present. The three-day integer required sufficient fentanyl to induce and maintain analgesia in some humans for three days, not in every human and not necessarily at Durogesic-equivalent levels.
2. The requirement could be assessed by in vivo plasma-level testing or by properly conducted and validated in vitro skin-permeation studies. Plasma levels above 0.2 ng/ml, or flux above approximately 1 µg/hr, indicated that the requirement was met at the lower edge of the claim. The claims were broad but not ambiguous and imposed no undue burden.
3. The Osmach and Mezolar Matrix patches infringed because their Durogesic bioequivalence established that they would induce and maintain analgesia in some humans for three days.
4. Under [2006] RPC 10 and [1972] RPC 457, anticipation required disclosure of the invention and the ability to perform it without undue effort. Samyang’s binary examples did not anticipate because they were not monolithic. Its Comparative Example 2 was a single acrylate slab satisfying the claim and anticipated it. The invalidity was capable of cure by amendment. Roy did not contain clear and unmistakeable directions to make a patch within the claimed thickness and three-day requirement.
5. Applying the structured approach in [2007] EWCA Civ 588, the claim was obvious over common general knowledge. The skilled person would consider both liquid-reservoir and drug-in-adhesive designs, and would regard neither a rate-controlling membrane nor saturation plus excess as essential. The claim was also obvious over Roy, the Yu Poster and the Yu Abstract. Permatec and Cygnus added nothing because the attacks depended on hindsight; the Hercon case was not pursued.
6. The patent was therefore invalid, subject to the accepted amendment in relation to Samyang. The infringement findings did not save the claims.

First-instance decision. No prior appellate decision is stated in the judgment.