Ralcon Research LLC & Anor v Ctavis Group PTC EHF & Ors

A second medical use claim is anticipated only by a clear and unambiguous disclosure of every claim feature which also makes the claimed therapeutic effect plausible. For obviousness, identifying a compound as worth investigating does not make its therapeutic use obvious. The court must assess the prior art’s practical direction, the skilled team’s common general knowledge, the uncertainties in the field and any expectation of success.

A research field may be established although small and recently formed. Its identity depends on the real position at the priority date and the field in which the objective problem lay. A drug’s suitability “for use” also depends on the disease, treatment context and nature and severity of its side effects.

The proceedings concerned the validity of a patent protecting the use of fluprostenol isopropyl ester (FIE) in a topical ophthalmic treatment for glaucoma and ocular hypertension. A supplementary protection certificate had been based on the patent. Both rights had expired, but validity remained material because interim injunctions had been supported by cross-undertakings in damages.

Infringement by the defendants’ generic products was admitted. The remaining issues were the identity of the skilled team, common general knowledge, anticipation by European Patent Application No 0 603 800, obviousness over the Stjernschantz article and an obviousness/insufficiency squeeze. The patent had previously been upheld in amended form by an EPO Technical Board of Appeal, but that proceeding involved different prior art, evidence and arguments.

1. The patent was valid. The allegations of anticipation and obviousness failed, as did the obviousness/insufficiency squeeze. No amendment was required.

2. For obviousness, the skilled addressee comprised a medicinal chemist and a pharmacologist specialising in prostaglandins. The objective problem was to retain the intraocular-pressure-lowering activity of prostaglandins while avoiding unacceptable side effects. A small but sufficiently well-defined research field concerned with prostaglandin analogues for glaucoma existed at the priority date. Its recent establishment, limited practical accomplishments and scientific uncertainty remained relevant to the assessment.

3. The Coleman receptor-classification system, including fluprostenol’s potency and selectivity as an FP-receptor agonist, formed part of the common general knowledge. The system was an analytical and classificatory tool, not a reliable means of predicting therapeutic efficacy, side effects or other mechanisms of action. Fluprostenol was known in that context as an analytical tool rather than as a glaucoma medicine.

4. European Patent Application No 0 603 800 did not anticipate the claims. Its only individualised disclosure of FIE was in a specific combination excluded by the claim’s proviso. References elsewhere to broad formulae, preferred esters or fluprostenol did not clearly and unambiguously disclose FIE within the claimed treatment. Further, the document contained no data making the claimed therapeutic effect plausible and enabling the second medical use.

5. The claimed use was not obvious over Stjernschantz. That article directed the skilled team towards structural development of phenyl-substituted prostaglandin analogues. It neither mentioned fluprostenol nor demonstrated that efficacy and side effects could be predicted solely from prostaglandin-receptor affinity and selectivity. Its account of the receptors responsible for side effects was hypothetical, and its results suggested possible correlation between activity and hyperaemia. The skilled team would not select FIE without invention and would have no positive expectation of therapeutic success. A hope sufficient to justify research or a low-cost gamble did not establish obviousness.

6. The patent made it plausible that FIE reduced hyperaemia compared with PGF2α isopropyl ester. The insufficiency squeeze therefore failed. In context, the long-term burdens of irritation and hyperaemia meant that PGF2α was not suitable “for use” in treating glaucoma despite its pressure-lowering effect.

This was a first-instance validity trial. The patent had previously been opposed before the European Patent Office and upheld in amended form by the Technical Board of Appeal in T1872/14 Travoprost/ALCON on 21 April 2016. That decision concerned different prior art, evidence and arguments and was of limited relevance to the present issues.