The never-ending debate on the value of second medical use patents

It is well established that a second medical use patent may be validly obtained in Europe for any second or further therapeutic use of a known drug, providing the use is novel and inventive. However, it can be difficult to enforce a second medical use patent if the drug is already marketed for an existing condition. For innovator companies that discover a new medical use, there is an inconsistency between the effort that goes into getting approval for the new medical use and the exclusivity that is available. Further, companies who base their entire business around re-purposing a known drug and obtaining second medical use patent protection to protect their rights can face problems seeking investment opportunities, since there is some doubt on their value. However, recent decisions suggest that such patents do have value, allowing branded products to use these patents to maintain price differentials justified by the new therapeutic indications, even after generics are on the market.

Second medical use patents are used to extend the patent protection available for a drug once the basic patent protecting the drug compound per se has expired. In theory, a generic version of a drug may not be marketed for the protected therapeutic indication(s) for as long as the use patent is in force. As a general rule, the Summary of the Product Characteristics for a generic version of a drug must contain the same information as that of the originator drug, including the therapeutic indications, dosages and method of administration. However, according to Directive 2001/83, Article 11, indications covered by patent law at the time a generic version of a drug is marketed need not be included. This means that generics companies may lawfully market a drug whilst a second medical use patent is in force if it “carves out” all references to the patented therapeutic indication(s) from the Summary of Product Characteristics and Patient Information Leaflet, leaving only references to non-patented indications. This is a practice known as “skinny labelling”. UK courts are unlikely to consider this a direct infringement of a second medical use patent because it is unlikely that the patentee is able to prove that the generic version of the drug is being manufactured or sold for the patented use.

In the UK, approximately 83% of prescriptions are written generically, i.e. without reference to the branded originator drug. Furthermore, approximately 95% of prescriptions do not state the indication for which the drug has been prescribed. Thus, in cases where a drug can be prescribed for multiple indications, a pharmacist dispensing the prescription will not know the indication for which the drug is being prescribed. It is therefore possible that a pharmacist will dispense a generic version of a drug for the treatment of a patented indication, despite positive steps taken by a generics company to remove a patented indication from a product label.

In a recent series of decisions (Warner-Lambert v Actavis (and others)), the UK High Court provided a decision on enforcement of second medical use patents having Swiss-type second medical use claims and provided, for the first time, detailed comments on the construction of Swiss-type second medical use claims (claims of the format “use of substance X for the manufacture of a medicament for the treatment of disease Y”). It is now clear that there is value in Swiss-type second medical use claims.

The subject of this series of decisions is Warner-Lambert’s blockbuster drug, pregabalin, marketed for epilepsy, generalised anxiety disorder (“GAD”) and neuropathic pain under a single trade mark, Lyrica®. Patent protection for pregabalin per se has expired, however a second medical use patent, EP(UK) 0 934 061, owned by Warner-Lambert is in force which has Swiss-type second medical use claims directed to the use of pregabalin for treating pain, and in particular neuropathic pain. Actavis has applied for marketing authorisation limited to the use of pregabalin for the treatment of epilepsy and GAD. Warner-Lambert then alleged that Actavis would infringe their second medical use patent and requested interim relief that Actavis’ product packaging include a statement that the product should not be dispensed for pain.

In Warner-Lambert v Actavis & Others [2015] EWHC 72, Arnold J denied the interim relief requested by Warner-Lambert on the basis that there was no serious issue to be tried. Furthermore, Arnold J held that even if there was a serious issue to be tried, he would not have granted interim relief on the balance of the risk of injustice.

Arnold J confirmed that Swiss-type second medical use claims are process claims, not product claims, and are directed at the manufacturer, not the doctor. Therefore, the relevant intention is that of the person who carries out the process – in the present case, Actavis or their manufacturer. Arnold J considered that the word “for” in Swiss-type claims “imports a requirement of subjective intention on the part of the manufacturer that the medicament or pharmaceutical composition will be used for the specified condition” (treatment of pain). However, since Warner-Lambert did not rely on any subjective intention on the part of Actavis, it was considered that there was no arguable case of infringement.

Arnold J considered that interim relief would cause “substantial unquantifiable loss” to Actavis if wrongly granted for two reasons. First, if Actavis were required to put a notice on their packaging it would delay their entry into the market and it would be difficult to quantify this loss, especially if other generics companies entered the market during that period. Secondly, and more importantly, the requirement to put a notice on the packaging would likely deter pharmacists from stocking Actavis’ product and could exclude Actavis from the non-patented market.

In his judgement, Arnold J considered that the best solution would be to ensure that doctors prescribe pregabalin by reference to the brand, Lyrica®, rather than by reference to the generic name, pregabalin.

It is unsurprising, then, that in the most recent decision (Warner-Lambert v Actavis & Others [2015] EWHC 485 (Pat) (02 March 2015)), the UK High Court issued an order requiring the NHS to give guidance that only the branded medicine, Lyrica®, should be prescribed and dispensed for the treatment of neuropathic pain. This appears to be a pragmatic solution for the enforcement of Swiss-type second medical use patents in the UK.

Interestingly, in a different decision on 27 January 2015 the Hague Court of Appeal held that Sun Pharmaceutical was committing indirect infringement of Novartis’ use patent EP 1 296 689 (held invalid by the UK courts for lack of novelty owing to an invalid claim to priority). Novartis’ use patent has Swiss-type second medical use claims directed to the use of zoledronic acid in the preparation of a medicament for the treatment of osteoporosis. Novartis’ commercial product Aclasta® is indicated for osteoporosis and Paget’s disease, whereas Sun Pharmaceutical obtained marketing authorisation limited only to Paget’s disease, an indication not covered by Novartis’ use patent. Despite the skinny label directed only to Paget’s disease, the Court Of Appeal considered that Sun Pharmaceutical had not taken sufficient steps to avoid infringement and an injunction was granted to Novartis. It is worth noting that Novartis had estimated that 97.3% of sales were attributed to the treatment of osteoporosis and Sun had won a tender to be the exclusive supplier of the generic version of zoledronic acid 5mg/100ml solution for infusion.

The recent decision by the UK High Court indicates that it will assist innovators in protecting their IP rights, and the recent decision in the Netherlands seems to be even more pro-patentee. The validity and infringement of Warner-Lambert’s patent is scheduled to be heard at full UK trial in June 2015 and it will be interesting to see whether the final outcome is eventually the same as the Hague Court of Appeal decision. Future developments will no doubt be followed closely by life science companies.

In addition, the Neurim judgement of July 2012 by the Court of Justice of the European Union (Europe’s highest court) certainly suggests that the CJEU is also assisting innovators in protecting their IP rights for second medical uses. The Neurim judgement held that a new medicinal product comprising a known active ingredient, indicated for a new therapeutic application that is protected by a new patent, may enable its proprietor to obtain an SPC.

It is worth noting that the recent UK decisions are exclusively concerned with Swiss-type second medical use claims. Enforcement of EPC 2000 second medical use claims (“product X for use in the treatment of Y”) is yet to be considered by the UK courts.

It remains to be seen how compliance by GPs and pharmacists will be measured and how second medical use patents will, in practice, be enforced.