Précis

In Actavis UK Ltd & Others v Eli Lilly & Company Limited [2015] EWCA Civ 555 (25 June 2015), the English Court of Appeal overturned a declaration of non-infringement which, unusually, had been granted in favour of Actavis in relation to the UK, Spanish, Italian and French designations of a European patent. The Court of Appeal has found that a patent claim in the form “Use of pemetrexed disodium in the manufacture of a medicament…” would be indirectly infringed by the supply of a product containing pemetrexed potassium as the active ingredient.

The Court of Appeal also took the opportunity once again to discourage the use of the prosecution history in construing a patent claim.

Background

Pemetrexed disodium is a chemotherapy treatment developed and marketed by Eli Lilly under the brand name ALIMTA™ since 2004. Its indications are the treatment of pleural mesothelioma and non-small cell lung cancer. In 2014, global sales of Alimta were $2.8bn (it was one of the top 50 global pharmaceutical products).

Eli Lilly had patent protection for pemetrexed disodium as a new chemical entity under European Patent No. 0 432 677. However, this patent is due to expire in December 2015. Eli Lilly also owns European Patent No. 1 313 508, covering “the use of pemetrexed disodium” in the manufacture of a medicament for use in combination therapy” with vitamin B12 and, optionally, folic acid (Claim 1). This claim is in the well-known “Swiss form”.

Planning to launch a generic product in which the active ingredient would be either pemetrexed diacid, pemetrexed ditromethamine or pemetrexed dipotassium, Actavis applied to the English Patents Court well in advance of the expiry of EP ‘677 for a declaration of non-infringement (“DNI”) covering the UK, France, Germany, Italy and Spain.

At first instance, Arnold J referred to the prosecution history of the patent when considering the construction of the claim. He found it relevant that the claim as filed referred to “an antifolate” as a class, rather than “pemetrexed disodium”. This had been narrowed in prosecution, first to refer to “pemetrexed” and then to “pemetrexed disodium” to overcome objections from the EPO of lack of support.

He also drew on the testimony of expert witnesses to analyse how the claims would be construed under French law, Italian law and Spanish law (the Oberlandesgericht in Düsseldorf having accepted jurisdiction to rule on the German designation of the patent).

In relation to infringement, Arnold J held that the essential element of the claim was the sodium salt of pemetrexed, and thus a substance containing pemetrexed dipotassium would not infringe Eli Lilly’s patent under English law. Arnold J also decided that English law, as lex fori, governed the conditions for admissibility of an application for a declaration of non-infringement. He ruled that Actavis had complied with those conditions, and hence granted the DNI in relation to the UK, French, Italian and Spanish designations of EP ‘508.

The judgment on appeal

Eli Lilly appealed against the finding of non-infringement and the granting of the DNI, arguing that claim extends to cover the use of Actavis’ proposed active ingredients.

As regards use of the prosecution history as an aid to construction, it was common ground between the parties that the prosecution history is formally admissible. However, the parties differed on the weight that the Court should place on it. The Court of Appeal said that it saw little purpose in reviewing the prosecution history as an aid to construction of the claim. At first instance, the Patents Court had suggested that in some circumstances consideration of the prosecution history can assist in ensuring the patentees do not abuse the system by accepting narrow claims during prosecution and then arguing for a broad construction of those claims for the purposes of infringement. The Court of Appeal refused to endorse this, emphasising that the light, which the prosecution history sheds on the ultimate question of construction, is likely to be extremely limited. This continues the trend under English law to discourage strongly the use of the prosecution history in claims construction.

The Court of Appeal upheld the finding of no direct infringement, accepting the judge’s conclusion that the claim was clearly limited to the disodium salt of pemetrexed.

However, the Court of Appeal found indirect infringement by Actavis under section 60(2) of the English Patents Act 1977, which prohibits the supply of a means, relating to an essential element of an invention, for putting the invention into effect.

The Court’s reasoning was that: the words “manufacture of a medicament” in Claim 1 were not only limited to the solid dosage form, but also covered an injectable solution arrived at by dissolving the solid dosage form in an appropriate solvent; as a result, the claim covered an injectable solution containing (disassociated) pemetrexed ions and sodium ions; whilst Actavis only planned to supply the solid dosage form, it admitted that its Summary of Product Characteristics would instruct the doctor or pharmacist administering its product to reconstitute and dilute it in saline (i.e. sodium chloride solution); the resulting solution would contain pemetrexed ions and sodium ions (as well as chloride ions), and hence fall within the scope of the claims (even though the source of the sodium ions was the saline solution, rather than the solid dosage form). According to the Court, the key point was that Actavis would supply the means relating to an essential element of the claim which would allow a pharmacist to put the invention into effect by reconstituting the substance. Interestingly, the Court of Appeal’s judgment contradicts a ruling on this point by theOberlandesgericht, which found that there was no indirect infringement.

Because of the Court of Appeal’s ruling that Actavis was not entitled to a declaration of non-infringement in the UK, the additional issue of which laws govern the grant of a declaration by the UK Courts for the non-UK designations of the European Patent fell away. However, as the Court had heard full argument on the point, it gave its view. It upheld the decision at first instance on this issue, holding that English law as lex fori governs the admissibility of an application for a DNI, even in respect of the French, Italian, Spanish designations of the EP.

Conclusion

Actavis deployed a clever litigation strategy in this case. It aimed to clear the path for its proposed generic product in 5 jurisdictions in a single set of proceedings, and the English Courts accepted that this type of cross-border relief is in principle possible. In order to achieve this aim, Actavis did not challenge the validity of EP ‘508: to do so would have defeated its strategy, as it would have meant that the English court did not have jurisdiction to deal with the DNIs in respect of the foreign designations. This is because the European jurisdiction rules provide that courts of the EU member state where the patent is registered have exclusive jurisdiction over the issue of validity.

Faced with this clever litigation strategy, Lilly managed to snatch victory from the jaws of defeat at the last moment, in light of its winning argument on indirect infringement.

However, this may turn out to have been a pyrrhic victory. Following judgment, Actavis proposed to modify its proposed new product by specifying that it is for reconstitution with dextrose, rather than saline solution. It argued, in light of the decision of the Court of Appeal, that this would not amount to indirect infringement (as there would be no source of sodium ions in solution) and hence would be lawful. Eli Lilly objected, on the basis that a person administering the Actavis product to a patient may dilute or reconstitute with saline even if directed to do so with dextrose and not with saline, and that this would be foreseeable to Actavis. This issue has been remitted for trial in the Patents Court. If Actavis turns out to been correct, this will have been an easy work-around, and it will have achieved its commercial aim of clearing the path for its product (though at a price – it will have to bear the doubtless significant legal costs of the proceedings to date).

[Stop-press news: on 12 December 2011, the Court granted judgment in favour of Actavis on this issue. Eli Lilly had admitted that that healthcare professionals in the four jurisdictions would follow the instructions contained in Actavis’ SmPC to reconstitute or dilute the solid dosage form with dextrose solution, at least until stability data for the product in saline was published by third parties. In those circumstances, the Court granted a declaration that Actavis would not infringe EP ‘508 by supplying its proposed generic products in the four jurisdictions in question prior to third party stability data being published].

As regards the comments of the Court of Appeals comments on the use of the prosecution history as an aid to construction, these reinforce previous judicial disapproval in the English Courts (at least prior to the decision at first instance in this case) of the practice. It now seems clear that any party wanting to rely on the prosecution history in patent litigation in the English courts will face an uphill struggle.

Finally, it is interesting to note that an alternative litigation strategy will become available to generic companies in these circumstances once the Unified Patent Court opens for business. Rather than having to forego a revocation action in order to get cross-border relief, a third party will be able to institute both a claim for a DNI and a revocation action in the Unified Patent Court and obtain a decision in relation to all designated states under the patent (unless the European patent in question is “opted out” by its proprietor from the jurisdiction of the Unified Patent Court before the action is filed).