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Patently problematic? The impact of the Eli Lilly/Actavis intellectual property battle

Published on 04/09/17 at 10:42am

The UK Supreme Court has sent shockwaves through the intellectual property world with its recent decision on Eli Lilly v Actavis [2017] UKSC 48, finding that Actavis directly infringes Eli Lilly’s patent on the anti-cancer combination therapy of pemetrexed and vitamin B12. Fiona Stevens, Partner at Gill, Jennings and Every, argues that the move seeming reintroduces a ‘doctrine of equivalents’ into the consideration of patent infringement by UK courts

The anti-cancer drug pemetrexed has been marketed as Alimta by Eli Lilly for more than a decade. The original New Chemical Entity patent and its UK Supplementary Protection Certificates (SPC) have both expired. In anticipation of the expiration of Eli Lilly’s SPC concerning pemetrexed (including pharmaceutically acceptable salt forms), Actavis planned to launch a product to compete with Alimta.  Three possible products were in contention: pemetrexed dipotassium, pemetrexed diacid, and pemetrexed ditromethamine.

Eli Lilly, however, owns a further patent (EP1313508), due to expire in 2021, relating to the co-administration of Alimta with vitamin B12. Co-administration with B12 was found to reduce the toxicity and other negative side-effects of pemetrexed that had previously limited its use in anti-cancer treatment. In view of the fact that its proposed competing products would be co-administered with vitamin B12 and folic acid, Actavis sought a declaration of non-infringement (DNI) of Eli Lilly’s patent EP1313508.

EP1313508 covers pemetrexed disodium co-administered with vitamin B12, or one of a list of derivatives of vitamin B12, for anti-cancer therapy. The relevant claims are:

1. Use of pemetrexed disodium in the manufacture of a medicament for use in combination therapy for inhibiting tumour growth in mammals wherein said medicament is to be administered in combination with vitamin B12 or a pharmaceutical derivative thereof…

12. A product containing pemetrexed disodium, vitamin B12 or a pharmaceutical derivative thereof, [optionally plus another component], as a combined preparation for the simultaneous, separate or sequential use in inhibiting tumour growth.

The UK Supreme Court found Actavis’ products to directly infringe this patent, overturning previous judgements from the Court of Appeal and the High Court. In doing so, UK patent law on infringement now appears to include a ‘doctrine of equivalents’ akin to that found in some European civil law jurisdictions.

Why is this decision so important?

This decision makes it easier for pharmaceutical patent owners to reduce competition from products that are similar, but not identical, to the literal wording of their patent claims. Following decisions such as Kirin-Amgen, the UK was previously considered to have closed the door to any kind of doctrine of equivalents and all along was considered to take the most literal approach of the major European patent litigation jurisdictions to interpreting patent claims.

Following the pemetrexed Supreme Court decision, the UK position on including equivalents within the scope of a patent claim is more closely aligned with that of countries such as Germany, which has traditionally been at the opposite end of the spectrum in terms of going beyond the literal terms of patent claims to decide whether or not a similar product or process constitutes an infringement.

Disclosure versus scope

It is generally considered that patent claims, which define the scope of the protection offered by the patent, should be self-contained. While the description can be used to help interpret the claims, it should be possible to understand where the boundaries of the claims lie without needing to take a fine-tooth comb to the description. 

The Eli Lilly vs Actavis decision goes beyond using the description to interpret the scope of patent claims, in fact using the description to broaden that scope. In this case, a combination of an antifolate and a methylmalonic acid lowering agent was described in the general description, whereas much more specific terms appeared in the claims and examples, namely a combination of pemetrexed disodium and vitamin B12 or a derivative. For Eli Lilly, the presence of the general statements relating to antifolates helped to extend the scope of protection beyond just pemetrexed disodium, to include other salt forms of the drug within the reach of infringement.

Chemical structures in patent claims

Precision of chemical structure is important in patent claims. In UK courts, it has previously been a well-accepted principle that structural claims should be interpreted literally when it comes to infringement, and that even simple structural variants are not within the scope of patent claims.

This decision casts doubt on this principle.  If a claim to a sodium salt can cover a potassium salt, then could a claim that is limited to an alkyl group in a certain position also be considered to cover an alkenyl group? In both cases the structures are clearly different, but they could be considered to be functional equivalents.

Second medical use claims vs composition of matter claims

It is worth exploring the fact that the Eli Lilly patent at issue contains ‘second medical use’ claims, as opposed to ‘composition of matter’ claims. The case law in this area has been developing over the past few years, such that patent owners can have reasonably broad composition of matter claims with respect to the data and compounds that are exemplified in the patent, but somewhat narrower second medical use claims. Second medical use claims also require a much higher standard of data. This has parallels with the regulatory process, in that there is a high bar for the approval of new chemical entities, whereas it should in theory be much easier to obtain regulatory approval for repurposed drugs. It is not uncommon for second medical use claims to be granted with a relatively narrow scope, and perhaps this is one reason for equivalents creeping into the claim interpretation. The real test will be whether the decision at issue is extended to other types of patent claim.

Will the generics industry shrink, or build a litigation war chest?

Let’s just recap what this decision actually means: a claim limited to sodium salts can cover potassium salts, if the circumstances are right. The ramifications of this are huge. Only time will tell whether generics companies will be more cautious about introducing a competing product into the UK market, be more willing to enter licence agreements, or even become more aggressive in trying to litigate away problematic patents. One thing is for sure: they may want to re-do some of their freedom-to-operate analyses.

Doctrine of equivalents without file-wrapper estoppel?

Another major point in the decision was the limited extent to which the file wrapper was taken into account. Little was made of the various admissions and claim limitations invoked by the patentee during prosecution. By contrast, the law in the US explicitly includes equivalents, but there is an absolute estoppel on admissions made by the patentee during prosecution. Is it right that you can have one without the other? The law of claim construction for patent infringement cases in the UK appears now to be at a point where a doctrine of equivalents has been re-introduced, but with only limited file wrapper estoppel to keep the reach of patent claims in check. 

Returning to the Eli Lilly case, the claims were limited from antifolates to pemetrexed disodium largely because the examiner contended that the claimed technical effect was not made credible for all antifolates, and therefore the broad claims were not inventive. By contrast, the Supreme Court’s finding of infringement relied on the infringer’s own findings, subsequent to the filing date of the patent in issue, that a variant (potassium, tromethamine or free acid) was functionally equivalent to the salt form claimed. These two findings are hard to reconcile.

As a final thought, while it is only right that innovator pharmaceutical companies should get fair reward and protection for their research and innovation, generics companies should have a degree of certainty that allows them to develop and market competing products.  These are the very principles on which competition and thus innovation flourishes. We can only hope that this recent decision does not upset this delicate balance.

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