Pemetrexed: UK Supreme Court rewrites scope of patent protection
In a ground-breaking decision (Actavis v Eli Lilly), the UK Supreme Court found Actavis’ proposed generic pemetrexed product to directly infringe Eli Lilly’s patent (EP 1313508), overturning the findings of the lower courts who found no direct infringement.
The case [see note 1 below] brings a doctrine of equivalents into UK patent law, as well as a limited doctrine of file wrapper estoppel, and will change the way in which the scope of protection conferred by a UK patent is assessed.
Pemetrexed is an anti-cancer drug developed by Lilly. However, when used on its own, the drug can cause serious side effects: Lilly found that these side-effects could be reduced if the drug was administered together with vitamin B12. Pemetrexed is marketed by Lilly as Alimta®, with the label stipulating administration with vitamin B12. The pemetrexed basic patent and supplementary protection certificate (SPC) expired in 2015. However, based on the above finding, Lilly obtained a second patent, expiring in 2021, covering the combination, which was the subject of the litigation.
The claims of the patent application as filed were drafted broadly, defining both pemetrexed and vitamin B12 in terms of their mechanism of action. These were objected to by the European Patent Office (EPO) on the grounds of insufficiency and lack of clarity. To attempt to address these objections, Lilly amended the claims to recite pemetrexed generally - but the EPO objected that these claims added subject matter, as the application as filed disclosed pemetrexed only in the form of its disodium salt. Lilly further limited the claims to recite pemetrexed disodium, and the EPO allowed the application.
Article 69 EPC and its Protocol, and prior UK case law, on scope of protection
For over 150 years, UK patent law has allowed, in varying forms, the scope of protection conferred by a patent to extend beyond its literal wording to ensure that infringement is not avoided by items which differ from the claim wording only as an immaterial variation. In Catnic v Hill & Smith [see note 2 below] the House of Lords ruled that a patent requires a “purposive construction” rather than “a purely literal one derived from applying to it the kind of meticulous verbal analysis which lawyers are too often tempted by their training to indulge” - thereby finding a steel lintel to infringe a patent claim even though its supporting structure deviated by 6 to 8 degrees from the vertical and the claim recited “vertical”. The Catnic test was refined further in Improver v Remington [see note 3 below] where the Patents Court formulated the following three questions:
- Does the variant have a material effect upon the way the invention works? If yes, the variant is outside the claim. If no – go to question 2.
- Would this have been obvious at the date of publication of the patent to a skilled reader? If no, the variant is outside the claim. If yes – go to question 3.
- Would the skilled reader nevertheless have understood from the language of the claim that the patentee intended that strict compliance with the primary meaning was an essential requirement of the invention? If yes, the variant is outside the claim. If no, the variant infringes the patent.
The “Improver questions” (later rebranded the “Protocol questions” by the Court of Appeal in Wheatley v Drillsafe ) were used for the next 15 years to determine whether a variant of a claimed item infringes a patent. However, the House of Lords once again considered the scope of protection conferred by a patent in Kirin-Amgen - simply by posing one question: “what would the person skilled in the art have understood the patentee to be using the language of the claim to mean?” This was a re-statement of the principle of purposive construction, which the Lords considered gave effect to the Protocol. The Improver questions were not dispensed with completely, but were considered merely guidelines, more useful in some cases than others
In all of the above, the UK courts have consistently been reluctant to apply a general doctrine of equivalents as used in the US and other jurisdictions. Indeed, in Kirin-Amgen the House of Lords opined that Article 69 “firmly shuts the door on any doctrine which extends protection outside the claims”. In the case of Virgin Atlantic v Premier Aircraft, the Court of Appeal, summarising Kirin-Amgen, explicitly stated “it follows there is no general ‘doctrine of equivalents’”.
The lower courts’ decisions
Actavis wished to market pemetrexed in the form of the free acid or a different salt. They sought a declaration of non-infringement of the patent, covering not just the UK but also France, Italy and Spain. Throughout the proceedings, Lilly argued that the scope of protection conferred by the patent extends to other salts of pemetrexed, at least by virtue of equivalents. Actavis counter-argued that it did not, and that the amendments made by Lilly before the EPO estopped them from making this argument in litigation.
At first instance, the Patents Court granted the declaration, on the grounds that the scope of protection was limited to pemetrexed disodium: the court also hinted at a doctrine of file wrapper estoppel, considering that patentees accepting a narrow form of claim during prosecution and then arguing that it covers something broader during litigation may be an abuse of the system.
The Court of Appeal agreed with the Patents Court’s finding that there was no direct infringement, applying the Improver questions and answering “no” to both questions 1 and 2. The court did find Actavis’ product would indirectly infringe the patent, on the grounds that, when reconstituting the product in saline, the disodium salt would be formed in situ. However, the Court of Appeal disagreed with the Patents Court’s view on file wrapper estoppel.
The Supreme Court judgment
The Supreme Court reversed the lower courts’ finding and ruled Actavis’ product would directly infringe the patent. Importantly, the Supreme Court ruled that Article 2 of the Protocol means that there is at least potentially a difference between the interpretation of the wording of the claim and the scope of protection conferred by it - specifically indicating equivalents must be taken into account. The court ruled that two issues must be considered in order to determine whether an equivalent, or variant, falls within the scope of protection:
i. Does the variant infringe any of the claims as a matter of normal interpretation? If not;
ii. Does the variant nonetheless infringe because it varies from the invention in a way or ways which is or are immaterial?
If the answer to either issue is “yes”, there is an infringement; otherwise, there is not.
The Supreme Court ruled that such an approach complies with Article 2 of the Protocol, as issue (ii) above “squarely raises the principle of equivalents”. This would appear to depart from Kirin-Amgen and to bring a general doctrine of equivalents into UK law.
The Supreme Court considered that issue (i) involves solving a problem of interpretation, according to “normal principles of interpreting documents”. Significantly, the court opined that, according to these normal principles, the Actavis products would not infringe under issue (i), as the free acid or alternative salts of pemetrexed could “in no sensible way” be said to fall within the term “pemetrexed disodium”.
In order to determine issue (ii), the Supreme Court revived the Improver questions in a revised form, as follows:
- Notwithstanding that it is not within the literal meaning of the relevant claim(s) of the patent, does the variant achieve substantially the same result in substantially the same way as the invention, ie, the inventive concept revealed by the patent? If no, no infringement - if yes, go to question 2.
- Would it be obvious to the person skilled in the art, reading the patent at the priority date, but knowing that the variant achieves substantially the same result as the invention, that it does so in substantially the same way as the invention? If no, no infringement - if yes, go to question 3.
- Would such a reader of the patent have concluded that the patentee nonetheless intended that strict compliance with the literal meaning of the relevant claim(s) of the patent was an essential requirement of the invention? If yes, no infringement - if no, the variant infringes the patent.
Answering “yes” to questions 1 and 2 and “no” to question 3, the Supreme Court found Actavis’ product directly infringing under issue (ii).
The Supreme Court also ruled that a “sceptical, but not absolutist” approach should be taken to considering the prosecution history when interpreting the scope of protection conferred by a claim. The court considered that reference to the prosecution history would only be appropriate in the following circumstances:
a. the point at issue is truly unclear from the specification and claims of the patent when read on its own, and the prosecution history unambiguously resolves the point; or
b. it would be contrary to the public interest for the prosecution history to be ignored.
Specifically, the court indicated that an example of (b) would be where the patentee had made it clear to the EPO that it was not seeking to contend that the patent, if granted, would extend its scope to a particular sort of variant, and then later argues that the variant infringes. This would appear to bring a limited form of file wrapper estoppel into UK law.
It could be argued that justice may have been served in this particular case - Lilly’s invention was the addition of vitamin B12, not the particular salt of pemetrexed. Given the Supreme Court’s answer on issue (i) above, it is unlikely that Lilly would have won under Kirin-Amgen: they therefore had to make new law to prevail. However, this may be at the cost of years of uncertainty ahead interpreting the scope of UK patents in all technical fields.
Prior advice concerning infringement in the UK may now require revision.
This may particularly be the case in chemistry in view of the difference in scope of protection which the Supreme Court considered as regards issues (i) and (ii), and in which cases are generally drafted in compositional rather than functional terminology.
Although the validity of the patent was not in dispute in this case, there also remains the question of whether immaterial variants should fall within the scope of the claim when considering novelty and/or inventive step - it is a long standing principle that a patent claim should be construed the same when considering both infringement and validity. This raises the prospect of a “squeeze” argument - in other words, if the scope of the patent covers the alleged variant, then it is invalid for lack of novelty and/or inventive step.
In the parallel German litigation, the German Supreme Court indicated that the use of a chemical name in a patent claim does not necessarily rule out that the “semantic content” of the claim excludes compounds which fall outside its literal meaning, but having equivalent effect. Whether and to what extent this is to be confirmed depends on the facts of that particular case. The case has been sent back to the lower courts to look at infringement under the doctrine of equivalents again.
The potential for file wrapper estoppel is a warning to patentees to be careful what they say before the EPO - both in written proceedings and at oral proceedings.
Opponents in opposition proceedings should take note of any statements made by the patentee in the proceedings and ensure any points made by the patentee in oral proceedings about the scope of protection are minuted by the Opposition Division or Board of Appeal.
It would be interesting to consider whether one additional line in the specification as filed - an intermediate fallback position reciting “pemetrexed or a pharmaceutically acceptable salt thereof” - may have saved the parties from years of litigation.
For applicants preparing PCT specifications for clients’ business critical inventions, it is always worth asking a European patent attorney to review the text before filing with future EPO prosecution in mind - the small additional cost of this simple check can save applicants from much larger expenses down the line.
We would be happy to carry out a pre-filing review of PCT specifications - please do get in touch, whether by email to firstname.lastname@example.org or by contacting your usual D Young & Co advisor, if this is of interest.
-  UKSC 48
-  RPC 183
-  FSR 181