On 12 July 2017 in Actavis UK Limited & others v. Eli Lilly and Company  UKSC 48, the UK Supreme Court ("UKSC"), in reversing both the High Court and the Court of Appeal, addressed the extent to which under the European Patent Convention 2000 ("EPC 2000"), a patentee may obtain protection against products or processes that are not covered by the literal meaning of the claims. In doing so, the UKSC modified what had been previously seen as the established approach of the UK courts towards 'equivalents'. In particular, while not disapproving the test, the Court has chosen to reformulate the three "Improver" questions that, since 1990, have been in common usage for aiding determinations as to what might constitute patent infringement.
Some commentators have suggested that the UKSC has merely confirmed the existing position under UK law. However, such a view ignores the fact that the UKSC has grasped the nettle by expressly finding fault with the guidance that had been provided by Lord Hoffmann in the decision of the House of Lords (the predecessor to the UKSC) in Kirin-Amgen Inc. v. Hoechst Marion Roussel Ltd  RPC 9. Consequently, the UKSC has decoupled the scope of protection available to patentees against equivalents from an overly zealous construction of the claims.
The UKSC has concluded that subsequent to the Improver decision, which was then reinforced by the judgment in Kirin-Amgen, there has been a tendency by the UK courts to place "..too much weight on the words of the claim…" and what the patentee might have anticipated or intended. Instead, the UK courts should have focused on whether, on a basis of fact and expert evidence, the variant is a true equivalent of the invention as described in the patent. Lord Neuberger, who gave the judgment in the UKSC, ventured to say that this wrong approach explains why in the Improver case, contrary to the courts in Germany, Italy and the Netherlands in relation to the same patent, Mr Justice Hoffman had held that there was no infringement.
This decision by the UKSC has also provided clarity as to (i) when a court may have recourse to the contents of the prosecution file for the purpose of assessing infringement, and (ii) how to address indirect infringement.
The dispute related to Lilly's European Patent (UK) No. 1313508 (the "Patent") and its corresponding designations in France, Italy and Spain concerning the use of pemetrexed disodium in the manufacture of a medicament for use in combination with Vitamin B12 or folic acid. Since 2004 the medicament has been successfully marketed by Lilly under the ALIMTA brand.
Pemetrexed is a member of a class of chemicals known as antifolates which inhibit cell division and thus are known to be effective against cancerous tumours. However, as with other antifolates, the use of pemetrexed as an anti-cancer drug was constrained because of potentially severe side effects.
The figure below shows the molecular structure of pemetrexed, with C, N, O and H being respectively carbon, nitrogen, oxygen and hydrogen. The presence of the two –CO2H units results in pemetrexed being known as pemetrexed diacid or as it is sometimes called a free acid.
When pemetrexed is dissolved in water, the hydrogen (H) units in the two –CO2H units separate from the molecule as positively charged entities and thus the rest of the molecule becomes an anion (a negatively charged entity).
Pemetrexed disodium, as referred to in the main claim of the Patent, has the same structure save that the two –CO2H units are replaced by two –CO2Na units, "Na" being the chemical symbol for sodium. A substance such as pemetrexed disodium, where the acidic hydrogens have been replaced by another element resulting in an electrically neutral product, is known as a salt.
In water, pemetrexed disodium will result in the two sodium atoms separating from the rest of the molecule as positively charged cations with the rest of the molecule becoming an anion. It is the pemetrexed negatively charged anion that it is of interest to the chemist. The sodium cation is often referred to as a counter ion.
Vitamin B12 and folic acid act to lower the levels of methylmalonic acid and the inventive concept behind the Patent is stated to be the discovery that the toxic and non-hematologic effects caused by antifolates can be reduced by the presence of methylmalonic acid lowering agents such as B12 without adversely affecting the therapeutic efficacy of antifolate drugs.
Although the Patent is entitled "Combination containing an antifolate and methylmalonic acid lowering agent” and the specification refers on occasions to antifolates as a class, the relevant claims 1 and 12 expressly extend to just one type of pemetrexed compound i.e. pemetrexed disodium.
The dispute arose because Actavis proposed to market a pemetrexed compound in conjunction with Vitamin B12 for use as a cancer treatment where the active ingredient was not pemetrexed disodium but was instead either (a) pemetrexed itself i.e. the free acid, or (b) pemetrexed where the hydrogens on the two CO2H units had been replaced by either (i) tromethamine or (ii) potassium. Lilly contended that such a proposal would directly infringe the Patent.
Further or in the alternative, Lilly argued that Actavis would indirectly infringe the Patent in accordance with section 60(2) of the Patents Act 1977 (the "Act") because pemetrexed disodium would still be present in the manufacture of the products and thus Actavis would be offering to supply, "…an essential element of the invention, for putting the invention into effect when it knows, or it is obvious to a reasonable person in the circumstances, that those means are suitable for putting, and are intended to put, the invention into effect…".
In the High Court, Arnold J held that the Actavis products neither directly nor indirectly infringed the Patent.
On appeal, the Court of Appeal upheld the judge's decision on there being no direct infringement but did reverse the High Court with regard to indirect infringement. The Court of Appeal ruled that it would be reasonable for Actavis to know that when the Actavis products are supplied to a doctor or a pharmacist, they are dissolved in a saline i.e. sodium chloride solution, which will contain both sodium cations and chloride anions. Accordingly, because of the known separation that occurs when salts are dissolved, it was reasonable for Actavis to have predicted that the solution which is administered would contain pemetrexed disodium.
Section 130(7) of the Act declares that the rules governing infringement are framed so as to have the same effects as the corresponding provisions of the EPC. Article 69(1) of EPC 2000 provides that the scope of protection conferred by a patent "… shall be determined by the claims… Nevertheless, the description and drawings shall be used to interpret the claims…".
However, what is deemed to be an infringement of a patent is not limited to the narrow language of the claims. In this regard, The Protocol on the Interpretation of Article 69 of the EPC 2000 (the "Protocol") states that:
Article 69 should not be interpreted as meaning that the extent of the protection conferred by a European patent is to be understood as that defined by the strict, literal meaning of the wording used in the claims, the description and drawings being employed only for the purpose of resolving an ambiguity found in the claims. Nor should it be taken to mean that the claims serve only as a guideline and that the actual protection conferred may extend to what, from a consideration of the description and drawings by a person skilled in the art, the patent proprietor has contemplated. On the contrary, it is to be interpreted as defining a position between these extremes which combines a fair protection for the patent proprietor with a reasonable degree of legal certainty for third parties.
For the purpose of determining the extent of protection conferred by a European patent, due account shall be taken of any element which is equivalent to an element specified in the claims.
The proper approach to Article 69 is as explained in the last sentence of Article 1 of the Protocol, namely to strike a balance between fair protection for the patentee and reasonable legal certainty for third parties. However, due regard should be paid under Article 2 to equivalents.
The UKSC followed the technical findings of the High Court as at the priority date of 2000, namely:
- The Patent was addressed to a skilled group consisting of an oncologist and a chemist.
- Antifolates were used in cancer chemotherapy but their use caused toxic side effects which it would be desirable to avoid or reduce.
- Pemetrexed was the subject of clinical trials for use in chemotherapy and it targeted multiple enzymes and was administered intravenously.
- The only form of pemetrexed which at that point had been shown to be effective and sage to any extent was the pemetrexed manufactured by Lilly under the ALIMTA brand.
- The characteristics of vitamin B12 and folic acid were well known.
- The choice or effect of the counter ion was the province of the chemist and, because the properties of different salt forms and free acids were difficult to predict, a chemist would need to address issues as to solubility etc.
- Salt screening is a routine but important exercise in determining the most suitable form of a drug.
- Solid salts consist of anions and cations regularly arranged in a fixed lattice structure and present in fixed proportions and in fixed relative positions.
- When a salt is dissolved in water, the ions dissociate forming free cations and anions in solution.
- Solubility of the salt form is a crucial consideration; if a salt is too soluble it cannot be made into a solid form. There can be many dead ends and false leads in attempting to prepare the salt of a parent molecule for the first time and one cannot predict a particular salt of a parent molecule and if made, what will be its properties and how would it affect the efficacy of a drug.
- Sodium was the preferred counter-ion and such salts are generally not toxic and reasonably soluble albeit they are not always easy to make.
- Potassium salts are also generally soluble but there were concerns about their potential toxicity especially where large quantities of the drug are involved.
- There were only a small handful of examples of tromethamine salts in use and it was known that they might well be too soluble for making and harvesting the solid form.
- Although the acidic parent molecule could be administered in its free acid form, it was often necessary for various reasons, including solubility, to change from the free acid to the salt form.
The UKSC held that, as a matter of ordinary language, the only type of pemetrexed compound to which the Patent's claims expressly extended, was pemetrexed disodium. Accordingly, the Court then turned its attention to Article 69 and the Protocol to assess whether the alternative pemetrexed molecules proposed by Actavis nevertheless fell within the protection afforded by the Patent.
Lord Neuberger reviewed a number of previous decisions by the UK courts that had considered the extent to which a variant to an invention as described in the claims of a patent would still infringe, in particular the Improver decision, which concerned a patent for a depilator known as the "Epilady". The device worked by hairs being trapped in and extracted by what was described in the patent as a rotating "..coiled helical spring….". The alleged infringer's device used a "..slotted rubber rod…" to achieve the same purpose.
In Improver, Hoffmann.J, when addressing whether the variant of the slotted rubber rod was a variant on the coiled helical spring which would still be covered by the patent, he had been anxious not to stray away from the language employed in the claims. For example, at paragraph 197, Hoffmann J had said that "…the rubber rod is not an approximation to a helical spring…". However, as Lord Neuberger explained when assessing if a variant falls within the claims of a patent, it is wrong to treat Article 2 of the Protocol as an exercise in construction [Paragraph 55]. To do so can cause the courts to fall into error.
Article 2, which deals with equivalents, is simply determining the scope of protection. Whether or not a variant infringes is to be answered not by interpreting the claim but by reference to facts and expert evidence addressing the issue of the extent to which the variant and the invention differ materially in terms of in function and outcome: "…the question is whether the variant achieves the same result in substantially the same way as the invention…". If so, the courts must then address whether it would be obvious to the notional addressee that there would have been no material effect and, if not, only then should the court assess whether a reader of the patent would have concluded that nonetheless the patentee intended that there be strict compliance with the literal meaning of the claims.
Clearly, in the Improver case, a rubber rod is not the same as a helical spring. However, faced with the Epilady and the variant using a rubber rod, the German, Dutch and Italian courts had, to the approval of Lord Neuberger, focused on the functionality of the respective products, not the descriptors in the patent. Thus, in Germany, the Düsseldorf Oberlandesgericht had held "…a person skilled in the art will not interpret the coil spring as a spring, but as an elastic body with gaps [for the entrapment of hairs] ….as it is obvious that the helical spring is not used as a spring per se…".
In the view of Lord Neuberger, it was too high a burden on the patentee to ask whether it would have been obvious to the notional person to consider whether the variant would actually work: "…In my opinion, the second [Improver] question is better expressed as asking whether, on being told what the variant does, the notional addressee would consider it obvious that it achieved substantially the same result in substantially the same way as the invention…" [Paragraph 62]. There should be an assumption that the notional addressee knows that the variant does work. Accordingly, in the instance of Actavis v Eli Lilly, although no chemist knows until it has been tested whether a particular salt form will be effective or suitable since testing is a simple routine exercise, it is fair and appropriate that the notional addressee is treated as knowing that the Actavis products do work.
Finally, Lord Neuberger rejected the notion as applied by the German courts when examining Article 69 that variants that are themselves inventive cannot be infringing equivalents [Paragraph 64].
Accordingly, on the basis of its decision, in a case where there is no literal infringement, the UKSC has reformulated the three Improver questions that a patentee must address in order to establish infringement, as follows [Paragraph 66]:
- 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, i.e. the inventive concept revealed by the patent?
- 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?
- 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?
The UKSC held that with regard to the Actavis products, the answers to question 1 and 2 were in the affirmative. The Court of Appeal and the High Court were found to have been in error in not treating the notional addressee as knowing that the Actavis products do actually work.
With regard to the third question about whether Lilly required strict compliance and that pemetrexed disodium was an essential requirement of the invention, the UKSC held [Paragraph 71] that "..the Court of Appeal adopted an approach which places too much weight on the words of the claim and not enough weight on article 2 of the Protocol…if one cannot depart from the language of the claim when considering those [the Improver] questions, what is the point of the questions in the first place…". Subject to the point about the prosecution history file, the UKSC could see no reason why Lilly intended to exclude any pemetrexed salts or the free acid other than pemetrexed disodium. Lord Neuberger speculated that the reason why the claims were limited to the disodium salt was because that was the "…only pemetrexed salt on which the experiments described in the specification had been carried out …".
Originally, the claims in the application by Lilly that eventually resulted in the Patent had referred to the use of a methylmalonic acid lowering agent [e.g. Vitamin B12] "..in combination with an antifolate…". The claims were entirely general as to the identity of the antifolate albeit claim 10 was a dependent claim "…wherein the antifolate is ALIMTA…". In response to objections by the EPO examiner, the prosecuting agent amended the claims such that they were limited to pemetrexed disodium i.e. ALIMTA. Actavis contended that in light of this prosecution history, the Patent should be interpreted as being limited to pemetrexed disodium.
In light of the manner in which the UKSC criticised the approach towards equivalents suggested by the Improver and Kirin-Amgen decisions, it approached the request by Actavis to refer to the prosecution file with a great amount of scepticism. It held that the prosecution file should serve as evidence only where (i) the point at issue is truly unclear from the specification and claims and the file would unambiguously resolve the point; or (ii) it would be contrary to the public interest to ignore the contents of the file. Only point (ii) was relevant to the Actavis v. Eli Lilly dispute and Lord Neuberger concluded that the only reason why the Patent claims were limited to the disodium molecule was because the teaching at that time did not extend to other antifolates.
Having found favour with the approach of the French, Spanish and Italian courts to the issue of equivalents, the UKSC inevitably held that that there was direct infringement of the UK, French, Italian and Spanish designations [Paragraph 102].
The UKSC dismissed the appeal by Actavis from the judgment of the Court of Appeal referred to above that there was indirect infringement under section 60(2) of the Act.
Whereas after Kirin-Amgen, there had been speculation as to whether regardless of Article 2 of the Protocol a doctrine of equivalents could be said to exist under UK patent law, the UKSC has clearly pronounced that Article 2 is broadly independent of the language used in the claims and that the test was, and remains one of, what represents a fair and reasonable degree of protection for the patentee.