“You win some and you lose some”, this is a phrase all too familiar to most people and more specifically to the market of pharmaceuticals. It is perhaps this phrase that most pharmaceutical companies live by during their existence! Patent infringement, claim invalidation, compulsory license and Generic companies are the most clichéd words that one comes across, whenever there is a mention of pharmaceutical patents. Eli Lilly (a cancer treatment drug) happens to be one such entity that has “been there, done that”!
Recently on June 25, 2015, Eli Lilly and Company announced that it had won the favor of the London court of appeals on a case ( EWCA Civ 555) pertaining to its cancer drug “Alimta® (pemetrexed disodium). The case was decided against a previous ruling in the favor of “Actavis UK Limited” where Actavis had claimed declaration of non-infringement (DNIs) of Eli Lilly’s European patent (UK) No. 1 313 508. The Court of Appeal reversed the decision of the High court and ruled that the Alimta vitamin regimen patent would be indirectly infringed by the generic competitor, Actavis UK Ltd. who intended to market certain alternative salt forms of pemetrexed in the United Kingdom before the expiration of Lilly’s UK patent in June 2021.
The Court of Appeal answered on many fronts, which are discussed later in this post. Prima facie the London court of Appeals held that commercialization of the alternative salt forms proposed by Actavis would constitute indirect infringement. It also held that there was no difference between the law in the UK and that in France, Italy and Spain and hence reversed the High court’s decision granting DNI over the Almita vitamin regimen patents in these countries as well. Cases involving Almita (a cancer treatment drug) were also brought before the courts of Germany and the United States sometime in the past year where the issue of obviousness – double type patenting was addressed. While Lilly lost out in Germany, it found a reason to cheer in the decision of the Court of Appeals for the Federal circuit, United States of America.
Facts of the case:
- Pemetrexed disodium is a cancer treatment drug which Eli Lilly has marketed under the brand name Almita since 2004. Lilly has patent protection for pemetrexed disodium by way of European Patent No. 0 432 677 (“the 677 patent”).
- Actavis sought the DNIs of the 508 patent in order to place themselves in a position to market a competing product to Alimta on the expiry of the 677 patent in December 2015.
- The 508 patent of Eli Lilly relates to the use of pemetrexed disodium in the manufacture of a medicament for use in combination therapy with vitamin B12 and, optionally, folic acid.
- The active ingredient in Actavis’ proposed product is one of (a) pemetrexed diacid, (b) pemetrexed ditromethamine or (c) pemetrexed dipotassium (“the Actavis AIs”).
Actavis’ case is fairly simple; they intend to use the Actavis AIs and not pemetrexed disodium as such, covered under the 508 patent’s claims. However, Lilly does not agree and contends that there will be either direct or indirect infringement of the 508 patent if Actavis launches any of the Actavis AIs in the UK or in any of the other states in relation to which DNIs are sought.
In the earlier decision of the High court, Arnold J found that none of Actavis’ proposed products fell within the scope of the patent and that Actavis (a cancer treatment drug) was entitled to the declarations sought in respect of each of the UK, French, Italian and Spanish designations of the patent. This is the same judgment that Eli Lilly had requested the Court of Appeals to reconsider on the ground that the judge had erred in understanding the key issues.
Key issues and findings:
The Key issue in the case was whether the word “Pemetrexed disodium” covered under the claims 1-12 of the 508 patent included other forms of Pemetrexed, such as pemetrexed diacid, pemetrexed dipotassium and pemetrexed ditromethamine. The task of the court was to determine what the skilled reader would have understood the phrase to mean? Lilly argued that the skilled person (an Oncologist) would interpret this term as any pharmaceutically acceptable and sufficiently soluble salt of pemetrexed. In contrast, Actavis (a cancer treatment drug) argued that a skilled person would not be limited to an oncologist but it would also include a chemist! And a chemist would read the term to only mean the specific compound. The High court and the Court of Appeals concurred that the skilled person would not only include an oncologist but also a chemist. The Court of Appeals based this decision on the finding that the invention required the use of the pemetrexed disodium, and the specification of the 508 patent expected the skilled person to be able to obtain it and make it into an injectable solution. No matter how the claim was formulated, the skilled addressee needs to manufacture the medicament and the manufacturing step is an essential requirement of the claim. The teams who deal with developing and making medicaments for use in treatment in the real world comprise specialists in a range of disciplines, and in this context would comprise both a medical oncologist and a chemist.
On the question of doctrine of equivalence, Actavis had argued that the skilled team would not know whether an alternative form of pemetrexed would be suitable until it had been tested.The court found that skilled oncologists did not think about drugs such as pemetrexed in their ionic form, nor did they consider issues regarding the choice of counterion or the effect, if any, of counterions on the efficacy, safety or other properties of the drug. Both parties’ experts agreed that the choice of salt form was really the province of the chemist and that the oncologist would not be involved in this.
Actavis also argued that the court should consider the prosecution history of the patent as an aid to construction. In this case, Lilly had amended the claims of the patent during prosecution from “antifolate” to “pemetrexed” and finally to “pemetrexed disodium” in order to overcome objections made by the examiner. In this regard the Court of Appeal observed that it was wrong to assume that the skilled reader would always read the prosecution history and also that it was not useful enough, to get into the prosecution history in order to discover that the patentee accepted a restriction to his claim against an objection of lack of support in the specification.
The most important question in this case was “Is the claim limited to the solid form?, the Court of Appeals averred from the decision of Arnold J. and held that undoubtedly even though solid pemetrexed disodium would not used as such i.e in the solid form, the skilled team, particularly the chemist, would understand from the 508 patent that pemetrexed disodium is also used to refer to solutions which contain pemetrexed ions and sodium ions in solution. The Court thus rejected the claim of Actavis (a cancer treatment drug) for DNIs.
As far as the DNIs in France, Italy and Spain were concerned the Court held that there was no detectable difference in the laws of France, Italy and Spain on the approach to contributory infringement and it should thus follow that, the declarations would also be refused in respect of those countries.
After this decision Actavis may now seek permission to appeal the decision to the UK Supreme Court. In addition, Actavis has stated it may ask the High Court to decide whether a different proposed product would infringe the patent. The Court of Appeal has ruled that the High Court will need to decide whether it will hear this new claim. If the High Court decides to hear Actavis’ case on the different proposed product, it might be another round of jousting between the two pharma majors.
The original judgment is available here
The post is authored by Gaurav Mishra