Court of Appeal upholds Lilly’s appeal against the DNIs granted to Actavis for its pemetrexed products

July 2015

The Court of Appeal, with Floyd LJ giving the leading Judgment, has set aside UK, French, Spanish and Italian declarations of non-infringement (“DNIs”) in respect of Actavis’ pemetrexed diacid, pemetrexed ditromethamine and pemetrexed dipotassium products (the “Actavis Products”)[1].   The Court of Appeal upheld Arnold J’s finding[2] that there was no direct infringement but reversed his findings in relation to contributory infringement. 

The Court of Appeal also agreed with Arnold J’s findings that the conditions for applying for a DNI were procedural and thus subject to the lex fori and that Rome II did not bring the conditions for applying for a DNI within the lex causae.   

Following post-Appeal submissions, the Court of Appeal declined to grant an amended form of the DNIs proposed by Actavis but did remit the issue of whether the supply or offer to supply of the Actavis Products with a recommendation to reconstitute them in dextrose (rather than saline) would infringe the Patent.  

Background

Pemetrexed disodium is an anti-cancer treatment that has been marketed as Alimta by Eli Lilly since 2004.  Pemetrexed and its pharmaceutically acceptable salts were protected by a Lilly patent and Supplementary Protection Certificate, which will expire on 10 December 2015.  

Actavis sought DNIs in respect of Lilly’s European Patent No. 1 313 508 (the “Patent”), which expires in June 2021.  Actavis did not challenge the validity of the Patent.  Claims 1-11 of the Patent were Swiss form use claims, i.e., “use of X in the manufacture of a medicament for treatment of disease B”.  Claims 12 to 14 were in the form “product X for use in treatment Z”.  The claims were limited by reference to the words “pemetrexed disodium” but the infringement arguments hinged on what the skilled person would have understood that phrase to mean.

Prosecution history

It was common ground between the parties that the prosecution history was not inadmissible as a guide to construction.  At first instance, Arnold J placed reliance on the prosecution history of the Patent as an aid to the construction of the claims.  At [111] of his Judgment, Arnold J acknowledged that Courts should be cautious in relying on prosecution history as an aid to construction but noted that in the real world anyone interested in ascertaining the scope of a patent would obtain a copy of the file and there was no good reason why the Court would shut its eyes to the prosecution history.  In this case, Arnold J considered that one good reason for this was to ensure that a patentee did not abuse the system by accepting narrow claims during prosecution and arguing for a broad construction for the purposes of infringement.    

On appeal, however, Floyd LJ did not endorse this reasoning.  The assumption that the skilled person would always read the prosecution was not valid.  Further, unless a restriction was to operate as a form of estoppel, it was a very rare case where the file would assist the Court in preventing abuse of the system.  Floyd LJ noted that patent offices were usually concerned with patentability not scope of protection and he was reluctant to create a position where the patent attorney profession would be required to caveat every acceptance of a limitation with a statement that this did not restrict the scope of protection.   In any event, Floyd LJ did not find it necessary to go to the prosecution history to arrive at a conclusion on the construction of the claims, read in the light of the specification. 

Direct infringement

The relevant issue of construction in respect of direct infringement was whether the claims were limited to use of pemetrexed disodium or if they extended to cover the Actavis Products.  Floyd LJ agreed with Arnold J’s assessment of the Protocol questions and that Actavis’ Products did not directly infringe the Patent.[3]  

It was common ground that the Actavis Products had no material effect on the way that the claimed invention worked.  The active anti-cancer compound was the pemetrexed anion and the Actavis Products were all bioequivalent to Lilly’s Alimta.  Therefore the first Protocol question was satisfied. 

However, the skilled chemist would not know and would not be able to predict that the Actavis Products would be sufficiently soluble to work.  It was not legitimate to consider what Actavis had actually done — the skilled person must be able to find the relevant information in the specification or based on the team’s CGK.  Floyd LJ also agreed with Arnold J that the manufacturing step in Swiss form claims necessarily included a requirement that the manufactured medicament was effective in treating the disease.  As the skilled chemist could not predict that a variant would be sufficiently soluble to work, he would also be unable to say that the variant would have no material effect on the way the invention works and the second Protocol question was not satisfied. 

On the third Protocol question, Floyd LJ also agreed with the Judge that the skilled team would understand that the Patent was clearly limited to the disodium salt.         

Contributory infringement

Although Floyd LJ found that the claims were limited to pemetrexed disodium, the relevant issue of construction in respect of contributory infringement was whether the claims were limited to the use of a solid form of pemetrexed disodium.

Lilly relied on the fact that once dissolved a salt dissociates into its constituent ions, it was commonplace to refer to a solution containing, e.g., sodium ions and chloride ions as being sodium chloride in solution.  The Patent’s specification did refer to pemetrexed disodium in the context of a solution in which there are sodium ions and pemetrexed ions in at least the same proportions as in pemetrexed disodium.  Therefore, the term “medicament” in the claims would cover both solid and injectable dosage forms.

In this context, Floyd LJ held that the skilled person would consider that an identical solution containing pemetrexed and sodium ions but arrived at in a different way would fall within the ambit of the claims.  The skilled person would also understand that the ratio of sodium ions to pemetrexed ions in the solid state (i.e., 2:1) should be maintained in the solution.  Floyd LJ did not consider that it was material that there might be an excess of sodium ions or if different ions were also present.      

Lilly argued that under s.60(2) of the Patents Act 1977, Actavis were providing a means relating to an essential element of the invention, when the Actavis Products were reconstituted in saline (per the label’s instructions), which meant that the solution would contain pemetrexed ions, sodium ions and the relevant ion from the Actavis Products.  Arnold J rejected this argument, finding that at no point was pemetrexed disodium used in the manufacture of a medicament.  This included third parties who reconstituted the Actavis Products in saline, who had not used pemetrexed disodium in the manufacture of the medicament.  Arnold J based this on his finding that pemetrexed disodium means just that and “not any form of pemetrexed that is pharmaceutically acceptable and sufficiently soluble”.     

Floyd LJ disagreed, however, upholding Lilly’s appeal.  While it was the case that solid pemetrexed disodium was not used, the skilled chemist would understand that pemetrexed disodium was used to refer to solutions which contain pemetrexed ions and sodium ions in solution.  Providing a means for releasing pemetrexed ions into a solution containing sodium ions related to an essential element of the invention where the invention calls for pemetrexed and sodium ions in solution.  According to the Court of Appeal, the invention was therefore put into effect when the pharmacist made the solution using the Actavis Products because at that stage pemetrexed disodium was present and used.  On that basis, Floyd LJ held that supply of the Actavis Products would amount to contributory infringement of the Patent.

The Rome II issue

Although he had held that the proposed use of the Actavis Products would amount to contributory infringement, Floyd LJ went on to consider whether Actavis was entitled to the DNIs sought under Rome II.  If the point had needed to be decided, the Court of Appeal recorded that they would have upheld the Judge’s findings on this point. 

The issue was whether by satisfying the lex fori (i.e., English law) test for the availability of a declaration, if Actavis could also obtain DNIs in respect of the French, Spanish and Italian designations of the Patent.  Lilly contended that Actavis must satisfy the requirements of the foreign law in the designated states, the lex causae. 

Article 1 (1) of the Rome II regulation states that the Regulation “shall apply, in situations involving a conflict of laws, to non-contractual obligations in civil and commercial matters”.  Article 1(3) states that the Regulation “shall not apply to evidence and procedure…”.  Article 8(1) provides that “the law applicable to a non-contractual obligation arising from an infringement of an intellectual property right shall be the law of the country itself”.  Article 15 sets out the scope of the law applicable to non-contractual obligations governed by the Regulation, including: “the basis and extent of liability” (Art. 15(a)); “the existence, the nature and the assessment of damage or the remedy claimed” (Art. 15(c)); “the measures which a court may take to prevent or terminate injury or damage” (Art. 15(d)); and “the manner in which an obligation may be extinguished and rules of prescription and limitation” (Art. 15(h)).

Article 1(3) therefore excludes evidence and procedure from the scope of the Regulation and under the private international law principle it is well recognised that procedure is governed by the law of the forum (lex fori).  The Court of Appeal observed that the distinction between substance and procedure is fundamental and underpins the principle that while a litigant cannot import an advantage of his own country he can rely on any procedural advantage afforded to a domestic litigant.

Floyd LJ considered that all of the rules for seeking a DNI were concerned with the admissibility of any action and of ensuring it was sufficiently well-defined for adjudication by the Court.  Although Article 15 applied the lex causae to a number of matters, which under English common law would have been treated as procedural, the Court of Appeal did not consider that it encompassed the rules for the admissibility of a DNI.    

Further, although it was not necessary to consider the factual issues that arose in relation to the application of the lex causae conditions for admissibility of the DNIs, Floyd LJ did not consider that the Judge had made any error in his assessment of the evidence of foreign law or its application to those facts.          

Conclusion

The Court of Appeal has now clarified the legal position with respect to DNIs and Rome II and reiterated the position of the relevance of the prosecution history to the scope of protection.  It is also interesting that the Court of Appeal’s decision overturning Arnold J’s decision that there was no infringement differed from the German Oberlandesgricht’s decision overturning the Landgericht Düsseldorf’s finding of infringement.  

The parties will now return again to the Patents Court for a decision on Actavis’ proposed dextrose work-around.  It is not clear whether that further hearing will be before the expiry date of the SPC on 10 December 2015, approximately three and a half years after Actavis’ initial request in July 2012.     


 [1] Longmore, Kitchin and Floyd LLJ. Actavis UK Ltd & Others v Eli Lilly & Company [2015] EWCA Civ 555 (25 June 2015).

[2] See Actavis UK Ltd & Others v Eli Lilly & Company [2014] EWHC 1511 (Pat) (15 May 2014). 

[3] Improver Corporation v Remington Consumer Products Ltd [1990] FSR 181, per Hoffman J at page 189.