ACTAVIS UK LTD v ELI LILLY & CO

Transcription

1 38 [2016] R.P.C. 2 ACTAVIS UK LTD v ELI LILLY & CO COURT OF APPEAL Longmore, Kitchin and Floyd L.JJ.: 9-12 March and 25 June 2015 H1 [2015] EWCA Civ 555; [2016] R.P.C. 2 Patent European Patent Declaration of non-infringement UK and non-uk designations Pharmaceuticals - Swiss form claims Pemetrexed disodium Construction Identification of the skilled team Direct infringement Protocol questions Equivalents Relevance of prosecution history Indirect infringement Means essential Availability of declaratory relief Applicable law Rome II Regulation Appeal to the Court of Appeal H2 Patents Act 1977, ss.60(1), 60(2), 71 European Patent Convention 2000, arts.2, 83, 84, 123(2) Protocol on the Interpretation of art.69 ( the Protocol ) European Parliament and Council Regulation 864/2007/EC ( Rome II ), recital (6), arts.1, 8, 15, 21, 22 Brussels Convention 1968, art.21 Civil Procedure Rules, r.52.10(2)(b) Patents Act, art.127 (Spain) Intellectual Property Code, art. L (France) Code of Civil Procedure, art.100 (Italy) The claimants in these actions (referred to collectively as Actavis ) were suppliers of generic pharmaceuticals and members of the Actavis group of companies. They sought declarations (pursuant to s.71 of the Patents Act 1977 and in the inherent jurisdiction of the court) that a product which they proposed to market did not infringe the UK, French, Italian or Spanish designations of European Patent No. 1,313,508 ( the 508 Patent ), the claims of which were directed to the use of a compound, pemetrexed disodium, in combination with vitamin B12 or a pharmaceutical derivative thereof (and optionally a folic protein binding agent) for inhibiting tumour growth in mammals. The Patent was not due to expire until Pemetrexed and its pharmaceutically acceptable salts were also the subject of a supplementary protection certificate ( SPC ) which was due to expire in December Lilly was the proprietor of both the SPC and the 508 Patent and it had marketed a cancer treatment of which pemetrexed disodium was the active ingredient under the name ALIMTA since This report concerns the judgment on appeal from a lengthy judgment of Arnold J. at the trial of the actions 1. The issues raised on appeal concerned, inter alia, the correct approach to the construction of the claims (including the role in such an exercise of (a) the requirement to take equivalents into account, and (b) patent prosecution history), the scope of contributory infringement, and choice of law in relation to whether declarations of noninfringement could be made in respect of the non-uk designations of the Reported at [2015] R.P.C. 6.

2 H3 H4 H5 [2016] R.P.C Patent. The last of these involved consideration of the relevant provisions of Regulation 864/2007/EC ( Rome II ). The factual background was essentially as follows. Actavis intended to launch a generic product with pemetrexed diacid, pemetrexed dipotassium or pemetrexed ditromethamine as its active ingredient (referred to in the judgment reported here as the Actavis AIs ) and to obtain regulatory approval for their product by reference to ALIMTA. They accepted that they could not market such a product until after the expiry of the SPC but sought determination of the infringement issues at a single trial with a view to launching their proposed product after that date. Lilly counterclaimed for infringement of the UK designation of the 508 Patent, but not the French, Italian or Spanish designations. It had also commenced proceedings for infringement of the German designation of the 508 Patent before the Düsseldorf Landgericht (although apparently seized of the matter after the Patents Court here), which had found in its favour. However on appeal to the Oberlandesgericht this decision had bbeen overturned by Actavis in relation to both Lilly s direct and indirect infringement allegations. The decision of the Oberlandesgericht was specifically relied upon by Actavis and is accordingly considered in the appeal judgment reported here. Only the decision of the Landgericht had been available to Arnold J. at trial. It should be noted that Lilly had earlier mounted an unsuccessful challenge to the court s jurisdiction to determine the issues arising in relation to the non-uk designations on grounds, inter alia, of forum non conveniens 2. Further, this was not a case in which the court was required to decline jurisdiction under art.22(4) of Council Regulation 44/2001/EC ( Brussels I ) as Actavis had undertaken not to challenge the validity of the 508 Patent or to contend that it was invalid in the present proceedings if the court accepted jurisdiction. Lilly had also unsuccessfully tried to argue, both in advance of the trial and at the trial itself that a number of the later actions, brought to overcome procedural objections raised by Lilly in actions of earlier date, should be struck out as an abuse of process. However these arguments had failed and did not arise on the appeal to which this report relates 3. The main issues at the trial of the actions 4 (in so far a relevant on the appeal) had been (i) the identification of the person or team skilled in the art to whom the claims of the 508 Patent were addressed; (ii) the construction of claims 1 and 12 of the 508 Patent and, in particular, of the term pemetrexed disodium ; (iii) the relevance of the prosecution history of the 508 Patent; (iv) whether there had been direct or indirect infringement of the UK, French, Italian or Spanish designations; and (v) identification of the law governing the issue whether a declaration of noninfringement could be made in relation to each of those designations (which depended on the proper interpretation of the Rome II Regulation). It was common ground that the law applicable to whether Actavis proposed acts would infringe each non-uk designation of the 508 Patent was the lex loci protectionis or lex causae, i.e. the substantive patent law of the relevant country. The evidence adduced by the parties was extensive and included expert evidence on foreign law supported by extensive references to legislation, case law and commentaries, all with accompanying translations. 2 [2012] EWHC 3316 (Pat) (Arnold J.). The forum conveniens issue was not considered in the later appeal to the Court of Appeal, which concerned the question whether there had been an agreement to accept service of the proceedings: see [2013] EWCA Civ 517, [2013] R.P.C See [2013] EWHC 3749 (Pat), Pat. Ct. and [2015] R.P.C. 6 at [361]-[375]. 4 Reported at [2015] R.P.C. 6 (Arnold J.).

3 40 ACTAVIS UK LTD v ELI LILLY &CO H6 H7 H8 The title of the 508 Patent was Combination containing an antifolate and methylmalonic acid lowering agent. Claims 1 to 11 were in Swiss form and claims 12 to 14 were product claims. Claims 1 and 12 read as follows: 1. Use of pemetrexed disodium in the manufacture of a medicament for use in combination therapy for inhibiting tumor growth in mammals wherein said medicament is to be administered in combination with vitamin B12 or a pharmaceutical derivative thereof, said pharmaceutical derivative of vitamin B12 being hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin or cobalamin. 12. A product containing pemetrexed disodium, vitamin B 12 or a pharmaceutical derivative thereof said pharmaceutical derivative of vitamin B12 being hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo10- chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin or cobalamin, and, optionally, a folic binding protein binding agent selected from the group consisting of folic acid, (6R)-5-methyl- 5,6,7,8-tetrahydrofolic acid and (6R)-5-formyl-5,6,7,8-tetrahydrofolic acid, or a physiologically available salt or ester thereof, as a combined preparation for the simultaneous, separate or sequential use in inhibiting tumor growth. At the trial of the actions, Actavis argued that the 508 Patent (at least for post-grant issues) was addressed to a team including (i) a medical oncologist and (ii) someone with experience in pre-formulation work (e.g. a process chemist or a formulation scientist) supported by an analytical chemist, and that the expression pemetrexed disodium meant pemetrexed disodium and nothing else. It was a precise chemical expression with a clear meaning. Further, the skilled team would have understood that this expression had been chosen to identify a specific chemical and this would have been confirmed by (a) the contrast between the reference to pemetrexed disodium on the one hand and the references to vitamin B12 or a pharmaceutical derivative thereof and a selected folic protein binding agent on the other and (b) the prosecution history of the 508 Patent, which confirmed that the limitation of the claims to pemetrexed disodium was both intentional and made for good reason and that the claims would have been invalid if construed more broadly. Lilly argued that the claim 1 of the 508 Patent was a Swiss form claim and directed only to a medical oncologist, although it accepted that claim 12 was directed to a medical oncologist and a chemist. It argued, inter alia, that the addressee of the 508 Patent did not have to be the same for each claim and could be different in other circumstances too, i.e. (i) when considering infringement as opposed to insufficiency and (ii) when considering different aspects of the assessment of infringement. In any event, the relevant persons would understand pemetrexed disodium to mean (at least) pemetrexed diacid and any salt of pemetrexed which was pharmaceutically acceptable (i.e. could be made, was safe, sufficiently stable and did not affect the efficacy of the drug) and sufficiently soluble. It would have been obvious to such persons that substitution of the free acid or a different salt would have no material effect on the way in which the invention worked, in particular because (a) the invention was about reducing the toxicity, while maintaining the efficacy, of pemetrexed and (b) the active chemotherapeutic principle was the pemetrexed anion, and the skilled team would therefore have concluded that pemetrexed disodium was being used in a figurative sense which Published by Oxford University Press for the Intellectual Property Office

4 H9 H10 H11 was exemplary of the means of obtaining the benefits of the invention. As to the history of the prosecution of the application, Lilly contended that, as a general rule, prosecution history was rarely useful as an aid to construction and that the present case was no exception. As to direct infringement of the UK designation of the 508 Patent, both parties argued their cases at trial at least partly by reference to the Protocol questions (also known as the Improver questions given that they had first been enunciated in Improver v Remington 5 ). There was no dispute that none of the proposed compounds were pemetrexed disodium accordingly to the primary, literal or acontextual meaning of that term but were variants, the main areas of dispute being essentially Protocol questions 2 (whether lack of material effect obvious) and 3 (whether strict compliance essential). Similarly, as to the French, Italian and Spanish designations, it was common ground that none of pemetrexed diacid, dipotassium or ditromethamine fell within the scope of the claims of the 508 Patent on a literal designation. The issue in each case was whether they fell within the scope of those claims applying the doctrine of equivalents as applied in those jurisdictions. The judgment at first instance had focused on whether claims 1 and 12 extended to pemetrexed diacid. This was Actavis lead candidate for manufacture and if this compound was caught, so too were the others 6. Further, Lilly argued that even if there was no direct infringement of claim 1 (claim 12 not being relied upon in this context), there was indirect infringement in this case. It contended that (i) the proposed pemetrexed compounds were means relating to an essential element of the invention as they provided a source of pemetrexed ions, (ii) such means was for putting the invention into effect in precisely the same manner as ALIMTA, (iii) Actavis had the requisite knowledge and (iv) the persons to whom Actavis supplied its product were not entitled to work the invention. Actavis admitted that in use their product would be reconstituted and/or diluted in much the same way as ALIMTA and result in a solution containing, inter alia, pemetrexed ions and sodium ions. Actavis also admitted (i) that it would be obvious to the skilled team that this would be so, and (ii) that their product would be administered in combination with vitamin B12 and folic acid and Actavis knew this. However Actavis denied any such infringement, contending that at no point was pemetrexed disodium used in the manufacture of a medicament by anyone. It was no answer to this to say that pemetrexed ions on their own constituted an essential element of the invention, as this was just another way of saying that the claim did not require pemetrexed disodium, but merely required any form of pemetrexed which made pemetrexed ions available. As to the law governing the declaration of non-infringement claims, Actavis contended that the rules for obtaining such relief in each jurisdiction were matters of procedure within the meaning of art.1(3) of Rome II and consequently fell outside the scope of the regulation. Consequently, the question of the applicable law fell to be determined by English private international law under which the applicable law was the lex fori as English law regarded such rules as procedural. Lilly argued that the rules for obtaining negative declaratory relief were not rules of procedure but fell within the scope of the lex causae as determined under art.15 of Rome II. Particular reliance was placed on art.15(c) with arts.15(h) and 22 being relied upon by way of analogy. There were also significant legal issues arising under 5 Improver Corp v Remington Consumer Products Ltd [1990] F.S.R. 181, Pat. Ct. 6 See [2015] R.P.C. 6 at [116]. [2016] R.P.C. 2 41

5 42 ACTAVIS UK LTD v ELI LILLY &CO H12 H13 H14 French, Italian and Spanish law in relation to the availability of declarations of noninfringement in the circumstances of the present case in the event that those were indeed the applicable laws when determining that question. At first instance 7 Arnold J. held that the claimants were entitled to all of the declarations of non-infringement of sought. Claims 1 and 12 were addressed to a team comprising both a medical oncologist and a chemist 8. As to construction generally, he held, inter alia, that consideration of the prosecution file could assist in ensuring that patentees did not abuse the system by accepting narrow claims during prosecution and then arguing for a broad construction of those claims for the purpose of infringement and the present case provided a good illustration of this. As a matter of principle, there was no good reason why prosecution history should be useful as an aid to construction only where the claims had been limited during prosecution to avoid objections of novelty or obviousness as opposed to objections of lack of support/ added matter or clarity 9. The judge held that answer to Protocol question 2 (whether lack of material effect obvious) was no. Although the underlying invention was an improved method of treatment, the only patentable invention was the use of the drug for the manufacture of a medicament for use in the combination therapy (claim 1) or a product containing the drug in combination with the other ingredient(s) for use in therapy (claim 12). Either way, the patentable invention involved making the medicament or product. If the proposed source of pemetrexed anions was not sufficiently soluble or was not pharmaceutically acceptable for some other reason, then as a practical matter the skilled team could not make that medicament or product and therefore could not obtain the benefit of the patented invention. To that extent, therefore, it would not have been obvious to the skilled team that pemetrexed diacid would have no material effect on the way the invention worked. The same applied in the case of pemetrexed dipotassium and ditromethamine 10. However, even if the answer to Protocol question 2 had been yes, the answer to Protocol question 3 (whether strict compliance essential) was yes. In particular (i) it was necessary to consider where the logic of Lilly s argument on construction led (particularly on the issue of validity) and (ii) the prosecution history supplied a clear answer why the claims had been limited to pemetrexed disodium and this shed light on the correct interpretation of the claims. If, as had been accepted in argument, Lilly would have been unlikely to have succeeded in obtaining a claim which explicitly referred to pemetrexed or any pharmaceutically acceptable and sufficiently soluble effectively been thereof on grounds of added matter, it could not be right to construe the term pemetrexed disodium in claims 1 and 12 as having that meaning for purposes of infringement 11. Having considered the points raised individually, Arnold J. had stood back and considered which construction of the expression pemetrexed disodium accorded with the Protocol and combined fair protection for the patentee and reasonable certainty for third parties overall and held that this was Actavis construction. Lilly had deliberately limited the claims of the 508 Patent to pemetrexed disodium. There was nothing in the specification or the common general knowledge of the skilled team to suggest to the skilled team that Lilly intended to use the expression pemetrexed disodium in anything other than its conventional sense or that it had made some 7 Reported at [2015] R.P.C At [61]-[63]. 9 See [111], [112]. 10 See [128]. 11 At [145]-[148]. Published by Oxford University Press for the Intellectual Property Office

6 [2016] R.P.C H15 mistake in using that expression, and the prosecution history showed that the opposite was the case. Confining Lilly to the scope of claim that it chose with the benefit of skilled professional advice provided Lilly with fair protection, and did not expose it to the risk of the Patent being invalid on the grounds of added matter and/or insufficiency. Construing the claim as extending to (at least) any form of pemetrexed which was pharmaceutically acceptable and sufficiently soluble would not provide a reasonable degree of certainty for third parties. Any other conclusion would fail to give effect to the Protocol and would be tantamount to treating the claims as a mere guideline 12. In arriving at his conclusion, Arnold J. had considered the decision of the first instance decision before the Düsseldorf Landgericht but did not follow it 13. The judge had then gone on to construe the 508 Patent in the context of its French, Italian and Spanish designations. In each case he had held that pemetrexed diacid, dipotassium and ditromethamine were not within the scope of the claims 14. Accordingly he held that dealing in pemetrexed diacid, dipotassium or ditromethamine would not constitute direct infringement of any of the designations of the 508 Patent in respect of which declaratory relief was sought 15. Arnold J. also had held that there would be no indirect infringement by Actavis of the UK designation of the 508 Patent. The fact that, when Actavis supplied their product to third parties who reconstituted (or in the case of diacid, diluted) the products with saline, there would be sodium ions and pemetrexed ions floating around, did not mean that those third parties were implementing the invention; they had not used pemetrexed disodium in the manufacture of a medicament as required under claim 1. It was no answer to this to say that pemetrexed ions on their own constituted an essential element of the invention, as this was just another way of saying that the claim did not require pemetrexed disodium, but merely required any form of pemetrexed which made pemetrexed ions available. The issue of indirect infringement only arose if claim 1 required pemetrexed disodium and not any form of pemetrexed that was pharmaceutically acceptable and sufficiently soluble. Further, given that it had not been contended that Lilly could succeed under any of the other designations if indirect infringement of the UK designation was not established, the judge concluded that Actavis would not indirectly infringe the French, Italian or Spanish designations either 16. H16 As to the law applicable to the declaration of non-infringement claims, Arnold J. held that the term remedy in art.15(c) of Rome II could not extend to any remedy. The wording of art.15(d) made it clear that there was a distinction between the question of principle as to whether an injunction should be granted, which would be a matter for the lex causae, and the procedural conditions to be observed, which would be a matter for the lex fori. 17 Even if a declaration of non-infringement was a remedy within the meaning of art.15(c) at all, art.15(c) should be interpreted as only having the effect that the question of principle as to whether it was available at all was a matter for the law applicable to the non-contractual obligation. It did not follow that rules of the kind presently under consideration, which were essentially concerned with whether it was necessary or possible for the court to consider the substantive issue at all, fell within it 18. Further, Lilly s reliance upon art.15(h) of Rome II was misplaced. 12 At [149]. 13 At [152]-[158]. 14 See esp. [164], [165], [179] and [187]. 15 At [189]. 16 At [199]-[201], [203]. 17 At [228]. 18 At [229].

7 44 ACTAVIS UK LTD v ELI LILLY &CO H17 H18 H19 There was no analogy to be drawn between a rule of limitation or prescription and those presently under consideration. The same applied to art.22 and the burden of proof 19. He concluded that the rules of national law in issue were accordingly matters of procedure within art.1(3) and were not governed by the law applicable to the non-contractual obligation in accordance with art.15. It followed that they were governed by English law 20. Given that it was not seriously disputed that, if Actavis established that dealings in their products would not amount to an infringement of the UK designation of the 508 Patent, then they should be granted a declaration of non-infringement in respect of that designation pursuant to the inherent jurisdiction of the Court, Arnold J. held that it was unnecessary to consider whether Actavis had satisfied the requirements of s.71 of the Patents Act Further, on the basis that the law applicable to the question of whether Actavis were entitled to a declaration of non-infringement in respect of the French, Italian and Spanish designations of the 508 Patent was English law, Actavis should be granted such relief in respect of those designations pursuant to the inherent jurisdiction of the Court because they had clearly demonstrated that they had a real commercial interest in obtaining such declarations and that such declarations would serve a useful purpose 21. The judge had then gone on to consider whether the same would have applied had he applied French, Italian and Spanish law instead and concluded that it would 22. Lilly appealed to the Court of Appeal. On the appeal the issues arising were essentially (i) whether the judge had been wrong to decide that there was no direct or indirect infringement of the 508 Patent under English law; (ii) whether he had been wrong to decide that the same result followed under the laws of France, Italy and Spain; (iii) if he had been wrong on issue (ii), whether he had also been wrong on the Rome II issue; and (iv) if the judge had been wrong on the Rome II issue, whether he had also been wrong on the factual issues relevant to the declarations of non-infringement which Actavis sought. As to direct infringement, Lilly argued that Arnold J. had been wrong on Protocol questions 2 and 3. It contended, inter alia, that the judge should have held that the 508 Patent was addressed only to an oncologist: (i) he should have addressed identification of the skilled reader by reference to the problem the 508 Patent solved, namely the effects caused by the administration of pemetrexed while retaining efficacy, (ii) the skilled reader would have taken no account of the reference to manufacture in claim 1 given that it was a Swiss form claim, (iii) not every peripheral role involved in bringing a product to market justified having a representative on the skilled team, and (iv) the evidence had shown that the oncologist was not concerned with the source of the pemetrexed anions, and the sodium ions present in the injectable solution were not relevant to the efficacy of the invention. It also contended that when asking the second Protocol question, it was permissible to assume that the skilled chemist knew that the Actavis AIs were soluble and that the judge had focussed on the wrong problem. The problem underlying the invention was not a manufacturing one but a therapeutic one. The oncologist would know that the source of pemetrexed ions would have no effect in this context. Lilly also argued, inter alia, that the skilled person reading claim 1 would understand that it included 19 At [231]. 20 At [236]. 21 At [305], [307]. 22 At [308]-[360]. Published by Oxford University Press for the Intellectual Property Office

8 H20 H21 H22 H23 H24 H25 [2016] R.P.C a solution containing pemetrexed ions and sodium ions and was not limited to pemetrexed disodium in solid form. As to indirect infringement, Lilly again contended that each of the AIs was an essential means. When the solid was reconstituted in saline, both pemetrexed ions and sodium ions would be present and the skilled person reading claim 1 would understand that it included a solution containing pemetrexed ions and sodium ions and was not limited to pemetrexed disodium in solid form. Actavis supported Arnold J. s conclusions and also relied upon the decision of the Düsseldorf Oberlandesgericht. As to Rome II, the question was once again whether Actavis, by satisfying the lex fori (i.e. English law) test for the availability of a declaration, could obtain declarations in respect of the non-uk designations as well. Lilly argued, inter alia, that the approach under Rome II should be that the court should apply the lex causae except in limited matters concerned with the constitution of the courts and method of trial which were deeply embedded in the procedural system of the domestic court, in the sense that they were integral and indispensable features of that country s legal system such that they could not be replaced by corresponding features of the lex causae. Further a number of the sub-paragraphs of art, 15 of Rome II either covered or were closely analogous to the rules in issue here, namely art.15(a), (c), (d) and (by analogy) the limitation rules in (h). A helpful test was to ask whether the rule was concerned with a decision on the merits. Following the handing down of the judgement of the Court of Appeal in draft, Actavis put forward suggested alternative forms of declaratory relief and asked the court to remit for trial in the Patents Court various issues concerning their proposed new product for reconstitution with dextrose. These are set out at [155] of the judgment reported here and these issues were also addressed by the Court of Appeal in a post-script at [148] to [162]. Held, allowing the appeal and setting aside the declarations of non-infringement, (1) The judge had been right to find that the 508 patent was addressed to a team which included a chemist in addition to the oncologist: (i) the skilled addressee needed to manufacture the medicament and the manufacturing step was an essential requirement of the claim, necessary to prevent the claim falling foul of the method of treatment exclusion from patentability. In the absence of evidence that pemetrexed disodium was generally available, manufacture of the medicament included making the active ingredient; (ii) in the real world, the teams developing and making medicaments for use in treatment comprised specialists in a range of disciplines; and (iii) if Lilly was correct on the issue of construction of claim 1 and it would be understood as extending to the use of active ingredients other than pemetrexed disodium, the choice of an appropriate alternative salt would not be something that the medical oncologist could assist with. It was unnecessary to express any concluded view on Actavis argument based on claim 12. ([33], [34]) (2) The claims of a patent specification were not to be approached on the basis that the literal meaning of the claims was to prevail unless it was possible to detect some ambiguity in them. Such an approach, if strictly applied, could result in the court construing the specification in a sense which the reasonable reader, aware of the context and background, would not have thought the author intended. The purpose of the specification (to identify and communicate a novel idea) and the identity of the audience (the addressee of the specification equipped with the common general knowledge in the art) were essential to determining the meaning which would be

9 46 ACTAVIS UK LTD v ELI LILLY &CO H26 H27 H28 H29 H30 conveyed by the words chosen in the claims of the patent. However, such a purposive construction did not justify going beyond the definition of the technical subject matter for which the patentee sought protection in the claims. ([42], [43]) Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46, [2005] R.P.C. 9, HL referred to. (3) The fact that English courts did not apply a general doctrine of equivalence to the construction of patent claims did not mean that the existence of equivalents which had no material effect on the way the invention worked had no bearing on the proper, purposive interpretation of a patent claim. It had long been the law that such equivalents formed part of the background of facts known to the skilled reader which would affect what that person understood the claim to mean. ([44]-[45]) Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46, [2005] R.P.C. 9, HL, considered. Catnic Components Ltd v Hill & Smith Ltd [1982] R.P.C. 183, [1981] F.S.R. 60, HL, referred to. (4) For the purpose of assessing the second Protocol question, the notional addressee would be taken not to have been presented with information which that person could not have derived from the patent or his or her common general knowledge about whether the variant would in fact have a material effect on the way the invention worked. The Protocol questions were no more than an aid to construction in suitable cases and in arriving at the skilled person s understanding of the language of the claim, it could not possibly be right to provide that person with information which he or she could not derive either from the specification or their common general knowledge. ([49]) Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46, [2005] R.P.C. 9, HL referred to. (5) The skilled reader of the patent in the present case would not, in the normal run of things, expect any of the Actavis active ingredients ( the Actavis AIs ) to convert into pemetrexed disodium when dissolved in aqueous solution, or vice versa. ([53]) (6) There were difficulties endorsing the judge s reasoning on the use of prosecution history as a guide to construction; (i) it assumed that the skilled reader would always read the prosecution history; and (ii) it suggested that the story told by the prosecution history would assist the court in preventing abuse of the system, which would be a very rare case indeed. Unless the acceptance of a restriction in a claim was to operate as some kind of estoppel against the patentee arguing for wider claims, (a proposition for which neither side contended and which Jacob J. rejected, at least on the basis of domestic estoppel, in Bristol Myers), there would always remain an issue as to whether the applicant needed to accept the restriction notwithstanding that he did so. In those circumstances, the light which the prosecution history sheds on the ultimate question of construction was likely to be extremely limited. ([58]) Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46, [2005] R.P.C. 9, HL; Rohm & Haas Co v Collag Ltd [2001] EWCA Civ 1589, [2002] F.S.R. 28, CA, and Bristol Myers Squibb Co v Baker Norton Pharmaceuticals Inc [1999] R.P.C. 253, Pat. Ct, referred to. (7) It was not useful to go to 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. However, it was always open to a party attacking the patent to argue that the claims as sought to be construed by the patentee lack support in the specification. ([59]) American Home Products Corp v Novartis Pharmaceuticals UK Ltd [2001] R.P.C. 8, CA, referred to. Published by Oxford University Press for the Intellectual Property Office

10 H31 H32 H33 H34 H35 Direct infringement in English law [2016] R.P.C (8) The argument that it should be assumed that the skilled person knew that the Actavis AIs were soluble was rejected. The skilled reader of the 508 Patent simply did not know and could not predict whether variants such as the Actavis AIs would be sufficiently soluble to work. It was not a legitimate exercise to feed information about the Actavis AIs to the skilled team to help them deal with technical concerns about the workability of variants. The answer to such concerns had to be found in the specification or from the skilled team s general knowledge. ([68]) Beecham Group Limited v Bristol Laboratories Limited (No. 1) [1978] R.P.C. 153, [1977] F.S.R. 215, HL and Pharmacia Corp v Merck & Co. Inc. [2001] EWCA Civ 1610; [2002] R.P.C. 41, CA distinguished. (9) As to the second Protocol question, the judge s reasoning had been correct. Once the claim included the step of manufacturing a medicament for treating a disease, it necessarily included a requirement that the manufactured medicament was to some extent effective for treating the disease. If the skilled chemist was unable to predict that a variant would be sufficiently soluble to deliver an effective amount of pemetrexed anions in solution, then he or she was unable to say that the variant would have no material effect on the way the invention worked. ([71]) (10) The judge had been right to hold, in answering the third Protocol question, that the skilled team would understand that the patent was clearly limited to the disodium salt, and did not extend to the diacid, or the dipotassium or ditromethamine salts. This was because (i) the specification contained passages wheretheinventionwasdescribedinverygeneral class termsandotherswhere the invention was clearly limited to pemetrexed disodium. When the reader came to the claims, therefore, he or she would appreciate readily that the patentee had chosen to claim narrowly and by reference to a single chemical, and not broadly by reference to any class; (ii) pemetrexed disodium was a highly specific chemical compound and there was no obvious leeway as a matter of language for giving it a broad construction; (iii) anti-folates were a known class, but the claim could not be to all anti-folates because that term was used in the specification but not chosen in the claims. As to pemetrexed, the disodium salt was the only salt known to be efficacious and safe; (iv) the only data contained in the specification were for pemetrexed disodium, and broader claims therefore lacked support and might have been unacceptable to the EPO; (v) there was a striking contrast between this very specific language and the general terms used in the claim for the methyl malonic acid lowering agent (any pharmaceutical derivative ) and the folic acid components (any physiologically available salt or ester thereof ) which the skilled reader could not fail to notice; and (vi) the skilled reader would have understood that there were plausible reasons why the patentee might have wished to limit to the disodium salt: e.g. the patentee might have been content with a claim limited to his commercial embodiment, ALIMTA. ([72]) (11) In the circumstances it was unnecessary to go to the prosecution history to arrive at the above conclusion when one could get there, straightforwardly, by reading the claims in the light of the specification. ([73]) (12) Although one form of the medicament covered by the claims of the 508 Patent would be a solid dosage form, it was obvious that another form was an injectable solution, arrived at by dissolving pemetrexed disodium in water. The skilled person

11 48 ACTAVIS UK LTD v ELI LILLY &CO H36 H37 H38 H39 H40 H41 reading claim 1 of the patent would consider that pemetrexed disodium was present in the medicament. To put it another way, if one asked what, for the patentee s purposes, constituted the presence of pemetrexed disodium, the skilled reader would understand that it included a solution containing pemetrexed ions and sodium ions. Further, there was no reason why the skilled reader who understood from the specification that a solution containing pemetrexed ions and sodium ions was regarded as pemetrexed disodium should assume that the method by which that solution was prepared was of concern to the patentee. ([76]-[78]) (13) The presence of ions other than sodium could not take the solution out of the claim. Infringement was not generally avoided if the alleged infringement had all those features and added something more. ([79]) Wenham Gas Co Ltd v The Champion Gas Lamp Co (1892) 9 R.P.C. 49, CA, referred to. (14) Thus on the proper construction of the claim, it did not extend to pemetrexed diacid or any other pemetrexed salts other than disodium and there could be no direct infringement by Actavis by dealing in the Actavis active ingredients ( the Actavis AIs ). ([80]) Indirect infringement in English law (15) If all that the doctor or pharmacist were doing was making an aqueous solution of one of the Actavis AIs, Actavis case of indirect infringement would add nothing to its case of direct infringement. A solution made by dissolving pemetrexed dipotassium in plain water resulted in a solution which contained only potassium ions and pemetrexed ions, and was therefore not within the claims because sodium ions were missing. However in the present case the facts could give rise to indirect infringement because, in the ordinary course, each of Actavis AIs would be dissolved and/or diluted in saline, which was a source of abundant sodium ions. ([83]) (16) Pemetrexed dipotassium was a means relating to an essential element of the invention, notwithstanding that potassium was dissociated and sodium caused to be present in order to put the invention into effect. The language of s.60(2) did not require the supply of an element of the claim, but a means relating to an essential element. A means for releasing pemetrexed ions into solution related to an essential element of the invention where the invention called for pemetrexed ions and sodium ions in solution, particularly as it was the presence of the pemetrexed ions in the manufactured medicament which was essential for its efficacy as a medicament. The invention was then put into effect when the pharmacist made up the solution using pemetrexed dipotassium (or the other Actavis AIs), because there came a stage in the course of that activity when pemetrexed disodium was present and was used. ([86]-[92]) Grimme Landmaschinenfabrik GmbH & Co KG v Scott [2010] EWCA Civ 1110, [2011] F.S.R. 7, CA applied. (17) The declarations of non-infringement which Actavis sought would accordingly be refused as a matter of English law. ([92]) Infringement under French, Italian and Spanish law (18) It having been common ground that there was no detectable difference in the laws of France, Italy and Spain on the approach to contributory infringement, it Published by Oxford University Press for the Intellectual Property Office

12 [2016] R.P.C H42 followed that the declarations sought should also be refused in respect of those countries. ([93]) (19) (Obiter) The judge had been right to hold that there had been no direct infringement under the laws of France, Italy and Spain. ([94]) H43 H44 H45 H46 H47 The German litigation (20) Whilst the decision of the Oberlandesgericht was entitled to great respect, its reasoning did not cause the court to change its view on the issue of contributory infringement: (i) if by its requirement that the means must be configured in such a way that a direct use of the invention is possible it was indicating that pemetrexed dipotassium could not be an essential means, that result was not open to this court; and (ii) applying the teaching of the patent, it was sufficient if the medicament in question contained sodium ions and pemetrexed ions in solution in a ratio of at least 2:1. However the Oberlandesgericht appeared to understand pemetrexed disodium as describing only that substance in solid form and as such had adopted a construction of the patent with which this court did not agree. ([99]) Rome II (Obiter) (21) As it had been concluded that the proposed use of the Actavis AIs would amount to contributory infringement of the 508 Patent, Actavis were not entitled to the DNIs sought and it was not necessary to decide the Rome II issues. However, (obiter) had it been necessary to do so, the conclusion reached would have been that Rome II did not have the result that the lex causae applied to the conditions for applying for a declaration of non-infringement. They were procedural and subject to the lex fori. The court was not persuaded that the judge had made any error in his assessment of the evidence of foreign law or its application to the facts either. ([100], [145], [146]) (22) Article 1(3) of Rome II was a rule about the vertical scope of the regulation and excluded evidence and procedure from its scope. Article 15 was not directly concerned with clarifying the distinction between substance and evidence and procedure and so was not a safe guide as to whether matters which did not fall within its scope were caught by Rome II. There was therefore a need for an autonomous EU criterion for allocating rules into one or the other category. ([130]- [133]) (23) The rules in issue in the present case were conditions of admissibility of actions, rather than rules concerned with the substance or content of parties rights. They were all concerned with whether the court should hear a dispute about substance and were not concerned directly with the substance itself. Such rules would traditionally, for private international law purposes, be classified as procedural and not substantive and should continue to be so treated unless Rome II required a different outcome. ([135], [136])) (24) Article 15 of Rome II should not be given a wider effect than its language suggested, treating the matters listed as no more than examples of a class of analogous matters now caught by Rome II. The regulation was intended to respect the private international law principle that the lex fori was applicable to procedural questions. Further, although art.15 applied the lex causae to a number of matters which English common law would have treated as procedural, none of these was apt to encompass the rules for admissibility of a declaration of non-infringement.

13 50 ACTAVIS UK LTD v ELI LILLY &CO H48 Accoridngly, had it been necessary to decide the point, the Court of Appeal would have agreed with Arnold J. The conditions were procedural, and subject of the lex fori. ([139]-[145]) (25) The Court of Appeal was not persuaded that Arnold J. had made any error in his assessment of the evidence of foreign law or its application to the facts either. ([146]) H49 H50 H51 H52 Relief (26) None of the alternative declarations which Actavis proposed would be made. So far as the declaration on direct infringement was concerned, this would not serve any useful purpose. It would provide Actavis with no protection for its products and presented the result of the litigation in a way which could be misleading. As to the proposed indirect infringement declaration, by making the declaration conditional on Actavis state of mind, it failed to record what the court had actually decided, namely that the supply of Actavis product for reconstitution in saline in their admitted state of knowledge would be an infringement of the patent. ([157], [158]) (27) There were obvious procedural advantages in the issue as to whether acts done in relation to a product recommended for reconstitution in dextrose infringed the 508 Patent being decided in the presently constituted proceedings, if it could be, with the minimum of additional formality and expense. They would be duly remitted in the exercise of the Court s power under CPR r.52.10(2)(b). This was entirely without prejudice to Lilly s right to contend that to raise the issue at this stage, either within this action or by way of a separate action, was an abuse of process. However, the issue would be remitted in the broadest possible terms, namely whether the supply or offer to supply of the Actavis AIs when recommended for reconstitution in dextrose would infringe the 508 Patent so that the patents judge could give the necessary directions for the proper identification of the issue and its trial. ([161], [162]) Observed per Floyd L.J. (in relation to the admissibility of patent prosecution history as an aid to construction): I have to say that a rule which merely discourages reference to material, as opposed to treating it as inadmissible, has obvious practical disadvantages, as in the absence of an exclusionary rule the cost and expense associated with its deployment will almost invariably be incurred. However, as we are not asked to decide that the material is altogether inadmissible, I will, somewhat reluctantly, leave it at that. ([56]) Cases referred to in the judgment: Actavis Group HF v Eli Lilly & Co [2012] EWHC 3316 (Pat), Pat. Ct. Actavis Group HF v Eli Lilly & Co [2013] EWCA Civ 517, [2013] R.P.C. 37, CA American Home Products Corp v Novartis Pharmaceuticals UK Ltd [2001] R.P.C. 8, CA Beecham Group Limited v Bristol Laboratories Limited (No. 1) [1978] R.P.C. 153, [1977] F.S.R. 215, HL Bristol Myers Squibb Co v Baker Norton Pharmaceuticals Inc [1999] R.P.C. 253, Pat. Ct. Catnic Components Ltd v Hill & Smith Ltd [1982] R.P.C. 183, [1981] F.S.R. 60, HL Don v Lippmann (1837) 2 Sh. & MacL. 682, (1837) 5 Cl & Fin 1, HL (Sc.) General Tire & Rubber Co Ltd v Firestone Tyre & Rubber Co Ltd [1972] R.P.C. 457, [1971] F.S.E. 417, CA Published by Oxford University Press for the Intellectual Property Office

14 [2016] R.P.C H53 Grimme Landmaschinenfabrik GmbH & Co KG v Scott (t/a Scotts Potato Machinery) [2010] EWCA Civ 1110, [2011] F.S.R. 7, CA Improver Corp v Remington Consumer Products Ltd [1990] F.S.R. 181, Pat. Ct. Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46, [2005] R.P.C. 9, HL Messier-Dowty Ltd v Sabena SA [2000] 1 WLR 2040, [2001] 1 All ER 275, CA Pharmacia Corp v Merck & Co. Inc. [2001] EWCA Civ 1610; [2002] R.P.C. 41, CA Rohm & Haas Co v Collag Ltd [2001] EWCA Civ 1589, [2002] F.S.R. 28, CA Wall v Mutuelle de Poitiers Assurances [2014] EWCA Civ 138, [2014] 1 WLR 4263, CA Wenham Gas Co Ltd v The Champion Gas Lamp Co (1892) 9 R.P.C. 49, CA Henry Carr Q.C., Thomas Mitcheson Q.C. and Stuart Baran, instructed by Hogan Lovells International LLP, appeared for the defendant/appellant. Richard Meade Q.C., Thomas Raphael Q.C. and Isabel Jamal, instructed by Bird & Bird LLP, appeared for the claimants/respondents. JUDGMENT FLOYD L.J. Introduction and issues 1 This appeal is from the judgment of Arnold J. dated 15 May 2014 and his consequent order in an action by companies in the Actavis group of companies (together Actavis ) for declarations of non-infringement ( DNIs ) of European Patent (UK) No and the corresponding national designations in France, Italy and Spain. I will refer to European Patent as the 508 patent or the patent. The patentee of the 508 patent and the appellant is Eli Lilly & Company ( Lilly ). The appeal first raises issues of substantive patent law, which I shall call the patent law issues. The first of the patent law issues concerns the correct approach under our law (and the law of certain other designated states) to the construction of the 508 patent claims, in particular the requirement under the European Patent Convention 2000 ( EPC 2000 ) to take account of equivalents as well as the extent, if at all, to which it is permissible to make use of the prosecution history of the patent in reaching conclusions about construction. The second of the patent law issues concerns whether the application of our law of contributory infringement (as well as that of the other designated states) justifies a finding of infringement in this case. 2 Depending on the outcome of the patent law issues, there are further issues about whether European Parliament and Council Regulation 864/2007/EC of 31 July 2007 ( the Rome II Regulation or Rome II ) means that the English court must apply the corresponding foreign laws governing the conditions for applying for DNIs in each of the foreign jurisdictions, or whether English law, as the lex fori, applies. I will call this the Rome II issue. Finally, if the foreign laws apply, there would be further issues about precisely what the foreign laws provide about the conditions for applying for DNIs in those countries and whether Actavis have complied with those conditions. I will call these the DNI factual issues notwithstanding that, as is well known, issues of foreign law are a rather special type of issue of fact.