Actavis UK Limited and others (Appellants) v Eli Lilly and Company (Respondent)

Hand-down Date:July 12, 2017
Cite as:[2017] UKSC 48

Trinity Term [2017] UKSC 48 On appeals from: [2015] EWCA Civ 555 and 556


Actavis UK Limited and others (Appellants) v Eli Lilly and Company (Respondent)

Eli Lilly and Company (Appellant) v Actavis UK

Limited and others (Respondents)

Eli Lilly and Company (Appellant) v Actavis UK Limited and others (Respondents) before

Lord Neuberger, President Lord Mance

Lord Clarke

Lord Sumption

Lord Hodge JUDGMENT GIVEN ON 12 July 2017 Heard on 4, 5 and 6 April 2017 Actavis and others Eli Lilly and Company Daniel Alexander QC

Thomas Mitcheson QC Andrew Waugh QC Stuart Baran (Instructed by Hogan Lovells International LLP) Thomas Raphael QC

Isabel Jamal

(Instructed by Bird & Bird LLP)

LORD NEUBERGER: (with whom Lord Mance, Lord Clarke, Lord Sumption and Lord Hodge agree)

  1. The issue raised on this appeal and cross-appeal is whether three products manufactured by the Actavis group of companies ("Actavis") would infringe a patent whose proprietor is Eli Lilly & Company ("Lilly"), namely European Patent (UK) No 1 313 508 ("the Patent"), and its corresponding designations in France, Italy and Spain.

  2. This judgment was circulated in draft to the parties' legal representatives in the normal way on 5 July 2017, on the basis that it would be handed down a week later. On the following day, just after midday, Actavis's solicitors emailed the Court expressing concern about the potential prejudice which their clients could suffer if they did not know of the outcome of this appeal until 12 July. Not least because publication of our decision could have an effect on the share prices of Actavis or Lilly or both of them, the Court proposed to the parties' respective solicitors that we should announce our decision at once, while maintaining the intention, in accordance with this Court's usual practice, to hand down the judgment a week after circulation of the draft. This was agreed by both solicitors, and accordingly on 7 July at 11.30 am, the following announcement appeared on the Court's website:

    "The Supreme Court allows Eli Lilly's appeal and holds that Actavis's products directly infringe Eli Lilly's patent in the United Kingdom, France, Italy and Spain. The Court dismisses Actavis's cross-appeal on the basis that if its products did not directly infringe, they would indirectly infringe to the extent held by the Court of Appeal."

    Accordingly, these are technically the reasons for those conclusions.

    The factual and technical background

    The factual background

  3. Pemetrexed is a chemical which has been known for some time to have therapeutic effects on cancerous tumours. However, when used for that purpose on its own, pemetrexed can often have seriously damaging, sometimes even fatal, sideeffects. Accordingly, its use as an anti-cancer drug was effectively precluded in

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    practice. The essential disclosure of the Patent was that the damaging side-effects could largely be avoided if a compound called pemetrexed disodium was administered together with vitamin B12. This has enabled pemetrexed disodium to be used for treatment in the form of a medicament which includes the vitamin. Such a medicament has been successfully marketed, under the brand name Alimta, by Lilly since 2004.

  4. The Patent primarily claims the use of pemetrexed disodium in the manufacture of a medicament for use in combination with vitamin B12 (and, optionally, folic acid) for the treatment of cancer.

  5. Pemetrexed itself is a member of a class of chemicals known as antifolates, and its molecular structure is shown below, with C, N, O and H being respectively the chemical symbols for carbon, nitrogen, oxygen and hydrogen; and the unallocated points on the chains and the rings being carbon.

  6. The presence of the two -CO2H units results in pemetrexed being an acid (hence it is also known as pemetrexed diacid), or as it is sometimes called, a free acid. When pemetrexed is dissolved in water, the hydrogens in those two units separate from the rest of the molecule as positively charged entities, protons, and the rest of the molecule becomes a negatively charged entity called an anion. The structure of pemetrexed disodium is similar except that, instead of the two -CO2H

    units, it has two -CO2Na units (Na being the symbol for sodium). Pemetrexed disodium dissolves in water, where the two sodiums separate from the rest of the molecule as positively charged entities called cations, and the rest of the molecule becomes an anion. Because it is the pemetrexed anion which is of interest, the sodium cation is often referred to as a counter-ion. A substance such as pemetrexed disodium, where the acidic hydrogens have been replaced, is known chemically as a salt.

  7. Although one might have thought that the actual invention should have been characterised as a disclosure that pemetrexed could be administered safely if it was combined in a medicament with vitamin B12, the claimed invention in the Patent is,

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    as mentioned in para 4 above, the manufacture of such a medicament. This formulation was required by the then-prevailing law contained in article 52(4) of the European Patent Convention 1973 ("EPC 1973"), which prohibited from patentability any method of treatment of humans or animals. This led to inventions which otherwise might have been expected to be expressed as being new therapeutic treatments being cast as manufacturing claims. Such claims are known as Swiss form claims, and they were illuminatingly discussed by Kitchin J in Ranbaxy (UK) Ltd v Astrazeneca AB [2011] FSR 45, paras 42 to 60. As he explained, the prohibition was substantially modified in article 53 in the European Patent Convention 2000 ("EPC 2000"), but that modification had not come into force when Lilly applied for the Patent.

  8. Actavis's proposed products involve pemetrexed compounds being used together with vitamin B12 for cancer treatment. However, rather than pemetrexed disodium, the active ingredient in those products ("the Actavis products") is (a) pemetrexed diacid, (b) pemetrexed ditromethamine, or (c) pemetrexed dipotassium. In other words, rather than including the disodium salt referred to in claim 1 of the Patent, the Actavis products include as the active ingredient (a) pemetrexed itself (ie the free acid), or pemetrexed with the hydrogens on the two -CO2H units replaced by (b) tromethamine, or (c) potassium. Actavis contend that, because they intend to use the Actavis products which do not include pemetrexed disodium, the claims of the Patent, which are expressed as involving the use of pemetrexed disodium, would not be infringed. By contrast, Lilly contends that there would be either direct or indirect infringement of the Patent if Actavis launch any of the Actavis products on the market in the UK or in France, Italy, or Spain. The allegation of direct infringement is based simply on the proposition that marketing or use of the Actavis products would infringe the Patent; indirect infringement is said to arise because pemetrexed disodium is claimed to be involved in the preparation of the Actavis products before they are administered.

  9. After a four-day trial, Arnold J decided that none of the Actavis products would directly or indirectly infringe the Patent in the UK or in France, Italy or Spain - [2015] Bus LR 154; [2015] RPC 6. The Court of Appeal allowed Lilly's appeal to the limited extent of holding that there would be indirect infringement in the four jurisdictions, but they agreed with the Judge that there would be no direct infringement - [2015] Bus LR 1068. Lilly appeals against the rejection of its case that there would be direct infringement, and Actavis cross-appeal against the rejection of their case that there would be no indirect infringement.

  10. As Floyd LJ explained in the Court of Appeal, the appeal raises the issue of the correct approach under UK law (and the law of the three other states) to the interpretation of patent claims, and in particular the requirement of EPC 2000 to take account of "equivalents", and also the extent to which it is permissible to make use of the prosecution history of a patent when determining its scope. The issue on the

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    cross-appeal is rather more fact-specific, namely whether the application of the law of contributory infringement justifies a finding of indirect infringement in this case.

  11. It is appropriate to start by setting out the relevant provisions of the Patent and the knowledge of its assumed addressee, topics on which my account is largely taken from the clear judgment of Floyd LJ in the Court of Appeal. I will then turn to the issue of direct infringement, which involves considering the proper approach to that issue generally, and also the relevance of the prosecution history. I will then consider the position in the three other states and finally I will address the issue of indirect infringement.

    The specification and claims in the Patent

  12. The Patent is entitled "Combination containing an antifolate and methylmalonic acid lowering agent", and it has a claimed priority date of 30 June 2000.

  13. The specification begins at para [0001] by stating that "[p]otentially, lifethreatening toxicity remains a major limitation to the optimal administration of antifolates". It then explains at para [0002] that antifolates work by inhibiting antifolate-requiring enzymes by competing with reduced folates for binding sites on those enzymes. The specification identifies several antifolate drugs as being in development, including Lilly's branded product Alimta.

  14. The specification then explains at para [0003] that a limitation to the development of these drugs is that they may be associated with substantial toxicity, including mortality, for some patients. These toxicity effects had led to the abandonment of the development of some antifolates. In para [0004] the specification explains that previous work had been done on the use of folic acid as a treatment for toxicity in this area. It also records work on vitamin B12 as a predictor of cytotoxic events.

  15. The specification then...

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