Actavis UK Ltd and Others v Eli Lilly & Company
| Jurisdiction | England & Wales |
| Judge | Mr Justice Arnold |
| Judgment Date | 12 February 2016 |
| Neutral Citation | [2016] EWHC 234 (Pat) |
| Docket Number | Case Nos: HC12E02962, HP13A01487, HP13B04212, HP13E04604, HP13B05505, HP14D00753, HP14A01611, HP14F01792 |
| Court | Chancery Division (Patents Court) |
| Date | 12 February 2016 |
[2016] EWHC 234 (Pat)
IN THE HIGH COURT OF JUSTICE
Rolls Building
Fetter Lane, London, EC4A 1NL
Mr Justice Arnold
Case Nos: HC12E02962, HP13A01487, HP13B04212, HP13E04604, HP13B05505, HP14D00753, HP14A01611, HP14F01792
Richard Meade QC, Thomas RaphaelQC and Isabel Jamal (instructed by Bird & Bird LLP) for the Claimants
Andrew Waugh QC, Joe Delaney and Katherine Moggridge (instructed by Hogan Lovells International LLP) for the Defendant
Hearing dates: 25–29 January 2016
Contents
| Topic | Paragraphs |
| Introduction | 1–6 |
| The procedural context of the Dextrose Remission Issue in more detail | 7–12 |
| The witnesses | 12–26 |
| Factual witnesses | 12–13 |
| Oncologists | 14–15 |
| Endocrinologist | 16–17 |
| Pharmacists | 18–23 |
| Foreign law experts | 24–26 |
| The law with respect to the Dextrose Remission Issue | 27–34 |
| Indirect infringement | 27–32 |
| Negative declaratory relief | 33–34 |
| Factual background to the Dextrose Remission Issue | 35–92 |
| A note on terminology | 35 |
| Alimta and the Alimta SmPC | 36–39 |
| Actavis' application for marketing authorisations | 40 |
| The Actavis Products and UK SmPC | 41–45 |
| Proposed variation to the UK SmPC for the Actavis Product | 46–51 |
| Proposed variations to the CP SmPC for the Actavis Product | 52 |
| The German SmPC for the Actavis Product | 53 |
| Administration of pemetrexed | 54 |
| Dexamethasone | 55 |
| Preparation of cytotoxic drugs for administration | 56–60 |
| The use of saline and dextrose solution as diluents for chemotherapy drugs | 61 |
| Stability data available to pharmacists | 62 |
| Storage as aseptic preparations | 63 |
| Published stability data for Alimta | 64 |
| Actavis' stability for the Actavis Product | 65 |
| Supply and distribution of the Actavis Product | 67–69 |
| Steps taken by Actavis to prevent the Actavis Product from being diluted in saline | 70–77 |
| Steps taken by Actavis in relation to the availability of stability data of its product in saline | 78–81 |
| Steps taken by Lilly to prevent the Actavis Product from being diluted in saline | 82–83 |
| Diabetes | 84–91 |
| Assessment of the Dextrose Remission Issue | 92–172 |
| The role of the oncologist | 94 |
| The role of the endocrinologist | 95 |
| The evidence of the pharmacists | 96 |
| The importance of the SmPC | 97–99 |
| Is it likely that stability data for the Actavis Product in saline will become available? | 100–109 |
| Would there be a motivation to use saline rather than dextrose solution as the diluent for the Actavis Product? | 110–136 |
| Italian and Spanish law | 137 |
| Is it likely that saline would be used to dilute the Actavis | 138–139 |
| Product despite the steps taken by Actavis to prevent this? |
|
| Letters to competent authorities and medical centres | 140–148 |
| Contractual terms | 149–153 |
| Questions from pharmacists about the use of saline | 154–161 |
| Lilly's case on infringement from launch | 162–171 |
| The stock-piling argument | 163–166 |
| The tender argument | 167–171 |
| Conclusion | 172 |
| The Letters Issue | 173–223 |
| Factual background | 173–206 |
| Applicable law and burden of proof | 207–208 |
| Actavis' case | 297 |
| Lilly's case | 210–213 |
| Contract | 214–216 |
| The law | 214 |
| Assessment | 215–216 |
| Promissory estoppel | 217–223 |
| The law | 216 |
| Assessment | 218–223 |
| Should a declaration be granted? | 224 |
| Conclusion | 225 |
| Summary of principal conclusions | 226 |
Introduction
Pemetrexed disodium is a chemotherapeutic treatment for lung cancer which has been marketed by the Defendant ("Lilly") or its subsidiaries under the brand name Alimta since 2004. As explained in more detail below, Alimta is marketed as a lyophilised (freeze-dried) powder with instructions to reconstitute it, and then dilute it, in a 0.9% solution of sodium chloride (known as "normal saline"). Pemetrexed and its pharmaceutically acceptable salts were protected by European Patent No. 0 432 677, which expired on 10 December 2010. The protection conferred by that patent was extended by Supplementary Protection Certificates ("the SPCs") which expired on 10 December 2015. Lilly also owns European Patent No. 1 313 508 ("the Patent") for the use of pemetrexed disodium in combination with vitamin B12 or a pharmaceutical derivative thereof and optionally a folic protein binding agent. The Patent will not expire until 15 June 2021.
On 27 July 2012 the Second Claimant commenced these proceedings seeking declarations of non-infringement ("DNIs") in respect of the French, German, Italian, Spanish and United Kingdom designations of the Patent with a view to clearing the way for the launch of a generic pemetrexed product on expiry of the SPCs. Subsequently other Claimants were joined, some of which later ceased to be Claimants, but for convenience I will refer to the relevant Claimant(s) from to time as "Actavis". Actavis initially sought DNIs in respect of a product the active ingredient in which was pemetrexed dipotassium. Subsequently Actavis also sought DNIs in respect of pemetrexed diacid and pemetrexed ditromethamine. Actavis applied for marketing authorisations for their products by reference to Alimta. At that stage Actavis proposed that their products should be reconstituted and/or diluted in normal saline, like Alimta. Actavis did not raise any issue with regard to the use of vitamin B12 etc. After unsuccessfully challenging the jurisdiction of this court with respect to the French, German, Italian and Spanish designations of the Patent (see my judgment dated 27 November 2012 [2012] EWHC 3316 (Pat) and the judgment of the Court of Appeal dated 21 May 2013 [2013] EWCA Civ 517, [2013] RPC 37, " Actavis I"), Lilly counterclaimed for threatened infringement of the UK designation. As explained in more detail below, Lilly also brought parallel proceedings in Germany, which led to Actavis discontinuing its claims in respect of the German designation shortly before the trial here.
In a judgment delivered on 15 May 2014 ( [2014] EWHC 1511 (Pat)), I held that Actavis' proposed dealings in its products would not amount to either direct or indirect infringement of the Patent. In a judgment delivered on 25 June 2015 ( [2015] EWCA Civ 555, " Actavis II"), the Court of Appeal upheld my decision with respect to direct infringement, but reversed it with respect to indirect infringement. In brief summary, the Court of Appeal held that the claims of the Patent were restricted to pemetrexed disodium, and therefore dealings in Actavis' products would not amount to direct infringement; but that, if Actavis' products were reconstituted and/or diluted in a sufficient quantity of saline, the resulting solution would fall within the claims because it contained both sodium ions and pemetrexed ions in a ratio of at least 2:1, and thus the supply of Actavis' products would amount to indirect infringement. Both sides have applied to the Supreme Court for permission to appeal against the Court of Appeal's decision, but unless and until the Supreme Court allows an appeal by one side or the other, the Court of Appeal's judgment is binding upon them and upon this Court. This judgment proceeds upon that basis.
When the Court of Appeal's judgment was supplied to the parties in draft, Actavis requested the Court of Appeal to remit for trial by the Patents Court an issue as to whether the supply of their products would constitute indirect infringement of the Patent if marketed with instructions to reconstitute and/or dilute the products with 5% dextrose solution instead of saline ("the Dextrose Remission Issue"). The Court of Appeal acceded to that request: see Actavis II at [155]–[156] and [160]–[162]. Although the Court of Appeal left it open to Lilly to apply to the Patents Court to strike out Actavis' claim for DNIs in respect of the supply of their products with instructions for reconstitution and/or dilution with dextrose solution as an abuse of the process, Lilly made no such application.
Actavis subsequently launched a pemetrexed diacid product ("the Actavis Product") in the UK on 21 December 2015. Actavis' evidence is that they are on track to launch the Actavis Product in France, Italy and Spain later this year. As explained in more detail below, the Actavis Product is a liquid product which does not require reconstitution, and the Summary of Product Characteristics ("SmPC") specifies that it is only to be diluted with dextrose solution. Lilly does not dispute that, if the Court of Appeal's judgment as to the scope of the claims is correct and if the Actavis Product is diluted with dextrose solution rather than saline, the supply of the Actavis Product does not amount to either direct or indirect infringement of the Patent. Lilly nevertheless resists the grant of DNIs in respect of the supply of the Actavis Product with instructions for dilution with dextrose solution. Lilly contends that it is foreseeable (and hence obvious) that the Actavis Product will be diluted with saline by some customers (or at least, that Actavis have not proved that it is not foreseeable) even though Lilly does not allege that Actavis are taking any steps to encourage the use of saline. By contrast with its stance at the first trial, however, Lilly has not counterclaimed...
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