Second medical use claims; full trial decision provides further guidance on infringement and validity of Swiss claims

20 November 2015

Full trial decision from the English Patents Court in Warner-Lambert v Actavis provides guidance on how second medical use patent rights may be respected by generic manufacturers and health services in the UK.
In March 2015, we reported on an interim ruling in Warner-Lambert v Actavis.  Our report can be read here.  Warner-Lambert had sought an interim injunction against Actavis to impose conditions that would prevent Actavis from supplying a market that was covered by Warner-Lambert’s second medical use patent for pregabalin for the treatment of pain.  The High Court refused the interim injunction, finding that there was no serious issue to be tried in relation to patent infringement.  The judge’s reasoning was based on a particular interpretation of the scope of a Swiss-type medical use claim.  In a further development, the High Court granted to Pfizer (parent company of Warner-Lambert) an order compelling the UK healthcare authority National Health Service England (NHSE) to issue central guidance to prescribers and pharmacists in relation to Warner-Lambert’s pregabalin product.
Warner-Lambert appealed the refusal of the interim injunction.  In the event, the appeal was dismissed by the Court of Appeal.  Nevertheless, the appeal judges applied a different interpretation to the scope of a Swiss claim, which is more favourable to patent holders (stating that reasonable foreseeability was the relevant test for infringement, not subjective intent of the manufacturer).  This interpretation, which takes into account not only the activities of the manufacturer but also the intentions of downstream parties, was considered and followed at full trial. 
The full trial decision by Arnold J was handed down on 10 September 2015 (Generics (UK) Ltd (t/a Mylan) v Warner-Lambert Company LLC [2015] EWHC 2548 (Pat)) and provides useful information on the impact that various actions by the parties themselves, and NHSE, have had in respecting Warner-Lambert’s patent.  These ad hoc actions may in future inform the development of a formal system that would separate the patented market for a substance from the non-patented market, thus facilitating the enforcement of second medical use patents.
Patented and non-patented markets for pregabalin
The dispute concerns the drug pregabalin, which is marketed by Warner-Lambert under the trade mark Lyrica® for three indications: epilepsy, generalised anxiety disorder (GAD) and neuropathic pain. Patent protection for the active compound per se has expired, opening up the possibility of generic competition.  Yet Warner-Lambert also holds a second medical use patent (EP 0934061B) with Swiss-type claims directed to:
Use of pregabalin and pharmaceutically acceptable salts thereof in the manufacture of a pharmaceutical composition for treating pain”. 
Generic drug manufacturer Actavis obtained marketing approval for generic pregabalin for treating epilepsy and GAD, i.e. the indications not covered by the claims of Warner-Lambert’s second medical use patent.  Actavis launched the generic product (under the trade mark Lecaent®) in February 2015 with a so-called “skinny label” referring only to the non-infringing indications, i.e. epilepsy and GAD.  Actavis also notified superintendent pharmacists that Lecaent® was not licensed for the treatment of neuropathic pain.
The pain indication accounts for about 70% of the market for pregabalin.  Understandably, Warner-Lambert feared that doctors would prescribe pregabalin for the treatment of neuropathic pain (i.e. without specifying a brand), and the pharmacist would dispense Actavis’s Lecaent® product without knowing that the pregabalin had been prescribed for neuropathic pain and not one of the indications for which patent protection had expired.
The litigation therefore concerns Warner-Lambert’s efforts to protect a patented market for its Lyrica® product, in the context of a healthcare system which generally favours the prescribing and dispensing of cheaper generic versions of a drug. 
Interpretation of the scope of a Swiss-type claim

Swiss-type claims are of the form:
Use of substance X in the manufacture of a medicament for treating indication Y”.
They are regarded as process claims, directed to the manufacturer of the medicament or pharmaceutical composition. 
In the judgement refusing the interim injunction, the High Court held that the word ‘for’ in a Swiss-type claim means ‘suitable and intended for’ and that the relevant intention was that of Actavis, as the manufacturer of the medicine.  On the evidence, Actavis had not intended Lecaent® to be used to treat pain.  This interpretation of ‘for’ places a burden on patent holders to prove subjective intent on the part of the manufacturer, and can also be seen as absolving downstream parties such as doctors and pharmacists from taking any steps to avoid the prescribing and dispensing of a generic drug for a patented indication.
On appeal, the appeal judges held that ‘for’ requires that the manufacturer knows, or it is reasonably foreseeable, that the drug will intentionally be used for the patented invention (in this case, pain).  Crucially, this does not require the manufacturer to have any specific intention to use the invention itself; instead, it is the knowledge or reasonable foreseeability of the intentions of downstream parties that is decisive.  The latter interpretation of Swiss-type claims has been followed at full trial.  Applying the interpretation to the infringement case, Arnold J held that the downstream parties whose intentions are relevant are prescribing doctors and dispensing pharmacists, but not patients.
Protecting the patented market
The full trial decision highlighted actions taken by Actavis, Pfizer and various healthcare bodies to inform and facilitate the avoidance of mis-prescribing or mis-dispensing of generic pregabalin for the pain indication.  Notably, in addition to writing to over 7,500 superintendent pharmacists, Actavis also wrote to every Clinical Commissioning Group (CCG) in England and corresponding bodies in Wales, Scotland and Northern Ireland advising that Lecaent® is not licensed for pain.  In compliance with the Court order, NHSE issued guidance to CCGs, advising that pregabalin should be prescribed for pain under the brand name Lyrica®, and that when pregabalin is prescribed for pain, Lyrica® should be dispensed.  Software packages used by GP practices within the UK have now been updated to provide warnings of the existence of patent rights when pregabalin is prescribed for the treatment of pain.
Although some of the new guidance on prescribing and dispensing practice may take time to become fully effective, Arnold J was persuaded that “it is reasonable to expect that, if it has not already happened by now, in the fairly near future most prescriptions for pregabalin for pain will be written by reference to the brand Lyrica”.
Arnold J noted that one effect of the law of direct infringement is that if a batch of a drug was considered to infringe a Swiss-type claim, because at its time of manufacture it was reasonably foreseeable that it would intentionally be used for the patented indication, then downstream parties dealing with the drug, such as pharmacists, would also be liable for infringement.  Such a warning provides an incentive to establish a robust system for protecting patented indications, to minimise risk of unwitting patent infringement by healthcare systems and professionals.  Indeed, in his closing comments, Arnold J called for a system for centralised and authoritative guidance to be issued to prescribers and other relevant stakeholders to separate the patented market for a drug from the non-patented market.
The infringement and validity cases
On the facts, Arnold J held that Actavis had not infringed the patent. In his view, the steps taken by Actavis to avoid Lecaent® being dispensed for pain were sufficient to minimise the risk of this occurring.  Although some instances of Lecaent® being dispensed for pain had been cited in evidence, the judge found that it is proper to regard a small number of exceptional cases as de minimis.  Subsequent actions by Pfizer and the NHS England guidance reduced this risk still further, such that subsequently manufactured batches of Lecaent® also did not infringe.
The infringement action was combined with a revocation action initiated by Generics UK Ltd and then Actavis in 2014, challenging the validity of the patent.  In this part of the full trial decision, the patent was held to be invalid for insufficiency on the basis that the specification did not make it plausible that pregabalin could be used to treat all kinds of pain.
Impact of the decision
The decision by the Court of Appeal and its application in the full trial decision is potentially of considerable significance to the pharma and biotech industries.  To succeed in an infringement action the patent holder must show that the manufacturer knew, or at least that it was reasonably foreseeable, that the generic medicine would be used for the patented indication.  The full trial decision provides initial guidance on how this ‘reasonable foreseeability’ standard may be applied and the action that a generic manufacturer may need to take to safeguard against being held to infringe Swiss-type claims.  In relation to validity of Swiss claims (and, by extrapolation, EPC2000 medical use claims), the full trial decision also highlights the importance of including credible supporting data in the application as filed.
The full trial decision of Arnold J is likely to be seen by some as controversial and an appeal by the patentee seems inevitable; this story may not yet be over.

Please contact Dr Stephen Smith for further information.

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