16 September 2015

Pregabalin: Patents Court calls for new system to deal with second medical use patents

On 10 September, Arnold J issued his much-anticipated decision in the dispute between Warner-Lambert/Pfizer and generic manufacturers Mylan and Actavis, a massive judgment coming in at 727 paragraphs. The case concerns the second medical use patent for pregabalin, marketed under the brand Lyrica for the treatment of epilepsy, generalised anxiety disorder (GAD) and neuropathic pain. The case arose out of an unprecedented situation, both for the parties, and also the UK healthcare systems, namely where a product has patent protection for its use to treat certain indications, but not others. 

Ultimately, the case was decided on the basis that the relevant claims were invalid on the grounds of insufficiency. However, in relation to infringement, whilst doubting the correctness of the Court of Appeal’s May 2015 decision interpreting second medical use patents, Arnold J applied that decision and found there was no infringement. Pfizer has confirmed that it intends to seek permission to appeal. 

Having 'lived' with the case for nine months, Arnold J also had time to contemplate how to deal with this situation going forward. He strongly urges for a system which will protect the monopoly provided by a second medical use patent, but which will also allow generic competition for non-patented indications. Under such a system, he calls for prescribers to be required to write prescriptions for the patented indication by reference to the patented product's brand name, and for non-patented indications using the generic name: for them to be able to do this, there must be centralised and authoritative guidance for prescribers and other stakeholders (such as software providers), albeit he recognises the challenges presented by the decentralised English healthcare system. In fact, an order was made in this case requiring NHS England to issue such guidance, but Arnold J’s plea is for a more formalised system, rather than an ad hoc outcome. As part of this, he stressed to both patentees and generic manufacturers that it is in their respective interests to co-operate with NHS England to enable it to issue such guidance. 

Background

We discussed the background to this case in our February and May Updates. Pfizer owns European Patent (UK) No 0 934 061 (the Patent) for the use of pregabalin for the treatment of pain, including neuropathic pain (an SPC for pregabalin would have extended protection to 17 May 2018 but was allowed to lapse for non-payment of fees). Lyrica is one of Pfizer’s most successful products, with global sales in 2013 of approximately $4.6 billion. 

The Patent is a second medical use patent with claims in Swiss form, i.e. “use of substance X for the preparation of a medicament (or pharmaceutical composition) for treating indication Y.” So, claim 1 is for the “use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain"

A number of generic manufacturers intend to launch, or have launched, generic pregabalin in the UK under a so-called ‘skinny label’, limited to the non-patented indications of epilepsy and GAD. Actavis’ product is called Lecaent; its SmPC and PIL state that the conditions for which it is indicated are epilepsy and GAD, but the PIL also includes 'blue box' wording notifying patients that it may be prescribed to treat other conditions.

Pfizer argued that Actavis’ launch of its product under a skinny label amounted to direct and indirect patent infringement, a claim which has required the courts to assess the requirements for infringement of second medical use claims. 

In May, the Court of Appeal upheld Arnold J’s January 2015 decision refusing Pfizer interim relief. However, it disagreed with him that there was no serious issue to be tried on infringement. Arnold J had interpreted "for" in Swiss form claims as importing a requirement of subjective intention by the manufacturer that the medicament or pharmaceutical composition would be used for treating the specified condition.  Floyd LJ disagreed and said that the skilled person would understand the word ‘for’ to be providing a link between the act of manufacture using pregabalin and the ultimate intentional use of the drug by the end user to treat pain. He decided therefore that there was no reason why the skilled person would conclude that the word ‘for’ implied subjective intent. In his view, they would understand that the manufacturer who knows (including having constructive knowledge), or could reasonably foresee, that some of his drug will intentionally be used for pain was making use of the patentee’s inventive contribution. 

Whilst in this decision Arnold J noted that the Court of Appeal's discussion on intention / foreseeability was obiter, he recognised that it was highly persuasive and that he should follow it unless he was entirely convinced that it was wrong.

In March, Arnold J issued an order requiring NHS England to issue guidance (which was made subject to a cross-undertaking in favour of NHS England, the Department of Health and a number of generic manufacturers in the event of a finding of invalidity). As a result of this, he thought it reasonable to expect that, in practice, in the fairly near future, most prescriptions for pain would be written by reference to the brand name Lyrica. 

Validity

Having considered the common general knowledge and prior art in some depth, Arnold J concluded that the relevant claims (directed at the use of pregabalin for the treatment of neuropathic pain) were not invalid on the grounds of obviousness. None of the prior art disclosed both pregabalin and use for the treatment of neuropathic pain and so the argument depended upon the skilled team reading (at least) two items of prior art together; whilst this was a permissible argument, obviousness was not made out.

However, Arnold J struck down claims 1, 3, 4, 6, 10, 11, 12, 13 and 14 for excessive claim breadth, i.e. insufficiency, concluding that the specification did not make it plausible that pregabalin was efficacious for treating neuropathic pain, idiopathic pain or fibromyalgia. Claim 1, in particular, was extremely broad, and it was "really quite extraordinary" that a compound would be useful for all the conditions listed. As for claim 3, which related to neuropathic pain, based on the data in the Patent, it would be impossible for the skilled team to make any reasonable prediction that pregabalin would be effective for treating central neuropathic pain (whilst it was just plausible that it would be effective to treat peripheral neuropathic pain, the claim was not limited in this way). 

Infringement

In case he was wrong on the question of the validity of claims 1 and 3, Arnold J went on to consider infringement: under sections 60(1)(c) and (2) of the Patents Act.

The claim to direct infringement under section 60(1)(c) requires that the defendant dispose of etc. any product ‘obtained directly by means of’ a claimed process. Actavis accepted that, if Lecaent was manufactured in accordance with the process claimed in claims 1 or 3 of the Patent, it was obtained directly by means of that process. The question before the Court was as to the nature of the mental element imported by the word 'for' in a Swiss form claim.

Whilst Arnold J expressed he had some “considerable doubts” as to the correctness of Floyd LJ’s interpretation in the Court of Appeal, he was unable to say that he was entirely convinced it was wrong and so he was obliged to apply it. 

Rejecting Pfizer’s argument that the test was one of pure foreseeability by the manufacturer that its pregabalin would be used for the treatment of pain, Arnold J stressed the central position of the requirement of intention, both of the prescribing doctor and (albeit after some hesitation) that of the pharmacist.

Looking at the position when Pfizer issued its claim in December 2014, Arnold J concluded that it was not foreseeable to Actavis that the Lecaent manufactured between June and October 2014 would be intentionally administered for the treatment of pain where it was dispensed in circumstances where the doctor had prescribed generic pregabalin for pain and the pharmacist did not know the indication for which it had been prescribed. In contrast, there would be intentional administration of Lecaent for pain if the pharmacist dispensed it when they knew that pregabalin had been prescribed for pain. However, this occurred in only a “small number of exceptional cases” which meant that it was de minimis. Further, Arnold J took into account the steps Actavis had taken including notifying superintendent pharmacists specifically that Lecaent was not licensed for the treatment of neuropathic pain. He reached similar conclusions for the position at February 2015 (when Actavis launched Lecaent), and July 2015 (at the conclusion of the evidence). 

Arnold J also rejected Pfizer’s claim for indirect infringement under section 60(2) of the Patents Act, noting the fundamental difficulty presented by the fact that claims 1 and 3 were claims to processes of manufacture, but there was no act of manufacture by any party downstream from Actavis (nor the prospect of such an act). Accordingly, Lecaent was not suitable for putting, or intended to put, the invention into effect: as it had either been put into effect by the point that Lecaent left Actavis or it had not been put into effect at all.

Arnold J went on to grant declarations that there was no infringement by doctors, pharmacists and patients, and also decided that certain communications issued by Pfizer were groundless threats of patent infringement proceedings, in respect of which Actavis qualified as a person aggrieved. 

Comment

Whilst there is the prospect of an appeal to the Court of Appeal (and perhaps ultimately this significant case will end up before the Supreme Court), this is a very favourable decision for generic manufacturers. In particular, where, as here, steps are taken which seek to prevent a generic drug being intentionally prescribed and dispensed for a patented indication, it appears that it will be very difficult to make out the necessary foreseeability requirement on the part of the manufacturer. 

It remains to be seen whether the Secretary of State will take up Arnold J's request for the implementation of a system of centralised and authoritative guidance for prescribers and other stakeholders.

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