Arnold Finds Pain Patent Insufficient

October 2015

Generics (UK) Limited Trading As Mylan v Warner-Lambert Company LLC and between

Actavis Group PTC EHF v Warner-Lambert Company LLC and between Warner Lambert Company LLC v (1) Actavis Group PTC EHF (2) Actavis UK Limited (3) Caduceus Pharma Limited

This case relates to the first substantive decision in the ongoing battle between Mylan, Actavis and Warner-Lambert in relation to the use of pregabalin for treating pain. 

This judgment relates to European Patent (UK) No. 0934061, a second medical use patent owned by Warner-Lambert. The patent had claims in Swiss form which were directed towards the use of pregabalin for treating pain.

Warner-Lambert markets pregabalin under the trade mark Lyrica through Pfizer Ltd (Pfizer) for the treatment of epilepsy, generalized anxiety disorder and neuropathic pain. Patent protection for pregabalin expired on 17 May 2013 and a supplementary certificate based on this patent was allowed to lapse for non-payment of fees. 

Generics (UK) Ltd (Mylan) and Actavis Group PTC EHF (Actavis) both filed claims for revocation. These claims were ordered to be tried together by Birss J on 2 November 2014. Warner-Lambert filed a claim for infringement by Actavis and Caduceus Pharma Ltd (Caduceus) and applied for an interim injunction in respect of the intended launch of a generic pregabalin product by Actavis under the trade mark Lecaent for the treatment of epilepsy and generalized anxiety disorder.

Arnold J dismissed the application for an interim injunction in a judgment of 21 January 2015 ([2015] EWHC 72 (Pat)). He subsequently dismissed an application by Actavis to strike out Warner-Lambert’s claim for infringement under section 60(1)(c) but acceded to an application by Actavis to strike out a claim for infringement under section 60(2) in a judgment of 6 February 2015 ([2015] EWHC 249 (Pat)). In a subsequent judgment of 2 March 2015 ([2015] EWHC 485 (Pat)), Arnold J made an order requiring the National Health Service Commissioning Board to issue guidance to in relation to dispensing of pregabalin.  In a subsequent decision of the Court of Appeal ([2015] EWCA Civ 556), the appeal of Warner-Lambert against the strike-out of the application under section 60(2) was allowed. However, the appeal against the refusal to provide an interim injunction was dismissed.

Claim 1 of the patent was directed to the treatment of pain. Claim 2 was directed to inflammatory pain and claim 3 to neuropathic pain. The subsequent dependent claims were directed to specific types of pain. Claim 6 was directed to phantom limb pain, claim 13 to idiopathic pain and claim 14 to fibromyalgia pain.

Common General Knowledge

Arnold J noted that he had previously reviewed the law as to common general knowledge in KCI Licensing Inc v Smith & Nephew plc [2010] EWCA Civ 1260, which was approved by the Court of Appeal. He additionally noted some points which were specific to this case.

One question was whether common general knowledge has a territorial dimension. On this issue, the judge considered that it must be shown that the matter in question was common general knowledge in the UK because it is concerned with a right in respect of the UK. In particular, the judge considered that this view was not contrary to Article 27(1) of TRIPS, which provides that “patents shall be available and patent rights enjoyable without discrimination as to the place of invention”.

The judge identified that there were three main issues on common general knowledge relevant to the assessment of inventive step. The first related to the use of gabapentin, a similar molecule, for the treatment of pain. Mylan and Actavis argued that it was part of the common general knowledge that gabapentin was being used off-label by clinicians for the treatment of pain and that it was regarded as having therapeutic promise for this indication. Warner-Lambert disputed both propositions.

Arnold J decided that it was not common general knowledge among anaesthetists or neurologists in the UK that gabapentin was being used off-label to treat neuropathic pain.

The second issue was whether it was common general knowledge that there was sufficient commonality between epilepsy and neuropathic pain that there was reasonable basis for thinking a drug that was an anticonvulsant might be effective in treating neuropathic pain.  The judge concluded that the skilled team would not have considered that there was reasonable basis for thinking that a new anticonvulsant might be effective in treating neuropathic pain.

The third issue was whether it was common general knowledge that work on drugs which targeted calcium channels was an area of interest. The judge concluded it was not.

There were also a number of issues of construction which were relevant in relation to Warner-Lambert’s arguments against the allegations of insufficiency. The judge considered that it was common general knowledge that neuropathic pain was characterized by secondary hyperalgesia and allodynia in a large majority of patients but not in a significant minority.  In some cases of secondary hyperalgesia and allodynia involved central sensitisation, but not all cases. In addition, Arnold J found that it was not common general knowledge that the rat paw formalin test, used in the patent, was predictive of efficacy for neuropathic pain.

Construction

A number of points of construction were raised. A main point of construction was in relation to the meaning of “pain”. Mylan and Actavis argued that the skilled person would interpret this based on the International Association for the Study of Pain (IASP) definition of pain. Warner-Lambert argued in favour of a narrower definition being restricted to types of pain characterised by hyperalgesia and/or allodynia and having a central sensitisation component. Arnold J concluded that the Mylan and Actavis construction was correct.

A second important point of construction was whether “neuropathic pain” was restricted to peripheral neuropathic pain or whether it also covered central neuropathic pain. The judge concluded that the term should be interpreted as encompassing both types of neuropathic pain.

Obviousness

Mylan and Actavis advanced a number of different inventive step arguments. These fell into two main groups. The first group starter from the position that it was common general knowledge that gabapentin was potentially useful for treating neuropathic pain. However, as the judge concluded this was not common general knowledge, this line of argumentation could not be successful. The second line of argument relied on using at least two documents together as a starting point. As the judge noted, whilst this is a permissible line of argument, it is more difficult to make the case.

Accordingly, the judge concluded that none of the claims of the patent was obvious over any of the prior art attacks.

Insufficiency

The judge provided some general observations in relation to insufficiency.

It is convenient to begin with some general observations. The first is that, even on Warner-Lambert's construction, claim 1 is extremely broad. Prof Woolf accepted that the idea that a compound would be useful for all the conditions listed in [0003] was really quite extraordinary. The second is that the specification expressly states that the data presented show that pregabalin is effective in the treatment of inflammatory pain, a statement which it is common ground that the skilled team would regard as entirely plausible. By contrast, the specification does not claim that the data presented show that pregabalin is effective in the treatment of neuropathic pain, let alone conditions such as idiopathic pain. Thirdly, the specification expressly mentions two recognised models of neuropathic pain, but presents no data from such models. Fourthly, as already noted, there is no mention in the specification of the unifying principle relied upon by Warner-Lambert, namely central sensitisation. Indeed, there is no suggestion in the specification that there is any unifying characteristic or principle which enables a prediction to be made in respect of conditions other than inflammatory pain. Fifthly, the skilled team would note that the specification does not refer to either hyperalgesia or allodynia when discussing the formalin test. Sixthly, the skilled team would appreciate that the data presented in the Patent do not discriminate between primary and secondary hyperalgesia, but it is only the latter that indicates the presence of central sensitisation. Furthermore, the skilled team would appreciate that it would have been quite easy to design the experiments in way that did measure secondary hyperalgesia. Seventhly, as counsel for Mylan and Actavis pointed out, it is telling that counsel for Warner-Lambert suggested to Dr Scadding and Prof Wood in cross-examination that there was sufficient data in the Patent to make obvious to try pregabalin for neuropathic pain. That is not enough for sufficiency.

Arnold J then summarised the position in relation to specific claims. In relation to claim 3, the judge noted it was necessary to divide consideration of central neuropathic pain and peripheral neuropathic pain. The judge considered that the issue in relation to peripheral neuropathic pain was finely balanced. He concluded that the data in the specification in combination was enough to make it plausible that pregabalin would be effective to treat peripheral neuropathic pain. However, the judge noted that the patent did not make it plausible that pregabalin would be effective to treat central neuropathic pain. As the claim was not restricted to peripheral neuropathic pain, the claim was invalid. The judge also found claims 4, 6, 13 and 14 invalid. As these claims were invalid, it followed that claim 1 was also invalid.

Infringement

Pfizer and Warner-Lambert’s claim for infringement was based on section 60(1)(c) and section 60(2) of the 1977 Act. Pfizer and Warner-Lambert relied on claims 1 and 3.

The judge provided a detailed review of the indications for which pregabalin was prescribed, the methods by which it was prescribed and the various steps taken by Actavis, Pfizer supply of pregabalin. The judge then moved on to consider the merits of claim under section 60(1)(c). Arnold J noted that the earlier decision by the Court of Appeal with regard to the mental element in Swiss form claims, whilst not binding, was highly persuasive, and therefore should be followed unless the judge was convinced it was wrong. Whilst the judge noted he had considerable doubts about Floyd LJ’s interpretation of the mental element, he was not entirely convinced it was wrong, and therefore he elected to follow it.

Pfizer put forward that the infringement should be assessed at the date of commencement of Pfizer’s claim, namely 8 December 2014. Pfizer’s secondary case was that the relevant date was when Actavis launched Lecaent, namely 17 February 2015. The third case was that the relevant date was when the evidence at trial was completed, namely 15 July 2015. The judge considered all three options.

In each case, the judge concluded that it was not foreseeable to Actavis that Lecaent would be intentionally administered for the treatment of pain. Therefore, the mental element required was not present. The judge therefore concluded that Actavis did not infringe claims 1 and 3.

In relation to the claim under section 60(2), the judge noted that claims 1 and 3 were claims to processes of manufacture, and there was no manufacture by any party downstream from Actavis. Therefore, the drug itself was not suitable for putting the invention into effect. Either the invention was already put into effect when it leaves Actavis’ hands or it is not put into effect at all.

Declaratory Relief

The judge agreed to provide a declaration of non-infringement in respect of Actavis, wholesalers, doctors who prescribed generic pregabalin for the treatment of pain, pharmacists who prescribe Lecaent and patients who take Lecaent.

Threats

Actavis alleged a large number of communications made by Pfizer to other parties amounted to threats. The judge reviewed a number of communications and found Pfizer to be liable for making groundless threats in some but not all cases.

Summary

Arnold J concluded by stressing the need for a system to allow protection of the monopoly conferred by a second medical use patent whilst allowing lawful generic competition for non-patented indications. The judge noted that responsibility fell with both patentees and generic companies to cooperate and provide NHS England with all the information and assistance it needs. 

The judge found that no claims were obvious over any of the prior art. Claims 1, 3, 4, 6, 13 and 14 were found to be invalid on the grounds of insufficiency. Even if claims 1 and 3 were valid, they were found to be not infringed. Pfizer were also found to be liable for making groundless threats.

[2015] EWHC 2548 (Pat)