No relief for Warner-Lambert as patent claims covering neuropathic pain held invalid
The Court of Appeal with Floyd LJ giving the leading Judgment, (Patten, Kitchin, Floyd LLJ;  EWCA Civ 1006; 13 October 2016) has upheld Mr Justice Arnold’s finding that Warner-Lambert’s patent covering use of pregabalin to treat pain was insufficient in part and that Warner-Lambert’s late application to amend in the UK was an abuse of process. Although this finding meant that neither of the claims alleged to have been infringed were valid, Floyd LJ went on to consider the arguments concerning direct and indirect infringement of Swiss form claims.
For direct infringement, the correct test for the required intention was an objective one: a person intends what he knows or can reasonably foresee as the consequences of his actions. In order to negate the existence of that intention, the manufacturer would need to demonstrate that he has taken all reasonable steps within his power to prevent the unlawful consequences occurring. In those circumstances, the manufacturer’s true objective would be a lawful one and he would be entitled to say that the foreseen consequences were not intended but an unintended incident of his otherwise lawful activity.
In relation to indirect infringement, the Court indicated that the process of manufacture of a pharmaceutical composition can include labelling by the pharmacist. On that basis, the acts and intention of pharmacists might be relevant in to contributory infringement.
The Court of Appeal have set out the meaning of “for” in a Swiss form claim but we do not have any clarity on what steps a manufacturer would need to take to overcome an allegation that it intended its product would be used for the patented indication. There was a great deal of disagreement between the parties as to what steps were reasonable (and permissible under the regulatory regime) for Actavis to take. Warner-Lambert’s position on what would be acceptable steps changed even during the course of the trial. However, Floyd LJ’s statement that the reasonable steps are those within the power of the manufacturer, does suggest that the Court may take into account whether certain factors, such as the structures of the health care system, would be properly considered to be outside the control of the manufacturer.
This Judgment also reminds patentees of the need to continually keep under review what amendments might be necessary depending on the claim construction that the Court might adopt and ensure they are considered, even if on a conditional basis, on a timely basis.
It is not currently known if the parties will seek permission to appeal to the Supreme Court and whether in light of the Court of Appeal’s Judgment on validity, an appeal would be allowed. If not, we expect that generic pharmaceutical companies will seek to switch their marketing authorisations from the skinny label to full label.
Warner-Lambert’s second medical use patent EP (UK) No, 0 934 06 (the “Patent”) covered the use of pregabalin for the preparation of a pharmaceutical composition for use in the treatment of pain. Actavis and others sought revocation of the Patent and Warner-Lambert had sued for infringement of claims 1 and 3. The claims of the Patent were in Swiss form, with claim 1 being the: “use of [pregabalin] or pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain”. Claim 3 was to the use according to claim 1, “wherein the pain is neuropathic pain”. The further claims were limited to various types of pain such as inflammatory pain (claim 2) which Lyrica was not licensed to treat. An earlier patent covering the pregabalin compound and its use for the treatment of epilepsy and generalised anxiety disorder (“GAD”) had expired in 2013. Although its branded pregabalin product, Lyrica was worth $4.6 billion globally and approximately $310 million in the UK in 2013, Warner-Lambert had allowed an SPC based on the earlier patent to lapse in 2013.
Marketing exclusivity for Lyrica expired in July 2014 and Actavis applied for a marketing authorisation for its generic version of pregabalin on a “skinny label” basis, for the non-patented indications of epilepsy and GAD. The dosages for all indications are similar. Actavis also took a number of steps including writing to superintendent pharmacists and clinical commissioning groups across the UK to emphasise that its product wasn’t for the treatment of pain. Advertising and marketing materials reinforced that message.
In January 2015, Arnold J refused Warner-Lambert’s application for an interim injunction to prevent Actavis launching its generic pregabalin product ( EWHC 72 (Pat)). In respect of direct infringement, Arnold J held that infringement of a Swiss form claim required a subjective intention on the part of the manufacturer that the product would be used for treating the patented indication. On that basis, Arnold J held that there was no serious question to be tried for either direct or indirect infringement. He then went on to strike out the indirect infringement grounds of Warner-Lambert’s case because there was no reasonable basis for alleging that Actavis had a subjective intent to infringe the patent. A February 2015 application by Warner-Lambert against NHS England resulted in a Court Order mandating guidance being issued to doctors about the patent position and prescribing Lyrica to treat pain.
In May 2015, the Court of Appeal upheld Arnold J’s decision to not grant an interim injunction but overturned his decision to strike out the indirect infringement case ( EWCA Civ 556). Rather unusually Floyd LJ giving the lead Judgment made lengthy obiter comments about the correct construction of Swiss form claims for the purposes of infringement. The subjective intention test was not correct. Intention was established if the manufacturer knew or it was reasonably foreseeable that infringement would occur.
The trial was heard over several weeks in June and July 2015 with Arnold J handing down his Judgment in September 2015 ( EWHC 2548 (Pat)). In that Judgment, he held that the patent was not obvious but a number of the claims (including claims 1 and 3) were insufficient and in any event not infringed on the Court of Appeal’s construction of Swiss form claims. Actavis were also successful in their threats counterclaim. All parties appealed.
After the main Judgment was handed down, Warner-Lambert sought to amend a number of claims, including claim 3 of the Patent in the UK to limit it to peripheral neuropathic pain to avoid the finding of insufficiency. Mylan and Actavis opposed the amendment and in November 2015, Arnold J decided that such an amendment amounted to an abuse of process ( EWHC 3370 (Pat)). This finding was appealed by Warner-Lambert.
The only issue of validity contested on Appeal was Arnold J’s finding that claims 1, 3, 4, 6, 13 and 14 of the Patent were invalid for insufficiency. This was based on the finding that the data in the Patent rendered plausible the claim that pregabalin would be effective in treating peripheral neuropathic pain but not central neuropathic pain. Mylan and Actavis contended there should have been more extensive findings of insufficiency and Warner-Lambert argued that the claims 1 and 3 were plausible.
Section 72(1)(c) of the Act sets out that a patent may be revoked for insufficiency where “the specification of the patent does not disclose the invention clearly enough and completely enough for it to be performed by a person skilled in the art”. Insufficiency may be deployed as an attack where the directions in the specification are not complete or clear enough for the invention to be performed by a skilled person and also, where the claim is excessively broad having regard to the patentee’s contribution to the art. Of particular importance, with regards to the latter, was the assertion that the invention will work across the scope of the claim must be plausible or credible.
All of Warner-Lambert’s challenges to the Judge’s findings about the common general knowledge (“CGK”) were dismissed. The Judge was correct in dividing neuropathic pain into peripheral and central neuropathic pain; this would be a distinction that would be understood by the skilled person. There was furthermore ample evidence to show that the skilled person would not expect central pain to possess a central sensitisation component.
Floyd LJ rejected Warner-Lambert’s primary argument, which sought to limit the scope of claim 1 to pain conditions having a central sensitisation component. This could not survive the finding that the conditions listed included ones where there was no CGK understanding as to their origin. Warner-Lambert’s other argument was essentially a construction they had sought to advance at trial and which the Judge held not to be open to them. Floyd LJ rejected this too as not every use in the specification of a term used in the claim would be interpreted by the reader as a definition. Floyd LJ observed that had Warner-Lambert intended to limit the claims to the listed pain conditions or to pain characterised by hyperalgesia or allodynia, it could have easily clarified this.
The Court upheld Arnold J’s finding that neuropathic pain in claim 3 included central neuropathic pain. The breadth of the claims made for pregabalin meant it was unlikely that the skilled person would interpret the omission of “peripheral” to mean that central neuropathic pain was excluded. Arnold J had held that the claims to peripheral and central neuropathic pain were plausible and implausible respectively. Floyd LJ observed that in this Action, it was unrealistic to suppose that the skilled addressee would conclude from a comparative evaluation of plausibility that neuropathic pain was confined to the peripheral kind. The skilled person would know from the CGK definition of neuropathic pain that it divided into two parts. Furthermore, there was insufficient evidence to provide any basis for the argument that experts did not distinguish between central and peripheral neuropathic pain when challenged on the claims. Warner-Lambert’s additional challenge based on their contention that the claims were plausible as all of the conditions were characterised by hyperalgesia and allodynia was rejected by the Court as it has not been fully raised as part of Warner-Lambert’s case and the evidence as a whole did not support them. On that basis, Floyd LJ upheld the Judge’s finding that claim 3 was not plausible across its breadth.
Floyd LJ also dismissed Actavis’ and Mylan’s Appeal against the finding that the claim that pregabalin was effective to treat peripheral neuropathic pain was plausible. They argued that the Judge had placed the bar too low in considering plausibility of the claims. However, Floyd LJ made it clear that the test for plausibility had a low threshold. A unifying principle between the two types of pain could justify a claim which included peripheral neuropathic pain. The fact that pregabalin effectively treated inflammatory pain which had a central sensitisation component and that a skilled person would know peripheral neuropathic pain also has a central sensitisation component, would suggest to the skilled person that pregabalin might be effective for peripheral neuropathic pain. This conclusion was further supported by evidence that the skilled team would be encouraged by the data in the patent to carry out tests to confirm pregabalin’s suitability for this use.
Abuse of Process
In relation to Warner-Lambert’s abuse of process appeal, the Court of Appeal upheld Arnold J’s Judgment and refused to allow the amendment of claim 3 of the Patent. An application to amend under s.75 is often made conditionally on a particular construction being adopted or unconditionally where the unamended claims are not defended. Actavis’ and Mylan’s objection to Warner-Lambert’s amendment was that it was abusive for a party to raise in a second set of proceedings matters which it should have raised in earlier proceedings between the same parties.
Floyd LJ observed that there were only two points in this Action which the Court would consider as potentially allowing a post-judgment amendment. These were (a) the fact that the subject matter of the proposed amended claim is or may have been already the subject of a finding in the main Judgment and (b) the extent to which the procedural history prevented Warner-Lambert from formulating the amendment sooner.
As to the first point, the amendment would have given Warner-Lambert an alternative route to a successful outcome, which was not dependent on winning the construction argument, effectively rendering the construction issue moot. As the construction issue was the only one in play at trial, Floyd LJ considered it was unfair to Mylan and Actavis to treat a trial in which only the construction issue was in play as equivalent to that in which the amendment was also an issue. If this had been the case, then they might have refocused their arguments and adduced further evidence to address the amendment.
Floyd LJ then considered whether Warner-Lambert had a good reason for not raising the amendment earlier. The central neuropathic pain point was late to emerge but Floyd LJ held that Warner-Lambert should have indicated no later than the commencement of the trial that it would seek to amend claim 3 in the event of an adverse finding on insufficiency.
In this Action all of the Patent claims were Swiss form claims, which are purpose-limited method claims. The Swiss form claim is used to get over two potential hurdles for second medical use claims: novelty and the prohibition against patenting methods of treatment of the human body. This is different to EPC 2000 claims, which are purpose-limited product claims, where the claim is to a product for use in treating the novel medical use.
Warner-Lambert alleged infringement of section 60(1)(c) (direct infringement, product by process) and s.60(2) (indirect infringement) of the Patents Act 1977. Section 60(1) sets out the direct infringement provisions that a person infringes a patent if, without the consent of the proprietor of the patent and where the invention is a process, “he uses the process or he offers it for use in the UK when he knows or it is obvious to a reasonable person in the circumstances, that its use there without the consent of the proprietor would be an infringement of the patent” (s.60(1)(b)) and “he disposes of, offers to dispose of, uses or imports any product obtained directly by means of that process of keeps any such product whether for disposal or otherwise” (s.60(1)(c). The s.60(1) provisions are torts of strict liability, which means that if any of the product infringes the claim, all of it would. There was no dispute that if Actavis’ pregabalin product was manufactured in accordance with the process claimed in claim 1, then it was obtained directly by means of that process.
Indirect infringement is governed by section 60(2) which sets out that a person infringes a patent if without the consent of the proprietor, he supplies or offers to supply in the UK a person not entitled to work the invention “with any of the means, relating to an essential element of the invention, for putting the invention into effect when he knows, or it is obvious to a reasonable person in the circumstances, that those means are suitable for putting, and are intended to put, the invention into effect in the UK”. This has a double mental element. Firstly, the state of mind of the supplier whether actual or constructive knowledge. The second mental element concerns the state of mind of a person who is supplied with the means and his intention to use them for the infringing purpose.
Claim 1 of the Patent was for: “use of [pregabalin] or pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain”. The key point on infringement was the meaning of the word “for”. The Court had to determine whose intention was relevant and what type of knowledge was required.
Actavis argued that if “for” meant foreseeability then the manufacturer would infringe a Swiss form claim at the time of manufacture if it could foresee that any of its product (even a tiny fraction) would be used to treat pain. This would be the case if the generic manufacturer did not intend such use and did everything in its power to prevent such use. As s.60(1)(c) was a tort of strict liability, all of the product would infringe and any party dealing with it such as wholesalers and pharmacists, would also infringe the Patent regardless of their knowledge. Actavis argued that the practical effect of this was to give Warner-Lambert a monopoly for all pregabalin as such, effectively extending their monopoly for the product over the non-patented indications.
Warner-Lambert’s position was that unless this construction was adopted, second medical use patents would effectively be unenforceable and there would be no incentive for patentees to seek to find new medical uses for known compounds.
Floyd LJ acknowledged that this was a difficult area of law. The Court was seeking to ensure that patentees are properly rewarded for the work done in finding a new use, whilst not excluding competitors from manufacturing and marketing the medicine for the known purpose. Floyd LJ reviewed various decisions of European Courts in relation to Swiss form claims noting that there was a spectrum of approaches. Some countries have gone for the “only packaging will do” approach, others whether there has been some element of encouragement and yet others considered what steps have been taken to prevent use of the patented indication. While acknowledging that the packaging did give an idea of the manufacturer’s intention, this alone did not provide the patentee with sufficient protection so the “packaging only” approach was rejected.
Floyd LJ rejected Actavis’ argument that there should be a subjective intention on the part of the manufacturer. He had no doubt that an objective approach was necessary. A person would intend what he knows or can reasonably foresee as the consequences of his actions. Floyd LJ then went on to consider what would be sufficient to negate the existence of intention and stated that it would be negatived where the manufacturer has taken all reasonable steps within his power to prevent the consequences occurring. In those circumstances, the manufacturer’s true objective would be a lawful one and he would be entitled to say that the foreseen consequences were not intended but an unintended incident of his otherwise lawful activity.
No guidance was given as to what steps would be considered sufficient for a manufacturer to fulfil this requirement. However, Floyd LJ did review the Judge’s application of the facts to the test set out by the Court of Appeal in its May 2015 Judgment. In dissecting the intention of the pharmacist, doctor and patient the Judge had fallen into error. The novelty of the claim relied on the purpose of the use of the drug and it is was only the manufacturer’s ability to foresee intentional use for the patented indication that was essential. On that basis, Floyd LJ noted that had the claims been valid, Arnold J would have needed to consider whether Actavis had taken all reasonable steps in their power to prevent their pregabalin product from being used to treat pain.
Floyd LJ did not accept Actavis’ argument that indirect infringement was impossible because of the nature of the claim, which in the absence of a pharmacist labelling the product meant that the manufacture was complete at the stage it left the manufacturer. The invention was “the use of pregabalin in the preparation of a pharmaceutical composition for treating pain”. The example of labelling by a pharmacist demonstrated that the process was not complete when pregabalin left the manufacturer. The process included a labelling step. On that basis, the pharmacist’s acts in preparing the composition for delivery to the patient could be considered as relevant acts of preparation, if done with the necessary intention.