Court of Appeal decision in Warner-Lambert v Actavis: further guidance on validity and infringement of second medical use patents
22 November 2016
In a series of complex and ongoing disputes involving Warner-Lambert and various generic drug companies, the Court of Appeal has upheld the High Court’s decision that Warner-Lambert’s second medical use patent for pregabalin is partially invalid and therefore not infringed by Actavis. We reported on the High Court decision here.
The Court of Appeal decision of 13 October 2016 (Warner-Lambert Company LLC v Generics (UK) Ltd (t/a Mylan) & Ors  EWCA Civ 1006) considered the validity and infringement of Swiss-type second medical use claims, which are of the form: “Use of substance X in the manufacture of a medicament for treating indication Y”. The decision confirms the need for the patent application as filed to make it at least plausible that the substance X would be effective in achieving the therapeutic effect, and that where the indication Y divides naturally into more than one part, it is necessary to consider each significant part of the claim scope. There being no valid patent claim asserted against Actavis, Warner-Lambert’s infringement case failed. Nevertheless, the Court of Appeal provided clarification of how the tests for infringement of Swiss-type claims could be applied. Although not binding, this guidance is likely to be given due consideration in future decisions of the UK courts.
Warner-Lambert’s patent held to be partially invalid for insufficiency
One aspect of the requirement for sufficiency of disclosure of a patent claim is that the specification should make the invention plausible. Floyd LJ of the Court of Appeal reviewed EPO and domestic case law to distil the general principles of the requirement for plausibility, and emphasised that it should be considered to be a “low, threshold test”. He noted that “claims will easily be seen to be not speculative where the inventor provides a reasonably credible theory as to why the invention will or might work. The same is true where the data in the specification is such that the reader is encouraged to try the invention”.
Warner-Lambert’s patent made broad claims as to the efficacy of pregabalin for the treatment of all types of pain, but did not provide a unifying principle as to why the limited data in the patent could be generalised. The reasoning of the judgement therefore relies heavily on expert evidence as to whether a unifying principle could emerge from the common general knowledge; and what the data in the specification would encourage the reader to do in order to “try the invention”.
Only Claims 1 and 3 of the patent were asserted in the infringement proceedings, the indications being “pain” and “neuropathic pain” respectively. It was recognised that, at the priority date of the patent, “pain” was classified into a number of different types, amongst them inflammatory pain and neuropathic pain. Neuropathic pain itself naturally divided into peripheral neuropathic pain and central neuropathic pain. The data in the patent clearly demonstrated that pregabalin was likely to be effective in the treatment of inflammatory pain; and the Court of Appeal upheld the finding at first instance that there was a sufficient mechanistic link between inflammatory pain and peripheral neuropathic pain to make it plausible that pregabalin would also be effective in the treatment of peripheral neuropathic pain. Specifically, it was common general knowledge that both of these types of pain may be characterised by “central sensitization”, a phenomenon in which various noxious stimuli act on nociceptor sensory fibres to trigger effects within the spinal cord. Expert evidence showed that the addressee of the patent would have been encouraged by the data pertaining to inflammatory pain to carry out simple tests, identified in the patent, to confirm the suitability of pregabalin for the treatment of peripheral neuropathic pain.
Key issues in the proceedings were whether Claims 1 and 3 should be construed to encompass central neuropathic pain; and whether the patent made plausible the efficacy of pregabalin for treatment of central neuropathic pain. The Court of Appeal upheld the first instance decision that pain meant “pain of any type”. A narrower interpretation of “pain” to include only those conditions characterised by central sensitization could not be justified in view of the specific listing of pain conditions for which there was no common general knowledge understanding as to their origin. Although there was some evidence of a usage of the term “neuropathic pain” to mean “peripheral neuropathic pain”, the patent made very broad claims as to the efficacy of pregabalin for treating pain of all kinds and so the context did not justify a narrow construction. Thus, Claim 3 was construed to encompass both peripheral and central neuropathic pain as indication. Central neuropathic pain was held to be a “significant part of the claim”, covering important conditions including stroke and multiple sclerosis, and could not be ignored when considering the plausibility of the claim. There were no data in the patent from which one could make predictions about the efficacy for central neuropathic pain, and the tests mentioned in the patent were not tests for central neuropathic pain. Therefore, both Claims 1 and 3 were held to be invalid.
Although Warner-Lambert had made a conditional application to amend Claim 3 to restrict it to peripheral neuropathic pain, this had been refused by the High Court as an abuse of process. The Court of Appeal has now upheld this decision, leaving no avenue open to Warner-Lambert to assert a valid claim against Actavis.
The decision highlights the importance of including in a patent application the technical rationale for why experimental data make an invention plausible in relation to all significant areas of a second medical use patent claim. This need not be a rigorously tested scientific hypothesis, merely a “reasonably credible theory”. The decision also shows the danger of including a laundry list of indications for which there is no reasonably credible support at the filing date.
Clarification of the tests for infringement of a Swiss-type claim
The Court of Appeal had already established a test for direct infringement of a Swiss-type claim in interim injunction proceedings in the present case. Direct infringement would be found if the manufacturer knows, or it is reasonably foreseeable, that the drug will intentionally be used for the patented indication, in this case treatment of pain. In applying this test at the High Court, the judge held that it is the intentions of the prescribing doctor and dispensing pharmacist that are relevant to establishing whether there is an intentional use for treating the patented indication.
Whilst the earlier analysis of the Court of Appeal as it relates to interpretation of Swiss-type claims is not binding law, Floyd LJ was at pains to comment on the High Court’s application of the infringement test. Floyd LJ considered it wrong for the judge to have dissected the requirement for intentional treatment of pain by separately considering the intentions of the doctor and the pharmacist. He observed that one would normally regard a person to intend what he knows or can reasonably foresee as the consequence of his actions. Floyd LJ considered that, to negate the assumption of intention, the manufacturer must take all reasonable steps within his power to prevent the consequences occurring. In the case at hand, the issue would be whether Actavis had taken all reasonable steps in its power to prevent its generic pregabalin product Lecaent® from being used to treat pain.
Floyd LJ also considered whether a Swiss-type claim could be subject to indirect infringement, which requires that means are provided by one party for putting the invention into effect (by another). The invention is the use of pregabalin in the preparation of a pharmaceutical composition for treating pain. Floyd LJ observed that the process of preparing the composition can continue through any packaging step performed by the manufacturer and includes the labelling step performed by the pharmacist.
Unless there is a further appeal to the Supreme Court, in which the patent is held to be valid in a relevant respect, the issue of the correct interpretation of Swiss-type claims or its application to the activities of Actavis will not finally be decided in these proceedings. Nevertheless, various other generic manufacturers are now operating in the pregabalin market in the UK, and Warner-Lambert is involved in separate proceedings against Sandoz. There appears to be a reasonable prospect that some of Warner-Lambert’s patent claims to specific types of peripheral neuropathic pain may be found to be valid and that binding law on the interpretation and infringement of Swiss-type claims will emerge from the ongoing litigation. Floyd LJ’s contribution on this topic in the present Court of Appeal decision is likely to be highly influential.