Construction, Abuse of Process and Insufficiency
On 14th November 2018 the UK Supreme Court (UKSC) handed down its judgment in the case of Warner-Lambert Company LLC v Generics (UK) Ltd and Actavis Group PTC.
The case concerned a drug called pregabalin, which is an analogue of gamma aminobutyric acid (GABA), a neurotransmitter. Pregabalin was developed by Pfizer/Warner-Lambert and is authorised for treatment of epilepsy, general anxiety disorder (GAD) and neuropathic pain. It is sold under the brand name Lyrica. The European patent for pregabalin expired in May 2013 and its data exclusivity in July 2014. This cleared the way for generic entry into the market for use of pregabalin in treating epilepsy and GAD as these uses were not protected by patents. However, Warner-Lambert held a European patent, EP-B-0934061 which included inter alia claims as follows:
Use of (s)-3-(aminomethyl)-5-methylhexanoic acid (pregabalin) or a pharmaceutical salt thereof in the preparation of a pharmaceutical composition for treating pain.
Use according to claim 1 wherein the pain is neuropathic pain.
Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction of the nervous system. There may be “peripheral neuropathic pain” or “central neuropathic pain” depending upon the location of the lesion or dysfunction. The Warner-Lambert patent did not expressly distinguish between these two types of neuropathic pain. Furthermore, animal experiments reported in the patent showed pregabalin to be effective against inflammatory pain and post-operative pain only.
Claims for revocation of the patent were lodged by Generics (UK) Ltd and Actavis Group PTC in 2014. In February 2015 Actavis launched a generic pregabalin product called Lecaent under a label which referred to use for epilepsy and GAD but not neuropathic pain (a so-called skinny label). In advance of this launch, in December 2014, Warner-Lambert brought an action against Actavis for infringement.
Prior to consideration by the UKSC, there had been seven High Court Judgments and two from the Court of Appeal addressing interim injunctions, sufficiency, inventive step, direct infringement, indirect infringement, unjustified threats and the right to amend.
By the time the case came before the UKSC the issues had been narrowed down to:
1. The construction of the claims;
2. The sufficiency of disclosure of the specification;
3. Amendments and abuse of process; and
4. The test for infringement of the patent for manufacturing for a limited use.
The parties were heard at trial in February 2018 before Lords Mance, Sumption, Reed, Hodge and Briggs.
This report concerns the issues of claim construction, abuse of process and insufficiency. Infringement is discussed in Part II.
During the course of the proceedings it had become important to understand the scope of claim 3, in particular, whether in its context it encompassed all neuropathic pain, i.e. both peripheral and central neuropathic pain, or whether it should be more narrowly construed to encompass only peripheral neuropathic pain. Warner-Lambert contended the latter on the basis that a paragraph in the patent, which set forth the pain conditions to be treated, did not include any example of central pain and on the basis that a “validating construction” should be applied to claim 3.
The lower courts had held that the narrow construction pleaded by Warner-Lambert was not appropriate and that claim 3 must be construed to encompass all forms of neuropathic pain. The UKSC upheld this position. It was not accepted that the paragraphs in the patent listing types of pain to be treated could have the effect of implicitly limiting the invention to peripheral neuropathic pain. In relation to neuropathic pain, the words “includes but not limited to” in the relevant paragraph would mitigate against such a construction. Further, it was held that, even if the “validating principle” had some limited role to play in construing a patent, a necessary condition to apply it would be that the claim at issue is inherently ambiguous. In this case claim 3 could not be considered ambiguous.
Sufficiency of Disclosure of the Specification
Mylan had attacked claims 1 and 3 on the basis that the invention was insufficiently disclosed. In particular, it was alleged that the animal tests provided in the patent did not make it plausible that pregabalin would be effective in the treatment of all forms of pain (claim 1) or all forms of neuropathic pain (claim 3). Warner-Lambert responded that a common linking feature of the claimed pain was a phenomenon called “central sensitisation” and this was a component of the animal test reported for inflammatory pain, in which pregabalin was shown to be effective. Mylan countered that many of the pain states listed were not known to have a central sensitisation component and it was not common general knowledge that central neuropathic pain had such a component. Thus, the phenomenon of central sensitisation could not render either claim 1 or claim 3 plausible across the scope.
Both the High Court and the Court of Appeal found that on consideration of the expert evidence presented, those skilled in the art would understand that inflammatory pain and peripheral neuropathic pain both had a central sensitisation component so that the results presented in the patent would make it plausible that pregabalin might be effective for peripheral neuropathic pain. However, those models did not make it plausible for treatment of central neuropathic pain due to a lack of the central sensitisation component. Thus, claims 1 and 3 were invalid due to insufficiency.
The UKSC in a 3-2 split judgement also found claims 1 and 3 invalid for insufficiency but took a more harsh position in finding that the specification did not even render treatment of peripheral neuropathic pain plausible.
In the detailed judgment led by Lord Sumption, the application of the “plausibility test” for assessment of sufficiency in relation to medical use claims was considered. Many decisions of the Technical Boards of Appeal of the EPO on the topic, as well as those of the English Courts, were used as authorities. The findings of Lord Sumption and agreed by Lords Mance and Reed were that the specification must make the proposition that a product is efficacious for the treatment of a given condition plausible. It is not made plausible by bare assertion, as such a low threshold would not serve the purpose of barring speculative or armchair claims. There must be something to cause the skilled person to think there is a “reasonable prospect” the assertion is true. Reasonable prospect in this context should be met by the test set out in T609/02 (Salk Institute) where, in connection with a broad medical use claim it is stated:
“The patent must provide some information in the form of, for example, experimental tests, to the avail that the claimed compound has a direct effect on the metabolic mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the patent per se”.
Lord Sumption also confirmed that since plausibility is one element of the test of insufficiency and it is established that a claim must be sufficient across its scope, so it must be plausible across the scope.
Applying these principles to claim 3 of the Warner-Lambert patent, Lord Sumption held that since neither the specification, nor common general knowledge provides any reason for supposing that pregabalin affects the central sensitisation mechanism and thus provides nothing to suggest that pregabalin works with peripheral neuropathic pain by blocking central sensitisation, even treatment of peripheral neuropathic pain is not made plausible by the specification. Thus, claim 3 was insufficient.
It would appear from the UKSC’s reasoning that in the case of a medical use claim the “plausibility test” is now a rather higher bar than before in the English Courts where previously it had been considered a low threshold test.
Amendment and Abuse of Process
In the light of the finding of first instance that the patent made it plausible that pregabalin would be efficacious in the treatment of peripheral neuropathic pain, Warner-Lambert sought to amend claim 3, based upon a passage in the description of neuropathic pain as “caused by injury or infection of peripheral sensory nerves”.
The application to amend was refused by the High Court and the Court of Appeal as being filed too late in the proceedings and thus an abuse of process. There was concern it would give rise to issues of clarity, added matter and insufficiency requiring a further trial and this could have been avoided by an application to amend before or even during the first trial. The UKSC unanimously agreed and upheld the principles set out in Nikken Kosahusho Works v Pioneer Trading Co ( EWCA Civ 906  FSR 4) whereby a distinction should be drawn between a) pre-trial amendments, b) post-trial amendments to delete claims found invalid and c) post-trial amendments designed to set up a new claim which had not been adjudicated upon at trial. If a type (c) amendment would provoke a validity challenge which would require a further trial, then this would mitigate against giving permission to amend where the amendment could have been brought forward earlier. This finding of the UKSC was of course moot given the claim in question had been held insufficient across the scope and could not have been saved by the proposed amendment in any case. However, it is useful confirmation for future litigants that they should be mindful of the “Nikken” principles when contemplating a request to amend.