Edward Cronan is a pupil barrister at Hogarth Chambers, and former solicitor. Edward studied Natural Sciences at the University of Cambridge and has previously been seconded to and worked in companies in the life sciences industry.
This article looks to summarize and then test the application of the recent Supreme Court decision on plausibility in Warner-Lambert v Actavis [2018] UKSC 56. The Supreme Court’s judgment has changed patent law in the UK. This article assesses the legal standard set out in the Supreme Court’s decision, and how it might be applied in practice.
The standard of plausibility advanced by Lord Sumption is broken down into its constituent elements by reference to his review of the case law. Those elements are then summarized in the form of three binary questions. Those binary questions are then applied to the High Court case of MSD v Shionogi [2016] EWHC 2989 (Pat) in order to illustrate how the new test of plausibility could function in a variety of scenarios.
Application of the Supreme Court’s new test shows that the circumstances where clinical trial data are required to make an invention plausible should be very limited. The concerns of Lord Mance and Lord Hodge, that Lord Sumption’s test may be seen as imposing a prima facie requirement for demonstration of therapeutic efficacy, are therefore hopefully unfounded.
The Supreme Court’s ‘Pregabalin’ decision, in Warner-Lambert v Actavis,1 is not an easy read. The Court’s decision in relation to plausibility (only one of three areas traversed by the Court) concerns the disclosure necessary to justify a monopoly on a new use of a known compound in the context of Swiss-form second medical use claims. The Court failed to reach a consensus decision; the resulting complexity is perhaps unsurprising. Given the increasing prevalence of repositioned medicines in pharmaceutical research, the Supreme Court’s judgment will be of growing importance.
We are left in a position of relative uncertainty: how should the Supreme Court’s decision in Warner-Lambert be applied in practice? This article aims to summarize the Supreme Court’s new test of plausibility in an approachable manner, and to illustrate it by applying the principles as summarized to real facts from life sciences patent litigation and medical research.
The judgment in Warner-Lambert raises a number of issues in relation to plausibility: what is the new standard? Could there now be a requirement for in vivo data? How should the concept be applied to issues of obviousness and industrial applicability? How each of these questions might be resolved is explored below by reference to the above-mentioned examples.
What is the new test of plausibility, and is it really new?
Lord Sumption’s speech in the Supreme Court judgment is perceived as raising the bar for the test of plausibility in the English courts. This is not least because the two dissenting speeches, of Lords Mance and Hodge, betray a concern that Lord Sumption’s standard imposes too high a requirement on patentees. Lord Sumption certainly makes it clear that he believes the Court of Appeal set the bar too low by stating a willingness to accept plausibility on ‘the slimmest of evidence’; however, the extent to which that statement represented practice in the High Court and Court Appeal is debatable.
Many practitioners have said that on first reading Lord Sumption’s speech, it was not immediately clear that the law of plausibility had been developed beyond the case law of the Boards of Appeal of the European Patent Office as presently applied. That was at least the case until Lord Hodge’s statement at [180]:
Where I differ from Lord Sumption is that, in agreement with Lord Mance, who has analysed the three cases of ALLERGAN, IPSEN and BRISTOL MYERS SQUIBB, I do not interpret those principles as requiring the patentee to demonstrate within its patent a prima facie case of therapeutic efficacy.
Lord Mance’s comments at [193]–[195] continued to ring alarm bells:
In my view, Lord Sumption’s analysis imposes too high a threshold, and imposes a burden on a patentee which the case law of the Board of Appeal of the European Patent Office does not justify …
195. For these reasons, I consider that it puts the test too high to suggest that ‘the specification must disclose some reason for supposing that the implied assertion of efficacy in the claim is true’ (Lord Sumption’s judgment, para 36). That amounts on its face to, or certainly risks being read as, a requirement that the plausibility of the claim must appear to be established prima facie through scientifically cogent reasoning or experimental evidence set out in the specification.
Lords Hodge and Mance, following the lengthy gestation period of this judgment, clearly came to believe that the position Lord Sumption had settled on risked raising the bar above that of the jurisprudence of the EPO, to the extent a patent would be required to demonstrate a prima facie case of therapeutic efficacy. What does this really mean?
The judges’ use of the term prima facie is perhaps unfortunate. It avoids saying what the other members of the Court think the standard advanced by Lord Sumption actually is. It avoids saying how this standard is different from the standard applied by the Court of Appeal. It uses Latin words that are liable to be interpreted inconsistently by different readers; the term prima facie can alternatively be defined as either ‘appearing so on first examination’ or ‘self-evident’. So, what is Lord Sumption’s new and potentially objectionable test of plausibility?
What is the Warner-Lambert plausibility test?
In paragraph 37 of the judgment, Lord Sumption (with the agreement of Lord Reed and Lord Briggs) lays out seven ‘points’ that ‘should be made’ in the context of considering the proper legal meaning of ‘plausibility’. It is this statement of the law as agreed upon by the majority of the Supreme Court that should now form the basis of any enquiry into the plausibility of a claimed invention.
Lord Sumption’s seven points are a mixture of statements of legal principle based on the preceding review of the case law and some direct citation of important points. These statements of the law should be seen to relate not just to plausibility in the context of sufficiency, but also obviousness, the relationship between which is discussed further below.
The best starting point for determining what the Warner-Lambert test is perhaps the speech of Lord Hodge at paragraph [179]. Lord Hodge tells us what aspects of Lord Sumption’s decision he agrees with; Lord Hodge prefers a lower standard, hence we know the aspects on which there is agreement to be a safe lower limit from which we can proceed. What Lord Hodge says is this:
I agree with Lord Sumption (paras 33-34) that those decisions do not place an onus on an objector to show that the implied assertion of therapeutic efficacy is implausible. I also agree with his view (paras 35-37) (a) that the patentee must disclose in its patent, when read in the light of the common general knowledge, the contribution to the art which justifies his monopoly and, to that end, (b) that the specification must disclose some scientific reason for thinking that the medicament might well have the claimed therapeutic effect.
What we know then is that the burden of proof remains on the patentee (positive plausibility); the patent must disclose its contribution to the art; and vitally that the specification must disclose some scientific reason for thinking that the medicament might well have the claimed therapeutic effect. The extent of any disagreement among the Supreme Court is therefore only with regard to any requirements over and above these.
The members of the Supreme Court consider themselves to have divergent opinions as to what constitutes ‘some scientific reason’, and how that reason must be disclosed. It is not altogether clear that the judges’ positions are in principle irreconcilable. It is however certainly the case that they might apply them differently to the facts in a case such as Warner-Lambert.
It has been suggested that the key difference between the two positions adopted by the Supreme Court is that Lord Sumption’s judgment places a greater weight on what must be disclosed in the patent itself. This may be the case; however, Lord Sumption’s requirement for a disclosure of reasonable scientific grounds should be interpreted in light of the requirement that the patent must make some technical contribution. In that context, the requirement for disclosure can be shown to be less onerous than it might otherwise be perceived.
The patent must properly claim an advance on the prior art, else it would be invalid for lack of inventive step. While Lord Sumption is considering plausibility in the context of sufficiency, his reasoning is grounded in the requirement for the patent to claim such a step. This is apparent from Lord Sumption’s third point in [37] of the judgment. He says:
the claimed therapeutic effect may well be rendered plausible by a specification showing that something was worth trying for a reason, i.e. not just because there was an abstract possibility that it would work but because reasonable scientific grounds were disclosed for expecting that it might well work. The disclosure of those grounds marks the difference between a speculation and a contribution to the art. This is in substance what the Technical Board of Appeal has held in the context of article 56, when addressing the sufficiency of disclosure made in support of claims extending beyond the teaching of the patent. In my opinion, there is no reason to apply a lower standard of plausibility when the sufficiency of disclosure arises in the context of EPC articles 83 and 84 and their analogues in section 14 of the Patents Act. In both contexts, the test has the same purpose.
It is this combination of sufficiency and obviousness perspectives that may have caused the test advanced by Lord Sumption to be perceived as raising the bar for plausibility.
Some scientific reason
In respect of the necessary scientific reason, Lord Sumption’s exact words are that an invention would be rendered plausible where ‘reasonable scientific grounds were disclosed for expecting that it might well work’ and that in the disclosure of the patent ‘there must be something that would cause the skilled person to think that there was a reasonable prospect that the assertion would prove to be true’. Lord Sumption develops his legal test for plausibility over the remainder of paragraph [37], the keys aspects of which are as follows.
In order for the skilled person to determine that there was a reasonable prospect the assertion would prove to be true (on scientific grounds), there must be a link between the compounds and the claimed efficacy. What is key is that this link does not need to be direct: it is chain of reasoning and evidence that connects the claimed molecules to the therapeutic effect.
Lord Sumption relies on the EPO Board of Appeal’s decision in Salk,2 saying that the skilled person will be satisfied provided there is a reasonable prospect only on the basis of information demonstrating a direct effect on a metabolic3 mechanism specifically involved in the disease. There must be demonstrated a direct effect on a mechanism; the mechanism must be specifically involved in the disease.
Unhelpfully, no direct commentary is provided on when to consider a set of linked conditions a single ‘disease’; however, given the focus elsewhere on the more precise term ‘therapeutic effect’, it would be sensible to construe a disease as being a condition or conditions amenable to treatment by a common therapeutic effect on a shared metabolic mechanism.4
Importantly, Lord Sumption does state that plausibility can be based entirely on reasoning, and requires no experimental evidence:
the effect on the disease process need not necessarily be demonstrated by experimental data. It can be demonstrated by a priori reasoning. For example, and it is no more than an example, the specification may point to some property of the product which would lead the skilled person to expect that it might well produce the claimed therapeutic effect; or to some unifying principle that relates the product or the proposed use to something else which would suggest as much to the skilled person.
This statement would not seem to exceed the Court of Appeal’s position that plausibility can be established on the slimmest of evidence. It is, however, an incomplete statement of Lord Sumption’s analysis.
At paragraph 31 of the judgment, Lord Sumption deals with the case of IPSEN,5 albeit in a manner roundly criticized by Lord Mance at paragraph [194]. Lord Sumption said of the IPSEN patent, ‘The patent comprised no experimental data supporting the drug’s claimed therapeutic effect, but it did contain a technical explanation of its effect and an experimental methodology by which this could be verified: see para 11.’6
Lord Sumption goes on to say, ‘This decision is authority for the proposition that plausibility can be demonstrated in the specification without experimental evidence, if there is no substantiated doubt about the theoretical case made for the efficacy of the invention’. He then cited INTERVET7 to support the proposition that there had to be something in the patent itself, even if only the theoretical case for its efficacy. That theoretical case will then be sufficient without experimental evidence, only where there is no substantiated doubt.
Lord Sumption’s requirements
The test put forward by Lord Sumption can therefore be summarized as follows:
Can the skilled person reading the patent in light of their common general knowledge determine a biological mechanism that is specifically involved in each therapeutic effect claimed by the patent?
If yes, does the patent specification contain experimental data in relation to a direct effect on that mechanism, and would those data lead the skilled person to believe the claimed compound(s) had a reasonable prospect of affecting that mechanism?
If no, are there other reasonable scientific grounds for expecting that the claimed compounds might well have the claimed therapeutic effect, and in the context would the skilled person consider there to be no substantiated doubt as to whether the claimed compound(s) would have such an effect?
Question 3 allows those patentees who have elected to file a patent without relevant in vitro data the possibility of providing an explanation as to why, notwithstanding the lack of such data, they are suitably confident in the case for the therapeutic efficacy of the drug.
It is important to note that Lord Sumption makes it explicitly clear that if in vitro experimental data are to be used to justify a therapeutic effect for a range of compounds, then the experimental data must have an effect on an identifiable process known or shown to be involved in the disease. This is not a requirement for demonstration by the patent of a therapeutic effect for those compounds. What however is required is that somewhere between provision of the compounds and the treatment of the disease the patentee has made a technical contribution to justify the grant of the monopoly. That technical contribution does not have to come from the same information that makes the invention plausible.
Where is the need for a technical contribution?
In some very rare instances, the patentee might be able to justify its monopoly solely by disclosing a scientific reason, but the case would need to leave no room for substantiated doubt. An example might be by disclosing that there is a surprisingly conserved sequence homology between two distantly related viruses. Such information could justify a second medical use for an existing antiviral notwithstanding that the sequence data of each virus were previously known. In such a circumstance, adequate toxicological data for the drug would demonstrate safety in patients and there might well be no substantiated reason to doubt the claims of efficacy. Ordinarily, however, some data will be required for there to be a technical contribution.
The patentee’s technical contribution could, for instance, be by way of data or explanation in relation to the first question, linking a known metabolic mechanism affected by known classes of compounds to a previously non-associated therapeutic effect. An example of this could be the medication bromocriptine, developed in the 1960s, which affects dopamine signalling. As the link between dopamine regulation and insulin production became better understood, bromocriptine was trialled as a medication for type-2 diabetes.8
Perhaps more typically, the patentee’s technical contribution could be in relation to the second question, by demonstrating for the first time by experimental data the effect of claimed compounds on a metabolic effect already known to be involved with a disease. An example of this might be the development of an antiviral medication such as ZMapp, which was rapidly developed in response to the Ebola outbreak in West Africa. ZMapp is composed of three chimeric antibodies that enhance the immune response by neutralizing viral particles in the bloodstream. The science behind the effects of antibody-based medicines on viral diseases is well known, and therefore data showing that the antibodies bind the virus in vitro will give good reason to consider therapeutic efficacy is plausible. In the case of ZMapp, the compounds were rushed into clinical trials with special permission from the US National Institutes of Health. While the trial was unable to run to conclusion due to the waning of the Ebola outbreak, the initial results were indeed highly promising9; a patent on ZMapp would have been rightly justified based on in vitro data.
In vivo, in vitro, in silico?
Is it necessary that data relate to a metabolic effect in vivo, or are in vitro data enough? The answer should be the latter. Nowhere in Lord Sumption’s judgment is a mention of in vivo testing to be found. The rationale lies in considering Salk, which founds the fifth and sixth characterisations of plausibility in Lord Sumption’s reasoning at paragraph 37 of Warner-Lambert. When Salk talks about the direct effect on a metabolic mechanism, it is making that statement on the basis of in vitro experimental data, and it is clear that Lord Sumption considered the case on that basis, referring to that testing at paragraph 29 of the judgment.
The patent in Salk, WO 92/05447, related to an unusually formulated method claim designed to capture an assay system for identifying compounds that selectively disrupted the function of transcription factor AP-110 without causing a steroid hormone response. The patentee sought to introduce a Swiss-form claim that covered a hormone or hormone analogue identified by the process of one of the earlier claims, for treatment of AP-1 stimulated tumour formation, arthritis, asthma, allergies and rashes. The interaction of AP-1 and those conditions were known to the skilled person, but the patent did not disclose any compounds identified by the method disclosed, or any testing to show such compounds had an effect on the claimed metabolic mechanism. The Board therefore (correctly) refused the claim.
The board stated that in vitro data would suffice, ‘if there is a “clear and accepted established relationship” between the shown physiological activities and the disease’.11 What Salk says, therefore, and what Lord Sumption is using it to establish, is that in vitro testing will be sufficient where in the state of the art the metabolic mechanism is known to be specifically involved in the therapeutic effect.
Where that link between the mechanism and the therapeutic effect is not established, in vivo data may well be required to prove that the compounds do in fact have the claimed therapeutic effect. This does not necessarily require clinical trials.
There should in fact be no barrier (as indeed there has not been to date) to having in vivo data which only proves that a metabolic mechanism is specifically involved in a therapeutic effect, with entirely independent in vitro data establishing the effect of the claimed compounds on the mechanism. The in vivo data would not need to relate to a clinical trial of a drug but could be based on genome wide association studies or cohort studies on environmental risks, for example. This is, in practice, how many metabolic mechanisms become targets for drug development.
Applying the Warner-Lambert test
As a pilot study of the test formulated by Lord Sumption, we can use the facts of MSD v Shionogi.12 Claim 1 of Shionogi’s patent as granted described compounds by way of a Markush formula, covering an incredible array of compounds by reference to certain substituents:
Shionogi’s patent stated the compounds were:
for the preparation of a pharmaceutical composition;
for use as an integrase inhibitor and
for preventing or treating a viral disease.
Shionogi sought by conditional amendment to limit Claim 1 for treatment of HIV. In the specification, Shionogi had, however, described the compounds as being ‘useful as antivirus agent, antiretrovirus agent, anti-HIV agent, anti-HTLV-1 (Human T cell leukaemia virus type 1) agent, anti-FIV (Feline immunodeficiency virus) agent, and anti-SIV (Simian immunodeficiency virus) agent, esp., anti-HIV agent and an integrase inhibitor’.
Mr Justice Arnold applied the law of plausibility as it was then and considered that ‘[t]here must be a real reason for supposing that the claimed invention will indeed have the promised technical effect.’ Arnold J went on to quote Lord Justice Kitchin (as he was then) in Regeneron Pharmaceuticals Inc v Genentech Inc,13 who stated that the patentee ‘must show, for example by appropriate experiments, that the product has an effect on a disease process so as to make the claimed therapeutic effect plausible’.
Shionogi relied on disclosure in the specification in relation to just 10 or 12 compounds within the claims, disclosed in a table of data for 27 compounds. The data related to in vitro binding assays, designed to show affinity of a drug candidate molecule for the target enzyme, in this case HIV integrase.
Applying Question 1 to Shionogi’s patent: linking mechanism and disease
The Shionogi patent claims a variety of therapeutic effects in its claim to treat a viral disease. The skilled person would consider the viral diseases in question to include those mentioned in the specification. The skilled person is told in this instance that the metabolic mechanism is integrase inhibitory activity: the claimed compounds are asserted to inhibit the ability of the viral genome to integrate itself into the host genome and thereby replicate itself.
There might be some argument as to the difference between the different viruses named in the specification, but all of them use a viral integrase to replicate their genetic material by using the host’s genetic machinery. The patent therefore discloses the specific involvement of a biological mechanism in a therapeutic effect, namely reducing viral load by inhibiting replication, for all viruses that feature an integrase enzyme. These would therefore pass Question 1.
The claim to viral disease is, however, too wide. It encompasses non-retrovirus viral pathogens such as influenza which have no integrase enzyme in their replication cycle. In respect of treatment of influenza, the skilled person would not be able to determine from the patent a mechanism that could be specifically involved in any therapeutic effect. Claim 1 as granted would therefore not pass the first question. Claim 1 as proposed to be conditionally amended would, however, pass the first question, as it is limited solely to HIV.
Applying Question 2 to Shionogi’s patent: linking compound and mechanism
Under Question 2, the wider viral disease formulation of Claim 1 would again struggle. The experimental data provided relates only to HIV. If limited to treatment of HIV only then Question 2 requires consideration of the expert evidence.
In MSD v Shionogi, the judge found that the expert evidence established that the skilled person would consider the sheer number of compounds made it extremely unlikely that substantially all14 the compounds claimed would have the claimed efficacy. The data in the specification were also held to have been derived from suboptimal testing procedures that the skilled person would consider unable to provide solid support even in respect of the 12 compounds for which results were available.
It was therefore clear that the skilled person would not consider that the data in the patent provided a sound basis on which to suppose that substantially all the claimed compounds would affect the metabolic mechanism determined in stage 1, ie the inhibition of HIV integrase. One of the key issues arising at this stage of the enquiry is what can be demonstrated as to the relevant metabolic mechanism by the different tests available. Here, the tests were in vitro but that would not in itself cause any issues in satisfying Question 2, were it not for the limited data and deficient testing protocol with respect to the number of compounds claimed.
There will of course be cases where the skilled person would not be confident of the ability of any in vitro test to establish in reliable fashion the effect of a compound on a particular metabolic mechanism. In such cases, the patent would additionally need to give the skilled person reason to believe the tests conducted could be predictive of therapeutic efficacy.
Applying Question 3 to Shionogi’s patent: relying on scientific reasoning
Shionogi contended in its expert evidence that notwithstanding the limited experimental data, the patent disclosed a principle of general application. Shionogi looked to use the patent’s claims to define a pharmacophore (a set of functional groups and their relative positions that would give rise to a common effect among molecules possessing them) that could justify the claimed inhibitory effect. Shionogi’s expert claimed the skilled person would see the compounds covered by the Markush formula of Claim 1 to have four common structural features necessary for integrase inhibitory activity. That contention was rejected as being unsupported by the specification of the patent [216].
The judge also considered factors that we might now consider to be ‘substantiated doubts’ about the efficacy of the claimed pharmacophore, these included:
a deleterious effect on any possible antiviral activity caused by the orientation of certain substituted groups on the Claim 1 Markush formula ([220]);
an inconsistent effect arising where one of the carbon ring structures in the pharmacophore would not have the common effect unless it was aromatic ([214]); and
compounds with toxic substituents, metabolically unstable compounds, highly lipophilic compounds and high molecular weight compounds ([257]).
In the face of these objections, which were not addressed in the patent, scientific reasoning alone was never going to make the claimed invention plausible. This might be different where the patentee provides a valid pharmacophore and is able to explain how it will interact with an active site and why it will do so selectively on the basis of some kind of structure–activity relationship. However, this level of knowledge will almost never be acquired without some kind of in vitro testing, which will be a much more reliable way of demonstrating both plausibility in relation to sufficiency and providing a technical contribution.
A notable exception to the need for provision of in vitro data that will be of growing importance is in silico data: computer modelling in drug design. Systems for machine learning and assessment of potential drug targets are growing more and more sophisticated. There should be no barrier in theory for a patent to be granted based entirely on scientific reasoning drawn from in silico testing, as and when we reach a time when the skilled person would think such testing would provide reasonable scientific grounds for expecting that the claimed compounds might well have the claimed therapeutic effect.
Even statistical modelling (or artificial intelligence) may provide sufficient information to give reliable scientific grounds to make the therapeutic efficacy of a compound plausible. This may be particularly likely to occur where the toxicology of the drug is already well known and it is being modelled for a second or later medical use. See, for example, the work undertaken in Project Rephetio15 using public data sets to make predictions on the possible clinical efficacy of repurposed drugs.
Location, location, location
Prior to Warner-Lambert, one of the great moving targets of the test of plausibility was the question of where it should appear. That has not been explicitly clarified. Where have we looked at plausibility in the past in the English courts and the EPO can be seen in The Venn diagram in Figure 116, which sets out the principle heading under which the issue was considered by the highest court or appellate body in each case.
Where plausibility has been looked at in the context of obviousness, this has been on the basis of AGREVO, which transposed the requirement for the patentee’s monopoly to correspond to and be justified by its technical contribution from the law of sufficiency. The Board of Appeal in that case acknowledged the transfer of jurisprudence (at 2.2.2 and 2.2.3 of that decision), as Lord Sumption recognized in his own speech.
At paragraph [23] of his speech, Lord Sumption sets out the difference between the application of the law of sufficiency and the law of obviousness as follows:
The Technical Board of Appeal treats the condition of sufficiency under EPC article 83 as satisfied if it is possible to work the invention across the scope of the claim from the information in the specification, interpreted in the light of common general knowledge at the priority date. It addresses the broader question whether the disclosed contribution to the art is commensurate with the monopoly claimed under EPC article 56, in the context of inventive step. In that context, its case law requires the formulation of a problem which the claims of the patent could be said to solve: see T 939/32 AGREVO/Triazole sulphonamides [1996] EPOR 171. It imports a requirement that the patent should disclose not just what the invention is and how to replicate it, but some reason for expecting that it will work. Plausibility was the standard to which the patentee was expected to demonstrate this.
This paragraph does not clearly articulate the stage of enquiry at which the plausibility objection should now be considered. What we do know from both paragraphs [17] and [37] of the judgment is that the plausibility test has the same purpose in both contexts.
By way of a practical example, we can take the case of Idenix v Gilead. Idenix concerned a patent for a very large number of compounds professing to have inhibitory activity with respect to the DNA polymerase of the Flaviviridae family of viruses (such as Yellow Fever, Dengue and Zika, viruses spread by ticks and mosquitoes).
Plausibility was principally considered by the Court of Appeal in the context of obviousness, with Lord Kitchin stating at paragraph [104] that ‘Gilead contended that the claims in issue were invalid for obviousness because they made no technical contribution to the art. It was, [Gilead] continued, simply not plausible that substantially all of the compounds falling within the scope of these claims would be effective against Flaviviridae.’ In the EPO’s problem–solution approach to the assessment of inventive step, the compounds failed not because that step was obvious, but because there wasn't a step at all. In the words of Arnold J at first instance ([451] on):
‘the Patent contains no experimental data to suggest that any of the claimed compounds may be effective’;
‘the Patent contains no rationale for the assertion that the claimed compounds may be effective’; and
‘the specification adds nothing to the common general knowledge of the skilled team’
The sufficiency perspective on the issue is that the patentee is claiming there to be a therapeutic effect for these compounds, but is that effect plausible to the skilled person based on the disclosure of the patent, read in light of the common general knowledge?
In a system where the problem–solution approach is not commonly used,17 it may now be more helpful to reserve the question of plausibility to the context of sufficiency. If the claim is determined to be plausible according to Lord Sumption’s approach, it is then necessary only to identify where the patentee’s technical contribution lies: most likely in connecting the metabolic mechanism to the therapeutic effect or connecting the claimed compounds to the metabolic mechanism. If that much is clear, the patent will be plausible both in the context of insufficiency and in the context of inventive step.
In relation to industrial applicability, the Supreme Court in Warner-Lambert has left the decision of the Supreme Court in Human Genome Sciences v Eli Lilly18 untouched, though it should be noted that, at [17] of the judgment, Lord Sumption states that the ‘principal conditions of validity, novelty, inventive step, industrial application and sufficiency are all, in one way or another, directed to satisfying [the patent bargain principle]’. Given how deeply Lord Sumption draws on the principle of the patent bargain in framing his statement on the law of plausibility, Warner-Lambert will certainly be relevant in any future cases where issues arise in relation to plausibility in industrial application.
Patentee practice
Patentee practice on the greater scale is unlikely to change: pharmaceutical patenting is driven on a global basis and international patent practice will not be moved by the Supreme Court’s decision. The timing of patent filing will continue to be driven by the US market and intelligence on the research progress of competing programmes. Pharmaceutical companies will continue to file at the EPO at similar points in their research. There is no reason the principles of the Warner-Lambert decision should not apply to EPC 2000 claims and first medical use claims of otherwise known compounds, howsoever phrased. In the first judgment on the issue The Hon. Mr Justice Arnold stated that such an approach was common ground between the parties.19
What would perhaps be a welcome development from the Court’s perspective is a more upfront attitude in patent applications as to the reasons the research is being carried out. As Lord Sumption says at [23] of Warner-Lambert, the plausibility concept is a gift to innovators: it exempts them from providing data on therapeutic efficacy, in recognition of the impossibility of conducting the confidential clinical trials this would necessitate. It must, however, be admitted that many patentees file significantly before this point.
Take the example of Salk. The patentee provided to the EPO the fruits of its later work, showing that the compounds of Claim 1 were later identified and that they did indeed have an effect on AP-1 stimulated transcription. While the Salk Institute never received the Swiss-form process claim they sought, they were ultimately granted a patent by the EPO, EP0552202B, which included the method claims relied on in creating those compounds.
In that case, identification of even a few compounds by the method claim in question could have justified the additional Swiss-form claim. As the identification procedure proposed included an AP-1 assay, the results of that assay may have been enough to render the claimed therapeutic effects on AP-1 mediated conditions plausible.
It is hard to believe that by the date of filing of the priority document not a single compound had been identified by the claimed methods, given the later successes. The data might be rough and ready, but it could be included. This is not to advocate a ‘throw-it-all-in’ approach to patent drafting, but only to propose that the UK courts may be more lenient in relation to plausibility where they are able to understand why a patentee was really pursuing the research at the date of the claimed invention.
Conclusion
The application of the new test of plausibility will undoubtedly take some time to bed in to UK jurisprudence. There is no reason it should impose an intolerable burden on patentees, and the lower courts will likely resist any attempt to construe the decision in that way. The summary proposed in this article is just one perspective on the Supreme Court’s decision: there are very strong arguments to be made, on behalf of both patentees and producers of generics, which are not canvassed here.
It will be interesting to see whether any synergy emerges between the decisions of the Supreme Court in Warner-Lambert and in Actavis v Lilly [2017] UKSC 48. As the law stands, a patent only needs to be rendered plausible in relation to what is claimed as a matter of ordinary interpretation, not in relation to any extended claim scope under the principle of equivalents. This may well provide an avenue for the establishment of enhanced claim scope by virtue of post-published evidence in relation to linked therapeutic conditions.
Footnotes
[2018] UKSC 56.
Case T 609/02 SALK INSTITUTE FOR BIOLOGICAL STUDIES/AP-I Complex (2004) ECLI:EP:BA:2004:T060902.20041027.
In a general sense, the word ‘metabolic’ should simply be read out of this language or replaced with biological.
Rose Hughes, writing on the IPKat blog in ‘No Pain, No Gain: Plausibility in Warner-Lambert v Actavis’ (IPKat, 26 November 2018) <http://ipkitten.blogspot.com/2018/11/no-pain-no-gain-plausibility-in-warner.html> accessed 1 March 2019, rightly points out the difficulties in relation to plausibility across the claim scope where therapeutic efficacy coincides on a limited basis with disease sub-types, e.g. HIV-1 only. The best answer to this issue based on the Supreme Court’s decision is that inefficacy against claimed disease sub-types would only arise as an issue of sufficiency in relation to the state of the art known by the skilled person, i.e. the patentee is not obliged to research or disclose any basis for differential efficacy within an umbrella indication, albeit that the patent may be rendered insufficient if the same is known in the art and not addressed in the patent.
Case T 578/06 IPSEN PHARMA/Prolonging survival of transplanted pancreatic cells (2011) ECLI:EP:BA:2011:T057806.20110629.
The Board’s description of WO 97/37675 as disclosing a technical explanation of the effect of the claimed compounds in extending the life of transplanted pancreatic islets could be considered generous, if not disingenuous. Other than the patent’s disclosure that both the agonist and the cells are in the proposed model organisms at the same time, there does not appear to be much to draw them together; the Board may have been overly swayed by the post-published evidence.
Case T 0716/08 INTERVET/Infectious salmon anaemia virus vaccine (2010) ECLI:EP:BA:2010:T071608.20100819.
Ralph A DeFronzo, ‘Bromocriptine: A Sympatholytic, D2-Dopamine Agonist for the Treatment of Type 2 Diabetes’ (2011) 34(4) Diabetes Care 789.
The PREVAIL II Writing Group, for the Multi-National PREVAIL II Study Team, ‘A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection’ (2016) 375(15) The New England Journal of Medicine 1448.
A transcription factor is a DNA-binding protein that affects gene expression. AP-1 is known to have an important role in multiple stages of the cell life cycle, including cell-type differentiation.
Case T 0158/96 PFIZER/Obsessive-compulsive-disorder (1998) ECLI:EP:BA:1998:T015896.19981028.
[2016] EWHC 2989 (Pat).
[2013] EWCA Civ 93.
‘substantially all’ is the test used by Lord Kitchin in [107] of his judgment in Idenix v Gilead [2016] EWCA 1089, which was not considered by the Supreme Court in Warner-Lambert by virtue of the nature of the claims.
D. S. Himmelstein and others, ‘Systematic Integration of Biomedical Knowledge Prioritizes Drugs for Repurposing’ (2017) 6 eLife e26726.
Case T 0409/91 Exxon/Fuel Oils; Case T 0939/92 AGREVO/Triazole sulphonamides [1996] EPOR 171; Case T 1329/04 JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE/Growth differentiation factor-9; Case T 1437/07 ALLERGAN/ Botulinum toxin for treating smooth muscle spasm; Case T 950/13 BRISTOL MYERS SQUIBB/Dasatinib in the treatment of chronic myelogenous leukaemia; [2013] EWHC 1737; Regeneron (n 13). Regeneron v Genentech [2013] EWCA Civ 93; Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737 (Pat); Hospira v Genentech [2014] EWHC 3857 (Pat); GlaxoSmithKline v Wyeth Holdings [2016] EWHC 1045 (Pat); Actavis Group PTC EHF & Anor v Eli Lilly and Company [2015] EWHC 3294 (Pat).
As to why, see Jacob LJ’s discussion of the issues in application of the problem–solution approach at [25]–[50] Actavis v Novartis [2010] FSR 18 (CA).
[2011] UKSC 51.
As supported now by paragraph [523] of Eli Lilly v Genentech [2019] EWHC 387 (Pat), handed down after this article was submitted.
