Plausibility after Warner-Lambert and G2/21
Summary
The ‘patent bargain’ is sacrosanct in any patent system ie the monopoly reward for the patentee disclosing his/her invention to the world for use after the bargain ends. With many pharma companies researching solutions for the same medical problems, there is pressure to file as early as they can, and obtain that monopoly on the next ‘blockbuster’ drug.
Doing so early runs the risk that what is claimed in the application as the technical contribution to the art, may not have sufficient support in terms of experimental or other data. The issue is then whether there is an inventive step disclosed or if the patent specification is sufficient. This is where the issue of ‘plausibility’ raises its head.
Notwithstanding the majority decision of the Supreme Court on the issue of plausibility in Warner-Lambert Co LLC v Generics (UK) Ltd [2018] UKSC 56, BMS sought to argue that a claim to a single compound should be assessed differently to the test applied to those for second medical use.
Lord Justice Arnold’s detailed consideration of the law, particularly his views on the (apparent) divergence between Warner-Lambert and the Enlarged Board of Appeal’s decision in G2/21 is an essential read for pharmaceutical companies, and the timing of claiming to have invented a drug.
Written by Paul A. Harris, Head of Litigation at Dehns.
Sandoz and Teva v Bristol-Myers Squibb [2023] EWCA Civ 472
Case background
BMS obtained a patent for lactam-containing compounds as a factor Xa inhibitor, which reduce the risk of blood clots and treat thromboembolic disorders. BMS subsequently obtained a SPC. Sandoz and Teva sought to invalidate the patent (and so the SPC) on the basis that the patent disclosed no inventive step or was insufficient, on the basis of plausibility. It was accepted that the date for assessing plausibility was the date of the original application. The closest prior art was an international application called WO 131, which was 326 pages long, and revealed various nitrogen containing heterobicycles as factor Xa inhibitors.
The parties agreed who the skilled person/team was, and their common general knowledge (‘CGK’). At the priority date, it was CGK that testing for potency of possible drug candidates could be achieved by off-the-shelf assays, and that the values of concentration and effectiveness (IC50 /Ki) must be in the nanomolar range: the 1-10 μM range was known not to be potent enough.
BMS’ Application set out detailed descriptions of preferred embodiments by reference to a number of broad Markush formulae. Specifically, Embodiment 8 was a list of 74 compounds, one of which was apixaban. Other embodiments listed hundreds of more compounds. However, and critically, there was no embodiment directed specifically to apixaban. BMS Application described methods of synthesising the claimed compounds.
BMS’ Application stated that compounds of the invention “are inhibitors of factor Xa and are useful as anticoagulants for the treatment or prevention of thromboembolic disorders in mammals” and their effectiveness “was determined” utilising the known assay. It then claimed that “…compounds were active if they exhibit a Ki of <10 μM. Preferred compounds of the present invention have Ki’s of <1 μM” and then proceeded to claim ever more preferred compounds ending with Ki’s of <0.001 μM. BMS’ Application stated, however, that effective inhibitors could have a Ki of less than 10 μM. Synthesis of the compounds was set out, the key one being Example 18: apixaban. Much was made by BMS of the amount that was synthesised (3g), arguing the skilled person would realise the amount implied this compound would have all the technical attributes. Finally, BMS’ Application set out claims corresponding to the Embodiments, but there was no direct claim to apixaban.
BMS’ EP(UK) as granted, specifically claimed apixaban as a single compound (or a pharmaceutically acceptable salt thereof), as Claim 1. Subsequently, clinical trials established the effectiveness of apixaban as a Xa inhibitor.
At first instance, the judge held the patent invalid and lacked plausibility. BMS appealed.
Decision
Arnold LJ reviewed all the relevant cases, including both Warner-Lambert and the later in time G2/21. BMS sought to distinguish aspects of both, and argue that the minority decision in Warner-Lambert (a second medical use case) which applied a less stringent test than espoused by Lord Sumption, should be adopted here because it was a single compound.
On the issue of approach, while postulating that of the majority in Warner-Lambert and that of G2/21 did not necessarily produce the same outcome, Arnold LJ stated he was bound by Warner-Lambert and did not consider G2/21 warranted him departing from it.
On the issue of applicability to single compounds, Arnold LJ stated that the underlying principles were applicable to single chemical compounds as to claims of classes of compounds and second medical use claims. The fundamental principle is that the scope of the patent monopoly must be justified by the patentee’s technical contribution to the art. When considering inventive step, it is necessary to consider what technical problem the claimed invention solves. If it is not plausible that the invention solves any technical problem then the patentee has made no technical contribution and no inventive step is involved.
For insufficiency, it is necessary to consider whether the specification sufficiently discloses the claimed invention. If it is not plausible that the invention solves any technical problem then the patentee has made no technical contribution and the specification does not disclose any invention. It follows that, in order for a claim to a single chemical compound to be patentable, the application must make it plausible, when read in the light of the skilled person’s common general knowledge, that the compound has the utility asserted for it. Moreover, it makes no difference whether the claim incorporates the use of the compound as a technical feature or whether the claim is simply to the compound per se and the assertion of utility is only to be found in the specification. This is because there is no invention in merely identifying a new chemical compound; invention can only lie in identifying its utility.
The Court upheld the judge’s decision and the appeal was dismissed.
Implication
The length of a description does not mean there will always be the necessary technical data, which justifies the therapeutic claims made by the patentee, and so their technical contribution to the art. While the external patent attorneys may ask for the relevant data, it could simply be with pressure of time and cost on the pharma company, it is not there and the application filed is the best that can be achieved. This is often in the expectation that challenging the patent would be risky. However, when large sums are at stake, and generics want to get in on the act, the risks will manifest themselves.
This is not the first time that a pharma company has been shown to have jumped the gun, or gone too broad in their claims: Regeneron v Kymab [2020] UKSC 27 is a case in point. Nevertheless, the cost benefit analysis, taking such risks into account, most likely still points to early filing: the opposition may well be kept off the grass until much later, and that it is potentially worth $billions.
