Plausibility hurdle in the UK shifted up a notch, as invalidity of BMS patent confirmed by Court of Appeal
22 May 2023
The UK Court of Appeal (CoA) confirmed the invalidity of Bristol-Myers Squibb (BMS)’s apixaban patent on 4 May 2023.1 The appeal decision centred on the question of plausibility and is the first UK decision to consider plausibility since the EPO Enlarged Board of Appeal’s decision G2/21.
The CoA held that BMS had not presented sufficient disclosure in the patent to show that the so-called “patent bargain” had been fulfilled, i.e., that BMS had disclosed the invention completely enough that the public can have the benefit of it when the patent expires. Notably, this decision is the first case in which the CoA has held a patent with a single claim to a pharmaceutical compound to be invalid based on the concept of plausibility.
BMS owns EP1427415 and a corresponding supplementary protection certificate (SPC), covering the compound apixaban that the company markets under the brand name Eliquis®. Apixaban is an inhibitor of Factor Xa and can be used for the treatment and prevention of blood clots.
Revocation proceedings were brought against BMS by generic drug manufacturers Sandoz and Teva, on the basis that the patent was invalid for lack of inventive step and insufficiency. The insufficiency attack argued that the patent did not make it plausible that apixaban would have any useful Factor Xa inhibitory activity. The UK High Court examined the issue of plausibility and, in April 2022, determined that the patent and the corresponding SPC were invalid for insufficency based on a lack of plausibility. BMS appealed.
The CoA upheld the High Court decision and rejected BMS’s appeal.
In doing so, the CoA relied on previous case law (Warner-Lambert v Generics2) for guidance on plausibility. The Supreme Court in Warner-Lambert held that a patentee is required to demonstrate that the specification discloses some scientific reason why the implied assertion of efficacy in the patent claim is true. Whilst experimental data is not necessarily required, a bare assertion or mere possibility of therapeutic efficacy is not enough. The Supreme Court in Warner-Lambert held that whilst post-filing data may be admissible in a dispute about sufficiency, the purpose for which they are admitted is strictly limited either to confirm the plausibility of the therapeutic use or to refute a challenger’s contention that it does not actually work. Post-filing data cannot, however, be used as a substitute for sufficient disclosure in the specification.
While BMS argued that the present apixaban case was factually dissimilar from Warner-Lambert, the CoA determined that it was bound by Warner-Lambert, with the recently issued EPO decision G2/21 not warranting a departure from this case.
1 Sandoz and Teva v Bristol-Myers Squibb  EWCA Civ 472
2 Warner-Lambert Company LLC v Generics (UK) Ltd (t/a Mylan) & Anor  UKSC 56
As discussed in our recent article, the EPO Enlarged Board of Appeal in G2/21 focused primarily on the relevance of plausibility to the assessment of inventive step. However, touching upon sufficiency of disclosure, they also stated that “In order to meet the requirement that the disclosure of the invention be sufficiently clear and complete for it to be carried out by the person skilled in the art, the proof of a claimed therapeutic effect has to be provided in the application as filed, in particular if, in the absence of experimental data in the application as filed, it would not be credible to the skilled person that the therapeutic effect is achieved. A lack in this respect cannot be remedied by post-published evidence”.
Accordingly, the CoA in the present case confirmed that post-filing data cannot be used as a substitute for sufficient disclosure in the specification. The specification of EP1427415 had no embodiment specifically directed to apixaban (instead, large numbers of compounds were disclosed as preferred embodiments by way of broad generic formulae and lists of compounds), and the effectiveness of apixaban as a Factor Xa inhibitor was only established in post-filing clinical trial data. The Court therefore held that there was nothing in the application supporting the assertion that apixaban is a Factor Xa inhibitor at all. As such, the CoA upheld the High Court decision and dismissed the appeal.
The failure to render a claimed invention plausible when drafting an application can have serious repercussions. Determining how much technical evidence is required on filing to overcome the plausibility hurdle requires careful attention. In the pharmaceutical and biotechnology sectors, which are highly competitive, a balance needs to be struck between filing too soon with limited supporting evidence and potentially not achieving “plausibility”, and filing too late with more data but potentially losing the advantage over competitors.
Heather West & Nicholas Jones
Life Sciences & Chemistry group
This publication is a general summary of the law. It should not replace legal advice tailored to your specific circumstances.
© Withers & Rogers LLP May 2023