Court of Appeal confirms invalidity of Bristol-Myers Squibb apixaban patent

In the case against Sandoz and Teva, the UK Court of Appeal has confirmed the invalidation of a Bristol-Myers Squibb patent for apixaban. This follows an appeal against High Court proceedings, which took place last year. Proceedings are also ongoing in the Netherlands and Ireland.

In April 2022, the court invalidated EP 14 27 415, which covers a blockbuster drug and SPC for the treatment and prevention of blood clots. Generic drug manufacturers Sandoz and Teva had brought proceedings against Bristol-Myers Squibb (case IDs: HP-2020-000042 and HP-2021-000003). They intended to clear the way and launch a generic version of the lucrative anticoagulant drug. Recently, its market share has increased due to a heightened demand during the global COVID-19 pandemic.

In July 2022, the High Court also invalidated four further Bristol-Myers Squibb formulation patents, EP 32 46 021, EP 30 17 811, EP 32 51 660 and EP 32 57 500 (case IDs: HP-2020-000048; HP-2021-000009), after judge Richard Meade found them invalid for obviousness over the ‘Carreiro’ prior art. The party has appealed the decision to the Court of Appeal, but this is stayed pending the outcome of parallel EPO Technical Boards of Appeal proceedings.

Apixaban in medical use

While EP 415 expired last year, its corresponding supplementary protection certificate is valid until 2026. Both cover the compound apixaban, which the company markets under the brand name Eliquis. By thinning the blood, the drug can help treat thromboembolic disorders such as blood clots, especially following hip or knee surgery.

Initally, Sandoz and Teva had claimed invalidity of EP 415, arguing that the patent does not make plausible that apixaban has useful factor Xa inhibitory activity, or would be useful in therapeutic situations. Nor, say the parties, could medical professionals use the patented drug for any other purpose. Since apixaban’s success depends on the use of an Xa inhibitor, the court examined the issue of plausibility to determine invalidity. Ultimately, the court invalidated the patent and corresponding SPC for lack of plausibility based on insufficiency.

Plausibility hot topic

For the Court of Appeal, this current case concerning apixaban is the first time its judges have held a patent with a single claim to a pharmaceutical compound invalid for lack of plausibility. It is also the first UK decision to consider the concept of plausibility following the European Patent Office’s decision in G 2/21, which it handed down in March 2023.

Here, the Enlarged Board of Appeal confirmed that experimental evidence submitted after filing a patent can be used to prove a technical effect for patentability. This means that the board will, in future, place greater obligation on the EPO Examining Division to take a closer look at an invention.

Christopher Sharp

The Court of Appeal thus considered a view on patentability as taken by the EPO, rather than purely via national patent judgments. In the first instance, the judge had concluded that a previous case involving Warner-Lambert against Generics (UK), which the Supreme Court decided in 2018 (case ID: UKSC 2016/0197), provided enough guidance on how to apply issues of plausibility in consideration of patent validity.

In the present hearing, Bristol-Myers Squibb argued that the current apixaban case is factually dissimilar from the Warner-Lambert case, given that it concerned second medical use claims.

Rejecting four points

Gemma Barrett

At the Court of Appeal, the judges upheld the first-instance decision and rejected Bristol-Myers Squibb’s four appeal claims.

Firstly, the court determined that the present case cannot be distinguished from that of Warner-Lambert, meaning it must apply the plausibility criteria when determining whether the claimed invention involves an inventive step and is sufficiently disclosed.

Secondly, the court notes that the conclusion of G 2/21 does not justify a deviation from previous plausibility case law.

Thirdly, the court confirmed that disclosure of subsequent data cannot substitute sufficient disclosure in the specification.

Finally, it declared that Bristol-Myers Squibb had not presented sufficient disclosure for the judge to accept that it had fulfilled its so-called ‘patent bargain’, e.g. that it had successfully protected the patented invention so it might be dedicated to public use.

Daniel Brook

Second-round advisors

In the Netherlands, Bristol-Myers Squibb is fighting against Sandoz, with a preliminary injunction decision over apixaban pending. In Ireland the company is up against Teva, with Pinsent Masons also representing Teva in this jurisdiction. Partner Ann Henry leads the team from the firm’s Dublin office.

As such, Teva has once again turned to Pinsent Masons, its usual advisor in Europe, for the appeal proceedings. The London office of the mixed firm regularly acts for the generic drug company, which has previously also worked with Bristows.

London-based IP boutique Bristows worked with Sandoz, which is a long-standing client for the firm. As such, both Sandoz and Teva had separate legal representation at trial, but split the advocacy between them.

WilmerHale is coordinating the European litigation for Bristol-Myers Squibb while also representing the company in US proceedings. The team, led by Matthew Shade, appeared as counsel alongside Hogan Lovells in the UK. The latter regularly features in pharmaceutical cases in London, especially for innovator drug companies. Partner Daniel Brook led the case in this instance.

For Bristol-Myers Squibb
8 New Square (London): Daniel Alexander
11 South Square (London): Anna Edwards-Stuart
Hogan Lovells (London): Daniel Brook (partner); associate: Emma Fulton (counsel)
WilmerHale (London): Matthew Shade (partner)

For Sandoz
8 New Square (London): Michael Tappin
Three New Square (London): Stuart Baran, Alice Hart
Bristows (London): Gemma Barrett (partner); associate: Adrian Chew, Jonathan Ross

For Teva
8 New Square (London): Justin Turner
Three New Square (London): Thomas Lunt
Pinsent Masons (London): Christopher Sharp (partner); associates: Krishna Kakkaiyadi, Chris Dixon

UK Court of Appeal, London
Richard Arnold, Christopher Nugee, Mark Warby