Rivaroxaban in the UK Court of Appeal: consideration of ethical barriers to invention

The Court of Appeal recently upheld Mr Justice Hacon’s finding that Bayer’s patent for a once-daily administration of rivaroxaban, an anti-coagulant medicine, was obvious. The unusual feature of this case was that there was no technical barrier to the invention, and the analysis considered whether the skilled team would have been held back by an ethical barrier by reference to the need for ethics committee approval of a Phase II trial.

A key takeaway from this decision is that ethical considerations are unlikely to form a standalone ground in the assessment of prospects of success for inventive step. However, the safety considerations for patients that fall within this ethical assessment are relevant, as the assessment of “success” for the usual test for obviousness would take such factors into account. 

Background

Rivaroxaban (trade mark: XARELTO), is Bayer’s largest selling drug, and the fourth best-selling drug in the world. Protection under the original patent for rivaroxaban (as extended by an SPC) expired on 1 April 2024. However this case concerned a further patent from Bayer claiming the use of rivaroxaban for the treatment of thromboembolic disorder, using a once-daily administration (EP (UK) 1,845,961, the “Patent”).  

Sandoz and a number of other pharmaceutical companies applied to revoke the Patent. If valid, the Patent would prevent them from supplying generic rivaroxaban for once daily administration, but not from supplying it for twice (or more) daily administration, following the expiry of the original patent and SPC protection. 

On 12 April 2024, Mr Justice Hacon revoked the Patent for lack of inventive step. The efficacy of once-daily administration had been disclosed in prior art conference posters reporting on Phase I trials. Hacon J held that, having read those posters, it would have been obvious for the skilled team to try such a dosage regime in Phase II trials. 

Bayer’s appeal

Bayer sought to appeal on a number of grounds. The key ground of note, and the unusual feature of this case, was the consideration of ethics as part of the usual assessment of whether there would be a reasonable prospect of success. 

The ultimate question was whether, having read the posters, the skilled team would have a reasonable expectation that a once-daily administration of a 30mg dose would be efficacious and safe. Given that the claim is not limited to a particular dose, the claim would be invalid if it would be obvious to try any size of dose once daily, with a reasonable prospect of success.
At first instance, in addition to the usual technical analysis accompanying the assessment of inventive step, Hacon J considered an additional “ethical” dimension. Although not raised by either party, this arose in his analysis because of uncertainty around the therapeutic window of rivaroxaban; administration of a range of once-daily doses could pose a risk of missing that window, thereby causing harm to patients, and could impact on whether or not an ethics committee would approve such a Phase II trial. 

Therefore, although there was no technical barrier to the claimed invention in this case, Hacon J additionally assessed “reasonable expectation of success” by reference to whether the skilled team would have a reasonable expectation of obtaining permission from an ethics committee to conduct a Phase II trial that included a once-daily regimen. 

Court of Appeal’s ruling

The Court of Appeal agreed with Bayer that on a strict legal analysis, ethics committee approval was not relevant to the assessment of prospects of success ([2024] EWCA Civ 562).  However, the safety considerations that went into Hacon J’s analysis effectively amounted to the same thing as the key question identified by the parties: namely, would the skilled team have a reasonable expectation that a once-daily regimen would be successful in terms of efficacy and safety? This is because “success” in terms of efficacy and safety in this case meant that the patients in the Phase II trial were not exposed to an unacceptable risk of being either under- or over-dosed. 

The court concluded that Hacon J had made no error in his assessment of obviousness. In light of the prior art posters, it was obvious to try a Phase II trial including a once-daily regimen, and the skilled team would have had a reasonable expectation that a 30 mg once-daily dose would be efficacious and safe.