Novartis and Freshfields defend Entresto at Dutch Court of Appeal

The Court of Appeal upheld the validity of Novartis’s EP 1 467 728, which protects the pharmaceutical combination of valsartan and sacubitril, as well as the related SPC. Synthon had argued that the patent lacked inventive step and should therefore be revoked, which would subsequently invalidate the SPC. This is the first ruling on the patent in Europe. Parallel proceedings are pending in the UK.

Valsartan is an angiotensin II receptor blocker (ARB) that prevents blood vessel constriction and fluid retention. Doctors mainly prescribe ARBs to treat high blood pressure, heart failure and chronic kidney disease. Sacubitril is an NEP inhibitor which helps lower blood pressure and has beneficial cardiac effects, particularly when combined with ARBs.

The two compounds form the basis of Novartis’s drug Entresto, which treats symptomatic chronic heart failure with reduced ejection fraction (HFrEF) in adults. The drug aims to reduce the risk of cardiovascular death and hospitalisation for heart failure.

Not obvious

The judicial panel comprised presiding judge J. I. de Vreese-Rood, Michel Bonneur and Rian Kalden, who also serves as a UPC judge. The Dutch Court found that, on the priority date, combining valsartan with sacubitril with a reasonable expectation of success would not have been obvious to a person skilled in the art.

While in general combinations of ARBs and NEP inhibitors were disclosed in prior art, this did not hold true for this specific combination. According to the ruling, ARBs and NEP inhibitors had significantly different pharmacological properties and the results of one combination could not simply transfer to another. The combination claimed in EP 728 therefore involved an inventive step. The judges also accepted that EP 728 credibly disclosed improved therapeutic effects compared to valsartan alone, without requiring proof of synergy.

The inventive step test applied by the Dutch court shows close similarities to the one applied by the UPC in Amgen vs Sanofi. The Court of Appeal’s dismissal upholds a decision from October 2023, when the District Court The Hague rejected Synthon’s nullity claim and confirmed the validity of EP 728 and its SPC.

Prior to the nullity suit, EP 728 survived opposition proceedings filed by Mundipharma. The latter withdrew the opposition in 2010.

Trusted advisors

Brinkhof led the revocation case for Synthon. The IP boutique has a long-standing relationship with the generic drug company and has advised it in several actions, most recently against Astellas over Xtandi. Partners Mark van Gardingen led the case for the Dutch pharma company in the appeal. Barbara Mooij and Eveline Lots assisted.

From Synthon’s in-house team Vice President Intellectual Property Litigation Dominique van de Kamp and patent counsel Arjanne Overeem and Michael Herschdorfer cooperated with the Brinkhof team.

Freshfields represented Novartis in both first and second instance proceedings. An Amsterdam-based team led by partner Rutger Kleemans handled the case. Ruben Laddé and Joyce van den Brink assisted. Patent attorney Jetze Beeksma of V.O. provided technical advice.

Internally at Novartis, Principal IP Counsel Denis Barbier led the case together with Principal IP Counsel Carmen Frigola-Deulofeu and Head Commercial IP for Novartis’s cardio, renal and metabolism division Christiane Marti.