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NL – Synthon v. Astellas and Medivation / Formulations of enzalutamide (Xtandi®)

27 Jan 2025

Synthon B.V. v. Astellas Pharma, Inc. and Medivation Prostate Therapeutics, LLC., District Court The Hague, The Netherlands, 22 January 2025, Case no. C/09/654337 / HA ZA 23-858

Astellas and Medivation have successfully defended EP 3 725 778 for formulations of enzalutamide in the Netherlands. Enzalutamide is the active ingredient in the drug Xtandi®, which Astellas markets in Europe for the treatment of prostate cancer. The District Court of The Hague dismissed the revocation claim filed by Synthon.

The grant of the patent had been opposed earlier but its validity was successfully defended before the Opposition Division, which, with its decision of 8 May 2024, maintained the claims of the main request and dismissed the oppositions. The case is currently pending before the Technical Board of Appeal.

Claim 1 of the main request (equal to claim 1 as granted) protects a solid pharmaceutical composition comprising a solid dispersion containing amorphous enzalutamide and a concentration-enhancing polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS).

In the Dutch proceedings, only the validity of the claims of the main request was defended. The court rejected Synthon’s arguments for revocation of these claims based on added matter and lack of inventive step.

According to the court, several formulation strategies were available for the skilled person for poorly water-soluble compounds like enzalutamide, thus dismissing Synthon’s argument that the skilled person would only consider an amorphous solid dispersion (ASD). The court noted that the choice of a particular formulation technique is highly dependent on the characteristics of a specific active substance, meaning that the skilled person would not have ruled out any particular technique in advance.

Additionally, the skilled person would have encountered many polymers as potential options. The court emphasised that the interaction between the polymer and the active substance is critical.

At the priority date, the skilled person according to the court lacked sufficient scientific rationale to predict whether a suitable alternative formulation for enzalutamide was feasible, whether a suitable ASD of enzalutamide could be achieved and whether such a formulation could provide a bioavailability comparable to that of Xtandi® capsules while maintaining adequate physical stability.

This process is complex and empirical, involving numerous decisions and extensive research, including both in vitro and in vivo studies, which require significant time and financial investment, with no guaranteed outcome. The skilled person would at most begin this endeavour in the hope of success (‘hope to succeed’), but would have no reasonable expectation of success without substantial technical evidence.

A copy of the judgment (in Dutch) can be read here.
A copy of the judgment (in an English machine translation) can be read here.