The District Court of The Hague has upheld a key formulation patent for Astellas Pharma's prostate cancer drug Xtandi, dismissing a revocation challenge filed by generic pharmaceutical company Synthon B.V. The January 22, 2025 ruling protects EP 3 725 778, which covers specific formulations of enzalutamide, the active ingredient in Xtandi used for treating prostate cancer.
Patent Protection for Complex Formulation Technology
The disputed patent protects a solid pharmaceutical composition comprising a solid dispersion containing amorphous enzalutamide and a concentration-enhancing polymer, specifically hydroxypropyl methylcellulose acetate succinate (HPMCAS). This formulation technology represents a critical component of Astellas' market position for Xtandi in European markets.
Synthon had argued that the formulation was obvious to skilled practitioners at the priority date, claiming it would have been apparent to formulate enzalutamide in amorphous form with a concentration-enhancing polymer as a solid dispersion. The generic company also challenged the patent on grounds of added matter, arguing that claims exceeded the scope of the original application.
Court Rejects Obviousness Arguments
The Dutch court firmly rejected both challenges, emphasizing the complexity and unpredictability of pharmaceutical formulation development. According to the court's analysis, several formulation strategies were available for poorly water-soluble compounds like enzalutamide, contradicting Synthon's assertion that skilled practitioners would only consider amorphous solid dispersion (ASD) approaches.
The judges noted that formulation technique selection depends heavily on the specific characteristics of individual active substances, meaning practitioners would not rule out particular techniques in advance. The court emphasized that interactions between polymers and active substances are critical factors that cannot be predicted without extensive empirical testing.
Empirical Development Process Deemed Non-Obvious
The court's decision highlighted the inherently complex and empirical nature of pharmaceutical formulation development. At the priority date, the court determined that skilled practitioners lacked sufficient scientific rationale to predict whether suitable alternative formulations for enzalutamide were feasible, whether suitable ASDs could be achieved, or whether such formulations could provide bioavailability comparable to existing Xtandi capsules while maintaining adequate physical stability.
The development process was characterized as involving numerous decisions and extensive research, including both in vitro and in vivo studies requiring significant time and financial investment with no guaranteed outcomes. The court concluded that practitioners would at most begin such endeavors with hope for success but would have no reasonable expectation of success without substantial technical evidence.
Broader Patent Landscape and Ongoing Litigation
This decision represents the latest development in extensive patent litigation surrounding Xtandi. The European Patent Office Opposition Division previously upheld the same patent in May 2024 following challenges from eleven opponents, including Synthon. However, an appeal against that decision remains pending before the Technical Boards of Appeal.
Synthon has filed additional nullity actions against the patent in Italy and Spain, indicating continued challenges across multiple European jurisdictions. The basic patent EP 1 893 196 covering enzalutamide itself, along with related supplementary protection certificates, faces separate invalidity actions in the Netherlands and other countries including the UK and Germany.
Market Impact and Legal Representation
The patent dispute involves market-leading legal firms, with Synthon represented by Amsterdam IP boutique Brinkhof and Astellas defended by Hoyng ROKH Monegier. The outcome affects competitive dynamics in the European prostate cancer treatment market, where Xtandi represents a significant therapeutic option.
Medivation Prostate Therapeutics, co-owner of the patent, was acquired by Pfizer in 2016 after collaborating with Astellas on enzalutamide development. The company focused on developing therapies for diseases with limited treatment options before its acquisition.
