On 18 June 2025, the District Court of The Hague handed down a judgment in combined invalidity proceedings on the merits between generics Accord and Sandoz v Astellas and The Regents of the University of California (“The Regents”). Both Accord and Sandoz had argued that the enzalutamide compound and use patent and the corresponding SPC lacked inventive step. The District Court rejected the generics’ argumentation and upheld the patent. It ruled that the generics’ reasoning to get to the claimed invention involved hindsight.
The Regents is the proprietor of EP 1 893 196 B2 (“EP 196”), which claims the compound enzalutamide and the use of the compound in the manufacture of a medicament for use in a method of treating a hyperproliferative disorder, such as prostate cancer. EP 196 will expire on 29 March 2026, with subsequent SPC that will be valid until 24 June 2028. Enzalutamide was developed by the Regents together with Astellas and Medivation, Inc. Medivation is the exclusive licensee of EP 196 and Astellas is the exclusive sub-licensee, with the right to enforce the patent and SPC in the Netherlands.
Decision of the District Court
The invalidity argumentation was based on two documents from the prior art. Two of the inventors of EP 196, Charles Sawyers and Samedy Ouk, presented their research on potent antagonists for the treatment of hormone-sensitive and hormone-refractory prostate cancer at a conference in a presentation (“the Sawyers presentation) and a poster (“the Ouk poster”), before the application filing date of the patent. The Sawyers presentation and Ouk poster show the structure of compound RD162. The claimed compound enzalutamide, also known as RD162’, differs from RD162 in that the cyclobutyl group on the 5-position of the middle ring is replaced by a dimethyl group. The central question of these proceedings is whether, starting from RD162, there was any inventive step involved in arriving at RD162’.
The parties all agreed that the technical effect of RD162’ is that it is at least as effective as RD162. The generics argued that the skilled person would not make modifications in the right-hand part of the compound, as the Sawyers presentation taught the skilled person that this part is responsible for strong antagonistic activity, nor would the left-hand part be modified, as this had already been optimised previously. According to the generics, the skilled person, adopting a try and see approach, would replace the cyclobutyl group, which is placed on the middle ring of the compound, with a dimethyl group. In addition, the dimethyl group had already been disclosed in the Sawyers presentation and Ouk poster.
However, the District Court decided that these documents from the prior art show that the research at the time was focused on modifying the right-hand part of the compound and that in the compounds that had been synthesised as part of said research, both the left-hand side and the middle ring with the cyclobutyl had remained the same. The skilled person would understand this to be the result of optimisation.
The District Court reasoned that it is not relevant whether the skilled person could have made such modification, but whether the skilled person would have done so in the expectation of solving the underlying technical problem or in the expectation of some improvement or advantage. The dimethyl in one of the compounds in the prior art had been replaced by a cyclobutyl at the 5-position of the middle ring of subsequently synthesised compounds, and the skilled person would therefore conclude that the cyclobutyl is the optimal choice. The skilled person would see no reason to return to dimethyl at the 5-position of the middle ring. Thus, the prior art contains a pointer away from using a dimethyl group on the 5-position. Only with hindsight, the skilled person could come to the claimed invention. Therefore, the District Court dismissed the generics’ claims to nullify the Dutch part of EP 196 and the SPC.
