Accord Healthcare Ltd., Accord Healthcare B.V., Sandoz AG v. The Regents of the University of California and Astellas Pharma Inc, District Court The Hague, The Netherlands, 18 June 2025, Case no. case number / docket number: C/09/654970 / HA ZA 23-903 and C/09/654975 / HA ZA 23-904
The Regents of the University of California and Astellas successfully defend a European patent relating to enzalutamide (Xtandi®) in the Netherlands
On 18 June 2025, the District Court of The Hague rendered judgment in invalidity proceedings started by Accord Healthcare and Sandoz versus The Regents of the University of California (the holder of European patent EP 1 893 196 B2 and SPC 300632 relating to the active ingredient enzalutamide) and Astellas (holder of an exclusive sublicense relating to the patent) on the other hand. Enzalutamide is the basis for the drug Xtandi®, a drug that has proven highly successful in the life-prolonging treatment of prostate cancer.
The androgen receptor (AR), which stimulates the growth of tumor cells, plays an essential role in the fight against prostate cancer. It is necessary to reduce the activity of the AR. A well-known treatment of the disease is, for example, androgen deprivation therapy, in which the AR is blocked by antiandrogens. In hormone-sensitive prostate cancer, overexpression of the AR can lead to hormone-resistant prostate cancer. Furthermore, it has been shown that in hormone-resistant prostate cancer, overexpression of the AR causes antiandrogens (such as Bicalutamide) to change from antagonists to agonists (an AR antagonist inhibits AR activity and an AR agonist stimulates AR activity).
Accord Healthcare and Sandoz argued that the patent was invalid due to lack of inventive step on the basis of a poster and/or slides allegedly presented at an international conference. Both documents disclose various compounds with better antagonistic activity than Bicalutamide, including compound RD162. The patent protects enzalutamide (referred therein as compound RD162′). The District Court held that it was not obvious to the average skilled person, based on either of the two documents mentioned, to replace the cyclobutyl at the 5-position of RD162 with a gem-dimethyl group in RD162′.
“5.39. With that, the curtain falls on the generics’ statements. Their attack fails because with retrospective knowledge of the invention, the focus is wrongly placed solely on substituting the R₁ and R₂ groups at the 5-position of the (middle) thiohydantoin ring of a cyclobutyl into a dimethyl. It follows from the above that the average skilled person would have no reason to make changes at the 5-position of the (middle) thiohydantoin ring in the sense that he would (‘would’) still change the ‘fixed’ cyclobutyl into a dimethyl. That he could (‘could’) do so, as indicated at the beginning of the reasonings, is not the test to be
applied.”
A copy of the decision (in English) can be read here.
