29 January 2025

NL District Court holds EP 2653873 of Biogen on DMF (Tecfidera) invalid

29 January 2025

On 22 January 2025, the District Court of The Hague handed down its judgement in the final relief proceedings initiated by Biogen against Sandoz, Polpharm, Neuraxpharm and Mylan (collectively referred to as “the Generics”). It ruled that EP 2653873 (“EP 873”) of Biogen on dimethyl fumerate (DMF, marketed as Tecfidera®), is invalid. EP873 protects the use of an orally administered pharmaceutical composition containing the active ingredient DMF for treating multiple sclerosis (MS) with an effective daily dose of 480 mg DMF. DMF has been known since the 1990s as a drug for treating psoriasis.

Inventive step

Shortly after the Generics listed their generic 480 mg DMF products in the G-Standard (pricelist) for October 2022 and after health insurers designated some of these products as preferential in NL, Biogen sued  the Generics for infringement of EP 873. The Generics counterclaimed for revocation of Biogen’s patent, inter alia arguing that EP 837 lacked inventive step or sufficiency of disclosure (G2/21).

The Generics relied on a clinical study that demonstrated the efficacy of 720 mg DMF per day and the potential for a lower dose to also be effective for the treatment of MS. The clinical study became part of the prior art through two pre-priority date presentations called ‘Kappos I’ and ‘Kappos II’. In the proceedings, both Biogen and the Generics acknowledge that Kappos I and II are full prior art and disclose the use of DMF as an effective drug for the treatment of MS. Starting from Kappos I or II, the Court found that the only difference between Kappos I or II and EP 837 relates to the 480 mg per day dosage set forth in claim 1. During the oral hearing it was established that both parties found that the administration of DMF to treat MS at a dose of 480 mg per day is as effective as administration of 720 mg per day. Therefore, the Court considered that the objective technical problem that the patent tries to resolve is to find an alternative treatment for MS that is as effective as the state of the art, namely the administration of DMF of a dose of 720 mg per day. Biogen argued that the objective problem was to find an improvement in the oral treatment of MS, but the Court rejected this argument and held that – unlike the apixaban case – the patent application (parent patent) of EP 837 did not describe an improved treatment.

In addition, the Court found that the purpose of the patent application was not to find the best dose of DMF, but to screen for potentially MS-active substances similar to DMF. Agreeing with the Generics, the Court is of the opinion (5.39) that the skilled person, starting from Kappos I and/or Kappos II, and the general common knowledge,  knows that the efficacy (and therefore the effectiveness) of DMF is dose-dependent and that lower doses are also effective for the treatment of psoriasis. The skilled person would therefore have a reasonable expectation of success that this problem for an alternative dose could be solved in an obvious way by testing lower doses of DMF. Contrary to Biogen’s argument, the skilled person would then carry out those tests. In this way, with routine testing and thus without inventive effort, the skilled person would find that a dose of 480 mg per day has a therapeutic effect. Therefore, claim 1 of EP 837 is obvious. The two auxiliary requests filed by Biogen are also dismissed by the Court.

Sufficiency of disclosure

The Court also addresses the ‘squeeze’ that the Generics identified, namely that in case EP 873 would be found inventive (quod non), it lacks sufficiency of disclosure and is (also) invalid for that reason. The Court held that the patent or application must sufficiently disclose the subject matter allowing the skilled person to apply the invention over the whole range claimed by the patent without undue burden. Second medical use claims bring about that it must be tested whether the therapeutic effect of the composition and dosage regimen for the claimed medical indication (in this case MS) is disclosed in the application/patent or, in the absence thereof, is credible. In relation to G2/21, the Court states that if the desired technical effect is part of the claim, but the patent does not prove or at least make plausible that this technical effect is achieved by the teachings of the patent, nor does the person skilled in the art assumes this on the basis of the common general knowledge or the cited literature, then there is insufficient disclosure. The Court found that that the application says nothing about the efficacy of the claimed dosage of DMF in treating MS. Since the Court does not consider any experimental data other than Kappos I and II, EP 873 is lacks sufficiency of disclosure.

Parallel proceedings 

The decision handed down by the District Court of The Hague is the first decision in final relief proceedings to hold (the NL part of) EP 873 invalid. To date, only Sweden has ruled in final relief proceedings on (the validity of) EP 873. The Swedish Court found EP 873 valid and imposed an injunction on the generic companies. Earlier Biogen commenced several PI proceedings in various European countries. In the Czech Republic, Denmark, Latvia, Slovakia, Estonia, Ireland and Sweden, PI’s were granted. In contrast, in Austria, Belgium, Portugal, Slovenia, Italy, France, Spain, Estonia, Germany, Norway and Hungary, PI’s were rejected because the patent was found invalid on a preliminary basis.

Conclusion

It remains to be seen if the NL judgement on the invalidity of EP 873 is going to be followed by other European jurisdictions.

Author
M.H.J. (Marleen) van den Horst

Attorney at Law & Partner

Author
B. (Benjamin) Niemeijer

Attorney at Law & Partner