Biogen v. Swiss Pharma, Court of Appeal of The Hague 10 September 2019

Biogen MA Inc (“Biogen”) is a pharmaceutical company marketing numerous medicinal products including Tysabri (or Antegren). The active pharmaceutical ingredient of Tysabri is natalizumab, which in turn is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. Swiss Pharma International AG (“Swiss Pharma”) is a subsidiary of the Polish-based Pharmaceuticals Works Polpharma S.A., a pharmaceutical company that manufactures and markets generic medicines.

Biogen is the proprietor of EP 1 485 127 titled “Administration of agents for the treatment of inflammation” (“EP 127”), claiming, inter alia, the use of an agent selected from an antibody or an immunologically active fragment thereof which bind to alpha-4 integrin or a dimer comprising alpha-4 integrin for preparing a chronically administerable pharmaceutical composition for reducing chronic pathological inflammation caused by multiple sclerosis wherein the agent is natalizumab to be administered every two weeks or monthly for a period of at least 6 months to the patient in an amount of 2 to 8 mg/kg patient.

As Swiss Pharma intends to enter the Dutch market with a natalizumab biosimilar falling under the scope of EP 127, it had sent a letter to Biogen in which Swiss Pharma had argued that EP 127 had been wrongly granted and asked Biogen to voluntarily revoke the patent or ask for an undertaking not to enforce EP 217 against Swiss Pharma. Biogen dismissed Swiss Pharma’ requests. In Germany, Swiss Pharma had initiated validity proceedings against the German designation of EP 127 which ended up in the revocation of this patent. With respect to the UK, Biogen had undertaken not to invoke the UK designation against Swiss Pharma.

In summary, Swiss Pharma argued that EP 127 was invalid due to lack of novelty and, alternatively, lack of inventive step. The relevant pieces of prior art that was being relied upon by Swiss Pharma were a number of documents that relate to the research that had been conducted with natalizumab as a possible treatment for multiple sclerosis at the end of the 1990s.

According to Swiss Pharma, the patent is anticipated by the so-called Conference Abstract, a summary of a presentation on research into MS treatment, which mentions the results of a Phase II clinical trial disclosing: “The patients in the three treatment groups were balanced for baseline demographic parameters; the mean age was 43,5 years, mean EEDS was 4.3 and 68% were relapsing-remitting and 32% secondary progressive. The mean number of new Gd-lesions was reduced by over 88% with Antegren compared to placebo; (p<0.0001). The reduction in Gd-lesions was apparent within 4 weeks of treatment. The proportion of relapse-free subjects was significantly higher in both Antegren treatment groups (=0.03). Antegren was well tolerated with a similar number of subjects experiencing treatment-emergent adverse events in each of the treatment groups. On a global measure of patient well-being, Antegren-treated patients felt significantly better compared to placebo (p=0.03).”

Biogen, who disputed the invalidity of EP 127, had argued that the feature “chronic pathological inflammation” was to be understood by the average skilled person as relating to the treatment of a certain aspect of MS, namely the treatment of “persistent enhancing lesions”. Biogen alleges that the effect on the “persistent enhancing lesions” is new and surprising in view of the prior art.

However, the Court of Appeal does not follow this reasoning and holds that this is an incorrect interpretation of the EP 127 as the persistent enhancing lesions is not mentioned and there is no reason to assume that the skilled person would under the patent as such. As this new technical effect (nor the mechanism of action of natalizumab which would have caused it) had not been disclosed, let alone being made plausible, Biogen is not entitled to rely on post-filed publications which support the alleged technical effect.

Therefore, the Court of Appeal of The Hague confirmed the first instance decision of the District Court of The Hague holding that EP 127 is invalid (in spite of a number of auxiliary requests that was filed by Biogen).

A copy of the decision (in Dutch) can be read here.

Headnote: Jeroen Boelens, NautaDutilh