Rituximab - Netherlands

On Feb 21, 2018, District Court the Hague handed down its decision in Rituximab case & revoked Dutch part of EP 2055313 patent for lack of inventive step.

Biogen holds EP 2055313 patent that relates to a ‘Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-CD20 antibody’.  Previously by a judgment of May 12, 2017, the preliminary relief judge rejected Biogen’s infringement claim because, according to his provisional judgment, there is a serious, not negligible chance exists that the patent is destroyed in a bottom procedure or becomes opposition revoked due to added matter.

Celltrion then initiated invalidity proceedings based on lack of inventive step which was the central issue here. Celltrion stated that EP’313 patent lacks inventive step based on McLaughlin which is the closest prior art along with other prior arts. Biogen said that McLaughlin does not see the treatment of CLL. McLaughlin deals with the treatment of lymphomas such as SLL and patients with CLL are explicitly excluded from research in McLaughlin. Court held that as explained the morphology, the immunophenotype and the molecular properties of tumor cells at CLL and SLL are the same (for this case is in the particularly relevant the equality of the CD20 proteins on the surface of the cells) In view of this, it cannot be said that McLaughlin is not real the starting point.

The difference measures of claims 1 and 3 of the EP’313 assistance request compared to McLaughlin are therefore 1) the application of rituximab for treatment of CLL and 2) the higher dose of 500-1,500 mg / m2. The technical effect of the different measures is an effective treatment of CLL patients with rituximab so that the objective technical problem can be formulated to provide effective treatment for CLL.

Court further said that McLaughlin first teaches the practitioner that the antigen CD20 occurs on more than one 90% of the surface of B cells in both lymphomas and chronic lymphatic leukemia (CLL) and that it is 'appealing for targeted therapy'. Expert testified that the finding of McLaughlin would prompt practitioner to try rituximab also in the treatment of CLL. Due to the higher amount of circulating B-cells, it would be logical to try higher doses, as also suggested by McLaughlin. Therefore practitioner would have felt comfortable to try higher doses on subsequent infusions due to the reported safety profile, which is very favorable.

Berinstein  et al is also an extra incentive for the skilled person to apply higher dosages to suit the treatment of SLL and therefore, as explained above, also CLL. The Biogen's defense that hinting at higher doses in Berinstein only applies to enlarged tum ears in the lymph ('bulky disease') fails. Because the practitioner would starts to use higher doses in more places general, and not exclusively in connection with 'bulky disease'. In the second place the doctor would recognize that the mechanism of action of rituximab at SLL and CLL would be the same and would certainly apply incentives in the context of SLL in the treatment of patients with CLL.

Court further held that Biogen has not stated that there would be other 'pointers-away' that would keep the practitioner from examining the use of rituximab in CLL patients at a higher dose than 375 mg / m2.

The conclusion is that the Dutch part of EP’313 will be destroyed, as advanced. This means that the other arguments that Celltrion has put forward, such as the claim that there is added matter, need no further discussion.