Tiotropium - Netherlands

On Dec 11, 2018, Court of Appeal affirmed the district court’s judgment that amended claims of patent covering inhalation capsule lack inventive step.

Previously, on Sep 07, 2016, District Court of the Hague revoked Dutch part of a European patent (EP1379220) held by Boehringer due to a lack of inventive step. Boehringer is the holder of European patent EP’220 for ‘Inhalation capsules with certain moisture content’, granted on 29 December 2004. EP’220 broadly claims capsule material that has reduced moisture content as a TEWS or halogen drier moisture content of less than 15%. In dependent claims it further narrow downs to less than 5%.  Teva initiated the proceedings for annulment of certain claims of EP'220. The District Court concluded that in absence of criticality of moisture content values, the technical problem is to provide an alternative capsule material for tiotropium to be administered by means of an inhaler. And this problem would be solved by the skilled person without inventive step in the light of an article titled “HPMC Capsules – An Alternative to Gelatin” (Ogura et al). Thus Teva’s claim for annulment of certain (amended) claims of EP’220 was granted.

Court of appeal while affirming the district court’s decision said that the tiotropium in powder form in a capsule for use in a DPI was already known from clinical trials on the priority date (described in Casaburi, among others). Boehringer has not substantiated why the average person skilled in the art, given the technical problems, would find it necessary to make some change. The difference measure to be taken into account only concerns the use of HPMC instead of gelatin as capsule material, without any specific benefit being attached to it. The conclusion is that the reduced moisture content as TEWS or halogen dryer moisture content of <5% (less than 4%, respectively, less than 2%, respectively) from amended claims 6 to 8, have no technical effect attached to it. It follows that the limit values ​​mentioned in claims 6 to 8 cannot be seen otherwise than as arbitrary choices, in which no inventive work can be based on the state of the art recognized. The court has therefore rightly conceded that the inventiveness cannot lie in those particular characteristics.

In addition, Boehringer's view cannot be accepted as correct, since it was known to the average person skilled in the art that disadvantages were associated with the use of gelatine capsules, in particular that such capsules become brittle if the moisture content of the gelatin drops below 10%. This allows the capsules to break easily during storage or use (especially during perforation) and thus become unsuitable for use. Preventing these problems places demands on production and storage conditions and / or packaging. Furthermore, it was known that gelatin can build up a static charge, as a result of which fine particles can stick to the inside of the capsule and the capsule is therefore not completely emptied. In addition - perhaps less, but not without importance - gelatine is an animal material, against the use of which some people object. In the opinion of the Court of Appeal, these drawbacks associated with the use of gelatin are sufficient motivation for the average person skill in the art to investigate the possibility of alternative capsule material, even though tiotropium itself is not sensitive to moisture.

Ogura states precisely that HPMC capsules are suitable for use with an inhaler and Boehringer has not substantiated why the average person skilled in the art would doubt this. Furthermore, it has not been stated or showed that doing research into perforations and the emptying properties of HPMC capsules would require more for the average person skill in the art than doing routine testing or otherwise producing an 'undue burden'. The fact that the average person refrains from research into the suitability of HPMC as capsule material because these capsules are not yet on the market and that a new market authorization is required for such a product cannot be accepted as well.

Therefore, this leads to the conclusion that the average person skilled in the art, starting from Casaburi and acquainted with Ogura, would find the solution to the problem at hand, without inventive work.