Rosuvastatin - Netherlands

On Jun 08, 2018, the Supreme Court of Netherlands upheld the decision of Court of Appeal & held that the AstraZeneca’s Crestor® patent is valid & would be infringed even though alternate salt is used.

Present case is dealing with the extent of the protection that is conferred by EP 0521471 patent. Specifically, the question is whether definition in the description of the claim feature “pharmaceutically acceptable salt” is limiting one. District Court, following an extensive substantiation held that the definition is limiting; but Court of Appeal reversed the decision & held that it is not. Resolution appealed to Supreme Court. Supreme Court followed Advocate General’s opinion of Nov 24, 2017 & dismissed the appeals in cassation.

Background:

Shionogi is a Japanese pharmaceutical company that is the holder of the supplementary protection certificate 300125 (SPC) for the Netherlands that has been granted for the product ‘Rosuvastatinum, if required in the form of a non-toxic pharmaceutically acceptable salt, in particular calcium salt’. The SPC, which is based on European patent EP 0521471 has been exclusively licensed to Astrazeneca B.V. In the Netherlands, Astrazeneca B.V. markets rosuvastatin calcium under the brand name Crestor®. The SPC expired on 29 June 2017. Claim 1 pertains to the compound rosuvastatin acid or a non-toxic pharmaceutical salt thereof. Specification in paragraph 7 defines the term “a non-toxic pharmaceutically acceptable salt” refers to a salt in which the cation is an alkali metal ion, an alkaline earth metal ion, or an ammonium ion”.

On 17 April 2014, Resolution initiated proceedings against AstraZeneca in accordance with the rules regarding accelerated proceedings on the merits in patent cases, in which Resolution inter alia moved that the District Court nullifies claims 1 and 2 of the Dutch part of EP 471 and the dependent claims, and further nullifies SPC 300125 to the extent that the subject matter of this SPC pertains to a compound other than rosuvastatin calcium and/or rosuvastatin sodium. Resolution developed Rosuvastatin product with zinc salt. By virtue of a judgment dated 15 July 2015, the District Court of The Hague nullified the SPC to the extent that the protection it confers extends to products other than the nontoxic pharmaceutically acceptable salts of rosuvastatin in which the cation comprises an alkali metal ion, an alkaline earth metal ion or an ammonium anion. The District Court held that the average skilled person would read the feature “a non-toxic pharmaceutically acceptable salt thereof” mentioned in EP 471 in conjunction with the definition that the invention previously discloses in paragraph [0007] of the description. AstraZeneca initiated an appeal against the District Court’s judgment. By virtue of a ruling dated 16 February 2016, the Court of Appeal of The Hague set aside the District Court’s judgment and dismissed Resolution’s claims.

Present appeal:

Resolution has brought an appeal in cassation against this ruling in time. On 16 December 2016, oral pleadings were held before the Supreme Court. The issue in this case is whether part of the protection has been “waived” in paragraph 7 of the description and in this scope, whether the waiver doctrine as formulated in the Van Benum/Kool ruling is still applicable law. Particularly, the question to be answered is how the claim feature ‘or a non-toxic pharmaceutically acceptable salt thereof’ in claim 1 of EP 471 must be interpreted.  Attorney General held that the waiver doctrine does not seem to be very compatible with the interpretation system of Article 69 EPC. This is in line with the system of Article 69 EPC and which could replace the waiver doctrine, is – within the scope of the point of view of the inventive idea – to allocate weight to whether and, if so how, according to the average skilled person there was an intention to limit the extent of the protection. In other words: according to the skilled person, was a specific limited extent of the protection deliberately chosen.  In view of the description considered as a whole, taking into account his general professional knowledge on the priority date, the average skilled person will understand that the invention pertains to a new group of statins – in particular the specifically claimed rosuvastatin – whose biological activity is superior to a known first generation of statins.

The Court of Appeal also used this method in present case. Specifically, average skilled person, based on his general professional knowledge, knows that the active ingredient at issue in this invention (just as in the earlier generations of statins) is the anion, which as such cannot exist independently or included in a tablet, but needs a cation “as a carrier”. The essence of the invention does not lie in the precise salts (anion-cation combinations), but in the new active anion. The two examples included in the description only describe the process for preparing two salt forms of rosuvastatin, without comparing these forms or subjecting them to further tests. Subsequently, the experiment was only performed with the sodium salt; the biological activity was not compared with the calcium (or other) salt, but with another statin known from the prior art. Therefore, finding a suitable salt form is not the inventive idea underlying the wording of the claim(s).

Also based on these findings, in contrast to the District Court, the Court of Appeal found that on the priority date, the average skilled person did not have valid reasons to assume that the patent proprietor only wanted protection for the salts of rosuvastatin mentioned in paragraph 7 and waived the broader protection that claim 1 offered according to its literal wording. This means that claim 1 must be interpreted such that the extent of the protection it confers extends to (in addition to the rosuvastatin acid) all non-toxic pharmaceutically acceptable salts of rosuvastatin, including those that are not mentioned in paragraph 7 of the description. Therefore, Court of Appeal did not err & appeals were dismissed.

Added subject matter:

Resolution took the position that claim 1 of EP 471 is invalid under “added subject matter” to the extent that the claim pertains to anything other than rosuvastatin sodium or calcium salt, because the original application allegedly does not directly and unambiguously disclose rosuvastatin acid or other salt forms to the average skilled person. The District Court held that only rosuvastatin acid constitutes added subject matter. However, Court of Appeal reversed & held that no added subject matter is involved, because claim 1 of EP 471 also extends to rosuvastatin acid as well as non-toxic pharmaceutically acceptable salts other than the sodium and calcium salt.” According to the Court of Appeal, the average skilled person reads salts and acids in the disclosure/is reminded of these in the Markush formula at position R4 of the original application. Thus, the Resolution’s appeal regarding added subject matter was dismissed.