On June 5, 2015, the 13^thFederal District Court of Rio de Janeiro invalidated Astrazeneca’s patent BR PI0003364-2 covering Crestor® (rosuvastatin). The Judge, the Honorable Marcia Nunes Barros, agreed with the arguments submitted by the Brazilian Patent Office and National Sanitary Vigilance Agency (ANVISA) that the patent was obvious over the prior art. The Honorable Barros is the same Judge that recently issued a decision holding that ANVISA was allowed to examine patentability requirements during prior approval/consent analysis under Article 229-C of the Patent Statute.

According to the decision, the use of the tribasic calcium phosphate to stabilize statins was expressly recommended in the prior art document PT 547 000E. Even though the use of the term “potentially” in the prior art did not denote certainty regarding stabilization, according to the Court, this meant that tribasic calcium phosphate was “probably useful for stabilizing statins”.

Additionally, although the prior art document recited a pH value of at least 8, preferably 9, for the stabilization of statins, the Court held that this pH value related to the stabilization of fluvastatin and not rosuvastatin. The Court referred to the Handbook of Pharmaceutical Excipients, which stated that tribasic calcium phosphate had a pH value of 6.8 at 20% solubility.

The Court held that a person of ordinary skill in the art (POSITA) would have known from PT 547 000E that tribasic calcium phosphate could be used to stabilize statins. Therefore, because the pH of a stabilizing agent varies based on concentration, a POSITA would have been motivated to investigate using tribasic calcium phosphate to stabilize a statin (in other words, it was “obvious to try”). The Court found this to be true because the pH value of 8 recited in PT 547 000E referred to the stabilization of a different statin (fluvastatin) and not rosuvastatin. Other prior art, such as WO 97/23200, described using a pH value of between 7.0 to 8.0 to stabilize the HMG-CoA inhibitor, E)-3,5-dihydroxy-7-[4′-4″-fluorophenyl-2′-cyclopropyl-quinolin-3′-yl]-6-heptenoic acid.

Therefore, according to the Court, a PHOSITA at the time of the invention would have understood that different statins required different pH values for stabilization. Even though tribasic calcium phosphate only had a pH value of 6.8 based on its solubility data, the Court held that a PHOSITA would have been motivated to test tribasic calcium phosphate as a stabilizing agent for rosuvastatin.

Interestingly, despite the fact that the court-appointed expert issued a report concluding that the patent was valid, the Judge mentioned international standards for assessing inventive step, including the U.S. Supreme Court’s decision in KSR Int’l Co. v. Teleflex, Inc., in concluding that the technical solution presented in the patent was obvious to try and that there was a reasonable expectation of success.

This post was written with contributions from Roberto Rodrigues and Luiza Cotia.