Quetiapine Formulation Patent Obvious – U.K. High Court

On March 22, 2012, the U.K.  High Court of Justice, Chancery Division held that AstraZeneca’s patent covering an sustained release formulation of the anti-psychotic drug quetiapine was invalid for obviousness.  The relevant claims of the patent read:

1. A sustained release formulation comprising a gelling agent and [quetiapine] or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients.

14. A formulation according to anyone of claims 1-13 wherein one of the one or more pharmaceutically acceptable excipients is a pH modifier.

15. A formulation according to claim 14 wherein the pH modifier is sodium citrate.

The problem the patent sought to address was the purported difficulties in formulating a sustained release formulation of a soluble medicament like quetiapine.  Specifically, the patent disclosed:

[003] While there are numerous sustained release formulations  known in the art which utilize gelling agents, such as hydroxypropyl methylcelluloses, it had been found to be  difficult to formulate sustained release formulations of soluble medicaments and gelling agents, such as hydroxypropyl  methylcellulose, for several reasons. First of all, active ingredients which are soluble in water tend to generate a  sustained release product which is susceptible to a phenomenon known as dose dumping. That is, release of the  active ingredient is delayed for a time but once release begins to occur the rate of release is very high. Moreover, fluctuations  tend to occur in the plasma concentration of the active ingredient which increases the likelihood of toxicity. Further,  some degree of diurnal variation in plasma concentrations of the active ingredient has also been observed. Finally, it has  been found to be difficult to achieve the desired dissolution  profiles or to control the rate of release of the soluble medicament.

Justice Arnold concluded that these “problems” were illusory and that a a sustained release formulation was an obvious possibility in order to achieve once daily administration.  Any concerns over quetiapine’s high first pass metabolism would not have been sufficient to deter the skilled team from pursuing a sustained release formulation.  Further, the validity of claims 14 and 15 were not saved by the addition of a pH modifier like sodium citrate, since such additions were part of the common general knowledge.

Justice Arnold also considered  the decision of the District Court of the Hague involving AstraZeneca and Sandoz that only two weeks earlier had  found the Dutch counterpart to be non-obvious.  While expressing “regret that different European Courts considering the validity of the same patent should reach opposite conclusions”, the Dutch decision was not sufficient to convince Justice Arnold that his finding of obviousness was incorrect.

A copy of the English decision may be found here.