Australia: Federal Court delivers significant judgment allowing launch of generic CRESTOR (rosuvastatin)

Introduction

Justice Jagot of the Federal Court of Australia has found three patents protecting AstraZeneca's CRESTOR (rosuvastatin) product invalid.

The revocation of the low dose HeFH and cation patents, subject to any appeal by AstraZeneca, opens the door for the many generic pharmaceutical companies with ARTG registrations (including those not party to the proceedings) to launch rosuvastatin products.

AstraZeneca has not yet announced an appeal against the judgment, but has issued a press release saying it is considering all legal options.

Of particular interest to originators and generics alike is the approach of the Court to the question of the "starting point" for the purposes of assessing inventive step. We consider this, and some other aspects of the decision, below.

Background

Rosuvastatin is a blockbuster statin, with total Australian annual sales of approximately $350 million.

An API patent, ie, a patent protecting the rosuvastatin chemical compound, was never filed in Australia. AstraZeneca does own a number of secondary Australian patents relating to rosuvastatin, including those asserted in this proceeding.

The generic parties, Apotex, Watson and Ascent, each attempted to launch generic versions of rosuvastatin in April 2012. AstraZeneca was awarded injunctions in late 2011 and early 2012 restraining the launch of these generic rosuvastatin products.

ARTG registrations for rosuvastatin products are also held by several other pharmaceutical companies.

Summary of the case

AstraZeneca asserted the following three patents against Apotex, Watson and Ascent.

• AU200023051 (low dose patent), relating to the use of a 'low dose' (most importantly, doses of 5 or 10mg) of rosuvastatin to treat hypercholesterolemia,
• AU2002214165 (HeFH patent), relating to the use of rosuvastatin to treat the condition heterozygous familialhypercholesterolemia (HeFH), a genetic condition that is characterised by hypercholesterolemia, and
• AU200051842 (cation patent), relating to a pharmaceutical formulation of rosuvastatin and an inorganic salt having a multivalent cation.
  Each of these patents is a 'secondary' patent.

Her Honour held that each of the three patents was invalid and liable to revocation. Her Honour also considered whether the patents would have been infringed if they were valid, and if a number of grounds for revocation asserted by the generics were not made out. A summary of Her Honour's conclusions is as follows:

Our note focuses on the reasons the asserted claims of each patent were found invalid on the grounds of lack of inventive step and novelty.

Inventive step

One of the key conclusions that Jagot J reached, relevant to the validity of each of the patents in suit, was the way in which the Court was to consider whether an invention claimed in a patent possesses an "inventive step". As this issue was of importance to each of the patents, it was considered before issues specific to those patents.

To be valid, a patent must possess an "inventive step". Under the Patents Act, an invention is considered to involve an inventive step unless it would have been obvious to a person skilled in the art of the relevant patent in light of the "common general knowledge" at that time, either separately from or together with prior art information (eg, a publication that would have been located through a literary search) that would have been available to them.

An important issue in a number of recent pharmaceutical patent cases has been whether knowledge of the pharmaceutical compound in issue can be assumed as part of the starting point for an invention if knowledge of that compound is not part of the "common general knowledge".

This is a significant issue relating to the validity of many pharmaceutical patents. It is particularly relevant to 'secondary' patents filed after disclosure of the pharmaceutical compound itself. Many of these patents are filed before the pharmaceutical has been marketed, and so it is relatively unlikely the compound will form part of the common general knowledge. A much higher hurdle is faced by a patent challenger if the relevant compound is not available as part of the "starting point" for the invention.

Jagot J held that the inventions identified in each of the patents in suit presupposed the existence of rosuvastatin. Knowledge of rosuvastatin was not, in view of the patents, part of the invention. This resulted in a lower threshold for the generic parties to demonstrate that each of the patents in suit lacked an inventive step (in which they were successful).

Recent Federal Court cases have differed in the approach taken to this aspect of determining the presence or absence of an inventive step. On Jagot J's reasoning, it is a case-specific matter to determine by reference to the specification. Applying Jagot J's reasoning, it may become relatively easier to revoke patents on the base of a lack of inventive step if they express a problem to be solved in relation to a particular pharmaceutical (which is common for secondary pharmaceutical patents).

Low dose patent

Novelty

The low dose patent was found to lack novelty when compared with documents referred to as the 471 patent and the Watanabe article.

The 471 patent, filed by Shionogi, is an 'API patent'. The 471 patent discloses a class of compounds suitable for treating hypercholesterolemia. The claimed class of compounds potentially included millions of different compounds including rosuvastatin. However, rosuvastatin was identified and given as a specific example of a compound suitable for treating hypercholesterolemia. The patent also disclosed a range of dosages for administration. The doses claimed in the low dose patent fell within these ranges. Therefore, the invention claimed in the low dose patent was disclosed in the 471 patent.

Jagot J contemplated that other compounds falling within the general class that were not specifically identified may not have been disclosed, however, given the very specific identification of rosuvastatin, that was not relevant.

The Watanabe article disclosed that rosuvastatin had greater activity than known statins pravastatin and lovastatin, and therefore greater potency in treating hypercholesterolemia. Watanabe did not expressly disclose the 5 to 10mg dosage range. However, Jagot J held that the skilled addressee of the low dose patent, armed with common general knowledge would have arrived at the claimed doses. The Watanabe article therefore disclosed the invention claimed in the low dose patent.

Lack of inventive step

Jagot J considered the relevant invention to be the discovery of a dosage range of a compound and that this invention was made on the assumption that the existence and nature of rosuvastatin was known. On this basis, her Honour held that the invention lacked an inventive step as it amounted to no more than the identification of a conventional starting dose for a compound within a known class for a known purpose.

Jagot J also held that, even if her view of the invention was incorrect, the low dose patent lacked an inventive step when compared with the 471 patent and the Watanabe article. The disclosure in both of these documents would have led the skilled addressee as a matter of course to try the claimed invention in the expectation "it might well produce a useful alternative to or a better result than currently achieved in the field". The existence of 11 (according to AstraZeneca) other potential statin candidates at the priority date did not detract from this conclusion.

HeFH patent

Novelty

The HeFH patent was found to lack novelty by reason of each of the following prior art disclosures:

• A SCRIP article that reported a study had recommended an aggressive approach to treatment of HeFH using statins, by reference to atorvastatin and simvastatin. The SCRIP article suggested that other "superstatins" in development, including rosuvastatin, could also fill the role.
• An open label extension study under which patients were prescribed rosuvastatin. This trial was preceded by a clinical trial comparing the effects of rosuvastatin and atorvastatin in patients with HeFH.
• The low dose patent, and a number of other publications, which disclosed use of rosuvastatin to treat hypercholesterolemia generally although not HeFH specifically. These were novelty destroying as the person skilled in the art would have therefore understood it could be used to treat HeFH.

Lack of inventive step

Her Honour considered the claimed invention to lie in using rosuvastatin (which was assumed to exist) as a method to treat HeFH. Her Honour also found that even if the invention didn't require the assumption of rosuvastatin's existence, rosuvastatin was part of the relevant common general knowledge for the HeFH patent. Given knowledge of the existence of rosuvastatin (either as an assumption on which the invention was based or through the common general knowledge), it was obvious to use rosuvastatin to treat HeFH.

Cation patent

Priority date problems

The cation patent claimed a priority date from a United Kingdom patent application (priority application) filed in January 2000. The generic parties successfully challenged the priority claim.

The cation patent had been significantly amended during the course of Australian prosecution, such that it was not entitled to claim priority from the United Kingdom patent.

The priority application related to a pharmaceutical composition of rosuvastatin and a tribasic phosphate salt in which the cation is multivalent. This composition was said to have advantageous stability. The priority application contained no reference to pharmaceutical formulations that did NOT include tribasic phosphate. However, none of the claims of the cation patent is limited to a composition containing a tribasic calcium phosphate salt – in fact, such a composition is expressly excluded from the claims. The cation patent was therefore not eligible to claim priority from the priority application.

Lack of novelty as a result of deferred priority date

Despite being unable to claim the priority date from the priority application, Jagot J held that the cation patent was not novel when compared to the priority application (as well as a number of related AstraZeneca patents validly claiming priority from it). These documents contained essentially the same disclosure as the cation patent.

Jagot J accepted AstraZeneca's argument that the cation patent claimed a pharmaceutical composition of rosuvastatin with a tablet coating comprising titanium dioxide and ferric oxide (inorganic salts in Jagot J's opinion with multivalent cations). Such a composition was disclosed in the priority application.

Lack of inventive step

Jagot J held that at the priority date, coatings containing titanium dioxide and ferric oxide were commercially available and commonly used (even if a compound being formulated had no stability issues). Her Honour held that there was therefore no invention in applying such a coating to a known compound. As the invention was found to presuppose knowledge of rosuvastatin, it was therefore not inventive to add such a coating to it. It was also accepted by her Honour that rosuvastatin was known by the deferred priority, and so similarly, it was not inventive to add a coating.

A copy of Jagot J's decision can be found here: Apotex Pty Ltd v AstraZeneca AB (No 4) [2013] FCA 162.

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