Court finds AstraZeneca patent to esomeprazole (NEXIUM) invalid for lack of sound prediction and obviousness
This was an application brought by AstraZeneca under the provisions of the Patented Medicines (Notice of Compliance) Regulations for an order prohibiting the Minister of Health from issuing a notice of compliance to Apotex for 20 and 40 mg esomeprazole magnesium tablets until after the expiry of Canadian Patent No. 2,139,653 (the ‘653 patent). If successful on the application, this would have prevented Apotex from marketing a generic version of NEXIUM in Canada for treating conditions wherein a reduction of gastric acid secretion is required until May 27, 2014. Apotex, on the other hand, sought early market entry by arguing that the ‘653 patent was invalid for lack of sound prediction, anticipation (or lack of novelty), and obviousness.
The ‘653 patent relates to an improved process for preparing highly optically pure esomeprazole, one of the enantiomers of the racemate omeprazole, that is stable against racemisation (i.e. recombination). Claim 8 was the claim at issue and could be read as claiming a salt (e.g. magnesium) of esomeprazole having an optical purity of 99.8% or greater. There was no provision as to utility (or use of the invention) in claim 8. This was an important fact, as the Court noted that where the invention relates to a new compound, utility does not need to be included in the claim, so long as it is described in the description portion of the patent. On the other hand, when the patent relates to a new use for an old, known compound, that new use must be set out in the claims. In this case, claim 8 was not directed to a new compound; it was directed to a previously known compound having a particular purity.
Moreover, utility of the compound was simply described in the description of the patent as follows:
It is desirable to obtain compounds with improved pharmacokinetic and metabolic properties which will give an improved therapeutic profile such as a lower degree of interindividual variation. The present invention provides such compounds, which are novel salts of single enantiomers of omeprazole.
However, nowhere in the patent, whether in the Examples or otherwise, was any information given to the person skilled in the art as to whether, in fact, the highly pure esomeprazole salt does give an improved therapeutic profile such as a lower degree of interindividual variation. Moreover, there was no evidence from any witness to say that there was anything in the disclosure of the ‘653 patent that would inform a person skilled in the art that the purified esomeprazole salt would fulfill this promise. As a result, there was a clear question as to whether the invention had a basis for a “sound prediction” as to utility.
The requirements for sound prediction are well established: 1) there must be a factual basis for the prediction; 2) the inventors must have as of the date of the patent application an articulable and sound line of reasoning from which the desired result can be inferred from the factual basis; and 3) there must be proper disclosure.
The facts of the present case did not show that as of the priority date, May 1993, or even the Canadian filing date, May 1994, that the inventors had either a factual basis for a prediction that an esomeprazole salt of a particular purity would have the utility indicated in the patent, nor did they have an articulable and sound line of reasoning for inferring such a result. In addition, clearly there was no proper disclosure in the patent in that respect. As a result, the patent was invalid for a lack of sound prediction.
As to anticipation, the question was, given that prior art German patent application DE 40 35 455 A1 (DE ‘455) described a process for separating the enantiomers of omeprazole (and salts) into “optically pure” fractions, did the description, particularly Examples 5 and 6 (incorporating Examples 1 and 2) “enable” what was claimed in claim 8 of the ‘653 patent, a purity of 99.8% (ee) or greater? In this respect, the Court found that to practice DE ‘455 “would at best only occasionally result in a product with the purity level stipulated in claim 8.” On this basis, there was no enablement such as would support an allegation of anticipation.
As to obviousness, the Court was satisfied on the evidence that, as of the claim date, May 1993, it was known that omeprazole could be separated into its enantiomers (+) and (-), that they would be useful, just as omeprazole was, in treating gastric problems, and that they could be processed in salt form with a salt such as magnesium. A purity of 95.6% (ee) for esomeprazole had been reported as having been achieved in the prior art, and such technique could have been used to increase that purity to 99.8% (ee) if desired. In the result, the ‘653 patent was also found to be invalid for obviousness.