Thursday, March 21, 2013

Utility / Obviousness Squeeze in Unpredictable Field

Novartis Pharmaceuticals Canada Inc v Teva Canada Ltd / zoledronate (NOC) 2013 FC 283 Hughes J
            ZOMETA ACLASTA / zoledronate / 1,338,895, 1,338,937

This NOC decision concerns a patent to zoledronate (‘937) and a separate patent to a broad class of compounds including zoledronate (‘895). Both patents were attacked for lack of utility, obviousness and insufficiency. The obviousness and utility issues were fairly straightforward on the facts, but the insufficiency argument raised two important points arising from Sildenafil 2012 SCC 60. This post will provide an overview and deal with the utility and obviousness points, and my next posts will deal with insufficiency.

Hughes J’s reasons are common to two applications brought by Novartis to prevent an NOC from being issued to Teva in respect of zoledronate, which is a bone mechanism regulator, used for treating conditions such as osteoporosis. The applications concerned ZOMETA and ACLASTA, which are different strength formulations. Both patents in issue relate to both formulations, and nothing in the decision turns on the strength of the formulations; the reasons would have been exactly the same if only one of the applications had been brought.

In the late 1960s researchers had discovered that a class of compounds known as bisphosphonates were useful (or perhaps more accurately, potentially useful) in controlling bone resorption, which is a bodily process implicated in bone diseases such as osteoporsis [84]-[95].

Research on second generation bisphosphonates focused on selecting molecules in the R1 and R2 position, and on “linkers” between these molecules and the geminal carbon. Both the inventors of the ‘895 patent, working for Boehringer, and the inventors of the ‘937 patent, working for Ciba-Geigy (now Novartis), developed a class of bisphosphonates with one CH2 linker molecule and a five-membered heteroaryl radical in the R1 position [57], [66]. The ‘895 patent claimed priority from a German application filed on 1 August, 1986, while the ‘937 patent claimed priority from a Swiss application, filed 21 November 1986 [9], [14]. The patents were placed in conflict under the old Act, and the parties settled so that Boehringer obtained the '895 patent with broad genus claims, and Ciby-Geigy obtained the '937 patent with claims to zoledronate alone. This is all by way of explaining why there are two patents in issue, rather than one patent with broad and narrow claims. Novartis listed both patents on the patent Register, presumably as licensee. 

The narrowest claim of the ‘895 patent, Claim 14, was the only claim in issue and it encompassed approximately 1.2 million compounds, one of which is zoledronate. The ‘937 patent had only two claims, to zoledronate and to zoledronate with pharmaceutical excipients.

The evidence accepted by Hughes J established that at the time of the filings, almost nothing was known about why bisphosphonates worked to inhibit bone resoption. It was not even known whether the mechanism was biological or physical-chemical. The target enzyme was not identified until the mid-1990s. Consequently, there was no structure / activity model allowing for prediction of the activity of any particular compound. Experimentally, small differences in structure could result in large differences in biological activity. This meant that each individual bisphosphonate had to be synthesized and tested in a biological model in order to assess its potency [153].

These factual findings led directly to the conclusion that neither invention was obvious [159], but also that Claim 14 of the ‘895 patent, to a broad class, was lacking in utility [167-68]: “In brief, the state of the art was at the empirical stage where compounds would have to be assessed individually.” This was a kind of obviousness / utility squeeze, favouring the individual compound claim; the lack of predictability that was the basis for a successful utility attack on the broad claim was also the basis for holding the individual compound claim to be non-obvious. As it happens, the ‘937 patent, which was held valid, expires on February 25, 2014, 3 weeks after the ‘895 patent, and an order of prohibition was granted accordingly.

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