Wednesday, November 4, 2015

Gilead v Idenix: Overview and Utility

Gilead Sciences, Inc v Idenix Pharmaceuticals, Inc 2015 FC 1156 Annis J
            2,490,191 2,527,657 / sofosbuvir / SOVALDI

In his first outing as a judge in a patent case, Annis J has delivered a decision of Arnoldian proportions (outstripping Arnold J’s own effort in the parallel UK case by 313 paragraphs). The case turned largely on the facts, with the bulk of the decision taken up with a meticulous review of the evidence on each point. The decision is primarily concerned with Gilead’s attack on the validity of Idenix’ 191 patent, which was held to be invalid for lack of utility and insufficiency (though Annis J did hold the 191 patent would have been infringed by Gilead’s product SOVALDI (sofosbuvir) had it been valid). Idenix’ counter-claim challenging Gilead’s 657 patent for lack of novelty and wilful misleading was dismissed. This post provides background and discusses the utility attack on the 191 patent. Legally the most interesting point is that Annis J followed Rennie J’s holding in Apotex / esomeprazole 2014 FC 638 (blogged here), that the requirement to disclose the basis for a sound prediction in the patent itself applies only to claims for a new use, and not to compound claims.

In the early 2000s both Idenix and Pharmasset (which was subsequently bought by Gilead), were working on nucleosides for the treatment of the Hepatitis C virus. Idenix discovered that some known nucleoside analogues with a 2’-C-Me/OH structure had activity in in vitro assays against the HCV class of viruses [27]. In 2002 and 2003 Idenix filed the US applications which were the priority documents for Idenix’s 191 patent [18]-[21]. Despite having only synthesized and tested compounds with a 2’-C-Me/OH structure, Idenix’ application also claimed compounds with a 2’-C-Me/F structure. CIPO objected to the application for lack of unity of invention, with the examiner having identified 15 different genera encompassed by the 23 “Forumlas” identified in the application. Indenix responded by narrowing the scope to the class of “Formula IX” compounds, claiming the 2’-C-Me/F genus. However, the disclosure was not amended [22]-[24]. (Presumably these compounds were selected because by that point – 2009 – it was apparent that the flouro compounds had the most promise.) The application was then granted as the 191 patent. The important point to take form this history is that none of the compounds claimed by the 191 patent had even been synthesized, much less tested, by Indenix as of the priority date, and they were barely discussed in the disclosure. Idenix started trying to synthesize the 2’-C-Me/F nucleosides in early 2002, but did not clearly succeed until March of 2005.

In the meantime, Pharmasset, having spotted an apparent gap in an earlier Idenix application, also set about synthesizing a 2’-C-Me/F nucleoside in early 2003 and succeeded a few months later (in May 2003) [42]-[43]. In the same month, Pharmasset filed the US application which ultimately matured to the 657 patent (now owned by Gilead after its acquisition of Pharmasset). Gilead subsequently commercialized SOVALDI, which is covered by the 657 patent. Anticipating an infringement action by Idenix based on the 191 patent, Gilead sought a declaration under s 60(1) that the 191 patent was invalid on the basis of lack of utility, overbreadth and insufficiency. Idenix counterclaimed for infringement and for a declaration that Gilead’s 657 patent is invalid.

Utility of the 191 Patent
It was common ground that utility of the patent had not been demonstrated as Idenix admitted that it did not test any compound falling within the scope of the claims of the ‘191 Patent until March 2005. Idenix therefore relied on sound prediction [221].

Annis J began the utility analysis by noting if the patent contains a promise, utility will be measured against that promise, though he noted that such a promise must be clear and unambiguous [227]. I must admit, though, that it is not entirely clear to me what standard for utility was actually applied. The parties agreed that the 191 patent contained a promise that the compounds “are useful” in the treatment HCV infections, in humans and other hosts [231], and this is evidently higher than the minimum scintilla necessary to establish utility in the absence of a promise (potential use against HCV would likely suffice). Annis J also held that the patent promised a satisfactory therapeutic index [238], and effectiveness in combination with low toxicity [240]. All of this suggests that utility was assessed against a standard which is higher than the minimum which would otherwise be necessary. But Annis J then stated explicitly that “the ‘191 Patent makes no promise of any specific result or level of treatment,” and “Gilead must therefore, prove that Idenix has not demonstrated or soundly predicted a scintilla of utility” [241].

In any event, this point was moot because Annis J concluded on the facts that there was no basis for a sound prediction of any antiviral activity in a 2’-C-Me/F nucleoside prior to its synthesis [255]; the patent would therefore lack utility whether the standard for utility was a mere scintilla or something higher.

The key question on the facts is whether the activity of the 2’-C-Me/F compounds could be predicted from the known activity of the 2’-C-Me/OH compounds [253]. The evidence was “overwhelming” that the answer was no, largely because the 2’ down position was recognized as a highly conserved and selective position, and fluoride is an unpredictable substituent particularly regarding potential toxicity [284], [376]. This case illustrates that the fact that a particular candidate compound is worth trying does not amount to a sound prediction of success [319].

More interesting in terms of the development of the law is that Annis J, following Rennie J’s holding in Apotex / esomeprazole 2014 FC 638 (blogged here), held that the requirement to disclose the factual basis and line of reasoning for sound prediction in the patent itself applies only to “new use” inventions [378]-[381]. Because the claim in the ‘191 patent was to a compound, the heightened disclosure requirement did not apply [380]. (Annis J went on to hold that if he was wrong, and there was such a requirement, the disclosure in the 191 patent was not adequate to support a sound prediction of utility [412].) The holding that there was no such disclosure requirement was strictly obiter (as was Rennie J’s), as Annis J had already determined there was no factual basis at all, disclosed or not. Nonetheless, while Annis J’s discussion was brief, he did not adopt Rennie J’s position out of comity, but because he agreed with the reasoning [380]. This adds to the weight of authority, though the point will ultimately have to be decided by the FCA.

No comments:

Post a Comment