Novo Nordisk A/S et al. v. Caraco Pharmaceutical Laboratories, Ltd. et al.

Docket No. 2011-1223

June 18, 2013

Brief summary: Synergistic results could not overcome prior art regarding combination of metformin with drug having “a similar mechanism of action” as repaglinide. Inequitable conduct charges were overcome by “carefully-chosen language” in declaration and attorney arguments.

Summary: Novo appealed DC decision that claim 4 of its US 6,677,358 relating to a method for treating diabetes using a combination of repaglinide (an “insulin secretagogue” (induces release by pancreas)) and metformin (an “insulin sensitizer” (reduces liver glucose production)) was invalid as obvious and that the ‘358 patent was unenforceable due to inequitable conduct. At the time the application was filed, combination therapy using such compounds was common. During prosecution, claim 4 was rejected as obvious and overcome by an expert declaration purporting to show synergy between the two compounds. Caraco presented additional art to the DC that concluded that the skilled artisan would have expected from that art the combination to yield some synergy. Novo argued that the DC improperly shifted the burden of persuasion to Novo, Caraco’s evidence was insufficient, and that the examiner’s original finding should have been afforded deference. The FC panel disagreed because: 1) “[o]nce the challenger has presented a prima facie case of invalidity, the patent owner has the burden of going forward with rebuttal evidence” even though “the ultimate burden of proving invalidity remains with the challenger throughout litigation” (citing In re Cyclobenzaprine (FC 2012); challenger under clear and convincing standard)); 2) the DC properly concluded that the prior art showed a combination of metformin and a drug of “a similar mechanism of action” as repaglinide produced “beneficial and even synergistic results” in Type II diabetes patients and some expert witness skepticism regarding Novo’s studies (and commercial sales evidence was not convincing (“not overall sales, but whether those sales represent ‘a substantial quantity in th[e] market” (citing In re Applied Materials (FC 2012)); and, 3) Novo’s argument that Kappos v. Hyatt (US SC, FC 2012) requires deference to the examiner’s findings was misplaced as that case only relates to appeals from the Patent Trial and Appeal Board under §145. Caraco also alleged that Novo’s “synergy” declarations and arguments that overcame the obviousness rejection represented inequitable conduct. The DC decision was made between when Therasense was heard and when it was decided; both pre- and post-Therasense standards therefore applied. The DC found that the declarant (Dr. Sturis) omitted the fact that the “two-hour data point” (the only data with a p<0.05) was not part of the original test protocol and "that a correction factor had not been applied to that p-value", and testified to reservations regarding the relevance of the rat data to humans. However, the FC concluded no IE because the declaration only stated that the data "indicated" and "strongly suggest[ed]" synergy and the examiner would have understood that the animal experiments were not definitive with respect to humans (e.g., fails the "but for" materiality test). Caraco also alleged that Novo’s counsel (Dr. Bork) committed IE by characterizing Dr. Sturis' declaration as providing "clear evidence of synergy" and "synergistic and surprising results" (e.g., "went beyond Sturis's 'strongly suggests' language"). The FC panel disagreed however, noting that Dr. Bork "employed carefully-chosen language" such as "indicated" and "evidence" (vs. "proof"). The DC decision regarding IE was therefore reversed. Judge Newman concurred with the IE decision but argued that Novo's claims were incorrectly held unpatentable because of the synergistic data (e.g., 800% more effective than additive, repaglinide not chemically similar to alleged comparator drug, decision based on hindsight, obviousness considered from view of one of orindary skill not the patentee).

This entry was posted in Generics / ANDA, Inequitable Conduct, Obviousness. Bookmark the permalink.

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