Addressing the issues of reasonable expectation of success and induced infringement of claims directed to a method of treatment in a particular patient population based on the results of a clinical trial, the US Court of Appeals for the Federal Circuit upheld the district court’s finding that the claimed method was not obvious and that language in the proposed package inserts induced infringement. Sanofi v. Watson Labs Inc., Case Nos. 16-2722; -2726 (Fed. Cir., Nov. 9, 2017) (Taranto, J). 

Watson and Sandoz filed abbreviated new drug applications seeking to market generic versions of Sanofi’s Multaq®. Sanofi sued, alleging infringement of a patent directed to decreasing a risk of cardiovascular hospitalization in patients meeting certain clinical criteria by administering dronedarone—the active ingredient in Multaq®. After a bench trial, the district court found infringement and rejected defendants’ obviousness argument. Defendants appealed.

On appeal, the Federal Circuit focused on obviousness and inducement of the method claims in the asserted patent. As to obviousness, the only issue on appeal was the district court’s finding of no reasonable expectation of success. Defendants had to prove by clear and convincing evidence that, as of the February 2008 critical date, a person of ordinary skill in the art would have reasonably expected dronedarone to effectively reduce cardiovascular hospitalization in the claimed patient population. Sanofi conducted a large-scale clinical trial called ATHENA from 2005 to 2008 that was designed to answer this very question. The results of the ATHENA trial formed the basis for the patents but did not constitute prior art. 

No other clinical trial prospectively examined the claimed effect of dronedarone in this particular patient population. Post-hoc analysis of the results from other clinical trials “suggested a potential reduced-hospitalization benefit,” but no more. On the other hand, a different clinical trial “showed dangers of dronedarone severe enough to have spurred early termination of the study,” and a “2007 article characterized the safety and efficacy data as confusing and severely challenged.”

To show reasonable expectation of success, defendants relied primarily on the disclosure of an article published in January 2008 that “describe[d] the rationale and design of the ATHENA study” and taught that “it is expected that treatment with this compound will result in a significant reduction in the need of rehospitalization for cardiovascular reasons.” Defendants’ expert described this statement as “a concrete assertion of fact about what the authors expected, and perhaps what a relevant skilled artisan should expect.” In contrast, Sanofi’s expert “testified that, in this context, the statement would be understood as nothing more than a statement of the hypothesis being tested in ATHENA.”

The district court credited the testimony of Sanofi’s expert over that of defendants’, and the Federal Circuit declined to overturn this factual determination. The Court ultimately concluded that “the district court did not commit clear error in finding that a person of ordinary skill in the art ‘would have been at best cautiously optimistic that dronedarone could reduce the risk of cardiovascular hospitalization and hospitalization . . . in the ATHENA patient population’ and that Watson and Sandoz had failed to prove obviousness by clear and convincing evidence.”

The Federal Circuit also affirmed the district court’s finding of inducement. The package insert for Multaq® indicates that it is used for reducing the risk of hospitalization in certain patients. The package insert also describes the results of the ATHENA trial as supporting this indicated use, and defendants’ proposed package inserts also include this language. The Court concluded that the “label thus directs medical providers to information identifying the desired benefit for only patients with the patent-claimed risk factors.” On these facts, the Court concluded that the “content of the label in this case permits the inference of specific intent to encourage the infringing use.”