On June 18, 2013, the Federal Circuit held that Novo Nordisk’s patent covering Prandin, a diabetes treatment, was obvious, and reversed the lower court’s finding of inequitable conduct.
Prandin is a Type II diabetes drug therapy that combines repaglinide, an insulin-release stimulator (secretagogue), with metformin, a glucose production suppressant (sensitizer). Novo began experimenting with repaglinide as a Type II diabetes therapy, but found that its secretagogue property was short-lived because it was quickly eliminated from the body. Novo then through its clinical research found that repaglinide was more effective when administered in combination with metformin and that the combination increased the longevity of repaglinide’s secretagogue qualities.
During prosecution, the PTO repeatedly rejected Novo’s application on the basis that the combination was obvious to try. Novo then submitted the results of a rat study showing that the combination therapy was more effective than the additive effect of the two drugs, convincing the examiner to allow the claims.
At trial, Caraco relied on prior art not submitted during prosecution to show that the results of Novo’s clinical research purporting to show unexpected results was not in fact unexpected. On appeal, Novo argued that the lower court wrongly placed the burden of proof on Novo to show that its patent was valid. The Federal Circuit disagreed, reasoning that Caraco’s production of new evidence simply persuaded the lower court that the patent was invalid, and that Novo’s introduction of evidence related to synergistic effects failed to persuade it otherwise.
The Court also rejected Novo’s argument that there was insufficient evidence to support a conclusion that the combination merely performed as expected. It noted that combination therapies using insulin sensitizers and insulin secretagogues were common at the time the patent was filed and that metformin was the most widely-used sensitizer. It also noted that the lower court had based its opinion on new prior art, expert witness testimony, and testimony by Novo scientists introduced by Caraco. The Court particularly noted that the lower court based its conclusions on the fact that the closest prior art to the repaglinide/metformin combination was a metformin/sulfonylurea combination, that such combinations were well-known in the art to produce synergistic results in controlling glucose levels, and that repaglinide was known as an insulin secretagogue having a similar mechanism of action to the sulfonylurea secretagogues. The Federal Circuit held that it was not erroneous for the trial court to conclude that the prior art rendered the combination obvious to try.
The Federal Circuit reversed inequitable conduct decision. The lower court had ruled that Novo’s omission of its earlier rat studies of the combination amounted to a material omission. The Federal Circuit disagreed, concluding that the omitted information was not material because the patentee could have explained it away.
Judge Newman dissented as to the obviousness issue. While not disputing that it was well-known that a combination of two drugs with different mechanisms for attacking diabetes may have synergistic effects, she wrote that it was not obvious that this particular combination would be.
Courts have held that many pharmaceutical combination patents are not obvious with arguably similar fact patterns. Whether this ruling, albeit only 2 to 1, signals the possibility of the Federal Circuit giving greater deference to the trial courts, who settle the factual disputes, remains to be seen.