In response to the obviousness challenge, Knoll sponsored several studies at three of the nations most prestigious medical research institutions: the Memorial Sloan-Kettering Cancer Center in New York, Stanford University School of Medicine in Palo Alto, and the University of California School of Medicine in San Diego.
In the Sloan-Kettering study, investigators found that the hydrocodone-ibuprofen combination, when administered in the ratios claimed in the patent, showed greater than additive effects and strongly suggested a synergistic interaction between the ibuprofen and hydrocodone.
In the Stanford study, investigators found that the hydrocodone-ibuprofen combination, when administered in the dose ratios specified in the patent, produced a synergistic effect that was much greater than the predicted effect based on the potency of the individual drugs.
In the University of California study, investigators found that the hydrocodone-ibuprofen combination produced a synergistic effect that would require at least an approximate 4- to 15-fold increase in the dose of either ibuprofen or hydrocodone delivered alone.
The Stanford investigators presented their findings to the Society for Neuroscience in November 2002, while the University of California investigators presented their findings to the American Pain Society in March 2003.
Accordingly, in studies conducted at three preeminent research institutions, independent teams of investigators who were not aware of each others workand who each used different protocols and methodologiesall reached the same conclusion: When hydrocodone and ibuprofen are administered in the ratios specified in the patent, they have an unexpectedly synergistic analgesic effecti.e., an analgesic effect greater than the sum of the analgesic effects of the hydrocodone and ibuprofen doses alone.
In the litigation, Knoll offered this evidence of unexpected benefits to rebut the obviousness challenge to the patent. The trial court refused to consider the evidence on the ground that these unexpected benefits or results were discovered after the patent had been issued.
The trial court believed that such unexpected results must have been known by the inventor at the time the patent was issued in order to be relevant. As a result, the trial court ignored Knolls new data showing unexpected benefits and held that the patent was invalid on obviousness grounds.
On appeal, Knoll argued that the trial court erred in excluding the new evidence of unexpected benefits. To support the claim, Knoll stressed that several of the other accepted ways to show non-obviousness (such as commercial success) relied on evidence obtained after the patent had issued. Therefore, by the same logic, the new evidence of unexpected benefits should also be considered.
The Federal Circuit agreed. In endorsing Knolls use of the new data, the Court held that a patentee could conduct new tests after the patent had issued to demonstrate the unique properties of the claimed invention. In so doing, the Court emphasized that the full range of an invention is not always understood at the time a patent application is filed.
The court explained, Evidence developed after the patent grant is not excluded from consideration, for understanding of the full range of an invention is not always achieved at the time of filing the patent application. It is not improper to obtain additional support consistent with the patented invention, to respond to litigation attacks on validity.
There is no requirement that an inventions properties and advantages were fully known before the patent application was filed, or that the patent application contains all of the work done in studying the invention, in order for that work to be introduced into evidence in response to litigation attack. Nor is it improper to conduct additional experiments and provide later-obtained data in support of patent validity.
On this basis, the Federal Circuit reversed the trial courts decision holding the patent to be invalid (Knoll Pharmaceutical Co. v. Teva Pharmaceuticals USA, 367 F.3d 1381, 1385; Fed. Cir. 2004).