Validity of a Patent
A recent decision relating to two generic drug companies’ challenges to the validity of an Eisai patent covering Aciphex® (rabeprazole) may have restored sanity to the obviousness analysis and allayed some fears. Eisai claimed a novel pyridine derivative that was more potent than prior art compounds at inhibiting gastric acid secretion.
Prevacid® (lansoprazole), a prior art compound, used to treat or prevent ulcers, was a structurally similar pyridine derivative.
These two compounds differ only in the substituent on the pyridine ring: rabeprazole has a methoxypropoxy group (OCH2CH2CH2OCH3), while lansoprazole has a trifluoroethoxy group (OCH2CF3).
In reviewing the judgment of nonobviousness from the district courts, the Court of Appeals noted that the KSR decision required the identification of a starting reference point from which one of ordinary skill in the art could identify a problem and pursue potential solutions. Next, KSR required some reason to make modifications to the prior art to achieve the claimed compound.
Finally and crucially, in Eisai, under an obvious-to-try analysis there had to be some reason for narrowing the prior art universe to a “finite number of identified, predictable solutions.” In other words, one of ordinary skill should have a basis for choosing the prior art compound to be the lead compound.
Here, the obvious structural and functional similarities between the two compounds suggested that lansoprazole could be a lead compound. Both lansoprazole and rabeprazole are small, lipophilic molecules having a molecular mass of about 360 g/mole. These similarities, however, were insufficient alone to support a finding of obviousness.
The Court of Appeals looked further and found that the function of lansoprazole as an antiulcer treatment would not lead one of ordinary skill to use it as a lead compound to discover a gastric acid inhibitor. In particular, the data for lansoprazole did not suggest that it inhibited gastric acid secretion. The function of lansoprazole does not, however, resolve the question of whether it would have been a desirable lead compound, and so the Court of Appeals looked to whether there were any contrary indications to lansoprazole as a lead compound.
As it turned out, the structural difference between lansoprazole and rabeprazole represented a contrary indication, a “teaching away”, to modifying lansoprazole to obtain rabeprazole even if lansoprazole had been selected as a lead compound. The evidence indicated that the fluorinated substituent of lansoprazole increased lipophilicity. One of skill in the art would have understood that increased lipophilicity was a desired characteristic in an antiulcer treatment.
There was no reason why one of ordinary skill would choose lansoprazole as a starting material and remove an advantageous feature of that compound. By moving in a direction contrary to conventional wisdom, Eisai discovered an unexpectedly superior proton pump inhibitor. Accordingly, the Court of Appeals affirmed the finding of nonobviousness.