Federal Circuit, December 11, 2013, 2013-1034
Case History: Galderma owns patents for acne treatment lotion marketed as Differin Gel 0.3% (7,838,558; 7,579,377; 7,737,181; 7,834,060 and 7,868,044). Tolmar filed an ANDA action seeking to market generic Differin Gel 0.3%, a topical acne medication. At the district court Tolmar argued that the Galderma patents were obvious in view of prior art to Shroot. The district court concluded that that Galderma patents were not invalid. Tolmar appealed to the Federal Circuit, which found the Galderma patents obvious.

Claim 5 of ‘558 patent, which was treated as representative, is directed to an acne lotion comprising 0.3% by weight of adapalene. The prior art Shroot patent teaches that adapalene can be used in concentrations “preferably between 0.01 and 1 weight percent".  As framed by the Federal Circuit, when the claimed invention (i.e. 0.3%) falls within the range disclosed by the prior art (i.e. 0.1% - 1%) the issue is whether there was motivation to select the claimed 0.3% composition.

In particular, where there is a range disclosed in the prior art, and the claimed invention falls within that range, the burden of production falls upon the patentee to come forward with evidence that (1) the prior art taught away from the claimed invention; (2) there were new and unexpected results relative to the prior art; or (3) there are other pertinent secondary considerations.

As to teaching away, the district court concluded that the prior art taught away from 0.3% adapalene because it teaches that increasing the dose of adapalene from 0.1% to 0.3% results in increased side effects. However, the Federal Circuit held that there is nothing in the prior art references to indicate that the side effects would be serious enough to dissuade the development of a 0.3% adapalene product.  Here, the Federal Circuit relied on its ruling in Depuy Spine, Inc. v. Medtronic Sofamor Danek, Inc. that a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into the invention claimed. Further, the Federal Circuit noted that “a teaching that a composition may be optimal or standard does not criticize, discredit, or otherwise discourage investigation into other compositions.”

As to unexpected results, the Federal Circuit stated that in order to be probative of non-obviousness, such results must be different in kind and not merely in degree from the results of the prior art.  According to the Federal Circuit, results which differ by percentages are differences in degree rather than kind, where the modification of the percentage is within the capabilities of one skilled in the art at the time.

Galderma had argued out that tripling the concentration of adapelene from 0.1% to 0.3% did not result in tripling of the side effects (in fact there was no significant increase of side effects). The district court  concluded that the comparable tolerability of 0.1% and 0.3% adapalene was unexpected in view of the prior art.

The Federal Circuit rejected the district court’s finding that tripling the concentration of adapelene from 0.1% to 0.3% did not result in tripling of the side effects as conclusive evidence of non-obviousness.   According to the court, "while we agree that this result was unexpected, it does not constitute an unexpected result that is probative of non-obviousness … where an unexpected increase in efficacy is measured by a small percentage, and the evidence indicates that skilled artisans were capable of adjusting the percentage, the result constitutes a difference in degree, not kind.