Lee Wright | July 23, 2014
Galderma Labs v. Tolmar, Inc.
December 11, 2013
Before NEWMAN, BRYSON, and PROST, Circuit Judges. Opinion for the court filed by Circuit Judge PROST. Dissenting opinion filed by Circuit Judge NEWMAN.
This Hatch-Waxman case is based on Tolmar’s filing of an Abbreviated New Drug Application (“ANDA”) seeking approval to market a generic drug (Differin® Gel,0.3%), which is a topical medication containing 0.3% by weight adapalene approved for the treatment of acne.
THE PRIOR ART
The various prior art showed:
Ranges for adapalene encompassing 0.3 %;
Specific amounts included 0.03% and 0.1 %; and
Taught the use of 0.3 % for other uses; and
0.1 % was the optimal concentration for the treatment of acne and that increasing the dose of adapalene was likely to increase side effects.
The District Court
The sole dispute was whether it was obvious to use a 0.3% adapalene composition for the treatment of acne as in Galderma’s patent.
The district court framed the obviousness inquiry as requiring Tolmar to provide motivation in the prior art to triple the concentration of adapalene from the optimal concentration of 0.1% to 0.3%.
The District Court found that Tolmar “failed to establish, by clear and convincing evidence, that the claimed inventions would have been obvious to a person of ordinary skill at the time of the invention.”
The district court also “relied heavily on evidence showing that increasing the dose of adapalene was likely to increase the incidence of certain side effects and evidence showing that 0.1% was considered the optimal adapalene concentration for the treatment of acne.”
In addition, the district court found: “that at least two secondary considerations, unexpected results and commercial success, additionally support the determination that the asserted claims are not invalid due to obviousness.”
The CAFC cited 35 USC 103 and stated that Tolmar is required to show that “the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.” 35 U.S.C. § 103.
The CAFC went on to state that there is “[n]othing in the statute or our case law requires Tolmar to prove obviousness by starting with a prior art commercial embodiment and then providing motivation to alter that commercial embodiment.”
The district court found that the prior art taught away from a 0.3% adapalene composition. The district court based its conclusion primarily on two related grounds. First, according to the district court, the prior art taught away from the selection of 0.3% adapalene for the treatment of acne:
1. Due to evidence of an increase in side effects for stronger doses; and
2. Evidence that 0.1% was the optimal concentration of Adapalene.
The CAFC disagreed, holding:
1. “A reference does not teach away, however, if it merely expresses a general preference for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into the invention claimed”; and
2. “A teaching that a composition may be optimal or standard does not criticize, discredit, or otherwise discourage investigation into other compositions.”
The CAFC agrees that the result of less side effects was an unexpected result.
However, the CAFC held that not all unexpected results are “probative of nonobviousness.”
“Unexpected results that are probative of nonobviousness are those that are ‘different in kind and not merely in degree from the results of the prior art’ … ‘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’ … ‘unexpected results where ranges of reaction time and temperature constituted only a difference in degree rather than in kind)”.
The CAFC held that “finding no unexpected results where improved yields over the prior art, measured by percentages, reflect a difference in degree, not in kind.” In re Aller, 220 F.2d 454, 456-57 (C.C.P.A. 1955) (emphasis added).
Thus, the CAFC held that “where an unexpected increase in efficacy is measured by a small percentage, as here, and the evidence indicates that skilled artisans were capable of adjusting the percentage, the result constitutes a difference in degree, not kind. So too, where an increase by a percentage is expected but not found, that result is also likely only a difference in degree.”
Filing of an ANDA
Galderma argued that the filing of an ANDA application to market a generic version of a drug was evidence of commercial success. The CAFC dismissed this argument, holding that the fact that an ANDA application was filed tells little about the commercial success relative to the prior art. The CAFC further noted that “this would likely be true for all Hatch-Waxman cases or even all patent cases generally.
Rise in Market Share
Galderma also argued that their market share rose quickly due to the 0.3% formulation.
The CAFC noted that patents by a third party blocked entry and when those patents expired, Galderma’s patent blocked entry. “Where “market entry by others was precluded [due to blocking patents], the inference of non-obviousness of [the asserted claims], from evidence of commercial success, is weak.”
Judge Newman dissented, arguing that the panel give scant attention to the district court’s analysis and instead “making their own findings, and applying flawed procedural and substantive law. My colleagues do not identify clear error in the district court’s findings; instead they distort the burdens of proof and production, ignore the applicable standard of proof and rely on their own factual determinations and creative theories of law, and eradicate the patent.”
A teaching that a composition may be optimal or standard does not fall within “teaching away”.
It remains difficult to prove secondary considerations of commercial success.
I disagree that there is a nexus between having a patent and market success. A patent may prevent infringers from the market but a patent does not necessarily lead to market success.
I continue to recommend presenting evidence from one skilled in the art. When an Applicant demonstrates substantially improved results and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary. In re Soni, 34 USPQ2d 1684, 1688 (Fed. Cir. 1995).
I am not sure the CAFC understood the depth of their holding that any percentage difference is one of kind and not one of degree. Any difference between two compositions can be measured in terms of percentages.
In some art small improvements may make a large difference in the properties of a compound. The rule that “small percentages” are automatically considered to be of “degree and not kind” appears to be the exact type of rule that KSR specifically warned against.
In In re Waymouth, 499 F.2d 1273, 1276, 182 USPQ 290, 293 (CCPA 1974) (emphasis added), the court held that unexpected results for a claimed range as compared with the range disclosed in the prior art had been shown by a demonstration of “a marked improvement, over the results achieved under other ratios, as to be classified as a difference in kind, rather than one of degree.” Compare In re Wagner, 371 F.2d 877, 884, 152 USPQ 552, 560 (CCPA 1967) (differences in properties cannot be disregarded on the ground they are differences in degree rather than in kind); Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (“we generally consider a discussion of results in terms of ‘differences in degree’ as compared to ‘differences in kind’ . . . to have very little meaning in a relevant legal sense”). MPEP 716.02.
The argument that “[n]othing in the statute or our case law requires Tolmar to prove obviousness by starting with a prior art commercial embodiment and then providing motivation to alter that commercial embodiment” appears to be counter to the “Lead Compound” analysis used for compounds. A lead compound is a compound in the prior art that would be “most promising to modify in order to improve upon its activity and obtain a compound with better activity.” Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007). The selection analysis may be guided by evidence of the compound’s pertinent properties, such as chemical activity or potency. See Eli Lilly & Co. v. Zenith Goldline Pharm., Inc., 471 F.3d 1369, 1378 (Fed. Cir. 2006).