By Kevin E. Noonan --
The Federal Circuit had the opportunity to provide guidance on a question now in its twilight: what is the standard for determining who is the true inventor under pre-AIA 35 U.S.C. § 102(f), in Cumberland Pharmaceuticals Inc. v. Mylan Institutional LLC.
The question arose in ANDA litigation between patentee and NDA holder Cumberland Pharmaceuticals and Mylan. Cumberland's drug, Acetadote®, is an acetylcysteine composition substantially free of chelating agents, used as an antidote for acetaminophen overdose. Acetylcysteine was known in the art as an acetaminophen overdose antidote, but was also known to degrade (through oxidation) when contaminated by heavy metals. The prior art taught stable formulations of the compound required including a chelating agent, typically EDTA (edetate disodium). Cumberland’s U.S. Patent No. 8,399,445 claims stable formulations of the drug without chelating agents, encompassing Acetadote® and Mylan's generic version thereof.
Mylan filed its ANDA and provided Cumberland with a Paragraph IV letter for both the '445 patent and parent U.S. Patent No. 8,148,356, stipulating to infringement of the '445 patent. Cumberland dropped its assertion of the claims of the '356 patent and the case went to trial on validity of the '445 patent. Mylan asserted in its Paragraph IV letter and at trial that the Orange Book-listed '445 patent was invalid as being anticipated under 35 U.S.C. § 102(f) or obvious under § 103 based on the suggestion from the FDA during regulatory approval.
Mylan's allegation of derivation stemmed from Cumberland's FDA application, wherein the agency requested information on "scientific and regulatory justification for the inclusion of Edetate as a component in the drug product." Cumberland responded with a letter explaining that EDTA was included to stabilize the formulation, and that not including EDTA would raise safety and efficacy issues. Cumberland performed a stability study according to the FDA's suggestion following FDA approval of the combination product (acetylcysteine + EDTA), ironically, using a Mylan predecessor company as a CRO.
The findings of this study were that EDTA was unnecessary to avoid oxidative degradation, leading to the '455 patented formulations.
The District Court found that Mylan failed to show that the '445 patent claims were invalid under § 102(f) because no one at the FDA had conceived of the invention. On the obviousness issue, the District Court held that there would have been no expectation of success for making a formulation lacking EDTA in view of the "prevailing skilled-artisan view that chelating agents were necessary to prevent degradation of acetylcysteine."
The Federal Circuit affirmed, in an opinion by Judge Taranto joined by Judges Moore and Reyna. On the anticipation issue, the Federal Circuit reviewed the question of prior conception as a matter of law, while reviewing the anticipation issue for clear error as a question of fact. For derivation, the law requires that there be a prior conception from the true inventor and communication to the entity named as an inventor. For conception, the panel asserted that the complete conception required for establishing derivation was to provide Acetadote® (or other compound meeting all the other elements of the '445 claims) in the absence of EDTA or other chelating agent; this limitation, found in every claim, turned out to be the lynchpin of the Court's reasoning affirming the District Court's opinion. The Federal Circuit stated that the evidence of record had not shown the District Court that anyone other than the named inventors had conceived of the claimed invention, construed as being formulations wherein EDTA was removed (and not replaced by another chelator). Indeed, the FDA letter itself was evidence for the District Court and the panel that no one at the FDA had conception. According to the panel, "[a] request for justification of the inclusion of EDTA, supported by data, is not the same as a suggestion to remove it, let alone to remove it and not replace it with another chelating agent." Even if the FDA's request prompted the research that led to the invention, that was not enough for derivation. "The kind of general research suggestion at issue here, whatever its role in an obviousness analysis, does not establish the conception required for derivation," according to the panel. And further, "[i]t simply does not follow from the fact that the study ultimately became a commitment recited in the 2004 FDA approval that it was someone at the FDA who originally proposed the study, let alone conceived of the invention eventually claimed in the '445 patent." The language of the FDA's requirement to:
Commit to evaluate the potential benefit of Edetate disodium on the stability of the drug product. The study shall include a comparison of the current concentration of Edetate to a formulation with a lower concentration and no concentration of Edetate. Generate stability data from the new proposed formulations including compatibility stability with infusion bags.
was inconsistent with the limitation that the claimed formulation contained no other chelators.
Regarding Mylan's contentions that the claimed invention was obvious (which was based in the combination of the label of Acetadote® containing EDTA, several FDA documents related to the requirement for the study that formed the basis of their anticipation arguments, and a published patent application related to a particular use for the drug), the Federal Circuit affirmed the District Court's rejection of them based on Mylan's failure to establish that the skilled worker would have had a reasonable expectation of success. This conclusion, a question of fact reviewed for clear error, was in turn based on the express claim requirement that the acetylcysteine in the formulation be stable in the absence of EDTA, wherein stability was an express claim requirement. Citing both documentary and testimony evidence from the record (including evidence from Mylan that their scientists recognized a risk of acetylcysteine oxidation in the absence of chelators), the panel concluded that the District Court's determination was not clearly erroneous.
It can be expected with enactment of the Leahy-Smith America invents Act that the precedential value of this decision regarding pre-AIA Section § 102(f) of the Patent Act will be limited. However, who the true inventor is remains a necessary requirement for patents in the U.S. (even if who is rewarded with a patent between two inventors is now the winner of the race to the Patent Office rather than the party who conceived first). While the factual nature of the inquiry makes it less amenable to broad precedential rules (whatever "rule" can be gleaned with need to be applied to the facts in each case, which can be expected to vary widely), the Federal Circuit's opinion reinforces the principle that mere suggestion is not enough for conception and that a person who conceives the invention as claimed should (even now) be the person entitled to the patent.
Cumberland Pharmaceuticals Inc. v. Mylan Institutional LLC (Fed. Cir. 2017)
Panel: Circuit Judges Moore, Reyna, and Taranto
Opinion by Circuit Judge Taranto