Case Name: UCB, Inc. v. Accord Healthcare, Inc., Fed. Cir. Nos. 2016-2610, 2016-2683, 2016-2685, 2016-2698, 2016-2710, 2017-1001 (Fed. Cir. May 23, 2018) (Circuit Judges Prost, Bryson, and Stoll presiding; Opinion by Stoll, J.; Dissent by Prost, C.J.) (Appeals from D. Del., Stark, C.J.)
Drug Product and Patent(s)-in-Suit: Vimpat® (lacosamide); U.S. Patent No. RE38,551 (“the ’551 patent”)
Nature of Case and Issue(s) Presented: The ’551 patent disclosed and claimed lacosamide, which belonged to a class of compounds known as functionalized amino acids (“FAAs”). Lacosamide was the R-enantiomer of N-benzyl-2-acetamido-3-methoxypropionamide. The specification taught that “the R stereoisomer is unexpectedly more potent than the corresponding S stereoisomer and the racemic mixture.” As of the effective filing date of the ’551 patent, no FAA had been approved as an antiepileptic drug. Also, prior to the ’551 patent, there was no public disclosure of pharmacological efficacy or safety data to support the use of any FAA as an anti-epileptic or anticonvulsant drug. The development of FAAs as anticonvulsants began in the 1980s with the inventor of the ’551 patent, Dr. Kohn. In 1985, Dr. Kohn first disclosed the anti-convulsant activity of a compound identified as “AAB,” which provided the proof of concept for the use of FAAs as antiepileptic drugs. In 1987, Dr. Kohn published a paper (“Kohn 1987”), which disclosed the anticonvulsant activity of different structural analogs of the parent AAB. Kohn 1987 reported results of different groups at each of the different R positions of the general FAA chemical structure. Kohn 1987 showed that the placement of an aromatic group at the R3 position showed improved anticonvulsant activity.
Dr. Kohn’s research led to the filing of ’729 in 1991, which was prior art to the ’551 patent. The ’729 patent disclosed a genus of FAAs. Its specification explained that the claimed compounds exhibited “central nervous system (CNS) activity which are[sic] useful in the treatment of epilepsy and other CNS disorders.” The ’301 patent was a continuation-in-part of the ’729 patent and was filed in 1993. The '301 patent was not prior art to the ’551 patent. Defendants relied on the ’301 patent only for their argument that the ’551 patent was invalid for obviousness-type double patenting. Like its parent ’729 patent, the ’301 patent claimed compounds of a general structure and recited several different substituent groups.
Defendants stipulated to infringement of claims 9, 10, and 13 of the ’551 patent but maintained that these claims were invalid for obviousness-type double patenting, obviousness, and anticipation. Following a bench trial, the district court concluded that the asserted claims of the ’551 patent were not invalid. Defendants appealed, arguing that the district court misapplied the legal standards for obviousness-type double patenting, obviousness, and anticipation, and that the prior art anticipated and/or rendered the ’551 patent obvious. The Federal Circuit affirmed the district court’s judgment that the asserted claims of the ’551 patent were not anticipated, obvious, or invalid for obviousness-type double patenting.
Why UCB Prevailed: Obviousness-type double patenting. Before the district court, the parties disagreed as to the correct legal test for obviousness-type double patenting. Defendants argued that only the differences between claims 44-47 of the ’301 patent and claims 9, 10, and 13 of the asserted ’551 patent were to be considered. UCB argued that the claims as a whole should be considered, including the commonalities between the claims and whether a POSA would have been motivated to also modify any of those commonalities when modifying the differences between the claims. The district court adopted defendants’ theory, but held that the asserted claims were not invalid for obviousness-type double patenting under either theory. The Federal Circuit found that the district court did not err by focusing its double-patenting analysis on the claims’ differences, as well as the claims as a whole. Turning to the merits, the issue was whether a POSA, starting with claim 45 of the ’301 patent, would have been motivated to place an unsubstituted benzyl at R and an unsubstituted methyl at R1 in combination with the methoxymethyl group at R3 with a reasonable expectation of success. Acknowledging this was a close case, the Federal Circuit found no clear error in the district court’s fact finding that there would have been no reasonable expectation of success in placing an unsubstituted benzyl and methyl in the claimed combination, and held that the asserted claims of the ’551 patent were patentably distinct from the ’301 patent.
Obviousness. Defendants asserted that claim 9 of the ’551 patent would have been obvious based on the LeGall prior-art reference and its disclosure of compound 107e as a racemic mixture. Defendants further asserted that LeGall alone, or in combination with the ’729 patent and Kohn 1991, rendered claim 9 obvious. The district court applied a lead-compound analysis, and concluded that a POSA would not have selected any FAA, let alone those from the prior art, as lead compounds in the lead-compound analysis. Defendants argued that it was wrong to use a lead-compound analysis because this case involved purification—not structural modification—of a known compound. The Federal Circuit was not aware of any authority holding that a lead-compound analysis was or was not required in cases involving purifying mixtures. If a lead-compound analysis was required here, the Federal Circuit held that the district court did not clearly err in finding that a POSA would not have selected compound 107e as a lead compound. LeGall contained no data that would have led a POSA to select compound 107e—among the many compounds disclosed in LeGall—as a lead compound. The district court further found that the data provided in LeGall for that class of compounds showed little potency. Kahn's compound 31 is also a nonaromatic compound like compound 107e, and UCG’s expert testified that nonaromatic compounds were not of interest as of 1996. Also, compound 31 had properties making it less stable and thus medicinal chemists would have avoided investigating its potential use in a pharmaceutical product.
Anticipation. Defendants argued that because LeGall disclosed the chemical structure of the racemic compound 107e, it necessarily disclosed the R-enantiomer (lacosamide) recited in claim 9 of the ’551 patent. The Federal Circuit held that the district court did not clearly err in finding that LeGall did not anticipate claim 9 of the ’551 patent. “The knowledge that enantiomers may be separated is not ‘anticipation’ of a specific enantiomer that has not been separated, identified, and characterized.” Additionally, “the novelty of an optical isomer is not negated by the prior art disclosure of its racemate.”
Chief Judge Prost dissented, disagreeing with the majority that the asserted claims of the ’551 patent were patentably distinct from the reference patent claims. To the extent the district court found that a POSA would not have had a reasonable expectation of success in selecting an unsubstituted benzyl for R and an unsubstituted methyl for R 1, it clearly erred. Although the district court found that that drug development is unpredictable, “obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success.” Chief Judge Prost found that “in reality, there were many tests conducted on FAAs with benzyl at R and methyl at R1.” Because the district court found that the prior art provided ample evidence showing that a POSA would have had a reasonable expectation of success in creating an FAA with anticonvulsant activity by selecting an unsubstituted benzyl for R and an unsubstituted methyl for R1, “I am left with the definite and firm conviction that a mistake has been committed.” Finally, Chief Judge Prost believed the district court erred when it did not consider LeGall in its primary double-patenting analysis.
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