IP Law Daily Validity of Vimpat® epilepsy drug patent affirmed on appeal
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Thursday, May 24, 2018

Validity of Vimpat® epilepsy drug patent affirmed on appeal

By Joseph Arshawsky, J.D.

UCB, Inc., UCB BioPharma SPRL, Research Corp. Technologies, Inc., and Harris FRC Corp. (collectively, "UCB"), the owner/licensees of U.S. Patent No. RE38,551 which covers lacosamide, an anti-epileptic drug marketed under the tradename Vimpat®, successfully resisted an appeal by generic manufacturers, as the U.S. Court of Appeals for the Federal Circuit found that claims 9, 10, and 13 of the ’551 patent were not invalid for obviousness-type double patenting, obviousness, and anticipation. Chief Judge Sharon Prost dissented, arguing that this was a case of double patenting (UCB, Inc. v. Accord Healthcare, Inc., May 23, 2018, Stoll, K.).

As disclosed in the ’551 patent, lacosamide is the Renantiomer of N-benzyl-2-acetamido-3-methoxypropionamide. For its R, R1, and R3 positions, lacosamide has an unsubstituted benzyl at R, an unsubstituted methyl at R1, and a nonaromatic methoxymethyl at R3. The specification teaches that "the R stereoisomer is unexpectedly more potent than the corresponding S stereoisomer and the racemic mixture." To date, Vimpat® remains the only approved functionalized amino acid (FAA) for the treatment of epilepsy. The generic manufacturers stipulated to infringement of claims 9, 10, and 13 of the ’551 patent but maintained that the claims are invalid for obviousness-type double patenting, obviousness, and anticipation. The Federal Circuit held that the district court applied the correct legal standards, and because there was no clear error in its underlying fact findings, the court affirmed the district court’s ultimate conclusion that the asserted claims are not invalid.

Prior art. A significant prior art reference was a thesis by graduate student Philippe LeGall. LeGall focused on 15 new FAAs and their potential anticonvulsant activities. Relevant here, LeGall disclosed compound 107e. Compound 107e is the racemate of the lacosamide compound claimed in the ’551 patent, meaning that instead of the isolated R-enantiomer (lacosamide) claimed in the ’551 patent, compound 107e is a mixture of both the R and S enantiomers. Similar to lacosamide, LeGall replaced the R3 position in compound 107e with a nonaromatic methoxymethyl group. LeGall discloses and provides anticonvulsant efficacy data for all 15 compounds except for compound 107e. The class of compounds to which compound 107e belonged all contained nonaromatic groups, and as a class, these compounds showed little to no potency.

The generic manufacturers also rely on U.S. Patent No. 5,654,301 (the ’301 patent) only for their argument that the ’551 patent is invalid for obviousness-type double patenting. Although lacosamide is not specifically disclosed in the ’301 patent, it is undisputed that lacosamide falls within the broad genus of claim 39 of the ’301 patent. The asserted ’551 patent discloses and claims lacosamide, a species of the genus disclosed in the ’729 and ’301 patents. The generic manufacturers argued that the compound described in the asserted claims of the ’551 patent is merely an obvious species of the genus claimed in the ’301 patent. Following a bench trial, the district court found that the differences between claim 45 of the ’301 patent and the asserted claims of the ’551 patent rendered the claims patentably distinct. Relying on, among other things, the lack of supporting efficacy data investigating the impact of placing an unsubstituted benzyl and methyl at R and R1, the district court concluded that it would not have been obvious to a person of ordinary skill in the art to make lacosamide by placing an unsubstituted benzyl at R or an unsubstituted methyl at R1 in combination with methoxymethyl at R3.

Obviousness-type double patenting. By statute, only a single patent may issue for the same invention. Nonstatutory double patenting, however, is a judicially-created doctrine, which "prohibits an inventor from obtaining a second patent for claims that are not patentably distinct from the claims of the first patent." In chemical cases, the double patenting inquiry is not whether a person of ordinary skill in the art would select the earlier compound as a lead compound, but rather whether the later compound would have been an obvious or anticipated modification of the earlier compound. The court agreed with the generic manufacturers that the obviousness-type double patenting inquiry requires consideration of the differences between the claims in the reference ’301 patent and the ’551 patent. In this case, both claims recite a methoxymethyl group at R3. Thus, the double patenting analysis requires determining whether the claims’ differences, i.e., unsubstituted benzyl and methyl at R and R1, would have been obvious to one of skill in the art. The district court did not err by focusing its double patenting analysis on the claims’ differences, as well as the claims as a whole.

"Because these claims only have a common methoxymethyl group at the R3 position, the question before us is whether a person of ordinary skill in the art, 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. We acknowledge that this is a close case, but because we discern no clear error in the district court’s underlying fact finding that there would have been no reasonable expectation of success in placing an unsubstituted benzyl and methyl in the claimed combination, we agree with the district court that the asserted claims of the ’551 patent are patentably distinct from the ’301 patent." The majority also took on the dissent, saying that far from ignoring LeGall, the district court squarely considered and addressed LeGall in its analysis.

The district court, relying on LeGall and crediting expert testimony, made extensive fact findings regarding the LeGall thesis. As the district court found, LeGall discloses no data whatsoever for compound 107e or any compound with a methoxymethyl group at the R3 position. The district court acknowledged that LeGall speculated that compound 107e "may" have good anticonvulsant activity based on its structural similarity to another compound. UCB’s expert testified, however, that a person of ordinary skill in the art looking to LeGall would have had no interest in pursuing that compound and that a person of ordinary skill would not have had a reasonable likelihood of success in pursuing an FAA with a methoxymethyl group at R3 as an anticonvulsant drug. The Federal Circuit found that the district court did not clearly err in crediting this testimony. "Because we hold that the district court’s finding regarding no reasonable expectation of success was not clearly erroneous, we are compelled to affirm the district court’s conclusion that the asserted claims of the ’551 patent are not invalid for obviousness-type double patenting."

Obviousness. The generic manufacturers asserted that claim 9 of the ’551 patent would have been obvious based on LeGall’s disclosure of compound 107e as a racemic mixture. Appellants further assert that LeGall alone, or in combination with other prior art references, render claim 9 obvious. The generic manufacturers also argued that the district court erred by using a lead compound analysis because this case involves purification, not structural modification, of a known compound. The Federal Circuit disagreed with the generic manufacturers. A lead compound analysis is not required in analyzing obviousness of a chemical compound when, in the inventing process, there was no lead compound. In any event, even if a lead compound analysis is required here, the court held that the district court did not clearly err in finding that a person of ordinary skill in the art would not have selected compound 107e as a lead compound. The court also evaluated the evidence before the district court. Based on this evidence, the Federal Circuit saw no clear error in the district court’s fact findings and sustained its conclusion that the asserted claims of the ’551 patent would not have been obvious.

Anticipation. Two generic manufacturers argued that because LeGall disclosed the chemical structure of the racemic compound 107e, it necessarily discloses the R-enentiomer (lacosamide) recited in claim 9 of the ’551 patent. The Federal Circuit affirmed this finding of fact by the district court and held that the district court did not clearly err in finding that LeGall does not anticipate claim 9 of the ’551 patent.

Dissent. Chief Judge Sharon Prost dissented because she believed that the district court clearly erred when it found there would not have been a reasonable expectation of success in selecting unsubstituted benzyl for R and unsubstituted methyl for R1. Therefore, the asserted claims of the ’551 are not patentably distinct from the ’301 patent.

The case is Nos. 2016-2610, 2016-2683, 2016-2685, 2016-2698, 2016-2710, and 2017-1001.

Attorneys: Dimitrios T. Drivas (White & Case LLP) for UCB, Inc., UCB BioPharma SPRL, Research Corp. Technologies, Inc. and Harris FRC Corp. Richard G. Greco (Richard G. Greco, Attorney at Law) and John W. Shaw (Shaw Keller LLP) for Accord Healthcare, Inc. and Intas Pharmaceuticals Ltd. M. Jeffer Ali (Carlson, Caspers, Vandenburgh, Lindquist & Schuman, PA) and Sarah Stensland (Patterson Thuente Pedersen, PA) for Alembic Pharmaceuticals Ltd.

Companies: UCB, Inc.; UCB BioPharma SPRL; Research Corp. Technologies, Inc.; Harris FRC Corp.; Accord Healthcare, Inc.; Intas Pharmaceuticals Ltd.; Alembic Pharmaceuticals Ltd.

MainStory: TopStory Patent FedCirNews

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