Horizon Medicines LLC v. Alkem Labs. Ltd.

Case Name: Horizon Medicines LLC v. Alkem Labs. Ltd., No. 18-1014-RGA, 2020 WL 7022591 (D. Del. Nov. 30, 2020) (Andrews, J.) 

Drug Product and Patent(s)-in-Suit: Duexis® (ibuprofen / famotidine); U.S. Patent No. 8,067,033 (“the ’033 patent”)

Nature of the Case and Issue(s) Presented: Duexis® is a tablet formulation indicated for relief from rheumatoid arthritis/osteoarthritis and is intended to decrease the risk of developing upper-gastrointestinal ulcers. The ’033 patent recited a pharmaceutical composition comprising (i) a first portion with 800 mg ibuprofen, (ii) a second portion with 26.6 mg famotidine, (iii) no more than 1% sulfamide, (iv) certain stability requirements, and (v) three-times-a-day dosing. The court presided over a bench trial, considered the parties’ post-trial briefs, and found that claims 1, 8, 11, and 14 of the ’033 patent were invalid for obviousness and not infringed. The court further found that the asserted claims were not invalid for indefiniteness.

Why Alkem Prevailed: The court construed “a first portion” to mean “an ibuprofen compartment that is not a core” and “a second portion” to mean “a famotidine compartment that is not a shell.” Under these constructions, Plaintiff asserted only doctrine-of-equivalent (“DOE”) infringement. Horizon applied DOE to more than one claim element—“a first portion” and “a second portion”—at the same time. The court found that this application violated the “limitation-by-limitation” rule of DOE and rejected Horizon’s infringement theory. The court went on to explain that even if it were to apply the “insubstantial differences” test or the “function-way-result” test, Horizon’s DOE argument would fail on the merits.

Next, the court addressed Alkem’s obviousness defense. The parties did not dispute that the withdrawal of Cox-2 inhibitors from the U.S. market in 2004-2005 created a market void for drug products used to manage pain and that the most widely prescribed nonsteroidal anti-inflammatory drug (“NSAID”), ibuprofen, was an obvious replacement. Horizon argued, however, that a skilled artisan would not know the “standard” dose of ibuprofen. The court disagreed, noting that a skilled artisan—wanting to administer the greatest dose to provide relief while balancing the standard recommended practice of using the lowest effective dose—would have been motivated, with a reasonable expectation of success, to administer 800 mg ibuprofen.

The court next found that a skilled artisan would have been further motivated to provide an alternative therapy for reducing the risk of ulcers associated with the administration of ibuprofen and that Alkem had demonstrated the benefits of using an H2RA, such as famotidine. The court also found that because the FDA had approved famotidine dosing regimens of 1, 2, and 4 times daily, it would have been obvious to dose 3 times daily. Finally, to achieve the stability claim limitations, the court found that a skilled artisan would have reasonably expected that separating famotidine from an incompatible API (e.g., ibuprofen) would have improved stability.

Finally, the court addressed Alkem’s indefiniteness defense. Alkem argued that the “no more than about 1% sulfamide” limitation was indefinite. In support, Alkem argued that the ’033 patent did not define “sulfamide”; provided no chemical name, structure, or specific method of testing for “sulfamide”; did not refer to the USP; and did not provide any method for identifying/quantifying “sulfamide” in a composition. The court disagreed, explaining that when a skilled artisan looked to the USP to identify the known impurities of famotidine, there was only one choice with a “sulfamoyl amide” functional group, and thus the patent was not invalid as indefinite.