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Sandoz Limited v Bristol-Myers Squibb Holdings Ireland Unlimited Company and Pfizer Inc. heard together with Teva Pharmaceutical Industries Limited v Bristol-Myers Squibb Holdings Ireland Unlimited Company and Pfizer Inc. v Teva UK Limited (Part 20 Defendant), High Court, London, UK, 15 July 2022, [2022] EWHC 1831 (Pat)

Bristol-Myers Squibb and Pfizer’s formulation patents protecting formulations of apixaban, the active ingredient in the blockbuster anticoagulant Eliquis®, have been held invalid in the English and Welsh High Court. Mr Justice Meade, handed down his decision revoking four apixaban formulation patents (EP (UK) 3 246 021 (“EP 021”), EP (UK) 3 017 811, EP (UK) 3 251 660 and EP (UK) 3 257 500) for lack of inventive step following revocation proceedings brought by Sandoz and Teva. The proceedings followed in the wake of Mr Justice Meade’s decision earlier this year in [2022] EWHC 822 (Pat) that Bristol-Myers Squibb’s compound patent for apixaban (EP (UK) 1 427 415) was invalid for lack of plausibility. Apixaban is an anticoagulant that is used in the treatment of thromboembolic disorders.

By trial, BMS/Pfizer had limited their case so that all four patents stood or fell on claim 1 (as proposed to be unconditionally amended) of EP 021. Claim 1 of EP 021 claimed a tablet (immediate release) comprising up to 5 mg of crystalline apixaban with a particle size distribution (D90) of less than 89 μm wherein the tablet dissolves such that at least 77% of the drug is in solution within 30 minutes, and the testing parameters to determine the dissolution rate. In his judgment, Meade J considered that the case came down to whether it was obvious to formulate an apixaban tablet of 2.5 mg or 5 mg with the claimed particle size and dissolution rate.

Sandoz and Teva claimed that EP 021 was obvious over a review article, Carreiro, which provided an overview of a number of ongoing and completed apixaban clinical trials, and of the pharmacokinetic properties of apixaban. Meade J decided, and the parties were not in dispute, that Carreiro gave the skilled team (comprising a clinician and a formulation scientist) the motivation to develop an immediate release tablet containing 2.5 mg and 5 mg of apixaban. However, Carreiro did not provide any further teaching on how the skilled team, namely the formulator, should formulate such a tablet. As a result, given the motivation to formulate apixaban over Carreiro had been established, Sandoz and Teva’s case on the formulation of an apixaban tablet relied on the common general knowledge of the formulator alone.

Central to the dispute was whether the skilled formulator would set a target dissolution rate that would fall within the claimed range and then seek to attain that rate using standard formulation methods; such as investigating particle size. BMS/Pfizer’s position was that the skilled team would have sufficient confidence that, because apixaban is a Biopharmaceutics Classification System Class III drug, no absorption problems as a result of dissolution would arise, and therefore such steps need not be taken.

Finding for Sandoz and Teva, Meade J held that the skilled formulator would target a dissolution rate of 85% in either 15 or 30 minutes and reduction of apixaban’s particle size to within the claimed threshold was one obvious way amongst others of achieving this (citing Brugger v Medicaid [1996] RPC 635). Meade J also noted that the formulator may not in fact encounter any problem at all as the target dissolution rate could be achieved without particle size reduction. If so in that case, there was no problem to be solved and so the patent did not make any technical contribution. In rounding off his judgment, Meade J noted that BMS and Pfizer could not argue that appreciation of the existence of a problem, i.e. in this case that the dissolution rate required optimisation, required invention as the formulator would be well aware that there might be such a problem with apixaban even though it was a Biopharmaceutics Classification System Class III drug.

A copy of the judgment can be found here.

Headnote by Christopher Stubbs, Bristows LLP