Sandoz Limited & Anor. v Bristol-Myers Squibb Holdings Ireland Unlimited Company & Anor.

For obviousness, the court must assess the facts as a whole, giving appropriate weight to motivation, possible research routes, effort and expectation of success. Routine testing can support obviousness even where the precise result cannot be predicted, provided the testing is part of the skilled person’s normal work and is undertaken for a concrete technical purpose. Where common general knowledge identifies a potential formulation problem, routine testing and known formulation measures may make the claimed solution obvious. A claim feature that makes no technical contribution cannot support inventive step. The existence of alternative obvious routes does not necessarily make one route less obvious.

The claims concerned four formulation patents for apixaban, an oral anticoagulant. Only claim 1 of EP(UK) 3 246 021 remained materially in issue, together with corresponding issues concerning the other patents. The claim covered an immediate-release tablet containing up to 5 mg crystalline apixaban, particles below a specified D90, and a specified dissolution rate under defined testing conditions.

Infringement was admitted if the patents were valid. The claimants alleged obviousness over the review article Carreiro, supplemented by common general knowledge concerning formulation, dissolution, particle size and the Biopharmaceutics Classification System. The central issue was whether the skilled formulator would routinely test and address dissolution-rate problems in the proposed apixaban tablets.

1. Disposition. All four patents were held invalid for obviousness over Carreiro. The proposed amendments were formally allowable but did not cure the invalidity.
2. Applicable approach. Obviousness had to be assessed on the facts of the case, considering the relevant circumstances including motivation, the possible avenues of research, the effort involved and the expectation of success. Appropriate caution was required because the formulation case was substantially based on common general knowledge, although Carreiro supplied the clinical starting point.
3. Common general knowledge. The skilled team comprised a clinician and a formulator. Carreiro would motivate the clinician to request immediate-release apixaban tablets in 2.5 mg or 5 mg doses. The formulator would routinely assess apixaban’s properties, recognise that it was a BCS Class III drug, and understand that high equilibrium solubility did not guarantee a sufficiently rapid dissolution rate. Slow dissolution could limit absorption and bioavailability.
4. Testing and formulation choices. The safe and natural approach was to aim and test for approximately 85% dissolution in 15 or 30 minutes. If a prototype dissolved too slowly, the formulator would first assess disintegration and could then use known measures, including particle-size reduction or excipient optimisation. The claimed D90 of 89 µm fell within ordinary common-general-knowledge particle sizes and was normal and unsurprising.
5. Sequential steps and technical contribution. The sequence of pre-formulation testing, prototype testing, disintegration assessment and particle-size selection was systematic and known to common general knowledge. The fact that the precise result could not be predicted in advance did not prevent obviousness where the research was routine and directed to a recognised problem. If no problem in fact arose, the claims made no technical contribution. The court also applied the principle that alternative obvious routes do not necessarily diminish the obviousness of the chosen route.