Teva UK Ltd & Ors v Astrazeneca AB

A patent lacks an inventive step where the skilled team would have been motivated to pursue the claimed formulation, would regard the relevant technical route as routine, and would have a reasonable expectation of success. A sustained-release formulation may be obvious where the prior art identifies the desirability of less frequent dosing and the formulation presents no real technical obstacle. An alleged formulation difficulty is not a bar to obviousness where it is illusory. Obviousness is assessed against the skilled team’s common general knowledge and information obtainable by routine investigation. A claim to a pH modifier is not inventive merely because one proposed use of the modifier was not common general knowledge, where the claim covers established uses and the general principle is apparent.

The claimants sought revocation of European Patent (UK) No. 0 907 364, owned by AstraZeneca, concerning a sustained-release formulation of quetiapine, an antipsychotic marketed as Seroquel. The challenge was confined at trial to obviousness over Gefvert, an abstract reporting receptor occupancy and pharmacokinetic observations concerning quetiapine.

The court considered the skilled team, common general knowledge, the properties of quetiapine that would be obtained by literature searching or routine testing, the relevance of high first-pass metabolism, and whether claim 1 and independently valid claim 15 involved an inventive step.

1. Obviousness framework. The court applied the structured approach in Pozzoli v BDMO SA [2007] EWCA Civ 588: identify the skilled person and common general knowledge, identify the inventive concept, identify the differences from the prior art, and decide whether those differences were obvious.
2. The skilled team comprised a clinician, pharmacologist, formulation scientist and pharmacokineticist. Its common general knowledge included the advantages of less frequent dosing, the routine use of hydrophilic polymers such as HPMC in sustained-release tablets, and the fact that information about a drug’s properties could be obtained by routine literature searches or testing.
3. Gefvert disclosed quetiapine’s short half-life, receptor-occupancy data and the potential desirability of a more convenient dosing regimen. The skilled team would conclude that a single 450 mg immediate-release dose daily was unlikely to provide efficacy. Once-daily administration was desirable for compliance and convenience. A sustained-release formulation and a higher immediate-release dose were both obvious possibilities.
4. The skilled team would not generally expect first-pass metabolism to be saturated at clinical doses. The available pharmacokinetic evidence indicated linear kinetics, which supported the opposite conclusion. High first-pass metabolism therefore did not deter development or reduce the expectation of success. HPMC was a routine matrix, and successful formulation would be achieved without difficulty. Claim 1 was consequently obvious.
5. Claim 15 was also obvious. It covered sodium citrate as a pH modifier for any purpose. Increasing solubility by use of a pH modifier was common general knowledge. Even assuming the relevant purpose was to reduce quetiapine’s solubility in gastric conditions, the general solution was obvious.
6. The Dutch decision on the parallel patent was carefully considered but not persuasive because the evidence, arguments, priority assumptions and treatment of first-pass metabolism differed materially. The patent was invalid.