Pfizer Inc v Uniqure Biopharma BV

Inventive step is assessed by asking the statutory question of obviousness in the light of all relevant circumstances. The court must avoid treating reasonable expectation of success, motivation, or the number of research avenues as independent legal hurdles. Where the skilled person would contemplate the claimed course, the question is whether it would have been worthwhile pursuing it. A reasonable expectation of technical failure may support an inventive step. Mere uncertainty is different and may make motive and other factors important. Secondary evidence, including the failure of skilled teams to pursue an apparently simple route and the unexpected nature of the result, may materially support inventiveness. A patent specification may also be read with some knowledge of patent drafting.

The action concerned the validity of European Patent (UK) 3 581 650, concerning a Factor IX mutant used in gene therapy for haemophilia B. Pfizer alleged that the claims lacked inventive step over Stafford, a PCT application disclosing substitutions at amino-acid position 338, and also pleaded insufficiency as a squeeze on enablement. The patentees and exclusive licensee brought a Part 20 claim alleging infringement; infringement was admitted if the patent was valid.

The central issue was whether the skilled team would have regarded the claimed R338L-FIX variant as an obvious course to pursue, with a reasonable expectation of success, after reading Stafford and the common general knowledge.

1. Construction. Claim 1 required nucleic acid suitable for gene therapy treatment of haemophilia B, without any minimum duration of treatment. The inventive concept was DNA encoding the R338L-FIX variant for that use.
2. Applicable approach. Obviousness is a multifactorial assessment. The factors identified in Actavis Group PTC EHF v ICOS Group [2019] UKSC 15 are relevant considerations, not successive hurdles. The weight of each factor depends on the facts. Obviousness may turn substantially on reasonable expectation of success, but that concept must not be elevated into a universal formula.
3. Expectation and motive. If the skilled person would have contemplated the claimed course, a reasonable expectation of technical failure supports inventiveness. Absence of any expectation as to the result does not itself prevent obviousness; in that situation motive may be important. A commercial objection does not establish inventiveness.
4. Prior art. Stafford clearly identified R338L-FIX as a possible substitution, but its preferred list was understood as patent drafting rather than scientifically supported teaching. The skilled team would have regarded the highly conserved 330–338 helix, the hydrophobicity of leucine and the absence of supporting data as giving a reasonable expectation of no success. The Stafford reference therefore did not make the claimed invention obvious.
5. Secondary evidence. The failure of numerous expert teams, including those associated with Stafford, to test R338L-FIX during the preceding decade, despite the test being routine, strongly supported an inventive step. The later discovery of the naturally occurring Padua variant was treated as an unexpected breakthrough.
6. Disposition. The claims involved an inventive step over Stafford. The insufficiency case was not pursued in closing. The Patent was valid and, infringement being admitted on validity, it was infringed.