CA-2025-001040 - [2025] EWCA Civ 903

Common general knowledge

The judge set out the common general knowledge of the skilled team at [71]-[144] and [206]-[218]. Given the scope of the issues on the appeal, I will take those passages as read. It is only necessary to explain four points.

First, the process of drug discovery proceeds through a number of stages, including the identification of a target, the generation of “hits” (compounds that show potential activity against the target), selection of “lead” compounds (those that show most promise), optimisation of leads through structural modifications, pre-clinical development and clinical trials. Activity is normally measured initially by in vitro, and later by in vivo, assays. A key property of a candidate compound is its potency, often expressed as IC₅₀ (half the maximal inhibitory concentration) or EC₅₀ (half the maximal effective concentration). Lower values indicate a more potent compound. It was common, at the stage of hit identification, to use an in vitro assay with a cut-off of 10 μM (i.e. to detect compounds with an IC₅₀ of 10 μM or less). However, compounds with such a level of potency would not be regarded as acceptable as a drug. For that, medicinal chemists would generally be looking for IC₅₀s in the low nanomolar range or better.

Secondly, SGLT2 was a known target at the priority date. It had been isolated, cloned and characterised in humans. It was found to be expressed in the kidney.

Thirdly, phlorizin is a naturally-occurring compound which was discovered in the early 1800s and was later noted to produce glycosuria and reduce blood glucose levels. It was demonstrated in the 1960s that phlorizin inhibits renal glucose reabsorption, and the skilled biologist/pharmacologist would be aware of studies using phlorizin, including to lower blood glucose in animal models. The skilled biologist/pharmacologist would (at least) assume that phlorizin inhibits SGLT2. Phlorizin was not suitable for the treatment of diabetes because it produced undesirable side-effects.

Fourthly, the investigation ofSGLT2 inhibitors as potential treatments for diabetes had become an established field by the priority date. Among others, a group of scientists employed by the Japanese pharmaceutical company Tanabe Seiyaku were active in this field.