Merck Sharp And Dohme Ltd v Shionogi & Co Ltd

A patent claim to a very broad class of chemical compounds is not inventive merely because it is limited to compounds that possess the desired activity. The specification must make it plausible that substantially all compounds within the claim share the relevant technical effect. A functional limitation cannot bypass that requirement.

For therapeutic-use claims, biochemical activity alone may be insufficient. Where the technical context requires it, plausibility may require cellular antiviral activity, acceptable toxicity and validation that the antiviral effect is caused by the claimed mechanism. A claim is also insufficient where performance across its breadth would require a vast research project involving undue burden. Narrowing a generic chemical formula does not generally add matter unless it singles out an undisclosed combination.

Shionogi alleged that MSD’s raltegravir product infringed European Patent No 1 422 218, entitled Antiviral agent. MSD denied infringement and challenged the patent on inventive-step, insufficiency and added-matter grounds.

The dispute concerned broad claims to compounds said to be integrase inhibitors for preventing or treating viral disease. Shionogi proposed unconditional and conditional amendments. The central issues were whether the specification made the claimed technical effects plausible across the scope of the claims, whether the invention could be performed without undue burden, and whether the amendments added matter.

1. Inventive step. The claims covered an extraordinarily large number of compounds. The specification disclosed limited biochemical assay data, no antiviral or toxicity data, and no validation work. It did not disclose a reliable structure-activity relationship or pharmacophore explaining why substantially all claimed compounds would possess integrase-inhibitory activity. The claimed technical contribution therefore did not justify the breadth of the monopoly.
2. A positive biochemical assay showed only integrase inhibition in vitro. In the relevant therapeutic context, the skilled team would also require cellular antiviral activity, toxicity testing and validation that the antiviral effect resulted from integrase inhibition. The specification made it implausible that substantially all claimed compounds would achieve those effects. The claims therefore lacked an inventive step.
3. Insufficiency. Plausibility is assessed first from the patent disclosure and common general knowledge, without later evidence. If plausibility is established, later evidence may be considered on whether the invention works across the claim without undue burden. Here plausibility was absent. In any event, testing the vast class would require a substantial research project with a high likelihood of failure. The claims were insufficient.
4. The claims were not ambiguous. The expression “non-interfering substituent” meant a substituent that did not prevent the compound from being an integrase inhibitor, even though that construction made the expression substantially redundant.
5. Added matter. The patent as granted did not add matter. The unconditional and first conditional amendments merely narrowed the generic disclosure and would have been permissible, but they did not cure invalidity. The second conditional amendment singled out an undisclosed combination of restrictions and was impermissible.
6. Raltegravir satisfied the structural and functional requirements of the claims. Accordingly, claims 1, 6, 8 and 14 would have been infringed if valid. All claims were nevertheless invalid for lack of inventive step and insufficiency.