Gilead Sciences Inc & Anor v Nucana Plc

For a Markush patent claim to be plausible, the specification and common general knowledge must provide a reasonable prospect that the asserted technical contribution will work across substantially the whole claim. A few successful examples cannot support a broad claim where structural changes are known to produce unpredictable effects and the patent supplies no meaningful structure–activity basis for extrapolation.

Added matter may arise from deleting alternatives from multiple lists where the amendment singles out a new class or provides a technical contribution not disclosed in the application as filed. The patentee’s motive for amendment is immaterial, but the substantive effect of the amendment is not.

Gilead sought revocation of two UK designations of European patents owned by NuCana, concerning phosphoramidate prodrugs of nucleoside analogues, including gemcitabine-like compounds. NuCana counterclaimed for infringement in relation to sofosbuvir and sought amendments to one patent.

The issues included added matter, plausibility, industrial applicability, insufficiency, obviousness over Shepard, and the allowability of the proposed amendments. The principal questions were whether the claimed technical effects were plausible across the scope of the Markush claims and whether the claims disclosed new subject matter by selecting narrower combinations from multiple lists.

1. Disposition. Both patents were held invalid for added matter, lack of plausibility, insufficiency and, in relation to the 2MU2FD intermediates, undue burden. The proposed amendments to EP190 also failed for added matter. The attack based on Shepard failed. Had the patents been valid, sofosbuvir would have infringed.
2. Added matter. Applying the disclosure comparison required by Article 123(2) EPC, the court held that restricting Y to fluorine and selecting a new set of alternatives for X did not merely shrink an existing generic class. It singled out a materially different class, combining preferred and non-preferred choices without an adequate pointer in the PCT. The fact that the amendment avoided inactive compounds, compounds said to be difficult to make, or the prior art reinforced the conclusion that a different invention had been introduced. The patentee’s motive was irrelevant.
3. Plausibility. The court applied the three-stage inquiry in Fibrogen v Akebia: identify the claim scope, identify what it means for the invention to work, and ask whether a reasonable prediction can be made that substantially everything within the claim will work. The patent data made activity plausible for only a few exemplified compounds in limited assays. The claims covered large numbers of compounds involving structural changes known to cause loss of activity. The skilled team would positively expect a significant number to lack meaningful cytotoxicity, so plausibility failed both under the binding approach in Warner-Lambert and on the possible ab initio implausibility approach.
4. Industrial application and insufficiency. Bare or merely measurable cytotoxicity was not a sufficient practical application. The proposed research-tool use depended on information not disclosed by the patents. The evidence also showed that significant numbers of compounds lacked the asserted activity in fact. The synthesis of 2MU2FD intermediates required more than ordinary trial and error. Expert primary evidence was more probative than the patchy secondary evidence of real-world teams.