Scinopharm Taiwan Ltd v Eli Lilly & Company

In assessing obviousness, the court must identify the skilled person, the relevant common general knowledge, the inventive concept and the differences from the prior art. A mosaic of documents is permissible only where it would itself be obvious to make that combination. In an “obvious to try” case, there must be a fair expectation of success, assessed in the circumstances of the particular case. Motivation may be relevant but is not an essential requirement. Evidence that a reaction might be improved by changing one parameter does not establish obviousness where the prior art and common general knowledge point away from the claimed pathway, and several alternative avenues remain open. The patent was valid because the claimed stereoselective process was neither obvious nor insufficiently enabled.

Scinopharm Taiwan Limited sought revocation of Eli Lilly & Company’s patent for a process for preparing β-anomer-enriched 2-deoxy-2,2-difluoronucleosides, including gemcitabine. The principal attack was obviousness over Chou read with Hertel 3 and, alternatively, with Hubbard, Kawakami, Howell and Vemishetti. Scinopharm also alleged insufficiency, contending that the patent did not identify conditions capable of consistently producing β enrichment across the claims.

The central question was whether it would have been obvious for the skilled process chemist to use an SN2 displacement pathway, rather than the SN1 pathway disclosed in the prior art, to obtain the claimed β-anomer enrichment.

1. Disposition. The allegations of obviousness and insufficiency failed. The patent was valid and the action was dismissed.
2. Applicable approach. The court applied the structured approach in Pozzoli v BDMO [2007] EWCA Civ 588; [2007] FSR 37. The skilled person was a process chemist experienced in nucleoside and glycosylation chemistry. Common general knowledge included the rarity of SN2 glycosylation reactions and the difficulty of stereochemical control.
3. Combination of documents. Two documents could be read together only if it was itself obvious to do so. Chou inevitably led the skilled person to Hertel 3, but Hubbard could properly be combined with them only because it would have been found in a routine search. Kawakami, Howell and Vemishetti could not be added without evidence that the skilled person would have found them.
4. Obviousness. The court applied the principles concerning “obvious to try” cases discussed in Conor v Angiotech [2008] UKHL 49. The skilled person would have expected the Chou and Hertel reactions to proceed by SN1. The documents gave no sufficient reason to pursue SN2, and fusion conditions had not altered the anomeric ratio in Hertel 3. The alternative of changing protecting groups was more logical. The claimed route involved practical difficulties, uncertain results, lower yield and an additional crystallisation step. It was therefore not obvious.
5. Subsidiary claims. Claims concerning concentration, triflate or fluorinated sulfonyloxy leaving groups and fusion conditions added no obvious subject matter, or were themselves not shown to be obvious.
6. Insufficiency. Although the claims did not specify every condition necessary to achieve β enrichment, the numerous examples and general teaching enabled the skilled person to identify suitable conditions and perform the invention across its scope.