Novartis Ag v IVAX Pharmaceuticals UK Ltd

A claimed microemulsion pre-concentrate must produce a dispersion possessing the defining characteristics of a microemulsion. The presence of some particles below the relevant size threshold does not suffice where the dispersion substantially contains larger particles. A lipophilic phase requires a distinct, substantially immiscible component that forms the dispersed phase; an amphiphilic surfactant cannot be treated as that phase merely because it carries the active ingredient.

For obviousness, industry failure is only secondary evidence and may be unreliable where patent protection discourages development. A claim covering an obvious alternative is invalid even if it also covers meritorious alternatives. A second component must be deliberately used, not merely present as an impurity.

Novartis sued Ivax for infringement of two patents concerning oral cyclosporin formulations. Ivax proposed to market Equoral, a formulation containing cyclosporin, surfactants, ethanol and related excipients.

The proceedings concerned construction, infringement and validity of GB 2,222,770, the Microemulsion Patent, and GB 2,380,674, the Second Component Patent. The principal issues were whether Equoral formed a microemulsion or emulsion pre-concentrate, whether it contained a distinct lipophilic phase and a deliberately used second component, and whether the claims were anticipated or obvious.

1. GB 2,222,770: construction and infringement. The skilled person could not rely on microemulsions as common general knowledge at the priority date and therefore had to use the specification and its references as a guide. The specification was misleading insofar as it suggested that a microemulsion possessed only one or more of the listed characteristics. The characteristics had to be considered together.
2. A dispersion containing some particles below 200 nm was not thereby a microemulsion where the dispersion also contained a substantial population of larger particles. Equoral produced both microemulsion-sized particles and larger particles, with no more than 14% of the active ingredient in the smaller particles. It was therefore not a microemulsion pre-concentrate.
3. The claim required a distinct lipophilic phase, substantially immiscible with the hydrophilic phase and destined to form the dispersed phase. Polyglycerol oleates were amphiphilic surfactants and could not be treated as the lipophilic phase. Equoral had no separately identifiable lipophilic phase. Infringement of ’770 failed.
4. Validity of ’770. Rosano did not make a cyclosporin microemulsion formulation obvious without hindsight. Failure by industry to make the invention earlier was only secondary evidence. It could be unreliable where patent protection reduced the incentive to undertake formulation work. The attack based on common general knowledge and Rosano failed, and ’770 was valid.
5. GB 2,380,674. The claim covered a pre-concentrate that spontaneously formed either an emulsion or a microemulsion. A second component had to be used as a component of the formulation; fatty acid impurities in other ingredients did not satisfy the claim. Equoral therefore did not infringe. Its dispersion was neither a microemulsion nor an emulsion within the specification because it lacked a lipophilic component.
6. Example X of Stuchlik did not anticipate on the accepted construction because its dispersion had particles up to 1000 nm. A complete example falling within a later claim can anticipate even where other, non-anticipatory examples are disclosed.
7. Obviousness of ’674. Applying the approach in Windsurfing International v Tabur Marine [1985] RPC 59, the addition of fatty acids to Neoral to improve cyclosporin solubility in the lipophilic phase was obvious from common general knowledge. Claim 1 was consequently invalid. The court reserved the question of appropriate relief.

Not stated in the judgment.