Background

In a High Court decision of September 2011, Mylan had obtained revocation of a basic patent and SPC owned by Novartis. Mylan intended to market a generic version of the drug covered by the patent, rivastigmine. Rivastigmine is the (-) enantiomer of a racemic compound known as RA7. Previous publications had disclosed the use of RA7 for treatment of Alzheimer’s disease, but had not suggested resolution of the compound into its individual enantiomers. It was known that different enantiomers of the same compound could exhibit different activities. Floyd J concluded that the narrowest patent claim (rivastigmine in a pharmaceutically acceptable form for use in the treatment of Alzheimer’s disease) was invalid for lack of inventive step. He further considered that such a pharmaceutical composition was conceptually obvious. Novartis appealed this decision on the grounds that Floyd J’s findings were based on errors of law and fact.     

The steps differentiating the earlier publications from the inventive concept were: (a) the choice of RA7; (b) its resolution into its enantiomers; and (c) the preparation of a pharmaceutical containing the (-) enantiomer. The question was whether these steps would have been obvious to the person skilled in the art at the priority date (March 1987).

Ruling

Novartis firstly submitted that the expectation of success in selecting RA7 for development would have been so low as to render the invention non-obvious. The Court of Appeal (Kitchin LJ) rejected this point, finding that Floyd J had considered the various stages of drug discovery and development entailed in selecting compounds to progress to pre-clinical research and had ‘ample material’ on which to conclude that it would be obvious to take RA7 into development.

Secondly, Novartis contended that Floyd J had found overall that it was obvious to try rivastigmine for treatment of Alzheimer’s disease without considering whether the skilled team would have had a fair expectation of success. Kitchin LJ rejected the submission that the court could only make a finding of obviousness where it was manifest that a test ought to work, giving the example that this would preclude a finding of obviousness where the results of an entirely routine test were unpredictable. He restated his approach in MedImmune v Novartis [2012] EWCA Civ 1234: “ultimately the court has to evaluate all the relevant circumstances in order to answer a single and relatively simple question of fact: was it obvious to the skilled but unimaginative addressee to make a product or carry out a process falling within the claim.” In research-dependent areas such as pharmaceuticals and biotechnology, workers might well have little idea as to expectation of success.

The Court found that Floyd J had correctly approached the questions of whether (i) it was obvious to take RA7 into development and (ii) it was obvious to attempt to resolve it.  Further, Kitchin LJ agreed with the Judge’s affirmative answers to those questions, finding that it required no insight or invention to follow the teaching of the earlier publications, to take the compounds disclosed as having promise and to investigate whether that promise translated into a useful therapeutic effect. The skilled team would consider that resolution of RA7 might bring practical benefits and would see resolution as a routine step. The appeal in respect of the error of law aspect was therefore dismissed.

In respect of Floyd J’s assessment of the expert evidence, Novartis argued that the inherent lack of predictability in the differing activities of enantiomers precluded a finding of obviousness as a matter of law. This was rejected. Resolving the enantiomers comprised experimentation driven by rational technical considerations, not experimentation in the hope that something might turn up; moreover, it was relatively easy to carry out.

Further points relating to Floyd J’s judgment of the expert evidence, whether it was common practice to resolve racemic compounds at the priority date, and the characterisation of the objective technical effect of the invention were all dismissed.

Comment

It is settled law that the prior disclosure of a racemic compound does not constitute disclosure of its enantiomers, and the inventiveness of the resolution of enantiomers has been considered in a number of cases (Generics (UK) Limited & Ors v H Lundbeck A/S [2009] UKHL 12, Generics (UK) Ltd v Daiichi Pharmaceutical Co Ltd & Anor [2009] EWCA Civ 646).  The outcomes of those cases have largely depended on the difficulty involved in resolving the enantiomers in each case.  The same is true in this case too.

More generally, this case provides another reminder that the statutory question when assessing obviousness is “was the invention obvious at the priority date?” and not “was it obvious to try?”.  While the ‘obvious to try’ test may in some cases be of assistance in answering the statutory question, in other cases it won’t be appropriate.  Even where it has a role, the ‘obvious to try’ test has seen its wings clipped in recent years, first, by the House of Lords in Conor Medsystems Inc v Angiotech Pharmaceuticals Inc & Ors [2008] UKHL 49 (requiring a reasonable expectation of success); and subsequently in Medimmune Ltd v Novartis Pharmaceuticals UK Ltd & Anor [2011] EWHC 1669 (Pat) where Arnold J proposed that the ‘reasonable expectation of success’ requirement should be further confined to within a reasonable time (subsequently approved by the Court of Appeal).