Glenmark Generics (Europe) Ltd & Anor (t/a Mylan) v The Wellcome Foundation Ltd & Anor

In assessing obviousness, the court must identify the skilled person, the common general knowledge, the inventive concept and the differences from the prior art. The question is whether those differences required invention. In pharmaceutical cases, an obvious-to-try route is insufficient without a fair or reasonable expectation of success, assessed in the light of all the circumstances. The skilled person is not required to pursue every apparently relevant prior-art proposal. An additive drug combination may be worth developing even without synergy, particularly where it improves efficacy and use is controlled to limit resistance. Commercial considerations are not technical evidence of obviousness unless they have conditioned the skilled person’s technical mindset. On the evidence, further clinical development of the claimed combination was technically worthwhile and the patent claims were obvious.

Glenmark and Mylan sought revocation of a patent for an anti-malarial composition comprising atovaquone and proguanil in a 5:2 ratio. Wellcome, the proprietor, and Glaxo, the exclusive licensee, counterclaimed for infringement. The only alleged ground of invalidity was obviousness, and the proposed generic products would infringe if the patent were valid.

The principal prior art was a February 1992 presentation disclosing atovaquone and proguanil combination therapy with promising clinical results. A July 1992 abstract also disclosed a 100% cure rate in clinical trials and continuing development. The central issues were whether the skilled team would have pursued the combination, whether the 5:2 ratio involved an inventive step, and whether a pharmaceutical composition containing the combination was independently valid.

1. The patent was invalid and had to be revoked. Claims 1 and 9 were obvious over both the Hutchinson presentation and the Hudson abstract.

2. The court applied the structured approach to obviousness: identify the skilled team and its common general knowledge; identify the inventive concept; identify the differences from the prior art; and ask whether those differences required invention. The inventive concept of claim 1 was the atovaquone/proguanil combination in a 5:2 ratio. The only difference from the Hutchinson presentation was the ratio, which was not said to have technical significance. The real question was whether proceeding with the combination was obvious.

3. The skilled team would not treat the Hutchinson presentation as irrelevant merely because the trial was small, uncontrolled and incomplete. It disclosed promising results, evidence suggesting synergy, good tolerability and a justification for further dose-ranging work. The team would regard a Phase 2b trial as technically straightforward and worth pursuing, notwithstanding the recrudescence of one patient who had vomited during treatment.

4. There was no preconception that a merely additive combination was irrational. Additive combinations could improve efficacy and help manage resistance, particularly where neither drug was wholly ineffective and deployment was controlled. The possibility of a better combination, criticism from the audience and commercial difficulties did not outweigh the technical case for development.

5. For an obvious-to-try argument, the relevant inquiry was whether the skilled team had a fair or reasonable expectation of success, evaluated with all relevant circumstances including the number and extent of research avenues, the effort required, the predictability of success and the nature of the necessary experiments. Technical obviousness, rather than commercial obviousness, was required. Secondary evidence was subordinate to properly qualified expert evidence, though it could be material, and hindsight had to be avoided.

6. Claim 9 was independently obvious. The skilled team would regard co-formulation as a sensible eventual objective because it simplified dosing and improved compliance. The Hudson abstract supplied an alternative and sufficient route to the same conclusion, since it disclosed the combination, a 100% clinical cure rate and continuing development.