The recent UK High Court decision has lessons for those seeking to protect Markush claims and prevent off-label uses of their medicines, explain Freshfields’s Christopher Stothers and Paul Abbott
Plausibility and other flavours of insufficiency have been to the fore in a range of recent UK Supreme Court and Court of Appeal judgments. They surfaced again in Lord Justice Arnold’s recent decision in the High Court in Akebia Therapeutics v Fibrogen, which invalidated almost all claims at issues across six asserted patents belonging to Fibrogen. As one might expect in a 137-page judgment, there are also numerous juicy tidbits of legal and practical relevance on other issues too. We’ve distilled five points of particular interest.
1. Claim too wide? Too bad
Most of the claims in issue in the case were defined by reference to a Markush formula (Formula (I)) together with functional features. However, the number of compounds potentially covered by Formula (I) was staggeringly large: an estimated 10183 possible structures were covered.
When considering whether a claim is insufficient for excessive breadth, the court undertakes a two-stage enquiry. The first stage asks whether it plausible based on the disclosure of the patent (plus CGK) that the invention will work across the full scope of the claim. Only if the answer is “yes” does the second question – whether there is evidence that in fact the invention does not work across the full scope of the claim – arise.
There was unchallenged evidence that there was no reason to suppose that substantially all the 10183 compounds would meet the functional requirements; indeed, there was good reason to expect that a very large number would not. The claimants valiantly argued that, because of the functional limitations, the claim scope was limited to compounds which worked so it necessarily followed that it is plausible the invention will work across the scope. That argument was firmly rejected by the Judge: on that basis the skilled reader would be left with the very substantial burden of finding compounds within the scope of Formula (I) which had the claimed activity. All such claims were insufficient for want of plausibility.
The clear lesson for holders of patents with Markush claims, therefore, is to think about how to narrow the claim before asserting – very broad Markush claims will not fly in the English courts absent evidence of sufficiency across their scope.
2. Claim too narrow? Too bad trying to assert it
Having lost the broad claims, the claimants’ infringement case hung on claims limited to single compounds (e.g. Compound C). The alleged infringing compound (vadadustat) is different from Compound C, so reliance was placed on the doctrine of equivalents as explained by the Supreme Court in Actavis v Lilly.
Arnold considered the case failed Lord Neuberger’s first Actavis question: does the variant achieve substantially the same result in substantially the same way as the inventive concept revealed by the patent? The inventive concept revealed by a claim to a specific compound is no broader than the use of that specific compound. The chemical structures of vadadustat and Compound C are quite different, and there was a lack of evidence to suggest that the two compounds bind to HIF-PH (which they both inhibit) in substantially the same way.
Even if Arnold was wrong on the above, he held the case would also fail the third Actavis question – would the skilled reader conclude that strict compliance with the literal meaning of the relevant claim was an essential requirement of the invention? Numerous reasons were given, including notably that the scope of claim by equivalence argued for by the claimants would be a claim so broad that it would suffer the same problems with insufficiency as the wider claims.
These points raise tricky issues for patent drafters, highlighting the need to identify some plausible basis for claims going beyond specific examples and thus not be too expansive when drafting claims.
3. Suing early for future off-label use? Good luck trying to establish intention
The infringement allegations in relation to one patent family raised several points around the tests for infringement of second medical use claims. Relevantly (a) vadadustat is not yet on the market – it is in Phase III trials, and (b) the intended product label for vadadustat does not cover the claimed uses. For the assessment of the infringement claim, the court had to consider both the defendants’ state of mind (at least in terms of what would be obvious to a reasonable person in the circumstances) and the state of mind of clinicians prescribing vadadustat (in terms of their intentions) at some indeterminate future point in time.
Central to this assessment was whether vadadustat has advantages over the drugs currently being deployed for the claimed uses, since vadadustat would only likely be prescribed off-label (or cross-label) for such uses if it did. Analysis of the currently available evidence indicated that such advantages were not (yet) established. In the circumstances, the defendants were not threatening to indirectly infringe the patents.
Arnold left the door open for a subsequent infringement claim (subject to patent validity) should new evidence emerge, so all is not lost for the claimants. However, this shows there remain limits to the English court’s willingness to make early determinations of questions which are still hypothetical.
4. Preparing expert evidence? Heed the guidance
Not for the first time, Arnold directed criticism at the parties’ legal teams regarding preparation of expert reports. One expert’s report contained several drafting errors which the Judge expected the lawyers to have picked up. Another expert was not asked to address in his first report two of his own prior publications which were relevant to issues in the case – contrary to specific guidance given in MedImmune v Novartis.
Arnold delivered a stark warning: if practitioners continue not to observe the standards required of them, the court will have to take steps to enforce those standards.
5. Need a technical primer? Yes, for all technically difficult cases
Arnold regretted that no technical primer had been prepared and issued guidance that a technical primer should now be regarded as mandatory in the most technically-complex cases in the Patents Court unless there are good reasons to the contrary. These are the cases which should only be heard by judges who practised (or still practice) patent litigation. The primer should cover technical areas which not in dispute, allowing experts to focus their evidence on contested matters. Practitioners will therefore need to be ready to get into this technical detail (with expert assistance), and often to narrow the issues, at an early stage of the case.