Following on from last week's post on the written description requirement in the US (IPKat), this Kat's attention has been drawn to yet another interesting decision from the Court of Appeal of the Federal Circuit (CAFC) in the life sciences field. In Teva v Corcept Therapeutics, the CAFC soundly rejected an obvious-to-try attack on a dosage regime claim. The reasoning of the CAFC makes a striking contrast to how the doctrine of "obvious-to-try" is applied by the EPO and the national courts of Europe.
Case background: Mifepristone dose regime to treat Cushing's syndrome
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| Grapefruit is a CYP3A4 inhibitor |
However, there were concerns about the safety of mifepristone at high doses in combination with strong CYP3A4 inhibitors, another treatment option for Cushing's syndrome. The label therefore specified that mifepristone dose should be limited to 300 mg/day when used with strong CYP3A inhibitors. The FDA also required Corcept to conduct post-approval studies to assess the safety risk of administering mifepristone in combination with strong CYP3A4 inhibitors.
As directed, Corcept conducted a clinical trial of mifepristone and strong CYP3A4 inhibitors combination therapy (Nguyen et al.). The patent (US10195214) was based on the results of this clinical trial, which was carried out in healthy volunteers. The patent particularly claimed a method of treating a patient by reducing their mifepristone dose from 1200 mg or 900 mg per day, to 600 mg in combination with a strong CYP3A inhibitor.
Teva brought post-grant review proceedings against the patent, arguing that the invention would have been obvious-to-try in view of the KORLYM label, alone or in combination with the FDA's guidance on drug-drug interaction studies. From Teva's point of view, the case was "an uncommonly clear-cut obviousness case", given that the prior art disclosed the problem, the solution and the way to find the solution.
Reasonable expectation of success does not require precise predictability
The CAFC decision related to the appeal from the PTAB decision that the claims were non-obvious. The CAFC agreed with the PTAB that, to invalidate the patent, Teva had to show that there was a reasonable expectation of success that the claimed mifepristone dose would be safe. The CAFC found no error in the PTAB's analysis of this point. The PTAB had found that Teva had failed to demonstrate that a skilled artisan would have had a reasonable expectation of success that administration of more than 300 mg mifepristone and a strong CYP3A inhibitor would be safe. In fact, the PTAB went further and found that the evidence, on the contrary, supported that a skilled artisan "would have had no expectation" that administering >300 mg mifepristone and a strong CYP3A inhibitor would be successful.
The CAFC agreed with the PTAB's analysis. The CAFC thus rejected Teva's argument that there was a clear case of obviousness, finding that Teva had failed to take account of the reasonable-expectation of success requirement. "At best, the prior art directed a skilled artisan to try combining the Korlym Label [...] and the FDA guidance. But without reasonable expectation of success, Teva did not prove obviousness". The patent was therefore found valid.
Final thoughts
We do not know yet how the EPO will view the claims in this case. Mifepristone has not been approved for use in treating Cushing's syndrome by the European Medicines Authority (EMA) and the corresponding European patent application (EP3589288) has not yet been granted. In EPO terms, it could be said that the safety concerns surround the higher mifepristone doses in combination with strong CYP3A inhibitor, in effect, "taught away" from the use of mifepristone at a high dose in combination with strong CYP3A inhibitors. However, if we compare the outcomes of other cases, the CAFCs reasoning in Teva v Corcept is in stark contrast to the reasoning we are used to seeing in Europe. According to the EPO guidelines, for example, "[e]ven an implicit prompting or implicitly recognisable incentive is sufficient to show that the skilled person would have combined the elements from the prior art " (G-IV-5.3).
In Europe, the obvious-to-try hurdle for dosage regime cases is thus much higher than the standard set by the CAFC in Teva vs Corcept. Whilst the fact of the cases differ, the PTAB and CAFC reasoning in Teva vs Corcept is markedly different, for example, to the reasoning of the UK High Court in Bayer v Teva [2021] EWHC 2690 (Pat) (IPKat) and Actavis v ICOS (IPKat), in which inventions arising from multi-step drug development programs were found obvious-to-try in view of a known treatment effect for a particular drug, regardless of whether there was an unpredictable technical effect. By contrast, in Teva v Corcept, a direct and public instruction from the FDA to carry out a clinical trial at the claimed doses was not considered detrimental to the inventiveness of the claimed doses.
From a US perspective, the decision in Teva v Corcept appears to incentivise later filing for dose inventions. Nonetheless, for global filings, the trickier challenges to patentability of dose claims in Europe cannot be ignored.
For the US view of the decision, see the write up over on Patently-O.
Further reading
- Bayer v Teva: Drug formulation patent found "the result of standard and routine considerations" ([2021] EWHC 2690 (Pat)) (28 Nov 2021)
- Second medical use dosage regimen claim successfully traverses both insufficiency and "obvious-to-try" attacks (T 0799/16) (8 March 2021)
- Canadian Federal Court considers whether Teva's COPAXONE second medical use patents were obvious-to-try (Teva v Pharmascience) (25 Jan 2021)
- Supreme Court confirms no hard line on inventive step test in finding Cialis dosage patent obvious (27 March 2019)
Reviewed by Rose Hughes
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Monday, January 17, 2022
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First thing I do when reading a case report on Patently-O is to see how the patent family member got on in the EPO. I dare say that there are lots of other blog followers who do the same thing. As retired judge Robin Jacob liked to say when opening one of his addresses to patent attorneys: There is a lot we can learn from the Americans, by i) studying what they do and then (pau......se) ii) not making the same mistake that they have made. Reliably, it's guaranteed to gain a laugh from a European audience. We await with interest the outcome of this case at the EPO.
ReplyDeleteBut Rose, is it still possible to change one word in your title, from "reign" to "rein". These spell-check tools are incorrigible.
Thank you for sharing this case and for your analysis. I'm not sure I follow the conclusions though, in particular regarding the difference in the EPO's approach on the obvious-try-attack.
ReplyDeleteI agree that "[e]ven an implicit prompting or implicitly recognisable incentive is sufficient to show that the skilled person would have combined the elements from the prior art " (G-IV-5.3).
However, similarly to CAFC, several BoAs deemed that a reasonable expectation of success is needed for finding the prompted combination obvious (see CL I.D.7.1: "... obviousness is not only at hand when the results are clearly predictable but also when there is a reasonable expectation of success" and "... even if it was obvious for the skilled person to try an experiment, it was not necessarily true that this person would have any reasonable expectation of success when embarking on it.").
In the present case, if I understand correctly, there was no reasonable expectation of success in view of the safety concerns surrounding the higher mifepristone doses in combination with strong CYP3A inhibitor; on the contrary, in view of such safety concerns, the expectation was that the combination would not be safe.
Accordingly, I think that the CAFC decision that “… without reasonable expectation of success, Teva did not prove obviousness” fits with the current practice of the EPO of the obvious-to-try-attack.
Am I missing something? Thoughts on the above?