Frankly, I am not so fond of the finasteride litigation, previously discussed here, here and there. But this may simply have something to do with the fact that I am sensitive to the issue of hair loss.
That said, I am grateful to Denis Schertenleib for drawing my attention to the cassation ruling issued a few days ago on this topic.
As a reminder, European patent No. EP 0724444 to Merck Sharp & Dohme Corp. relates to the second medical use of finasteride for the treatment of androgenic alopecia, with a particular dosage regimen.
The French part of EP’744 was declared invalid twice by the Paris Cour d’appel: the first time for lack of novelty (what I would call the Actavis part of the lawsuit), and the second time for insufficiency of disclosure (the Teva part of the lawsuit).
Merck did not bow and tried its luck in front of the Cour de cassation – to no avail.
The cassation ruling (Teva part) is interesting in that it confirms the sufficiency standard to be applied in the field of therapeutic inventions.
Merck argued that the appeal decision (which, again, can be found on this page) was legally incorrect on 9 different grounds – or “branches“, as they are nicely called in the supreme court parlance. As I tend to find cassation decisions unreadable, I will try to reformulate these grounds in my own words.
On a general standpoint:
1. The question that the appeal judges should have addressed is only whether the drug with the right dosage could be manufactured by the skilled person.
2. The appeal judges mixed up sufficiency with novelty and inventive step, as they examined whether there was a “specific technical teaching” in the patent, and wrongly looked for a comparison of the invention with the state of the art in the patent. They should have focused on whether the information in the patent made it plausible that the claimed dosage was therapeutically effective.
Example 4 of EP’444 describes a protocol for measuring haircount in subjects. As I commented in my earlier post, its conclusion is rather vague and unspecific in terms of technical effect achieved, which led it to be disregarded by the Cour d’appel. The following grounds were raised in relation with this example 4:
3. The appeal judges failed to realize that the example 4 shows the technical effect linked to the claimed low dosage of finasteride.
4. The appeal judges said that clinical tests are not required for showing a therapeutic use, but then contradicted themselves when they disregarded the example as not corresponding to an actual clinical test.
5. The appeal judges failed to realize that the example provides a methodology making it possible for the skilled person to verify the claimed therapeutic use.
As for example 5 of the patent, it is supposed to show a reduction in the amount of dihydro testosterone (DHT) in the scalp of patients taking finasteride. But it is also quite imprecise and kind of looks like a paper example (just like example 4). The following grounds were raised in relation with this example 5:
6. The same contradiction already mentioned in item 4. happened again when the appeal judges discussed example 5.
7. The appeal judges failed to realize that example 5 shows that the claimed dosage has an effect on the metabolic mechanism involved in alopecia – so that example 5 indirectly also supports the technical effect linked to the claimed low dosage of finasteride.
8. The appeal judges held that the example was doubtful in view of the leaflet of the Propecia drug, without checking if this leaflet was available to the skilled person at the priority date.
9. The example mentions a reduction in the amount of DHT in the scalp of patients after 6 weeks, which is why the Cour d’appel found it doubtful, as the effect on hair growth is supposed to occur after 12 weeks at least. But the court should have realized that this is normal as hair growth can only occur after the reduction in the amount of DHT.
As usual, the Cour de cassation did not address in a detailed manner each criticism and basically simply stated that the Cour d’appel was right and that the grounds of cassation are ill-founded.
In particular, there is (alas) no general discussion on the level of plausibility required from a patent, and on the conditions under which post-published evidence may be relied upon.
Items No.8 and 9 in the above list were treated slightly differently, though. Those were found to relate to a redundant ground (“un moyen surabondant“) in the appeal decision, which means that the Cour de cassation refrained from stating whether they are correct or not, as anyway there are enough correct grounds in the appeal decision for it to be confirmed.
The key part of the ruling is translated in its entirety below (I have taken the liberty of dividing up the never-ending single sentence of the ruling into hopefully more intelligible bits):
[…] Firstly, when a claim relates to a [second] therapeutic application of a substance or composition, obtaining this therapeutic effect is a functional technical feature of the claim. Therefore, in order to meet the requirement of sufficiency of disclosure, it is not necessary to clinically demonstrate this technical effect; but the patent application must directly and unambiguously reflect the claimed therapeutic application, so that the skilled person can understand, based on commonly accepted models, that the results reflect this therapeutic application.
The decision mentions first that, regarding claim 1 […], the description does not indicate what the technical advantage or effect resulting from this type of oral administration is. It does not contain any element showing the potential efficacy of any finasteride dosage, and does not comprise any information on the new effect of the claimed dosage and the particular properties of this new therapeutic application. The dosage between 0.05 and 1.0 mg is unrelated to the administration rate and patient body weight. Then, according to the decision, the description of the patent only mentions the “surprising and unexpected” discovery of this new therapeutic application, without describing its particular pharmacological properties relative to the state of the art, which only derive from an arbitrary selection. In view of these findings, the Cour d’appel was in a position to deduce that the patent application did not directly and unambiguously reflect the claimed therapeutic applications; and that the skilled person unaware of any specific technical teaching was not able to reproduce the invention and had to implement a research program him/herself; so that [claims 1 to 3 were] insufficiently disclosed.
Secondly, regarding the the examples cited in the description of the patent, the appeal decision […] disregarded examples 1 and 2, which relate to the preparation of finasteride, the manufacturing process of which was known for years; and example 3, which does not relate to androgenic alopecia.
[The decision] notes on the one hand that example 4 discloses a photographic protocol for detecting hair growth by counting on a period of twelve months and holds that, since [the example] does not give any information on the conditions of a potential test and does neither describe the experiments nor the technical effect resulting from the lowering of the claimed dosage relative to prior art dosages, this example appears to be a measurement method and cannot be considered as a report on a trial.
[The decision] notes on the other hand that example 5 does not provide any detail on the experimentation or protocol applied when finasteride is administered for six weeks. The results have shown a significant reduction in the amount of DHT but have not established hair growth or the stop of hair loss. [The decision] holds that, in the absence of any comparison criterion, whereas the reduction in DHT levels in scalp due to the administration of finasteride was already known, this example does not make it possible to compare the effects of the claimed dosage relative to a higher dosage, of the order of 5 mg, disclosed in the state of the art.
Based on these findings, the Cour d’appel did not misrepresent the patent and did not require a clinical demonstration of the therapeutic effect of the new dosage. [Thus, the Cour d’appel rightly] considered that these examples did not directly and unambiguously reflect the claimed therapeutic application and could not remedy its insufficiency of disclosure as already noted above.
This approval of the approach taken by the appeal judges is of course important for all practitioners in the pharma field.
The trend is now once and for all confirmed, per which patents considered as “paper patents“, i.e. seen as overly speculative at the date of filing, will not fare well in France.
Before concluding this post and wishing all readers happy holidays, a final word on two procedural aspects.
First, Merck also criticized the appeal decision for holding Teva’s nullity claim admissible, although, when the first instance judgment was issued in the Teva part of the lawsuit, the patent had already been revoked by the Tribunal de grande instance in the Actavis part of the lawsuit.
The Cour de cassation held that:
[…] The Cour d’appel rightly stated that the decision revoking a patent has an absolute effect [with respect to third parties] only once it is res judicata, that the [Actavis first instance] judgment was under appeal, and deduced that the Teva companies were admissible in seeking the revocation of the same patent.
This is a welcome clarification.
The last point is that Merck of course also filed a cassation appeal against the other appeal decision in which the same patent was revoked for lack of novelty, as requested by Actavis. Here, the Cour de cassation trod the easiest path and simply dismissed the cassation appeal in a distinct ruling by noting that the patent claims have now been definitely held invalid in view of the Teva ruling.
Too bad for us commentators, as the Actavis part of the lawsuit also involved some interesting legal points.
With that, as promised, I wish all readers happy holidays.
CASE REFERENCE: Cour de cassation, chambre commerciale, December 6, 2017, Merck Sharp & Dohme Corp. v. Teva Pharmaceutical Industries Ltd. & Teva santé, pourvoi No. 15-19726.