Some readers may have a sense of déjà vu when reading today’s post, as I am going to talk once again about the finasteride saga.
In Lionel Vial’s first post and second post on the topic, it was explained how the Cour d’appel de Paris confirmed the revocation of the French part of Merck’s patent No. EP 0724444 (EP’444) for lack of novelty. The case was remarkable in that the court endorsed the principles set out by the Enlarged Board of Appeal in G 2/08: they held that second medical use claims containing a dosage regimen feature are not excluded from patentability and that novelty can be conferred by the dosage regimen feature. Yet, the court also held that, in this case, the claimed invention was in fact not novel over the prior art. This ruling was the result of a revocation claim brought by Actavis.
But there was another case in parallel to this one, with a revocation claim brought by Teva. This led to another ruling on the same date, where the same panel of the Cour d’appel confirmed again that the French part of EP’444 was invalid – but on a different ground, namely insufficiency of disclosure. So, I should probably say a word on this one as well, not only because Teva was represented by my former colleagues of August & Debouzy, but also because the court’s reasoning is in my view as interesting as in the Actavis case.
Readers may remember that the main claim of EP’444 was the following:
The use of 17β-(N-tert-butylcarbamoyl)-4-aza-5- alpha-androst-1-ene-3-one for the preparation of a medicament for oral administration useful for the treatment of androgenic alopecia in a person and wherein the dosage amount is about 0.05 to 1.0 mg.
Here are now Merck’s explanations regarding the nature of their invention, in the court’s own words:
They state that the technical problem to be solved was to identify a compound the mode of administration of which would offer the best guarantee in terms of safety (low dosage) and efficiency, so as to provide an improved treatment of androgenic alopecia. They explain that they have very surprisingly discovered that the oral administration of low daily doses of the finasteride compound, from 0.05 mg to 1.0 mg, was particularly effective for treating this condition.
The court examined whether the description of the patent was sufficiently clear and complete to enable the skilled person to carry out this invention. In this respect, they relied on the following standard:
Regarding an invention relating to a further treatment, even if, as rightly put by the appellant, it is not necessary to demonstrate clinically the therapeutic effect, nevertheless the pharmaceutical effect demonstrated in the application must directly and unambiguously reflect the claimed therapeutic applications, so that the skilled person understands based on commonly accepted models that the results reflect these therapeutic applications.
The inventor must indicate that the result was investigated and exists, by any experimental or non-experimental information, which establishes and makes explicit the claimed pharmaceutical effect, as from the filing date.
In other terms, second medical use inventions are subjected to a somewhat stricter sufficiency test that other inventions. The basic test for most inventions is whether it is possible to make the claimed product or implement the claimed use without undue burden. The stricter test applied here demands in addition that evidence of the pharmaceutical effect be present in the application itself. Data form clinical tests is not required, as those are usually conducted quite late in the drug development process. But some kind of research must at least have been conducted and some results obtained, that the skilled person can interpret as reflecting the claimed therapeutic use.
This seems like a sound approach in order to curb speculative patents, or “paper” patents, which could be used as an evergreening weapon, so as to preempt mere ideas or working hypotheses and block all future R&D efforts.
To some extent, I think the Boards of appeal of the EPO have adopted a similar principle, notably in T 609/02. An entire section of the patent attorney bible Case Law of the Boards of Appeal of the European Patent Office, 7th edition, September 2013 (II.C.6.2) is precisely dedicated to the particular “level of disclosure” which is required for medical use claims.
This is not to say that the principle is applied with the same strictness in Munich as in Paris. Practically speaking, the heightened sufficiency test mainly seems to be used by the Boards to strike out claims seeking to cover excessively large classes of compounds for certain uses, notably classes of compounds defined according to their purported function or use (also known as reach-through claims), as well as medical use claims wherein there is no demonstration of a direct link between the claimed compound(s) and the medical treatment at stake; but patents such as the present one, directed to a new dosage in an already known medical use of a given compound, are probably much more immune to an insufficiency challenge at the EPO.
Anyway, the Cour d’appel was clearly dissatisfied with the contents of the EP’444 patent:
[…] The description does not indicate what is the advantage or the technical effect resulting from this type of oral adminsitration. It does not contain any element showing the potential efficacy of the lower finasteride dosage, so that this mode of administration has no relevance for the skilled person.
The purpose of the invention according to the description is to reduce the amount of administered finasteride relative to the acceptable dosage already known from the prior art for an indication already disclosed, but the description does not comprise any information on the novel effect of the claimed posology and the particular properties of this new therapeutic application. […]
Moreover, no relevant and convincing result is provided in order to justify the claimed and yet undescribed pharmaceutical effect.
The court turned in particular to the example section in the EP’444 patent and held that none of the examples was relevant to the claimed therapeutic use.
I had a look at this example section myself, and it seems that the court made a good point here. Examples 1 and 2 relate to methods for making finasteride. They are thus irrelevant to the claimed therapeutic use. Example 3 discloses protocols for the preparation and dosage of 5α-reductase – but no results.
Example 4 describes a protocol for measuring haircount in subjects. Its conclusion is rather vague, though: “Using the above-described methodology, it can be shown that administration of finasteride, in dosages per day per patient of, for example, 1 mg/day or 0.2 mg/day, are useful in the treatment of androgenic alopecia, and promote hair growth in patients with this condition“. This is still largely unspecific in terms of technical effect(s) achieved and has the air of a prophetic example.
Finally, example 5 is sufficiently short to be reproduced here in its entirety: “In another test, finasteride was orally administered for 6 weeks to men with male pattern baldness at doses of 0.2 mg/day and 1.0 mg/day (and, for comparison, 5.0 mgs/day). The results of this test showed a significant reduction in DHT content in scalp tissue of the test participants“. Again, this is largely unspecific in terms of the improvement in the treatment of patients that can be achieved using to the claimed dosage of 0.05 to 1 mg finasteride.
As a line of defense, Merck provided external evidence such as an expert opinion and results from a study conducted in 1993 – the same year the priority application was filed. The court paid little attention to this external evidence and simply stated that it is of no relevance.
This is of course a crucial point. How much you allow a patent proprietor to rely on post-published evidence of a technical effect can make a world of a difference in terms of validity in the pharma and biotech field.
The court’s final conclusion was worded as follows:
[…] The skilled person is unable to reproduce the invention, since he is kept unaware of any specific technical teaching, and he must therefore perform a research program on his own.
As to the obvious question, why rely on different invalidation grounds in the two parallel nullity suits for knocking the same patent out, I assume that the answer is that courts in this country are very strictly bound by the submissions of the parties, and the plaintiff’s submissions were probably different in the respective cases.
Anyway this striking example of overkill does tell us something about our judges’ approach to what they may perceive as “weak” patents. Sometimes we get the impression that once a court is convinced that the invention at stake does not bring a contribution to the art which is specific and significant enough – and is therefore unworthy of patent monopoly – the ground on which they decide to invalidate the patent is not that important.
So, in this case, lack of novelty was as good as insufficiency of disclosure, given the absence of a “specific technical teaching” (as stated in the Teva judgment) or of a “different technical teaching” (as stated in the Actavis judgment). I am pretty sure that if there had been yet a third parallel case, the patent could also have been invalidated for lack of inventive step in view of the same findings.
As a last word on this finasteride saga (until a report on a potential cassation appeal?), the court noted in the decision that the EP’444 was found valid in the UK, Germany, Italy and the Netherlands. Oops! So much for pan-European consistency.
On the other hand, based on the slim contents of EP’444, I have sympathy for the position of our local judges. Merck’s invention may have been a real and valuable one – this is very possible. But one cannot really tell so based on the patent itself.
CASE REFERENCE: Cour d’appel de Paris, Pole 5, 2ème chambre, January 30, 2015, Merck Sharp & Dohme Corp. v. Teva Santé et al., RG No. 10/23603.