Paris court rules that formulation patent is so plausible as to be obvious

• Ruling outlines tension between plausibility and obviousness
• Court uses lower threshold than EPO and lower court on 'obvious to try' test
• MSD v Ethypharm (aprepitant)

To qualify for patent protection inventions must be novel, involve an inventive step (obviousness) and be susceptible of industrial application. Sufficiency of disclosure is a formal requirement according to which a patent application must also disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.

Plausibility is not a legal requirement as such but is a concept developed by case law mainly in the context of insufficiency and obviousness, and primarily in the pharmaceutical sector, and requiring the technical contribution made to the art by purported invention to be "credible, as opposed to “speculative”.

The Patent

MSD's patent relates to nanoparticulate compositions comprising aprepitant having absorded a surface stabilizer maintaining an average particle size of less than 1000 nm.

Aprepitant is an anti-emetic drug marketed for the prevention of nausea and vomiting associated with certain chemotherapies and was already known in the prior art. The use of surface stabilizers in nanoparticulate compositions, the so-called NanoCrystal formulation, was also known as a possible solution to enhance the bioavailability of poorly soluble products, although it had actually been tested with a verified effect on bioavailability on very few products only, and not on aprepitant.

Therefore the invention consisted in applying the NanoCrystal technology to aprepitant in order to enhance its biovailability. [A1] In the patent, MSD stated that the claimed composition "unexpectedly" improved the bioavailability of the drug. However, the patent did not include experimental data to support such assertion.

Background

The patent was upheld at the EPO in opposition proceedings.

The question of whether the patent claims were plausible was considered in relation to inventive step. To support its case on this point, MSD relied on post-published evidence showing an increased bioavailability of the claimed composition. The Board of Appeal accepted the evidence on the basis that, despite the lack of supporting data in the patent, the improvement of bioavailability was disclosed and derivable from the patent. As a consequence, it found that the problem the patent claimed to address had been credibly solved.

The Board of Appeal further considered that the invention was not obvious in view of the prior art. This was because it considered that the skilled person trying to overcome the low bioavailability of aprepitant would be faced with multiple avenues it could pursue. In this respect, the Board of Appeal reflected on the different factors that can be linked to low oral bioavailability of a drug and the fact that each of those factors have a variety of possible solutions to be tested. This is true even for low bioavailability specifically linked to poor solubility of the drug, it said.

Ethypharm brought revocation proceedings before the Paris Court of First Instance in respect of the French counterpart of the patent. Ethypharm claimed, in particular, that the invention was speculative and not plausible. However, in a judgement handed down on 26 January 2018, the Paris court shared the views expressed by the EPO and upheld the validity of the patent.

The court said that for either sufficiency or inventive step there is no requirement to demonstrate the technical effect with experimental data in the patent specification, as long as such technical effect is specified in the patent and plausible.

The Court also said that when that is the case, external evidence, for example internal studies performed before the application date or post-published evidence, can then be taken into account to confirm that the technical effect does exist, so as to demonstrate there has been an inventive step.

On obviousness, the court shared the views of the EPO and said that that there were too many factors and other routes and solutions to consider in relation to low oral bioavailability issues and that the NanoCrystal technology had not been explored enough for the skilled person to try that solution with a reasonable expectation of success.

It further held that general allegations made about the potential capabilities of the NanoCrystal technology by its proprietors in advertising were not specific enough or sufficiently supported by data to be considered as particularly relevant by the skilled person.

The Decision

Ethypharm pursued its case against the validity of MSD's patent before the Paris Court of Appeal. On 29 October, the court overturned the earlier ruling of the Paris Court of First Instance and revoked the patent. It determined that while MSD's patent claims were plausible and sufficiently disclosed, they were obvious.

On plausibility, the Court of Appeal focused on the insufficiency argument and considered the standard set by the French Supreme Court in 2017 in the MSD v Teva case on finasteride. It had said that while a clinical demonstration is not required, the specification must at least include some evidence relating to the therapeutic effect. However, the Court of Appeal said this test was for second medial use claims and did not directly apply in this case as it concerned product claims.

The Paris Court of Appeal said: "The condition of sufficiency of disclosure does not require a clinical demonstration of the alleged therapeutic effect, however when obtaining such therapeutic effect is a functional technical feature of the claim and the claim is on a second therapeutic use of a product or composition the patent application must directly and unambiguously reflect the claimed therapeutic use. This being said, it is not always necessary for the patent specification to include tests; such condition is not required for product claims."

The Court of Appeal then agreed with the first instance judges that the prior art disclosure relating to the NanoCrystal technology as a solution to improve the bioavailability of poorly soluble products, which is cited in MSD's patent, made it plausible that such solution would be effective on aprepitant. It said that the skilled person would not be prevented from carrying out the invention just because the specification did not include experimental data showing an actual improvement of bioavailability on aprepitant.

On obviousness, the Court of Appeal applied the EPO’s “obvious to try” test, which has only been used in a very limited number of cases in France. The Court of Appeal said: "It is necessary to determine whether the skilled person facing the technical problem to be solved at the [priority date], and in view of the prior art, would be prompted to try the solution proposed by the invention with a reasonable expectation of success, and would have reached the invention."

When applying the test in this case, the Court of Appeal seems to have used a lower threshold than the EPO and the first instance judges. It considered the general statements made about the NanoCrystal technology being applicable to potentially any poorly soluble product, together with the few specific examples disclosed in the prior art, as rendering it obvious for the skilled person to try that solution on aprepitant, even though other solutions were available.

In other words, the Court of Appeal found the invention so plausible that it was obvious.