The salt of the judgment

When you are in private practice, you sometimes get to work with clients who come up with very creative legal arguments. Or you get to work with clients whose competitors are unfortunately very creative. Rating the chances of success of such creative arguments can be difficult, especially when there is not yet any case law to refer to.

Let us take one example. A patent protects a molecule M1. A competitor markets a drug containing a molecule M2. When this drug is taken up in the body of the patient, molecule M2 is converted to M1. Is this a situation of contributory infringement?

It is not so common for thought-provoking ideas such as this one to be actually tested in court. I was thus quite happy to hear about Shionigi & AstraZeneca v. Biogaran, thanks to Lionel Vial (the decision does not appear on the INPI database). So, if you would like to know the answer to the above question, you may directly go to the end of this post to find out about the guidance offered by the presiding judge of the Paris Tribunal de grande de instance, Marie-Christine Courboulay.

But not so fast, as other aspects of the case are very worth being reviewed.

The patent at stake is EP 0521471 owned by the Japanese pharmaceutical company Shionigi, and licensed to the Swedish group AstraZeneca. The patent covers a drug for the treatment of hypercholesterolemia, called rosuvastatin.

The patent is already relatively old, as it was filed in 1992 and claims a priority of 1991. It went unopposed and expired in 2012. But a Supplementary Protection Certificate (SPC) was granted in 2005 by the French Institut national de la propriété industrielle (INPI), extending the duration of protection until June 29, 2017. And then on top of that, a pediatric extension was granted in 2015, further extending the duration of protection till December 29, 2017.

The SPC was granted for the product simply identified as “rosuvastatin”, based on a Dutch Marketing Authorization (MA) for the drug Crestor, which contains a calcium salt of rosuvastatin.

Biogaran developed a generic version of rosuvastatin. In 2014, Biogaran warned AstraZeneca and Shionigi that they had applied for an MA for the zinc salt of rosuvastatin, and stated that this product did not infringe the SPC. AstraZeneca and Shionigi did not agree with the latter statement.

Two years later, Biogaran obtained its MA and announced that it intended to launch the generic drug in July 2016 – i.e. before the term of the extended SPC.

As a result, AstraZeneca and Shionigi filed a motion for preliminary injunction (PI) in front of the judge in charge of urgency proceedings (juge des référés) on April 26, 2016. The judge issued her order on July 4, 2016.

The criteria assessed by the juge des référés for deciding on the PI are whether infringement is likely, and whether there is any serious validity challenge.

In the present case, Ms. Courboulay deemed that there is no serious validity challenge; but that, on the other hand, infringement is not likely.

As a preliminary step in the reasoning, the claims of the patent were interpreted in view of the description. It is certainly a very good thing when a patent is construed as a first step, and thus in a consistent way for both validity and infringement.

In the present case, this preliminary interpretation step led to a result which may come as a shock to a number of foreign patent attorneys but which seems to be in keeping with the tradition of French patent law.

Claim 1 of the EP’471 patent reads as follows:

The compound (+)-7-[ 4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl)-(3R,5S)dihydroxy-(E)-6-heptenoic acid or a non-toxic pharmaceutically acceptable salt thereof.

This is the full name of rosuvastatin, either in the form of an acid or of a salt – any possible salt, it would seem.

Dependent claims 2, 3 and 4 respectively and specifically relate to the acid form, to the calcium salt and to the sodium salt of rosuvastatin.

The judge referred to article 69 EPC and the interpretative protocol, and made the following comments as to which rosuvastatin salts are protected by the patent:

[The patent] is drafted as disclosing a new pharmaceutical active substance, rosuvastatin, and the pharmaceutically acceptable salts of this substance, and the cited examples are only indicative and do not limit the protection to the only cited examples. However, the description and notably paragraph 007 provides examples of pharmaceutically acceptable non-toxic salts of rosuvastatin and makes reference to two families of metallic ions which were commonly used in the formulation of tablets of statins already known at the priority date, and in particular alcaline metal ions and alcaline earth metal ions. […] Thus, the pharmaceutically acceptable non-toxic salts are in these two families […], as the patent does not give any indication to the skilled person to select a salt in another family. On the contrary, the description focuses on these salts because they were already commonly used for the formulation of statin tablets; it does not provide any other lead, so that the skilled person will select a salt in the families offered by the patent as being the only relevant families for statins. He/she will not try to select salts of other families as the patent does not teach anything in this respect. 

Therefore, only salts belonging to the cited families, namely alcaline metals like sodium or alcaline earth metals like calcium, or those which can be part of the most commonly used cations for the formulation of statin tablets are concerned by the patent. The other salt families are not mentioned and thus excluded from the scope of protection of the patent

In summary, claim 1, taken at face value, covers any pharmaceutically acceptable salts of rosuvastatin. But according to the judge, the actual scope of the patent is narrower, as only two families of salts are covered: alcaline metal salts (such as sodium) and alcaline earth metal salts (such as calcium).

So beware: the interpretation of the claims in view of the description can result not only in a broadening of the scope of protection relative to the literal wording of the claims, but also in a restriction of the scope.

Just to be clear, this finding does not seem to be related to the existence of an SPC. The (re)definition of the scope of the patent was made with respect to the patent, not the SPC. See in particular the following comment in the judgment:

Although the Crestor MA designates the calcium salt of rosuvastatin, the scope of the […] SPC extends to all forms of rosuvastatin as covered by the EP’471 patent.

A judgment to be taken with a grain of salt?

Again, the limitation of the patent devised by the judge may come as a surprise from a European perspective. But I think it is in keeping with traditional French practice. French judges have consistently had a large degree of discretion in defining the scope of protection based on the overall teaching of the patent – or spirit of the invention.

Maybe another way to look at this would be to consider that the invention was sufficiently disclosed in the patent only for the two salt families explicitly mentioned (and exemplified) in the patent, which, as far as I understand, were the two usual salt families for other similar drugs at the priority date. Using other salts would have required further research.

Anyway, the consequence of this interpretation of the claim is that there was no direct infringement of the patent. Indeed, the Biogaran product is a zinc form of rosuvastatin, and zinc does not belong to the alcaline or alcaline earth metal families.

And now comes the last part of the judgment, which deals with an auxiliary argument by the claimants, which was articulated as follows:

Biogaran commits acts of contributory infringement because it provides essential means for implementing the invention [….]. The salt form under which rosuvastatin is administered decomposes as follows, as soon as it reaches the gastro-intestinal system of the patient. The salt is dissolved, which leads to the separation of the cation (for example the calcium or zinc ion) and of the anion (namely rosuvastatin in anionic form). Since the pH of the stomach is low (less than the pKa of the acid group of rosuvastatin), the rosuvastatin anion surrounded by H+ protons attracts them so as to make the free acid form of rosuvastatin. […] Therefore the invention is implemented in vivo, in the patient’s stomach, after the administration of the Biogaran rosuvastatin, which thus infringes the EP’471 patent by contributory infringement. 

An interesting theory, but which did not hold water for the judge:

The act of infringement in suit can only be the supply or marketing of the drug, and not the decomposition of the drug in the patient’s body. […]

Contrary to what is argued by the plaintiffs, contributory infringement does not consist in providing means allowing the decomposition of the rosuvastatin salt in anionic rosuvastatin and salt in the human body. This is a consequence of the ingestion of the drug in the body, and of its mode of action but it is not an essential means of the invention, which only relates to the formulation of the rosuvastatin tablet. […]

[Contributory infringement] cannot be relied upon in the context of an artificial auxiliary argument […] whereas the Biogaran product is a generic of Crestor and thus clearly intended for the same therapeutic indication.

Biogaran does not supply any means but a product equivalent to the one protected by the EP’471 patent and the SPC so that contributory infringement is neither established nor likely.

The reasoning is very clear. Contributory infringement is a notion intended to target suppliers of only part of an invention. It is “artificial” and therefore wrong to try to extend this notion to the situation of a drug which undergoes a chemical transformation into a patented compound only in the patient’s body.

It is remarkable, though, that the judge noted in passing that the Biogaran product is equivalent to the claimed invention. It seems that the plaintiffs did not argue infringement under the doctrine of equivalence. Would the outcome have been different if they had? Maybe we will find out with the case on the merits (assuming it proceeds to trial).

CASE REFERENCE: Tribunal de grande instance de Paris, ordonnance de référé, July 4, 2016, Shionigi Seiyaku Kabushiki Kaisha & Astrazeneca UK Ltd v. Biogaran, RG No. 16/56067.

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