by Dr. Brigitte Böhm, Patent Attorney and Partner at Weickmann & Weickmann
An additional supplementary protection certificate may not be issued for a new formulation of a previously authorised active ingredient of a medicinal product protected by a patent. Even when the active ingredient is used in a new galenic combination which enables a greater efficacy, a marketing authorisation received for the new formulation does not constitute the first authorisation to place the respective product on the market as a medicinal product. This is the ruling of the European Court of Justice (ECJ) which was published on March 21, 2019 (Az.: C 443/17). The ruling is a further disappointment for the pharmaceutical industry which had with some justification hoped for a different decision. In spite of the considerable expenses for research and development in the field of medicinal products and the requirements of a time-consuming approval procedure for the new medicinal product, companies can only count on a relatively short period of protection for the improved formulation.
Pharmaceutical companies generally have to obtain authorisation for new medicinal products via a national or European approval procedure before the new product may be placed on the market. In this process, the efficacy, safety and quality of the medicinal product is examined on the basis of documentation which the manufacturer is obliged to provide. The preclinical and clinical studies required for this approval procedure are time–consuming and costly, whereby in some cases the costs incurred for a single approval for a medicinal product can amount to a triple digit figure in millions of euros. The approval is not only required for new active ingredients, but also for new indications with known active ingredients and partly also for new formulations of active ingredients which have already been approved.
In order for an invention to be granted a patent, the invention has to be new, i.e. not previously known, and to be based on an inventive step. In the light of these conditions, it is necessary to file patent applications very early on in the product development process. Due to the duration of the required approval procedures, the pharmaceutical industry is, in comparison to other sectors of the economy, at a disadvantage because an innovative product may only be placed on the market after an approval has been granted and therefore it usually takes many years before the new product can be commercially exploited. The remaining effective patent term and the resulting unique position of the patent holder for the marketing of the medicinal product - which in turn has to contribute towards the amortisation of the research and development costs - is correspondingly shortened. In order to promote the then declining research into new medicinal products, in 1990 the supplementary protection certificate was introduced on the basis of an EU regulation which to a certain extent and under certain conditions enables an extension of the patent term for medicinal products (and plant protection products).
In the case at issue, in 2017 the High Court of Justice in England requested a preliminary ruling from the ECJ. The object of the proceedings pending in the UK of the Abraxis Bioscience LLC company against the Comptroller General of Patents was the extension of the patent protection for Abraxane®, a medicinal product for the treatment of cancer. The European patent EP 0 961 612 protects nanoparticles of the active ingredient called "paclitaxel" bonded to human albumin (nab-paclitaxel). This new pharmaceutical form enables the active ingredient of the medicinal product to pass the cell membrane more easily and therefore leads to a greater efficacy of the substance in comparison to previous pharmaceutical forms.
Paclitaxel was previously already the subject of an approval for placing the product on the market in the EU, whereby the substance was marketed by other companies. Regarding the substance "nab-paclitaxel" which is the subject of discussion in connection with the current ruling, after the execution of further approval procedures in 2008 by EMA, the European Medicines Agency, a separate authorisation to market the product was issued. Based on the corresponding European patent, Abraxis applied for a supplementary protection certificate. However, the British patent office rejected the application, on the basis of article 3(d) of EU regulation no. 469/2009 according to which the received marketing authorisation must also be the first marketing authorisation for the corresponding product. Abraxis appealed against this ruling at the High Court of Justice of the United Kingdom especially on the grounds of the ECJ ruling Neurim Pharmaceuticals (C-130/11).
The High Court of Justice ruled that from this earlier judgement the interpretation of article 3(d) of the regulation was ultimately not clear and therefore requested a preliminary ruling from the ECJ on the following question:
"Is article 3(d) of the regulation 469/2009 to be interpreted as permitting the grant of a supplementary protection certificate where the marketing authorisation referred to in article 3(b) of that regulation is the first marketing authorisation within the scope of the basic patent to place the product on the market as a medicinal product and where the product is a new formulation of an old active ingredient?"
Already the opinion of the advocate general was a first forewarning that Abraxis Bioscience LLC could not expect a positive result. In line with this opinion, the ECJ has now ruled that article 3(d) of EU regulation no. 469/2009 should be construed that an approval for a new formulation of a known active ingredient cannot be regarded as the first marketing authorisation for the respective product if the active ingredient in a different pharmaceutical form was already the object of a previous approval. Referring to the ruling in the case of GlaxoSmithKline Biologicals (C-210/13), the ECJ justified its position that the expression "active ingredient" can only be understood as to include substances which themselves have a medical effect on a human or animal organism. This is not true in the case of albumin.
On the grounds stated in the Explanatory Memorandum to the proposal for a council regulation made in 1990 to create a supplementary protection certificate for medicinal products, the ECJ also maintains that a product protected by a supplementary protection certificate can only be a new active ingredient or a new combination of active ingredients. This does not include, however, minor changes to a previously approved medicine. A minor change is understood to mean, for example, a new dosage, use of a different salt or ester, or also a different pharmaceutical form of the active ingredient. The ECJ furthermore concludes in the present case with reference to its ruling on GlaxoSmithKline Biologicals that while an excipient may contribute to the pharmaceutical form of a medicinal product and even ensure the therapeutic efficacy, the relevance of this contribution of the excipient "cannot be regarded as a sufficiently precise test" in order to define a new product such as, for example, a new combination of active ingredients. Ultimately albumin is used as an excipient for the active ingredient. Due to the fact, however, that the substance does not have any therapeutic effect of its own, a new composition of the active ingredient according to article 1 (b) of the EU regulation no. 469/2009 is not given. According to the ECJ, a sine qua non condition is missing because under these circumstances, there is no product different from the paclitaxel which is already on the market.
As a further basis for its ruling, the ECJ examined whether the first approval granted for the marketing authorisation of Abraxane® by EMA was nevertheless the first required marketing authorisation for a medicinal product, namely as far as this marketing authorisation allowed for the first time the marketing of a product which is protected by the patent in question.
For the evaluation of this question the ECJ again refers to the statements of the advocate general in his opinion and comes to the conclusion, now with reference to the ruling in the case Medeva (C-322/10), that also in this regard a marketing authorisation can only be seen as a first marketing authorisation if it is the first approval for the corresponding product as defined by article 1(b) of the regulation. Consequently, also under this aspect it is not the invention protected by the patent, namely the combination of the active ingredient with albumin as excipient which can be seen as a product, on the basis of which a first marketing authorisation was issued, but merely the active ingredient itself. Therefore, according to the ECJ, in the present case also under consideration of the patented invention it cannot be relied on a first marketing authorisation for the product.
The arguments of Abraxis Bioscience LLC with reference to the ECJ ruling Neurim Pharmaceuticals (C-130/11) - which was deemed by many to be the start of a more liberal further development of the ECJ case law - have clearly been rejected in the present ruling. At the least, the Neurim-Pharmaceuticals case, where a new use of the product (veterinary medicinal product versus use in human medicine) was taken as a ground for a further supplementary protection certificate, cannot be interpreted to mean that a new formulation - even if found to be eligible for a patent - is also sufficient for granting a supplementary protection certificate. Again the ECJ bases its opinion on a narrow interpretation of the term "product" in article 1(b) and in article 3(d) of the regulation. According to that, such product can only be a substance with a therapeutic effect or a combination of two or more substances with therapeutic effect.
The ECJ was not influenced by the argument that the necessity of an approval process for medicinal products is a disadvantage for the pharmaceutical industry in comparison to other industrial sectors because research and development as well as long and expensive approval procedures lead to a considerably reduced period of time with patent protection for the marketing of its products. On the contrary, the court refers, as already the advocate general did in his opinion, to recitals in the proposal for the creation of the regulation. Even if this proposal was based on the motivation to remedy an insufficient protection for pharmaceutical inventions , all the interests at stake need to be taken into account including those of public health. The legislation therefore did not aim at promoting all pharmaceutical research projects, but merely the first marketing of a new active ingredient or a new combination of active ingredients as a medicinal product.
Hopes dashed for more liberal case law
The political considerations at the time are still highly explosive even today. In the health sector the pharmaceutical industry has not been fully deregulated. This is in sharp contrast to other industries which are not subject to the barriers described here. The question of whether the considerations discussed in 1990 are still up-to-date is evidently answered quite differently by the stakeholders of the involved parties. A disadvantage to the pharmaceutical industry in comparison to other industrial sectors nevertheless remains and the hopes of a more liberal case law in the wake of the Neurim Pharmaceuticals case, have been dealt a severe blow with the current ruling. Also in the future, a supplementary protection certificate is not available for a new patent-protected formulation (which formulation again has had to go through an approval or authorisation procedure), if the active ingredient included in this new formulation has already been placed on the market based on a previous authorisation.
The author, Dr. Brigitte Böhm, is a Partner at the law firm of Weickmann & Weickmann PartmbB in Munich. She provides companies with extensive consulting services in connection with the securing, defense and enforcement of patents and utility models in the areas of chemicals, biotechnology, pharmaceutics, food technology and associated areas.
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