[author: Kevin E. Noonan]
Again in only the span of a few months, the views of the Advocate General of the European Court of Justice (ECJ) have been adopted by Court. Previously, this pattern resulted in a ban on patenting human embryonic stem cells (see "European Court of Justice Renders Stem Cell Decision"). Last Thursday, the Court agreed with the AG that Supplementary Protection Certificates (SPCs) should be made available for new pharmaceutical uses for known products, providing innovator drug companies with an additional five years of patent protection under circumstances where patent term had been running during the time taken for regulatory approval.
The case came to the ECJ from the UK Court of Appeals, after the Intellectual Property Office (IPO) rejected grant of an SPC to Neurim Pharmaceuticals Ltd., which had developed a formulation of melatonin for treating insomnia. (Melatonin, produced in the pineal gland, has long been known to be involved in maintaining circadian rhythms in animals including humans.) In this case, the grounds for the IPO's denial of SPC protection was a previous approval of a different melatonin formulation for use in sheep breeding; under the IPO's interpretation of the law, the sheep use constituted a "first medical use" of the compound, thus precluding grant of an SPC on the insomnia formulation to Neurim.
Five Questions were Presented to the ECJ from the UK Court of Appeals:
1. In interpreting Article 3 of Regulation 469/2009 ("the SPC Regulation") when a marketing authorisation (A) has been granted for a medicinal product comprising an active ingredient, is Article 3(d) to be construed as precluding the grant of an SPC based on a later marketing authorisation (B) which is for a different medicinal product comprising the same active ingredient where the limits of the protection conferred by the basic patent do not extend to placing the product the subject of the earlier MA on the market within the meaning of Article 4?
2. If the grant of the SPC is not precluded, does it follow that in interpreting Article 13(1) of the SPC Regulation, "the first authorisation to place the product on the market in the Community" needs to be an authorisation to place a medicinal product on the market within the limits of the protection conferred by the basic patent within the meaning of Article 4?
3. Are the answers to the above questions different if the earlier marketing authorisation has been granted for a veterinary medicinal product for a particular indication and the later marketing authorisation has been granted for a medicinal product for human use for a different indication?
4. Are the answers to the above questions different if the later marketing authorisation required a full application for marketing approval in accordance with Article 8 (3) of Directive 2001/83/EC (formerly a full application under Article 4 of Directive 65/65/EEC)?
5. Are the answers to the above questions different if the product covered by authorisation (A) to place the corresponding medicinal product on the market is within the scope of protection of a different patent which belongs to a different registered proprietor from the SPC applicant?
In May, Advocate General Trstenjak promulgated an Opinion on the matter, concluding that a proper interpretation of the law would entitle Neurim to an SPC on its insomnia formulation. The Opinion was set forth as a response to a request for clarification of the law from the UK IPO. The Opinion cast the inquiry as whether "authorisation to place the product on the market as a medicinal product within the meaning of letter (b) must be the first authorisation to place that product on the market as a medicinal product." The Opinion also set forth the relevant provisions of the law:
Article 1 of Regulation No 1768/92, which is entitled 'Definitions', provides:
'For the purposes of this Regulation:
(a) "medicinal product" means any substance or combination of substances presented for treating or preventing disease in human beings or animals and any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans or in animals;
(b) "product" means the active ingredient or combination of active ingredients of a medicinal product;
(c) "basic patent" means a patent which protects a product as defined in (b) as such, a process to obtain a product or an application of a product, and which is designated by its holder for the purpose of the procedure for grant of a certificate;
(d) "certificate" means the supplementary protection certificate;
3. Articles 3 to 5 of Regulation No 1768/92 read as follows:
'Article 3 – Conditions for obtaining a certificate
A certificate shall be granted if, in the Member State in which the application referred to in Article 7 is submitted and at the date of that application:
(a) the product is protected by a basic patent in force;
(b) a valid authorisation to place the product on the market as a medicinal product has been granted in accordance with Directive 65/65/EEC or Directive 81/851/EEC, as appropriate;
(c) the product has not already been the subject of a certificate;
(d) the authorisation referred to in (b) is the first authorisation to place the product on the market as a medicinal product.
Article 4 – Subject-matter of protection
Within the limits of the protection conferred by the basic patent, the protection conferred by a certificate shall extend only to the product covered by the authorisation to place the corresponding medicinal product on the market and for any use of the product as a medicinal product that has been authorised before the expiry of the certificate.
Article 5 – Effects of the certificate
Subject to the provisions of Article 4, the certificate shall confer the same rights as conferred by the basic patent and shall be subject to the same limitations and the same obligations.'
4. Article 7 of Regulation No 1768/92, which is entitled 'Application for a certificate', provides:
'1. The application for a certificate shall be lodged within six months of the date on which the authorisation referred to in Article 3(b) to place the product on the market as a medicinal product was granted.
2. Notwithstanding paragraph 1, where the authorisation to place the product on the market is granted before the basic patent is granted, the application for a certificate shall be lodged within six months of the date on which the patent is granted.
5. Article 13 of Regulation No 1768/92, which is entitled 'Duration of the certificate', provides:
'1. The certificate shall take effect at the end of the lawful term of the basic patent for a period equal to the period which elapsed between the date on which the application for a basic patent was lodged and the date of the first authorisation to place the product on the market in the Community reduced by a period of five years.
2. Notwithstanding paragraph 1, the duration of the certificate may not exceed five years from the date on which it takes effect.
In its synopsis of the facts, the Opinion sets forth the claim of Neurim's European Patent for which the SPC was requested:
A pharmaceutical formulation, for use in correcting a melatonin deficiency or distortion in the plasma melatonin level and profile in a human subject, which comprises melatonin in combination with at least one pharmaceutical carrier, diluent or coating, wherein the melatonin is present in the formulation in controlled-release form adapted to release melatonin following administration to a human patient, over substantially the whole of a single nocturnal period of at least about 9 hours, such that melatonin release occurs according to a profile which, taking into account the existing nocturnal profile, simulates a normal human endogenous melatonin nocturnal profile in plasma, in that administration of the formulation at the beginning of said at least about 9 hour single nocturnal period causes melatonin to be detectable in the plasma in an amount which increases to a peak in the course of said period and subsequently decreases to a post-peak minimum essentially at the end of said period.
Market authorization in Europe was granted in 2007 for Neurim's product (Circadin), 15 years after Neurim filed its patent application thus leaving only five years of term for its patent.
The Opinion also described the parties submitting written observations and oral argument before the ECJ: Neurim Pharmaceuticals, the United Kingdom Government, the Portuguese Government, and the European Commission. The Commission and Neurim argued that Article 3d does not preclude grant of an SPC on a "medicinal product comprising an active ingredient where an earlier marketing authorisation (A) has been granted which is for a different medicinal product comprising that active ingredient" (with the caveat that the "limits of the protection" from the "basic patent" would not "extend to the medicinal product the subject of the earlier marketing authorization" and all other requirements of Article 3 are met). The UK and Portuguese governments took the position that a "second" SPC should not be granted on a medicinal product where the active ingredient had previously been the subject of an SPC.
Advocate General Trstenjak addressed the first question by considering a "literal interpretation" of the language of the regulation, and then assessing the result to determine whether it is consistent with "the schemes and objectives" of the SPC regulations to come to his conclusion as to the first Question Presented. In this analysis, the AG determined that the literal meaning of the words of the regulation would preclude grant of a subsequent SPC where a previous SPC had been granted on a medicinal product containing the same active ingredient. However, the AG then determined that such a result would be contrary to the "schemes and objectives" of the regulation. Specifically, the AG noted that is was certainly the case that the same active ingredient could be the subject of patent protection for different formulations and uses, as was the case here: Neurim had a patent for its Circadin insomnia forumation and Hoechst had a patent for its Regulin product for use in sheep breeding (which had expired in 2007). As a consequence, the AG's Opinion states that "[i]t must therefore be assumed that, in principle, Article 3(a) permits the grant of more than one supplementary protection certificate for a product." The AG reached the same conclusion with regard to Article 3(b), because that Article provides for market approval for, inter alia, human and veterinary uses. The AG's Opinion thus concludes that "Article 3(b) also permits, in principle, multiple supplementary protection certificates for products which are used as active ingredients in different medicinal products." While Article 3(c) by its plain wording would seem to preclude grant of a subsequent SPC on an active ingredient that had received a prior SPC, the AG concluded that "requirement may not be construed as meaning that only one supplementary protection certificate could be granted for a patented active ingredient or for a patented combination of active ingredients" in view of the ECJ's case law. Because there is thus a "common feature" of Articles 3(a), (b) and (c), the AG concluded that "the schematic context" of Article 3(d) also suggests that this Article would also permit grant of more than one SPC.
The AG then discussed "teleological" considerations, that is, directed at a consideration of the purpose of the SPC regulations. Here, the AG noted that "the aim of granting supplementary protection certificates for medicinal products is essentially to extend the term of patent protection for active ingredients used in medicinal products." Recognizing that protracted regulatory approval proceedings can seriously reduce the patent term remaining when regulatory approval is finally achieved. The AG appreciates the "view of the European Union legislature" to be that SPCs are needed and granted to remedy the insufficiencies in patent protection occasioned by these long delays in regulatory approval. Thus:
Those rules [i.e., the SPC Regulations] are intended to achieve a balance between the various interests at stake in the pharmaceutical sector. Those interests include, on the one hand, the interests of the undertakings and institutions, some of which pursue very cost-intensive research in the pharmaceutical sector and therefore favour an extension of the term of protection for their inventions in order to be able to balance out the investment costs. On the other hand, there are the interests of the producers of generic medicines who, as a consequence of the extension of the term of protection of the active ingredients under patent protection, are precluded from producing and marketing generic medicines. It is also relevant in this connection that, in general, the marketing of generic medicinal products has the effect of lowering the prices of the relevant medicinal products. Against that background, the interests of patients lie between the interests of the undertakings and institutions conducting research and those of the producers of generic medicines. That is because patients have an interest, on the one hand, in the development of new active ingredients for medicinal products, but, on the other, they also have an interest in those products then being offered for sale as cheaply as possible. The same applies to State health systems in general which, in addition, have a particular interest in preventing old active ingredients from being brought onto the market in slightly modified form under the protection of certificates but without genuine innovation and thereby artificially driving up expenditure in the health sector.
Applying these factors to the case before the Court, the AG recommended that the "absolute preclusive effect" resulting from a prohibition of a subsequent SPC to Neurim for its Circadin product "would be not compatible with the objectives of [the SPC] Regulation." Conversely, granting an SPC under these circumstances is consistent with Article 54(5) of the European Patent Convention (EPC), which "expressly recognises the patentability of 'second and further medical uses' of substances whose use in other medical processes already forms part of the state of the art." In the AG's view, "it would therefore be contrary to the aims of Regulation No 1768/92 if, in a case like the main proceedings, an application for a supplementary protection certificate would inevitably be unsuccessful because the patented active ingredient has already been placed on the market in another medicinal product." The AG emphasizes that the prohibitions of Article 3(c) remain, that "prohibit the grant of more than one certificate for each basic patent" (emphasis in original).
The AG then recognized that while his Opinion is consistent with one line of cases in the ECJ (including Medeva, Georgetown Unversity and Others, and AHP Maufacturing), it is inconsistent with other cases where the ECJ has interpreted the law more stringently. These cases include Synthon, and Generics (UK), but the AG appears to believe that the Opinion is more consistent with the "first line" of ECJ cases and thus is a sound legal representation.
The AG rendered a recommendation on Questions 2 through 5 more summarily, stating that the term of the SPC for the subsequent approved use is to be made using the same rubrics and limitations as any other SPC. Question No. 3 the AG answered in the negative, because the "crucial question" is that the product seeking a subsequent SPC does not fall under the scope of any "basic patent" for which a previous SPC was awarded. Similarly, the fourth and fifth questions were not deemed particularly relevant in view of the AG's recommendations on the first three Questions.
The AG thus concluded that:
[A] supplementary protection certificate for a product which is protected by a basic patent in force may be granted only on the basis of the first authorisation which permits that product to be placed on the market as a medicinal product which is within the scope of protection conferred by the basic patent in the Member State for which the application is made. The fact that the same product has previously been authorised as a medicinal product for human use or a veterinary medicinal product in the Member State for which the application is made does not preclude the grant of a supplementary protection certificate based on a later authorisation to place that product on the market as a new medicinal product, provided the first-authorised medicinal product is not within the scope of protection conferred by the patent designated by the applicant as the basic patent.
The ECJ's decision to follow the AG's recommendation, while coming as no surprise, certainly changes the landscape for the better for pharmaceutical patents and products in Europe. It is frequently the case that new uses can be found for old, well-established and characterized drug compounds, and extending the benefit of SPC protection can be expected to shift the investment scales to encourage such new uses. In a world where the drug pipeline from traditional pharmaceutical companies has dwindled, these considerations may prove crucial to addressing previously unmet medical needs.