SPCs on combination products - is it specified?

It is almost 20 years since SPCs were introduced across the European Union, firstly for medicinal products, and later for plant protection products, that require authorisation by a regulatory body prior to marketing. The aim of SPCs is to compensate the patent holder for the patent term lost due to the need to obtain regulatory approval. In the EU, SPCs can extend the term of protection for such a patented product by up to five years². As the term of the SPC is often the time when the product achieves its peak sales, obtaining SPCs is of critical importance to the pharmaceutical and agrochemical industries.

Thousands of SPCs have been granted for medicines and plant protection products containing a single active ingredient which has obtained regulatory approval. However, the award of SPCs for products containing a combination of active ingredients has been a controversial matter in EU countries. This issue is particularly important for vaccines, which frequently contain a combination of active ingredients: health authorities often insist that multiple vaccines be administered in a single dose to minimise the cost and inconvenience to patients.

Over recent years, a number of conflicting decisions have issued from national courts regarding SPCs for combination products. Three particular questions have arisen:

1. Can an SPC be granted for an authorised medicinal product which contains a combination of active ingredients (A + B) when the basic patent protects only active ingredient A (or a combination of A and an unspecified further active) and does not specifically claim the combination A + B?
2. Can an SPC be granted for an authorised medicinal product containing only active ingredient A even when the marketing authorisation additionally refers to other active ingredients in addition to those claimed in the patent (A + B; A + C; A + B + C; and so on)?
3. Can an SPC be granted for an authorised medicinal product which contains a single active ingredient (A) when the basic patent protects only a combination A + B and does not specifically claim A alone?

These questions resulted in the above cases being referred to the CJEU. The Medeva case, which considered both questions (1) and (2), related to a vaccine for diphtheria, tetanus, whooping cough, polio and meningitis which contained between eight and 11 active ingredients, only two of which were specifically claimed in the basic patent. The Georgetown University case, which considered only question (2), related to the human papilloma virus (HPV) vaccines Gardasil® and Cervarix® used to prevent cervical cancer, and which contain a number of active proteins. The University of Queensland case related to the same cervical cancer vaccines, but considered both questions (1) and (2) and also the applicability of these questions to process patents. The Yeda case considered questions (1) and (3) and related to the anticancer drug Erbitux® (cetuximab).

The Daiichi Sankyo case related to the combination anti-hypertensive product Olmetec Plus® (olmesartan medoximil and hydrochlorothiazide), but considered only question (1).

Two opposing arguments were put to the CJEU regarding question (1). These reflected the conflicting positions adopted by the referring national IP offices and courts. Some parties argued only the literal wording of the claims was relevant for deciding the question of whether the product was ’protected‘ by the basic patent, and therefore any combination products containing active ingredients not specifically recited in the claim wording should be excluded from SPC protection. Other parties argued that an ’infringement test‘ should be adopted, and that any product containing the authorised active and which would have infringed the basic patent should be considered ’protected‘ by the basic patent and therefore the SPC: if such an ’infringement test‘ were to be adopted, an authorised medicinal or plant protection product containing A + B would infringe a basic patent reciting only A in the claims.

There is currently no European Union law which determines the scope of protection of a patent: harmonisation of the national patent laws of European countries is based on the European Patent Convention (which is an inter-governmental agreement independent of the EU) rather than EU legislation. However, the CJEU pointed out that the EU SPC regulations provide that any SPC confers the same rights as conferred by the basic patent and is subject to the same limitations and the same obligations. Based on this, the CJEU considered in Medeva (and followed in Daiichi Sankyo) that Article 3(a) of the medicinal products SPC regulation (469/ 2009) precludes the grant of an SPC relating to active ingredients which are not specified in the wording of the claims of the basic patent.

Furthermore, the CJEU ruled that if a patent claims that a product is composed of two active ingredients but does not make any claim in relation to one of those active ingredients individually, an SPC cannot be granted on the basis of such a patent for the one active ingredient considered in isolation. The combined effect of the above rulings means question (1) can be answered as follows:

• An SPC must not be granted for an authorised medicinal product which is a combination of two active ingredients (A + B) if the literal wording of the basic patent claims A in isolation. This applies even if the claims use “comprising” or similar language which does not exclude the presence of another active.
• An SPC must not be granted for an authorised medicinal product which is a combination of A + B if the literal wording of the basic patent claims a combination of A with another unspecified active ingredient.
• An SPC may be granted for an authorised medicinal product which is a combination of A + B if the literal wording of the basic patent claims A in combination with the specified active ingredient B.

Regarding question (2), in both the Medeva and Georgetown cases the CJEU referred in detail to the objectives behind SPCs and the particular issues regarding combination products, especially vaccines. The CJEU considered that, if the holder of a basic patent relating to an innovative active ingredient (or an innovative combination of active ingredients) were to be refused an SPC on the ground that the marketed product also contained other active ingredients or combinations which may have other therapeutic purposes and may or may not be protected by another basic patent in force, the objectives of the SPC Regulation could be undermined. The CJEU was also of the opinion that such an approach would tend to favour the development of monovalent medicinal products, in particular vaccines, which may not be in the interests of patients or health authorities. For these reason, in the Georgetown University case, question (2) was answered as follows:

• An SPC may be granted for an active ingredient (A) if the wording of the claims of the basic patent relied on specifies A, even if the authorised medicinal product contains not only that active ingredient but also other active ingredients (A + B, A + C and so on).

In the Medeva case, for the same reasons, the CJEU similarly ruled that question (2) can be answered in a similar manner for SPCs based on basic patents specifying a combination of actives (A + B) even if the authorisation covers A + B + C, A + B + D and so on.

In the Yeda case, the CJEU also followed the reasoning given in Medeva and extended it to answer question (3) as follows:

• An SPC must not be granted for an authorised medicinal product which contains a single active ingredient (A) when the wording of the claims of the basic patent specifies only a combination A + B and does not relate to A alone.

In the University of Queensland case, the CJEU also followed the reasoning given in Medeva and extended it to the situation where, when the basic patent relied upon relates to a process for producing a product, Article 3(a) also precludes the grant of an SPC relating to a product other than that identified in the wording of the claims of the basic patent as the product deriving from that process. The CJEU ruled it irrelevant whether it is possible to obtain the product directly as a result of that process.

It is difficult to understand how the clear reasoning applied by the CJEU regarding the underlying purpose of SPCs to answer question (2) was not also applied to questions (1) and (3). Moreover, it is unclear from the rulings how specific the claim language has to be for the product to be ’specified‘ in the claim wording. For example, do claims to products defined by therapeutic class (for example, antibiotics) or by general Markush formulae ‘specify’ the individual active ingredients they cover? In addition, do biologic patents that claim, for example, antibodies to a particular antigen without disclosing the antibody ’specify‘ the antibody that is eventually authorised?

The decisions reached in these cases, as well as denying SPC protection for the products in question, may also leave the validity of granted SPCs for some combination products, both medicinal and plant protection, in some doubt. In addition, in the Medeva decision the CJEU also opined that when a patent protects a product, Article 3(c) permits only one SPC to be granted for that basic patent. This comment (which itself refers back to a similar comment in the earlier Biogen decision regarding multiple SPCs for the same product) was not referred to in any of the questions referred to the CJEU, and could be considered an aside. However, if followed in a later decision it may make it difficult to obtain two or more separate SPCs for different authorised products covered by the same basic patent, even though basic patents which support more than one SPC already exist.

In view of these decisions, we would recommend the following changes be considered for future pharmaceutical and plant protection patent applications covering a single active ingredient A, either as a species or as part of a broader genus of compounds:

• New applications: if a likely commercial product A has already been identified, these should include claims explicitly directed to any specific combination products (A + B, A + C, and so on) considered likely to be of commercial interest at the time the application is filed. For example, for pharmaceutical patent applications, the specific actives B, C and so on may be marketed products (or those currently undergoing clinical trials) for the same therapeutic indication as A. Before deciding to include such combinations explicitly in the text, the possible prior art effect on a later patent application specifically directed to such combinations should be considered.
• Pending European patent applications: if active ingredient A has received or is likely to be submitted for regulatory approval, these applications should be reviewed to ensure that any specific combinations of actual or potential commercial importance, but which are currently disclosed in the description only, are included in the literal wording of the claims when granted.
• Granted European patents: if active ingredient A has received or is likely to be submitted for regulatory approval, these should be reviewed to consider whether any specific combinations of actual or potential commercial importance which are disclosed in the application as filed, but not specified in the literal wording of the claims as granted, could be claimed using the EPO’s post-grant limitation procedure. Such a limitation may not extend the protection conferred by the patent. However, if the granted patent contains a claim to a combination of A with another unspecified active ingredient, such a claim could be validly limited by specifying the active as B, C and so on.

Notes

1. Medeva C-322/10; Georgetown University C-422/10; Yeda C-518/10; University of Queensland C-630/10; Daiichi Sankyo C-6/11
2. For pharmaceutical products a further six-month extension to the SPC term can be obtained if agreed paediatric studies are carried out, whatever their outcome.

Useful links

Full text of decision C-322/10 Medeva
Full text of decision C-422/10 Georgetown University
Full text of decision C-630/10 University of Queensland
Full text of decision C-518/10 Yeda
Full text of decision C-6/11 Daiichi Sankyo