Supplementary Protection Certificates (SPCs) were introduced in Europe to address a call for enhanced patent protection for pharmaceuticals that required regulatory approval to be placed on the market. The SPC provides a form of patent term extension for authorized medicinal products based on the product which is the subject of a marketing authorization which is protected by a relevant patent which is in force in the country concerned. The SPC system in Europe presents applicants with several challenges and, in particular, for combination products of more than one active substance.
A recent decision of the Court of Justice of the European Union (CJEU) with respect to SPCs for a product based on a combination of pharmaceutically active substances (C-121/17 – Teva UK Ltd & Others v. Gilead Sciences Inc. / Truvada®) shows that there is now a clearer line of jurisprudence on how to protect such inventions.
The take-home message for SPC applicants for combination products is to make sure that the relevant patent contains a sufficient disclosure which enables the identification of the active ingredients in the product in order to satisfy the requirement for the associated basic patent to protect the pharmaceutical product concerned. For patents with claims to combinations of active substances, there are certain forms of wording in the claims that should now be avoided.
This article provides an overview of the decision C-121/17 and considers the impact on claim drafting in patents directed to combination pharmaceutical products.
The original European Union (EU) Regulation (EC) 1768/92 entered into force in 1993 and has been amended and codified over the years. The relevant EU Regulation is now known as Regulation (EC) 469/2009 with relevance to pharmaceutical products. The SPC Regulation was amended most recently by the so-called “manufacturing waiver” Regulation (EU) 2019/933.
From the very beginning, the Recitals in the Regulation referred to the purpose of the new SPC law as harmonizing protection across the single market in Europe and providing incentives for the development of new medicines. However, it is also clear that the emphasis in the Recitals in the Regulation is to provide a fair balance between the needs of the innovator companies as well as the generics companies that will launch products after the relevant patents and data exclusivity provisions are expired.
The text of Article 3(a) of the Regulation specifies that an SPC may be granted provided that:
“the product is protected by a basic patent in force”
Reference to the “product” is defined by Article 1(b) which states that “product” means the active ingredient or combination of active ingredients of a medicinal product”.
The “basic patent” referred to in Article 3(a) is defined in Article 1(c) as meaning “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”.
Article 1(a) defines a “medicinal product” as 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”.
Finally, Article 3 contains some further important requirements in order for an SPC to be granted. Article 3(b) requires a valid authorization to place the product on the market as a medicinal product has been granted in accordance with Directive 2001/83/EC or 2001/82/EC, as appropriate. Article 3(c) also has an important proviso that an SPC shall not be granted if the product has already been the subject of an SPC.
The language used in the Regulation (Recitals and Articles) has led the CJEU to determine that the SPC law in Europe is really about the protection of active substances and not pharmaceutical products more widely. For example, reformulations or new dosage forms of active substances already on the market or medical devices incorporating an active substance have all been variously excluded from SPC protection.
The SPC law set out in the applicable EU Regulations is effective in the member states of the European Union (EU) and European Economic Area (EEA). The UK has left the EU but has decided to copy the EU law on SPCs into its domestic law and to recognize the existence of SPCs granted or applied for under the previous EU system. Other countries, such as Switzerland, also have a form of SPC protection which is modelled on the EU SPC law.
Combination products are a promising area in the treatment of many diseases. A co-therapy approach where patients are dosed with more than one active substance, either as separate dosages or within a single dosage form, is now a growing area for the development of new medicines. The combined drug treatment regimen requires a marketing authorisation to be placed on the market (even if one or both of the active agents is already authorized for use as a pharmaceutical). Combination products also arise in the area of vaccines where multiple components can be used to prepare the active form of the vaccine.
Many patents directed to a novel chemical entity will have claims drafted to a broad general formula in claim 1, followed by later dependent claims which define more particularly the preferred identities of the substituent groups in the general formula. Somewhere towards the end of the list of claims there will usually be claims which name specific active substances. Such patent applications will usually also contain experimental data to show the invention in practice in order to satisfy the sufficiency of description requirement of patentability, i.e. synthetic examples of how to make the claimed compounds and usually also some in vitro and/or in vivo examples of the biological effects of the compound. It would also be fairly typical for such patents to include claims directed to combinations of the compounds of the invention with other pharmaceutically active substances.
However, the rationale of the decisions of the CJEU in the field of SPCs means that such patents may be ineffective when it comes to providing the basis for an SPC to be granted to a combination product if the claim language and/or content of the patent does not meet a certain threshold test. The CJEU has been asked to consider a number of referrals over recent years on the question of the protection afforded by the basic patent to the product for which SPC protection is sought.
Protection by a basic patent
At first glance, the requirement for a product to be protected by a basic patent in force would appear to be rather generous and could be seen as merely requiring that the product merely falls within the claims of the patent, i.e. “protection” under the patent might look like an “infringement” test. However, this interpretation has been roundly and repeatedly quashed by the CJEU.
Instead, a patent is only recognized as protecting a product for the purposes of SPC protection if the patent discloses the invention represented by the product. This interpretation is seen most clearly in the CJEU decisions dealing with combination products of more than one active substance. There has been some uncertainty as to whether this extended to a requirement for evidence that the patent contains a description of the “core inventive advance”. Such a narrow definition of the protection requirement has also now been confirmed as not applicable as a means for assessing the validity of an SPC application.
Consequently, there is a middle-way in how the “protection” under the basic patent should be considered. The test does not relate to “infringement” of the claims of the patent by the product, nor is there a requirement for the “core inventive advance” to be considered. While some patents may well exemplify the specific combination of active substances, tomother patents will be held as providing protection to the combination of active substances provided that the disclosure is such that at the priority date the patent can be seen as containing a teaching of the combination.
In the recent decision of the CJEU in the case C-121/17, concerning the product Truvada® (a combined formulation of emtricitabine and tenofovir disoproxil for use in the treatment of HIV in humans), the validity of an SPC to a combination product was considered in view of the claims in the basic patent. The CJEU was able to consider the case law in this area to date and provide guidance to applicants for SPCs for combination products.
In C-121/17, the relevant claim 27 in the basic patent relied on for the corresponding SPC for Truvada® was worded as follows:
“A pharmaceutical composition comprising a compound according to any one of claims 1-25 together with a pharmaceutically acceptable carrier and optionally other therapeutic ingredients.”
The claims 1-25 contained a general formula which included tenofovir disoproxil and claim 25 also specifically named the active compound. The words “other therapeutic ingredients” in claim 27, however, were neither defined nor explained in the basic patent. At the priority date of the patent there was no evidence that emtricitabine was known to be effective for the treatment of HIV in humans.
In C-121/17, the CJEU decided that:
the combination of those active ingredients must necessarily, in the light of the description and drawings of that patent, fall under the invention covered by that patent, and
The court did not require that claims actually mention the combination of active ingredients. However, the court did direct that that it should be possible for the skilled person to determine that the combination of active ingredients of which the product which is the subject of the SPC necessarily falls under the invention covered by that patent, and whether each of those active ingredients is specifically identifiable on the basis of the prior art at the filing date or priority date of that patent.
In summary, a patent with broad generic claims, which only references the combination of active substances as an option and where one of the components is not known at the priority date for the stated authorized use will not be enough for a valid SPC application.
The decision may be frustrating for innovator pharmaceutical companies looking to extend effective patent term for products after the long process of bringing a product successfully to the market where the patents in their portfolio were filed in the past, perhaps before the product development strategy was fully realized. However, there are some actions that patent proprietors can take to safeguard their position at an early stage during the examination of the underlying basic patent in order to avoid such problems.
Strategies for success
Given where the CJEU has got to now on SPCs what can innovator companies do to improve their chances of success for combination products?
1. For patent applications to new chemical entities and/or with claims to combinations of active substances:
include claims directed to combinations of active ingredients known to be effective at the priority date (with a full description in the specification – this is essential);
avoid use of claim language to “optional” combinations;
review applications on filing and at allowance to check that claim language is not limited to “optional” combinations;
include experimental data (where possible) to the combination (this is desirable in case the position of the CJEU evolves further);
2. Consider filing rolling series of filings at 18 months from priority date of preceding filing so as to make most use of the novelty only requirement for an improvement filing to a combination (assuming no other intervening art)