On 12 December 2013, the CJEU handed down three eagerly awaited decisions on SPCs: C-443/12, Actavis UK Ltd v Sanofi; Case C-484/12, Georgetown University and Case C-493/12, Eli Lilly and Company Ltd v Human Genome Sciences Inc. The first two decisions provide some clarity for patentees on SPCs for combination products and Article 3(c) of the regulation (“regarding the number of SPCs per patent per product), while the third dealt with Article 3(a) of the regulation as it relates to antibody products “protected by a basic patent”. Interestingly, the third decision, in obiter comments, hints at the approach it would take on questions concerning third party SPCs. There are some practical points that a patentee and patent attorneys can take away from these decisions, with regard to best drafting practice for patent applications and best filing practice and product definition for SPCs.
Sanofi has market authorisations for Aprovel (irbesartan) and CoApprovel (irbesartan and hydrochlorothiazide, a diuretic). Claim 1 of the relevant patent is directed to a compound of generic formula encompassing, inter alia irbesartan, claim 7 claims irbesartan specifically and claim 20 refers combinations of the new compounds with a diuretic. Sanofi had granted SPCs for each of the two products. Actavis intended to market a generic version of both products and wished to clear the way by applying to revoke the SPCs in the English court. The referred questions were whether the combination product was specified in the wording of the claims (Article 3(a)) and whether, for a situation where multiple products are protected by a patent, whether a SPC can be granted for each, ie. whether the CoAprovel SPC was valid in light of the the earlier SPC for irbesartan (Article 3(c)).
The first question had been touched on in the earlier Medeva case C-322/10, but the English court took the view that that decision did not provide a clear test as to whether a product is protected by a “basic patent”. Our hopes for further clarification on the Article 3a issue were dashed, as the court ruled only on the Article 3(c) issue (one SPC per patent). In so doing the court has created a new concept, that of the “core inventive advance”. The court decided that the SPC granted on the CoAprovel product was invalid, since an SPC had already been granted for the “product”. This decision concludes that there can be only one SPC per core inventive advance per patent.
The court said:
However, in circumstances such as those in the main proceedings, even if the condition laid down in Article 3(a) of Regulation No 469/2009 were satisfied, for the purpose of the application of Article 3(c) of that regulation, it cannot be accepted that the holder of a basic patent in force may obtain a new SPC, potentially for a longer period of protection, each time he places on the market in a Member State a medicinal product containing, on the one hand, the principle active ingredient, protected as such by the holder’s basic patent and constituting, according to the statements of the referring court, the core inventive advance of that patent, and, on the other, another active ingredient which is not protected as such by that patent.
I have added emphasis to what I believe are the most important points in the decision. The first point is that the decision would not have changed if Article 3(a) were satisfied, i.e. even if hydrochlorothiazide was specified in the claims. The second point is that irbesartan is seen to be the “core inventive advance” and that hydrochlorothiazide is not “protected as such” by the patent. This is not to be confused with the wording used in 3(a) as they are two very different issues. I believe that the issue here is that a medicament comprising hydrochlorothiazide as the only active ingredient, would not infringe the patent in issue.
The court also referred to Article 13, which dictates that, upon expiry of the initial SPC, the holder thereof may no longer, in connection with the basic patent used as the basis for the grant of the SPC, oppose the marketing by third parties of the active ingredient which was the subject of the protection conferred by that SPC. This means that, after that date, it must be possible for third parties to place on the market not only medicinal products consisting of the formerly protected active ingredient but also any medicinal product containing that active ingredient in combination with another active ingredient that is not protected as such by the basic patent or any other patent. This would preclude the possibility of a valid CoAprovel SPC. The court referred to the objective of the Regulation, to compensate the patentee for delays in exploitation of his invention, and also the need to balance the interests of the pharmaceutical industry and public health as regards encouragement of research.
As an interesting point, the court made reference to the fact that there was no synergy between the drugs, and that CoAprovel merely conferred an additive effect. This was used to support the court’s opinion that irbesartan was the core inventive advance. It was implied that the situation would be different if the patentee had support in the specification for arguing that the Combination claim related to a second core inventive advance. It was also implied that the situation would be different if the patentee had a separate patent on the combination, for instance where the claims could be argued to relate to a different core inventive advance to that of the original patent.
We think it is worth considering a divisional strategy assuming there is basis, to claim combination products in the situation that during pendency of an application, combination products are being developed, or plans are being made to do so.
The independent patentability of specific combinations and dosage forms of such must be reviewed as development progresses, as it may well be worth filing separate patent application on potentially commercially relevant combination products. (It is interesting to note that Sanofi has some protection in the form of a narrowly defined specific formulation of irbesartan and HCTZ with excipients, EP1275391, based on a 1996 filing. This would have had no value as basis for a SPC since the term of protection runs longer than 15 years from the first MA in the EU/EEA for CoAprovel.)
When drafting initial applications on NCEs take care not to speculate unduly about combinations, where specific unobvious combinations may be developed in future, to avoid prejudicing novelty/inventive step of later developments.
When deciding on the SPC filing strategy, if one of the options is to base a SPC on a patent which has already served as basis for an earlier SPC, the test whether Art 3(c) of the Regulation precludes its validity has to determine whether the second product relates solely to the core inventive advance of the first product. If it can be argued that it relates also to a second core inventive advance, the second SPC may be valid.
SPCs on combination products may be at risk of being held invalid, if based on a divisional patent, where the parent has formed the basis for a SPC on one of the components, embodying the core inventive advance, and where the core inventive advance of the divisional is no different to that of the parent, ie the claims of the divisional are obvious over the claims of the parent.
On the positive side for patentees, it was accepted that, had CoAprovel been granted an MA first, this could have formed the basis for a SPC for the irbesartan, not limited to the combination. This confirms the decision in Georgetown 1 (C-422/10).
This decision promised lots, but did not deliver on all issues. As a recap of the facts, Georgetown filed eight SPC applications relying on the MA granted to Sanofi on 20 September 2006 for the medicinal product Gardasil, containing HPV-6, HPV-11, HPV-16 and HPV-18 purified proteins, and on the MA granted to GlaxoSmithKline on 20 September 2007 for the medicinal product Cervarix, containing HPV-16 and HPV-18 purified proteins. Two of those applications concerned the combination of HPV-6, HPV-11, HPV-16 and HPV-18 and the combination of HPV-16 and HPV-18. Four other applications were for SPCs in respect of, respectively, HVP-16, HPV-18, HPV-6 and HPV-11 individually.
Among the questions referred was whether it was possible to have more than one SPC per patent, and on whether surrender of an SPC had retroactive effect. Unfortunately, no decision was issued on the second point.
On the first point, it was decided:
In circumstances such as those in the main proceedings, where, on the basis of a basic patent and a marketing authorisation for a medicinal product consisting of a combination of several active ingredients, the patent holder has already obtained a supplementary protection certificate for that combination of active ingredients, protected by that patent within the meaning of Article 3(a), Article 3(c) of that regulation must be interpreted as not precluding the proprietor from also obtaining a supplementary protection certificate for one of those active ingredients which, individually, is also protected as such by that patent”.
On first reading the decision might appear to be contradictory to the Actavis decision. How is it that an SPC was available for Gardasil, but also for the single HPV-16 protein, but that SPCs were not available for Aprovel and CoAprovel? This is how the court dealt with that point:
Accordingly, the facts in the main proceedings may also be distinguished from those in the case which gave rise to the judgment in Actavis Group PTC and Actavis UK… The issue in that case was whether, on the basis of that basic patent but a subsequent MA for a medicinal product containing that same active ingredient in combination with another active ingredient not protected as such by that patent, the patent holder was entitled to apply for a second SPC relating to the combination of the active ingredient which had already led to the grant of an SPC and the active ingredient not protected as such by that patent.
In the present case, the court held that both HPV-16 and the combination product were protected by the patent, within the meaning of Article 3(a), and therefore the grant of more than one SPC is not precluded. This does appear to be contradictory to the statement in Actavis that an SPC was not allowed for CoAprovel irrespective of Article 3(a). However, we notice two important distinctions. The first is that the SPCs for the Georgetown combination product and HPV-16 would expire on the same date, meaning that third parties could market the combination product without fear of infringement, once the HPV-16 SPC expired (c.f. Article 13 of the regulation). The second distinction is that each and all of the elements of the combination product are protected by the basic patent, and each arguably represents an innovation in its own right.
The second issue the referring court had raised related to the retroactive effect of withdrawals of SPCs. Since the Court decided that multiple SPCs were not precluded in this situation, they avoided the need to answer those additional questions. It is to be recalled that the Advocate General’s opinion took the view that such withdrawals were not retroactive, and so withdrawal of a one SPC (or application) in favour of a further application, could not render the further application registrable.
Human Genome Sciences (HGS) discovered the neutrokine alpha protein and filed patent applications that disclosed and claimed it and related polynucleotides and antibodies. Since neutrokine alpha is involved in inflammation and immune responses, antibodies that inhibit its activity were of particular interest for the treatment of autoimmune diseases.
HGS has developed and received approval for such a monoclonal antibody called belimumab (Benlysta®) in the treatment of systemic lupus erythematosus (SLE). Eli Lilly is independently developing another such antibody called tabalumab in different indications, and is concerned that HGS may secure an SPC on tabalumab based on Lilly’s marketing authorisation. In an effort to prevent this, Lilly sought a declaration that any such SPC would be invalid, at least, because the Lilly antibody is not specified in the HGS patent claims as required under Article 3a of the SPC regulation.
The High Court, in hearing Lilly’s petition referred the following questions to the CJEU:
(1) What are the criteria for deciding whether “the product is protected by a basic patent in force” in Article 3(a) of Regulation [No 469/2009]?
(2) Are the criteria different where the product is not a combination product, and if so, what are the criteria?
(3) In the case of a claim to an antibody or a class of antibodies, is it sufficient that the antibody or antibodies are defined in terms of their binding characteristics to a target protein, or is it necessary to provide a structural definition for the antibody or antibodies, and if so, how much?
In considering the first question the court notes the Commission’s acknowledgement “that to insist upon a literal reference to the active ingredient in the claims of a basic patent would be unduly restrictive”, but it continued “it should be immediately evident from the claims of a basic patent that the active ingredient for which an SPC is sought is actually claimed by that patent.”
The court reiterated that determining the scope of a patent’s claims is a matter for national courts, but it reiterated that an infringement test is not appropriate for this determination. The regulation did not specifically rule out that a product could be adequately specified in the claims if defined functionally on condition “that the claims relate, implicitly but necessarily and specifically, to the active ingredient in question.”
Another, thornier question has been raised by Lilly in the national proceedings from which this referral sprang – is a patentee entitled to an SPC where they have played no role in obtaining market authorisation of the competitor’s product. The court commented that “if an SPC were granted to the patent holder, even though – since he was not the holder of the MA granted for the medicinal product developed from the specifications of the source patent – that patent holder had not made any investment in research relating to that aspect of his original invention, that would undermine the objective of Regulation No 469/2009, as referred to in recital 4 in the preamble thereto.”
So this decision is good news for patentees having generic claims to antibodies that are defined by their binding specificity, and it may be that this issue is now settled insofar as it relates to single antibody products. However, the court’s comments concerning third party SPCs are sufficiently ambiguous to suggest that a number of new referrals will be necessary to grapple with a new unforeseen problem facing the regulation.