Gardasil: Israel draws closer to EU practice on combination products

Liad Whatstein (now practising as Liad Whatstein & Co) has just sent The SPC Blog the following report on an decision recently handed down by the Israeli Patent Office in connection with a patent term extension (PTE) for combination products. In essence the Israeli Patents Commissioner held that a patent claiming a single active ingredient was eligible for a PTE in connection with a combination product that comprised additional active ingredients. This decision, adds Liad, brings Israeli law in closer conformity with EU law in connection with SPCs for combination products. Writes Liad:

Gardasil is a quadrivalent vaccine comprising the proteins HPV18 L1, HPV16 L1, HPV11 L1 and HPV6 L1. Each of the four proteins in the vaccine protects against a separate strain of the Human Papilloma Virus (HPV). Merck's Israeli patent covers the HPV18 L1 protein and a composition comprising the protein. It does not specifically claim the other proteins included in Gardasil.

Under sections 64D(1) and 64A of the Israeli Patents Act, in order to be eligible for extension, the patent must claim the "material" ("the active ingredient in the medicinal product"). The Israeli PTO initially rejected Merck's PTE petition on the ground that the Israeli patent did not claim all the active ingredients in the product (i.e. there was no "match" between the scope of the patent and the "material").

The office's approach was in line with the approach taken in the past by several Patent Offices in Europe but was rejected by the Court of Justice of the European Union (CJEU) in Medeva and subsequently in Queensland & CSL which also related to Gardasil. It was also opposed to the traditional approach taken by the USPTO.

Merck appealed to Patents Commissioner. On 11 January 2015 the Commissioner overruled the decision and granted the PTE petition. In reaching his decision, the Commissioner noted that each protein in Gardasil was produced in separate fermentation and was a standalone API. Accordingly, the fact that HPV 18 L1 was combined with three other active ingredients in the product did not undermine the eligibility for patent term extension for the patent claiming a single protein.

Significantly, the Commissioner essentially adopted the patentee's approach solely based on analysis of the relevant statutory provisions and related Israeli case law, and completely disregarded the CJEU Medeva ruling. Nevertheless, the Commissioner's decision is an important precedent that brings Israeli law in closer conformity with EU law in connection with SPCs for combination products.

Generally, the Israeli Office is attentive to the legal situation and judicial developments in major jurisdictions. One exception is with respect to the peculiar and rather restrictive PTE system under Israeli law (for a short overview of these peculiarities see earlier SPC Blog post here). The Office has traditionally taken a restrictive approach in interpreting the PTE provisions, often resulting in denial of PTE eligibility. It is yet to be seen whether the recent decision may be a first step in the direction of more balanced decisions on patent term extensions.

Liad represented the patentee in the proceedings.

Synflorix: SPC can be based on covalently bound active ingredient -- in principle ...

This morning the Court of Justice of the European Union (CJEU) delivered its judgment in Case C‑631/13, Arne Forsgren v Österreichisches Patentamt, a request for a preliminary ruling under Article 267 TFEU from the Oberster Patent- und Markensenat, Austria. The CJEU obviously didn't consider this a tough case to decide, since it dispensed with an Opinion from Advocate General Bot.

The factual background runs as follows. Forsgren owned a European patent (EP0594610B1, ‘the basic patent’) relating to ‘Protein D ‒ an IgD-binding protein of Haemophilus influenzae’.  Protein D is present in a pneumococcal vaccine for paediatric use, ‘Synflorix’, the marketing of which was authorised by Commission Decision C(2009) 2563 for ‘Synflorix — Pneumococcal polysaccharide conjugate vaccine (adsorbed)’. From the wording of the marketing authorisation (MA) for Synflorix, it appears that Synflorix was composed of 10 pneumococcal polysaccharide serotypes which were conjugated to carrier proteins and adsorbed on to aluminium phosphate. In eight of those serotypes, Protein D was the carrier protein. The therapeutic indications set out in the MA were for

‘Active immunisation against invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age’. 

According to the MA, the excipients of that vaccine were sodium chloride and water for injections.

In September 2009 Forsgren applied to the Österreichisches Patentamt for an SPC for Protein D. No, said the office, since Protein D was just an excipient. On appeal, the Board of Appeal of the Österreichisches Patentamt agreed: while Protein D had a therapeutic effect against the Haemophilus influenzae bacterium, it wasn't present as such in Synflorix, being covalently bonded to other active ingredients. Accordingly, Protein D couldn't be authorised as a medicinal product within the meaning of the SPC Regulation. Forsgren appealed further to the Oberster Patent- und Markensenat, which decided to stay proceedings and to refer to the CJEU the following questions for a preliminary ruling:

‘1. Under Article 1(b) and Article 3(a) and (b) of [Regulation 469/2009], provided that the other conditions are met, may [an SPC] be granted for an active ingredient protected by a basic patent (in this case, Protein D) where that active ingredient is present in a medicinal product (in this case, Synflorix) as part of a covalent (molecular) bond with other active ingredients but none the less retains an effect of its own?

2. If Question 1 is answered in the affirmative:

(a) Under Article 3(a) and (b) of [Regulation No 469/2009], may [an SPC] be granted for the substance protected by the basic patent (in this case, Protein D) where that substance has a therapeutic effect of its own (in this case, as a vaccine against the Haemophilus influenzae bacterium) but the marketing authorisation for the medicinal product does not relate to that effect?

(b) Under Article 3(a) and (b) of [Regulation 469/2009], may [an SPC] be granted for the substance protected by the basic patent (in this case, Protein D) where the marketing authorisation describes that substance as a ‘carrier’ for the actual active ingredients (in this case, pneumococcal polysaccharides), where the substance, as an adjuvant, enhances the effect of those substances, but where that effect is not expressly mentioned in the marketing authorisation for the medicinal product?’

This morning the CJEU (Eighth Chamber) ruled:

1. Articles 1(b) and 3(a) of Regulation 469/2009 ...  must be interpreted as not precluding, in principle, the possibility that an active ingredient can give rise to the grant of a supplementary protection certificate where the active ingredient is covalently bound to other active ingredients which are part of a medicinal product.

2. Article 3(b) of Regulation 469/2009 must be interpreted as precluding the grant of a supplementary protection certificate for an active ingredient whose effect does not fall within the therapeutic indications covered by the wording of the marketing authorisation.

Article 1(b) of Regulation 469/2009 must be interpreted as meaning that a carrier protein conjugated with a polysaccharide antigen by means of a covalent binding may be categorised as an ‘active ingredient’ within the meaning of that provision only if it is established that it produces a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the marketing authorisation, a matter which it is for the referring court to determine, in the light of all the facts of the dispute in the main proceedings.

There may be some further comment from the blog team but, in the meantime your comments are most welcome.