Biotech’s UK SPCs application fails over nature of ‘active ingredients’

Charlotte Weekes and Catherine Drew of Pinsent Masons, who specialise in intellectual property law and regulatory matters in life sciences, were commenting after the High Court in England and Wales refused an appeal by US biotech company Halozyme, Inc. over two applications for SPCs.

Halozyme has separately combined recombinant human hyaluronidase – an enzyme found to have properties helpful to the administration of drugs in patients – with two existing medicinal products: trastuzumab, which is sold under the brand name Herceptin; and rituximab, which is marketed as MabThera. It applied to the UK Intellectual Property Office (IPO) for SPCs for the respective combination products. In March last year, the IPO rejected the applications on the basis that the products were not eligible for SPCs.

SPCs are available to obtain in the UK and EU and enable pharmaceutical patent holders to effectively extend the period for which they can exercise monopoly rights over the sale of medicinal products they have invested a lot of time and money into developing. SPCs are only available for ‘products’ that fall within the scope of SPC law and meet eligibility criteria set out in the legislation.

To be eligible for an SPC, the product must be “protected by a basic patent in force”; a marketing authorisation must have been issued to place that product on the market as a medicinal product; the product must not already have been the subject of an SPC; and the marketing authorisation relied on must be the first to place the product on the market as a medicinal product. For the purposes of SPC law, a product is defined as the active ingredient or combination of active ingredients of a medicinal product.

In assessing Halozyme’s SPC applications, the IPO’s hearing officer considered that recombinant human hyaluronidase does not constitute an active ingredient and that its respective combination with trastuzumab and rituximab did not make it a ‘product’ for the purposes of SPC law.

In reaching that view, the hearing officer considered case law developed by the Court of Justice of the EU (CJEU), the EU’s highest court, on the definition of an ‘active ingredient’. That case law, the hearing officer summarised, requires an ingredient to be shown to have a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the marketing authorisation that is relied on to support an SPC application.

The hearing officer reflected on the fact that while Halozyme claimed, for the purposes of its SPC applications, that recombinant human hyaluronidase did have a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the marketing authorisation, this was not supported by the description of that ingredient in the marketing authorisation itself.

Recombinant human hyaluronidase was described in the marketing authorisation as an excipient – a description that the hearing officer said was “entirely consistent” with the way the ingredient had been tested during the regulatory process, as evidenced in regulatory documentation. An excipient, the hearing officer said, facilitates the delivery of the active ingredient to where it can exert its therapeutic impact, but this, they considered, is not enough to demonstrate it is an active ingredient in its own right.

The hearing officer said other evidence can be adduced to support applications for SPCs, to supplement the information provided in the marketing authorisation. This, they said, includes the Summary of Product Characteristics (SmPC) and the European Public Assessment Report (EPAR) – documents pertaining to the regulatory approval process overseen by the European Medicines Agency (EMA). However, they said that evidence cannot be used to provide information for which there is no basis in the SmPC or EPAR.

In the High Court, Mr Justice Meade upheld the hearing officer’s decision and refused Halozyme permission to appeal to the Court of Appeal. He stressed that the High Court appeal was confined to a review of the hearing officer’s decision rather than a re-hearing of arguments raised before the IPO.

Mr Justice Meade said the case raised two central questions: what it is legitimate to consider to decide whether recombinant human hyaluronidase is an active ingredient; and whether recombinant human hyaluronidase is an active ingredient based on the materials that it is legitimate to consider.

On the first question, the judge considered it would be best to wait until after the CJEU had ruled on a referral made to it by the Czech Supreme Administrative Court in another case that also concerns Halozyme, where the CJEU has been asked, among other things, whether the inclusion of a substance in the category of excipients in an marketing authorisation for a medicinal product excludes the possibility of that substance constituting an active ingredient, and what evidence is required to support this.

Despite this, the judge considered that even if Halozyme’s evidence from outside the regulatory documents were taken into consideration in the context of its UK SPCs applications, recombinant human hyaluronidase still did not meet the criteria for constituting an active ingredient. He said that finding was one that was reasonably open to the IPO’s hearing officer.

Weekes said: “As well as providing important guidance as to when a product can be deemed a combination of active ingredients, the ruling provides a useful reminder that Patent Court judges in England and Wales will, on appeal, conduct a review a decision of the UKIPO’s Hearing Officers and not conduct a full rehearing.”

“When it comes to SPCs, we are always talking about questions which remain and from a UK perspective this decision leaves open the question of which documents should be considered when determining the nature of the components of a product for which an SPC has been sought. The judge’s view is that that question is better determined in a future case that comes before the UK courts after the CJEU first rules on the matter. In the UK, judges are no longer bound by CJEU case law but they clearly consider it still to be of interest and potentially persuasive,” she said.

Drew added: “The hearing officer proceeded on the basis that the regulatory documentation was the primary documentation to consider and rejected Halozyme’s ability to rely upon the basic patent and scientific literature, much of which was not before the EMA when marketing authorisation was sought for the medicinal products in question.”

“Mr Justice Meade also highlighted the ‘fatal error’ of Halozyme in misconstruing the clinical trial data comprised within the dossier for the marketing authorisation application for the medicinal product in question. Halozyme sought to argue that the data demonstrated the hyaluronidase enzyme was having a treatment effect on the cancer concerned, whereas in fact the trial was set up as a non-inferiority trial,” she said.

“In this way, the hearing officer and in turn Mr Justice Meade effectively prevented Halozyme from arguing a contrary position to the IPO as had been argued before the medicines regulator. Such an approach has to be correct, to ensure consistency in all aspects of the regulatory framework governing medicinal products,” Drew said.