Sheena Linehan takes a look at the recent legal cases impacting the life sciences landscape
Issues arising from the repurposing of medicines for new uses are a dominant theme in this roundup of legal judgments from the past six months.
The UK Supreme Court has dismissed Warner-Lambert’s appeal concerning its patent for a new medical use of pregabalin for the treatment of pain, and the European Union Court of Justice (CJEU) has ruled as lawful an off-label use of Avastin for treatment of eye diseases.
Other significant rulings include the English Patent Court’s award of a declaration that GlaxoSmithKline would not infringe Vectura’s yet-to-be-granted patents, and the CJEU ruling against the award of supplementary protection certificates (SPC) for medical device/drug combinations which have received regulatory approval under the EU Medical Devices Directive.
November 2018 – UK Supreme Court judgment in Warner Lambert v Actavis
Warner-Lambert’s second medical use patent for pregabalin for the treatment of pain was held invalid for failing to sufficiently disclose a technical contribution. It would need to have been evident from the patent as filed that it was at least plausible that pregabalin would be effective for the treatment of neuropathic pain. The Court’s view was that if the patent had been valid, it would not have been infringed by Actavis’ generic pregabalin product. A key consideration was that the package leaflet in Actavis’ product did not refer to the patented pain indication, but only to the indications for which patent protection had expired.
Although the Supreme Court’s reliance on plausibility as an aspect of sufficiency of disclosure is binding on lower courts, its views on infringement of second medical use patents are not, because they were delivered as obiter dicta, ie the decision on validity determined the outcome of the case, and the additional remarks on infringement were in a sense superfluous. The law appears unsettled in both areas, and a different approach could be taken in the future, particularly following the swearing-in of IP specialist Lord Justice Kitchin to the Supreme Court in October 2018.
Second medical use patents may be more vulnerable to attack following the Supreme Court’s decision if they lack sufficient technical evidence for why it is plausible that the medicinal product would be effective for the new indication.
February 2019 – CJEU decision in Staat der Nederlanden v Warner-Lambert, Case C-423/17
Under the EU’s decentralised marketing authorisation (MA) procedure, a generic manufacturer may rely on the MA of the originator’s reference medicinal product, to avoid lengthy clinical trials.
Typically, the summary of product characteristics (SmPC) of the generic medicinal product would be the same as that of the reference medicinal product. However, where the reference product is still subject to patent protection in relation to certain medical uses or dosage forms, the generic manufacturer may request limitation of the SmPC, ie to ‘carve out’ the patented uses or dosage forms.
It was the practice of the Dutch MA authority not to publish such carve-outs. Warner-Lambert brought a claim against The Netherlands that the agency’s practice would encourage prescription of generic pregabalin for the patented pain indication.
The CJEU decided that, where the applicant or holder of an MA for a generic medicinal product provides the competent national authority with a package leaflet or SmPC with a carve-out for still protected indications or dosage forms, that constitutes a request for a limitation of the scope of the MA of the generic medicinal product in question. As the MA is limited by the carve-out, the national authority must publish the package leaflet and SmPC with the requested carve-out.
Infringement of second medical use patents is possible in the Netherlands, if a producer of a generic medicine has not made an effort to prevent it being prescribed for a patented indication, following Sun v Novartis [2017]. A carve-out of patented indications or dosage forms may be a relevant factor in avoiding infringement.
The CJEU ruling takes a step towards EU harmonisation of the practice around authorisation of generic medicines where patent rights protecting certain uses or dosage forms of the originator’s product remain in force.
November 2018 – CJEU decision in Novartis Farma v Italian Medicines Agency and Roche Italia, Case C-29/17
Avastin and Lucentis are both anti-vascular endothelial growth factor (VEGF) monoclonal antibody products. Avastin is marketed by Roche and is used at a high dose in cancer treatment. Lucentis is marketed by Novartis and is used at a lower dose in treatment of eye diseases. Off-label use of Avastin for treatment of eye diseases has vexed Novartis in several European territories.
According to this ruling of the CJEU, repackaging of Avastin in pharmacies for the purpose of its off-label use, involving splitting of a vial of Avastin into separate doses, does not significantly change its fundamental characteristics, and repackaged Avastin still falls within the scope of the EU Medicinal Products Directive. As such, it is recognised as a licensed medicine. The Directive does not impact national law that allows Avastin to be repackaged for its off-label treatment of eye diseases, provided that the process of repackaging is prescribed by a doctor via an individual prescription and carried out by a pharmacist.
This follows the UK High Court judgment of September 2018 in Bayer v NHS Darlington Clinical Commissioning Group, which approved as lawful a policy of offering Avastin as a preferred treatment to certain eye disease patients as a cost-saving measure. Although the High Court had accepted the view of the UK Medicines and Healthcare Products Regulatory Authority (MHRA) that repackaged Avastin was an unlicensed medicine, Clinical Commissioning Groups were entitled to conclude that Avastin and licensed anti-VEGF agents including Lucentis were of equivalent safety and efficacy.
These decisions mark a significant shift from the principle that it is for the manufacturer of a medicinal product to control the uses to which it is put. The CJEU ruling may increase the off-label prescribing of Avastin for treatment of eye diseases in Europe.
December 2018 – English Patents Court ruling in Glaxo Group v Vectura
GSK has succeeded in obtaining an ‘Arrow declaration’ in a patent dispute with Vectura concerning inhalable medicine formulations. This is a relatively new form of discretionary legal remedy, in which the Court grants a declaration that a party’s product or process was known or obvious at the priority date of the other party’s patent(s). Such a declaration can be used as a defence in a later infringement suit arising following grant of secondary patents, and is intended to provide commercial certainty to the claimant that its product will not infringe yet-to-be-granted patents.
The Arrow declaration is an example of legal innovation that makes the English courts an attractive forum for patent litigation. An Arrow declaration awarded in the UK could potentially be used in settlement negotiations by generic manufacturers seeking to clear the way in Europe.
October 2018 – CJEU decision in Boston Scientific, Case C-527/17
Supplementary Protection Certificates (SPCs) are IP rights which extend patent protection for an authorised medicinal product for up to five years, and are intended to compensate the right holder for the delay in marketing its product due to the lengthy marketing approval process. The CJEU has now ruled out SPCs for medical device/drug combinations that have received regulatory approval by virtue of a CE certification under the EU Medical Devices Directive. This followed a reference by the German Federal Patent Court in relation to Boston Scientific’s application for a SPC on the basis of CE certification for a paclitaxel-eluting stent.
This ruling will disappoint innovators in the med tech sector, but at least clarifies that SPCs are not available for medical device/drug combinations which have received regulatory approval under the EU Medical Devices Directive.
Upcoming cases
The UK Supreme Court heard an appeal in Actavis v ICOS in November 2018, and its judgment is expected imminently. This is another second medical use patent case, concerning obviousness of a daily dosing regimen of tadalafil in the treatment of erectile dysfunction. The judgment will consider whether a dosage regimen arising from a routine clinical trial could nevertheless be inventive by virtue of its efficacy being surprising.
The Supreme Court appeal in Regeneron v Kymab is one to watch. The hearing, which is yet to be scheduled, will consider whether Regeneron’s patents sufficiently disclose a genetic modification technology for producing humanised antibodies in mice. A key issue is whether the notional skilled person could have used the invention by adapting the teaching of an Example in Regeneron’s patents.
Sheena Linehan is a patent attorney and life sciences specialist at leading IP firm, Potter Clarkson www.potterclarkson.com
