Could a clinical trial publication kill a patent?

R&D productivity is an ongoing challenge for the pharmaceutical industry. Deloitte’s eighth annual pharmaceutical innovation study reported R&D returns declining to 3.2% in 2017 for large-cap pharma, down from 10.1% in 2010. Two factors are seen as driving the decline –

An increase in the average cost of the development process – now around $ 2bn to reach the market from about $ 1.2bn in 2010
A decline in average peak sales.

Astra Zeneca decided to address this problem very publicly, with the publication in 2014 of its 5R framework paper. An analysis of its track record led to the identification of five technical determinants of project success and pipeline quality: the right target, the right patient, the right tissue, the right safety and the right commercial potential. Since then AZ has cut project numbers and seen a marked improvement – the success rate of drug candidates has jumped from 4% in 2005-2010 to 19% in 2012-2016.

Early culling of drug candidates and increased focus on fewer projects leaves a bank of molecules in discontinued projects, but these might still have useful applications elsewhere. Pfizer’s blockbuster Viagra famously emerged from clinical trials of the drug for cardiovascular disease. AZ uses an Open Innovation Portal to allow external scientists to access these and find ways of developing them for other uses. And many drugs are successfully developed by companies in-house for use in other indications.

Patent protection for a product can be effectively extended by filing for protection of second medical use patents, and patents for treatment and dosing regimes. Patent protection will also be supplemented by any regulatory data protection in place for the product in question.

However, carrying out the clinical trials necessary to establish efficacy of a repurposed drug or dosing regime could undermine the patentability of that innovation.

One example of this problem arose in the European Patent Office in 2017. Novartis filed for patent protection for a new method of administering biophosphonates to treat osteoporosis. The drug would be administered annually.

One of the pieces of prior art filed in opposition proceedings was a document providing information for patients in the context of a clinical study investigating different dosage regimes. Novartis argued that the document was not publicly available. There was a special relationship between the trial sponsors, patients and supervising doctors so that a tacit secrecy agreement applied.

The EPO Board of Appeal disagreed. There was no special relationship obliging patients to keep the document secret and in fact, patients were encouraged to discuss their participation in the clinical study with others. The document did not disclose the invention completely, but it would create an expectation of success that was not undermined by other literature. The Board decided that the patent was obvious in the light of the clinical study disclosure.

This makes life difficult for those trialling repurposed drugs and new formulations or dosage regimes. Without the evidence from the clinical study you might find your patent application rejected on the basis of lack of support.

Disclosure of information about clinical studies is set to increase with the disclosure reforms envisaged by the Clinical Trials Regulation, and with the need to provide full information to patients under the GDPR. So we can expect these kinds of problems to arise more often. While clinical trial sponsors cannot avoid the need to inform patients about the trial, or to make the disclosures required under the legislation, being aware of the issues may help inform strategy. Filing patent applications as early as possible and against clear strategic objectives, protecting molecule code numbers and seeking protection of commercially confidential information within the transparency rules can help to reduce the risk of patents later coming up against challenges of invalidity.

James Fry