Clinical trials and stratified medicine—maximising patent exclusivity

It is important to understand the likelihood of obtaining the required degree of exclusivity, whether through strong patent protection, data exclusivity or orphan designation. Richard Korn and Stephanie Pilkington look at how patent exclusivity can be enhanced as development progresses.

Since patent applications are often filed at an early stage in the development of a drug, long before clinical trials are contemplated, there is a danger that the clinical and regulatory teams dealing with the trials may take the patent situation for granted.

Conversely, patent attorneys are typically handed responsibility for obtaining valid patents, assessing third-party rights and clearing the way to market, but have no professional role in the clinical trials. This separation of patent and clinical/regulatory teams can easily lead to potentially patentable and highly valuable new inventions being overlooked.

It may be possible to strengthen the patent position for a drug by paying careful attention to clinical trials. A significant quantity of data arises from clinical trials, some of which may give rise to patentable new inventions for aspects including new dosage regimes, formulations, combinations, medical indications, and biomarkers of success or failure.

Since the trials may be conducted many years after the initial patent filing, this may prolong the period of exclusivity significantly past the normal or extended patent term. It also provides an opportunity to obtain a broader territorial scope of patent protection and may even allow a patent position to be secured for a project that previously relied solely on protection arising from data exclusivity or orphan drug marketing exclusivity.

Detailed and timely communication between patent attorneys and the clinical/regulatory experts conducting clinical trials is important if such opportunities are to be identified and exploited.

New dosage regimes

The patentability of a novel and inventive dosage regime for a drug that was previously known for treating that medical indication has been confirmed at the European Patent Office, and in European countries such as Germany and the UK, although not in France.

Phase I and II trials routinely include dose escalation studies to identify appropriate doses of a drug for therapeutic use. These studies have the potential to result in patentable inventions, for example, if they show that the drug is therapeutically effective at a dose that was not expected to be active and would not otherwise have been used.

New formulations

It is standard practice in the pharmaceutical industry to identify improved formulations of successful drugs and to attempt to patent the new formulations to extend the duration of patent protection. Supporters of this practice consider it to be legitimate lifecycle management; its detractors, however, condemn this ‘evergreening’ as an abuse of the system that delays the introduction of generic medications and negatively affects public health.

What is sometimes overlooked is that the new formulation must meet the same requirements as any other invention in order for a patent to be granted. In order to be non-obvious, it will usually be necessary to show that the new formulation has a surprising or unexpected property.

The standards required to demonstrate patentability of new formulations are typically quite high, but vary from country to country. India, for example, has introduced a requirement into its patent law that a new form of a known substance will not be patentable unless it results in enhancement of the known efficacy of that substance. So, new formulations may not be patentable in India without data from a clinical trial.

New indications

In phase III trials, the efficacy of a drug is tested on relatively large patient groups, often in comparison to current treatments. Patients enrolled in these trials undergo a thorough medical examination prior to, during and at the conclusion of the trial in order to assess efficacy in relation to predetermined medical endpoints and to identify adverse events.