An inherent tension exists at the nexus between IP and clinical trials arising from the requirements for obtaining patent protection and the disclosure requirements for registration of a clinical trial. This tension has escalated in Australia due to a recent court decision in which it was found that disclosure of untested clinical trial hypotheses can invalidate a patent. As such, patent applicants may wish to think twice before awaiting the outcome of a planned clinical trial before seeking patent protection.
Australia adheres to the Declaration of Helsinki, which provides that information relating to clinical trial protocols must be registered in a publicly accessible database before the first participant is recruited.[i] Typically, key details about the design, conduct and administration of planned clinical trials in Australia are registered in the Australian New Zealand Clinical Trials Register (ANZCTR). In addition, companies may issue announcements and press releases in relation to clinical trials to tout their success and/or attract investors, and unless a trial is conducted under confidentiality agreements, participants are free to discuss the trial and may engage in online discussion forums or post about the trial on social media. As a result, details of planned clinical trials are in the public domain before the trial even commences.
However, the fundamental requirements for patentability in any jurisdiction are that the claimed invention be novel (new) and inventive (non-obvious) when compared with information made publicly available at the relevant priority date. Therefore, any of the information discussed above may be used to support an invalidity challenge to a patent if made public before the priority date. As such, early filing of a patent application can have advantages, like avoiding the risk of an invalidating self-disclosure and deterring competitors.
Filing a patent application too soon can also be problematic. In most jurisdictions, patent applications must also contain adequate support for the claimed invention. There is a risk that an application filed too soon will lack the data needed to provide adequate support, or that surprising effects observed during the course of a clinical trial (e.g., in relation to the dosage, mode of administration, patient group, etc) are not described in the application. Therefore, implementing a suitable patent strategy involves a delicate balance between the risk of creating an invalidating self-disclosure and the need to obtain supporting data for the claimed invention, but finding that balance can be challenging.
Pharmaceutical company Mylan recently learned the hard way that unproven clinical trial hypotheses can invalidate a patent when the Australian Full Federal Court found that certain claims of one of its Lipidil® (fenofribrate) patents, directed to methods and uses involving fenofibrate for the treatment of diabetic retinopathy, lacked novelty and/or inventiveness in light prior-published clinical trial information.[ii] As a result, Mylan’s infringement case against Sun Pharma’s proposed launch of its generic fenofibrate products in Australia failed, leaving Sun Pharma free to enter the market.
In that case, Mylan had published a clinical protocol before the priority date of the patent in which it hypothesised, among other things, that use of a fibrate to lower triglyceride levels and raise HDL cholesterol levels in patients whom were already receiving a statin drug for treatment of LDL cholesterol levels, would reduce the rate of development or progression of diabetic retinopathy. Mylan had also published two clinical studies that used methods subsequently claimed in one of the patents. These documents were found to deprive Mylan’s patent claims of novelty, regardless of the fact that the hypotheses disclosed in those documents had not actually been tested before the patent application was filed. In contrast, the UK Supreme Court has confirmed that proof of concept is required in order to deprive a claim of novelty in that jurisdiction; a reasoned hypothesis is not sufficient.[iii]
The Australian Full Federal Court also found that certain claims of the same patent lacked inventiveness in light of a further clinical study, which “proffered the suggestion” that that lipid-lowering may decrease the risk of hard exudate formation and associated vision loss in patients with diabetic retinopathy. In view of that disclosure, the Court considered that the use of fenofibrate (which reduces elevated triglyceride levels and increases HDL cholesterol levels) in combination with statins (which reduce elevated LDL cholesterol levels) for treating diabetic retinopathy would be obvious.
As suggested above, second hand information about the clinical trial can also be problematic. For example, the High Court of Australia found Astra Zeneca’s Crestor® (rosuvastatin) patent, directed to methods of using low doses of rosuvastatin to treat high cholesterol, to be invalid for obviousness in view of the mere mention in a journal article that a clinical trial of rosuvastatin was in progress. That information, when taken together with the knowledge that statins were effective in the treatment of high cholesterol and that low doses of statins were available on the market, was considered enough to render obvious the use of low dose rosuvastatin for treating high cholesterol.
Clinical trial information and related disclosures have also been used to challenge the validity of patent claims in other major jurisdictions, including the US and Europe. While these challenges have had varying degrees of success, they nonetheless highlight the benefits of filing a patent application before disclosing the invention in clinical trial information, and that the laws of different jurisdictions should be taken into account when drafting a patent application.
The decisions discussed above serve as important reminders to implement an IP strategy that balances the timing and content of a patent application with the obligation to register a clinical trial, particularly in Australia. Further, clinical trial registrants often disclose more information than is needed in order to register the trial. Therefore, it is important to be aware of the minimum requirements for registering a clinical trial, as it may be possible to register a trial without disclosing key features of the invention.
As with any public disclosure related to an invention, it is also vitally important to be aware of the risks associated with disclosing clinical trial information before the disclosure is made public. That includes disclosures that might not traditionally be thought of as prior art, including information about clinical trials in registries and provided to trial participants, journal articles, posters and conference presentations, social media posts and press releases. We therefore recommend consulting with a patent attorney to ensure an appropriate IP strategy is in place before registering a clinical trial.
[i] WORLD MEDICAL ASSOCIATION, INC. DECLARATION OF HELSINKI: Ethical Principles for Medical Research Involving Human Subjects, Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964
[ii] Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd  FCAFC 116
[iii] See, e.g., Regeneron Pharmaceuticals Inc v Genentech Inc  EWHC 657 (Pat); Hospira UK Limited v Genentech Inc  EWHC 1796 (Pat);  RPC 1; Hospira UK Ltd v Genentech Inc  EWHC 1094 (Pat)