While the case of Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd1 (‘Mylan v Sun Pharma’) was decided a little over a year ago, some of the repercussions of the decision are only starting to become apparent. We have become aware of Examiners raising objections, based on Mylan v Sun Pharma, that entries in websites reporting clinical trial activity are novelty destroying. Of most concern is the situation where the patent applicant’s proposal for clinical trials is cited against their own patent application. This means that inventors of pharmaceutical products and methods must very carefully consider and balance the need to publish details of their own research proposal, which often must be made public for reasons discussed in this article, with the ability to validly seek patent applications in Australia and internationally. For inventors that cannot file for patent protection prior to commencing clinical trials, this results in a game of chance, where they gamble on whether an Examiner will find the publication of their clinical trial protocol and consider it to be relevant during examination.
Mylan v Sun Pharma case summary
Mylan v Sun Pharma is well known for the finding that Swiss-style claims require ‘objective intention’ on the part of the manufacturer in order to establish infringement (as reported in our previous article). However, to date, little attention has been given to invalidity in the light of a publication of a report of a clinical trial.
In the first instance,2 Mylan sued Sun Pharma over the marketing of a number of fenofibrate drugs, which Mylan alleged infringed three of their existing patents (AU 731964, AU 2003301807 and AU 2006313711, ‘the 711 Patent’). As part of the proceedings, the trial judge held that the method of treatment claims in suit in the 711 patent were not novel in light of the publication of The Accord Eye Study Protocol (the ACCORD protocol). The ACCORD protocol hypothesised that daily doses of 160mg of fenofibrate could be used to treat diabetic retinopathy, a regimen which later became the subject of method of treatment claims in the 711 patent.
On appeal, Mylan argued that this amounted to nothing more than a reasoned hypothesis for a possible treatment. However, the Full Federal Court upheld the decision, stating:
“We do not accept that a documentary disclosure containing an hypothesis cannot be an anticipatory disclosure that deprives an invention of novelty. In such a case the question, simply put, remains: what does the prior document disclose?… [I]f, as a matter of interpretation, the document nonetheless discloses that which is later claimed as an invention, that disclosure will anticipate the invention and deprive it of novelty.”
The Court remained unconvinced by Mylan’s submissions that a prior art document must show that the therapeutic effect is achieved in order to be anticipatory. These submissions were based on two UK decisions (Regeneron Pharmaceuticals Inc v Genentech Inc  EWHC 657 (Pat) and Hospira UK Limited v Genentech Inc  EWHC 1796 (Pat);  RPC 1). However, this argument was dismissed on the grounds that the UK cases proceeded on the case law of the Boards of Appeal of the European Patent Office, and that in contrast, the principles developed under Australian case law impart no requirement of therapeutic success.
The problem with publication
The difficulty with the position reached in Mylan v Sun Pharma is that there is an expectation placed on those conducting such trials that the registration of clinical trials in a public database should occur. Given that registration (and subsequent publication) of clinical trial protocols can sabotage future patent applications if published before the priority date, the question becomes: is it absolutely necessary to register? If so, is there a way to protect future patent applications from an early clinical trial publication?
Is it necessary to register a clinical trial?
According to the Australia New Zealand Clinical Trials Registry (ANZCTR), it is not a formal legal requirement to register your clinical trial. However, there appears to be a significant moral obligation, with regulatory bodies in Australia strongly endorsing registration through five key initiatives:
- The Declaration of Helsinki,3
- The International Committee of Medical Journals Editors (ICMJE),4
- The National statement on Ethical Conduct in Human Research,5
- Australian Code for the Responsible Conduct of Research,6 and
- The Therapeutic Goods Association (TGA) guidelines.7
Foremost among these initiatives is the Declaration of Helsinki, a document developed by the World Medical Association (WMA) and widely regarded as the cornerstone document for ethical conduct of medical research including on human subjects. The Declaration clearly outlines that the registration of clinical trials is essential, and that such registration should include clear descriptions of the research protocol to be followed. The Australian government clinical trials website explicitly mentions the Declaration of Helsinki, implying support for the doctrines outlined therein.8
The Declaration of Helsinki is supported by the International Committee of Medical Journals Editors (ICMJE), who have stated that they will not consider a trial for publication unless it is registered in a publicly accessible database prior to the enrolment of the first participant. In addition to high impact ICJME member journals such as the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association and the British Medical Journal, a further ~6,400 academic journals claim to follow ICMJE guidelines.
These sentiments are further reinforced in both The National Statement on Ethical Conduct in Human Research and the guides accompanying the Australian Code for the Responsible Conduct of Research (2018), which all researchers performing clinical trials are bound by. The guidance provided by the National Statement is clear:
“For any research project that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes, researchers must register the project as a clinical trial on a publicly accessible register complying with international standards (see information on the International Clinical Trials Registry Platform (ICTRP) on the World Health Organisation website) before the recruitment of the first participant.”
Furthermore, TGA guidelines for clinical trials using ‘unapproved’ therapeutics require that the use of the therapeutic must be performed through the Clinical Trials Notification (CTN) or Clinical Trials Approval (CTA) schemes. The therapeutic goods legislation in Australia necessitates that the use of therapeutic goods in both schemes be in accordance with, among other requirements, the National Statement on Ethical Conduct in Human Research, which expressly supports trial registration as outlined above.
Finally, according to the ANZCTR, ethics committees are increasingly requiring prospective registration (before enrolment of the first participant) as a requirement of ethical approval.9
Overall, it appears that failure to register clinical trials can have significant consequences, ranging from an inability to publish the data in leading journals to potential rejection of the trial on ethical grounds. In this regard, while it is not technically necessary to register a clinical trial, the ethical burden coupled with the potential risks are increasingly making this process a de facto requirement.
For many indications, Australia may be only one of many jurisdictions in which a clinical trial is being conducted. Alternatively, given the Australian stance, it may be tempting to outsource the clinical trials to another jurisdiction, such as the United States or Europe. In either case, the pertinent question is: what rules and regulations apply in these jurisdictions?
In the United States, we understand that Section 402(j) of the Public Health Service Act requires that ‘applicable’ clinical trials are registered within 21 calendar days after the first human subject is enrolled,10 and that such a registration must include details about the purpose, design, patient population, intervention, outcome measures, and results among other details. Notably, phase I trials don’t appear to be ‘applicable’ clinical trials for the purposes of this law. We also understand that the United States requires that clinical trial sponsors disclose the results of clinical trials within 12 months of trial completion. While there are provisions for the delay of publication of clinical trial results when seeking regulatory approval, by this time the damage may have already been done.
We further understand that clinical trials in the European Union are governed by the Clinical Trials Directive, which requires that clinical trials be registered in the European Clinical Trials Registry (EUCTR).11 Further, Article 57(2) of Regulation (EC) No. 726/2004 stipulates that certain information in this register be made available to the public, such as the products being tested, the route and form of administration, concentration, the medical condition to be treated and objectives of the trial.12 Since the introduction of the 2012 EC guideline 2012/c302/03, clinical trial sponsors are also required to disclose the results of each trial within 12 months of trial completion. Phase I trials appear to be exempt from reporting results unless they relate to a paediatric investigation plan.
When considered together with the regulatory stance on Australian clinical trials, the decision in Mylan v Sun Pharma leaves patent applicants with precious few options. On one hand, the knowledge gleaned from publication of a clinical trial procedure may be considered to lead directly to the invention. On the other hand, knowing that any clinical trial publications can be used against them during prosecution, applicants may be forced to apply for patent protection at an earlier stage than anticipated. Given the increasingly strenuous support requirements in Australia, this carries with it the risk that the disclosure might not be sufficient to support the claims. In Australia, new matter can be added to divisional applications, opening the possibility of addressing this issue. The grace period for self-disclosure available to patent applicants in Australia will help in some cases, but navigating such a path could be treacherous.
The Full Court acknowledged that there was “some broad support for Mylan’s position… in the case of Swiss type claims and purpose-limited product claims allowed under the European Patent Convention 2000” (at 111). EPC 2000 claims are not interpreted in the same way in Australia as in Europe. Nevertheless, this passage does suggest that a claim which includes the actual achievement of the therapeutic effect as a functional technical feature of the claim, as opposed to a mere statement of purpose or intention, might survive the type of scrutiny applied in Mylan v Sun Pharma. While Swiss-style claims appear to receive favourable consideration in this passage, the Full Court did not reverse the earlier finding that all claims in suit were invalid, and the patent did include Swiss-style claims. We speculate that inclusion of a positive statement such as “wherein effective control of diabetic retinopathy is achieved” at the conclusion of a claim might satisfy this requirement, but without conviction.
Overall, this decision seems to further widen the divide between the research and patent worlds, as researchers are forced to weigh up ethical obligations against their patent rights. This is particularly true for inventions originating from publicly funded research where, ironically, a patent application covering the invention may be found invalid over a publication designed to satisfy obligations placed on researchers by government authorities. In our view, a legislative response to exclude publications of proposals for clinical trials on websites of the type discussed herein as prior publications is necessary to deal with the difficulties created by Mylan v Sun Pharma.
- Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd  FCAFC 116
- Mylan Health Pty Ltd (formerly BGP Products Pty Ltd) v Sun Pharma ANZ Pty Ltd (formerly Ranbaxy Australia Pty Ltd  FCA 28
- World Medical Association (2018). WMA – The World Medical Association-WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, viewed 29 July 2021, https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/.
- International Committee of Medical Journal Editors, Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals, viewed 29 July 2021, http://www.icmje.org/icmje-recommendations.pdf.
- National Health and Medical Research Council (NHMRC), National Statement on Ethical Conduct in Human Research (2007), viewed 29 July 2021, https://www.nhmrc.gov.au/about-us/publications/national-statement-ethical-conduct-human-research-2007-updated-2018.
- National Health and Medical Research Council (NHMRC), Australian Code for the Responsible Conduct of Research, viewed 29 July 2021, https://www.nhmrc.gov.au/about-us/publications/australian-code-responsible-conduct-research-2018.
- Australian Government Department of Health, Therapeutic Goods Administration, Clinical trials, viewed 29 July 2021, https://www.tga.gov.au/clinical-trials.
- National Health and Medical Research Council (NHMRC), Trial registration, viewed 29 July 2021, https://www.australianclinicaltrials.gov.au/trial-registration.
- Australian and New Zealand Clinical Trials Registry, Is registration of clinical trials mandatory in Australia or New Zealand, viewed 29 July 2021, https://www.anzctr.org.au/Faq.aspx.
- Public Health Service Act 42 U.S.C § 282(j).
- Council Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (2001) Official Journal L 121, p. 34.
- Council Regulation 726/2004 on laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (2004) Official Journal L 136, p. 1.
1 Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd  FCAFC 116 (3 July 2020)
2 Mylan Health Pty Ltd (formerly BGP Products Pty Ltd) v Sun Pharma ANZ Pty Ltd (formerly Ranbaxy Australia Pty Ltd  FCA 28 (22 January 2019)
10 Public Health Service Act 42 U.S.C § 282(j)
11 Council Directive 2001/20/EC
12 Council Regulation 726/2004