While the case of Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd[1] was decided in July 2020, 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 earlier  clinical trial proposal 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.

The Mylan v Sun Pharma decision

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. However, 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 [2012] EWHC 657 (Pat) and Hospira UK Limited v Genentech Inc [2015] EWHC 1796 (Pat); [2016] RPC 1). However, this argument was dismissed on the grounds that the UK cases were governed by decisions 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 difficulty with the position reached in Mylan v Sun Pharma is that there is an expectation placed on those conducting such trials that registration of the trial 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?

Official and unofficial requirements for trial registration

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 to register, 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 involving human subjects. The Declaration clearly outlines that 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 cites the Declaration of Helsinki and its principles, implying support for the doctrines outlined therein.[8]

The Declaration of Helsinki is supported by the International Committee of Medical Journals Editors (ICMJE), who 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 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) before granting  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.

Applicants for Australian patent applications are likely to have conducted their clinical trials in another jurisdiction such as the United States or Europe. However, each of these jurisdictions have policies which require registration and disclosure of at least some of the methods and objectives. Outlines of such studies may commonly be found on web sites such clinicaltrials.gov.

Conclusions

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. Filing premature applications runs the risk that key pieces of data or surprising advantages discovered during the clinical trial phase will be omitted, and hence the application may lack adequate support for the full breadth of 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 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.

[1] Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] 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 [2019] FCA 28 (22 January 2019)

[3] The Declaration of Helsinki

[4] The International Committee of Medical Journals Editors (ICMJE) recommendations

[5] The National Statement on Ethical Conduct in Human Research

[6] Australian Code for the Responsible Conduct of Research

[7] TGA guidelines

[8] Australian Government website on trial registration

[9] ANZCTR Website