Unproven hypotheses in clinical trials can be novelty-destroying
Bryan Leaw and Karen Sinclair
In a unanimous decision (Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd  FCAFC 116), an enlarged full bench of the Full Federal Court of Australia recently ruled that the disclosures and hypotheses of a clinical trial protocol can be “novelty-destroying”. The Court referenced European outcomes relied on by Mylan, however found that Australian law differed to European case law which held that the achieved therapeutic effect is a functional technical feature of the claim.
The patent in suit was Australian patent 2006313711 (the 711 patent), directed to the second medical use of fenofibrate in treating diabetic retinopathy. The 711 patent claims included Swiss-style use claims and method of treatment claims directed to the treatment or prevention of retinopathy by administration of fenofibrate. Diabetic retinopathy is the most common eye disease seen in diabetic adults and arises due to changes in the blood vessels in the retina.
During examination, the ACCORD Eye Study Protocol (the ‘ACCORD Protocol’) was raised as prior art. The Eye Study Protocol formed part of a larger ACCORD Trial (The Action to Control Cardiovascular Risk in Diabetes), which was a randomised clinical trial on cardiovascular disease in patients with type 2 diabetes. The ACCORD Trial’s three primary aims centred around the lowering of blood glucose, lowering of blood pressure, and the lowering of serum triglycerides whilst raising of serum HDL-C levels (the so called ‘good’ cholesterol). The ACCORD Protocol specifically examined the effects of treatment on diabetic retinopathy.
The ACCORD Protocol hypotheses
In the discussion of potential diabetic retinopathy treatments, the ACCORD Protocol referred to a previous study (ETDRS 18, or the Early Treatment Diabetic Retinopathy Study Report No 18); supporting a contention that reducing serum trigylcerides would lower the risk of progression to high risk proliferative diabetic retinopathy. High risk proliferative diabetic retinopathy represents the most severe stage of retinopathy, where the retina – starved of nutrients due to blocked blood vessels – sends signals to trigger the growth of new blood vessels. These blood vessels however develop abnormally and may leak blood, leading to vision loss and possibly blindness.
Based on the ETDRS 18 Study, the ACCORD Protocol presented a hypothesis (emphasis added):
In type 2 diabetic patients whose low density lipoprotein cholesterol levels have been reduced appropriately by statin therapy, will the additional fibrate therapy, to reduce triglyceride levels and raise high density lipoprotein cholesterol levels, decrease the risk of DR [diabetic retinopathy]?
In other words, the ACCORD Protocol hypothesized that: in a subset of patients who already achieved adequate glycaemic control through statin therapy (by reducing LDL-C, the so called ‘bad’ cholesterol), could the risk of diabetic retinopathy be reduced by administering fibrate?
Claims lack novelty considering the ACCORD Protocol
The Court held that, based on a close reading of long-standing law in Bristol-Myers Squibb Company v FH Faulding & Company Limited  FCA 316; 97 FCR 524 (BMS v Faulding) and Merck & Co Inc v Arrow Pharmaceuticals Ltd  FCAFC 91; 154 FCR 31 (Merck v Arrow), methods of treatment and Swiss-type claims may be found to lack novelty in light of prior clinical trials. Specifically, the Court agreed with findings in the previous cases; that anticipation of a method of treatment claim does not require the clinical trials to have been conducted. Instead, whether such disclosure qualifies as an anticipation turns on the facts of the case.
Here, the Court found that the ACCORD Protocol qualified as an instruction for a ‘purposeful administration of fenofibrate at the claimed dosages with a statin’ aimed at treating or preventing diabetic retinopathy. Importantly, the Court noted that ‘validation of the ACCORD Protocol’s hypothesis was certainly not required’ to find that the method of treatment claims lacked novelty. At :
What is required is that the prior document discloses that which is subsequently claimed as an invention. If that is disclosed, the invention cannot be new.
A divergence with European law?
In oral argument, Mylan relied on two UK High Court of Justice decisions to support the proposition that the ACCORD Protocol advanced no more than a ‘reasoned hypothesis’ for treatment, and not an actual method of treatment.
The Court held however that the UK cases proceeded on the case law of the Boards of Appeal (of the European Patent Office), where the ‘achievement of the therapeutic effect is a functional technical feature of the claim’. In effect, the claims in Europe imported a meaning of established efficacy. Under European law, claims to a second medical indication and purpose-limited product claims can therefore only be found to lack novelty if the prior disclosure discloses that the therapeutic effect would be achieved. Based on the principles of BMS v Faulding and Merck v Arrow, the same cannot be said for Mylan Health Pty Ltd v Sun Pharma ANZ.
Implications for pharmaceutical patents in Australia
This case may have far-reaching implications for pharmaceutical patent holders or applicants in Australia. Mylan Health Pty Ltd has made a special leave application to appeal to the High Court on this aspect of the decision. Unless special leave is granted, the decision of the enlarged bench creates a precedent for the proposition that clinical trials can indeed deprive method of treatment and second medical indication claims of novelty. The court took the view (by way of a notice of contention) that whilst the ACCORD Protocol was a double-blind randomised clinical trial, and thus the outcomes were not known at the trial design stage by the investigators or the participants, the challenge to novelty should not fail purely on that basis.
Consequently, healthcare companies and researchers must be mindful of the implications on patentability even when drafting clinical trial protocols. Writing a trial protocol which is later construed to direct, recommend, teach or suggest the use of the medicament in the treatment of the disease, even when the certainty of treatment outcomes is not yet known, constitutes a novelty-destroying prior art disclosure. Early involvement of IP specialists throughout the research and development phase of an invention could mean the difference between having patent protection or none. On the other hand, Australian patent holders should be wary that novelty (and indeed, inventive step) of their patent could be challenged on the basis of pre-existing and prior published clinical trial data.