Patenting clinical stage inventions: beware of clinical trial disclosures

By Tony Shaw PhD, Candace Wu PhD
Intellectual Property Patents & Trade Marks

Clinical trial disclosure can form part of the prior art base 9 min read

Australia is becoming a go-to destination for clinical trials thanks to its clinical trials infrastructure, networks and capability across the life sciences. Patent protection for pharmaceutical and biotech inventions in Australia often includes method of treatment and Swiss-style claims, which are purpose-limited. A number of Australian cases have established that these types of claims can be anticipated by information in a clinical trial that provides a 'reasoned hypothesis' that a claimed treatment may be effective, even if that hypothesis has not been tested or validated.

Many pharmaceutical and biotech companies continue to develop therapies for COVID-19 and 'long COVID' and are pursuing patent protection in parallel with clinical trials. However, publicly available clinical trial information can form part of the prior art base and care must be taken to balance the disclosure required for a clinical trial and that required to properly support a claim to a method of treatment in an Australian patent.

In this Insight we examine the issue in the context of relevant Australian caselaw and provide some guidance on how to manage the risk.

Clinical trial information in Australia: relevant caselaw

Like many jurisdictions that observe the ethical principles of the Declaration of Helsinki, clinical trials in Australia must adhere to Good Clinical Practice (GCP). The Therapeutic Goods Administration (TGA) has also adopted ISO 14155 (Clinical investigation of medical devices for human subjects—Good Clinical Practice) which articulates standards for the design, conduct, recording and reporting of clinical investigations carried out in human subjects for regulatory purposes. GCP requires information relating to clinical trials to be registered in a publicly accessible database and this information may include details such as the clinical trial protocols, and primary and secondary endpoints. All of this information can be prior art and can be used to assert that the claims of subsequent patents lack novelty, an inventive step or both.

BristolMyers Squibb Co v F H Faulding & Co Ltd [2000] FCA 316

In Bristol‑Myers Squibb Co v F H Faulding & Co Ltd [2000] FCA 316 (Bristol-Myers Squibb) the Federal Court considered that a series of Phase I clinical trials reporting on dosage safety did not anticipate method of treatment claims. The court noted that Phase I trials were designed to test for safety rather than efficacy. In contrast, a published abstract describing an ongoing clinical trial was viewed differently. The abstract described Taxol's activity against certain forms of cancer (based on previous Phase I and II studies), the objective of evaluating the feasibility of shorter infusion time and establishing the maximum tolerated dose. The court considered the abstract was an enabling disclosure of the claimed methods of treatment and, therefore, such claims were found to lack novelty.

InterPharma Pty Ltd v Hospira Inc (No 5) [2019] FCA 960

In InterPharma Pty Ltd v Hospira Inc (No 5) [2019] FCA 960, the court viewed patient consent forms for Phase II clinical trials as not anticipatory. The patent in question claimed the use of dexmedetomidine for ICU sedation. In one consent form (the Duke Form) the purpose of the study was described as the testing of dexmedetomidine as an anaesthetic adjunct, and sedation was only referred to as a potential side effect. In another consent form (the 249 Form), dexmedetomidine was disclosed as a sedative drug and the purpose of the study was to evaluate the efficacy, safety and dose titratability of dexmedetomidine in ICU sedation. The heart of the dispute was whether the 249 Form disclosed dexmedetomidine as suitable for use for sedation in an ICU. The court found that while the investigators would reasonably expect that administration of dexmedetomidine would sedate patients, the skilled person would understand that sedation was not a certainty. The court held that the 249 Form disclosed the 'possibility' of the use of dexmedetomidine as an ICU sedative but this was a hypothesis to be tested rather than a disclosure that dexmedetomidine was suitable for ICU sedation and consequently the 249 Form did not anticipate the claimed invention.

Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116

However, the Full Federal Court in Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116 (Mylan) upheld a decision which invalidated a patent (the 711 Patent) for, amongst other things, lack of novelty based on an untested hypothesis in a clinical trial protocol (the ACCORD Protocol). The 711 Patent claimed the use of fenofibrate for preventing diabetic retinopathy. The ACCORD Protocol disclosed a primary hypothesis that 'a therapeutic strategy that uses a fibrate to lower triglyceride levels and raise HDL-C levels in patients already receiving a statin drug for treatment of LDL-C levels will reduce the rate of development or progression of diabetic retinopathy compared to a strategy in which a statin alone is used'. The patentee argued that the ACCORD Protocol could not anticipate the claimed invention because it advanced no more than a 'reasoned hypothesis' for treatment and did not enable the use of fenofibrate to prevent diabetic retinopathy. The Full Court was unpersuaded and stated that validation of the ACCORD Protocol’s hypothesis was certainly not required for it to deprive the claims of novelty. The Full Court reasoned at [106] (emphasis added):

… it is not a requirement for a patentable invention that the invention, as claimed, be based on scientific proof or substantiation: Generic Health Pty Ltd v Bayer Pharma Aktiengesellschaft [2018] FCAFC 183; 267 FCR 428 at [135]. That being so, no greater requirement is imposed on a prior documentary disclosure in order for it to be anticipatory. 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.

Further, the Full Court found that the invention claimed in the 711 Patent was obvious in light of an observational study (ETDRS 22) conducted as part of a larger clinical trial. Data from the ETDRS 22 study suggested that a reduction of serum lipid levels may help prevent vision loss associated with retinal 'hard exudates'. Relevantly, the 711 Patent defines 'diabetic retinopathy' to include severe non-proliferative grades of diabetic retinopathy, proliferative grades of diabetic retinopathy, macular oedema and 'hard exudates'. The Full Court noted that the reformulated Cripps question is an aid in the assessment of inventive step and that the question does not require certainty of outcome.

However, the Full Court also noted that a test formulated in terms of 'worth a try' and 'mere possibility' was rejected by the High Court (Aktiebolaget Hässle v Alphapharm Pty Limited [2002] HCA 59) and is not enough to reach the threshold of obviousness—to reach this threshold there must be an expectation of success. In this case, the Court found that the skilled person would have been directly led by ETDRS 22 to try fenofibrate (because of its effectiveness in reducing serum lipid levels) in the expectation that this might well prevent or slow the development or progression of retinal 'hard exudates'. That is, the answer to the reformulated Cripps question can be 'yes', even if the skilled person cannot be certain that the method of treatment will be provided by following routine steps, as long as the skilled person in the art is led to try the claimed invention.

The Full Court in Mylan confirmed that clinical trial information, including untested but reasoned hypotheses published before the priority date of a patent application, can deprive method of treatment and Swiss-tyle 'use' claims of novelty and an inventive step.

Astellas Pharma Inc. v Aragon Pharmaceuticals, Inc. [2022] APO 36

The finding in Mylan was applied recently in an Australian Patent Office decision, Astellas Pharma Inc. v Aragon Pharmaceuticals, Inc. [2022] APO 36 (Astellas), where the delegate considered the situation in Astellas to be similar to that in Mylan.

The delegate concluded that when properly construed, method of treatment and Swiss-style claims are directed to a therapeutic purpose rather than a therapeutic effect. In other words, prior art does not need to disclose a therapeutic effect to anticipate a method of treatment or Swiss-style claim, it is the therapeutic purpose that is relevant. Such findings are at odds with the position in Europe (eg see decisions T 158/96, T 715/03 and T 385/07) and the UK (eg see Regeneron Pharmaceuticals Inc v Genentech Inc [2012] EWHC 657 (Pat), Hospira UK Limited v Genentech Inc [2015] EWHC 1796 (Pat); [2016] RPC 1, and Hospira UK Ltd v Genentech Inc [2014] EWHC 1094 (Pat)) where the novelty of medical use claims over clinical trial information has been repeatedly acknowledged.

Ultimately, method of treatment and Swiss-style claims in Australia can lack novelty and an inventive step in light of clinical trial information that provides a 'reasoned hypothesis' that has not been scientifically tested or validated.

However, clinical trial information can nevertheless deprive the medical use claims of an inventive step. This is because in the UK and Europe, purpose-limited therapeutic claims require achievement of the claimed therapeutic effect while in Australia there is only a requirement that the administration of the claimed drug is for the purpose of the claimed therapeutic effect. Ultimately, method of treatment and Swiss-style claims in Australia can lack novelty and an inventive step in light of clinical trial information that provides a 'reasoned hypothesis' that has not been scientifically tested or validated. While this is considered on a case-by-case basis, it is problematic if the clinical trial information is specific enough to be considered equivalent to the claimed invention.

The Delegate in Astellas agreed with the opponent that even if the claims were novel on the basis that the clinical trial information does not disclose the claimed therapy, the claims would lack support because the specification merely disclosed the same level of information as the clinical trial information that was considered as prior art. In particular, the Delegate found:

…the only clinical example in the specification does not disclose the [therapy], so if the skilled reader would not have recognised the [therapy] in the citations then they could hardly be said to have read it in to the example in the specification – and consequently the claims would not correspond to the technical contribution…

Therefore, when arguing against clinical trial information as prior art, a patentee must take care to avoid placing themselves in a position that undermines their ability to assert that the claims are supported by the specification, particularly where the specification provides no more information than the clinical trial information.

Managing the risk

Publicly available clinical trial information can pose a significant risk to a patent or patent application. This risk may be managed by:

  • being aware of all relevant clinical trial information that is publicly available anywhere in the world and considering its potential effects in pre-filing patentability assessments;
  • carefully considering what information is required when registering a clinical trial with a view to avoiding disclosures that may be problematic for patent protection; and
  • devising prosecution strategies to address clinical trial information that has been published before the priority date of your claims, including (if applicable) considering invoking the grace period provision that is available in Australia.