3 min read

Following a cacophony of dire warnings and lobbying over the past decade from the Australian biotechnology and medical sectors, and the sudden sharp focus of middle Australia on the critical importance of onshore manufacturing facilities such as those capable of mRNA vaccine production, the Federal Government has announced the introduction of a $206.4m patent box for Australian medical and biotechnology industries as part of the 2021-2022 Federal Budget handed down on 11 May 2021.

Named quite literally after a tick box historically present on income tax forms, a patent box provides tax incentives designed to encourage companies to commercialise and manufacture patented technology locally. From 1 July 2022, Australia’s proposed patent box is slated to tax income derived from eligible patents at a concessional corporate tax rate of 17%, rather than the standard corporate tax rate of 30%, or 25% for small and medium enterprises (SMEs).

While the specifics are yet to be established, the patent box is proposed to apply to income derived from granted Australian patents in the medical and biotechnology sectors filed after the budget announcement (ie, after 11 May 2021), providing that at least a portion of the research and development (R&D) of the technology occurred in Australia. The following example was provided with the Federal budget papers: A company selling a patented product makes $175 million in net income directly attributable to the patent. If 80% of the R&D associated with the patented product occurred in Australia, then 80% of the income (ie, $140 million) would enjoy the concessional 17% tax rate. 

The measure is intended to incentivise Australian companies to invest in and perform their R&D, commercialisation and manufacturing of patented technologies onshore. It has been warmly received by the Australian biotechnology sector with Lorraine Chiroiu, CEO of AusBiotech, stating that the organization whole-heartedly commends the initiative: “This tax incentive will address the gap that leaves our IP vulnerable, retain home-grown IP, and support Australian innovators and manufacturers. It will make the commercialisation of IP and manufacturing in Australia more genuinely viable for businesses.”

Cochlear’s CEO, Dig Howitt, has similarly commented: “Incentivising companies of all sizes to keep their intellectual property and manufacturing in Australia will generate substantial economic benefits through royalties, licence fees, tax revenues, supply chains, jobs, and capital investment.”

CSL CEO Dr Andrew Nash concurs, stating, “CSL welcomes the introduction of a patent box which will help decrease the flow of intellectual property from local medical research going overseas. It will drive the growth of advanced manufacturing jobs, capital intensive investment and sovereign capacity in medical technology and biotechnology manufacturing.”

A number of countries already have patent box regimes, including the UK, Belgium, Spain, France, the Netherlands, Luxembourg, Switzerland, and China. Australia’s patent box is set to follow the Organisation for Economic Co-operation and Development (OECD)’s guidance on patent boxes to meet internationally accepted standards.

The Government has indicated that it will consult with industry on the design of the patent box and explore whether the regime should be extended to include clean energy patents. Lobbying from that sector is already well underway.

On a technical note, several years typically elapse between patent filing and patent grant. Accordingly, it could be some three or four years before the patent box regime begins to provide significant benefit. Patent grant can, however, be brought forward by various means including requesting early national phase entry in Australia followed by expedited examination. If you require advice on this issue, Shelston IP would be happy to help.     

Authored by Karen Heilbronn Lee, PhD and Allira Hudson-Gofers

3 min read

Gliknik, Inc. v CSL Behring Lengnau AG [2020] APO 46 (“Gliknik”) concerned a patent application for engineered proteins intended for use as replacements for intravenous immunoglobulin.  The application included claims directed to methods of treating autoimmune or inflammatory diseases as well as a Swiss-style claim directed to the same diseases.  Gliknik, Inc. opposed the application on several grounds including that the specification did not sufficiently disclose the invention as claimed.

The standard for “sufficient” disclosure was raised in Australia following the commencement of the Intellectual Property Laws Amendments (Raising the Bar) Act 2012 and its assessment has been approached by the Australian Patent Office with the following two-step enquiry:

  1. Is it plausible that the invention can be worked across the full scope of the claim?
  2. Can the invention be performed across the full scope of the claim without undue burden?

In Gliknik, the Patent Office considered for the first time the plausibility of a Swiss-style claim. Following the principles recently set out by the Full Federal Court in Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116, the Delegate observed that Swiss-style claims confer a monopoly in respect of a method of making a medicament.  They are not product claims, nor are they method of treatment claims – the monopoly extends to the point where the medicament is made.

Nevertheless, Swiss-style claims are purpose-limited in the sense that the medicament resulting from the method is characterised by the therapeutic purpose for which it is manufactured, as specified in the claim.  Unlike method of treatment claims, however, a Swiss-style claim does not require that the therapeutic effect be achieved. Our analysis of Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116, including the court’s construction of Swiss-style claims, is available here.

Having construed the claims, the Delegate in Gliknik then considered whether the plausibility standard of therapeutic effectiveness (for method of treatment claims) differed from that of therapeutic purpose (for Swiss-style claims).  In the absence of Australian jurisprudence, the Delegate turned to UK authorities, and in particular, the principles set out by Sumption LJ in Warner-Lambert Company LLC v Generics (UK) Ltd [2018] UKSC 56.  Although that case concerned the plausibility of efficacy rather than purpose, the Delegate reasoned that, if the efficacy of a product is not plausible, then it would follow that an intention to treat would not be plausible.  The Delegate concluded that substituting the word “efficacy” for “purpose” in Sumption LJ’s comments would not provide any substantial difference to the plausibility analysis.

Turning then to the disclosure of the specification, and the evidence of the common general knowledge in the field, the Delegate found it plausible that the engineered proteins of the invention could effectively treat some, but not all, conditions specified in the claims.  For certain conditions, the specification provided no more than a speculative assertion and so the claims were found to be insufficiently enabled.

This decision shows that the Australian Patent Office will apply a similar standard of plausibility to method of treatment claims as it will to Swiss-style claims. For each type of claim, the disclosure of the specification, supplemented by the common general knowledge, must make the efficacy of the treatment plausible.

Authored by Michael Christie, PhD

7 min read

Boehringer Ingelheim Animal Health USA Inc. v Intervet International B.V. [2020] FCA 1333

Key takeaways:

  • For novelty purposes, expert evidence does not make up for a lack of sufficiently clear and unambiguous directions in the prior art or for a lack of teaching that would inevitably result in the invention
  • Invention was a “substantial departure” from known formulations, particularly in the face of a long-standing need for combination anthelmintic treatments and was thus not obvious
  • Lack of utility was not established in the circumstances


Merial Inc (now Boehringer Ingelheim Animal Health USA Inc (Boehringer)) appealed from an opposition decision in respect of Australian patent application AU 2011268899 (the application).

The invention described in the application relates to injectable formulations comprising a macrocyclic lactone and levamisole for controlling parasites in animals, and the use of such formulations in the preparation of a medicament for controlling parasites.

The problem addressed by the application was that some parasites develop a resistance to anti-parasitic drugs. Combinations of known drugs had been used in the art to overcome this resistance, but it was desirable to develop an injectable formulation for a combination of a macrocyclic lactone and levamisole, two of the most widely used and effective antiparasitic (anthelmintic) drugs.

However, such combinations have been difficult to formulate, for three main reasons:

First, levamisole and macrocyclic lactones are chemically incompatible and tend to react with each other when combined.  Secondly, levamisole and macrocyclic lactones are stable under different pH conditions (levamisole requires a pH of about 3.0-4.0 to be stable, while macrocyclic lactones require a pH of around 6.0-7.0).  Finally, levamisole salts are soluble in water, whereas macrocyclic lactones are not water soluble but are soluble in organic solvents, and are commonly formulated in oils and organic solvents.

The invention in the application addressed these issues by adopting a non-aqueous solvent system comprising oil and an organic solvent, in which the macrocyclic lactone is in solution, and the levamisole is a salt in particulate form (that is, in suspension).  This type of formulation achieves a separation of the macrocyclic lactone and the levamisole, thus addressing the issue of chemical incompatibility.

Claim 1 of the application is as follows:

  1. An injectable formulation of a macrocyclic lactone and levamisole in a non-aqueous solvent system comprising oil and an organic solvent, wherein the macrocyclic lactone is in solution and the levamisole is a salt in a particulate form, and wherein the levamisole salt is present in the range of between 10-35% w/v.

The Appeal

Boehringer was unsuccessful in its opposition in the Patent Office and appealed on various grounds:

(a)          Lack of novelty.  Boehringer contended that various claims were not novel in light of Chinese patent application CN 1375291A (CN 291).

(b)          Lack of inventive step.  Boehringer contended that the claims did not involve an inventive step because they were obvious in the light of the common general knowledge considered alone, or the common general knowledge combined with CN 291.

(c)           Lack of utility.  Boehringer contended that the invention claimed in each of the claims was not useful, in that the claims of the application include embodiments that do not achieve the promise of a physically and chemically stable suspension formulation of a macrocyclic lactone and levamisole.


CN 291 was a patent application published on 23 October 2002 for an invention titled “Veterinary Compound Injection Containing Levamisole or Salts thereof”.

Example 3 of CN291 set out an oil injection containing a combination of ivermectin (a macrocyclic lactone) and levamisole hydrochloride.  However, it was clear that the concentration of levamisole HCl in Example 3 at 5% w/v did not fall within the scope of claim 1 of the application, which specified 10-35% w/v.  Further, Example 3 did not set out any manufacturing steps, or any description of what was intended to be made.  Moreover, it did not describe the levamisole HCl as being in particulate form (or in a suspension).

Boehringer submitted that Example 3 of CN 291 was to be read in conjunction with claim 3 of CN 291, which discloses levamisole HCl in the amount of 10-20% w/v, and with page 3 of the specification, which discloses that preferably the levamisole HCl is present in the amount of 10-20% w/v.  Further, Boehringer submitted that a skilled person reading CN 291 as a whole would understand that CN 291 contained a direction, recommendation or suggestion to make the Example 3 formulation using 10-20% w/v levamisole HCl, because they would consider the 5% w/v concentration of levamisole HCl stated in Example 3 to be far too low for cattle, particularly in light of the other teaching in CN 291.

Based upon expert evidence, Boehringer further argued that the skilled person would expect the levamisole HCl in Example 3 to be suspended in the solvent system and to be present in particulate form, because the skilled person would expect that levamisole HCl will not dissolve in the solvent system of Example 3.  To support this view, Boehringer provided details of two formulations prepared by its expert witnesses following the guidance of CN 291 that fell within the scope of claim 1 of the application.

However, Moshinsky J was not convinced, finding that there was no sufficiently clear and unambiguous direction to modify Example 3 by applying the higher concentration level described elsewhere.  Further, the Court emphasised that Example 3 did not describe the intended formulation as one in which the levamisole HCl is in particulate form.

In addition, the appellant’s expert formulator conceded under cross-examination that the formulation in Example 3 could be a suspension or a solution.

The Court was not swayed by the experiments conducted by the appellant as they involved a number of departures from the teaching of Example 3, and did not establish that any steps used to manufacture a formulation having the composition of Example 3 would inevitably contain levamisole HCl in particulate form.

Inventive Step

Boehringer contended that that it would have been obvious to the notional skilled person or team, based on the common general knowledge alone, or in light of the common general knowledge together with CN 291, to make a suspension formulation using an oil or organic carrier as a base and a co-solvent such as benzyl alcohol (an organic solvent), in which the macrocyclic lactone was in solution and the levamisole salt was in suspension.  It submitted that the skilled person would appreciate that, in such a composition, the levamisole salt would be in particulate form, and that they would know to use a concentration of levamisole salt sufficient to achieve the desired dose in a product for cattle having a dose volume rate of 1 mL/25 kg, which results in a formulation in accordance with claim 1 of the application.

However, the Court found that an oily formulation with levamisole present as a particulate was a substantial departure from known formulations, particularly (and most significantly) in respect of levamisole.  The expert evidence had also shown that, in order to be effective, levamisole needed to reach a high peak concentration in the animal’s gut rapidly, and preferably underwent similarly rapid clearance from the animal to meet regulatory requirements.  As there were no existing formulations of levamisole as a particulate in oil, a carrier often used to slow down absorption of a drug, it was not clear in the common general knowledge whether an effective peak concentration of levamisole could be reached in the animal using such a formulation.  Further, the evidence showed that there is a risk that an active ingredient formulated as a suspension will not be dispersed evenly throughout the formulation, or may result in agglomeration of the particles.

Based upon the evidence, it was held that a solution appeared to be preferable to a suspension for an injectable formulation, and that the above uncertainties as to efficacy, as well as others, would point away from the adoption of such an approach.

Secondary evidence such as the long-standing need for combination treatments of levamisole and a macrocyclic lactone and the desirability of having such a combination in injectable form were also held to support the existence of an inventive step.

Moreover, it was held that CN 291 would not provide any direct assistance to the notional skilled team in addressing the known chemical incompatibility of levamisole and macrocyclic lactones, a finding that was conceded by experts for Boehringer during cross-examination.

Lack of Utility

Boehringer submitted that the stability data in Intervet’s patent application WO 2017/108954 A1 (WO 954) (which Intervet accepted disclosed formulations falling within the scope of claim 1 of the application in suit) demonstrates that not all formulations falling within the scope of the claims of the application achieve the promise of being physically and chemically stable.  In particular, Boehringer relied on data in Table 4 of WO 954 for 2 months, at which point a loss of stability was shown.

However, the figures in Table 4 for 3 months – this being the relevant period for the purposes of the promise – did not show such a loss of stability.  Accordingly, it was held that the data in Table 4 did not establish that the invention failed to meet the promise of stability (that is, stability for 3 months under accelerated conditions).  Moreover, it was found that the data in Table 4 was inherently unreliable, and, even if it had shown a loss of stability as at 3 months, the Court would not have been satisfied that the invention failed the promise of stability.

Costs of amendment applications

In a subsequent judgment (Boehringer Ingelheim Animal Health USA Inc. v Intervet International B.V. (No 2) [2020] FCA 1433, The Court dealt with the costs of two interlocutory amendment applications.

In respect of each interlocutory application to amend, the Court found that “Intervet sought something in the nature of an indulgence.”  Referring to Les Laboratoires Servier v Apotex Pty Ltd (2010) 273 ALR 630 at [59]; cf Eli Lilly and Co v Pfizer Research and Development Co NV/SA (2003) 59 IPR 234, the Court held that in such cases, the patentee may be ordered to pay the costs of the amendment application, regardless of the outcome.

Accordingly, Boehringer’s request that each party bear its own costs was appropriate, particularly in circumstances where there was no adjudication on the merits of either application because Boehringer had ultimately consented to the amendments.

Authored by Ean Blackwell

4 min read

Ono Pharmaceutical Co., Ltd. et al [2020] APO 43 (16 September 2020)


Australia’s Patents Act provides a patent term extension (PTE) to account for the delays that can occur when obtaining regulatory approval for a pharmaceutical substance.   The extension can last for up to five years and is available when the following requirements are met:

  • the patent, in substance, discloses and claims a pharmaceutical substance per se, or a pharmaceutical substance when produced by recombinant DNA technology;
  • goods containing or consisting of the pharmaceutical substance are included in the Australian Register of Therapeutic Goods (ARTG); and
  • the first regulatory approval for the pharmaceutical substance occurred more than five years after the filing date of the patent.

The length of a patent term extension is equal to the period between the filing date of the patent and the date of the earliest first regulatory approval, reduced by five years.

The decision

Ono Pharmaceutical Co., Ltd. et al [2020] APO 43 concerned a request to extend the term of a patent covering anti-PD-1 antibodies.  The patent included claims for two blockbuster drugs; Merck Sharp & Dohme’s KEYTRUDA and the patentee’s OPDIVO, both of which received regulatory approval in Australia, but on different dates.  The question at issue, then, was which regulatory approval date was relevant for deciding the patentee’s PTE request.

The patentee hedged its bet, filing two PTE requests; one based on KEYTRUDA, which received regulatory approval on 16 April 2015, and another based on OPDIVO, which received regulatory approval on 11 January 2016.  From the patentee’s perspective, the request based on OPDIVO was preferred as it would result in a longer extended term (an additional 8 months, 26 days).  However, the Patent Office refused that request, finding that KEYTRUDA was included on the ARTG first and therefore should form the basis of the request.  The patentee disagreed and requested to be heard.

In the hearing, the patentee submitted that the “first regulatory approval date” should be the approval date of their own product, OPDIVO.  This, they argued, was consistent the purpose of the extension of term provisions, that being to restore the time lost by patentees in gaining marketing approval, and to compensate the patentee for the additional time, expense and difficulty in developing and commercialising a new drug.

The patentee argued that the reference to “first” regulatory approval in the Act was only important when multiple regulatory approval dates existed for the same substance, such as for different delivery forms (e.g. capsules, gel capsules, tablets, slow-release, different amounts, etc) that manifested in different ARTG registrations.  According to the patentee, it was only logical, given that the regime is intended to be beneficial and remedial, that it can only be about rewarding patentees for their work and, by implication, not the work of others.  If not, the patentee would not receive the full extension of term for their product.

The Delegate accepted that the PTE regime was designed to encourage the development of new drugs, but rejected the patentee’s broader purposive construction of the Act.  Such a construction, the Delegate noted, would encourage companies to develop a substance that is not new and seek regulatory approval as late as possible, secure in the knowledge that a PTE will be granted for the (not new) substance.  According to the Delegate, this type of scheme would not incentivise new drugs. Rather, it would incentivise new extension applications.

The Delegate acknowledged that there is some ambiguity in the words of the Act insofar as they do not say one way or the other whether the relevant pharmaceutical substance is only that belonging to the patentee, or whether it includes other, equivalent substances owned by third parties.  But the Delegate also noted that this ambiguity had been dealt with previously by the Patent Office in G.D. Searle LLC [2008] APO 31.  In that case, the Patent Office held that an application for PTE must be based on the earliest inclusion on the ARTG of a pharmaceutical substance falling within the scope of the claims, irrespective of the sponsor of the goods.  Moreover, in Pfizer Corp v Commissioner of Patents (No 2) [2006] FCA 1176, the Federal Court of Appeals held that “the term of the extension is based on the earliest inclusion, regardless of the identity of the sponsor. It is not open to the Commissioner to calculate the term of the extension only on the basis of goods sponsored by the Patentee.”

The Delegate therefore found that the substance with the earliest regulatory approval date for the purpose of the PTE request was KEYTRUDA, not OPDIVO.  As such, the patentee’s request for a PTE based on OPDIVO was refused.


In circumstances where a patent claims more than one registered pharmaceutical substance, this decision confirms that the earliest registered substance will be used to determine eligibility for a PTE and to calculate the length of the extension, irrespective of whether the registered substance is owned by the patentee or by a third party.  Patentees should therefore be aware of all pharmaceutical substances covered by their claims, not just those they are seeking to commercialise. If a patent application covers more than one pharmaceutical substance, an applicant may be well-advised to file one or more divisional applications to ensure that each registered substance is quarantined within its own patent, thus enabling maximum extensions to be sought for each patent separately.

Authored by Ean Blackwell and Duncan Longstaff

9 min read

Australia’s Full Federal Court recently delivered judgment in an appeal in a significant patent case: Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116.  The case concerned three patents relevant to Mylan’s oral lipid-lowering agent, Lipidil® (fenofibrate).

An enlarged Full Court bench comprising 5 judges (Middleton, Jagot, Yates, Beach and Moshinsky JJ) was appointed to hear and decide Mylan’s appeal.  This was because Mylan sought to clarify the Full Court’s previous statement in Merck & Co Inc v Arrow Pharmaceuticals Ltd [2006] FCAFC 91; 154 FCR 31 that the characterisation of an alleged anticipation as a “suggestion” in relation to the invention, is “not necessarily fatal to a novelty argument”.  Mylan submitted this statement by the Full Court did not countenance “mere speculation” or “the presentation of no more than a reasoned hypothesis” as an anticipatory disclosure.  On this basis, Mylan submitted to the Full Court (unsuccessfully, as explained below) that the trial judge (Nicholas J) had erred in finding that a hypothesis stated in a prior art document relating to a clinical study deprived methods of treatment claims of novelty.

The Full Court’s decision also provided important guidance in relation to the approach taken by Australian courts in considering obviousness, the construction and infringement of ‘Swiss-style’ claims under Australian patent law and the extent to which consistory clauses alone can provide fair basis for a claim.

Method of treatment and Swiss-Style claims lack novelty in light of clinical trial protocol

The Full Court considered whether method of treatment and Swiss-style claims could be anticipated by prior art comprising a protocol for a clinical trial of the claimed method.

Mylan argued that such a protocol could not be novelty-defeating, because at most it identified a hypothesis that required testing, and could not be understood as teaching or recommending that the claimed method be put to clinical use.  The Full Court rejected that analysis and upheld the trial judge’s finding that Mylan’s method of treatment and Swiss-style claims lacked novelty.

The Full Court held that, in assessing novelty, the key question is whether the information disclosed in the prior art is sufficiently specific and complete to be equal to the invention that is later claimed.  If so, then even a protocol for a trial to test the claimed method could be novelty-defeating.  The Full Court acknowledged that, in this respect, Australia’s law on novelty differs from the law applied by UK courts in cases such as Regeneron Pharmaceuticals Inc v Genentech Inc [2012] EWHC 657 (Pat) and Hospira UK Limited v Genentech Inc [2015] EWHC 1796 (Pat), which hold that the prior art must disclose actual achievement of the relevant therapeutic effect to be novelty-defeating.

This aspect of the Full Court’s decision arguably fails to give due consideration to the proper meaning and importance of words such as “treat” and “prevent” in method of treatment and Swiss-style claims.  As Mylan contended, at the stage of disclosing the protocol for a clinical trial, it is not known whether the product or method under consideration does in fact “treat” or “prevent” the particular condition or illness of interest, and there is a significant prospect that it will later prove ineffective or unsafe.  The approach of the Full Court and the primary judge makes clear that the nature and extent of the prior-published clinical trial protocol or other document will be critical in each case.  Those case-specific factual issues will be especially important in future cases, as it would seem a harsh outcome for patentees for statements of unproven hypotheses, theories, ideas or suggestions to anticipate and invalidate (for lack of novelty, putting aside considerations of obviousness which depend on the common general knowledge and availability of prior art) claims to a method that the patentee has subsequently proven effective and safe in “treating” or “preventing” the particular condition or illness.

Obviousness of formulation and method of treatment claims

Australian Courts generally assess obviousness by asking whether, before the priority date, a skilled person presented with the same problem as the patent owner would have been “directly led to try the claimed subject matter with a reasonable expectation of success” (referred to as the “modified Cripps question”).  Historically, that test has been applied in a strict manner by Australian courts, leading a number of patents to be upheld in Australia that have been invalidated on obviousness grounds in other jurisdictions.

Recently, however, Australian courts have adopted a more flexible interpretation of the Cripps test.  This Mylan case continues that trend.  The trial judge held two of Mylan’s patents (one relating to nanoparticulate formulations of fenofibrate, the other relating to methods of preventing or treating retinal damage associated with diabetes by administering fenofibrate) invalid on obviousness grounds, and the Full Court upheld those findings.

The following aspects of the Court’s obviousness analysis are notable:

  • Mylan’s patent for a nanoparticle formulation of fenofibrate included claims which required the use of specified surface stablizers.  The trial judge did not find that the skilled person would have been directly led to select those specific stabilizers with an expectation that they would be effective. Rather, he found that the claimed stabilizers were logical to try and that routine, trial-and-error testing would have demonstrated their suitability.  The Full Court agreed this was sufficient to support an obviousness finding.
  • In relation to Mylan’s method of treatment patent, an expert gave evidence that, before the priority date, his expectation of success with the claimed method would have been less than 50%.  The trial judge held that evidence was not inconsistent with a finding of obviousness, because the Cripps test does not require a numerical assessment.  Again, the Full Court agreed with that analysis.

The test for obviousness applied by Australian courts remains more demanding upon the party seeking revocation than the approach taken by (for example) the European Patent Office or the UK courts.  However, the Mylan decision continues a trend in Australian patent cases towards a more flexible application of the obviousness test that is somewhat closer to the approach taken by the European Patent Office and UK courts.  This serves to emphasise the importance of careful preparation of the obviousness defence in close collaboration with inventors and key expert witnesses.

Defining the scope of Swiss-style claims

The claims asserted by Mylan included Swiss-style claims.  Swiss-style claims are typically drafted in the form “Use of [active ingredient] in the manufacture of a medicament for the treatment of [disease or disorder]”.  They came about from the need to satisfy particular requirements for patentability which formerly applied under the European Patent Convention.  Although these requirements do not exist in Australia, Swiss-style claims are routinely included in Australian patents as their scope is different from that of method of treatment claims, which are also permitted under Australian law.

The Full Court in this Mylan case examined the interpretation of Mylan’s Swiss-style claims, having regard to the decision of the UK Supreme Court in Generics (UK) v Warner-Lambert [2018] RPC 2, and provided guidance on determining the scope of such claims under Australian law.

One of the Swiss-style claims asserted by Mylan recites:

 “Use of fenofibrate or a derivative thereof for the manufacture of a medicament for the prevention and/or treatment of retinopathy, in particular diabetic retinopathy”.

The Full Court confirmed that the claim, if valid, conferred a monopoly in respect of the method or process of making the medicament, and that the method or process is complete upon manufacture.  The monopoly did not extend to a method of treatment – that being the province of method of treatment claims.  The Full Court also confirmed that Swiss-style claims are purpose-limited in the sense that the medicament resulting from the method or process is characterised by the therapeutic purpose for which it is manufactured, as specified in the claim.  The Full Court rejected the “outward presentation” test that was favoured by Lords Sumption and Reed in the UK Warner-Lambert case.

In the first instance decision, the primary judge said that the the crucial question concerning the infringement of a Swiss-style claim was whether the manufacturer had made or will make the medicament with the intention that it be used in the treatment of the designated condition.  On this basis, to prove infringement of a Swiss-style claim, it would not be enough to show that it was “reasonably foreseeable” that a generic product would be put to the use referred to in those claims (although foreseeability could be relevant in the overall analysis).  The trial judge held that, to prove infringement of Swiss-type claims, it would be necessary to show that the generic intended that its product be put to the use referred to in the Swiss-style claims.

The Full Court disagreed with this approach, instead finding that infringement of a Swiss-style claim is concerned with what the allegedly infringing manufacturer has done, not what it intended to do.  That is, not what a generic manufacturer intended, but what the generic product is for.  According to the Full Court, a single factual question arises when considering infringement:  as the product of the claimed method or process, is the medicament for the specified therapeutic purpose?  The question, the Full Court said, is answered having regard to “all the circumstances of the case”.

The Full Court pointed to several such “circumstances” that will be relevant in determining the therapeutic purpose of the medicament as defined by a Swiss-style claim.  First, the court noted that the physical characteristics of the medicament as it emerges as a product of the manufacturing process, including its formulation and dosage, packaging and labelling, and its patient information, will be an important consideration.  So too will evidence of the manufacturer’s actual intention in making the medicament, where such evidence is available.  Both factors are relevant considerations, but neither is determinative.

On the facts of this case (which included “skinny labelling” confining the approved indications of the generic product to indications outside the conditions within Mylan’s method of treatment claims), the Full Court held that Mylan had not proved that Sun’s fenofibrate products were “for” the second medical use covered by Mylan’s Swiss-type claims.

The Full Court also gave consideration to the reasonably foreseeable use or uses to which the medicament would be put after manufacture.  But while a reasonably foreseeable use may be relevant in deciding the therapeutic purpose of a medicament, it is also not determinative:  it might be reasonably foreseeable that a product might be put to a particular use, but it does not necessarily follow that the product, as manufactured, is for that use.

The Full Court agreed with the primary judge that mere suitability of a medicament for a claimed purpose cannot be determinative of the question of infringement of a Swiss-style claim.  The fact that the patent has been granted on the basis of a second medical use means that there are multiple uses to which the medicament could be put.  Evidence of suitability for use was therefore considered ambiguous and could not alone answer the question whether the medicament, as manufactured, is one for the specified therapeutic purpose.

Ultimately, the Full Court found that the Swiss-style claims, if valid, would not have been infringed by the manufacture of Sun’s competing product.  Of particular relevance to the Full Court’s decision was the fact that the competing product could be used in a large number of diseases other than retinopathy.

The decision validates the importance of including both Swiss-style claims and method of treatment claims when protecting a therapeutic use in Australia.  Both types of claim are permitted in Australia, and although their scope is limited to the specified therapeutic use, each will directly capture a different infringer.  In particular, Swiss-style claims provide a more direct avenue than method of treatment claims for pursuing manufacturers of competitive pharmaceutical products, rather than the medical practitioners who perform the treatment.

Consistory clauses may not provide fair basis if too broad 

Mylan’s third patent, relating to an immediate-release micronized formulation of fenofibrate, was found by both the primary judge and the Full Court to be invalid for lack of fair basis.  The Full Court endorsed the primary judge’s reasoning that the disclosure elsewhere in Mylan’s patent specification made clear that the invention was to the immediate release fenofibrate composition and a method for preparing it, whereas Mylan had advanced a construction of a consistory clause and corresponding claims to the effect that the invention extended to any composition of fenofibrate which satisfies the specified dissolution profile.  The Full Court affirmed that, as Sun Pharma had submitted, this is “a paradigm example of claims which travel beyond the matter disclosed in the specification”, amounting to invalidity for lack of fair basis.

The fair basis test considered in this case still applies to Australian patents for which examination was requested prior to 15 April 2013, when the “Raising the Bar” amendments came into effect.  The ‘fair basis’ requirement is generally considered to be a lower standard for patentees than the ‘support’ requirement that replaced it from 15 April 2013, which Australian Parliament expressly intended to align more closely with requirements under European law.  Therefore, if a consistory clause alone will not necessarily provide fair basis, that risk is likely to be even more significant for more recent patents and pending future patent applications required to meet the higher standard of support (such as an “enabling disclosure”).

Authored by Duncan Longstaff and Michael Christie, PhD

4 min read

The Intellectual Property Laws Amendment (Raising the Bar) Act 2012 was introduced in Australia with the intention of aligning Australia’s written description requirements with those in the UK and Europe. Under the new Act, a specification must disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art (section 40(2)(a)) and the claims must be supported by the matter disclosed in the specification (section 40(3)).

In some cases, patent applicants can submit data not included in the specification as filed (so called post-filing data) in an effort to overcome section 40 objections. But there are currently no guidelines in Australia’s Patent Manual of Practice and Procedure concerning the use of post-filing data.  A recent decision in BASF Corporation [2019] APO 34 confirms that post-filing data can assist in overcoming section 40 objections provided the data is confirmatory in nature.


The decision in BASF relates to two patent applications – Application No. 2017204400 (the 400 application) and Application No. 2017204506 (the 506 application) – filed by BASF Corporation (the Applicant).  The 400 application relates to synergistic mixtures of Bacillus subtilis MBI600 and a second compound selected from a range of fungicidal or insecticidal compounds and plant growth regulators. The 506 application relates to synergistic mixtures of Bacillus pumilus INR7 and a second compound selected from a wide range of fungicidal or insecticidal compounds and plant growth regulators, or Bacillus subtilis MBI600. The applications describe several strategies by which synergy may be assessed and disclose data demonstrating synergistic mixtures, none of which were claimed.

The issues and findings  

In maintaining support and sufficiency objections against both applications, the Examiner adopted the two-step enquiry set out in Evolva SA [2017] APO 57:

Does the specification provide an enabling disclosure of all the things that fall within the scope of the claims, and in particular:

(a) Is it plausible that the invention can be worked across the full scope of the claim?

(b) Can the invention be performed across the full scope of the claim without undue burden?

The Examiner was satisfied that there would be no undue burden for the skilled person to perform the claimed invention as the claims were substantially narrowed during prosecution. However, the Examiner alleged that the applications failed the plausibility test (step (a)). In response, the Applicant submitted post-filing experimental data showing synergistic activity of some of the claimed mixtures. This was rejected by the Examiner who alleged that the specifications were speculative, and in the absence of a principal of general application supporting broad applicability of synergy at the filing date, the post-filing evidence of synergy cannot be used to demonstrate sufficiency (and support) of the specifications. The Examiner referred to the UK Supreme Court judgement in Warner-Lambert v Generics & Anr [2018] UKSC 56 (Warner-Lambert; previously reported here) which states (emphasis added):

“Sufficiency of disclosure must be satisfied at the effective date of the patent, ie on the basis of the information in the patent application together with the common general knowledge then available to the skilled person. Acknowledging sufficiency of disclosure on the basis of relevant technical information produced only after this date would lead to granting a patent for a technical teaching which was achieved, and, thus, for an invention which was made, at a date later than the effective date of the patent…”

The Applicant requested the matter be heard by the Patent Office. With regard to the role of post-filing data, the Delegate noted the absence of authority on this issue and observed “This is a matter which has not received attention following the implementation of the Raising the Bar Act, and so, in accordance with the guidance in the Explanatory Memorandum, I will have regard to UK and European case law as to the role of such evidence in relation to questions of support and sufficiency.”

Turning then to UK authorities, the Delegate cited Lord Sumption in Warner-Lambert at [72]:

“This does not mean that subsequent data is never admissible in a dispute about sufficiency, but the purpose for which it is admitted is strictly limited.  Where the asserted therapeutic effect is plausible in the light of the disclosure in the patent, subsequent data may sometimes be admissible either to confirm that or else to refute a challenger’s contention that it does not actually work … it cannot be a substitute for sufficient disclosure in the specification.”

The Applicant argued that the post-filing evidence submitted in this case: 1) supplemented the evidence contained in the specifications; and 2) refuted the contentions of the Examiner regarding the unpredictability of synergy. The Applicant submitted declaratory evidence from an inventor attesting that the disclosure in the specifications of synergy between a particular Bacillus and a chemical pesticide having a given mechanism of action makes it more or less likely that synergy will be observed with a different chemical pesticide with a different mechanism of action. Accepting the Applicant’s evidence, the Delegate found that the post-filing data confirmed the expectation of the skilled person having regard to the specification as filed and the common general knowledge as at the filing date.  Accordingly, the claims were found to be fully supported and sufficiently enabled by the specification as filed.


This decision confirms that post-filing experimental data can help establish sufficiency and support provided the data confirms the information disclosed in the specification as understood by a skilled person in the art.  In our experience, post-filing data can be, and has been, persuasive in overcoming written description objections.

Authored by Michael Christie, PhD

9 min read

Biological molecules, including polypeptides and, in some cases, nucleic acids, can be patented under Australian law.  The level of disclosure that is required to support and enable a claim to a polypeptide will depend on several factors, including:

i.    the identity of the person skilled in the art;

ii.   the information disclosed in the specification;

iii.  the function of the polypeptide; and

iv.  the specific sequence being claimed.

This article briefly describes how each of these factors contributes to the determination of a claim’s scope under Australian practice.

The person skilled in the art

In considering whether a claim is sufficiently enabled, the Australian Patent Office will ask:

i.   whether it is plausible that the invention could be worked across the full scope of the claim; and

ii.  whether the invention can be performed across the full scope of the claim without undue burden.

The answer to both questions will depend on the identity of the hypothetical person skilled in the art.  The skilled person may carry out ordinary methods of trial and error and may use their common general knowledge to supplement the information contained in the patent specification.[1]  Where the subject matter of the invention is inherently complex – protein engineering may be one example – a substantial amount of work may be required, and indeed expected, for a person skilled in the art to perform the claimed invention.  When seeking to claim a large number of polypeptides, a patent applicant will therefore be well served if they can frame the invention as one which lies within a complex technical field, where the “ordinary” skilled person is highly qualified and capable of complex experimental techniques.

The skilled person played a prominent role in Evolva SA [2017] APO 57 (“Evolva”), a case which concerned the use of uridine-5′-diphospho-dependent glycosyltransferases (UGTs) to glycosylate mogrol.  The specification described only five UGTs, but the claims encompassed the use of polypeptides having at least 90% sequence identity to any one of them.  The examiner rejected the claims, alleging that an undue burden would be placed on the skilled person who would have to produce every polypeptide encompassed by the claims and then perform an assay on each to identify those which exhibited the desired activity.  In arriving at the decision, the examiner characterised the skilled person as being “a single synthetic chemist, perhaps a PhD candidate”.

The matter was heard before a Delegate of the Commissioner of Patents who ultimately allowed the application including claims that defined polypeptides having at least 90% sequence identity to any one of the five UGTs described in the specification.  Crucial to the Delegate’s decision was the characterisation of the person skilled in the art.  Contrary to the examiner’s characterisation, the Delegate considered that a team, comprising biotechnologists and synthetic chemists, would be the “person” to whom the specification is addressed.[2]  Needless to say, the team of people described by the Delegate was considered to have a much wider breadth of skills and knowledge at their disposal when it comes to assessing the plausibility of, and to performing, the invention as claimed.

 The information disclosed in the specification

Australian law does not prescribe a level of experimental data that must be disclosed by a patent specification to enable a polypeptide claim of a certain scope.  Of course, an abundance of experimental data will, in many cases, help to enable a claim that encompasses a broad range of polypeptides, particularly when it comes to demonstrating the plausibility of the claimed invention.  However, plausibility can also be demonstrated by a priori reasoning.[3]  In the absence of extensive experimental data, a broadly drafted claim may be enabled where the specification discloses a technical rationale that makes the claimed invention plausible to a person skilled in the art and provides guidance for the skilled person to perform the invention across the full scope of the claim.

To take a simple example, a claim which defines an antibody solely by reference to its target-binding specificity will typically be enabled provided the target is new and the specification sufficiently describes the epitope and has shown the antibodies can be raised against it.  In such cases, the specification need only disclose one such antibody since raising antibodies against the epitope is considered to be a principle that can be generally applied to produce antibodies across the entire scope of the claim.[4]  In each case, the question to ask is whether, based on the disclosure of the specification, including any a priori reasoning provided therein, a person skilled in the art would find the claimed invention plausible and could work the invention across the full scope of the claim.

The function of the polypeptide

A novel polypeptide may be defined in a claim either structurally, such as by its amino acid sequence, or functionally, for example, by its target-binding specificity or its enzymatic activity.  But somewhat paradoxically, a narrower claim which includes both structural and functional limitations can, in some cases, be found insufficiently enabled.

Take, for instance, our antibody example above.  While an antibody defined solely by its target-binding specificity may be fully enabled, further defining the antibody by reference to one or more of its complementarity determining regions (CDRs) will often render the claim insufficiently enabled.  The Patent Office takes the position that the disclosure of the epitope is not a principle of general application that can be applied to generate the antibodies in the claimed subset, to the exclusion of other antibodies not encompassed by the claim.[5]  In performing the claimed invention, a person skilled in the art would have to raise antibodies against the epitope and then perform an additional sequencing step to identify those that fall within the claimed subset.  This, in the Patent Office’s view, would place an undue burden on the person skilled in the art.

There is no general rule, however, prohibiting the inclusion of functional and structural limitations in a claim.  In Evolva, the claims in question defined a method of producing a mogroside compound using a UGT having at least 90% sequence identity to any one of five UGTs described in the specification.  Given what was known about the structure and function of UGTs, including the information disclosed by the specification, the Delegate found that the skilled person would consider it plausible that functional variants to a level of identity of at least 90% could be identified and would be useful in the claimed methods.[6]  On the issue of “undue burden”, the Delegate observed that the specification provided sufficient information about the manner in which UGT variants may be generated and tested.  Although such tests may involve time-consuming experimentation, they did not, it was found, present difficulties that would require the skilled person to undertake any prolonged research or experimentation that would be considered an undue burden in the relevant field of technology.[7]

The decision in Evolva contrasts with the more recent decision in Gary B Cox v MacroGenetics, Inc. [2019] APO 13, where the Patent Office rejected claims directed to deimmunized therapeutic proteins having an extended serum half-life. The therapeutic proteins comprised an albumin-binding domain (ABD) that could bind to serum albumin and thereby extend the half-life of the entire protein.

Claim 1 of the application defined a polypeptide comprising a variant ABD, the variant ABD having an amino acid sequence that differs from wild-type ABD by comprising one of two combinations of amino acid substitutions.  Importantly, the claim also included two functional limitations, namely that the ABD is deimmunized and that it is albumin-binding.

The use of the inclusive term “comprising” in claim 1 allowed for the variant ABD to have any number of mutations, provided it included those specifically recited in the claim. While acknowledging that the level of skill possessed by the relevant person skilled in the art would be high, it was not apparent to the Delegate that the skilled person would appreciate what mutations could be combined with those specified in the claim whilst achieving the functional limitations of the claims.[8]  To the contrary, evidence suggested that combinations of mutations would have an unpredictable effect on albumin-binding and could even introduce immunogenic regions.[9]  The Delegate found that the work required to identify variants having the desired properties, particularly the ability to bind albumin, while systematic and iterative, is unpredictable, with limited guidance provided by the specification.  The effort required to perform the invention across the full scope of the claims was described as being “in the nature of a research project” and therefore constituted an undue burden.[10]

The specific sequence being claimed

Certain polypeptides, and indeed certain regions within a polypeptide, may be more likely than others to tolerate amino acid variation without compromising the functionality of the polypeptide.  Large structural proteins, for instance, may tolerate a greater level of variation compared to smaller antigen-binding proteins or enzymes.

When it comes to antibodies, for example, one might expect that an amino acid change within a CDR would be more likely to affect binding specificity compared with an amino acid change within a framework region. (Of course, amino acid changes within the framework region can still impair the folding within, or the pairing between, the variable domains.)  Given the significant role played by the CDRs in dictating binding specificity, the Patent Office may allow a greater degree of sequence variability within the variable domain than it would within the CDRs themselves.  For claims which define an antibody solely by its heavy and light chain variable regions, the Patent Office has allowed 90% sequence identity.[11]

In some cases, mutations within a polypeptide may have unpredictable effects on the polypeptide’s function.  In Gary B Cox v MacroGenetics, Inc. [2019] APO 13, evidence was adduced showing that mutations would have an unpredictable effect on certain properties of the claimed polypeptide; properties that were included in the claims as functional limitations.[12]  Given the unpredictability in the art, and the lack of guidance provided by the specification, the Delegate found that the work required to perform the invention across the full scope of the claims would constitute an undue burden, and so the claims were found to be insufficiently enabled.[13]


When patenting polypeptides, there is no general rule that dictates the level of sequence variation that may be encompassed by any particular claim.  Certain proteins may be more resilient than others to amino acid changes, or the changes may have predictable consequences on the protein’s function, in which case, a broad range of protein variants may be validly claimed.  A large number of variants may also be claimed in circumstances where the person skilled in the relevant art is highly qualified and capable of complex experimental techniques that could be employed to perform the invention across the full scope of the claims.  Examples in the specification which demonstrate the functionality of protein variants can also help, but so too can a technical rationale which makes the claimed invention plausible and workable across the full scope of the claims.

[1] Eli Lilly & Co v. Human Genome Sciences, Inc [2008] RPC 29, [239]. Evolva SA [2017] APO 57, [24].

[2] Evolva, [54].

[3] Warner-Lambert v. Generics (t/a Mylan) & Actavis [2018] UKSC 56.

[4] The Australian Patent Office Manual of Practice and Procedure, s 2.11A Annex A.

[5] The Australian Patent Office Manual of Practice and Procedure, s 2.11A Annex A.

[6] Evolva, [62].

[7] Evolva, [68].

[8] Gary B Cox v MacroGenetics, Inc. [2019] APO 13, [95].

[9] Gary B Cox v MacroGenetics, Inc. [2019] APO 13, [97]-[99].

[10] Gary B Cox v MacroGenetics, Inc. [2019] APO 13, [107].

[11] See, for example, Australian Patent No. 2015242981.

[12] Gary B Cox v MacroGenetics, Inc. [2019] APO 13, [97]-[99].

[13] Gary B Cox v MacroGenetics, Inc. [2019] APO 13, [107].

Authored by Michael Christie, PhD

11 min read

Switching patients from an originator biologic (the reference product) to a biosimilar version has been a topic of keen interest in recent years, both in Australia and globally, as more biosimilars have emerged onto the market. This trend has flowed from the expiration of data exclusivity and patent protection for a number of important originator biologics. While biosimilar medicines have been available in Australia for over a decade, biosimilars to the disease‐modifying antirheumatic drugs (DMARDs) (e.g. infliximab, rituximab, etanercept and adalimumab biosimilar products) have only come onto the market in the last 2-5 years. As at February 2020, the Schedule to Australia’s Pharmaceutical Benefits Scheme (PBS) listed 86 originator biologics, with 17 of these biologics having one or more biosimilar brands.[1]

Despite more biosimilars becoming available as alternatives to established biologics, and initiatives by the Australian Government to reduce the administrative burden of switching for prescribers and to enhance consumer confidence in biosimilars, the uptake of biosimilar products has remained limited in Australia.

There are strong financial incentives for the Australian Government to seek to increase the uptake of biosimilars and thus drive competition and lower prices for biological medicines in Australia. In the 2018-2019 financial year, biologics accounted for 8 of the top 10 PBS-subsidised drugs by expenditure.[2] Further, the majority of blockbuster biologics are intended for long-term use in chronic diseases, adding significantly to the cost of subsidising their supply.

In this article, we examine some concerns that have been raised in relation to the practice of biosimilar substitution by pharmacists, and review the current medical consensus on substitution and interchangeability. We also consider Australia’s regulatory arrangements for biosimilar approval and substitution, which present some unique opportunities for promoting wider biosimilar adoption.

Concerns related to switching

Unlike generic versions of small molecule medicines, which are assumed to be identical (in relevant respects) to the originator drug, biosimilars are highly similar, but not identical, to their reference biologic, which has raised concerns about their substitutability. When biosimilars first emerged, interchangeability was an issue of considerable controversy, with concerns expressed about:[3]

  • whether efficacy and safety would be compromised when patients were switched between a biologic and biosimilar product or from one biosimilar to another, and in particular when multiple switching occurs;
  • whether switch-related immunogenicity (neutralising antibodies against the biosimilar product and/or any naturally occurring counterpart protein) may be triggered when switching from a biologic to a biosimilar (or between biosimilars); and
  • whether it is desirable for biosimilar sponsors to be permitted to seek marketing approval for multiple additional indications by extrapolation from the reference biologic’s data, once biosimilarity has been established for a single indication.

These concerns have in some respects remained, despite evidence and better understanding concerning the safety and efficacy of individual biosimilars, as discussed in further detail below.

Terminology – interchangeability and substitutability

The use of terminology in this area varies between jurisdictions, and has been the source of some confusion. In Australia and Europe, interchangeability generally refers to the practice of changing one medicine for another equivalent medicine by the treating physician, with the clinical decision to exchange one medicine for another medicine (with the same therapeutic intent in a given patient by the prescribing doctor) referred to as switching.

The term substitution, as used in Australia, refers to the practice of dispensing one medicine instead of another equivalent and interchangeable medicine by a pharmacist, without requiring consultation or approval from the prescriber.

By contrast to Australian usage, in the United States the term ‘interchangeable biosimilar’ refers to a regulatory standard, whereby a pharmacist is permitted to substitute an interchangeable product for the reference product without consulting the prescriber, subject to individual state regulations. The United States’ ‘interchangeable biosimilar’ designation is roughly equivalent to Australia’s substitution practices, although no biosimilar to date has obtained interchangeable status in the United States.

The issue of structural variability

Much of the concern about switching patients from biologics to biosimilars arises from the inherent structural variability of biologic molecules. Biologics are pharmaceutical products that contain one or more active substances that are derived from living cells or organisms. A common form of a biologic medicine currently in use is a monoclonal antibody. A biosimilar is a version of a reference (approved) biologic that has established similarity to its reference product in terms of quality, safety and efficacy.

Biologics and biosimilars differ from traditional small-molecule drugs, with the latter being structurally simple, chemically synthesised and easily characterised. Biologics, on the other hand, are large, highly complex molecules that are not easily characterised. Biologics are also sensitive to manufacturing process conditions, particularly in relation to post-translational modifications, such as glycosylation patterns. This can lead to variability in the final structure of individual molecules, referred to as micro-heterogeneity, which can lead to a risk of product divergence.[4] Slight variation may also occur between each batch of a biologic manufactured, referred to as batch-to-batch variation.

Is switching considered safe?

The propensity for minor structural variability in biologics, as described above, has given rise to concerns that biologics and biosimilars may be less suitable for pharmacy-level substitution than traditional, small-molecule medicines. On the other hand, there has now been over 10 years of real-world clinical experience with switching involving biosimilars that have been launched,[5] as well as a growing number of studies regarding the safety and efficacy of switching, such as between certain erythropoietin-stimulating agents, filgrastim, insulin, adalimumab, rituximab, infliximab and etanercept, and their corresponding biosimilars.[6]

Australia’s biosimilars regulatory scheme

In Australia, the Therapeutic Good Administration (TGA) has responsibility for registration and marketing authorisation of medicines (focusing on safety, efficacy and manufacturing quality) while the Pharmaceutical Benefit Advisory Committee (PBAC) advises the Australian Government on whether supply of a medicine should be subsidised (focusing on cost-benefit analysis) as well as advising on brand substitutability and other matters relating to the PBS.

Due to the complexity of biologic molecules and their propensity for structural variation, establishing biosimilarity requires more rigorous regulatory processes than those applied to establishing bioequivalence of generic medicines. The TGA assesses each biosimilar based on the totality of available data, comparing it to the reference product in terms of its physicochemical structure, biological activity, preclinical data (pharmacokinetic and pharmacodynamic data) and clinical trials data (efficacy, safety and immunogenicity). Regulatory approval for a biosimilar requires that no clinically meaningful differences exist and that the biosimilar molecule is therapeutically equivalent to the reference medicine.[7]

In general, a Phase III clinical trial for a single indication will be sufficient to confirm biosimilarity (together with preclinical and physiochemical data). Once biosimilarity is established, it may be possible for a biosimilar to be approved for other indications by so-called ‘indication extrapolation’ from the reference product’s data.[8] An Australian consensus statement on the use of biosimilars in haematological conditions published by an expert panel in April 2020 reported that post-approval experience has confirmed that extrapolation of indications is a safe practice.[9]

Australia’s approach to substitutability

‘a’ flagging

The Australian Government has taken a relatively pro-substitution approach to biosimilars, with substitutable biosimilars denoted in the Schedule of Pharmaceutical Benefits with an ‘a’ superscript (a-flagged). However, the prescribing physician can prevent pharmacy-level brand substitution by ticking the “brand substitution not permitted” box on the prescription form.[10] Where a prescription indicates that no substitution is allowed, it is an offence under section 103(2) of the National Health Act 1953 for a pharmacist to dispense a brand other than that specified on the prescription. Where brand substitution is permitted, good pharmacy practice further requires that the pharmacist consult with the patient before substituting another brand. These safeguards are intended to ensure that no uncontrolled substitution occurs in practice in Australia.

As noted previously, the PBS (as at February 2020) lists 86 originator biologics, with 17 reference biologics having one or more biosimilar products,[11] with all but a few biosimilars being ‘a’ flagged to their reference product.

PBAC assessment of biosimilar substitutability

The PBAC first announced in April 2015 that biosimilar products would be ‘a’ flagged to their reference product as a default position in Australia.[12] However following consumer consultation, this position was revised in July 2015, with the PBAC instead stating that recommendations for ‘a’ flagged status would be made on a case-by-case basis. This change in stance, the Committee indicated, was meant to reassure consumers that biosimilars would not, simply by virtue of being a biosimilar, be provided with automatic substitutability. The PBAC further advised that the following matters would be relevant considerations in support of ‘a’ flagged PBS listing status:[13]

  • TGA determination of biosimilarity to the reference biologic;
  • absence of any evidence to suggest significant differences in clinical effectiveness or safety compared with the reference product;
  • absence of any evidence identifying patient populations where the risks of using the biosimilar product are disproportionately high;
  • availability of data that the biosimilar was safe and effective in treatment-naïve patients initiated on the biosimilar product; and
  • availability of data to support equivalent safety and effectiveness when switching between the reference product and the biosimilar.

In March 2018, the PBAC once again revised its position on the assessment of brand equivalence and substitution for biosimilars, this time noting that the TGA’s determination of biosimilarity adequately covered matters of safety and efficacy. The PBAC’s simplified criteria now includes only the following matters:[14]

  • TGA determination of biosimilarity;
  • availability of supportive data relating to the effects of switching between the reference product and the biosimilar product(s); and
  • practical considerations relating to substitution by the pharmacist at the point of dispensing (e.g., strength of formulation and number of units per pack).

The PBAC indicated that where there is insufficient data to support ‘a’ flagging, additional data should be collected to facilitate future reconsideration. The Committee has also made clear that its preference is to extrapolate biosimilarity across all indications proposed for subsidy rather than requiring indication-specific data.

The United States’ ‘interchangeability’ designation

By contrast, in the United States interchangeability is a regulatory standard with a higher bar in terms of the clinical data required. The Food and Drug Administration (FDA) released updated guidance for biosimilar interchangeability in May 2019,[15] which contemplates two categories of licensed biosimilars – ‘biosimilars’ and ‘interchangeable biosimilars’. However, to date, no biosimilar products approved for marketing in the United States have been designated as ‘interchangeable’ by the FDA.[16]

The United States is currently the only country that requires a biosimilar sponsor to submit additional clinical trials data to obtain an interchangeability designation.[17] Qualifying ‘interchangeable’ products must demonstrate to the FDA’s satisfaction that they may be expected to produce the same clinical result as the reference product in any given patient. The FDA requires sponsors to conduct switching studies for any biosimilar that is administered more than once. Such studies must incorporate at least two separate exposure periods for each of the products tested (i.e. at least three switches between reference biologic and biosimilar). In order to produce this data, biosimilar sponsors must expend significant resources to conduct clinical switching studies satisfying these requirements. Once the product meets the requirements of an interchangeable biosimilar for at least one indication, the sponsor may seek to be licensed for additional indications for which the reference product is licensed by extrapolation.[18]

Does substitution occur in Europe?

Unlike the FDA, the European Medicines Agency (EMA) has not adopted a stance on interchangeability and does not regulate interchangeability, nor substitution practices, which fall under the authority of individual European Union (EU) member states.[19] In this regard, it is reported that no pharmacy-level substitution occurs in the EU,[20] and moreover no EU member has deemed that switching studies are a necessary requirement for biosimilar substitutability.[21]

By way of example, the United Kingdom does not permit pharmacy-level substitution and instead leaves this to the prescribing physician’s discretion.[22] France went as far as introducing laws granting pharmacy-level substitution of biosimilars for treatment-naïve patients only, but it is yet to put this into practice as a result of opposition to the implementation of substitution practices.[23]

‘a’ flagging and skinny-labelling strategies

Sponsors of both biologics and biosimilars should take note of the interplay between ‘a’ flagging and so-called ‘skinny-labelling’ strategies aimed at carving out patent-protected indications to allow a biosimilar supplier to potentially avoid patent infringement by arguing that it does not have reason to believe its product would be put to an infringing use. The PBAC is only permitted to list a product on the PBS in respect of indications for which the product has been granted marketing approval by the TGA. Thus one potential approach for biosimilar sponsors is to limit their application for marketing approval to only those indications for which patent protection has expired or is unlikely to withstand a validity challenge. However, it is not clear that such an approach will avoid patent infringement in respect of a non-indicated use. Australian courts have grappled with these indirect infringement issues in recent years, which are legally complex and highly dependent on the specific facts attending the products, patent and market relevant to the innovator and generic/biosimilar products in question.

The way forward?

The slow market uptake of biosimilars in Australia has generally been attributed to the understandable lack of familiarity and comfort with biosimilar products by treating physicians, pharmacists and patients alike.

It is to be expected that confidence in biosimilars will increase with time. It is also likely to be enhanced through substitution policies and initiatives (such as Australia’s practice of ‘a’ flagging biosimilars on a case-by-case basis), clearer guidelines on interchangeability and substitutability designations, expert medical consensus statements on biosimilar use, as well as pricing incentives. In this regard, it will be of interest to see how the market uptake of biosimilars develops over this decade.

[1] PBS. ‘Biological Drugs and Brands listed on the Pharmaceutical Benefits Scheme’. http://www.pbs.gov.au/info/browse/biological-medicines-currently-listed-on-the-pbs#P. Accessed 23 May 2020.

[2] PBS. ‘PBS Expenditure and Prescriptions Report 1 July 2018 to 30 June 2019’. http://www.pbs.gov.au/statistics/expenditure-prescriptions/2018-2019/PBS_Expenditure_and_Prescriptions_Report_1-July-2018_to_30-June-2019.pdf. Accessed 23 May 2020.

[3] Gregory G.P. et al. ‘A consensus statement on the use of biosimilar medicines in hematology in Australia’. Asia-Pacific Journal of Clinical Oncology. April 2020. https://doi.org/10.1111/ajco.13337; Weise M et al. ‘Biosimilars: what clinicians should know’. Blood. 2012;120:5111‐5117.

[4] Ramanan S and Grampp G. ‘Drift, evolution, and divergence in biologics and biosimilars manufacturing’. BioDrugs. 2014;28(4):363–72.

[5] Ibid; La Noce A. and Ernst M. ‘Switching from reference to biosimilar products: an overview of the European approach and real-world experience so far’. European Medical Journal. September 2018. https://emj.europeanmedical-group.com/wp-content/uploads/sites/2/2018/09/Switching-from-Reference….pdf. Accessed 23 May 2020.

[6] McKinnon R. et al. ‘Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review’. BioDrugs (2018) 32:27–52. https://doi.org/10.1007/s40259-017-0256-z.

[7] TGA. ‘Biosimilar medicines regulation – Version 2.2’. https://www.tga.gov.au/sites/default/files/biosimilar-medicines-regulation.pdf. Accessed 23 May 2020.

[8] As above note 3

[9] As above note 3, Table 2 – Table of Recommendations.

[10] Department of Health. ‘Biosimilar medicines: the basics for health care professionals’. March 2017. https://www1.health.gov.au/internet/main/publishing.nsf/content/biosimilar-awareness-initiative/$File/Biosimilar-medicines-the-basics-for-healthcare-professionals-Brochure.pdf. Accessed 23 May 2020.

[11] As above note 1.

[12] PBAC. ‘Reimbursement of Biosimilar Medicines’. PBAC Special Meeting April 2015. http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2015-04/2015-04-biosimilars.pdf. Accessed 23 May 2020.

[13] PBAC. ‘Consumer Hearing on Biosimilars’. PBAC Meeting July 2015. http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2015-07/consumer-hearing-record-on-biosimilars-2015-07.pdf. Accessed 23 May 2020.

[14] PBAC. ‘Public summary document – Considering brand equivalence/substitution for biosimilar medicines’. PBAC meeting March 2018. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2018-03/Biosimilar%20medicines-psd-march-2018. Accessed 23 May 2020.

[15] FDA. ‘Considerations in demonstrating interchangeability with a reference product: guidance for industry’. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdfAccessed 23 May 2020.

[16] Centre for Biosimilars. ‘Boehringer Ingelheim Policy Chief Discusses Biosimilar Outlook’. 8 May 2020. https://www.centerforbiosimilars.com/conferences/festival-of-biologics-2020/boehringer-ingelheim-policy-chief-discusses-biosimilar-outlook. Accessed 23 May 2020.

[17] Welch A. R. 2017. ‘What Systems Are Needed to Create a Viable Biosimilar Market?’ Biosimilar Development. https://www.biosimilardevelopment.com/doc/what-systems-are-needed-to-create-a-viable-biosimilar-market-0001

[18] Ibid; Murphy A. et al. ‘New FDA Guidance on Biosimilar Interchangeability’. Life Science Leader, July 2019. https://www.lifescienceleader.com/doc/new-fda-guidance-on-biosimilar-interchangeability-0001. Accessed 23 May 2020.

[19] La Noce A and Ernst M. ‘Switching from reference to biosimilar products: an overview of the European approach and real-world experience so far’. European Medical Journal. 2018;3[3]:74-81.

[20] As above note 17.

[21] As above note 19.

[22] As above note 17.

[23] Ibid.

Authored by Duncan Longstaff

5 min read

The Australian Patent Office’s decision in The University of British Columbia [2020] APO 15 (20 March 2020) considers how the “raised bar” requirements of support (section 40(3)), enablement (section 40(2)(a)) and best method (section 40(2)(aa)) are to be assessed. The decision is a reminder that these requirements are now more onerous than they were previously in Australia, and (with respect to the ‘best method’ requirement) in other major jurisdictions. When drafting specifications intended for prosecution in Australia, especially in biotechnology and pharmaceutical areas which are often struck by unpredictability, inventors should provide, and attorneys must include, not only as much detail as possible on the experimental methods for producing, evaluating and testing but also the best method known to perform the claimed invention. 


The claimed invention related to antibodies exhibiting selectivity for the ‘eta’ isoform of the 14-3-3 protein over other isoforms of that protein. The ability of the antibodies to discriminate between the isoforms has utility in the diagnosis of inflammatory conditions such as arthritis. The claims, as proposed to be amended, were directed to methods of determining the presence of the eta isoform of the 14-3-3 protein in a sample using the antibodies, and kits containing an immobilised antibody.

The applicant (The University of British Columbia) requested a hearing after receiving a third adverse examination report for its patent application (No. 2015202689), which maintained objections raised under section 40 with respect to the requirements for clear enough and complete enough disclosure, support and best method of performance. The Examiner reserved his opinion on novelty and inventive step pending resolution of the section 40 issues. The applicant submitted a declaration from the inventor, Dr Marotta, during prosecution. This declaration proved to be very useful for the hearing and was closely considered by the Delegate, as detailed below.   

Issues and findings

The Delegate (Dr Stephen Barker, the Deputy Commissioner of Patents) considered the following section 40 issues:

a)   Section 40(2)(a) – enablement
b)   Section 40(3) – support
c)   Section 40(2)(aa) – best method

In relation to the first issue, enablement, the Delegate cited the approach taken in the earlier Patent Office decision Evolva SA [2017] APO 57 (Evolva), which confirmed that enablement of a claim should be determined according to a 2-step approach involving “plausibility” and “undue burden”. The Delegate stated that the Evolva decision “sets out a proper understanding of the law” (emphasis added) and noted at [7] the guidance in Evolva as to relevant factors for enablement:   

“EP and UK decisions have provided some general guidance on factors that come into consideration, including: uncertainty and a lack of predictability, incomplete experimental details and a lack of guidance in the specification including instructions on how to proceed in case of failure.”

Turning to the question of “plausibility” the Delegate further cited Evolva at [43]:

“the scope of the monopoly, as defined in the claims, must correspond to the technical contribution the patentee has made to the art. If the assertions made in the specification are not plausible then it cannot be reasonably said that the patentee has made a contribution to the art.”

and at [44]:

“an invention that is plausible may still fail on sufficiency if the specification essentially sets out a research programme and there is an undue burden of experimentation required to put it into practice. If an invention is implausible then it would inherently require an undue burden of experimentation to put it into practice (if at all).”

Applying the approach from Evolva and on the basis of Dr Marotta’s declaration, the Delegate was satisfied that the specification provided a general method of producing hybridomas and sufficient description of how to distinguish hybridomas that produce the desired antibodies. He accepted that the required testing is routine in the art and is not onerous.

As to the second issue, support, the Commissioner cited CSR Building Products Limited v United States Gypsum Company [2015] APO 72 (CSR), which suggested that to meet the (relatively) new Australian requirement of support, the claims should correspond to the technical contribution to the art. The Delegate referred to the indication in CSR at [113] that:

“An important question will often be whether the technical contribution to the art is a general principle or the specific examples in the specification.”

The Delegate found that both the specification and information provided by Dr Marotta indicated that the technical contribution was the use of select epitopes to produce antibodies selective to the eta isoform. Accordingly, the Commissioner decided there was a principle of general application and thus the claims, although broader than the examples disclosed in the specification, were supported.    

For the final issue, best method, which is not a major consideration in jurisdictions outside of Australia (i.e. Europe and the US), the Commissioner referred to Kineta, Inc [2017] APO 45 (Kineta) at [18]:

“it is necessary to determine what method is disclosed in the specification, and then to ask whether there is any evidence that the applicant was aware of a better method of performing the invention.”

The Delegate explained at [21] that the specification identified four immunogens and their use in preparing hybridomas for producing the antibodies of interest, and that there was no evidence that the applicant was aware of a better method.

The objections raised under section 40 were therefore all overruled by the Delegate. However, the application will now undergo examination for novelty and inventive step. The deadline for acceptance is 3 months post the date of the hearing and may be extended upon request by the applicant at the discretion of the Commissioner.  


This recent decision highlights some of the leading Patent Office decisions in Australia regarding enablement (Evolva), support (CSR) and best method (Kineta). While assessment of these requirements will continue to be required on a case-by-case basis, the findings here shed further light on how the Australian Patent Office is likely to assess section 40 provisions, particularly given the limited guidance provided by Australian courts on the “raised bar” requirements of sufficiency and support.   

When drafting specifications in the areas of biotechnology and pharmaceuticals intended for prosecution in Australia, it is important that inventors provide, and attorneys must include, not only as much detail as possible on the experimental methods for producing, evaluating and testing but also the best method known to perform the claimed invention. 

The decision is also a good reminder that a declaration from the inventor (in some cases more preferably from an independent expert) can assist in showing that a skilled person can perform the claimed invention on the basis of the disclosure in the specification. Further, the ability to request a hearing is worth considering to address an Examiner’s maintenance of objections in Australia. This effectively “stops the clock” on the acceptance deadline and provides an opportunity for the matter to be heard by a hearing officer who may take a different view to the primary and/or supervisory Examiner.

Authored by Duncan Longstaff