Otsuka Pharmaceutical Co Ltd v Sun Pharma ANZ Pty Ltd [2025] FCAFC 161

(2) Accordingly, the Patent Extension was invalid;

Otsuka Pharmaceutical Co Ltd v Sun Pharma ANZ Pty Ltd [2025] FCAFC 161 | Case summary | Zoe

[22]

The suspending agent will be present in an amount within the range from about 0.2 to about 10% by weight, preferably for about 0.5 to about 5% by weight based on the total weight of the sterile injectable formulation. Examples of suspending agents suitable for use include, but are not limited to, one, two or more of the following: sodium carboxymethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, hydroxypropylethyl cellulose, hydroxypropylmethyl cellulose, and polyvinylpyrrolidone, with sodium carboxymethyl cellulose and polyvinylpyrrolidone being preferred. Other suspending agents suitable for use in the vehicle for the aripiprazole include various polymers, low molecular weight oligomers, natural products, and surfactants, including nonionic and ionic surfactants, such as cetyl pyridinium chloride, gelatin, casein, lecithin (phosphatides), dextran, glycerol, gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride [etc]...

Carboxymethyl cellulose or the sodium salt thereof is particularly preferred where the desired mean particle size is about 1 micron or above.

The bulking agent (also referred to as a cryogenic/lyophilize protecting agent) will be present in an amount within the range from about 1 to about 10% by weight, preferably from about 3 to about 8% by weight, more preferably from about 4 to about 5% by weight based on the total weight of the sterile injectable formulation. Examples of bulking agents suitable for use herein include, but are not limited to, one, two or more of the following: mannitol, sucrose, maltose, xylitol, glucose, starches, sorbital, and the like, with mannitol being preferred for formulations where the mean particle size is about 1 micron or above. It has been found that xylitol and/or sorbitol enhances stability of the aripiprazole formulation by inhibiting crystal growth and agglomeration of drug particles so that desired particle size may be achieved and maintained.

The buffer will be employed in an amount to adjust pH of an aqueous suspension of the freeze-dried aripiprazole formulation to from about 6 to about 8, preferably about 7. ... Examples of buffers suitable for use herein include, but are not limited to, one, two or more of the following: sodium phosphate, potassium phosphate, or TRIS buffer, with sodium phosphate being preferred.

The freeze-dried formulation of the invention may optionally include a pH adjusting agent which is employed in an amount to adjust pH of the aqueous suspension of the freeze-dried aripiprazole within the range from about 6 to about 7.5, preferably about 7 and may be an acid or base depending upon whether the pH of the aqueous suspension of the freeze-dried aripiprazole needs to be raised or lowered to reach the desired neutral pH of about 7. ...

The freeze-dried aripiprazole formulations may be constituted with an amount of water for injection to provide from about 10 to about 400 mg of aripiprazole delivered in a volume of 2.5 mL or less, preferably 2 mL for a two to six week dosage.

[41]

(1) The person skilled in the art would be aware that a number of variable factors can affect the length of time of the release of aripiprazole from the depot in the Formulations claimed (PJ [206]). One variable is dosage of aripiprazole, but there is nothing in the PTE Claims to limit the dosage amount, the specification allowing for a dosage in the range of 0.1 to 600mg per 1 mL (PJ [208]). Another is particle size. It was common general knowledge that particle size has an impact on release (PJ [214]), however, the Patent does not describe the mathematical relationship between particle size and absorption/release (PJ [215]). Another is volume. The pressure associated with the administration of larger volumes (2 mL or more) of formulation can decrease the time that it takes for the drug to dissolve (PJ [216]). Other factors include whether the formulation is injected subcutaneously or intramuscularly and, if the latter, the site of administration (PJ [218]).

(2) Claim 1 has a release period of at least one week, claim 16 has a release period of at least two weeks (PJ [219]), yet they claim the same range of mean particle size (of about 1 to 10 microns) (PJ [220]). Other claims have other variations, where the mean particle size range is the same but the release periods are different (such as claims 6 and 19). From these, it is apparent that the same particle size alone will not provide the same release period (PJ [222]) and that other factors, in addition to particle size, will play a role in the duration of the release of aripiprazole, as noted in (1) (PJ [223]).

(3) Each of the PTE Claims claim many different embodiments within each claim - allowing for variation in mean particle size, variations of dosage and variations in respect of the vehicle. But each must meet the stated release period. The person skilled in the art must accordingly make choices concerning matters not referred to in the PTE Claims (such as dosage concentration, frequency, volume and site of administration) by reference to the result to be achieved (PJ [224]).

(4) Contrary to Otsuka's submission, the patent does not teach that release period is an inherent feature of the particle size alone (PJ [225]). The passages on p 2, lines 11 to 14 and p 3, line 22 to p 4, line 10 do not provide a teaching that the release period is an inherent property of the formulations such that there is a direct correlation between that metric and particle size - other factors must come into play (PJ [228]-[235]).

[46]

The essential question is whether the PTE Claims should be construed such that the Relevant Feature is not a limitation required to be demonstrated in respect of each claim or whether, as Otsuka contends, a product possessing the other features of the claim will necessarily have the Relevant Feature (being the release of aripiprazole over the specified period of at least one week (for the Controlled Release Injectable Formulation Claims) or at least two weeks (for the Freeze-dried Controlled Release Formulation Claims)).
For the following reasons we do not consider that Otsuka has identified error in the reasoning of the primary judge.
First, the language of each of the claims includes as a positive integer the requirement of a formulation that upon injection "releases aripiprazole over a period of at least one week" for the Controlled Release Injectable Formulation Claims and "at least about two weeks" for the Freeze-dried Controlled Release Formulation Claims. Those words on their face require that the integer be satisfied.
Secondly, the formulation that follows in each case "comprises" the elements then described. The word "comprises" is defined in the body of the specification to mean "includes", and does not mean the exclusion of any other integer or step (p 22a, lines 1-5). Accordingly, the definitive list of components to be included within the formulation is not identified. Nor do the claims identify beyond broad generalisation the contents of the formulation. For instance, claim 1 is for (a) aripiprazole with the particle size specified, in (b) "a vehicle therefor" plus (c) water. Other integers added by dependent claims generically identify suspending agents, bulking agents, buffering agents and the like, each of which is broadly described in the specification.
Thirdly, the primary judge found that the person skilled in the art would be aware that there are a number of variable factors that will affect the release time of aripiprazole from the depot (at PJ [206]), including the dosage amount, the volume and the injection site. That finding is not challenged on appeal, though Otsuka claims that these variable factors only affect the extent (if any) to which the release time is above the claimed minimum period (as opposed to whether the claimed minimum period is met or not). It is apparent that the primary judge did not accept that proposition and we see no basis upon which it should be overturned.
Fourthly, in forming an understanding of the PTE Claims, the primary judge considered the claims as a whole, which form part of the specification (Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8; 207 CLR 1 at [15]-[16]), and identified aspects of those claims that the person skilled in the art would understand to reflect a teaching that there is a necessary scope for variance in dosage and other factors that will affect the release period (PJ [206]). In this regard, her Honour noted that the Freeze-dried Controlled Release Formulation Claims require a release period of at least about two weeks (PJ [219]). For those claims the formulation includes aripiprazole having a mean particle size of about 1 to 10 microns and a vehicle therefore (claim 16) or, in the case of claim 19, a mean particle size of 2 to 4 microns. Like claim 16, claim 1 also comprises aripiprazole with a mean particle size of about 1 to 10 microns. Yet, the combination claimed in claim 1 is for a formulation which releases aripiprazole over "at least one week". In PJ [221] the primary judge provides other examples where the same mean particle size range is specified in claims which have different release periods.
Her Honour concludes, as a matter of the logic of the claim set as a whole, that the same particle size alone will not provide the same release period (PJ [222]). The person skilled in the art is directed to select the particle size within the stated range, excipients and water but must make other choices concerning matters such as dosage concentration, dosage frequency, volume and site of administration by reference to the result to be achieved (PJ [224]). This accorded with the expert evidence accepted by the primary judge to the effect that in order to determine whether a given formulation fell within the Relevant Feature in the PTE Claims, experimentation would be required - see, for example, PJ [206], [290]-[293]. This addresses Otsuka's argument on appeal that the variable factors only affect the extent (if any) to which a formulation's release period is above the claimed minimum period.
Whilst it is apparent that an important part of the invention is the selection of particle size, we do not consider that the primary judge erred in concluding that particle size and other variables must be considered by the person skilled in the art in order to achieve the release rates identified in the PTE Claims.
Ground 4 of the NoA must be dismissed.

[49]

In section 6.2, the primary judge considered that, having found the Relevant Feature to impose a limitation by result, the person skilled in the art must be able to adjust the Formulations to ensure that they satisfy that feature (PJ [237]).
Her Honour considered the significance of the term "release" as used in the claims in section 6.2.1 of her reasons, noting that the experts agreed that "release" of aripiprazole is the dissolution of aripiprazole molecules from the depot at the injection site (PJ [240]). "Release" is not the same as "absorption" which her Honour found, accepting the evidence of Professor Evans, to take place after the drug has been dissolved within bodily fluid (that is, released) when it can be absorbed by passing through membranes to enter the bloodstream (PJ [241]). Her Honour noted that "release" is also not the same as "blood plasma concentration" which provides information about the concentration of the drug substance in the blood at a particular point in time (PJ [242]-[243]).
The primary judge accepted the evidence that while release has an effect upon blood plasma levels, blood plasma levels are not the same as the release of the aripiprazole from the particle depot at the injection site and there can be a delay between the cessation of the release and the disappearance of the drug from the blood plasma (PJ [244]), and depending on a number of factors, an active ingredient can be circulating in the blood for significant periods after the last of the drug has been released from a formulation (PJ [245]).
After considering these matters the primary judge concluded that the reference to "release" in the PTE Claims is not "release as measured by blood plasma concentration of aripiprazole", and the Patent does not use blood plasma concentration to refer to "release" as that term is used in those claims (PJ [246], [247]).
The primary judge in section 6.2.2 accepted that the only manner by which release might be determined which is disclosed in the Patent is the blood plasma concentration data and descriptions contained in Examples 1 to 4 and Figures 1 to 3 (PJ [248]). Her Honour noted Otsuka's submission that the teaching of the Patent cannot be departed from and that the person skilled in the art would be able to determine whether the Relevant Feature is present in a formulation otherwise possessing the features of the PTE Claims by taking blood plasma concentration measurements of aripiprazole at various times following injection, that the Patent teaches that such concentrations can be and are used to determine release and that the Patent indicates that analysis of such concentrations acts as a surrogate for determining the release period (PJ [250]).
After setting out Example 4 and Figure 3 from the Patent, the primary judge levelled some criticism at Figure 3 including that it shows significant variability across limited data points and that various data points were hard to discern. She noted that the x axis was not divided into increments which would allow the release boundaries in the claims to be discerned (PJ [255]). Her Honour said that importantly, Figure 3 does not purport to depict or even refer to "release" and that expert witness Professor Winter observed that "release is nowhere measured" in the Patent (PJ [256]). In this regard, the primary judge quoted from a passage of the evidence of Professor Winter given in the JER as follows at [257]:

[53]

Her Honour relied on the evidence of Professor Winter in this regard, who explained that the Patent did not inform the reader how release is determined, although Professor Winter accepted that the patentee wished to support its conclusions on release with Example 4 and Figure 3 (PJ [261]).
The primary judge concluded:
1. Further, even if it could be said that the evidence established that some formulations, such as that in Example 1, would achieve minimum periods of release, that is not the end of the matter. That is because the issue is whether the person skilled in the art is able to determine whether other formulations which lie closer to the boundaries of the PTE Claims, such as with a mean particle size that may or may not achieve a specified minimum release period depending on the formulation, will fall within the PTE Claims. For example, a formulation with a mean particle size of about 1 micron for release over a period of at least two weeks, such as that contemplated by claim 16, would require the day on which the formulation stops releasing (rather than being measurable in blood plasma) to be measured with precision in order to determine whether it released for less or more than two weeks.
2. In summary, the Patent does not show the person skilled in the art how to determine whether or not each formulation that otherwise satisfies any of the PTE Claims falls inside or outside the release boundary specified in the Relevant Feature. The Patent is silent as to how the person skilled in the art is to extrapolate from the disclosed blood plasma concentration data to a determination of the release of aripiprazole from the depot. As the person skilled in the art is not given that information, the person skilled in the art is not able to use that information to enable them to determine whether all formulations which otherwise fall within any of the PTE Claims take the Relevant Features.
3. For this reason, the PTE Claims are bad for ambiguity because the instructions in the Patent for attaining the Relevant Feature are meaningless to those skilled in the art: BlueScope at [719]. Contrary to Otsuka's submissions, these matters would cause difficulty to a manufacturer wishing to satisfy himself that he is not infringing the PTE Claims.

[63]

In relation to Ground 2 of the NoA, Otsuka submits that the primary judge erred in failing to find as a matter of construction that blood plasma concentration showed or was a surrogate for the release period and that the method disclosed in the specification for the identification of whether the claimed minimum release period is met is the measurement of blood plasma concentration of aripiprazole over time. It submits that each of the Figures in the Patent is a plasma concentration versus time profile of aripiprazole and that these teach that aripiprazole blood plasma concentration is to be used to identify whether aripiprazole is continuing to release at a point in time. No other method is disclosed or suggested. When the specification is considered as a whole in light of the common general knowledge, it is, Otsuka submits, clear from Example 4 that the release period can be identified by measuring blood plasma concentration over daily intervals. The primary judge erred at PJ [246]-[247] because Otsuka did not contend that "release" in the PTE Claims should be understood to mean "as measured by blood plasma concentration of aripiprazole" but rather that the claims, read in the context of the specification as a whole in the light of the common general knowledge, would be understood by the person skilled in the art to explain how to identify the release period. In this regard Otsuka relies on a number of passages of the evidence of Professor Winter, the expert preferred by the primary judge.
Otsuka submits that having found at PJ [257] that there was in effect no practical means of measuring release from a depot before a drug's entry into the blood, the effect of the primary judge's construction was to require identification of a release period by a means which was not possible, which is contrary to principle. It submits that the importance of Example 4 is that it teaches that blood plasma concentration is used to identify whether aripiprazole is continuing to release at a point in time and that the accepted evidence of Professor Winter that blood plasma concentration cannot provide an actual duration of release or be used to measure release should be understood in the context where the PTE Claims do not require an actual duration or measurement of release but only for release to occur for longer than the minimum specified period, which is denoted in terms of weeks, not days or hours.
Sun Pharma defends the reasoning of the primary judge. It submits that Otsuka seeks to vary the plain meaning of the Relevant Feature by reference to the specification, contrary to authority. It submits that Otsuka does not confront the finding that the specification does not disclose how blood plasma concentration measurements can be used to determine whether a formulation has the Relevant Feature and that there is no teaching in the Patent. The expert evidence did not support a conclusion that the person skilled in the art could simply measure the blood plasma concentration to identify whether a formulation had the Relevant Feature. Even if the evidence established that some formulations would have the Relevant Feature, the person skilled in the art would not know how to understand whether other formulations, closer to the boundary, fall in or outside the claim.
In relation to Ground 3 of the NoA, Otsuka submits that the primary judge erred in finding that blood plasma concentration did not provide a workable standard by which to identify whether the claimed minimum release period was met, citing the UK Court of Appeal in General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd [1972] RPC 457; (1971) 1A IPR 121 at 167-168 and the Full Court in Austal Ships Sales Pty Ltd v Stena Rederi Aktiebolag [2008] FCAFC 121; 77 IPR 229 at [13]-[16] which emphasise, respectively, that the issue of definition is to be considered as a practical matter with little weight given to puzzles set out at the edge of a claim and that expressions in claims must be understood in a "practical, commonsense manner". Otsuka relies on the finding at [257] that release from an intramuscular depot in vivo in humans is not practicably measurable with precision to support its contention that "surrogate parameters" are required using a workable standard, bearing in mind the relative imprecision required by the claims in the form of a minimum specified period.
Otsuka submits that there is an inherent contradiction in the findings of the primary judge. It submits that on the one hand, at PJ [188] the primary judge accepted evidence from Professor Winter that ABILIFY MAINTENA released aripiprazole over a period of at least one or two weeks based on Professor Winter's evidence in the JER and the confidential Otsuka documents, and yet on the other hand her Honour found that the claims lacked clarity. It submits that the primary judge erred in relying on the confidential Otsuka documents to support what the person skilled in the art would take into consideration, as those documents were not referred to in the Patent and did not form part of the common general knowledge. Furthermore, even if they were consulted, there was no evidence that any variability in inter-patient blood plasma concentration shown in the documents affected the identification of whether the minimum release period in the PTE Claims was met. Otsuka submits that the person skilled in the art could determine the release of aripiprazole in a formulation from a depot upon administration simply by testing the amount of the drug in blood plasma at different time points, and that the primary judge wrongly set aside evidence recited at PJ [251] and [287] on the basis that it relates to the use of blood plasma concentration to determine the dosage interval of a formulation, when it was common general knowledge that dosage interval for a drug is based on its release period.
Sun Pharma submits that the reasoning of the primary judge contained no error. Having rejected that blood plasma concentration provided a sufficient means for establishing release as required by the claims, the primary judge correctly reviewed the evidence and found that other common general knowledge means could not be used to determine release, and consequently surrogate parameters would need to be used requiring onerous and time-consuming testing. It submits that the problems found by the primary judge do not lie as puzzles at the edge of the claim, but that for the claims to define the invention and be clear and succinct the limitation must enable the person skilled in the art to determine whether all aripiprazole formulations that otherwise fall within the PTE Claims fall in or outside the boundary of the limitation. Sun Pharma submits that there is no contradiction between the finding, based on Professor Winter's evidence, that the ARTG Goods (that is, ABILIFY MAINTENA) fell within the claims and the lack of clarity finding because the confidential Otsuka documents showed that aripiprazole was present in blood plasma for several weeks longer than the required minimum threshold of 7 days, and Professor Winter's view was expressed with considerable reservation, noting that blood plasma concentration was not used as a direct means of estimating release, that there were "intermediate steps" taken in that document and that he was unable, based on that study, to determine whether the Relevant Feature was present in formulations that are very close to either side of the boundary of the claim 1 Relevant Feature. Sun Pharma submits that, contrary to the contention advanced by Otsuka, the person skilled in the art could not determine the release of aripiprazole by testing blood plasma concentration at different time points, as the primary judge found at PJ [288] that the use of blood plasma concentration to determine dosage was not the relevant question and, at best, only formed part of any process to determine release period.

[71]

In the present case, the challenge to the validity of the PTE Claims was confined to lack of definition within s 40(2)(b) and lack of clarity within s 40(3).
Despite this, there is no dispute as to the meaning of the words in the PTE Claims. The Relevant Feature is encompassed in the language "which upon injection releases aripiprazole over a period of at least" or "at least about" one week or, in the case of claim 16 and its dependent claims, two weeks. The primary judge found, and it is not challenged on appeal, that "releases aripiprazole" refers to the dissolution of aripiprazole molecules from the depot at the injection site (PJ [240]). There is nothing lacking in clarity in those words.
The dispute between the parties concerns whether or not those words serve to define the invention, or are clear and succinct, when the integer is understood to be a limitation claimed by reference to the result achieved.
In General Tire the UK Court of Appeal considered whether or not a claim failed to define sufficiently the scope of the claims in the patent ((1972) RPC 457 at 507), the legislative requirement there being whether the scope of the claim was "sufficiently and clearly defined". This was by reference to what the Court described as an integer of claim 1 requiring that the polymerisation product of the claim shall have a computed "Mooney plasticity" of at least 90. What was denoted by "computed Mooney plasticity" was explained in the body of the specification and was a measure of viscosity using a Mooney viscometer.
The Court made several observations that have resonated in Australian patent law since.
The first is that the mere fact that knowledge, skill and even some experimental tests may be necessary in putting a patented invention into practice is not sufficient to invalidate the patent if the nature of the invention is adequately described: General Tire at 514, quoting from British Thomson-Houston Co Ltd v Corona Lamp Works Ltd (1922) 39 RPC 49; Sanofi v Amgen Inc (No 3) [2025] FCA 387 at [208] (Nicholas J).
The second is that the duty of the patentee is to state clearly and distinctly, either in direct words or by clear and distinct reference, the nature and limits of what it claims. If using language that is avoidably obscure or ambiguous, the patent is invalid: General Tire at 514, quoting from Natural Colour Kinematograph Co Ltd v Bioschemes Ltd (1915) 32 RPC 256 at 266.
The third is that allowance must be made for any difficulties of the particular patent in issue. The Court adopted the language of Lord Simonds in Raleigh Cycle Co Ltd v H Miller & Co (1948) 65 RPC 141 at 149, that "a greater degree of clarity than the subject reasonably admits of is not to be demanded of the patentee": General Tire at 515_._ One relevant difficulty in the present case is, as the primary judge found, there was no means known to the person skilled in the art of measuring release at the injection site.
The fourth is that it is not the duty of the inventor to define the scope of its claim so as to ensure that it can never be difficult to decide the question of infringement, but only to enable the court to formulate the question which a skilled addressee, wishing to avoid infringement, should ask itself. However, that is not on the basis of any hypothetical infringer. The test is more practical. In this regard, the Court relevantly said at 515-6:

[78]

The passage in Austal Ships at [14], which was cited by the primary judge in her conclusion at PJ [296], sets out a lengthy quotation from Blanco White in which some general propositions in relation to ambiguity are stated. However, the extract in Austal Ships does not quote from the passage at [4-704] extracted above.
In the present case we have upheld the primary judge's finding that the Relevant Feature amounts to an integer that defines the invention by reference to the result achieved, being the release period of aripiprazole. The present challenge is that the claim is not clear or succinct or does not define the invention by reference to that result.
In Sigma Pharmaceuticals (Australia) Pty Ltd v Wyeth [2011] FCAFC 132; 119 IPR 194 (Bennett, Nicholas and Yates JJ), one contention was that the phrase "therapeutic blood plasma concentration" where used in certain claims was not clear and succinct within s 40(3) (see [116] per Bennett J and [257] per Yates J). Justice Yates (Nicholas J agreeing generally at [133]) said:
1. Based on the argument developed on appeal, there seems to be no error suggested in the primary judge's acceptance that the phrase should be given its ordinary English meaning as referring to a single daily dosing of a formulation of venlafaxine hydrochloride that achieves a blood plasma concentration of venlafaxine that is therapeutically effective. The import of the appellants' submissions is that, so understood, the phrase is unclear: it does not provide a workable standard because there is no way of predicting in advance what the therapeutic concentration for a particular formulation will be, thereby enabling the person skilled in the art to avoid the possibility of infringement. In advancing these submissions the appellants did not suggest that the determination of the therapeutic efficacy of a given formulation of venlafaxine hydrochloride itself presents a challenge to the person skilled in the art.
2. In my view the appellants' contention raises, in a conventional way, a criticism that can be made of many claims limited by result. As a general rule, however, such claims do not fail for lack of clarity simply because further steps must be taken by the person skilled in the art, in the nature of trial and error or routine testing not involving invention, in order to understand when the result will be achieved: No-Fume Ltd v Frank Pitchford & Co Ltd (1935) 52 RPC 231 at 238, 245-246 and 247-249. The necessity for, or extent of, the work required in that regard may point to the possibility of insufficient description, but no challenge to validity of that kind has been raised in this respect.

[83]

In our view, the appropriate course is to have regard to the passages from the chapter concerning ambiguity, to which we have referred and extracted above at [83].
It is apparent from the authorities to which we have referred that the drawing of the line between the two classes of things must be considered at a practical level, not by reference to impractical hypotheses at the margins. Nor, as Sigma makes plain, is clarity to be resolved by a question of whether one can predict in advance whether something falls within the claims, as to which see Sanofi v Amgen Inc (No 3) per Nicholas J at [203].
The test propounded by Sun Pharma was set out by the primary judge as being that the person skilled in the art would not be able to determine whether or not all aripiprazole formulations (i.e. all embodiments) that otherwise meet the requirements of the PTE Claims fall within or outside the Relevant Feature based on the information in the Patent and the common general knowledge, even allowing for routine experimentation (PJ [191]). It is apparent that this places the bar too high. This was a test posed to the experts in question 3 of the JER, and, as the primary judge's reasons make clear, adopted by Professor Winter (PJ [239], [249]) and ultimately embraced by the learned primary judge (PJ [265]). In our respectful view, this reflects error. The question is not to be based on a hypothetical consideration of whether or not infringement of any embodiment within the scope of the claim may be difficult to ascertain.
Accordingly, it is appropriate on appeal for the Court to consider the position.
In Ground 2, Otsuka contends that the error of the primary judge lay in failing to find as a matter of construction of the Patent that blood plasma concentration showed or was a surrogate for the "release of aripiprazole" as set out in the PTE Claims. There is force in this contention.
The Patent, in the Brief Description of the Invention, makes plain that the invention concerns the release of aripiprazole, in therapeutic amounts, over a period of "at least about one week, and preferably over a period of two, three or four weeks and up to six weeks or more" (p 2, lines 12-14). It discloses that mean particle size of the freeze-dried aripiprazole formulation from about 1 to 30 microns is "essential" in formulating an injectable which achieves this release rate (p 3, lines 22-25), and that the smaller the mean particle size, the shorter the period of extended release (p 3, lines 26-27). In Example 1, an aripiprazole microsuspension preparation is described with particles determined to have a mean particle size of 2.5 microns (p 19, line 4).
In Example 3, a single dose depot study using an aripiprazole formulation prepared in Example 1 injected intramuscularly into fifteen rats is reported at doses of 12.5, 25 and 50 mg/kg. The Patent states that blood samples for evaluation of systemic exposure were collected on days 1 (after 6 hours), 2, 4, 7, 10, 15, 22, 28, 36 and 43 and analysed for aripiprazole (p 21, lines 22-29).
The results are reported in Figure 1, which is described as showing "mean plasma concentrations vs. time profiles of aripiprazole in rats" (p 21, lines 29-30; p 35):

[90]

The claims follow immediately after the examples, commencing on page 23 of the patent.
It will be apparent from the foregoing that the Patent contains no definition of "release". It is a term, as the primary judge found, that was well understood by those skilled in the art (PJ [71], [240]). Nor does the specification contain any description of how to measure the release of aripiprazole over time. The primary judge accepted evidence from Professor Winter that measuring the release of aripiprazole from the intramuscular depot with enough precision to determine whether a formulation would fall in or outside the claim boundaries was not possible with the technology in existence at the priority date or the date on which the experts gave their evidence (PJ [257], [265]).
However, the Patent makes plain by its reporting of the results of the examples that it measured the onset of release and sustained release of aripiprazole by reference to blood plasma levels. All of the reported examples do so, in stating that the corresponding figures show "mean plasma concentrations vs. time profiles of aripiprazole". There can be little doubt that the patentee was there using such blood plasma levels (measured as blood plasma concentration of aripiprazole) as a means for approximating release rates, even accepting (as the primary judge found) that release is not the same as blood plasma concentration (PJ [242]-[245]). There was no dispute between the experts that this is what the patentee intended. As the primary judge found at PJ [248], the only manner by which release might be determined that is disclosed in the Patent is the blood plasma concentration data and descriptions contained in Examples 1-4 and Figures 1-3.
It was Otsuka's case before the primary judge that the measurement of blood plasma concentration was a proxy for the release of aripiprazole at the injection site. This the primary judge rejected at PJ [258] by rejecting the premise of the statement in Example 4:
1. In Example 4, it is stated by reference to Figure 3 that, "[i]n all cases aripiprazole plasma levels showed a fast onset of release and sustained release for at least 30 days". However, as release (within the meaning of the PTE Claims) is not shown in Figure 3, only blood plasma concentration is shown, there will be at least some dela_y_ between release and entry of the drug substance into the plasma and as the drug substance can remain in the blood plasma after the release has ceased, the basis for asserting that Figure 3 "shows" release (whether fast or sustained) is neither apparent nor explained, and there must have been some intermediate analysis performed which underlies this statement.

[91]

Much of the primary judge's reasoning was based on the contention, drawn from the evidence of Professor Winter, that there would be a "delay" between release and entry in the blood stream and that accordingly blood plasma concentration could not be an accurate measure of release.
However, the degree of precision required is governed by the nature of technology involved as disclosed in the Patent. Here, the metric required by the claims is that the release be "at least" one week or "at least about" two weeks. This metric is used to distinguish the long-acting slower release drug formulation from the immediate release formulation in order to increase the rate of compliance (p 2, lines 3-5). Specificity as to the precise time at which the release occurs is not required by the Patent or the claims. A "workable standard" for the person skilled in the art would permit for a degree of approximation.
Furthermore, the patentee does not need to supply proof that the invention works. An inventor patents a process and not its scientific explanation: Generic Health at [133]. The reasoning of the primary judge reflected a view that it was necessary for the patentee to prove that the release of aripiprazole was accurately measured by the taking of a plasma concentration vs time curve. This is not a requirement under s 40(2)(b) or s 40(3). To the extent that it might have been asserted that the invention claimed did not achieve the promise of the invention (in supplying a sustained release dosage form of aripiprazole), that is a ground of invalidity appropriately considered under the ground of want of utility within s 18(1)(c) of the Patents Act. The grounds of invalidity are conceptually distinct and must be considered separately: Lockwood Security Products Pty Ltd v Doric Products Pty Ltd [2004] HCA 58; 217 CLR 274 at [46]. We do not, by this observation, mean to suggest that the claims may lack utility.
However, it was not Otsuka's case that the blood plasma concentration curve "showed" release. Rather, it was that blood plasma concentration was the means by which the Patent described the assessment of fast onset versus sustained release could be established, and thus the person skilled in the art could determine whether the Relevant Feature was present. In our respectful view, that it is a correct construction of the disclosure of the Patent.
Otsuka next challenged the finding of the primary judge that the Patent does not provide a "workable standard" for measuring release by reference to blood plasma concentration levels (that is, plasma concentrations versus time profiles of aripiprazole present in the bloodstream).
In this regard, the primary judge reasoned in the italicised passage at PJ [258], extracted above, that an "intermediate analysis" was performed to ascertain release as described in Example 4. However, in our respectful view, this misstates the disclosure of the patent. No intermediate analysis was mentioned. Her Honour's view was reliant on the evidence of Professor Winter, who gave evidence that there is "additional thinking" undisclosed in the patent as to how there can be a correlation between release of aripiprazole and blood plasma concentration levels measured (PJ [259]-[262]). However, as we have noted, the evidence of Professor Winter was based on the incorrect premise that scientific proof was required as the standard of the disclosure of the Patent.
Her Honour went on to say:
1. Further, even if it could be said that the evidence established that some formulations, such as that in Example 1, would achieve minimum periods of release, that is not the end of the matter. That is because the issue is whether the person skilled in the art is able to determine whether other formulations which lie closer to the boundaries of the PTE Claims, such as with a mean particle size that may or may not achieve a specified minimum release period depending on the formulation, will fall within the PTE Claims. For example, a formulation with a mean particle size of about 1 micron for release over a period of at least two weeks, such as that contemplated by claim 16, would require the day on which the formulation stops releasing (rather than being measurable in blood plasma) to be measured with precision in order to determine whether it released for less or more than two weeks.

[93]

In our respectful view, this misstates the test. The question applicable to the PTE Claims is not whether it may be hard to determine whether unstated, hypothetical formulations at the margins of the claims fall within their scope. As General Tire and later authorities make clear, the test is more pragmatic and requires consideration of a particular formulation, not a series of hypothetical formulations that are not in dispute.
In this regard, Sun Pharma did not advance a case that a particular formulation could not be considered by reference to a concentration vs time analysis as conducted in Example 3. Its case was based upon the theoretical construct that all conceivable embodiments falling within the scope of the claims should be ascertainable. However, the onus lying on Sun Pharma was to demonstrate, in more practical terms, that the infringement of more realistic, practical formulations within the claims could not be determined. As was stated in General Tire, a claim is not necessarily lacking in definition simply because cases may arise in which it is difficult to decide whether there has been infringement.
In the JER, Professor Winter accepted that for the intramuscular depot formulation of Example 1 (as applied in Example 4) "a release of more than one week is likely for the formulation studied but cannot be proven due to the lack of precision" (emphasis added). Leaving aside the irrelevant question of proof, it is apparent from this answer that Professor Winter accepted that the metric used in Figure 3 (being a plasma concentration vs time profile) could be applied to ascertain that release was of more than one week. Similarly, he also accepted that the standard of release over a period of "at least about two weeks" was likely for the formulation studied in claim 16. This was also the view of Professor Evans. Accordingly, to the extent that there was available evidence of a practical, real-world example of the application of the test set out in the Patent, it indicated that the person skilled in the art would be able to ascertain whether that example fell within the scope of the claims.
In our respectful view Otsuka has demonstrated error in the reasoning of the primary judge. Applying the correct approach to claim clarity within s 40(3) and claim definition in s 40(2)(b), we have found that Sun Pharma did not demonstrate that the claims fail to satisfy the requirements of s 40(2)(b) and s 40(3) of the Patents Act. Accordingly, Grounds 1, 2 and 3 of the NoA must be allowed.

[156]

Those provisions, and in particular (b), provide explicit acknowledgment that a "therapeutic substance", for the purposes of the Customs Regulations, included a formulation. Regulations 5A to 5G concerned the importation into Australia of therapeutic substances, and the purpose of reg 2(2) was to make clear that permissions, designations and the like in relation to a particular formulation did not constitute a permission etc. in relation to all other formulations of the product in question. Other aspects of regs 5A to 5G reinforced the conclusion that a "therapeutic substance" included formulations. For example, reg 5A(2)(c) excluded from the operation of a particular provision a "therapeutic substance imported by a passenger in a ship or aircraft" that was "for the personal use of the passenger or a member of his family". It would appear that the central concern of that exclusion was to permit people to travel with their medication; which, in the ordinary course, would be a formulation. In any event, the detail of the regime in regs 5A to 5G is presently unimportant, save to observe that it demonstrates beyond argument that a "therapeutic substance" in the Customs Regulations included a formulation.
A different approach was taken in the Customs Regulations to dealing with the importation of "drugs". That was the concern of reg 5, which defined "drug" in sub-reg (20). The core of that definition was, in (a), "a chemical, compound, or other substance or thing, that is included in the Fourth Schedule". The Fourth Schedule then listed various chemical compounds and their isomers and derivatives (including salts). The definition in sub-reg (20) then went on to further define a "drug" to include various other substances by reference to that core concept, including, for example in (d), "a substance or thing ... that contains, or consists in part of" the drug listed in the Fourth Schedule.
Fundamentally, the difference in the approach to defining a "therapeutic substance" and a "drug" may be described as follows. The defining feature of a "therapeutic substance" was the use to which it may be put. The defining feature of a "drug" was the presence of a particular thing. It follows that it may be accepted that, without more, the adoption of the concept of "therapeutic substance" from the Customs Regulations would be consistent with an intention to include formulations.
That was the point being made by Perram J, in Cipla at [55], where his Honour observed that reg 2(2)(b) of the Customs Regulations "assumes that a pharmaceutical substance may be manufactured according to a formulation". Of course, the Customs Regulations do not contain any reference to "pharmaceutical substances", the relevant term being "therapeutic substance". But what his Honour was plainly saying was nothing more than that the concept upon which the term "pharmaceutical substance" as it is found in the Patents Act was explicitly based (namely, a "therapeutic substance" within the meaning of the Customs Regulations) did include formulations.

[157]

It will be recalled that the EM 1989 stated that the new patent extension regime would "be available for 'therapeutic substances' in the terms of the [Customs Regulations], with added limitations". Having determined that "therapeutic substances" within the meaning of the Customs Regulations included formulations, the obvious next question is whether the "added limitations" operated to exclude them.
We think that the limitation of relevance for present purposes is the second identified by the 1989 EM, which was expressed in the legislation with the words "whose application (or one of whose applications) involves a chemical interaction, or physico-chemical interaction, with a human physiological system" or "action on an infectious agent, or on a toxin or other poison, in a human body".
So what do those words mean?
The requirement that the application of a "pharmaceutical substance" must involve an "interaction" or "action" of the specified kinds immediately and naturally puts the focus on the substance which itself produces the therapeutic effect, as distinct from any excipients present in a given formulation with such a substance. Excipients, by definition, are not therapeutically active. They are the non-therapeutic ingredients of dosage forms. It is only the active ingredient that can have a chemical or physico-chemical interaction with a human physiological system, or that can act on an infectious agent, or on a toxin, or other poison, in a human body.
That is to say, the natural and ordinary meaning of the words of sub-paragraphs (a) and (b) of the definition of "pharmaceutical substance" operates to limit substances falling within the definition to those which are "active" (i.e., capable of "interacting with" a human physiological system in specified ways, or "acting on" certain harmful presences). In that way, the limitation may be seen to confine the otherwise broad concept borrowed from the Customs Regulations to those substances that are "active".
The intended focus of the definition on "active" ingredients is confirmed by the extrinsic material to which we have referred. The reference in the Supplementary EM 1989, for example, to the "mode of action" of certain kinds of pharmaceutical substances supports the conclusion that the key characteristic of the new concept was that it was "active". Similarly, the reference in the EM 1989 to the fact that extensions would be sought for more "drugs" than was previously the case seems to us naturally to refer to the relevant active chemical compound, rather than the variety of ways in which it might be formulated.
Other features of the new regime point in the same direction. It will be recalled that the definition of "marketing approval certificate" referred to an approval of "the marketing of the substance, or a product containing the substance". At [47] of Cipla, Perram J in his review of the extrinsic materials, commented that he did not consider the distinction in this definition between "the substance" and a "product containing the substance" as throwing any light on the meaning of pharmaceutical substance "since the range of products which may contain pharmaceutical substances is capable of extending to items such as bottles and dispensers". However, in our respectful view, in the context of substances being approved for use in humans, the "product" referred to in the definition of a "product containing the substance" is more likely to be a formulation containing the substance, such as a tablet or solution for injection, rather than a bottle or dispenser containing a formulation, as there would be no requirement for a bottle containing the formulation (e.g. a bottle of tablets) to be separately approved for use in humans.
Otsuka submitted that if the legislature had intended the term "pharmaceutical substance" to be limited to only APIs, then that term could have been used.
To the extent this submission was directed at the concept of a "pharmaceutical substance" as a whole, it is clear that substances that may not be, or may be argued not to be, APIs as that term is commonly used are intended to be included within the scope of the defined term. There exists a broad array of "active" substances from molecules such as aripiprazole, to monoclonal antibodies and antigens or recombinant proteins produced by recombinant DNA technology (the latter subsequently being recognised in s 70(2)(b) of the Patents Act). As the second sub-paragraph in the definition of "pharmaceutical substance" highlights, in addition to a chemical interaction, or a physico-chemical interaction, with a human physiological system, the concept includes substances whose application involves action on:

[164]

All of these references support our construction of the term "pharmaceutical substance" as being limited to active substances or API(s), and not including formulations. (In Cipla, Perram J, at [84], considered that the use of the word "may" in the passage from [8] of the REM 1998 undermined the strength of any conclusion that could be drawn from that passage. We think, however, that it is plain enough that the possibility contemplated by the word "may" related only to the potential for either combinations or single active ingredients. We do not think that that passage can be read as to encompass the possibility of pharmaceutical substances comprised of anything other than active ingredients. His Honour also regarded the passage quoted from [23] as "textually weak"; with respect we do not agree.)
Some care is required, however, to ensure that statements or assumptions about the meaning of an existing provision, plainly not intended to be amended or to have its meaning changed, are not used illegitimately in the construction of the provision itself: see, e.g., Hunter Resources Ltd v Melville [1988] HCA 5; 164 CLR 234 at 241 (Mason CJ and Gaudron JJ) and Australian Education Union v Department of Education and Children's Services [2012] HCA 3; 248 CLR 1 at [33] (French CJ, Hayne, Kiefel and Bell JJ). See also R v Aubrey (2012) NSWCCA 254; 82 NSWLR 748 at [37] (Macfarlan JA).
Certainly, the simple fact that the drafter of the REM 1998 assumed that the definition of "pharmaceutical substance" meant what we have found it to mean would not provide any support for our construction. And we do not think that the words of the 1998 Amendment Act, considered on their own and in isolation, could be said to provide any additional support for our construction (that is to say, over and above the features to which we have already referred). The real question is whether it is possible to look "afresh" at the definition, in light of the evident legislative purpose of the new extension regime as revealed by the extrinsic material to which we have referred.
In Deputy Federal Commissioner of Taxes v Elder's Trustee & Executor Co Ltd [1936] HCA 64; 57 CLR 610, Dixon, Evatt and McTiernan JJ held that a particular piece of legislation, construed on its own terms, would have a particular meaning. A later piece of legislation was passed, however, on the assumption that the earlier legislation bore a different meaning. Their Honours said (at 625-6):

[165]

Doubtless the true explanation is that, in drafting the Act of 1930, it was supposed that the exclusion by the Act of 1914 of Crown leases from the exemption took effect for the financial year beginning 1st July 1914. But, in our opinion, the supposition ought not to lead us to give that effect to the Act of 1914. "An Act of Parliament does not alter the law by merely betraying an erroneous opinion of it" (Maxwell, Interpretation of Statutes, 6th ed. (1920), p. 544, and, per Lord Atkinson, Ormond Investment Co v Betts (1928) AC 143 at 164). "Where the interpretation of a statute is obscure or ambiguous, or readily capable of more than one interpretation, light may be thrown on the true view to be taken of it by the aim and provisions of a subsequent statute" (per Lord Atkinson (1928) AC 143 at 164). In Cape Brandy Syndicate v Inland Revenue Commissioners (1921) 2 KB 403 at 414, Lord Sterndale said: "I quite agree that subsequent legislation, if it proceed upon an erroneous construction of previous legislation, cannot alter that previous legislation; but if there be any ambiguity in the earlier legislation, then the subsequent legislation may fix the proper interpretation which is to be put upon the earlier." In reference to this statement, Lord Buckmaster said in Ormond Investment Co v Betts at 156: "That is, in my opinion, an accurate expression of the law, if by 'any ambiguity' is meant a phrase fairly and equally open to divers meanings". But it is not permissible to construe an unambiguous phrase in an earlier Act by an erroneous assumption of its effect contained in a later Act which did not purport to alter or amend the earlier Act (per Lawrence LJ, Port of London Authority v Canvey Island Commissioners (1932) 1 Ch 466 at 493).

In the present case the Act of 1930 did not intend to amend the Act of 1914. It was not concerned with it and was dealing with a matter unconnected with the question for what financial year the amendments made by the Act of 1914 first took effect. On that question it did no more than proceed upon an assumption. It was a question depending, not on an ambiguous word or phrase, but on the absence from the Act of 1914 of any express statement of the financial year first to be affected. The ordinary rules of interpretation supplied the deficiency ....

[170]

Of course, where later legislation amends the very Act in question, then s 11B of the Acts Interpretation Act, which is consistent with the common law in any event (see Commissioner of Stamps v Telegraph Investment Co Pty Ltd [1995] HCA 44; 184 CLR 453 at 463 (Brennan CJ, Dawson and Toohey JJ)), requires that the two acts be read together as a combined statement of the will of Parliament. As a result, the "effect of the amending Act may be to alter the meaning which remaining provisions of the amended Act bore before the amendment" (at [14]).
Here, the relevant statutory provision the construction of which is at issue is a definition. The 1998 Amendment Act introduced a new set of substantive provisions constituting the new extension regime, but which operated by reference to a defined term that had first been included in relation to the previous extension regime. That defined term was not picked up by any pre-existing substantive provision that remained in the Patents Act after it was amended. That seems to us to raise a quite different question from that presented by a subsequent Act which proceeds upon a particular view concerning the meaning of a substantive provision that continues to have operation.
In the circumstances with which we are concerned, the traditional approach to statutory construction, as we have already described, involves reading the words of a definition into the substantive provisions to which it relates. That approach recognises that defined terms do not have a meaning and operation independently of the substantive provisions that incorporate them. It follows, we think, that if a new substantive regime, that makes use of a pre-existing defined term, is enacted on an assumption as to the meaning of that defined term, that fact is capable of altering the meaning of the defined term. Whether or not it will do so, of course, will depend on the particular circumstances. But at least as a matter of principle, we think that it is possible to regard the amending Act as doing more than merely "betraying an erroneous opinion" of the meaning of the existing definition; it may be, in effect, reenacting the definition afresh for the purposes of a new substantive regime intended to have a particular operation. At the very least, provided the defined term is "obscure or ambiguous, or readily capable of more than one interpretation", it is difficult to see why "light may [not] be thrown on the true view to be taken of it by the aim and provisions of a subsequent statute" (Elder's Trustee at 625-6).
We, of course, consider that the original meaning of the defined term "pharmaceutical substance" is consistent with the assumption as to its meaning in the EM 1998. It follows that we agree that the 1998 Amendment Act did not intend to effect any change to the meaning of that term. But, if we were wrong about that, would the 1998 amendments have altered the term's meaning?
In addition to the passages we have set out above which make explicit the assumption that "pharmaceutical substances" are limited to active ingredients, the passage in the REM 1998 quoted by the High Court in Alphapharm HC at [58], that we have set out above under the heading "The preexisting state of the law", observed that "[t]he development of a new drug is a long process, estimated to average around 12 years, which requires a new chemical entity to be patented early in the process". The "chemical entity" to which reference is made is plainly the active ingredient in a product that is ultimately brought to market. It is clear that it was patents of that kind to which the extension regime introduced by the 1998 Amendment Act was intended to apply.
We would also observe that our construction of "pharmaceutical substance" as the active substance(s) is consistent with the broader purpose of the current extension regime, with the policy objectives evinced in the extrinsic materials.
ARTG registration of a medicine containing a new chemical or biological entity follows years of research and development and a comprehensive review by the Therapeutic Goods Administration (TGA) of the medicine's quality, safety and efficacy. The number and extent of biopharmaceutic studies required to obtain regulatory approval for a new formulation of an already approved active ingredient is less than those required for regulatory approval of a medicine containing a new chemical or biological entity.
A construction of "pharmaceutical substance" which has the effect of restricting extensions of terms to patents for newly discovered drugs, such as new chemical or biological entities or APIs, that have taken an extended effort and time to achieve regulatory approval is consistent with the object articulated in the extrinsic materials to which we have referred above. We repeat the majority's articulation of the purpose of the extension scheme in Alphapharm HC at [60], which was cited by the Full Court in Merck Sharp & Dohme Corp. v Sandoz Pty Ltd [2022] FCAFC 40; 291 FCR 26 at [70]:

[180]

This express clarification of the distinction between an API and a formulation, and the express recognition that an API is the relevant "pharmaceutical substance", is entirely consistent with what we regard as the correct construction of "pharmaceutical substance".
As to the definition of "pharmaceutical patent" in s 119A(3) of the Patents Act, the EM 2006 at 43 [159] stated that the definition was "intended to cover all patents that a generic pharmaceutical company would need to exploit in order to seek inclusion of a good... on the ARTG". It was intended that patents claiming the following "methods, products and uses relating to a pharmaceutical substance" would be covered by the definition of "pharmaceutical patent". The list included "(a) a pharmaceutical substance per se; or... (d) a method of administering a pharmaceutical substance; or... (f) a product or formulation incorporating a pharmaceutical substance or a mixture of pharmaceutical substances, including products such as layered or coated tablets..." (emphasis added). It may thus be seen that, once again, the EM 2006 was drafted on the assumption that a "pharmaceutical substance" was limited to active ingredients.
Again, the mere fact that the drafter of the EM 2006 construed the existing definition of "pharmaceutical substance" in a particular way is not relevant to the task of construction. On our approach, of course, it is not necessary to rely on the EM 2006 to support our construction. It follows that the question whether the meaning of "pharmaceutical substance" was altered by the 2006 amendments does not arise. The arguments on that subject may be acknowledged to be more finely balanced than those in relation to the effect of the 1998 amendments that we have addressed above. The contours of that debate were outlined by Perram J in Cipla at [95]-[105]. In circumstances where, on our reasoning, the issue is hypothetical, and indeed proceeds from a premise that we deny, we do not propose to enter into it.
Ultimately, therefore, in our view, the 2006 amendments are not relevant to the proper construction of the term "pharmaceutical substance".

[193]

The High Court explained the somewhat complex but relevant background to the Lundbeck Cases at [23]-[34] of Alphapharm HC.
Lundbeck marketed the antidepressant Cipramil. The active ingredient in Cipramil was the racemate of citalopram. A racemate, or racemic mixture, comprises two enantiomers in equal measure. Enantiomers are non-superimposable mirror images of each other and are designated (+) or (-) based on how they rotate polarised light.
The racemate was described and claimed in the Citalopram Patent owned by Lundbeck which expired on 5 January 1993. Cipramil was included in the ARTG on 9 December 1997.
Lundbeck subsequently obtained a patent for the purified or isolated (+)-enantiomer of citalopram (the Escitalopram Patent), which it marketed under the name Lexapro. Lexapro was registered on the ARTG in September 2003. The isolated enantiomer (+)-citalopram was therapeutically more active in treating depression than the racemate.
Claim 1 of the Escitalopram Patent claimed (+)-enantiomer of citalopram and non-toxic acid addition salts thereof. Claim 2 claimed a particular salt. Claims 3 to 4 claimed pharmaceutical compositions comprising the active ingredient claimed in claim 1 and, respectively, together with a pharmaceutically acceptable carrier or excipient. Claim 6 claimed a method for the preparation of the compound claimed in claim 1. The specification of the Escitalopram Patent set out the relevant claims as follows:
1. (+)-1-(3-dimethylaminopropyl)-1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile and non-toxic acid addition salts thereof.
2. The pamoic acid salt of (+)-1-(3-dimethylaminopropyl)-1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile.
3. A pharmaceutical composition in unit dosage form comprising as an active ingredient, a compound as defined in claim 1, together with a pharmaceutically accepta[ble] carrier or excipient.
4. A pharmaceutical composition in unit dosage form comprising, as an active ingredient, the compound of claim 2, together with a pharmaceutically acceptable carrier or excipient.
5. A pharmaceutical composition in unit dosage form, according to claim 3 or 4, wherein the active ingredient is present in an amount from 0.1 to 100 milligram per unit dose, together with a pharmaceutically acceptable carrier or excipient.

[212]

The emphasis added to the word "in" in the above passage misstates the definition of "pharmaceutical substance", which requires a chemical interaction or physico-chemical interaction, with a human physiological system. As can be seen by the passage, the two are not equivalent. The disintegration of a modified release dosage form in the GI tract into its constituents is not an interaction with a human physiological system. It is not a "therapeutic use" either as it is a disintegration of a dose form to release the active ingredient or API into a form which can then be absorbed into the body. That is to be contrasted with the therapeutic effect of pain alleviation which is brought about by the interaction of the known drug oxycodone with the nerve cells or receptors in the spinal cord and brain, following the dissolution of said dose form or excipient. That is, the only chemical or physico-chemical interaction relevant to the definition of "pharmaceutical substance" under Sch 1 of the Patents Act is the interaction of oxycodone with the relevant receptors.
The mischaracterisation of the disintegration of the OxyContin matrix in the GI tract as a relevant chemical or physico-chemical interaction with a human physiological system infects the subsequent reasoning in Spirit (see [61], [64]-[66], [74] and [75]). The only substance involved in a chemical or physico-chemical interaction with a human physiological system is oxycodone, the substance long used for alleviating pain.
At [64] Rares J noted that the definition of "pharmaceutical substance" requires the mixture to be, relevantly, for therapeutic use and "whose application involves" a chemical interaction with a human physiological system. Rares J further observed that the word "involves" relates to the application of the substance or mixture. OxyContin's first relevant chemical interaction, via its disintegration in the GI tract, is an essential aspect of his Honour's reasoning in finding OxyContin to be a pharmaceutical substance. With respect, we find that essential aspect of his Honour's reasoning incorrect.

[215]

According to the specification of the 862 Patent, a GLP-1 agonist is a peptide that binds to the GLP-1 receptor and exhibits insulinotropic activity, stimulating the secretion of insulin. Liraglutide is a GLP-1 agonist.
At the heart of Cipla was the question whether the two formulations of liraglutide disclosed in the claims of the 862 Patent are claims for a "pharmaceutical substance". Put simply, are formulations within the definition of "pharmaceutical substance"? At [38] Perram J found that a "pharmaceutical substance" included a formulation (a mixture of active ingredients and excipients).
At [58], Perram J noted that he saw nothing in the terms of the 1989 Amendment Act or the EM 1989 that provided support for the idea that a "pharmaceutical substance" could not include a formulation. As we discussed above, however, a pharmaceutical substance is a sub-class of a "therapeutic substance" as defined in the Customs Regulations. The express requirement in the definition that the pharmaceutical substance have a chemical or physico-chemical interaction with a human physiological system, or involves action on an infectious agent, or on a toxin or other poison, in a human body, involves elements absent from the definition of "therapeutic substance", and explains why a pharmaceutical substance does not include a formulation. It is really at that point that our reasoning diverges from his Honour's.
We do note, however, that at [186] of Cipla, Perram J accepted that if the High Court's reference to "tablet" in footnote 40 of Alphapharm was not read as an illustration of a method, it was inconsistent with the construction that his Honour had reached. Perram J concluded that if the tablet reference was not merely an illustration of a method claim then, as it was not obiter dictum, he would not follow it.
We consider that the High Court used "tablet" in footnote 40 as an example of what is not a pharmaceutical substance per se, i.e. claims to the active ingredient plus other integers concerning excipients in a dose form such as a tablet or modified release tablet, rather than the pharmaceutical substance or active therapeutic ingredient itself. As we have observed above at [221], Claims 3 and 4 of the patent in suit in Alphapharm FC and Alphapharm HC claimed pharmaceutical compositions in unit dosage form comprising the active ingredients from claims 1 and 2, respectively, together with a pharmaceutically acceptable carrier or excipient. An example of the unit dosage form claimed would be a tablet.

[218]

Sun Pharma contends that regardless of the construction of "pharmaceutical substance" adopted, the Freeze-Dried Controlled Release Formulations do not satisfy s 70(2)(a) of the Patents Act as their application does not involve a chemical interaction, or physico-chemical interaction, with a human physiological system. Sun Pharma propounds a different construction of "application" to that adopted by the primary judge as meaning "use" or "purpose" at PJ [133] (and in Cipla at [124]): the use to which the substance is put. Sun Pharma interprets "application" to mean a "physical application" of the pharmaceutical substance.
Sun Pharma further contends that the Freeze-Dried Controlled Release Formulations are not disclosed in the specification of the Patent nor do they in substance fall within the scope of the claim or claims of the specification.
Otsuka adopts the meaning of "application" given by Perram J in Cipla at [124]: "a use to which the substance is put".
In Cipla Perram J rejected the construction of "application" propounded by Cipla as "the application of the pharmaceutical substance to the target in the human physiological system (in th[at] case the GLP-1 receptor)", on the basis that a formulation was not "applied" in that sense at the relevant target; only its active pharmaceutical ingredient is. At [114] Perram J accepted that the excipients in the formulations did not bind to the GLP-1 receptor, thus the formulation could not be applied on Cipla's meaning.
At [116], Perram J set out two meanings of "application" from the Macquarie Dictionary: "1. the act of putting to a special use or purpose: the application of common sense to a problem... 5. the act of applying: the application of salve to a wound" (emphasis in original). At [117] Perram J explained the first meaning was to be preferred, saying that his Honour did not think it would be correct usage of "application" to discuss of an antibiotic being applied to an infectious agent, or a blood thinner being "applied in that sense". At [123] Perram J observed that his understanding of "application" as meaning "use" was consistent with the fact that a substance may have other uses that do not involve interaction with a human physiological system, such as use in animals.
For the reasons outlined above, we consider that the term pharmaceutical substance is limited to active substances and that formulations do not fall within the definition of pharmaceutical substance. Our construction does not depend upon which meaning of "application" is adopted. A meaning of "application" which does not require the implication or injection of a "target" into the definition is to be preferred. However, whilst we prefer the meaning adopted by Perram J, given "application" arises in the context of the definition of "pharmaceutical substance", we consider that the use to which the substance is put should be the therapeutic use or purpose to which the substance is put, or to be put. This is consistent with the statutory wording in the definition of "pharmaceutical substance" as meaning "for therapeutic use whose application (or one of whose applications" involves...". Evidently, the word "application" is informed by the words "therapeutic use".
As the primary judge observed at PJ [133], the "application" in the present case is the treatment of schizophrenia and related disorders. Aripiprazole is the pharmaceutical substance which is used to treat schizophrenia. Aripiprazole is formulated into the Formulations in order to be put to its therapeutic purpose. It is the aripiprazole molecules contained within the Formulations that undergo a physico-chemical interaction with a human physiological system when they bind with receptors in the brain.
As Professor Winter explained in his evidence:

[220]

Whilst the therapeutic purpose to which the Freeze-dried Controlled Release Formulations are to be put is the treatment of schizophrenia, this example shows why it is the active ingredient or API which is the pharmaceutical substance, rather than the formulation. The Freeze-dried Controlled Release Formulations provides the means by which the stability of the aripiprazole is maintained whilst stored prior to use. In order to be administered to a patient, the Freeze-dried Controlled Release Formulations must first be reconstituted into an injectable solution for delivery into the body. Upon injection, it is the aripiprazole molecules that undergo the physico-chemical interaction with a human physiological system, i.e. the relevant receptors in the brain, to produce the therapeutic effect of treating schizophrenia.
At PJ [134] the primary judge referred to Bennett J's comments in Alphapharm FC at [242] (with whom Middleton J agreed) that the pharmaceutical substance per se claimed in a patent "may not have the necessary therapeutic use or enable the required physico-chemical interaction unless formulated". The primary judge took from this that the reconstitution of a freeze-dried substance for administration was no different to the formulation of an active ingredient into a dosage form.
As discussed above, Bennett J's comments in Alphapharm FC at [242] go to a different issue, the meaning of "pharmaceutical substance". Her Honour recognised that an active ingredient is seldom administered on its own without excipients, or in the case of a peptide, other than in an injectable form. Bennett J's comments should not be taken as accepting that the dosage formulation containing the active ingredient and excipients is itself a "pharmaceutical substance". That understanding is inconsistent with Bennett J's earlier comments at [238] that "[t]he definition of pharmaceutical substance focuses on the ingredient for therapeutic use that involves the relevant type of interaction". It is clear from Bennett J's comments at [238] and [242] that she considered "pharmaceutical substance" to be limited to active ingredients. This is confirmed by her conclusion at [244] that "the pharmaceutical substance per se is the molecule, the (+)-enantiomer":

[230]

Otsuka relies on the decisions in Pharmacia and Spirit to support its submission that the new and inventive substance, being the Formulations, is a product and a pharmaceutical substance per se. That the claims have process or in-use features does not have the consequence that the claims are not to a new and inventive substance (the Formulations) rather than a process or method (PJ [176]). As outlined above, neither Spirit nor Pharmacia are of assistance.
Sun Pharma likens Otsuka's argument to that of the appellant in Boehringer, in that it effectively reads out of s 70(2)(a) the words "per se". On Otuska's argument it is enough that the specification discloses one or more pharmaceutical substances (the Formulations), whether as the sole element of the invention or in combination with other elements.
For the reasons outlined above, we consider that the term pharmaceutical substance is limited to active pharmaceutical substances and that formulations do not fall within the definition of pharmaceutical substance. Thus, the Formulations are not within the definition of pharmaceutical substances, and accordingly they are not pharmaceutical substances per se.
In any event, the claims to the Formulations, although expressed as product claims rather than method or process claims, do include process integers in addition to the pharmaceutical substance (aripiprazole) itself. Like the appellants in Boehringer, Otsuka's approach reads out of s 70(2)(a) of the Patents Act the words 'per se': see Boehringer at [38].
As Allsop J noted at [40] in Prejay, the definition of "pharmaceutical substance" refers to a substance, which must have a purpose or use- therapeutic use, and whose application involves the other matters identified in the definition. The definition is of a particular kind of substance, but it is a substance, and only a substance. Likewise, the Full Court observed in AbbVie at [56] that s 70(2) is concerned with pharmaceutical substances, "not additional or other matter concerning or involving the use of pharmaceutical substances".
On the test articulated by Allsop J at [41] in Prejay: if the use of the substance (in this case aripiprazole) outside the particular administration regime in the claims is outside the scope of the claim, then it cannot be said that the substance per se falls within the scope of the claim. The use of aripiprazole to treat schizophrenia by immediate release tablet was known before the priority date and falls outside the claims of the patent in suit. The claims to the Formulations are not claims to a pharmaceutical substance per se. They are claims to a new modified release dosage form of aripiprazole, limited by method of delivery, dissolution and release time.
At PJ [99] the primary judge listed five propositions that she gleaned from the authorities. The fifth of these was that a new and inventive method of using an existing pharmaceutical substance (such as in a new method of treatment) does not qualify for an extension. The primary judge postulated that this could extend to a new and inventive method of delivering a pharmaceutical substance. The Formulations fall into this fifth category, the formulations are new (and as there was no inventive step challenge) inventive methods of administering (or delivering) the known pharmaceutical substance, aripiprazole. Aripiprazole was first included in the ARTG in the form of Otsuka's ABILIFY tablets on 21 May 2003 (PJ [5]), before the priority date of the Patent. Consistent with the primary judge's reasoning at PJ [99(5)], the Formulations should not qualify for an extension based on the Patent. The Formulations are not a pharmaceutical substance per se.

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