Alphapharm Pty Ltd v H Lundbeck A/S

Federal Court of Australia (Full Court)|2015-09-22|Before: Yates JJ

BACKGROUND TECHNOLOGY 18 It is helpful to set out some relevant aspects of the background chemistry which are not in dispute: (+)-citalopram is the (+)-enantiomer of citalopram; (+)-citalopram is also known as (S)-citalopram or escitalopram; Citalopram is a racemic mixture that contains equal amounts of the (+) and (-) enantiomers of citalopram; Citalopram and escitalopram are different chemical entities with different physical properties and different pharmacological activities. 19 The background chemistry has been described in some detail in the Decision and does not need to be repeated. However, Alphapharm adduced evidence before the Delegate from Dr Oppenheim. We refer to some of that evidence of particular relevance, concerning a "substance" and enantiomers: Substance 36. Generally speaking, a compound - whether it is the API or an excipient - will be made up of particles of that compound which are themselves made up of individual molecules of the API or the excipient. From a chemical point of view, a compound can also be described as a substance. However, in some instances the word "Compound" when it is used in pharmaceutics can also denote a mixture of two substances, that is "a compound of substances" (in the sense that two substances may be taken and "compounded" together). 37. A molecule is the smallest unit, or the simplest form, of a substance. A molecule consists of two or more atoms that are arranged in a particular way and held together by chemical bonds. For example, a molecule of water consists of one atom of oxygen and two atoms of hydrogen. … 50. The structure of molecules is fundamental to chemistry. The atoms contained in a molecule and the way in which they are connected will determine the properties of that molecule. Stereochemistry is the study of how the atoms of a molecule are arranged spatially. In other words, it is the study of the three-dimensional structure of molecules. … Racemic mixtures 65. A racemic mixture, or racemate, is a mixture that contains equal amounts of enantiomers. Assuming that the enantiomers have only one chiral centre, a racemic mixture will not rotate plane polarised light (as the rotation of one enantiomer in this mixture is offset by the rotation of the corresponding enantiomer). 66. It is possible to have an "enantiomeric excess" of one enantiomer, in which some degree of optical rotation of that mixture will exist (i.e., when there is an excess of one particular enantiomer). In this situation you do not have a racemic mixture, nor do you have an "enantiopure" system (a substance that contains only one of the enantiomers). 67. While enantiomers appear very similar, they are not identical compounds. They exist in a three-dimensional form and are extremely important in biological pathways and processes. Different enantiomers can have different effects and interactions. This is most clearly seen in some medicines in which one enantiomer may have a therapeutic effect and the other may not. 68. An enantiomer, or more precisely, an enantiopure system, can be obtained by resolution or asymmetric synthesis. These processes are described below. Resolution and asymmetric synthesis 69. Resolution is a process in which a racemic mixture or an enantiomeric excess system is separated (i.e., resolved or isolated) into its component enantiomers. A resolution can be carried out in various ways. Most commonly, it is done by crystallisation or by chiral column chromatography. 20 Dr Oppenheim recognised that the claim of the Patent is a claim to a compound and that the claim is to an optically active compound, (+)-citalopram. Dr Oppenheim said that 'I did not recognise what this compound is but I did note that it is optically active from the "(+)" symbol, which denotes that it is a dextrorotatory compound'.

LEAVE TO APPEAL 21 Leave to appeal to the Full Court is required by s 158(2) of the Act which provides: Except with the leave of the Federal Court, an appeal does not lie to the Full Court of the Federal Court against a judgment or order of a single judge of the Federal Court in the exercise of its jurisdiction to hear and determine appeals from decisions or directions of the Commissioner. 22 In Genetics Institute Inc v Kirin-Amgen (1999) 92 FCR 106 at [13], the Full Court stated that: The Federal Court's jurisdiction to grant leave is a discretionary jurisdiction the exercise of which will only be constrained by express legislative provision. In the case of the jurisdiction conferred by s 158(2) no such provision exists, and we do not accept the contention of the applicant that the reference in that provision to "leave" was intended to entrench a particular test to be applied by the Court when determining applications made under it. 23 It follows that there is a general discretion to grant leave to appeal which 'must not be constrained by elevating particular approaches in particular cases to the status of rules of general application' (Pfizer Corporation v Commissioner of Patents (2006) 155 FCR 578 at [12]). 24 Where, as here, there have been two hearings of Alphaharm's opposition, namely before the Delegate and the primary Judge, the Full Court should exercise its discretion to grant leave to appeal with "care" (Pfizer at [8]), in particular where the matters primarily in issue are essentially questions of fact (Kirin-Amgen at [16]). Leave to appeal against a decision dismissing an opposition should only be granted 'where the applicant has demonstrated a clear prima facie case of error in the decision appealed from, such that the likely effect of the decision would be to allow an invalid patent to proceed to grant' (Kirin-Amgen at [23]; Pfizer at [8]).

The primary Judge's decision 25 At [39] the primary Judge said: As Bennett J reasoned [in the Decision], the (+)-enantiomer was a pharmaceutical substance that the racemate in Cipramil contained. [The claim] of the patent identified, as its subject-matter, the isolated form of that molecule. The isolated (+)-enantiomer was the pharmaceutical substance per se for the purposes of s 70(2)(a). That substance, being the molecule, is contained in both Cipramil and Lexapro. 26 Alphapharm points to the first two sentences of this passage concerning the construction of the claim adopted by the majority of the Lundbeck Full Court. It argues that the Lundbeck Full Court found that the isolated (+)-enantiomer is the pharmaceutical substance but did not make a finding that the isolated (+)-enantiomer was a pharmaceutical substance per se. That is, Alphapharm says, a claim to an isolated (+)-enantiomer is not to a pharmaceutical substance per se but a claim to the substance further limited by a requirement as to purity of manufacture. Alphapharm says that at [244] of the Decision, Bennett J concluded that it is the molecule, the (+)-enantiomer, that is the pharmaceutical substance per se. Therefore, Alphapharm submits, the primary Judge erred in finding that the claim of the Patent was a claim to the isolated (+)-enantiomer which satisfied the conditions in s 70(2)(a) of the Act. On Alphapharm's present construction, the claim is outside the operation of s 70(2)(a) of the Act and Lundbeck is not entitled to an extension of the term. 27 Alphapharm submits that the analysis by the primary Judge of the relevant issue, characterised by his Honour as 'the per se issue', is attended by sufficient doubt to warrant its reconsideration by the Full Court. Alphapharm says that the primary Judge mischaracterised its case as being directed to the construction of s 70(3)(a) of the Act and the satisfaction of the requirement in that provision that "goods containing, or consisting of" the relevant pharmaceutical substance be included in the ARTG. Alphapharm says that its argument was not that Cipramil does not contain the pharmaceutical substance (+)-citalopram for the purposes of s 70(3)(a) of the Act. Rather, its contention was that the claim is not a claim to a pharmaceutical substance per se for the purposes of s 70(2)(a) of the Act. 28 Lundbeck submits that Alphapharm has not demonstrated any prima facie case of error on the part of the primary Judge and that his Honour correctly found that the claim describes a pharmaceutical substance per se for the purposes of s 70(2)(a) of the Act. Lundbeck contends that Alphapharm's construction of the claim to include a further integer or limitation of isolation or purity such that the claim is no longer to a pharmaceutical substance per se, is wrong and inconsistent with the Decision. In particular, Lundbeck points to the reasons of Bennett J at [131] and of Middleton J at [252] where their Honours considered the subject matter of the claim as 'a specific reference to the (+)-enantiomer, distinct from the (-)-enantiomer and not as present in the racemic mixture' (at [131]) and to the 'separated, isolated or pure (+)-enantiomer' at ([151]).

Substantial injustice 29 Alphapharm contends that there would be substantial injustice if leave to appeal were to be refused, supposing the decision of the primary Judge to be wrong. Alphapharm would then be prevented from challenging the correctness of the primary Judge's decision with the result that the term of the Patent would be extended and proceedings for infringement of the Patent during the extended term would be enabled. 30 Alphapharm also submits that the case raises an important matter of public interest, namely, the construction of s 70(2)(a) of the Act. In deciding whether an extension of term is granted, there should be a balancing of the competing interests of the patentee who has suffered regulatory delay on the one hand and the public interest on the other (Alphapharm Pty Ltd v H Lundbeck A/S (2014) 108 IPR 459 at [60]).

Conclusion on leave to appeal 31 Alphapharm contends that the primary Judge conflated s 70(2)(a) and s 70(3) of the Act and that his Honour incorrectly dealt with 'the per se issue' as a s 70(3)(a) issue, when it arises under s 70(2)(a). That mischaracterises his Honour's reasoning. The primary Judge dealt with both issues, first with s 70(3) and then with s 70(2)(a) and concentrated on the interaction between the two. However, in doing so, his Honour focussed on s 70(3) and did not make explicit his reasons as to the alleged "additional integers" in the claim. His Honour considered Bennett J's reasons in the Decision which, as his Honour read them, accepted that the (+)-enantiomer was the pharmaceutical substance per se for the purposes of s 70(2)(a). 32 Alphapharm contends that the primary Judge did not squarely address the issue of whether, as it says, the claim for the compound is further defined by a purity integer or limitation or is a claim to a pharmaceutical substance per se. 33 The primary Judge's approach was, perhaps, explained by the submissions before him from Alphapharm. Alphapharm stated that it did not press any independent grounds of appeal relating to s 70(3)(a) of the Act but did say that the question of compliance with s 70(3)(a) remained relevant. It is, however, clear from Alphapharm's outline of submissions before the primary Judge that the primary assertion was that s 70(2)(a) of the Act was not satisfied. 34 In any event, his Honour did not directly consider whether the claim is to a substance further limited by a requirement as to purity of manufacture (the isolated (+)-enantiomer) and not a claim to a pharmaceutical substance per se as required by s 70(2)(a) of the Act. It follows that the decision of the Delegate has not been directly considered. 35 This application also represents Alphapharm's only course in challenging the extension of term of the Patent, which has significant consequences to Alphapharm. If Lundbeck is successful, the term of the Patent will be extended and Lundbeck's infringement proceedings against Alphapharm can proceed. 36 Unlike Kirin-Amgen, this application does not concern a pre-grant opposition where proceedings for revocation remain available. This application proceeds in the context of essentially undisputed facts and involves a question of construction of a claim and of s 70(2)(a) of the Act, being matters of law and of importance in the application of s 70(2)(a). 37 Alphapharm's application for leave to appeal should be granted.

THE DECISION OF THE DELEGATE 38 The Delegate considered whether the claim was directed to the pharmaceutical substance per se. He concluded at [39] that the pharmaceutical substance is escitalopram ((+)-citalopram) on its own without the mirror image (-)-enantiomer. The Delegate then cited the Decision at [231], where Bennett J said that there was no dispute in the Lundbeck Full Court that 'the pharmaceutical substance for the purpose of s 70(2)(a) is (+)-citalopram'. The Delegate recognised that the dispute was whether or not the claim was directed to a pharmaceutical substance per se and concluded that it was. This was because, as he said at [45], 'by definition a pure compound is a substance "alone"' and accordingly a pharmaceutical substance per se. 39 The Delegate's reasoning was straightforward: Bennett and Middleton JJ concluded that the reference to (+)-citalopram in the claim without more indicates that it is the separated or isolated or pure enantiomer that is claimed. "Per se" means taken alone 'essentially without reference to anything else' (Pharmacia Italia SpA v Mayne Pharma Pty Ltd (2006) 69 IPR 1 at [94]). By definition a compound is a "substance" alone. As a pure compound it must be a pharmaceutical substance per se. Pure escitalopram is read as free of the negative enantiomer. If the pharmaceutical substance is viewed as pure citalopram, the claim is directed to the pharmaceutical substance and nothing more than the pharmaceutical substance. 40 This was considered with and supported by the evidence of Professor Oppenheim at [163], where he stated that the molecule must be 100% pure if it is separated and isolated. 41 The Delegate accepted that escitalopram in its pure form was not used in the preparation of Cipramil but also that Cipramil has within it molecules of escitalopram. He noted that in the Lundbeck Full Court, Bennett J concluded that, given that the racemic mixture includes both the (-)-enantiomer and the (+)-enantiomer, Cipramil must "contain" the (+)-enantiomer. The Delegate agreed that this approach was correct.

THE DECISION OF THE PRIMARY JUDGE 42 On appeal, the primary Judge dealt with three issues which he characterised as 'the per se issue' the 'prior extension issue' and 'the erroneous grant issue'. It is 'the per se issue' that is the subject of this appeal. His Honour described the issue in these terms (at [6(1)]): … the pharmaceutical substance per se disclosed in [the claim] of the patent was the pure, isolated or separated form of the molecule, being the (+)-enantiomer, for the purposes of s 70(2) of the Act, and that that pure form of the molecule was not included in the goods registered as "CIPRAMIL Citalopram hydrobromide 20mg tablet blister pack" on the ARTG with a start date of 9 December 1997 for the purposes of s 70(3). The Cipramil tablets were produced as an exploitation of the properties of the racemate (the per se issue). 43 The relevant issue before the Lundbeck Full Court was, as stated by Bennett J (at [117]): Does (+)-citalopram in [the claim] of the Patent denote and claim the purified or isolated (+)-enantiomer, or the (+)-enantiomer whether alone or as part of a mixture, or the (+)-enantiomer as present in a racemate? 44 Alphapharm Pty Ltd and Arrow Pharmaceuticals Pty Ltd had submitted to the Lundbeck Full Court that the claim was to 'a unique molecule possessing a unique three dimensional configuration', that the phrase "(+)-citalopram" refers to the physical thing, this molecule, and that the independently existing (+)-enantiomer would be infringed by mixtures containing that enantiomer and by the racemate. 45 Alphapharm put the case to the primary Judge, recorded at [36]: The opponents argued that if the pharmaceutical substance per se were the pure, isolated or separated (+)-enantiomer, then the racemate in Cipramil could not have been found to contain it. That is, they contended that Bennett J found in [244] that the molecule, as opposed to the isolated molecule, was the pharmaceutical substance per se, because the molecule was part of the racemic mixture in Cipramil and was not isolated. 46 The primary Judge rejected that contention. Citing Bennett J's reasons at [241], his Honour said at [38]-[39]: 38 The racemate "contains" both enantiomers just as a cake, in Lindgren J's analogy, "contains" milk and eggs, although they no longer have a separate existence in the mixture or cake. Thus, in [241] and [244], Bennett J found that the pharmaceutical substance per se, for the purposes of s 70(2)(a), was the isolated (+)-enantiomer and that molecule was contained in the racemate even though the (+)-enantiomer was not isolated in the mixture. 39 As Bennett J reasoned, the (+)-enantiomer was a pharmaceutical substance that the racemate in Cipramil contained. [The claim] of the patent identified, as its subject-matter, the isolated form of that molecule. The isolated (+)-enantiomer was the pharmaceutical substance per se for the purposes of s 70(2)(a). That substance, being the molecule, is contained in both Cipramil and Lexapro.

ALPHAPHARM'S SUBMISSIONS 47 Alphapharm accepts that the (+)-enantiomer is a pharmaceutical substance. The essence of its argument is that in the Decision, the subject matter of the claim was construed as the separated, isolated or pure enantiomer, which introduces a further criterion or limitation such that the claim is no longer a claim to the enantiomer per se. This is because the requirement that it be the substance per se means that there must be no further criterion (News Limited v South Sydney District Rugby League Football Club Limited (2003) 215 CLR 563 at [56]). Of course, it says, Cipramil cannot "contain" the separated molecule, the molecule free of the racemate, so it follows that what is contained in Cipramil is not the subject matter of the claim. Putting Alphapharm's submissions another way, for the pharmaceutical substance per se the subject of the claim to comply with the requirements of s 70(2)(a) of the Act, it would be the isolated enantiomer and there are no goods included in the ARTG containing the pharmaceutical substance as required by s 70(3)(a) because the racemate contains the (+)-enantiomer and the (-)-enantiomer together. 48 Accordingly, Alphapharm submits, Lundbeck is not entitled to an extension of term of the Patent. 49 Alphapharm does not challenge the construction of the claim as adopted by the majority in the Decision. It says that the construction of the claim means that s 70(2)(a) is not satisfied. It points to the conclusion in the Decision that the racemate did not anticipate the separated enantiomer because it did not describe or disclose the separated or isolated or pure enantiomer and says that this means that it could not contain that enantiomer. 50 The issue, as distilled in this appeal, is whether the Decision demonstrates that the claim was held to include the criterion that the (+)-enantiomer was isolated or pure, either as an additional integer or by way of limitation. If so, Alphapharm contends, the claim is not to the molecule or to the compound. If it were, it says, the Lundbeck Full Court would have found, as did Emmett J who characterised the claim as a claim to the molecule, that it was anticipated by the Cipramil Patent which claimed the racemate.

THE LINDGREN J DECISION 51 As the Decision concerned an appeal from the Lindgren J Decision, those reasons provide the context for the reasoning of the Lundbeck Full Court. A consideration of the Lindgren J Decision and of the Decision demonstrates that Alphapharm has not correctly characterised the claim. 52 Justice Lindgren dealt with the question of a claimed extension of the term of the Patent for escitalopram oxalate (the oxalate of the (+)-enantiomer of citalopram). His Honour was considering, inter alia, Alphapharm's contention that the relevant first inclusion in the ARTG was the inclusion of Cipramil, that is citalopram the racemate. As his Honour noted at [8], the proceedings raised issues concerning the relationship between citalopram and escitalopram, that is between the racemate and the enantiomers. 53 The hearing before Lindgren J was an appeal from Dr Barker as the Delegate. Dr Barker had decided (as set out in [51] of the Lindgren J Decision) that notwithstanding that escitalopram was a new chemical entity having properties different from those of the racemate, the question was whether Cipramil, the racemate, did in fact "contain" escitalopram or, put another way, whether escitalopram was present (to some extent) in Cipramil. Accordingly, the term of the escitalopram patent was properly extended by reference to the date of registration of the racemate and the medication that contained the racemate, not the date of registration of the medication containing the (+)-enantiomer. 54 In order to understand Lindgren J's reasoning, it is necessary to set out again some of the background technology, as explained by his Honour. Justice Lindgren explained (at [69]) that it was common ground that in 1988 (the relevant date) had an ordinary skilled but not inventive chemist been given a two dimensional structural formula with a single chiral centre, he or she would have recognised the presence of two enantiomers. His Honour also noted that, generally speaking, chiral molecules exist in nature only as one enantiomer. However, when chiral molecules are synthesised in a laboratory, there is a 50% probability that either enantiomer will be produced, so that the two enantiomers are produced in equal parts. That mixture is a racemate. To obtain unequal mixtures of enantiomers or a single enantiomer some specific step must be taken in the synthesis. 55 It was not possible for a chemist to look at the structure and determine which would be the (+) and which the (-)-enantiomer. It is only as a result of testing with plane polarised light that one can know which enantiomer is which (at [75]). 56 Justice Lindgren set out his conclusion at [116] to [117], relevantly: … The symbol (+)- in [the claim] (and in claim 2) indicates the particular enantiomer that is distinguished by the feature of rotating plane-polarised light to the right (under standard conditions… ). The property of rotating plane-polarised light to the right (clockwise) or to the left (anticlockwise) which distinguishes one enantiomer from the other and each from the racemate, is able to be detected only when that enantiomer is present other than as a part of the racemate. … The skilled addressee in 1988 would have understood [the claim] to refer specifically to (+)-citalopram. In the absence of a context permitting otherwise, the skilled addressee would not have understood the claim to the invention of (+)-citalopram to refer to that compound merely as part of the unresolved racemate. Rather, the skilled addressee would have understood the claim to the invention of (+)-citalopram to refer to that compound as something that had an existence independent of that of the racemate. 57 His Honour also explained that the (+) distinguishes that enantiomer from the (-)-enantiomer and from it being merely part of the racemate or of some other mixture. It implies distinctness from the racemate (at [119]). 58 His Honour was careful to point out at [119] that it is not that the (+)-citalopram compound does not exist when it is part of the racemate, and that this would be understood by the skilled addressee, but rather that the (+) or (-) symbol, devoid of any context suggesting otherwise, implies distinctness from the racemate. There was no suggestion that there was any countervailing context. Accordingly, his Honour concluded, 'the unqualified reference to the (+)-enantiomer of citalopram in [the claim] refers to something different from that enantiomer as an indistinguishable part of the unresolved racemate' (at [123]). Justice Lindgren also referred to Ortho-McNeil Pharmaceutical Inc v Mylan Laboratories Inc 348 FSupp2d 713 (ND WVa 2003) where Keeley DCJ said that the term "S(-)" clearly and plainly limits the claim language to the levorotatory enantiomer. Those skilled in the art clearly understand the term "S(-)" to denote affirmatively only the levorotatory enantiomer of a racemic compound, and not the racemic compound itself. 59 At [142] the present issue was, apparently, raised: Senior counsel for Alphapharm makes the point that the use of "individual", "pure", "separated" and "isolated" or derivatives of those terms is a two-edged sword: Why were they omitted from [the claim] if not to suggest that what was claimed was not to be limited by such qualifiers? Notwithstanding the force of this submission, I think that if [the claim] is ambiguous (as indicated earlier, I do not think it is), the specification as a whole teaches that [the claim] refers to the independently existing (+)-enantiomer, and not to merely the (+)-enantiomer when a part of unresolved (±)-citalopram. 60 Justice Lindgren clarified his position again at [145]: I would have understood an unqualified reference to (+)-citalopram, whether in the open literature or in a patent, to refer to that compound when other than merely part of the unresolved racemate. 61 Justice Lindgren's conclusion on construction was set out at [153]: In summary, the reference in [the claim] to [(+)-citalopram] is a specific reference to the enantiomer of citalopram that rotates plane-polarised light to the right, and, there being no context suggesting a different possibility, is not apt to refer to the (+)-enantiomer merely as present in the racemate. 62 In dealing with the question of anticipation by the Cipramil Patent, his Honour said that it 'did not expressly or by implication otherwise disclose the individual enantiomers'. In further discussion, his Honour referred to the 'independent existence of the enantiomers' and the 'independently existing (+)-enantiomer' in concluding that the patent for the racemate did not anticipate the claim to one of the enantiomers. 63 His Honour characterised his conclusion at [447] as being that the (+)-enantiomer is present in the claim as 'an independent molecule'. 64 As to the pharmaceutical substance per se, his Honour observed that the racemate, citalopram, is the pharmaceutical substance per se in the Cipramil Patent (at [509]) whereas the (+)-enantiomer of that racemate is the pharmaceutical substance per se in the Patent. That is, his Honour also concluded that the (+)-enantiomer of the claim is a pharmaceutical substance per se for the purposes of s 70(2)(a) of the Act. 65 In each case, for the purpose of s 70(2)(a) and s 70(3)(a), Lindgren J also concluded at [509] that Cipramil clearly signified the inclusion in the ARTG of goods that consisted of or contained the citalopram racemate, and that the inclusion of Lexapro in the ARTG clearly signified the inclusion in the ARTG of goods that consisted of or contained (+)-citalopram. 66 His Honour identified 'the precise question' before him, being whether Cipramil was goods that contained the pharmaceutical substance (+)-citalopram for the purposes of s 70(3)(a) of the Act. Justice Lindgren observed that the expression 'per se' was not repeated in s 70(3)(a) and, for reasons on which he elaborated, concluded that the expression did not carry over into other provisions where it was not used. Accordingly, his Honour concluded that it is sufficient that the goods that are included in the ARTG "contain" only non-essentially or incidentally the pharmaceutical substance that is required to be disclosed per se in the complete specification. Further, his Honour observed (at [512]) that both (+)-citalopram and racemic citalopram are for a therapeutic use which is of the same kind in each case and that the therapeutic benefit of citalopram comes from the presence in it of (+)-citalopram.

THE DECISION 67 Justice Bennett acknowledged, at [120], that it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification and that when the claim is unclear, it may be defined or clarified by reference to the body of the specification (Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1 at [15]). Her Honour pointed out that the language of the claims may have no positive meaning when read apart from the specification but that the meaning may become clear and the invention sufficiently defined when the claim is read using the body of the specification as a dictionary of the jargon and for the purpose of ascertaining the nature of the invention (citing Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588 at 616). 68 In the Lundbeck Full Court, as in this application, Alphapharm Pty Ltd and Arrow Pharmaceuticals Pty Ltd submitted that the essential error in Lindgren J's reasoning was that his Honour impermissibly added an integer to the claim. Their submission was that the claim was to "a unique molecule" and that it would be infringed by the independently existing (+)-enantiomer and by the racemate. Alphapharm Pty Ltd and Arrow Pharmaceuticals Pty Ltd directly argued that references by Lindgren J to "individual" or "pure" impermissibly imported an additional integer into the claim. 69 Lundbeck's response, as set out at [131] and following, included the submissions that the (+) symbol indicates that the enantiomer rotates plane-polarised light, a property not manifested in the racemate, and that the claim, as found by Lindgren J, is a specific reference to the (+)-enantiomer, distinct from the (-)-enantiomer and not as present in a racemic mixture. 70 Justice Bennett noted at [131]: '[t]hat is, Lundbeck says, [the claim] is to the isolated, purified or separated (+)-enantiomer'. That submission needs to be understood in context. It also framed the language of Bennett J's reasons. 71 Again, at [138], Bennett J recorded Lundbeck's submission, that the skilled addressee would read the claim 'as being to the isolated (+)-enantiomer, that is the pure (+)-enantiomer'. Lundbeck's submission was that this did not add a limitation to the claim but represented a construction of the term in the claim as it would have been read by the skilled addressee. 72 At [151], Bennett J said: '[t]hat is, [the claim] is to the separated or isolated or pure (+)-enantiomer'. It is apparent that, in context, her Honour was not considering levels of purity, as is made clear from the Decision at [157] to [160]. At [157] Bennett J expressly rejected the suggestion that the claim imported a limitation of purity. In that context her Honour drew a distinction between a limitation of purity and an 'isolated, separated enantiomer, not in a mixture or in a racemate'. 73 It is quite clear that those words "isolated" and "pure" were not intended to add a further qualification or limitation to the claim. Rather, they imported the concept of "separate", as is evident from [149] where her Honour said: The invention is also said to be concerned with a method to resolve the racemate into the individual isomers. While the specification refers to the enantiomers, in the plural, it is in the context of their separate identity. 74 Her Honour then referred to the evidence that the skilled addressee would read the claim as referring to the isolated (+)-enantiomer, in contrast to the (+)-enantiomer as present in the racemate or in a mixture with the (-)-enantiomer. Clearly, in context, the word "isolated" referred to a resolution of the racemate into the separate enantiomers. This is further clarified by the following paragraph (at [152]) where her Honour referred to Dr Barker's decision in Emory University v Biochem Pharma Inc [1999] APO 50, where Dr Barker discussed a claim to a (-)-enantiomer and the separation of the enantiomers from the racemate. 75 Turning to the alleged anticipation by the racemate disclosed and claimed in the Cipramil Patent, Bennett J said (at [194]) that while the skilled addressee knew that the racemate could be resolved into enantiomers, there was nothing to tell him or her to do so. Her Honour also noted that the Cipramil Patent was silent as to the means of obtaining the enantiomers. That is, Bennett J drew a distinction between the enantiomers unseparated or unresolved in the racemate and separated to yield the (+)-enantiomer of the claim. Justice Bennett took the view that the question that must be asked is whether Cipramil contained the same pharmaceutical substance per se disclosed and claimed in the Patent, namely the (+)-enantiomer. 76 Justice Bennett agreed with Lindgren J that the racemate was a good that contained the pharmaceutical substance (+)-citalopram. This reasoning constituted acceptance of (+)-citalopram as a pharmaceutical substance per se. 77 Her Honour discussed this question in some detail at [229] to [247]. 78 The construction of the claim, as understood by the skilled reader, does not import a limitation of purity. This is also made clear in the reasons of Middleton J. His Honour agreed with the reasons of Bennett J and dealt specifically with the submission that Lindgren J had impermissibly added integers that are not found in the claim. His Honour said at [252] that the claim 'simply identifies the substance (+)-enantiomer'. 79 This construction did not involve reading into the claim a limitation of "independently existing" or "existing independently" of the racemate any more than it expands the context in which the (+)-enantiomer is to be found. Any reference to the (+)-enantiomer in the claim indicates that it is the separated or isolated enantiomer that is claimed. In other words, it is implicit in the way that the claim is worded, where the Patent is entitled '(+)-enantiomer of citalopram and processes for the preparation thereof', that the claim is only to the isolated or separated (+)-enantiomer. 80 Accordingly, on the construction of the claim determined in the Decision, there is no further limitation imported into that claim. That was the clear conclusion of Bennett and Middleton JJ in the Decision. It is also consistent with their Honour's reasoning and conclusion as to s 70 of the Act and as to whether citalopram, the racemate, contained the pharmaceutical substance per se, being the (+)-enantiomer or escitalopram disclosed and claimed in the Patent.

CONSIDERATION OF ALPHAPHARM'S SUBMISSIONS 81 Alphapharm's submissions followed this path: The claim has been construed in the Decision to be akin to the "pure or isolated or separated" enantiomer. This is a claim to a pharmaceutical substance limited by a requirement as to purity. Accordingly it is not a claim to a pharmaceutical substance per se. A claim limited by the requirement, that it be separated or isolated or pure, is not a claim to the substance itself but rather to the substance defined in a particular environment as having been subjected to a particular process. Accordingly it is not a claim to the substance itself as required by s 70(2)(a) of the Act (Prejay Holdings Ltd v Commissioner of Patents (2003) 57 IPR 424 at [24]). As the claim was not a claim to the pharmaceutical substance per se, it is outside the operation of s 70(2)(a) of the Act and does not entitle Lundbeck to an extension of term. 82 Alphapharm submits that, because of the evidence accepted by Lindgren J that a skilled person looking at the structure of citalopram would have recognised the presence of two enantiomers and would have been able to depict them, a claim to the enantiomer per se would necessarily have been invalid. Alphapharm then submits that in order to find that the (+)-enantiomer citalopram was novel, Lindgren J and Bennett and Middleton JJ construed the claim as being not to the enantiomer itself but rather to the enantiomer further defined or limited by the requirement that it be separated or isolated or pure. This ignores the wording of the claim, which does not import, in terms, the limitation that it be "isolated" (cf D'Arcy v Myriad Genetics Inc (2014) 313 ALR 627 at [1]). 83 It also ignores the reasoning of each of Lindgren J, Bennett and Middleton JJ in concluding that the racemate did not anticipate the (+)-enantiomer. This was not because the claim should be read as being to the isolated enantiomer but, as explained in the Decision at [193]-[195], the disclosure of the racemate was not a disclosure to the skilled addressee of the (+)-enantiomer. As explained at [193], the skilled addressee would have understood that (±)-citalopram (the racemate) consisted of the (+)-enantiomer and the (-)-enantiomer and would have been able to identify the formulae for the enantiomers but would not have known in the absence of experimentation which was the (+)-enantiomer and which was the (-)-enantiomer. That is, there was no prior disclosure of the enantiomer independently existing. As Bennett J explained at [194], the skilled addressee knew that the racemate could be resolved into the enantiomers but there was nothing to tell him or her to do so. It could not even be said that there were clear and unmistakable directions to obtaining the enantiomers. Accordingly, it does not follow that a claim to the enantiomer per se would necessarily have been invalid. 84 Alphapharm makes it clear that it is not contending that the racemate does not contain the pharmaceutical substance (+)-citalopram for the purposes of s 70(3)(a) of the Act. For the purposes of this appeal, Alphapharm's contention is that the claim, as construed by the Full Court, is not a claim to a pharmaceutical substance per se for the purposes of s 70(2). 85 Alphapharm says that the Lundbeck Full Court made no finding, as set out by the primary Judge, that the isolated (+)-enantiomer was the pharmaceutical substance per se and submits that this leads to the distinction that it contends for between the (+)-enantiomer itself and the isolated (or separated or pure) (+)-enantiomer. Further, says Alphapharm, the primary Judge was in error in suggesting that the isolated (+)-enantiomer is contained in Cipramil. 86 As explained above, Alphapharm's submissions in this regard do not accord with the reasons of the majority of the Lundbeck Full Court. 87 Alphapharm relies upon the reasoning of Emmett J, in dissent in the Lundbeck Full Court, in particular where his Honour said (at [61]) '[The claim] by itself simply identifies the substance, in whatever surroundings it may exist'. Accordingly, his Honour found that the invention so far as claimed in the claim was anticipated by the racemate. However, that part of Emmett J's reasoning came with a qualification where his Honour said 'putting aside how the relevant and skilled addressee might understand the reference in [the claim], [the claim] by itself simply identifies the substance, in the surroundings where it may exist'. This qualification changes the impact of his Honour's reasoning. The construction of the claim as accepted by the majority did not put that understanding aside. 88 Alphapharm also contends that Lundbeck had submitted in the Lundbeck Full Court that the requirement of 'separated or isolated or pure' was part of the text of the claim perceived by reading 'the (+) symbol'. It relies upon the fact that this submission was accepted by Lindgren J at [119] and [123] and on the emphasis on the (+) symbol in Bennett J's reasons. However, again, Alphapharm ignores Bennett J's reasoning generally and specifically in rejecting a limitation as to purity (at [157]). Similarly, Middleton J stated that he was not reading into the claim a limitation of "independently existing" (at [252]). However, Alphapharm submits that this is because Lindgren J and Bennett and Middleton JJ considered that the integer or limitation did not need to be read into the claim as it was already part of the claim. Alphapharm also submits that separation, isolation and purification each refers to a process so that the claim is not to the enantiomer in itself, which it repeats would not have been novel, but only to the enantiomer when separated or isolated or purified. 89 On the basis that the claim does import a limitation, in effect an additional integer, Alphapharm relies upon Prejay where the Full Court said at [24] that 'for a substance to fall within s 70(2)(a) it must itself be the subject of a claim' and it is not enough that it appears in a claim in combination with other integers or as part of the description of a method or process. This, the Full Court said, was implementation of a policy to confine extensions to patents that claim invention of a substance itself. However, Alphapharm then submits that the Patent does not "claim invention of a substance itself" but rather claims invention in the separation, isolation or purification of the substance. This, it should be pointed out, strays into the language of a method claim. Alphapharm submits that, while the subject matter of Prejay and of Boehringer were different, the subject matter of this claim does not conform with the reasoning and policy as to what constitutes a pharmaceutical substance per se. 90 In the Boehringer appeal, the Full Court, in the course of the reasons, set out Heerey J's conclusions about the critical issue. That included a statement by his Honour that, for the purposes of s 70, the type of claim to a pharmaceutical product that is subject to extension rights is 'a new and inventive product alone' and that s 70(2)(a) makes extension rights available when the claim is for a pharmaceutical substance as such, as opposed to a substance forming part of a method or process. It is of interest that the respondent's submissions in that case, as recorded by the Full Court (at [35]) in the context of what constitutes a pharmaceutical substance per se, refers to 'the pharmaceutical substance, standing alone'. This was in the context of a pharmaceutical substance in combination with a device but it does demonstrate the understandable use of words like "alone" or "isolated" or "separated" or "pure" - not to add an integer to the claim but to explain the difference between a new pharmaceutical substance and a pharmaceutical substance in combination with something else. 91 In seeking to describe the difference between the racemate containing the two enantiomers and the claim to one of the enantiomers, Bennett and Middleton JJ used expressions such as "pure", "isolated" and "separated", the same language used by Lindgren J. Another way of describing the subject matter of the claim was 'specific reference to the (+)-enantiomer, distinct from the (-)-enantiomer and not as present in the racemate mixture' (the Decision at [131]). In seeking to differentiate between the racemate and the (+)-enantiomer, the word "itself" could just as easily have been used and would have carried the same meaning in context. 92 Justices Bennett and Middleton did not read into the claim an additional integer, nor did they add something to the words of the claim. Their reasoning was that the claim is to the (+)-enantiomer and nothing else. The term "pharmaceutical substance per se" simply means the pharmaceutical substance "in itself". In Boehringer, Heerey J observed that per se meant 'by or in itself' 'intrinsically' or 'essentially' (at [7]). The Full Court approved that approach on appeal (at [37]). 93 Semantics aside, it is clear that the claim describes a pharmaceutical substance per se. The substance was, as explained by Lindgren J at [536], a new chemical entity. The racemate and the (+)-enantiomer had different physico-chemical interactions manifested in different pharmacodynamics and pharmacokinetics (the Decision at [234]). The claim is to (+)-citalopram, irrespective of how it is produced. The isolated (+)-enantiomer plainly qualifies as a pharmaceutical substance per se and the primary Judge was correct in concluding that it satisfies s 70(2)(a) of the Act. 94 As pointed out by Lundbeck, Alphapharm's submission that Bennett and Middleton JJ construed the claim to include an additional integer or a limitation, such that the claim was no longer to the (+)-enantiomer as a pharmaceutical substance per se, is wholly inconsistent with their Honours' conclusion that the subject matter of the claim satisfied s 70(2)(a) of the Act, such that Lundbeck was entitled to an extension of term based upon Cipramil but not on Lexapro.

CONCLUSION on the appeal 95 Reasons of a court are not to be construed as if they were a statute. They must also be read and understood in the context of the issues that were before the Court. 96 It is clear from the Decision that the expressions such as "separated or isolated or pure" did not import any concept of degree of purity. Quite clearly, Bennett J used the expression as a hendiadys, to explain that the (+)-enantiomer alone was claimed - without the (-)-enantiomer or the racemate. That is, it was the enantiomer itself. Put another way, it was the enantiomer per se. 97 The appeal should be dismissed.

notice of contention 98 Lundbeck filed a draft notice of contention upon which it proposed to rely in the event that leave to appeal was granted. Although it is not necessary for us to decide the matters raised in the draft notice of contention, we can briefly state our views in relation to it. 99 It was contended by Lundbeck that Alphapharm Pty Ltd and Aspen Pharma Pty Ltd (Arrow Pharmaceuticals Pty Ltd is a wholly owned subsidiary of Aspen Pharma Pty Ltd) were estopped from arguing that the claim of the Patent is not directed to a pharmaceutical substance per se for the purposes of s 70(2)(a) of the Act because that issue was decided against them by Lindgren J and, on appeal, by the Lundbeck Full Court. 100 The first point to make concerning the issue estoppel for which Lundbeck contends is that it cannot bind Apotex Pty Ltd or Sandoz Pty Ltd. They were not parties to the proceedings before Lindgren J and the Lundbeck Full Court, nor is there any evidence from which it might be concluded that either of them was a privy of Alphapharm Pty Ltd or Aspen Pharma Pty Ltd: Tomlinson v Ramsey Food Processing Pty Limited [2015] HCA 28 at [35]. Accordingly, Lundbeck's argument, even if accepted, could never be dispositive of Apotex Pty Ltd's and Sandoz Pty Ltd's appeal. 101 The second point to make relates to the scope of the previous decisions. There are a number of statements in the judgments of Lindgren J and the Lundbeck Full Court suggesting that the (+)-enantiomer of citalopram was a pharmaceutical substance per se for the purposes of s 70(2)(a) of the Act. However, even if these suggestions rise to the level of a finding, it does not follow that Alphapharm is estopped from denying the correctness of that finding. 102 The question whether the (+)-enantiomer of citalopram was a pharmaceutical substance per se was not an issue that was necessarily and directly determined by either Lindgren J or the Lundbeck Full Court in deciding whether the extension of the term of the Patent was valid (Ramsay v Pigram (1968) 118 CLR 271 at 276; Kuligowski v Metrobus (2004) 220 CLR 363 at [40]). 103 It was also contended by Lundbeck that even if there was no relevant issue estoppel, an Anshun estoppel (Port of Melbourne Authority v Anshun Pty Ltd (1981) 147 CLR 589) should be held to arise to the same effect because it would be unreasonable to permit Alphapharm to contend in this proceeding that the (+)-enantiomer of citalopram is not a pharmaceutical substance per se. This argument was put on the basis that Alphapharm had contested Lundbeck's application under s 223 of the Act for an extension of time within which to file its application for an extension of the term of the Patent based upon Cipramil. 104 It was submitted by Lundbeck that had the point raised in this proceeding been taken and accepted in the extension of time proceeding before the Tribunal (Re Aspen Pharma Pty Ltd and Commissioner of Patents (2012) 132 ALD 648), the Full Court (Aspen Pharma Pty Ltd v H Lundbeck A/S (2013) 216 FCR 508) and the High Court (Alphapharm Pty Ltd v H Lundbeck A/S (2014) 108 IPR 459), it would have been determinative because it would inevitably follow that any extension of time would be futile. 105 The principal issue in the extension of time proceedings was whether the relevant decision-maker acted in excess of power in granting the relevant extension of time. We are not satisfied that it was unreasonable for Alphapharm not to raise the quite different issue which we have had to consider in an earlier proceeding that was primarily directed to the question whether it was within the power of the Commissioner to grant the extension of time sought by Lundbeck under s 223 of the Act. I certify that the preceding one hundred and five (105) numbered paragraphs are a true copy of the Reasons for Judgment herein of the Honourable Justices Bennett, Nicholas and Yates.

Patents Act 1990(Cth)ss 70(2)(a), 70(3)

PROCEDURAL HISTORY OF THIS PROCEEDING 5 Following the Decision, Lundbeck applied to the Commissioner of Patents (the Commissioner) for an extension of time in which to apply for an extension of the term of the Patent, based on ARTG registration of Cipramil. This would extend the term of the Patent to 9 December 2012, to include a time in which the (+)-enantiomer of citalopram was marketed by parties other than Lundbeck. The Commissioner granted the extension of time and that decision was confirmed on appeal to the Administrative Appeals Tribunal (the Tribunal) (Re Aspen Pharma Pty Ltd and Commissioner of Patents and Anor (2012) 132 ALD 648). Alphapharm Pty Ltd, Apotex Pty Ltd, Aspen Pharma Pty Ltd and Sandoz Pty Ltd (together Alphapharm) appealed the Tribunal's decision to the Full Court (Aspen Pharma Pty Ltd v H Lundbeck A/S (2013) 216 FCR 508), which dismissed the appeal. Alphapharm Pty Ltd appealed the Full Court's decision to the High Court (Alphapharm Pty Ltd v H Lundbeck A/S (2014) 108 IPR 459), which dismissed the appeal. Lundbeck then applied for an extension of the term of the Patent, which was determined by a delegate of the Commissioner of Patents (the Delegate), who granted the extension. 6 The application to extend the term of the Patent was opposed before the Delegate by Alphapharm. As recorded in the Delegate's decision, Alphapharm argued that claim 1 is not a claim to a pharmaceutical substance per se, that is, not to the substance alone or "as such" within the meaning of that term as discussed in Boehringer Ingelheim International v Commissioner of Patents [2000] FCA 1918 per Heerey J (Boehringer) and on appeal (Boehringer Ingelheim International GmbH v Commissioner of Patents (2001) 52 IPR 529 at [37]). Alphapharm argued that claim 1 contains "other integers" in addition to the pharmaceutical substance per se. 7 The Delegate extended the standard term of the Patent from 13 June 2009 to 9 December 2012. The primary Judge upheld the Delegate's decision (Alphapharm Pty Ltd v H Lundbeck A/S (2014) 110 IPR 59). 8 This is an application by Alphapharm for leave to appeal the decision of the primary Judge. The application for leave to appeal and the appeal were heard together. 9 The determinative issue in this appeal concerns the reasoning of the Lundbeck Full Court as set out in the Decision.

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