The 981 Patent is not confined to racemic mixtures
114 In isolation from the text of the 981 Patent, structural formula I in claim 1 could depict absolute stereochemistry or relative stereochemistry. Relative stereochemistry describes the position of substituents of a compound relative to each other, that is, either both on the same side or on opposite sides of a plane of reference. If structural formula I were intended to depict absolute stereochemistry, the parties and the expert witnesses were in agreement that it would depict the R-trans enantiomer of the class of compounds referred to in the formula. However, neither party contended that structural formula I on its proper construction should be confined to the R-trans enantiomer of the compounds of structural formula I. On the contrary, the parties and the expert witnesses agreed that structural formula I was intended to depict relative stereochemistry.
115 The short issue, therefore, is whether structural formula I, in the context of the specification as a whole, would be understood by the skilled addressee of the patent as a formula which is to be confined to trans racemates and which excludes the R-trans enantiomer and S-trans enantiomer of the compounds of the invention.
116 For the reasons set out below, I do not accept that claim 1 should be construed in this way. In my opinion, the compounds of claim 1 are not confined to trans racemates but also include the R-trans enantiomer and the S-trans enantiomer.
117 Both in the title of the 981 Patent and in the body of the specification, the class of compounds claimed by the patent is referred to by the chemical name 'trans…'. The term trans denoted relative stereochemistry to a person skilled in the art as at 30 May 1986. There are two trans enantiomers. The use of the term trans does not discriminate between them. Consequently, it tends to indicate that both enantiomers of any compound of the class defined by structural formula I are included within the scope of the claims.
118 The skilled addressee of the patent would know, as at 30 May 1986, that it was common practice amongst medicinal chemists and others working in the drug discovery field to use a single structural formula to represent each enantiomer individually and mixtures of them. The skilled addressee would also know that those working in the field commonly published on new chiral compounds without determining the absolute stereochemistry of the compounds. Before 30 May 1986 it was common practice in publications on chiral compounds, where absolute stereochemistry was not intended to be specified, to depict relative stereochemistry by drawing one enantiomer. In such a case, the drawing of the enantiomer was arbitrary and was understood by those in the field as a conventional way of representing the two enantiomers and mixtures of them having that relative stereochemistry.
119 The skilled addressee of the 981 Patent would also be aware, as at 30 May 1986, that if a diagram of a single enantiomer was intended to depict a racemate, to the exclusion of the enantiomers, it was common practice to add an additional descriptor, such as (±), RS or (rac), to make it clear that the structure, although drawn as a single enantiomer, represented only a racemate. In the absence of such a descriptor, or some other textual indication, the drawing of a single enantiomer in a way that represented relative stereochemistry would be taken as a reference to both enantiomers and mixtures of them, including racemates.
120 Claim 5 of the 981 Patent uses the (±) sign so as clearly to indicate that claim 5 was confined to racemic mixtures. That descriptor is not applied to claim 1 or other claims. Arguably, this provides a slight indication that claim 1 was not intended to be limited to racemic mixtures. It also shows that the patentee was aware of particular means by which claims could be limited to a claim to a racemic mixture. This factor is not irrelevant because it is consistent with other indicators that the patent does not exclude the individual enantiomers. However, I am not disposed to attach significant weight to it: see Ranbaxy (UK) Ltd v Warner-Lambert Company [2006] EWCA 876 ('Ranbaxy UK') at [30] per Jacob LJ; see also the warnings given about the incautious use of the expressio unius maxim of construction in Houssein v Under Secretary, Department of Industrial Relations and Technology (NSW) (1982) 148 CLR 88 at 94 and Wentworth v NSW Bar Association (1992) 176 CLR 239 at 250.
121 Perhaps the most important background consideration against which the claims of the 981 Patent must be construed is that the skilled addressee would know that HMG-CoA reductase inhibitors, such as the class of compounds referred to in claim 1, are enantiomeric and that one enantiomer is very likely to be more active than the other. The skilled addressee would also know that the biological activity of a racemate will be different from that of the single enantiomers, and that the active or more active enantiomer will be approximately twice as active as the racemate. In these circumstances, confronted by a structural formula in claim 1 that shows relative stereochemistry, the skilled reader would consider that the structural formula was intended to claim both enantiomers, as well as racemic mixtures. I do not think that the skilled addressee would read the structural formula as one that was intended to exclude the more active enantiomer.
122 Reading the specification as a whole, the skilled addressee would discern that the patentee had not isolated the individual enantiomers and that the absolute stereochemistry of the more active enantiomer, and that of the less active enantiomer, had not been defined. The skilled addressee would also know that, while it had not yet been done by the patentee, it was a routine step to obtain the individual enantiomers by resolving the racemic mixture, and that it was also possible to make the individual enantiomers by chiral synthesis. In those circumstances, the skilled addressee would expect, in the absence of a clear indication to the contrary, that claim 1 of the patent was intended to include the more active enantiomer.
123 A construction of claim 1 that includes the two trans enantiomers is strongly supported by the passage that appears at pg 6 of the specification. After referring to the class of trans compounds comprising the invention and the two asymmetric carbon centres which the compounds of structural formula I possess, the specification states:
'This asymmetry gives rise to four possible isomers, two of which are the R-cis- and S-cis- isomers and the other two of which are the R-trans- and S-trans- isomers. This invention contemplates only the trans- form of the compounds of formula I above.'
The passage specifically refers to the R-trans and S-trans isomers, distinguishing them from the R-cis and S-cis isomers. The passage draws this distinction in order to include the R-trans and S-trans isomers within the compounds of formula I above, while excluding the R-cis and S-cis isomers from the class of compounds contemplated by the invention. In other words, when the last sentence in the passage refers to 'the trans form', it is referring to the R-trans and S-trans isomers referred to in the previous sentence, both as individual isomers and as the components of a racemic mixture.
124 In my view, this is the plain and natural meaning of the language used in the passage. It is the way in which Professor Easton and Professor Scammells said that the passage would be read, and I consider that it is the way in which the passage would be read and understood by the skilled addressee as at 30 May 1986.
125 I do not accept Ranbaxy's submission that this passage only intended to convey to a skilled addressee the fact that trans racemates fall within the scope of structural formula I, but that cis racemates do not. This submission was based upon Dr Cunningham's evidence at para 4.58 of his affidavit sworn 27 July 2006:
'This passage means no more than that the compounds of structural formula I possess two asymmetric centres on the mevalonolactone moiety, and thus exist in four stereoisomeric forms; two of them are trans and two are cis. It is a simple principle of chemistry that a compound with two asymmetric centres has 4 isomers. This passage in the patent tells the reader that the compounds of Structural Formula I are in the trans form and not the cis form. However, this is already clear from the rest of the patent - all disclosures are directed to the desired trans form rather than cis form. It is clearly the trans form (trans racemates not cis racemates) that are the compounds of Structural Formula I.'
This explanation does not grapple with the specific distinction which the passage draws between the R-cis and S-cis isomers on the one hand and the R-trans and S-trans isomers on the other. The passage does not refer in terms to trans racemates or cis racemates. It does not draw any distinction between trans racemates on the one hand and the R-trans and S-trans isomers on the other. It would distort the plain meaning of the words used in the last sentence of the passage to read it as saying that the invention contemplates only trans racemates of the compounds of formula I and so excludes the R-trans and S-trans isomers individually as well as the R-cis and S-cis isomers individually and in racemic mixture.
126 Claim 1 must be construed in a practical, commonsense manner, with an eye to the utility of the invention, and avoiding a construction which is overly meticulous or unduly technical. In my opinion, there is real force in Warner-Lambert's submission that it is neither a practical nor a commonsense construction of structural formula I to confine it to trans racemates and to interpret it as excluding the R-trans enantiomer.
127 The construction of claim 1 and structural formula I that I prefer is supported by my findings as to the common general knowledge that should be attributed to the skilled addressee as at May 1986. Because of the major developments that had been published in the field of HMG-CoA reductase inhibitors, including the Alberts paper, the Stokker I and Stokker II papers, the Willard Patent, and the Kathawala Patent application, it was generally known that the RR enantiomer was very likely to be the active, or more active, enantiomer, and that conversely it was very likely that the S enantiomer would be inactive or substantially less active. It was also generally known that the ring-opened form of the upper lactone portion of the natural compounds had been found to be significantly more active than the lactone form. The 981 Patent itself provides some confirmation of this. The statement in the 981 Patent that the Willard Patent disclosed certain compounds which, in the 4R-trans isomeric form, are inhibitors of cholesterol biosynthesis forms part of the context in which the claims of the 981 Patent must be construed. The Full Federal Court's decision in Bristol-Myers Squibb Company v FH Faulding and Co Limited (2000) 97 FCR 524 ('Bristol-Myers') at 536 [30] indicates that this statement in the patent specification is to be regarded as an admission by the patentee that it forms part of the common general knowledge existing in the relevant field as at the priority date of the patent.
128 In these circumstances, in the absence of any clear indication or language to the contrary, the skilled addressee as at May 1986 would read claim 1 as encompassing both individual enantiomers, as well as mixtures of them. As Warner-Lambert submitted, it would make no sense to exclude patent protection for the more active enantiomer. The point was well made by Professor Easton in the course of his affidavit evidence when he said that to confine the subject of the 981 Patent to racemic mixtures would exclude the thing (the active or more active enantiomer) that he, and any person working in the field as at May 1986, would know to be the key to the useful activity of the compounds disclosed by the patent.
129 It is not in dispute that structural formula I would be construed by the skilled addressee as including a trans racemate of the compounds of the formula. But there is no reason why the skilled reader would construe the formula as meaning only the trans racemate, thereby excluding both the R-trans and the S-trans enantiomers. In the absence of a clear indication to the contrary, it offends common sense to construe structural formula I in that way.
130 Ranbaxy attempted to turn this argument around and use it against Warner-Lambert's construction. It argued that the literature available to the skilled addressee of the 981 Patent at May 1986 had widely reported that the 4S-trans enantiomers of HMG-CoA reductase inhibitors were essentially inactive, and consequently it would make no sense at all to the skilled addressee that the 981 Patent should be read as claiming the inactive enantiomer. The argument is unconvincing at several levels. First, even if the premise could be made good, it does not address the lack of sense in construing claim 1 so that it fails to claim the active enantiomer. Put another way, it makes sense to claim both enantiomers as well as the racemate, if that is the simplest way of ensuring that claim 1 extends to the active enantiomer. Secondly, the evidence does not make good the proposition that the skilled addressee of the 981 Patent would know or assume that the S-trans enantiomer was entirely inactive. My finding based on the expert evidence given by Professor Easton, Dr Roth and Professor Scammells is that it was generally known in the relevant field at 30 May 1986 that it was very likely that the active or more active enantiomer was the R-trans enantiomer, and that the S-trans enantiomer was inactive or less active; but the skilled addressee would not have ruled out the proposition that the S-trans enantiomer had some level of activity.
131 I have expressed my finding in these terms because the evidence as a whole does not support the more absolute terms in which Dr Scallen expressed his expectations in his affidavit evidence. Dr Scallen said that even before the US equivalent to the 981 Patent was published in 1987, he knew from general principles of medicinal chemistry that only one enantiomer of any compound that was synthesised as a potential HMG-CoA reductase inhibitor would be expected to be active in the target biological system. In addition, he said that from journal articles and patents he had read, together with his own laboratory experience of HMG-CoA reductase inhibitors, he knew that 'it was almost a certainty' that the inhibitory activity of any new HMG-CoA reductase inhibitors that were developed would lie essentially in the R-trans enantiomer rather than the S-trans enantiomer. Dr Scallen said that his views in this respect were similar to those recorded in an internal Warner-Lambert document, entitled 'Minutes of the Atherosclerosis Project Team Meeting of May 28 1987' in which it was stated that 'the team, based on literature precedent, has assumed that all the biological activity resided in the RR enantiomer (same absolute configuration as lovastatin)'. I consider that the strength of Dr Scallen's views reflect his exceptionally detailed knowledge of, and involvement in, the development of HMG-CoA reductase inhibitors. It is noteworthy that, in cross-examination, Dr Scallen expressed his view a little less dogmatically: he said it could be put as a very high probability, although he accepted that he would wish to confirm it by doing laboratory experiments.
132 Dr Cunningham did not express his expectations as absolutely as Dr Scallen. As I have already mentioned, he spoke in terms of a common expectation by the skilled team that the biological activity of HMG-CoA reductase inhibitors would reside in one enantiomer with a 4R-trans configuration. He also expressed his evidence by saying that virtually all of the target inhibitory activity would rest in the R-trans configuration, with the S-trans configuration exhibiting virtually no activity at all. In his affidavit evidence, Dr Cunningham conceded that the S-trans enantiomer may also have had some slight ability to bind with perhaps one site in the target enzyme. In the course of cross-examination, Dr Cunningham said it was very likely that the compounds the subject of the 981 Patent would be compounds in which the R-trans enantiomer would be the active enantiomer. He said that was his expectation but one would not know until one had isolated the enantiomers and tested them. He also said that there was a very high probability that the S enantiomer would be inactive. But again he accepted that until the SS enantiomer was tested, one could not be absolutely certain that it was inactive, although all of the indications from the literature were that it would be inactive.
133 Ranbaxy pointed to various factors in support of its construction of claim 1. The relevant factors can be divided into those appearing within the four corners of the specification, and those arising extrinsically.
134 Ranbaxy relied heavily on the fact that the specification describes only the preparation of racemates, reports biological activity only in relation to racemates and does not provide any methods for obtaining the individual enantiomers or unequal mixtures of them. The argument is encapsulated in paras 4.7 to 4.10 of Dr Cunningham's affidavit sworn 27 July 2006:
'Taken in context, Structural Formula I, either when appearing in the body of the specification of the Racemate Patent, or in the claims, represents trans racemates and nothing else.
In summary, this is because the methods of synthesis described in the Racemate Patent produce only trans racemates and there is no reference anywhere in the Racemate Patent to anything other than trans racemates. There is no reference in the Racemate patent to any of (i) resolution of trans racemates to obtain single enantiomers, (ii) asymmetric synthesis of single enantiomers, or (iii) single enantiomers in general.
If Structural Formula I was intended to represent a single enantiomer, then somewhere in the Racemate Patent I would expect to find a reference to resolution of trans racemates to obtain single enantiomers, or asymmetric synthesis of single enantiomers. There are no such references.
(i) Methods of Synthesis
In my first affidavit, I have stated that the Racemate Patent discloses and claims processes to produce racemates. The only methods or processes disclosed and claimed are those which produce racemates.'
Dr Cunningham's observation that there is no reference anywhere in the patent to anything other than trans racemates depends on his very narrow reading of the passage at pg 6 of the specification, which I have already rejected.
135 Ranbaxy pointed out that the summary of the invention in the specification describes four aspects of the invention, the second of which is a method of preparing the compounds of structural formula I. Ranbaxy then made the following points. The method of the invention is described both textually and diagrammatically by reference to a number of reaction steps. Those reaction steps produce only racemates. The method does not produce the R-trans enantiomer individually, the S-trans enantiomer individually, or unequal mixtures of the S-trans and R-trans enantiomers. In order to produce the RR enantiomer and SS enantiomer individually, it would be necessary to resolve the racemic mixture or to take some sort of stereoselective step. The specification contains no reference to a resolution step or any other stereoselective step and there is no direction to employ such steps. In Table 1 in the specification, each of the compounds whose biological activity is recorded is a racemate. Table 1 does not report on the biological activity of the R-trans enantiomer, the S-trans enantiomer or unequal mixtures of the S-trans and R-trans enantiomers.
136 The examples are illustrative only, as the text of the specification states, but Ranbaxy contends that it is significant that they produce only racemates. The reactions of example 1 produce racemic atorvastatin lactone; example 2 produces racemic atorvastatin sodium salt; and the reactions of examples 3 and 4 produce racemates which according to structural formula I are not atorvastatin.
137 The body of the specification uses the notation RR on several occasions. In the abstract, the notation signifies relative stereochemistry. But, in the context in which notation is used at pgs 10, 22, 23 and 24 of the specification, it refers to a trans racemate on each occasion. Ranbaxy contends that this is another indication that the invention claimed is confined to trans racemates of the compounds of structural formula I.
138 Warner-Lambert submitted that the plain meaning of claim 1 is not to be read down or glossed by any implications drawn from the parts of the specification that I have just mentioned. In my opinion, the features of the specification to which Ranbaxy points are outweighed by the other considerations I have mentioned. The examples are illustrative only. Further, I do not attach any weight to the fact that the specification does not specifically address the resolution of racemates into separate enantiomers. On the evidence before me, that was a matter of routine chemistry that formed part of the common general knowledge of the skilled addressee of the patent.
139 Relying on Dr Cunningham's evidence, Ranbaxy also submitted that there was a standard practice of representing the structure of a racemate, to the exclusion of the enantiomers, by depicting the enantiomer having the same absolute configuration as the naturally occurring substances (in this case compactin and mevinolin which are both active in the form of the 4R-trans enantiomer).
140 In his evidence, Dr Cunningham said it is difficult to represent a racemate graphically without additional text: it would require the drawing of the two enantiomers side by side. As at 30 May 1986, Dr Cunningham in his affidavit sworn 27 July 2006 said that the following methods were used in publications to refer to racemates with two or more chiral centres:
'(a) A graphical representation of one enantiomer of a racemate with a statement in the accompanying text of the document that the graphical representation is intended to refer to the racemate rather than the depicted enantiomer.
(b) A graphical representation of one enantiomer of a racemate with an attached notation such as racemic (rac), dl or (±) adjacent to the name of the compound to indicate that the graphical representation is intended to refer to the racemate rather than the depicted enantiomer.
(c) A graphical representation of one enantiomer of a racemate in a document which discusses only racemates indicates that the graphical representation is intended to refer to the racemate rather than the depicted enantiomer.
(d) A graphical representation of one enantiomer of a racemate in a document which describes a product or products obtained in an achiral environment is intended to refer to the racemate rather than the depicted enantiomer.
(e) By default, in some software packages over the last 20-25 years (eg the MDL family of software - ChemBase, MACCS, ISIS/Draw, ISIS/Base and others) the absolute configuration of one enantiomer was drawn, but the diagram was assumed to represent a racemate unless an additional chiral "flag" was added explicitly…
(f) A graphical representation of both enantiomers of a racemate. (As discussed above, for practical reasons, this method was not commonly employed).'
Dr Cunningham added that the use of a notation such as (±) or (rac) adjacent to the name of the compound has always been very common.
141 In my opinion, the evidence before the Court does not establish that there was any standard practice as at 30 May 1986 of depicting the racemate, and only the racemate, by drawing an enantiomer that has the same absolute configuration as the naturally occurring substance. In his evidence, Dr Cunningham did not refer to any material that established the existence of such a practice. The suggested practice is, moreover, rejected by the evidence given by other experts.
142 In his affidavit evidence, Professor Easton said that a structural formula depicting relative stereochemistry represents the enantiomers individually and in mixtures, including racemic and scalemic (unequal) mixtures. In his affidavit evidence, Dr Roth said that it was common for medicinal chemists, including himself, to use a single structural formula to represent each enantiomer individually and mixtures of them. Professor Scammells said in his affidavit evidence that as at May 1986 it was common practice in publications on chiral compounds, where the absolute stereochemistry was not intended, to be specified to depict relative stereochemistry by drawing one enantiomer: in such a case the drawing of one enantiomer was arbitrary and was understood by those in the field to represent the two enantiomers and mixtures of them having that relative stereochemistry. Dr Scallen did not give any evidence to support the practice suggested by Dr Cunningham. On this point, I accept the evidence given by Professor Easton, Dr Roth and Professor Scammells.
143 Ranbaxy also argued that its construction of claim 1 should be preferred because in May 1986 there were practical difficulties in resolving enantiomers on a commercial scale. There were two standard methods for preparing enantiomers in May 1986: resolution of a racemate and chiral synthesis. While resolution was a well known technique used extensively in the laboratory, Ranbaxy contended that it would have been difficult and not economically viable to produce a complex molecule like atorvastatin on a commercial scale. It said that resolution is an extremely wasteful process in that yields cannot exceed 50 per cent. It relied on Dr Watson's affidavit evidence that resolution was a process that was quite well known in Australia prior to 1986 although generally it gave a poor yield of the desired enantiomer and may not be suitable for the production of commercial quantities of one particular enantiomer. Ranbaxy also said that chiral synthesis of single enantiomers involved a high degree of practical difficulty, even if it could be used in theory to produce a single enantiomeric compound for use as the active ingredient in a drug product. In contrast, Ranbaxy said that racemates were more readily and cheaply prepared than single enantiomers. In particular, it said that many drugs, including HMG-CoA reductase inhibitors, were produced as racemic mixtures as at May 1986, and it relied on evidence from Dr Watson and Dr Cunningham that up to at least 1986 most new compounds would have been commonly produced in racemic form.
144 Ranbaxy relied principally on Dr Cunningham's evidence to support these contentions. In paras 4.37 and 4.38 of his affidavit sworn 27 July 2006, Dr Cunningham said:
'… It would not have been feasible to use the methods of resolution available to me in May 1986 to obtain quantities of the R-trans enantiomer sufficient for commercial sale as the active ingredient in a drug product. I do not know of any significant commercial drug product produced anywhere in the world prior to May 1986 where the synthetic active ingredient was a single enantiomer produced by resolution from the racemate.
From my knowledge (including knowledge I obtained from my peers working in other pharmaceutical companies and from my reading of the literature) I believe that by May 1986 few, if any, totally synthetic drugs were produced as pure enantiomers. They were all or nearly all racemates or were achiral. As at May 1986 (and today) synthetic racemates were and are more readily and cheaply prepared than single enantiomers. The methods of production of pure enantiomers generally require more complex synthesis and the use of more expensive raw materials or reagents in what is often a longer synthesis. The costs associated with production of pure enantiomers could be more than twice the costs associated with production of the racemate. As the active enantiomer would be expected to have only about twice the activity of the racemate in vitro, and this increase may not translate in vivo then production of the enantiomer would often not be an attractive option from a commercial perspective.'
Dr Cunningham retreated somewhat from this evidence in cross-examination, accepting that resolution or chiral synthesis could be used to obtain a single enantiomer drug. In my view, the evidence before the Court establishes that it would have been feasible to produce a single enantiomer drug as at 30 May 1986. There was evidence that pharmaceutical companies had been able to produce single enantiomer synthetic drugs either by way of resolution from the corresponding racemic mixture or by chiral synthesis prior to May 1986. Numerous single enantiomeric drugs were on the market prior to May 1986. Dr Cunningham was aware of 50 of them in the mid 1980s.
145 As at 30 May 1986, there was in fact some incentive to produce single enantiomeric drugs. In the United States, the Food and Drug Administration ('FDA') published a 'Guideline for submitting supporting documentation in drug applications for the manufacture of drug substances' in February 1987. The Guideline indicated that where the new compound contained one or more chiral centres, the sponsor should ideally have separated the various potential stereoisomers or synthesised them independently. The Guideline was circulated in draft prior to 30 May 1986 and, when it was eventually published, it reflected matters of which people in the field were well aware, including the fact that enantiomers and racemates could display vastly different biological properties (recall the thalidomide example I have given above at [35]).
146 Ranbaxy argued that the actions that Warner-Lambert had to take after 30 May 1986 to develop and market a single enantiomeric drug showed that the practical difficulties to which it pointed were very real. In particular, Ranbaxy referred to the fact that Warner-Lambert encountered difficulties with racemic atorvastatin lactone in mid 1987; at that point it decided to resolve the racemate into its individual enantiomers; and on 1 February 1989 Warner-Lambert filed a United States patent application directed to the process it had developed for the chiral synthesis of enantiomers of atorvastatin lactone. Assuming that it is appropriate on a question of construction to have regard to these subsequent events, these matters do not affect my conclusion as to the proper construction of the 981 Patent. On the evidence before me, there was a common expectation prior to 30 May 1986 that single enantiomeric drugs could be commercially produced whether by way of resolution or chiral synthesis. The fact that there were numerous single enantiomeric drugs on the market by that stage confirmed this expectation. The possibility that difficulties may be encountered in developing an enantomeric drug for commercial sale does not have the consequence, in my view, that the 981 Patent should be read down so that it only claims racemic mixtures. It must be borne in mind that the patent is concerned with the grant of a monopoly in respect of the claimed compounds for a period of 20 years. There is no reason to doubt that there was a general expectation that means could be found to develop methods of synthesising single enantomeric drugs for commercial sale over that time frame. To my mind, it is unreasonable to suppose that the patent was intended to be confined to racemates simply because difficulties might arise in the near term in producing a single enantiomeric drug on a commercial scale. In any event, I have grave doubts that subsequent conduct of the kind to which Ranbaxy refers in this argument (as distinct from the surrounding commercial circumstances at 30 May 1986) can properly be used as an extrinsic aid to the proper construction of the 981 Patent: cf FAI Traders Insurance Co Ltd v Savoy Plaza Pty Ltd [1993] 2 VLR 437; see also Kirin-Amgen at 452 [28].
147 Ranbaxy's remaining argument focused on one aspect of Warner-Lambert's construction of the 981 Patent. As already noted, Warner-Lambert argued that structural formula I encompasses the racemate, the R-trans enantiomer individually, the S-trans enantiomer individually and unequal mixtures of the S-trans and R-trans enantiomers. Ranbaxy criticised the inclusion of the last category of compounds within the scope of structural formula I. It submitted that there is no reference in the 981 Patent to any unequal mixtures or how to achieve them. It said that it is highly unlikely that, for the purposes of producing a final pharmaceutical product, one would produce an unequal mixture of enantiomers where each enantiomer is present in a substantial proportion. Moreover, it contended that producing an unequal mixture is impractical: it would require a manufacturer to first obtain the two enantiomers and then recombine them in unequal proportions, or alternatively one enantiomer could be added to a racemate. Either way, Ranbaxy said that this would involve much greater expense and difficulty than simply making the racemate.
148 I am not persuaded that these matters should have the consequence that unequal mixtures are excluded from the scope of structural formula I if it is otherwise capable of applying to them. The patentee may have had its own reasons for expressing claim 1 by reference to a structural formula that extends to unequal mixtures of enantiomers. More importantly, Ranbaxy's argument is aimed at a peripheral issue. Even if its criticisms had some substance, they do not mean that structural formula I should be interpreted as excluding the individual enantiomers and as being limited to the racemate.