THE CROSS-CLAIMANTS' CASE FOR INFRINGEMENT OF THE COMPOUND PATENT
18 The invention protected by the compound patent is entitled "difluoro antivirals and intermediate therefor". The complete specification states that the invention "provides a new difluoro carbohydrate and new antiviral nucleosides prepared by coupling the new carbohydrate with appropriate bases". For present purposes it is sufficient to note that the specification discloses a carbohydrate as follows -
Where R is one of a number of possible bases including the following -
The specification discloses that R1 in this base may be a number of different atoms or groups, including hydrogen.
19 Claim 1 in the patent corresponds with the description given above in the complete specification. Later claims are narrower than Claim 1. The particular combination of carbohydrate and base to which I have referred in the previous paragraph also falls within Claim 4, which is narrower than Claim 1 by confining R in the carbohydrate to the base set out above. Claim 6 is narrower again. It corresponds with Claim 4, save that R1 in the base must be hydrogen.
20 Structurally, gemcitabine is the same as the compound referred to in Claim 6 of the compound patent, and also falls within Claims 1-4. In his affidavit sworn on 16 June 2008, Professor Easton of the Research School of Chemistry, Institute of Advanced Studies, Australian National University, concluded that gemcitabine fell within Claims 1-4 and 6 of the patent. At the structural level, the cross-respondent did not take issue with that conclusion. If that were all that is involved in the question, it would seem to be established prima facie at least that the production and sale of gemcitabine would infringe the compound patent.
21 However, as the complete specification makes clear -
The structural drawings above do not indicate the stereochemistry of the compounds of the present invention. Compounds of all configurations are believed to be useful, and the stereochemistry of the compound is not to be construed as a limitation.
The specification goes on to state that the configuration of naturally occurring ribose is preferred, and that the preferred configuration of the "juncture" between the ribose (ie the carbohydrate) and the base be such that the base lies above the plane of the ribose, and the hydrogen below. As it happens, that is gemcitabine. As indicated, however, the specification goes no further than to indicate that such a configuration is preferred. It is not required.
22 The submission of counsel for the cross-respondent on infringement was that the patent disclosed only the racemate, and not the β anomer. They submitted that "a purified stereoisomer does not infringe a claim to a compound that has no reference to stereochemistry". They relied upon the evidence of Professor Jackson, of Monash University, who said in his affidavit sworn on 26 September 2008 that "none of the claims is directed toward any one stereoisomer and, thus, none to Gemcitabine."
23 The first aspect of the dispute with respect to infringement of the compound patent, therefore, comes down to this. The cross-claimants assert that, by being indifferent to stereochemistry, the patent covers all anomeric forms of the structural compounds specified in it. Since it covers all forms, it covers the β anomer which corresponds with gemcitabine. The cross-respondent, by contrast, asserts that the very indifference of the patent with respect to stereochemistry shows that the patent is confined, as a matter of construction, to the racemate. Any organic chemist following only the learning disclosed by the patent would produce the racemate. Although he or she would, presumably, well understand that the racemate consisted of a number of anomers, he or she would not be instructed by the patent to produce any one of them, and would think, correctly in the submission of the cross-respondent, that the stereochemical composition of the resulting mixture was immaterial. It follows, according to the cross-respondent, that a compound which consists only, or very substantially, of a particular anomer will not infringe the patent.
24 It seems, perhaps surprisingly, that there is no decided case which deals directly with this point. That is to say, the question whether a compound consisting of a particular anomer infringes a patent which specifies the racemate does not appear to have been directly decided by a court. However, counsel for the cross-respondent claimed to have considerable support from observations made in a number of cases concerning pharmaceutical patents in recent years.
25 Counsel for the cross-respondent referred to Ranbaxy Australia Pty Ltd v Warner-Lambert Company LLC [2008] FCAFC 82. One of the questions which arose in that case was described by the Full Court as follows (at [54]-[55]):
There is no challenge to the validity of the Broader Patent. The question of infringement of the Broader Patent depends upon the proper construction of the complete specification for the Broader Patent. Ranbaxy contends that all Claims of the Broader Patent should be construed so as to be restricted to the racemate form of the compounds disclosed. Ranbaxy contends, therefore, that its product, which contains only the R enantiomer of atorvastatin calcium, will not infringe the Broader Patent. Warner-Lambert, on the other hand, contends that the Broader Patent extends to all forms of the compounds of the claimed invention.
The primary judge concluded that Structural Formula 1 refers to the following forms of the compounds disclosed, as well as to the racemate:
· the R-trans enantiomer, individually,
· the S-trans enantiomer, individually, and
· unequal mixtures of the R-trans enantiomer and the S-trans enantiomer.
Accordingly, his Honour concluded that Ranbaxy's intended importation and sale of its product would infringe Claim 1 and certain other Claims of the Broader Patent. In its appeal, Ranbaxy contends that the primary judge erred in rejecting its contention that the Broader Patent was restricted to the trans-racemates of the compounds disclosed.
Their Honours in the Full Court upheld the primary Judge's conclusion that Structural Formula 1, as it was described, disclosed the two enantiomers mentioned, and was not confined to the racemate. It was by reason of that holding that their Honours dismissed this aspect of the appeal. However, in the course of their reasons, the Full Court said (at [60]):
However, if the Broader Specification, as a whole, only disclosed and claimed the racemate, the claim to the racemate would not extend to claim the enantiomers.
Although this observation cannot be regarded as part of the ratio decidendi of Ranbaxy, it has the authority of the Full Court, and is very recent. It supports the position taken in the present case by the cross-respondent.
26 The other authorities upon which the cross-respondent relied were not concerned with infringement. Rather, they were concerned with the question of anticipation, and in some respects applied the "reverse infringement" test for novelty. The cross-respondent submitted that the authorities in this line are relevant because, if a compound disclosed in a prior publication did not anticipate the patent, it would not infringe the patent if produced after grant. In Alphapharm Pty Ltd v H Lundbeck A/S [2008] FCA 559, it was contended that an invention which consisted of a purified enantiomer had been anticipated by an earlier patent which made no reference to individual enantiomers. Lindgren J said (at [171]):
The Australian Citalopram Patent did not refer to "enantiomers". It did not expressly or by implication otherwise disclose the individual enantiomers. It disclosed the racemate and enabled the obtaining of it. Whether this anticipated the present invention turns on my construction of the Patent - see Section C above. The skilled but non-inventive addressee reading the Australian Citalopram Patent would have understood that (+/-)-citalopram consisted of the (+)-enantiomer of citalopram and the (-)-enantiomer, each as to 50%, and would have been able to identify the formulae for the S and R enantiomers, but would not have known, in the absence of experimentation, which was (+) and which was (-). These facts would not, however, point specifically to the independent existence of the enantiomers which is, according to my construction of the Patent specification, of the essence of claim 1. If I had construed claim 1 as referring to (+)-citalopram when present in the unresolved racemate, the Australian Citalopram Patent would have been an anticipation. But because of my construction outlined at Section C above, a person taught by the Australian Citalopram Patent, although taught to desire to obtain the racemate, would not be taught to desire to obtain the specific (+)-enantiomer in its own right.
It follows, according to the cross-respondent, that a compound which consists of one enantiomer only does not infringe a patent which is not concerned with anomeric forms.
27 Apotex Pty Ltd v Sanofi-Aventis [2008] FCA 194 involved an application for revocation upon the ground that the patent, which claimed an enantiomer, was disclosed by earlier publications which were said to involve racemic mixtures only. Gyles J said (at [45]):
On the other hand, the formula identified as derivative 1 or example 1 in the French patent and corresponding patents (PCR 4099) has the identical formula to the enantiomer in suit. I am satisfied that the skilled but not inventive reader of the French and corresponding patents would understand that the derivative in question (in common with all of the derivatives) was the racemate and that all of the technical explanations as to the means of obtaining that (and other) derivatives and as to the testing of them related only to the racemate and not to any individual enantiomer. There is no express suggestion that either enantiomer had in fact been separately obtained or tested for efficacy or toxicity. That said, it was commonly known, and was spelled out in the French patent, that the compound in question was a racemate with one chiral centre and two enantiomers - one dextro and the other levo. There were express references to the enantiomers in both the body of the specification and in the claims of the French and corresponding patents, with the detail most clearly spelled out in the Canadian patent. The express references to the enantiomers in the French and corresponding patents (particularly the Canadian patent) plainly carry the claim that the enantiomers are within the compounds disclosed.
Gyles J referred to various passages in the earlier patents that were claimed to be anticipatory, and said that they were "consistent only with a disclosure of, and a claim to, each enantiomer … separate from the racemate and from each other." (at [46]). His Honour also held (at [47]) that the "patentee was asserting that the relevant qualities of each enantiomer were not to be relevantly distinguished from any particular racemate or the other enantiomer." His Honour continued (at [48]):
The claims for the separate enantiomers could be described as bare claims for efficacy without any foundation being shown for them in any part of the complete specification. There is no basis for knowing what, if any, efficacy or toxicity would apply to either enantiomer of any particular racemate.… No doubt, if only the racemate were claimed, there would be a large risk that this would not protect against competition from a drug with one of the enantiomers as the active ingredient, which might be as efficacious as, and perhaps more efficacious than, the racemate as an active ingredient.
28 In what Gyles J described as a digression, his Honour referred to the judgment of Lindgren J in Alphapharm, to the judgment of Young J ((2006) 71 IPR 46) and of the Full Court in Ranbaxy, and to other authorities. In the course of that, his Honour referred to a text in the following terms (at [74]):
In the Encyclopedia of United Kingdom and European Patent Law (Sweet & Maxwell Limited, 1977-2007), footnote 3 on page 1109 includes the following:
"It has, for instance, been held that publication of the existence of an "optically active" compound is not publication of the separated optically active forms, even though any chemist would appreciate that they must exist and could be prepared: I.C.I. (1971) unrep. (No. 1,069,343 opposed by Sandoz, P.A.T.). The case could have been treated as a "selection" patent, but it was not. But cf. ante, s2-015. A similar view was taken by the EPO in PFIZER/Penem (T1048/92) [1995] E.P.O.R. 207 but not in SANOFI/HOECHST Enantiomers (T296/87) [1990] E.P.O.R. 337 and in (T658/91) [1996] E.P.O.R. 24. The cases seem to be distinguished by the degree to which the earlier publication specified that Enantiomers formed part of the disclosed invention."
Later, the authors said (5-110 on page 1110):
"The teaching of a racemate does not amount to the teaching of a single enantiomer (at least in the absence of the clear identification of the relevant chiral site and an indication that the enantiomers are encompassed by the disclosure)."
(T296/87 was the European Patent Office decision as to an application corresponding with the patent in suit.)
29 In the present case, the cross-respondent submitted that the facts of Apotex were "very different from the present case" in that, in Apotex, although the prior patents disclosed the racemate, they did not disclose only the racemate: they disclosed also the existence of separate entantiomers. It was, according to the cross-respondent, upon this basis that Gyles J held that these earlier patents anticipated the patent in suit (which claimed an enantiomer).
30 This brings me to the second aspect of the dispute with respect to the infringement of the compound patent. Counsel for the cross-claimants asserted that the patent in the present case did recognise the existence of different stereochemical forms of the compounds claimed. In this sense, they submitted, the patent should be construed as extending not merely to the racemate, but to the different anomers as elements thereof. Although they did not so submit in terms, I rather gather that they would contend that the present case has, in these respects, a deal in common with Apotex. Counsel also derived support from the identification of what is described as the preferred configuration in the complete specification. That is the β anomer of the compound which is, structurally, specifically covered by Claim 6 (and, structurally, is within Claims 1-4 also). According to the cross-claimants, an organic chemist would readily appreciate that the β anomeric form of the compound covered by Claim 6 was the subject of the patent.
31 The questions whether the patent makes a claim for the β anomeric form, and if it does not whether that form is nonetheless covered by the patent because it is structurally so covered and the patent covers all anomeric forms, require for their resolution a construction of the patent. That will be the task of the trial Judge. They are the very questions by reference to which, it seems, the question of infringement in relation to the compound patent will be determined. By reference to the authorities, particularly Ranbaxy and Apotex, the cross-respondent's point is of some apparent force. It is not so self-evidently likely to succeed, however, as to compel the conclusion that the cross-claimants do not have a serious question to be tried. I shall take the relative apparent strengths of the parties' positions into account later, when I turn to general discretionary considerations and to the balance of convenience.
32 Because the compound patent is within a term of extension, the cross-respondent has the opportunity to rely, and does rely, upon s 78 of the Patents Act. Relevantly, it provides as follows:
If the Commissioner grants an extension of the term of a standard patent, the exclusive rights of the patentee during the term of the extension are not infringed:
…
(b) by a person exploiting any form of the invention other than:
(i) a pharmaceutical substance per se that is in substance disclosed in the complete specification of the patent and in substance falls within the scope of the claim or claims of that specification; ….
It was submitted on behalf of the cross-respondent that, if gemcitabine does fall within one of the claims in the patent, it is nonetheless not "a pharmaceutical substance per se that is in substance disclosed in the complete specification". In this respect the cross-respondent's submission had a degree of overlap with its submission on the question of infringement. It is said that gemcitabine may be the purified β anomer of one of the compounds structurally covered by the patent, but is not "per se" disclosed therein. That is said to be because the patent does not specifically disclose the β anomer, as distinct from the racemate. Given the approach which I have taken on the matter of infringement, however, I could not find that the cross-respondent's defence under s 78 was so self-evidently correct as leave the cross-claimants without a serious question to be tried. There appears not to be much authority with respect to the operation of s 78(b)(i), and one could well imagine the cross-claimants in the present case submitting at trial that gemcitabine is disclosed per se, either because the complete specification, as a matter of construction, discloses all anomers, or because it contains a specific identification of the preferred configuration, which happens to be gemcitabine.