FEDERAL COURT OF AUSTRALIA

Pharmacia Italia S.P.A v Mayne Pharma Pty Ltd [2005] FCA 1078

INTELLECTUAL PROPERTY – patents – claim for infringement – clarity of expression used in a claim – exclusionary integer – principles of construction – whether permissible to qualify a claim by reference to the body of specification – whether substance of invention taken.

Patents Act 1990 (Cth), ss 40(2)(b), 117, 120

Assidoman Multipack (formerly Multipack Wraparound Systems) v Mead Corporation [1995] RPC 321 cited

Attorney‑General v Prince Ernest Augustus of Hanover [1957] AC 436 cited

Catnic Components Ltd v Hill & Smith Ltd (No. 1) [1982] RPC 183 discussed

Clark v Adie (1875) LR 10 Ch. App. 667 cited

Commonwealth Industrial Gases Ltd v MWA Holdings Pty Ltd (1990) 180 CLR 160 followed

Décor Corporation Pty Ltd v Dart Industries Inc (1998) 13 IPR 385 applied

Electric & Musical Industries Ltd v Lissen Pty Ltd (1936) 54 RPC 23 cited

Flexible Steel Lacing Co v Beltreco Ltd (2000) 49 IPR 331 cited

General Tire & Rubber Co. v Firestone Tyre & Rubber Co Ltd (No. 1) [1972] RPC 457 cited

Improver Corp v Remington Consumer Products Ltd [1990] FSR 181 cited

Interlego AG v Toltoys Pty Ltd (1973) 130 CLR 461 cited

Kimberly‑Clark Australia Pty Limited v Arico Trading International Pty Limited and Others (2001) 207 CLR 1 applied

Kirin‑Amgen Inc v Hoescht Marion Roussel Ltd [2005] 1 All ER 667 cited

Leonardis v Sartas No. 1 Pty Ltd  (1996) 67 FCR 126 cited

Marconi v Mullard (1923) 40 RPC 159 cited

Martin Engineering Co v Trison Holdings Pty Ltd (1989) 14 IPR 330 cited

Mayne Pharma Pty Ltd and Mayne Pharma plc v Pharmacia Italia SPA [2005] EWCA Civ 137 considered

Minerals Separation North American Corp v Noranda Mines (1952) 69 RPC 81 cited

Minnesota  Mining and Manufacturing Co v Beiersdorf (Australia) Ltd [1979‑1980] 144 CLR 253 cited

Nesbit Evans Group Australia Pty Ltd v Impro Ltd and Anor (1997) 39 IPR 56 cited

Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 cited

Olin Corporation v Super Cartridge Co Pty Ltd and Anor  (1977) 51 ALJR 525 applied

Populin v H.B. Nominees Pty Ltd (1982) 41 ALR 471 applied

Radiation Ltd v Galliers & Klaerr Pty Ltd (1938) 60 CLR 36 applied

Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd and Ors (1988) 81 ALR 79 cited

Root Quality Pty Ltd and Anor v Root Control Technologies Pty Ltd and Others (2000) 177 ALR 231 cited

Walker v Alemite Corp (1933) 49 CLR 643 applied

Welch Perrin and Company Proprietary Limited v Worrel (1961-1962) 106 CLR 588 followed

GS Banker and CT Rhodes, Modern Pharmaceutics (1979)

Dictionary of Pharmacy, Pharmaceutical Products Press, 2004

PHARMACIA ITALIA S.P.A and PFIZER (PERTH) PTY LIMITED v MAYNE PHARMA PTY LTD and F H FAULDING & CO LTD and FAULDING HEALTHCARE PTY LTD

VID 439 OF 2003

CRENNAN J

5 AUGUST 2005

MELBOURNE

THE COURT ORDERS THAT:

1.         The parties to prepare short minutes of final orders on liability in accordance with these reasons and include any other orders or directions as appropriate for the further disposition of the matter.

Note:    Settlement and entry of orders is dealt with in Order 36 of the Federal Court Rules.

REASONS FOR JUDGMENT

Introduction

1                     This proceeding concerns the alleged infringement of Australian Patent No. 598197, entitled ‘Injectable ready-to-use solutions containing an antitumor anthracycline glycoside’ (‘Patent’) within s 117 of the Patents Act 1990 (Cth) (the ‘Patents Act’). The first applicant, Pharmacia Italia S.p.A, a company incorporated in Italy, is the registered proprietor of the Patent; the second applicant, Pfizer (Perth) Pty Limited, a company incorporated in Australia, is a manufacturer of pharmaceuticals (together, ‘the applicants’). Since 23 July 2003 the second applicant has been the exclusive licensee in Australia of the invention described in the Patent in relation to epirubicin hydrochloride.

2                     The first respondent, Mayne Pharma Pty Ltd is a manufacturer, distributor and exporter of pharmaceutical products.  The second and third respondents are F H Faulding & Co Ltd, and Faulding Healthcare Pty Ltd respectively. The three respondent companies form part of the Mayne Pharma group of companies, all of which are incorporated in Australia (together, ‘the respondents’). The applicants allege that the respondents have infringed certain claims of the Patent by ‘manufacturing, selling, using and keeping a ready –to‑use antitumor anthracycline glycoside solution as claimed in the Patent’ (the ‘respondents’ product’) and have made application to this court under s 120 of the Patents Act.

3                     It is noted that on 23 July 2003 an order by consent was made in the following terms:

‘The decisions of the questions of law and issues of fact in respect of the validity (if put in issue by way of Cross-claim) and liability for infringement of Australian Letters Patent 598197 be made separately from and before any other question in the proceeding.’

Accordingly, the only question to be resolved by the Court, at this stage, is whether the respondents have infringed certain claims of the Patent by making and selling epirubicin hydrochloride in injectable ready-to-use solutions.

4                     The primary issue of infringement is whether the respondents’ product has been ‘reconstituted from a lyophilizate’ as that phrase is used in Claim 1 of the Patent, which states that the invented pharmaceutical product ‘has not been reconstituted from a lyophilizate’.  A secondary issue is whether the specific occasions on which the respondents used sodium hydroxide, in addition to hydrochloric acid, to adjust the pH of the solution avoid infringement, when Claim 1 of the Patent refers to the pH being adjusted ‘solely with a physiologically acceptable acid’ (emphasis added).

5                     The invention, the subject of the Patent relates to:

(a)    a pharmaceutical product, being a stable intravenously injectable ready-to-use solution of an antitumor anthracycline glycoside, e.g. doxorubicin;

(b)   a process for preparing such a solution, [providing] the same in a sealed container; and

(c)    a method for treating tumours by the use of the ready-to-use solution.

6                     The priority date of the Patent is 2 August 1985. Anthracycline glycosides are anticancer drugs which were well known at the priority date.  It appears that at that time they were commercially available solely in the form of lyophilized preparations (in a solid form) that needed to be reconstituted into an injectable form (a liquid) before administration to a patient. 

7                     Lyophilization is a process which is colloquially described as ‘freeze-drying’ whereby the temperature of the subject material is lowered to freeze it.  A vacuum is drawn then the temperature is raised such that the frozen solvent (usually water) sublimates directly from a solid to a gas.  Accordingly, a ‘lyophilizate’ is the dried or solid form of a product which was formerly in a liquid form and has undergone lyophilization. 

8                     Anthracycline glycosides cannot be administered to a patient in their lyophilized solid form yet they are unstable in aqueous solution and degrade, resulting in both a loss of pharmaceutical activity and the precipitation of solid particles, which prevents them from being administered intravenously.  Because of the problems related to instability, anthracycline glycosides were not manufactured in the form of ready-to-use solutions before the priority date.  As mentioned above, they were only marketed in the form of a lyophilized solid in a vial, which was required to be reconstituted into a liquid form before the product could be injected into a patient.

9                     In the body of the Patent specification it is noted that the manufacturing and reconstitution of such preparations expose the personnel involved to risks of contamination which are particularly serious because of the toxicity of the antitumour substances. The complete specification states:

‘To administer a lyophilized preparation, double-handling of the drug is required, the lyophilized cake having to be first reconstituted and then administered and, moreover, in some cases, the complete dissolution of the powder may require prolonged shaking because of solubilization problems.’ (p2)

10                  The complete specification indicates that the invention is targeted at circumventing the problems of handling cytotoxic material safely:

‘As the risks connected with the manufacturing and the reconstitution of a lyophilized preparate would be highly reduced if a ready-to-use solution of the drug were available, we have developed a stable, therapeutically acceptable intravenously injectable solution of an anthracycline glycoside drug, e.g. doxorubicin, whose preparation and administration does not require either lyophilization or reconstitution.’ (p2)

The cOmplete Patent specification

11                  The entitlement of the complete specification is set out in paragraph 1 above.  The body of the Patent specification describes the product, process and method of treatment which are defined in the claims thus:

‘The present invention relates to a stable intravenously injectable ready-to-use solution of an antitumour anthracycline glycoside, e.g. doxorubicin, to a process for preparing such a solution, and provide the same in a sealed container, and to a method for treating tumours by the use of the said ready-to-use solution.’

12                  Then follows a description of relevant prior art and the problems which the invention seeks to overcome as set out in paragraphs 9 and 10 above.

13                  The complete specification then sets out the consistory clause for the product, which underlines Claim 1, as follows:

‘According to the present invention, there is provided a sterile, pyrogen-free, anthracycline glycoside solution which comprise a physiologically acceptable salt of an anthracycline glycoside dissolved in a physiologically acceptable aqueous solvent therefor at an anthracycline glycoside concentration of from 0.1 to 50 mg/ml, which has not been reconstituted from a lyophilizate, and the pH of which has been adjusted from 2.5 to 5.0 solely with a physiologically acceptable acid.  Preferably the solution of the invention is provided in a sealed container.’

14                  The language of the consistory clause for the product is then reflected in a preferred embodiment as follows:

‘According to a particularly preferred embodiment of the invention, there is provided a sterile, pryogen-free, doxorubicin solution which consists essentially of a physiologically acceptable salt of doxorubicin dissolved in a physiologically acceptable solvent therefor at a doxorubicin concentration of from 0.1 to 50 mg/ml, which has not been reconstituted from a lyophilizate and the pH of which has been adjusted from 2.5 to 5.0 solely with a physiologically acceptable acid.’

15                  The complete specification then sets out the consistory clause for the process as follows:

‘The invention also provides a process for producing a sterile, pyrogen-free anthracycline glycoside solution with a pH of from 2.5 to 5.0, which process comprises dissolving the physiologically acceptable salt of the anthracycline glycoside, which salt is not in the form of a lyophilizate, in the physiologically acceptable solvent therefor; adding solely a physiologically acceptable acid to adjust the pH within the said range as desired; passing the resulting solution through a sterilising filter and, optionally, adding an additional component selected from a co-solubilizing agent, a tonicity adjustment agent and a preservative, for instance of the kind previously specified, to the solution prior to passing the solution through the sterilising filter.’

16                  The complete specification then proceeds:

‘With the solutions of the invention it is possible to obtain compositions having a very high concentration of the anthracycline glycoside active substance even at 50 mg/ml and more.  This constitutes a great advantage over the presently available lyophilized preparates wherein high concentrations of anthracycline glycoside can only be obtained with difficulty because of solubilization problems encountered in reconstitution, mainly with saline.  The presence of the excipient, e.g. lactose in the lyophilized cake, and its generally high proportion in respect of the active substance, even up to 5 parts of excipient per part of active substance, has a negative effect on solubilization so that difficulties may arise in obtaining dissolution of the lyophilized cake.’ 

17                  Then the complete specification sets out the consistory clause for the method as follows:

‘… according to the invention there is also provided a method of inhibiting the growth of a tumour, in particular one of those indicated above, which comprises administering to a host suffering from said tumour an injectable solution according to the invention containing the active drug substance in an amount sufficient to inhibit the growth of said tumour. The injectable solutions of the invention are administered by rapid intravenous injection or infusion according to a variety of possible dose schedules.’

18                  Further, in terms of preferred embodiments, the complete specification then provides 12 examples which ‘illustrate but do not limit in any way the invention’ and they include the dissolution of doxorubicin, and the adjustment of the solution’s pH, followed by the filtration and containment of the solution in sealed vials. The stability of the 12 solutions is then described over various periods of time.

19                  The invention is the subject of 26 claims.  The pharmaceutical product (solution) claims are claims 1 to 19 and 22.  The process claims are claims 20, 21, 23 and 24 and the claims relating to a method of treatment using the product are claims 25 and 26.

20                  The applicants allege the respondents have infringed:

(a)        product claims 1 to 3, 5 to 10, 14 and 15; and

(b)        method claims 25 and 26.

21                  Claim 1 is the only independent claim relating to a solution of the invention and the only claim that refers to the invention as a solution ‘which has not been reconstituted from a lyophilizate’ and ‘the pH of which has been adjusted from 2.5 to 5.0 solely with a physiologically acceptable acid.’

22                  The parties are agreed that resolution of the construction of Claim 1, in respect of those parts emphasised below, will resolve the controversy between them.  Claim 1 is now set out with numbers (1) to (6) interpolated to identify its six integers: 

‘1.      (1)        A sterile,

(2)        pyrogen‑free

(3)        anthracycline glycoside solution

(4)        which comprises

(i)     a physiologically acceptable salt of an anthracycline glycoside

(ii)   dissolved

                                           (a)   in a physiologically acceptable aqueous solvent therefor

(b)     at an anthracycline glycoside concentration of from 0.1 to 50 mg/ml,

(5)        which has not been reconstituted from a lyophilizate

(6)        and the pH of which

(i)     has been adjusted from 2.5 to 5.0

(ii)     solely with a physiologically acceptable acid.’

23                  It is also necessary to set out Claim 20, the process claim, relied on by the respondents as an aid to construing Claim 1:

‘20.    A process for producing a sterile, pyrogen-free, anthracycline glycoside solution with a pH of from 2.5 to 5.0, according to any one of the preceding claims; which process comprises dissolving a physiologically acceptable salt of the anthracycline glycoside, which salt is not in the form of a lyophilizate, in a physiologically acceptable aqueous solvent therefore; adding solely a physiologically acceptable acid to adjust the pH within the said range as desired; passing the resulting solution through a sterilising filter; and, optionally, adding an additional component selected from a cosolubilizing agent, a tonicity adjustment agent and a preservative to the solution prior to passing the solution through the sterilising filter.’

24                  The invention is for a new combination.  Accordingly, to establish infringement, the applicants must demonstrate that the respondents have taken ‘each and every one of the essential integers’: Populin v H.B. Nominees Pty Ltd (1982) 41 ALR 471 at 475.  The respondents have admitted their product has the features of the new combination in Claim 1 except those covered by integer (5) and the emphasised part of integer (6)(ii).

25                  Each of the respondents is involved in one of the manufacture, distribution or sale of the respondents’ product.  In a written outline of submissions, the respondents’ product is described as:

‘. . . a sterile, pyrogen-free anthracycline glycoside solution which comprises a physiologically acceptable salt of an anthracycline glycoside dissolved in a physiologically acceptable aqueous solvent therefor at an anthracycline glycoside concentration of from 0.1 to 50 mg/ml.  The pH of the solution has been adjusted to a figure within the range of 2.5 to 5.0.’

26                  The respondents assert that their product does not infringe the Patent because, at an early stage in the manufacturing process, the dissolution of bulk lyophilizate takes place, and that therefore their solution has been ‘reconstituted from a lyophilizate’, a feature of production which it asserts is expressly excluded by Claim 1 of the Patent.  It can be noted in this context that the applicant conceded that the bulk powder used in the manufacture of the respondents’ product is a lyophilizate.

27                  The applicants assert that the Patent is to be construed such that the words ‘which has not been reconstituted from a lyophilizate’ in Claim 1 are limited to mean the process that takes place just prior to administration of the solution to a patient. They submit that the expression means (and thereby excludes from the monopoly claimed) solutions made up shortly before administration to a patient, which were known at the priority date and does not mean the dissolution of the lyophilizate in the respondents’ method of manufacture.  Therefore, it is submitted, the respondents’ product is within the scope of Claim 1. 

28                  Thus the two questions to be resolved by the court are whether (i) the respondents’ product has been ‘reconstructed from a lyophilizate’ as the phrase is used in Claim 1 and (ii) the pH of the respondents’ product has been adjusted solely with a physiologically acceptable acid.

29                  The claims in a complete specification define the invention: s 40(2)(b) of the Patents Act.  They mark out the monopoly operating to disclaim what is not specifically and definitely claimed: Walker v Alemite Corp (1933) 49 CLR 643 at 656. This is to ensure that the public and specifically a manufacturer will not have difficulty being satisfied that a claim  is not infringed: General Tire & Rubber Co. v Firestone Tyre & Rubber Co Ltd (No. 1) [1972] RPC 457 at 515 (‘General Tire & Rubber Co.’).  There are no special rules for the interpretation of patent specifications: Décor Corporation Pty Ltd v Dart Industries Inc (1998) 13 IPR 385 at 391 (per Lockhart J) (‘Décor’).  The approach to be taken is discussed by the High Court in Kimberly‑Clark Australia Pty Limited v Arico Trading International Pty Limited and Others (2001) 207 CLR 1 at [24] (‘Kimberly-Clark’):

‘It is well settled that the complete specification is not to be read in the abstract; here it is to be construed in the light of the common general knowledge and the art before 2 July 1984, the priority date; the court is to place itself “in the position of some person acquainted with the surrounding circumstances as to the state of [the] art and manufacture at the time”.’ 

30                  The parties were substantially in agreement that the skilled addressee for the purposes of this case was a ‘team’ as is appropriate with highly developed technology: General Tire & Rubber Co. at 485.  The team included not only a pharmacist working in a hospital but also persons involved in the manufacture of cytotoxic drugs for hospital pharmacists, as at the priority date 2 April 1985.

31                  Speaking broadly, it was contended for the applicants that the word ‘reconstituted’ as it occurs in the phrase ‘has not been reconstituted from a lyophilizate’ in Claim 1 was a term of art.  It was conceded that the word had an ordinary English meaning in pharmaceutical science but it was contended that it also had a specialist meaning in pharmaceutical science.  Thus the word ‘reconstitution’ was capable of having more than one meaning. It was submitted that ambiguity or lack of clarity could be dispelled by resort to the body of the specification.

32                  Alternatively, if ‘reconstituted’ as used in Claim 1 is not a term of art, it was contended that the complete specification, ie. the context showed the expression was used in a special and narrow sense.  Either way the exclusionary integer would indicate to the skilled addressee that the invention did not cover known prior art.

33                  It was contended for the respondents that the word ‘reconstituted’ as used in Claim 1 is not a term of art.  Next, it was submitted it was a word of ordinary English meaning, which as a matter of principle precluded resort to the body of the specification to qualify Claim 1.  Further, the express terms of Claim 1 were relied on as not limiting the phrase in contention, to solutions in a vial or to injectable solutions.  It was submitted that the applicants’ attempts to construe the exclusionary integer narrowly should fail.

34                  Numerous experts gave evidence about the meaning of the term ‘reconstituted’ which is unexceptional given the terms of the dispute: Minnesota  Mining and Manufacturing Co v Beiersdorf (Australia) Ltd [1979‑1980] 144 CLR 253 at 270 (‘Minnesota Mining’); Leonardis v Sartas No. 1 Pty Ltd (1996) 35 IPR 23 at 36.

35                  The applicants’ experts did not dispute the fact that ‘reconstitution’ has a usual, or as they put it, general meaning, perhaps best exemplified by the relevant entry in the 1982 Supplement to the Oxford English Dictionary:

‘reconstituted, that has been constituted or formed anew; applied spec. to food which has been dehydrated and subsequently made ready for use by adding liquid.’

36                  It was also conceded by the applicants that the word ‘reconstituted’ was used in the pharmaceutical sciences with a usual but narrower meaning of describing the step of putting lyophilized material into solution.  This is exemplified in an entry after the priority date in the Dictionary of Pharmacy, Pharmaceutical Products Press, 2004:

‘reconstitution  process of adding a solvent or suspending liquid (usually purified water) to a previously prepared spray‑dried or freeze‑dried drug formulation intended to be used in a short period of time (usually within two weeks) after the addition (generally refrigerated following reconstitution); example: reconstitution of an antibiotic suspension’

37                  Professor Stella, an American Professor of Pharmaceutical Chemistry, gave evidence on behalf of the applicants that as at the priority date, in 1985, all anthracycline glycosides were supplied for use as lyophilizates prepared in a particular way to produce an intravenously injectable solution. 

38                  Dr Williams, a specialist pharmacist in manufacturing from Westmead Teaching Hospital in New South Wales, gave evidence on behalf of the applicants of his experience also as at the relevant date.  He gave evidence that anthracycline glycosides were provided to pharmacists in single dose sealed vials:

‘. . . which had to be prepared by the pharmacist for administration to the patient by a reconstitution.  A reconstitution was carried out as part of the general dispensing process in response to receipt of a prescription. The doses were reconstituted immediately prior to the administration to a patient, either on the day of administration or no more than one day before administration.’

He also gave evidence he performed many such reconstitutions and trained many others in the procedure:

‘Pharmacists used the term “reconstitution” to describe the act of adding a sterile diluent to a sterile solid drug in a vial (or, rarely, in an ampoule) to dissolve or suspend the drug in order to prepare an injection, installation or irrigation, and a product which is reconstituted has been prepared in this way.

In the specific context of reconstituting cytotoxic drugs for intravenous injection, other important aspects of a reconstitution include the fact the resulting product must be fully dissolved and that the reconstituted solution must be free of pyrogens.

Reconstitution technique is an important element of pharmacy training and practice.  Hospital pharmacists, in particular, may perform reconstitutions many times a day; larger hospitals including Westmead have dedicated reconstitution units including cytotoxic reconstitution units, as I have mentioned.  Accordingly, reconstitution is a well known procedure and the term “reconstituted” is well understood by pharmacists.’

He did not accept that ‘reconstitution’ was a synonym for ‘dissolution’ in the context of hospital pharmacy practice. 

39                  The applicants also relied on the evidence of Dr Marshall, a Consulting Pharmaceutical Scientist from South Australia who gave the following evidence:

‘I have been asked . . . to consider what term or expression would be used by pharmaceutical formulation chemists to describe the step where a lyophilizate is put into solution as part of a manufacturing process.  The words I would use are “dissolve” or “dissolution”.  The words “dissolve” and “dissolution” are in my experience frequently used both orally and in writing (such as in operating manuals or manufacturing instructions) in describing processes involving putting solid pharmaceutical compounds into solution. I cannot recall (before or after 1985) seeing the words “reconstitute” or “reconstitution” used in a technical document (of which I have seen hundreds) relating to the process of dissolving pharmaceutical compounds in the manufacturing of pharmaceuticals or formulations of such pharmaceuticals. 

The word “reconstitution” is, however, used in the pharmaceutical industry in relation to finished product powders, whether lyophilized or not, which are dissolved or suspended before administration to a patient . . .’

40                  Dr Marshall referred to the text Modern Pharmaceutics by Gilbert S. Banker and Christopher T. Rhodes (1979) which states:

‘Several ophthalmic drugs are prepared as sterile powders for reconstitution by the pharmacist before dispensing to the patient… The sterile powder is usually manufactured by lyophilization and is packaged separately from the diluent, and a sterile dropper assembly is provided.  In powder form these drugs have a much longer shelf life than that of their solution forms.  The pharmacist should use only the diluent provided with the product since it has been developed to maintain the optimum potency and preservation of the reconstituted solution.  The pharmacists should use great care in performing the reconstitution to prevent microbial contamination of the sterile product and dropper.  Each product has an expiration date for the reconstituted solution which should be explained to the patient along with the proper storage conditions and method of usage.’

41                  Professor Peter Stewart, Head of the Department of Pharmaceutics, Victorian College of Pharmacy, upon whom the applicants also rely, echoed the evidence of Dr Marshall as follows:

‘Reconstitution has a particular meaning in the context of pharmacy.  It refers to the following fundamental steps taken shortly before administration of the drug to the patient. 

(a)    Taking a solid form of an active pharmaceutical compound (plus any excipients).

(b)     Adding a solvent to the solid to make an acceptable delivery system.

The delivery system produced by reconstitution is referred to as “reconstituted”.’

Dr Stewart also gave evidence that:

‘For injectable delivery systems reconstitution is usually a matter of hours before administration.’ 

42                  Dr Richard Oppenheim, a chemist with some 30 years experience in the area of ‘human pharmaceuticals’, was at the relevant time a member of the Pharmaceutics faculty of the Victorian College of Pharmacy in Melbourne.  He gave clear evidence on behalf of the respondents that:

‘The term “reconstitution” refers to the process of adding a suitable and appropriate liquid or liquid system to a solid that has previously been associated with that liquid or some other liquid system, to form a solution, dispersion or suspension suitable for its intended use. If a solid has undergone the process of reconstitution by the addition of a suitable liquid or liquid system, the resultant solution, dispersion or suspension is said to have been “reconstituted”.’

He also gave evidence of an instance of doxorubicin being available as bulk lyophilizate for research purposes only, as at the priority date.  In this respect, his knowledge and experience differed from that of the other experts.

43                  Dr Kenneth Brown, Consultant Pharmaceutical Scientist in Pharmaceutics, from New South Wales, provided a similar assessment as follows:

‘The process of reconstitution does not necessarily involve bringing the solution back to exactly the same form as the previous solution.  The practical essence of reconstitution is the re-association of the lyophilizate with solvent.

In the pharmaceutical sciences “reconstitution” includes the reconstitution of a lyophilized product by a pharmacist immediately prior to administration.  However, this is not the only meaning of the term. “Reconstitution” is a broad and non-specific term which applies at any time a lyophilizate is redissolved into a solvent or passes into solution.’ 

44                  The respondents’ experts did not disagree that ‘reconstitution’ has a meaning, in the pharmaceutical sciences, of ‘reconstitution of a lyophilized product prior to administration to a patient’. However, they did not accept that reconstitution in that pharmacy context can only occur shortly before administration to a patient.  When cross-examined about the references to ‘lyophilized cake’ and the reconstitution of ‘a lyophilized preparate’ which occur in the passages extracted respectively in paragraphs 9 and 10 above describing the prior art, Dr Oppenheim agreed these reference were to material in a vial, that is, they were references to the drug as it was available in a hospital environment.  Dr Brown also agreed that the reference to ‘lyophilizate preparate’ extracted in paragraph 10 above is a reference to the product available in the hospital environment.

45                  I now turn to consider submissions in more detail.  Mr Caine, of senior counsel, appearing for the applicants conceded that the term ‘reconstituted’ has a general meaning in the context of pharmaceutical sciences to describe the step of putting lyophilized material into solution.  However, he submitted that ‘reconstituted’ was used also as a term of art in the context of cytotoxic drugs which meant the process of preparing a liquid dosage form of a cytotoxic drug before administration to a patient.  He submitted that the essence of the invention is a reformulation of a known drug in a ready-to-use solution which was something that had never before been achieved.  I agree with that description of the essence of the invention.  He then submitted the context of the specification makes it clear that the phrase in contention in Claim 1 was a disclaimer in respect of the prior art.  It was a reference to the lyophilised preparation, known at the priority date, which needed to be made up before administration. 

46                  It was further submitted that the process undertaken by the respondents is one in which a manufacturer produces a lyophilized material, in bulk, and supplies it to one of the Mayne entities, which then takes that freeze-dried, raw material and makes it into a ready‑to‑use solution. The applicants assert that the bulk lyophilization from the supplier entity is different from the prior art disclaimed and dealt with by the inventors in the Patent specification.  Mr Caine’s submissions are that the reconstitution referred to in the complete specification is reconstitution which involves a lyophilized cake in a vial; and that it is this specific reconstitution which is carved out from the definition of the monopoly of Claim 1. 

47                  The applicants submit that the complete specification refers to the dangers involved in the systems, as they were in 1985, being risks to the staff who had to reconstitute the lyophilized preparations shortly before administration because the preparations were unstable in solution over a longer period of time. This was the problem sought to be overcome through the invention of the ready-to-use solution.  The invention did not involve the problematic process of reconstitution just prior to administration.  Therefore, the applicants submit that the act of reconstitution just prior to administration is that which is sought to be disclaimed in Claim 1 through use of the phrase ‘which has not been reconstituted from a lyophilizate.’ 

48                  Mr Macaw, of senior counsel for the respondents, submitted that the words ‘reconstituted from a lyophilizate’ as occurring in Claim 1 bear an ordinary meaning and no special sense for them exists in the pharmaceutical industry, which would confine the meaning to a subset of their usual or ordinary meaning.  It was contended that the meaning of the exclusionary integer of the claim including the word ‘reconstituted’ is plain and unambiguous, and in accordance with well‑settled principle, the meaning of the exclusionary integer could not be qualified by resort to the body of the specification. 

49                  It was next submitted that even if resort were had to the body of the specification to clarify the expression in contention, such resort supports the ordinary meaning.  Reliance was placed on the inventor’s failure in the body of the specification to expressly state that ‘lyophilized preparates’ referred to in the body of the specification (about which Drs Brown and Oppenheim were cross‑examined) were confined to what was known as at the priority date.  Reliance was also placed on the fact that Claim 1 was not confined to a solution in a sealed container, as occurs in dependent Claim 2, and also placed on the fact that there was a broad reference to containers in the body of the specification which was arguably not confined to vials or ampoules. 

50                  Further, the respondents relied on the consistory clause for the process in the body of the specification and the definition of the process in Claim 20 as it referred to ‘anthracycline glycoside, which salt is not in the form of a lyophilizate’ to support an argument that the dissolution of a salt was synonymous with ‘reconstitution from a lyophilizate’. 

THE SKILLED ADDRESSEE

51                  As at the priority date the skilled addressee would have known that:

·        anthracycline glycosides were well known compounds in the antineoplastic group of agents which were used widely as antitumour drugs;

·        antineoplastic drugs, because of their toxicity, posed serious risks to persons handling them, whether manufacturing workers or pharmacists, medical personnel or nurses;

·        the active ingredient in the solution was subject to stability problems with the attendant risk that the product deteriorated; and

·        the lyophilized preparations, existing as at the priority date, for administration to cancer patients, came in the form of lyophilized cake in a vial, the lyophilized cake containing the active substance and an excipient.

52                  The process of administration of the drug available at the relevant time was also known to the skilled addressee as follows:

·        administration required reconstitution of the lyophilized cake and sometimes prolonged shaking was required to achieve complete dissolution; and

·        commercially available anthracycline glycosides came in the abovementioned form.

53                  It is necessary to apply well‑settled principles concerning the proper construction of a patent specification and claims forming part of a complete specification.  The court’s task is to make a ‘commonsense assessment’ of what the expression ‘which has not been reconstituted from a lyophilizate’, as used in Claim 1, conveys ‘in the context of then‑existing published knowledge’: Populin v H.B. Nominees Pty Ltd (1982) 41 ALR 471 at 476.

54                  Reference has already been made to the relevant observations in Kimberly‑Clark at [24] that the court is ‘to place itself in the position of some person acquainted with the surrounding circumstances as to the state of [the] art and manufacture at the time’.  As observed by Lockhart J in Décor at 391:

‘The words used in a specification are to be given the meaning which the normal person skilled in the art would attach to those words, both in the light of his own general knowledge and in the light of what is disclosed in the body of the specification: British Thomson‑Houston Co Ltd v Corona Lamp Works Ltd (1921) 39 RPC 49 per Viscount Haldane at 67, per Lord Shaw at 89; Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59 per Stephen J at 60.’

55                  In Décor, at 400, Sheppard J distilled ten rules of construction from the authorities:

‘(1)      The claims define the invention which is the subject of the patent.  These must be construed according to their terms upon ordinary principles.  Any purely verbal or grammatical question that can be answered according to ordinary rules for the construction of written documents is to be resolved accordingly.

(2)       It is not legitimate to confine the scope of the claims by reference to limitations which may be found in the body of the specification but are not expressly or by proper inference reproduced in the claims themselves.  To put it another way, it is not legitimate to narrow or expand the boundaries of monopoly as fixed by the words of a claim by adding to those words glosses drawn from other parts of the specification.

(3)       Nevertheless, in approaching the task of construction, one must read the specification as a whole.

(4)       In some cases the meaning of the words used in the claims may be qualified or defined by what is said in the body of the specification.

(5)       If a claim be clear, it is not to be made obscure because obscurities can be found in particular sentences in other parts of the document.  But if an expression is not clear or is ambiguous, it is permissible to resort to the body of the specification to define or clarify the meaning of words used in the claim.

(6)       A patent specification should be given a purposive construction rather than a purely literal one.

(7)       In construing the specification, the court is not construing a written instrument operating inter partes, but a public instrument which must define a monopoly in such a way that it is not reasonably capable of being misunderstood.

(8)       The body, apart from the preamble, is there to instruct those skilled in the art concerned in the carrying out of the invention; provided it is comprehensive to, and does not mislead, a skilled reader, the language used is seldom of importance.

(9)       Nevertheless, the claims, since they define the monopoly, will be scrutinised with as much care as is used in construing other documents defining a legal right.

(10)     If it is impossible to ascertain what the invention is from a fair reading of the specification as a whole, it will be invalid.  But the specification must be construed in the light of the common knowledge in the art before the priority date.’

56                  Particularly relevant are the principles that the specification as a whole must be read and the context of a specification may qualify the prima facie meaning of a word or expression in a claim.  If a word used in a claim is not a term of art, by reference to the technical knowledge possessed by persons skilled in the art, and is used in a plain, clear and unambiguous way in a claim, there should be no resort to the body of the specification to aid in the construction of the claim: Welch Perrin and Company Proprietary Limited v Worrel (1960-1961) 106 CLR 588 at 610; Electric & Musical Industries Ltd v Lissen Ltd (1936) 54 RPC 23 at 41.  That principle is subject to the proviso that any lack of clarity or ambiguity in a claim can be resolved by resort to the body of the specification: Interlego AG v Toltoys Pty Ltd (1973) 130 CLR 461 at 457/8 (per Barwick CJ and Mason J); Décor at 391; Marconi v Mullard (1923) 40 RPC 159 at 175.

57                  There is no inconsistency in the principles governing construction of patent specifications as explained by Hely J in Flexible Steel Lacing Co v Beltreco Ltd (2000) 49 IPR 331 at [73] – [76] and especially [78].  It is as true of patent specifications, as of statutes (or any documents), as noted by Viscount Simonds in Attorney‑General v Prince Ernest Augustus of Hanover [1957] AC 436:

‘. . . words, and particularly general words, cannot be read in isolation: their colour and context are derived from context (at 461) . . . the elementary rule must be observed that no one should profess to understand any part of a statute or of any other document before he has read the whole of it.  Until he has done so he is not entitled to say that it or any part of it is clear and unambiguous (at 463).’

58                  Similarly, the meaning of a word in a particular context may involve some limitation on its application in a patent claim, but such a meaning can only be derived from the context in which the word is used: see some examples, Henriksen v Tallon [1965] RPC 434 at 445 (per Reid LJ); Minnesota Mining at 261 ff, esp. 272 (per Aickin J) and Décor at 410-411 (per Sheppard J). 

59                  The word ‘reconstituted’ as it appears in the relevant expression in Claim 1 is not a term of art used to refer to the dissolution of a lyophilized product so as to produce a solution suitable for intravenous injection shortly thereafter.  It is clear however that both the word ‘reconstituted’ and the expression of which it forms a part in Claim 1 are used in a special sense in the specification.  Alternatively, because the word is capable of more than one meaning it lacks clarity.  It is permissible to have resort to the body of the specification both to see whether a word or expression has a special meaning or whether it requires clarification because the ordinary, or usual, meaning is not sufficiently precise.  To find a word or expression is used in a special sense it is only necessary that an intention to so use the word or expression is plainly indicated in the specification: Minerals Separation North American Corp v Noranda Mines (1952) 69 RPC 81 at 96. 

60                  The body of the specification shows the expression ‘which has not been reconstituted from a lyophilizate’ in Claim 1 disclaims preparations known in the prior art, the better to mark out the monopoly and to define the invention.  References in the body of the specification to lyophilized preparations known as at the priority date were references to lyophilized preparations in a vial.  Contextually, the exclusionary integer refers to a ready‑to‑use solution, produced from a lyophilizate in a vial which needed to be reconstituted before administration to a patient; that is what was known at the priority date and that is what is disclaimed by the exclusionary integer, so as to be excluded from the monopoly claimed for the invention.  A reference in dependent Claim 20 to a process which is not confined expressly to such preparations does not detract from such a conclusion.  Accordingly, the claim for infringement by reference to integer (5) of Claim 1 is made out.

61                  It next becomes necessary to consider whether the respondents’ product infringes by reference to integer (6)(ii) of Claim 1.  In relation to a process used after August 2004, the respondents admit the pH has been adjusted to be within the stated range by use of a physiologically acceptable acid being hydrochloric acid.  Accordingly, textual infringement has occurred in respect of product produced by that process.

62                  An original process used before August 2004 involved production of certain product where the adjustment of the pH of the solution to within the range specified in Claim 1 was achieved also by the use solely of hydrochloric acid.  That product accordingly also constitutes a textual infringement.  However, there was a third batch where after hydrochloric acid was used to adjust the pH of the solution to be within the claimed range of 2.5 – 5.0 (adjusted to 2.7 (or 2.8)) the respondents then added a minor amount of sodium hydroxide to further adjust the pH to 2.9.  Thus there was no textual infringement with this product.  However, the question in respect of an infringement of a combination patent is whether the essence or substance of an invention underlying its form has been taken, such that in substance and effect an infringement has occurred: Clark v Adie (1875) LR 10 Ch. App. 667 at 675 (per James LJ) referred to with approval by Dixon J in Radiation Ltd v Galliers & Klaerr Pty Ltd (1938) 60 CLR 36 at 51/52 (‘Radiation Ltd’).  There Dixon J eschewed literalism as an approach to assessing whether an alleged infringement fell within the language of the claim:

‘But, on a question of infringement, the issue is not whether the words of the claim can be applied with verbal accuracy or felicity to the article or device alleged to infringed.  It is whether the substantial idea disclosed by the specification and made the subject of a definite claim has been taken and embodied in the infringing thing.’ 

That approach continues to apply unless the claims make it clear that the relevant area has been deliberately left out of the claim: Olin Corporation v Super Cartridge Co Pty Ltd and Anor  (1977) 51 ALJR 525 at 530 (per Gibbs J); Minnesota Mining at 286 (per Aickin J).  Immaterial variations will not escape infringement: Populin at 475.

63                  In Commonwealth Industrial Gases Ltd v MWA Holdings Pty Ltd (1990) 180 CLR 160 (‘CIG’) Menzies J dealt with a combination patent in respect of which a defendant consciously sought to avoid infringement by making a slight modification in manufacture to a particular part of a piece of equipment.  He said at 167:

‘Patent rights are not to be set at naught by such a subterfuge which . . . added nothing to the equipment and was made merely in an attempt to take full advantage of the invention while avoiding infringement of the plaintiff’s letters patent by a modification so small as to be insignificant.’

Menzies J went on to find the modification in manufacture did not avoid an essential feature because the defendant’s product was so close as to still ‘take the invention’. 

64                  The addition of a minor amount of sodium hydroxide, which avoids textual infringement in respect of integer 6(ii) is a modification so small as to be insignificant.  The consequence of adding a minor amount of sodium hydroxide was to produce water and sodium chloride both of which were already present in large quantities in the solution.  The consequential variations in total water and sodium chloride present were within normal manufacturing tolerances.  This is a modification which makes no material difference and in substance the invention is still taken.  It cannot be said the modification was deliberately left outside the claim.  Accordingly, the respondents’ product for which the respondents use sodium hydroxide, in addition to hydrochloric acid, to adjust the pH is a product which is no different relevantly from the invention.  Accordingly, the respondents do not thereby avoid infringement of Claim 1. 

65                  It needs to be mentioned that on this aspect of the dispute, the applicants relied on a principle of ‘purposive’ construction as advanced by Lord Diplock in Catnic Components Ltd v Hill & Smith Ltd (No.1) [1982] RPC 183 (‘Catnic Components’), cited in numerous Australian cases.  The respondents submitted there was no place for a purposive approach to construction on the facts of the case, because the word ‘solely’ in the relevant integer was a word of clear and ordinary meaning and because it is reasonable to infer the restriction was deliberate on the part of the patentee.

66                  It has been recognised in numerous authorities that Lord Diplock was expounding the relevant common law rather than advancing any novel principle of infringement, as is made plain, in any event, in Catnic Components at 242/243: see Kirin‑Amgen Inc v Hoescht Marion Roussel Ltd [2005] 1 All ER 667 at [33]-[35] and [42]-[43] (per Hoffman LJ); Assidoman Multipack Limited (formerly Multipack Wraparound Systems) v Mead Corporation [1995] RPC 321 at 330-333 (Aldous J); PLG Research Ltd v Ardon International Ltd [1995] RPC 287 at 309 (per Millett LJ).  See also Rhone‑Poulenc Agrochinie SA v UIM (1986) 12 FCR 477 at 498 (per Lockhart J); Azuko Pty Ltd and Anor v Old Digger Pty Ltd (formerly SDS Digger Tools Pty Ltd) (2001-2002) 52 IPR 75 at 99 (per Beaumont J); Leonardis v Sartas No 1 Pty Ltd (1996) 67 FCR 126 at 148 (per Burchett, Hill and Tamberlin JJ); Nicaro Holdings Pty Ltd & Ors v Martin Engineering Co (1989) 91 ALR 513 at 528/529 (per Gummow J); Rehm Pty Ltd v Webster’s Security Systems (International) Pty Ltd and Ors (1988) 81 ALR 79 at 92 (Gummow J); Martin Engineering Co v Trison Holdings Pty Ltd (1989) 14 IPR 330 at 347/348 (Burchett J): cf Root Quality Pty Ltd and Anor v Root Control Technologies Pty Ltd and Others (2000) 177 ALR 231 at [39] and [44] (Finkelstein J) (‘Root Quality’).

67                  Lord Diplock suggests in Catnic Components, at 243:

‘The question in each case is: whether persons with practical knowledge and experience of the kind of work in which the invention was intended to be used, would understand that strict compliance with a particular descriptive work or phrase appearing in the claim was intended by the patentee to be an essential requirement of the invention so that any variant would fall outside the monopoly claimed, even though it could have no material effect upon the way the invention worked.’

68                  Following that suggestion,  Hoffman J in Improver Corp v Remington Consumer Products Ltd [1990] FSR 181 at 198 suggested that the court should ask itself, what have come to be known as the three ‘Improver’ questions, as an aid to ‘purposive’ construction:

‘(1)    Does the variant have a material effect upon the way the invention works?  If yes, the variant is outside the claim.  If no –

(2)     Would this (i.e., that the variant had no material effect) have been obvious at the date of publication of the patent to a reader skilled in the art.  If no, the variant is outside the claim.  If yes  ‑

(3)     Would the reader skilled in the art nevertheless have understood from the language of the claim that the patentee intended that strict compliance with the primary meaning was an essential requirement of the invention.  If yes, the variant is outside the claim.’

69                  It is not necessary for the resolution of this case to do other than apply the Australian authorities referred to above.  I note, however, that some Australian courts have derived assistance from the Catnic Components approach in deciding the ambit of the monopoly of a claim: see for example Nesbit Evans Group Australia Pty Ltd v Impro Ltd and Anor (1997) 39 IPR 56 and Root Quality.  Had I regarded it as being of assistance to ask the Improver questions of the variant, the conclusion would have been that the variant is not outside the claim.

UK PATENT

70                  A corresponding patent in the United Kingdom was the subject of a judgment of the English Court of Appeal dated 17 February 2005, reported as Mayne Pharma Pty Ltd and Mayne Pharma plc v Pharmacia Italia SPA [2005] EWCA Civ 137.  The Mayne parties had sought a declaration of non‑infringement in respect of Pharmacia’s equivalent United Kingdom Patent 2,178,311 (‘UK Patent’).  A counterclaim for infringement followed and the issue, as here, was whether Mayne’s product fell within Claim 1 (worded slightly differently).  At first instance, a Deputy Judge found non‑infringement.  The Court of Appeal construed Claim 1, as contended for by Pharmacia and upheld the appeal.  On 10 March 2005 the Court of Appeal refused an application for leave to appeal to the House of Lords.  A petition to the House of Lords directly for leave to appeal was then in prospect.

71                  The applicants and respondents filed supplementary submissions dated, respectively, 24 and 11 March 2005.  Essentially the applicants contended the principles of construction were consistent with those expressed in Populin and Décor and there was no basis upon which the position in Australia could be distinguished from that reached by the Court of Appeal. 

72                  The respondents drew attention to a distinction between Claim 1 in the Patent and Claim 1 in the UK Patent; the latter included the words ‘injectable, ready‑to‑use’ after the word ‘An’ at the beginning of Claim 1 and before the epithet ‘sterile’ in line 1.

73                  The respondents noted in their submissions that in the United Kingdom the ‘overarching principle of construction is contained in Article 69 of the European Patent Convention’ and there is no equivalent to Article 69 in Australia.  The compatibility between the principles of construction in Article 69 and the Catnic Components approach, (which stated the law applicable to the 1949 U.K. Act) is explained by Aldous J in Assidoman at 332-333, which explanation was approved in Kirin‑Amgen Inc at [46] (per Hoffman LJ).

74                  The respondents also relied on the fact that the process claims in the United Kingdom (claim 31) and Australia (claim 20) contained similar directions.  The respondents urged again that the words in Claim 1 ‘which has not been reconstituted from a lyophilizate’ refer to and include product which is reconstituted from a bulk lyophilizate at some point because the process claim is not limited to product which is reconstituted in a vial.

75                  The decision of the English Court of Appeal is persuasive, to the extent that the complete specifications of the Patent and the UK Patent are very similar, although not identical, and there is a commonality of applicable principles. 

76                  It can be noted, however, that I have reached the conclusions set out above on the evidence before me and by applying principles as settled in the abovementioned Australian authorities.  Orders will not be made today.  The parties can prepare short minutes of final orders on liability in accordance with these reasons and include any other orders or directions as appropriate for the further disposition of the matter.

Associate:

Dated:              5 August 2005