Aktiebolaget Hässle v Alphapharm Pty Ltd
[1999] FCA 628
•12 MAY 1999
FEDERAL COURT OF AUSTRALIA
Aktiebolaget Hässle v Alphapharm Pty Ltd
[1999] FCA 628INTELLECTUAL PROPERTY – patents – combination patent – pharmaceutical formulation – validity – patent granted under Patents Act 1952 (Cth) – effect of transitional provisions of Patents Act 1990 (Cth) – obviousness – common general knowledge – relevant non-inventive worker in field – whether common general knowledge of skilled formulator includes material which formulator might find by conducting research available to and used by formulators – whether such material, though not being common general knowledge, would be found and used by skilled formulator during routine steps performed in attempting to formulate invention – whether combination of integers claimed obvious – novelty – relationship between novelty and obviousness – whether “paper anticipation” – invention – manner of manufacture – whether lack of inventiveness in combination apparent on face of specification – whether invention contrary to law or generally inconvenient – whether invention a method of treatment of human body – priority date – amendment – “alkaline core material” – whether claims of amended specification disclosed previously undisclosed matters – obtaining amendment by fraud, false suggestion or representation – whether ground of obtaining amendment by false suggestion or representation available under Patents Act 1952 (Cth) – whether fraud alleged – alleged inconsistent statements to Patents Office – whether inconsistent – whether fraud – alleged false representations as to fair basis, novelty, inventive step and utility in patent – whether available as separate ground of revocation – whether false representation in specification as to effect of prior art – whether false representation in specification arising out of omission of experimental material – fair basis – claims alleged to include certain chemical compounds which did not produce result claimed for invention – whether claim fairly based only if it excluded such compounds – sufficiency – relevance of allegation that claims not limited to formulations which achieve purpose claimed for invention – whether specification disclosed best method of performing invention – ambiguity – whether certain technical terms in specification ambiguous, reading specification as a whole – inutility – relevance of allegation that claims not limited to formulations which achieve purpose claimed for invention
WORDS AND PHRASES – “common general knowledge” – “obvious” – “inventive step” – “novel” – “mechanical equivalents” – “invention” – “manner of manufacture” – “generally inconvenient” – “fraud” – “false suggestion” - “fairly based” – “describe the invention fully” – “clear and succinct” – “ useful”
Patents Act 1990 (Cth) ss 3, 7, 18(1), 40(2), 40(3), 114(1), 138(3)(b), 138(3)(e), 233, Sch 1
Patents Act 1952 (Cth) ss 40(2), 100(1)(c), 100(1)(d), 100(1)(e), 100(1)(g), 100(1)(h), 100(1)(k), 100(1)(m), 100(1)(n), 100(1)(o)
Patent Regulations 1991 (Cth) reg 3.14NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1993) 44 FCR 239 applied
Winner v Ammar Holdings Pty Ltd (1993) 41 FCR 205 cited
Wellcome Foundation Ltd v V.R. Laboratories (Aust) Pty Ltd (1981) 148 CLR 262 applied
Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 applied
WR Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) 25 IPR 481 applied
Allsop Inc v Bintang Ltd (1989) 15 IPR 686 cited
British Acoustic Films Ltd v Nettlefold Productions (1936) 53 RPC 221 cited
Graham Hart (1971) Pty Ltd v S W Hart & Co Pty Ltd (1978) 141 CLR 305 cited
Meyers Taylor Pty Ltd v Vicarr Industries Ltd (1977) 137 CLR 228 applied
General Tire & Rubber Co v Firestone Tire & Rubber Co Ltd [1972] RPC 457 applied
Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 referred to
Prestige Group (Australia) Pty Ltd v Dart Industries Inc (1990) 26 FCR 197 cited
MJA Scientifics International Pty Ltd v SC Johnson & Son Pty Ltd (Federal Court of Australia, Sundberg J, 24 July 1998, unreported) referred to
NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1995) 183 CLR 655 cited
Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd (1998) 152 ALR 604 referred to
Commissioner of Patents v Microcell Ltd (1959) 102 CLR 232 referred to
May v Higgins (1916) 21 CLR 119 distinguished
Fallshaw Holdings Pty Ltd v Flexello Castors and Wheels Plc (1993) 26 IPR 565 cited
Sami S Svendsen Inc v Independent Products Canada Ltd (1968) 119 CLR 156 cited
National Research Development Corporation v Commissioner of Patents (1959) 102 CLR 252 referred to
Bristol‑Myers Squibb Company v FH Faulding & Co Ltd (1998) 41 IPR 467 cited
Anaesthetic Supplies Pty Ltd v Rescare Ltd (1994) 50 FCR 1 cited
Re Mond Nickel Co Ltd’s Application [1956] RPC 189 referred to
Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 applied
Olin Corporation v Super Cartridge Co Pty Ltd (1977) 180 CLR 236 distinguished
CCOM Pty Ltd v Jiejing Pty Ltd (1994) 51 FCR 260 cited
Société des Usines Chimiques Rhone‑Poulenc v Commissioner of Patents (1958) 100 CLR 5 cited
F. Hoffman‑La Roche & Co AG v Commissioner of Patents (1971) 123 CLR 529 cited
Patent Gesellschaft AG v Saudi Livestock Transport and Trading Company (1997) 37 IPR 523 applied
Rescare Ltd v Anaesthetic Supplies Pty Ltd (1992) 111 ALR 205 applied
Elconnex Pty Ltd v Gerard Industries Pty Ltd (1992) 25 IPR 173 applied
Decor Corporation Pty Ltd v Dart Industries Inc (1988) 13 IPR 385 applied
Coopers Animal Health Australia Ltd v Western Stock Distributors Ltd (1986) 6 IPR 545 distinguished
Norton and Gregory Ltd v Jacobs (1937) 54 RPC 271 citedAKTIEBOLAGET HÄSSLE AND ASTRA PHARMACEUTICALS PTY LIMITED v ALPHAPHARM PTY LIMITED
NG 884 OF 1998
LEHANE J
SYDNEY
12 MAY 1999
IN THE FEDERAL COURT OF AUSTRALIA
NEW SOUTH WALES DISTRICT REGISTRY
NG 884 OF 1998
BETWEEN:
AKTIEBOLAGET HÄSSLE
First ApplicantASTRA PHARMACEUTICALS PTY LIMITED
(ACN 009 682 311)
Second ApplicantAND:
ALPHAPHARM PTY LIMITED
(ACN 002 359 739)
RespondentALPHAPHARM PTY LIMITED
(ACN 002 359 739)
Cross ClaimantAKTIEBOLAGET HÄSSLE
First Cross RespondentASTRA PHARMACEUTICALS PTY LIMITED
(ACN 009 682 311)
Second Cross RespondentJUDGE:
LEHANE J
DATE OF ORDER:
12 MAY 1999
WHERE MADE:
SYDNEY
THE COURT ORDERS THAT:
1.The respondent file and serve, not later than 26 May 1999, short minutes of the orders which it considers should be made consistently with the reasons for judgment published on 12 May 1999.
Note:Settlement and entry of orders is dealt with in Order 36 of the Federal Court Rules.
IN THE FEDERAL COURT OF AUSTRALIA
NEW SOUTH WALES DISTRICT REGISTRY
NG 884 OF 1998
BETWEEN:
AKTIEBOLAGET HÄSSLE
First ApplicantASTRA PHARMACEUTICALS PTY LIMITED
(ACN 009 682 311)
Second ApplicantAND:
ALPHAPHARM PTY LIMITED
(ACN 002 359 739)
RespondentALPHAPHARM PTY LIMITED
(ACN 002 359 739)
Cross ClaimantAKTIEBOLAGET HÄSSLE
First Cross RespondentASTRA PHARMACEUTICALS PTY LIMITED
(ACN 009 682 311)
Second Cross Respondent
JUDGE:
LEHANE J
DATE:
12 MAY 1999
PLACE:
SYDNEY
REASONS FOR JUDGMENT
The first applicant, a Swedish corporation, is registered as the patentee of Australian Patent number 601974, the patent in suit, to which I shall refer as the patent (or, in contexts where it is necessary to distinguish it from other patents, the patent in suit). The term of the patent is twenty years from 23 April 1987; its claimed priority date is 30 April 1986. The second applicant is registered as the exclusive licensee of the patent. It is a New South Wales company and is related to the first applicant. Both applicants are members of the Astra pharmaceuticals group whose head office is in Sweden; I shall refer to them indiscriminately, and to the group to which they belong, as Astra.
The patent is principally for an oral pharmaceutical preparation the active ingredient of which is a compound known as omeprazole. That compound is itself the subject of a patent (which I shall call the compound patent) held by Astra, Australian Patent No. 529654. Omeprazole was first synthesised in 1979. When absorbed in the upper part of the small intestine it inhibits gastric acid secretion.
Astra sells in many parts of the world, including Australia, a preparation manufactured in accordance with the patent, the trade name of which is “Losec”. Losec is a very effective, very successful and therefore very valuable product. During the period 1 July 1997 to 30 June 1998 1,550,675 packs of Losec were sold under the Commonwealth Pharmaceutical Benefits Scheme at a cost to the government of $141,368,031 and at a total cost (including patient contribution) of $153,538,227. Published information for that year indicates that the amount paid under the Scheme for Losec was considerably greater than the amount paid for any other branded drug; and, ranked generically in order of amounts spent under the Scheme, omeprazole came second, behind simvastatin (4,069,518 packs of which were dispensed at a cost to the government of $182,849,540).
Astra enjoys a monopoly in omeprazole formulations in Australia, principally, no doubt, because it is the proprietor of the compound patent. The compound patent is, however, shortly to expire. The respondent, Alphapharm, markets “generic” drug formulations. It proposes, when the compound patent expires, to import and sell in Australia a pharmaceutical preparation containing omeprazole for therapeutic use in the treatment of gastrointestinal diseases (the “Alphapharm product”). Astra claims that Alphapharm, by doing so, will infringe the patent. It seeks a declaration and an injunction, and ancillary orders. Alphapharm, by cross claim, claims on a number of grounds that the patent is invalid and seeks an order that it be revoked.
The patent
The patent has been amended. The amended specification was filed on or about 30 May 1997 and the amendment was allowed under s 104 of Patents Act 1990 (the 1990 Act). I shall need to consider the effect of the amendment, but it is convenient to defer that consideration. I shall use the term “the patent” to refer to the patent as it has been amended; I shall use the term “the unamended patent” to refer to the specification as it stood before the amended specification was filed. Where I refer to “the specification” or “the claims”, I mean, except where I indicate otherwise, the amended specification or claims.
It is necessary to describe the specification in considerable detail and to quote substantial portions of it.
First, the field of the invention is described as follows:
“The present invention is related to a new stable pharmaceutical preparation containing omeprazole for oral use, to a method for the manufacture of such a preparation and to a method of affecting gastric acid secretion when using them.”
The specification then turns to the background of the invention. It describes the “pioneering work” of Astra in developing the compound, omeprazole, its utility in the treatment of gastric and duodenal ulcers and the circumstance that it “is not easily formulated into a satisfactory pharmaceutical composition”. It proceeds to set out “a number of important facts relevant to the formulation of omeprazole” established by further “pioneering work” by Astra.
“Omeprazole is susceptible to degradation/transformation in acid reacting and neutral media. The half‑life of omeprazole in water solutions at pH‑values less than four is shorter than ten minutes. Also at neutral pH‑values the [degradation] reaction proceeds rapidly. The stability profile is similar in the solid phase. The degradation of omeprazole is catalyzed by acidic reacting compounds and is stabilized in mixtures with alkaline reacting compounds. The stability of omeprazole is also affected by moisture and organic solvents.
Thus an oral dosage form of omeprazole should be protected from contact with the acid reacting gastric juice in order to reach the small intestine without degradation where it can be absorbed.
The rate of release of omeprazole from a pharmaceutical dosage form can influence the total extent of absorption of omeprazole to the general circulation. Thus a fully bioavailable dosage form of omeprazole must release the active drug rapidly in the proximal part of the gastrointestinal canal.”
That states the general nature of the perceived problem. Omeprazole is unstable and degrades rapidly in an acid or neutral solution. Its stability is also affected by moisture and organic solvents. In order to work as a drug, it must be released rapidly when it reaches the top of the small intestine; but it must be protected from acidic gastric juice on its way through the stomach.
The consistory clause follows that general statement of the problems:
“In order to meet these requirements the present invention provides an oral pharmaceutical preparation containing omeprazole as the active ingredient, characterized in that it is composed of: (A) core material containing omeprazole together with an alkaline reacting compound, or an alkaline salt of omeprazole optionally together with an alkaline reacting compound; (B) one or more inert reacting subcoating layer(s) on said core material; and (C) an outer layer, which is an enteric coating, said inert reacting subcoating layer(s) between the said core material and said outer layer comprising tablet excipients which are soluble or rapidly disintegrating in water, or polymeric, water soluble, filmforming compounds, optionally containing pH‑buffering, alkaline compounds. The preparation may be in the form of a tablet or a plurality of pellets which may be encapsulated into capsule form for example.”
The invention so claimed is a combination of three integers, first, the “core material”, secondly, the sub‑coating layer or layers and, thirdly, an outer layer, which is an enteric coating. The specification proceeds:
“Ordinary enteric coatings, are made of acidic compounds. If covered with such a conventional enteric coating, omeprazole rapidly decomposes by direct or indirect contact with it, with the result that the preparations become badly discolored and lose omeprazole content with the passage of time.
It has been found that in order to enhance the storage stability, the cores which contain omeprazole should also contain alkaline reacting constituents. When such a core is enteric coated with an amount of a conventional enteric coating polymer such as, for example, cellulose acetate phthalate, that permits the dissolution of the coating and the active drug contained in the cores in the proximal part of the small intestine, it also will allow some diffusion of gastric juice through the enteric coating into the cores, during the time the dosage form resides in the stomach before it is emptied into the small intestine. The diffused water of gastric juice will dissolve parts of the core in the close proximity of the enteric coating layer and there form an alkaline solution inside the coated dosage form. The alkaline solution will interfere with the enteric coating and eventually dissolve it. In accordance with the present invention this is prevented by the subcoating layer.”
That suggests that the invention solves two particular problems. One is that, though in order to pass through the stomach to the small intestine omeprazole needs to be protected by an enteric coat, contact of omeprazole with such a coat, which is acidic, causes the omeprazole to decompose. The solution to that problem is that the core to be coated contain “alkaline reacting constituents”. Additionally, however, (it is said) some gastric juice will diffuse through the enteric coat and, unless prevented, will dissolve part of the core, forming an alkaline solution which in turn will attack the enteric coat from within. That problem is solved by the addition of the “subcoating layer”.
The specification then deals in more detail with each of the three integers. First, the core:
“Omeprazole is mixed with inert, preferably water soluble, conventional pharmaceutical constituents to obtain the preferred concentration of omeprazole in the final mixture and with an alkaline reacting, otherwise inert, pharmaceutically acceptable substance (or substances), which creates a ‘micro‑pH’ around each omeprazole particle of not less than pH = 7, preferably not less than pH = 8, when water is absorbed to the particles of the mixture or when water is added in small amounts to the mixture.”
A number of examples are given of suitable substances for that purpose. The creation of a microenvironment of omeprazole with a pH between 7 and 12 is preferred. The same result can be achieved by using “an alkaline reacting salt of omeprazole such as sodium, potassium, magnesium, calcium etc. salts of omeprazole … either alone or in combination with a conventional buffering substance as previously described”. The mixture is then formulated into pellets or tablets, the pellets or tablets comprising the cores.
The specification then deals with the sub‑coat:
“Separating layer
The omeprazole containing cores must be separated from the enteric coating polymer(s) containing free carboxyl groups, which otherwise causes degradation/discolouration of omeprazole during the coating process or during storage. The subcoating layer, in the following defined as the separating layer, also serves as a pH‑buffering zone in which hydrogen ions diffusing from the outside in towards the alkaline core can react with hydroxyl ions diffusing from the core towards the surface of the coated articles. The pH‑buffering properties of the separating layer can be further strengthened by introducing in the layer substances chosen from a group of compounds usually used in antacid formulations such as, for instance, magnesium oxide, hydroxide or carbonate, aluminium or calcium hydroxide, carbonate or silicate; composite aluminium/magnesium compounds such as, for instance A12O3.6MgO.CO2.12H2O, (Mg6A12(OH)16CO3.4H2O), MgO.A12O3. 2SiO2.nH2O or similar compounds; or other pharmaceutically acceptable pH‑buffering compounds such as, for instance the sodium, potassium, calcium, magnesium and aluminium salts of phosphoric, citric or other suitable, weak, inorganic or organic acids.
The separating layer consists of one or more water soluble or in water rapidly dissolving [sic] inert layer, optionally containing pH‑buffering compounds.”
That indicates that the sub‑coat is required to deal not only with the “diffused water of gastric juice” but also with the problem that omeprazole will degrade if an enteric coat is immediately applied to it: that problem, apparently, requires for its solution both the use of alkaline material in the core and the sub‑coat. It indicates also that the “separating layer”, or sub‑coat, must dissolve or disintegrate in water. It may be interpolated that the evidence made it clear that that is required to be so because, if the omeprazole is to be fully bioavailable (will be absorbed so as to produce the desired therapeutic affect), it must be absorbed in the small intestine. The pH of liquids in the small intestine is considerably less acidic (has a higher pH) than the gastric juice in the stomach. The enteric coat, which will remain intact in the acid environment of the stomach, will disintegrate when it reaches the small intestine; and the sub‑coat must dissolve or disintegrate too, so as to release the active ingredient as quickly as possible.
The method of applying the sub‑coat is then described. The material used for it “is chosen among the pharmaceutically acceptable, water soluble, inert compounds or polymers used for film‑coating applications”, of which a number of examples are given. The preferred thickness of the sub‑coat is stated: not less than 2 microns; preferably not less than 4 microns for pellets; preferably not less than 10 microns for tablets.
The enteric coating is the next dealt with, in terms which I need not now describe. The specification proceeds:
“Thus, the special preparation according to the invention consists of cores containing omeprazole mixed with an alkaline reacting compound or cores containing an alkaline salt of omeprazole optionally mixed with an alkaline reacting compound. The alkaline reacting compound and/or alkaline salt of the active ingredient, omeprazole, enhance the stability of omeprazole. The core suspended in water forms a solution or a suspension which has a pH, which is higher than that of a solution in which the polymer used for enteric coating is just soluble. The cores are coated with an inert reacting water soluble or in water rapidly disintegrating coating, optionally containing a pH‑buffering substance, which separates the cores from the enteric coating. Without this separating layer the resistance towards gastric juice would be too short and/or the storage stability of the dosage form would be unacceptably short. The sub‑coated dosage form is finally coated with an enteric coating rendering the dosage form insoluble in acid media, but rapidly disintegrating/dissolving in neutral to alkaline media such as, for instance the liquids present in the proximal part of the small intestine, the site where dissolution is wanted.
Final dosage form
The final dosage form is either an enteric coated tablet or in the case of enteric coated pellets, pellets dispensed in hard gelatin capsules or sachets or pellets formulated into tablets. It is essential for the long term stability during storage that the water content of the final dosage form containing omeprazole (enteric coated tablets, or pellets) is kept low, preferably not more than 1.5% by weight. As a consequence the final package containing hard gelatin capsules filled with enteric coated pellets preferably also [contains] a desiccant, which reduces the water content of the gelatin shell to a level where the water content of the enteric coated pellets filled in the capsules does not exceed 1.5% by weight.
Process
A process for the manufacturer [sic] of the oral dosage form represents a further aspect of the invention. After the forming of the cores the cores are first coated with the separating layer and then with the enteric coating layer. The coating is carried out as described above.
The preparation according to the invention is especially advantageous in reducing gastric acid secretion and/or providing a gastrointestinal cytoprotective effect. It is administered one to several times a day. The typical daily dose of the active substance varies and will depend on various factors such as the individual requirements of the patients, the mode of administration and disease. In general the daily dose will be in the range of 1‑400 mg of omeprazole. A method for the treatment of such conditions using the novel oral dosage form represents a further aspect of the invention.”
There follows a series of examples of formulations according to the invention (or integers of it), to some aspects of which it will be necessary to return. The “discussion” following the examples suggests that they demonstrate that it is possible, if an enteric coat is applied directly to the core, to achieve either acceptable resistance to gastric juice or acceptable storage stability (that is, without degradation of the omeprazole) but not both. Acceptable storage stability may be achieved by increasing the quantity of alkaline substances in the core; but if that is done then, “without the separating layer of the invention, the resistance to dissolution in acid becomes unacceptably low and much or all of the active substance will degrade already in the stomach and thus, it has no effect on the gastric acid secretion”. Additionally, it is said, the final example (a comparative test) shows that a low water content is important: a content of 2 per cent by weight resulted in the formulations being “virtually totally degraded”.
A further consistory clause follows:
“The further comparative test shows the great importance of a low water content in the preparation.
Thus in order to prepare pharmaceutical formulations of omeprazole for oral use, which exert good stability during long‑term storage as well as good stability during the residence in the stomach after administration, the preparation is made in the following way:
a) Omeprazole together with an alkaline reacting compound or compounds or an alkaline salt of omeprazole optionally mixed with alkaline reacting compounds are included in the core material.
b) The core material is subcoated with one or more inert, in water soluble or in water rapidly disintegrating layers, which separate the core material from the enteric coating. The subcoating layer may optionally contain pH‑buffering compounds.
c) The subcoated cores are coated with an acid insoluble enteric coating, optionally containing plasticizers.”
There is then a report of biopharmaceutical studies, which for the present it is unnecessary to describe, followed by the claims, which I shall set out in full:
“The claims defining the invention are as follows:
1. An oral pharmaceutical preparation in the form of a tablet or pellet containing omeprazole as the active ingredient, characterized in that it is composed of:
(A) core material containing omeprazole together with an alkaline reacting compound, or an alkaline salt of omeprazole optionally together with an alkaline reacting compound; (B) one or more inert reacting subcoating layer(s) on said core material; and (C) an outer layer, which is an enteric coating, said inert reacting subcoating layer(s) between said core material and said outer layer comprising tablet excipients which are soluble or rapidly disintegrating in water, or polymeric, water soluble, filmforming compounds, optionally containing pH‑buffering, alkaline compounds.
2. A preparation according to claim 1 wherein the sub‑coating layer comprises one or more of magnesium oxide, magnesium hydroxide or composite substance [A12O3.6MgO.CO2.12H2O or MgO.A12O3. 2SiO2.nH2O], wherein n is not an integer and less than 2.
3. A preparation according to claim 1 or 2 wherein the subcoating comprises two or more sub‑layers.
4. A preparation according to any one of claims 1 to 3 wherein the subcoating comprises hydroxypropyl methylcellulose, hydroxypropyl cellulose or polyvinylpyrrolidone.
5. A preparation according to any one of claims 1 to 4 wherein said core material comprises omeprazole and a pH‑buffering alkaline compound rendering to the microenvironment of omeprazole a pH of 7‑12.
6. A preparation according to claim 5 wherein the alkaline compound comprises one or more of magnesium oxide, hydroxide or carbonate; aluminium hydroxide; aluminium, calcium, sodium or potassium carbonate, phosphate or citrate; the composite aluminium/magnesium compounds A12O3.6MgO.CO2.12H2O or MgOA12O3. 2SiO2.nH2O, where n is not an integer and less than 2.
7. A preparation according to any one of claims 1 to 4 wherein said core material comprises the sodium, potassium, magnesium, calcium or ammonium salt or other alkaline salt of omeprazole.
8. A preparation according to any one of claims 1 to 4 wherein said core material comprises an alkaline salt of omeprazole mixed with an inert, alkaline compound.
9. A preparation according to any one of claims 1 to 8 wherein the enteric coating comprises hydroxy propyl methylcellulose phthalate, cellulose acetate phthalate, copolymerized methacrylic acid/methacrylic acid methyl ester or polyvinyl acetate phthalate, optionally containing a plasticizer.
10. A preparation according to any one of claims 1 to 9 wherein the water content of the final dosage form containing omeprazole doses not exceed 1.5% by weight.
11. A preparation according to any preceding claim, wherein said one or more subcoating layer(s) is not less than 2 microns thick.
12. A pharmaceutical preparation in the form of a capsule containing a plurality of pellets as claimed in any preceding claim.
13. A process for the preparation of an oral pharmaceutical formulation in the form of a tablet or pellet containing omeprazole, in which cores containing omeprazole mixed with an alkaline reacting compound or compounds or an alkaline salt of omeprazole optionally mixed with an alkaline reacting compound or compounds are coated with one or more inert reacting subcoating layers, whereafter the subcoated cores are further coated with an outer layer which is an enteric coating, said inert reacting subcoating layer(s) between said core material and said outer layer comprising tablet excipients which are soluble or rapidly disintegrating in water, or polymeric, water soluble, filmforming compounds, optionally containing pH‑buffering, alkaline compounds.
14. A process according to claim 13 wherein an oral pharmaceutical preparation according to any one of claims 1 to 11 is prepared.
15. An oral pharmaceutical preparation obtained by the process according to claim 13 or 14.
16. The use of a preparation according to any one of claims 1 to 12 and 15 for the manufacture of a medicament for the treatment of gastrointestinal diseases.
17. A method for the treatment of gastrointestinal disease, characterized in that a preparation or medicament according to any one of claims 1 to 12, 15 and 16, respectively, is administered to a host in the need of such treatment in a therapeutically effective amount.”
Validity: cross claim
It is convenient to deal first with the cross claim for revocation. Alphapharm claims that the patent is invalid on several grounds. The alleged invention, Alphapharm says, is not a manner of manufacture within the meaning of s 6 of the Statute of Monopolies 1624 (UK); it was not novel when compared with the art base as it existed before the priority date; it did not involve an inventive step having regard to the prior art base before the priority date; the specification lacks sufficiency, in that it does not describe the invention fully including the best method known to Astra of performing it; it is not clear, succinct or fairly based; the alleged invention is not useful; and the patent was obtained by false suggestion. Alphapharm says also that none of the claims in the patent are fairly based on the specification filed with the unamended patent. The consequence, Alphapharm says, is that the patent (following its amendment) is governed, as to validity, by the 1990 Act and not by the Patents Act 1952 (Cth) (the 1952 Act) and none of the claims of the patent are entitled to a priority date earlier than 30 May 1997. I shall consider that submission later in these reasons and shall assume, for the purpose of my consideration of the other grounds of invalidity, that it is incorrect. Astra conceded that if it were true that, following the amendment, the priority date is 30 May 1997, or later, then the patent is invalid: that must be so, if only because Losec has been on the market in Australia, and widely used here, for several years.
(a) Statutory regime
The 1952 Act, under which the patent was granted, has been repealed and replaced by the 1990 Act. However, s 233 of the 1990 Act provides:
“233 (1)Subject to this Chapter and the regulations, this Act applies in relation to a standard patent or a petty patent granted under the 1952 Act as if the patent had been granted under this Act.
…
(4)Objection cannot be taken to a patent mentioned in subsection (1), and such a patent is not invalid, so far as the invention is claimed in any claim, on any ground that would not have been available against the patent under the 1952 Act.”
The effect of that provision was described by Lockhart J (with whom Northrop J agreed and Burchett J, subject to qualifications which do not matter for present purposes, agreed generally) in NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1993) 44 FCR 239 at 253, 254:
“In my opinion the evident intent of s 233(4) is to ensure that the grounds of revocation under the 1990 Act (which, though in some cases are expressed in different terms, are essentially the same as the grounds previously available under s 100 of the 1952 Act) apply as the grounds for revocation of a 1952 Act patent; but with this important qualification, namely, that the elements of each ground of revocation under the 1990 Act apply only to the extent that they replicate in substance the elements that previously constituted a ground of revocation under the 1952 Act. Hence, if a ground of revocation under the 1990 Act omits an element which was a necessary part of a ground under the 1952 Act, the patentee has the benefit of it. On the other hand, if a ground under the 1990 Act contains an element not previously present under the 1952 Act, it cannot apply in aid of revocation of a 1952 Act patent. In short, a 1952 Act patentee is not to be worse off than he would have been if the 1952 Act had continued to operate, but he may be better off if the 1990 Act treats a former element of a ground of revocation as being no longer necessary.”
(See also Winner v Ammar Holdings Pty Ltd (1993) 41 FCR 205 at 206, 208 per Davies J).
It is, perhaps, rash to attempt to summarise yet further. The effect of the provision, and of Lockhart J’s construction of it, is, however, in my view that a 1952 Act patent may be revoked under (and only under) the 1990 Act, but only on a ground, available under the 1990 Act, which would also have been available against the patentee under the 1952 Act. Where the same ground appears in each Act, but in different terms, the 1952 Act patentee is entitled to the benefit of the more confined of them. Thus, under the 1990 Act, the 1952 Act patentee may be better off, but cannot be worse off, than previously.
(b) Obviousness; lack of inventive step
It is convenient to deal with this ground first. A great deal of evidence and argument was devoted to it and, in my view, it is not easy to discuss the Statute of Monopolies ground intelligibly except against the background of a discussion of obviousness.
The scheme of the 1990 Act, in relation to this ground, starts with s 138(1), which permits the Minister or any other person to apply to a prescribed court for an order revoking a patent. Subsection 138(3) provides that:
“After hearing the application, the court may, by order, revoke the patent, either wholly or so far as it relates to a claim, on one or more of the following grounds, but on no other ground: …
(b) that the invention is not a patentable invention; …”
Section 18(1) tells us that, for present purposes, a “patentable invention” is:
“An invention that, so far as claimed in any claim: …
(b)when compared with the prior art base as it existed before the priority date of that claim: …
(ii)involves an inventive step; …”
The next step is s 7(2), which provides:
“For the purposes of this Act, an invention is to be taken to involve an inventive step when compared with the prior art base unless the invention would have been obvious to a person skilled in the relevant art in the light of the common general knowledge as it existed in the patent area before the priority date of the relevant claim, whether that knowledge is considered separately or together with either of the kinds of information mentioned in subsection (3), each of which must be considered separately.
(3) For the purposes of subsection (2), the kinds of information are:
(a)prior art information made publicly available in a single document or through doing a single act; and
(b)prior art information made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art in the patent area would treat them as a single source of that information;
being information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood and regarded as relevant to work in the relevant art in the patent area.”
The final stage in the journey is the dictionary in Sch 1, made applicable by s 3. The “patent area” means Australia together with the continental shelf, waters above the continental shelf and air space above Australia and the continental shelf (possibly giving rise to interesting speculation as to where relevant documents might be expected to be found or relevant knowledge to exist). “Prior art base” means, for present purposes:
“(i)information in a document, being a document publicly available anywhere in the patent area; and
(ii)information made publicly available through doing an act anywhere in the patent area; and
(iii)where the invention is the subject of a standard patent or an application for a standard patent – information in a document publicly available outside the patent area; …”
“Prior art information” is information that is part of the prior art base.
The journey required by the 1952 Act is considerably shorter. Section 100 provides, so far as is relevant for present purposes:
“100 (1)A standard patent may be revoked, either wholly or in so far as it relates to any claim of the complete specification, … on one or more of the following grounds, but on no other ground: …
(e)The invention, so far as claimed in any claim of the complete specification … was obvious and did not involve an inventive step having regard to what was known or used in Australia on or before the priority date of that claim; …”
Section 233(4) of the 1990 Act requires a comparison of grounds, not of outcomes on particular facts. It is easy enough to provide a glib summary of its effect. To attempt to work out in detail whether, and to what extent, either “obviousness” ground is more confined than the other is, perhaps, to undertake a rather more daunting task. Fortunately, it is not a task which I need to undertake. Argument proceeded on the basis that that, at least, which was obvious for the purposes of 1952 Act was also obvious when tested by the 1990 Act, so that in practical terms all that was required here was to ascertain whether, in terms of the 1952 Act, the invention, so far as claimed in any claim of the complete specification appearing in the patent, was obvious and did not involve an inventive step having regard to what was known in Australia on or before the priority date.
The principles to be applied are very well established. The question to be asked was stated by Aickin J, with whom Gibbs ACJ and Stephen, Mason and Wilson JJ agreed, in Wellcome Foundation Ltd v V.R. Laboratories (Aust) Pty Ltd (1981) 148 CLR 262 at 270, as follows:
“It is as well to bear in mind that the question of obviousness involves asking the question whether the invention would have been obvious to a non‑inventive worker in the field, equipped with the common general knowledge in that particular field as at the priority date, without regard to documents in existence but not part of such common general knowledge.”
and:
“… what has to be proved by evidence in any case in which obviousness is relied upon is the state of common general knowledge in Australia.”
Equally well known is his Honour’s discussion, in Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253, of the concepts of obviousness and of common general knowledge, with particular reference to combination patents. Aickin J said this, at 292, 293:
“The notion of common general knowledge itself involves the use of that which is known or used by those in the relevant trade. It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge ...
An allegation of want of inventive step is not made out by saying you may take one or two, or twenty-one or twenty-two, prior publications and then select from them appropriate extracts or pieces of information, which will add up to the invention claimed and so demonstrate that it was obvious. So to proceed is to mistake the nature of an invention and the nature of the objection of obviousness. The question is, is the invention itself obvious, not whether a diligent searcher might find pieces from which there might have been selected the elements which make up the patent. If this were not so, there could never be a valid patent for a new combination of old integers. The proper question is not whether it would have been obvious to the hypothetical addressee who was presented with an ex post facto selection of prior specifications that elements from them could be combined to produce a new product or process. It is rather whether it would have been obvious to a non-inventive skilled worker in the field to select from a possibly very large range of publications the particular combination subsequently chosen by the opponent in the glare of hindsight and also whether it would have been obvious to that worker to select the particular combination of integers from those selected publications. In the case of a combination patent the invention will lie in the selection of integers, a process which will necessarily involve rejection of other possible integers. The prior existence of publications revealing those integers, as separate items, and other possible integers does not of itself make an alleged invention obvious. It is the selection of the integers out of, perhaps many possibilities, which must be shown to be obvious.
It is in relation to this process that the misuse of hindsight is most common. When once an idea or an object or a process or a combination, admittedly novel, has been published, it is very easy to say after perhaps months of search and study in the Patent Office and the public libraries that the integers into which the patent might be dissected could be found scattered amongst the prior documents by a person who already knew the solution to the problem and therefore knew what to look for and what to discard. But that process does not demonstrate lack of an inventive step. The opening of a safe is easy when the combination has been already provided.”
There was in this case no significant dispute as to who was properly to be regarded as the hypothetical “non‑inventive worker in the field”: that person is one who is experienced in the practical work of formulating drugs for therapeutic use. There is an obvious difficulty in applying to such a person the epithets customarily applied to the hypothetical skilled worker: “non‑inventive”, “unimaginative … with no inventive capacity” (Minnesota Mining and Manufacturing at 260 per Barwick J) or at least “not particularly imaginative” (WR Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) 25 IPR 481 at 492 (per curiam)). The evidence showed that the typical practical formulator is a highly qualified pharmaceutical chemist, whose qualifications frequently if not usually include a doctorate: a qualification usually associated with a demonstrated capacity for original research. The skilled worker for present purposes is a member of that class, though not a particularly imaginative or inventive one. In that respect, of course, this case is not unique, or even particularly novel: see Allsop Inc v Bintang Ltd (1989) 15 IPR 686 at 700 and the authorities there cited.
The question as to what in this case constitutes common general knowledge is more difficult. Alphapharm and its witnesses relied upon a number of documents as relevant to the question of obviousness: documents, particularly, dealing with the properties of omeprazole, steps taken by Astra towards the ultimate formulation described in the patent and particular aspects of the formulation, notably the use (in formulating drugs to be taken orally) of a sub‑coat. The evidence given by witnesses called by Alphapharm all proceeded on the basis that a formulator, seeking to formulate omeprazole at the priority date, would have conducted literature searches and other inquiries, perhaps including patent searches, and would by those means have found some or all of the documents relied on which would in turn have led the formulator, by a series of routine steps, to the invention claimed in the patent. It was not suggested that information contained in the documents could be taken into account if it did not form part of the common general knowledge; it was submitted, however, that the information did indeed form part of that knowledge. In Minnesota Mining and Manufacturing, shortly following the passage I have already quoted, Aickin J said, at 294, 295:
“There may be some fields of endeavour in which those who work therein study and make themselves familiar with all patent specifications as they become available for inspection in one or in many countries so that what was contained therein becomes common general knowledge in that particular trade or field of manufacture in the country in question. …
But this is not so in all fields or in all countries. There was no evidence in the present case that those working in Australia in the field of adhesives or of surgical tapes followed such a practice or that any of the specifications relied upon was part of the common general knowledge of those working in these fields in Australia.
The respondent relied upon a number of prior specifications which had been available in Australia for public inspection before the priority date as providing a basis for the argument that the invention claimed was obvious. For the reasons which I have set out above I do not regard such specifications as capable of sustaining that argument without evidence that they were part of common general knowledge at that time. There was no such evidence and accordingly it is not necessary for me to examine those specifications.”
Similarly, in WR Grace, the Full Court, in the course of dismissing an appeal from an order that a patent be revoked, said of a series of trade articles relied on by the successful petitioner (at 493):
“It is necessary, of course, for the material in the articles to have become part of the stock of the common general knowledge of the hypothetical skilled addressee … and it is not sufficient that it is simply public knowledge. It must become part of the common stock of knowledge of the hypothetical skilled addressee in relation to the art or science.”
That approach has, of course, abundant support in the authorities. So, for example, in a passage relied on by Astra, Luxmoore J said in British Acoustic Films Ltd v Nettlefold Productions (1936) 53 RPC 221 at 250:
“In my judgment it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates. A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art.”
Similarly, in Minnesota Mining and Manufacturing Barwick CJ said at 260:
“The attribution to the ‘unimaginative man with no inventive capacity’ of all that might be found by diligence in the registries of patent specifications is not only unreal and unduly restrictive of the development of new methods of manufacture, but basically it is fictional rather than real.”
And, in a very different context, Aickin J said in Graham Hart (1971) Pty Ltd v S W Hart & Co Pty Ltd (1978) 141 CLR 305 at 329:
“What the expression ‘common general knowledge’ refers to is that which is part of the ordinary equipment of all persons engaged in the relevant art, i.e. part of their general background knowledge which they put to use in the exercise of that branch of industry or manufacture.”
Thus the submission of counsel for Astra was that common general knowledge must be distinguished from knowledge which was available and more than likely would have been found by a person skilled in the art in the course of the relevant task: common general knowledge of what is in a document is not established if a practitioner says – or several practitioners say – that the document would have been found. Alphapharm on the other hand submitted that the common general knowledge of the skilled formulator in Australia included both materials which were to hand, either in the formulator’s own possession or in a library, but also material which the formulator might find by conducting research, such as computer searches, available to and used by formulators. Thus (presumably) if the evidence showed that the hypothetical, not particularly imaginative skilled formulator would, if presented with the task of formulating an oral dosage form of omeprazole, have made, as a routine step in the process of formulation, literature searches resulting in the discovery of documents containing information of which the formulator previously was unaware, then that information should be treated as part of the relevant common general knowledge even in the absence of any evidence of its general assimilation and acceptance by the formulating community. If that is the necessary consequence – as I think it is – of Alphapharm’s submission, then the submission is a bold one indeed in the light of the authorities to which I have referred and one which, in my view, it is not open to me to accept. Even if it were open, I am by no means sure, in any case, that I would accept it: it seems to me well outside the bounds of what would normally be understood by the phrase “common general knowledge” or of the statutory expression which it encapsulates, “what was known or used”.
It may not necessarily follow, however, that documents which would have been found on search, but do not form part of the common general knowledge, are simply irrelevant. Common general knowledge is, after all, the stock of knowledge on the basis of which one asks whether what is claimed to be an invention was obvious and did not involve an inventive step. It may be that to make use of the result of a routine literature search is no different in concept from making use of a series of routine experiments where common general knowledge would have suggested either to the hypothetical formulator attempting to formulate omeprazole. Before considering that proposition further as a matter of principle, however, it is desirable to place matters in context by considering some of the evidence.
(i) Aphapharm witnesses
Alphapharm called five witnesses who gave expert evidence bearing on the issue of obviousness. Dr James Steven Rowe graduated with a degree of Bachelor of Pharmacy (University of Sydney) in 1966. Later he was awarded successively the degrees of Master of Science and Doctor of Philosophy in Pharmaceutics by the University of London. Before travelling to the United Kingdom in 1971 he was employed in Sydney by two pharmaceutical companies and was engaged in the formulation and testing of various dosage forms. Between 1971 and 1976 he was employed by ER Squibb where he obtained experience in testing and formulating pharmaceutical dosage forms. After a period as a research fellow and lecturer in the School of Pharmacy, University of London, Dr Rowe became, in April 1983, a director of H R Healthcare Limited where his work involved, according to his evidence, the development of many formulations of tablets and capsules. He returned to Sydney in September 1986 and from then until August 1990 was the Technical Manager of Abbott Laboratories in Sydney. There he was responsible for new product and process development for various affiliated companies; during that period he did extensive development work on film and enteric coating. Since August 1990 Dr Rowe has been a director of a consulting company engaged in product development, formulation, stability testing and advising on matters such as regulatory affairs and marketing for pharmaceutical, veterinary and personal care industries.
It was not suggested that Dr Rowe did not fall into the relevant class of skilled formulators. It was said, however, that his evidence could not be relevant to the subject of common general knowledge in Australia as at the priority date, because he returned to Australia only after the priority date. That, I think, is taking an unduly literal view of the matter. He worked in Australia, in the relevant field, for a substantial period commencing a few months after the priority date; that, I think, qualifies him to give relevant evidence as to common general knowledge in Australia as at the priority date.
Dr Michael John Story graduated in Chemical Engineering at the University of Adelaide. His doctorate, also in Chemical Engineering, was awarded by the University of Cambridge in 1967. Between 1973 and 1976 he held a number of positions in F H Faulding & Co Ltd in Adelaide. Those positions involved considerable “hands on” formulation of pharmaceutical preparations, particularly enteric coating. It involved also the supervision of a group of formulation chemists. He was responsible for development of the formulation of capsules containing enteric coated pellets of erythromycin and capsules containing enteric coated pellets of doxycycline hyclate; he also prepared studies for the development of other products using coated pellet technology including enteric coated aspirin and sustained release theophylline. Between 1986 and 1990 Dr Story worked in the United Kingdom; from 1990 to 1996, after returning to Australia, he was again involved in pharmaceutical formulations. He is at present a consultant to the pharmaceutical industry. There is no doubt that Dr Story was, subject to one matter, within the relevant class of skilled formulators. That one matter is that Dr Story is named as sole inventor in one patent and as one of two joint inventors in three others. The earliest, a US patent with the priority date in 1986 (claimed on the basis of a British patent) postdates only by a brief period (if at all) the priority date of the patent in suit. On that footing, Astra submitted that he could not be regarded as non‑inventive. I have already referred to the difficulty of finding a precise dividing line between the imaginative and unimaginative, or the inventive and non‑inventive, in this field; but there is no doubt that Dr Story was qualified to give evidence as to common general knowledge in Australia at the priority date and as to the practice of formulators in Australia at that time.
Both Dr Rowe and Dr Story had read and considered the patent before preparing their evidence and had had drawn to their attention, by Alphapharm’s solicitors, a number of the documents said to be included in the prior art. Dr Philip Andrew Marshall was in a different position. He had not seen the patent nor had he had any documents drawn to his attention. It was not disputed that Dr Marshall fell within the relevant class of skilled formulators. He had had substantial experience in the field, particularly during employment in a number of positions with Faulding Pharmaceuticals in Adelaide between 1982 and 1991.
Dr William James Thiel is a Senior Lecturer in the Department of Pharmaceutics, Victorian College of Pharmacy, Monash University. He has for many years taught students in the formulation of pharmaceutical tablets and pellets, the coating of tablets and pellets and controlled and sustained drug release techniques. He had also, before the priority date, had involvement with industry. The first such involvement, which commenced in 1985 and concluded in 1997, involved collaboration on two projects for the controlled release delivery of veterinary pharmaceuticals. Secondly, Dr Thiel has on numerous occasions been consulted by pharmaceutical companies to assist with the solving of particular problems. He has also had considerable involvement in research in areas related to drug formulation, and he is an inventor named in two patents.
Dr John Jaye Ashley held, from 1965 to 1994, the positions of Lecturer and then Senior Lecturer in the Department of Pharmacy, University of Sydney. Formulation was among the subjects which he taught during that period. He did not, however, give evidence of any particular “hands on” formulation experience or of any experience in industry.
Plainly, in my view, the evidence of Dr Rowe, Dr Story and Dr Marshall is, of the evidence in Alphapharm’s case, of particular significance in relation to obviousness and, in dealing with the attack on validity based on obviousness, I shall concentrate on their evidence. Before doing so, however, I shall discuss briefly some of the alleged prior art referred to in the evidence. But first there is one general observation which should be made about the evidence. The case was heard on a final basis as a matter of some urgency, given the impending expiry of the compound patent. The application is dated 27 August 1988. The matter first came before the Court for directions on 23 September 1998. The trial occupied three weeks beginning on 8 March 1999. The period available for the preparation of the evidence, both on all the issues going to validity and on infringement, was not very long, and a number of affidavits were prepared and sworn either shortly before, or in some cases during, the trial. The trial itself, given the extent and complexity of the issues and the evidence, was somewhat compressed, undoubtedly in order to fit within the three weeks which were available. One matter scarcely touched upon during the trial was each party’s objections to the evidence led by the other. Lists of objections indicating grounds of objection were handed up but there was no argument about any of them; there were written and brief oral submissions, to which I shall return, about the relevance of the evidence given by two experts called by Astra, Professors Rees and Rhodes. The parties joined in urging me to deliver judgment, if possible, by 30 April. In all those circumstances, I do not propose to attempt to deal in this judgment with the detailed objections to evidence. I have, of course, read all the affidavits. The use I have made of the evidence in reaching my conclusions will, I hope, sufficiently appear from these reasons.
(ii) The documents
I shall deal in turn with a number of the prior art documents. I shall not by any means deal with all of the documents referred to in the evidence, but the expert evidence is best understood against a background knowledge of certain documents which were emphasised both in evidence and in submissions.
(A) Pilbrant and Cederberg
This is an article published in 1985 in the Scandinavian Journal of Gastroenterology, the authors of which were Dr A Pilbrant and Dr C Cederberg, entitled “Development of an oral formulation of omeprazole”. Both Dr Pilbrant and Dr Cederberg were members of the scientific and medical team within Astra dedicated to the development and formulation of omeprazole. Both gave affidavit evidence and Dr Pilbrant was cross‑examined. The article reported, among other things, on certain in vitro and limited in vivo studies of a solid dosage form of omeprazole in the form of enteric coated pellets. The tests measured, particularly, the rate of dissolution and absorption in the small intestine and the protection afforded by an enteric coat against acid in the stomach. In broad terms, it was found that omeprazole in suspension, administered with a substantial quantity of sodium bicarbonate, was satisfactorily absorbed within the small intestine and that similar bioavailability was achieved by administering enteric coated pellets to a fasting subject (or perhaps more accurately, before breakfast). Particularly, however, the article reveals a number of important aspects of omeprazole. It is “very slightly soluble in water, but is very soluble in alkaline solutions”; it degrades “very rapidly in water solutions at low pH‑values”; preformulation studies had shown that “moisture, solvents and acidic substances have a deleterious effect on the stability of omeprazole and should be avoided in pharmaceutical formulations”. Additionally, there were two principal options for the formulation of an oral solid dosage form of omeprazole: a “conventional oral dosage form from which omeprazole is released and absorbed rapidly enough to avoid degradation in the stomach” and an enteric coated dosage form; but the former of those was ruled out because the pilot bioavailability study showed that more than half of the omeprazole in that form degraded in the stomach. An enteric coated dosage form, it was said, “offers the best possibilities”. It must, however, “be perfectly coated and acid resistant, since, if any drug leaks out of the dosage form in the stomach, it is almost immediately degraded. The same is the case if an acidic medium can diffuse into the dosage form through pin‑holes or damage in the enteric‑coating”. Pilbrant and Cederberg was published in Australia before the priority date.
(B) The omeprazole salts patent
This is Australian Patent number 563842, the proprietor of which is Astra. The invention claimed is principally a series of compounds which are alkaline salts of omeprazole. The patent also claims pharmaceutical compositions containing any of the salts as the active ingredient and administration by various means including oral administration: one of the dosage forms claimed is an enteric coated tablet. The patent discloses the instability of omeprazole: particularly that “upon storage without any special precautions being taken, it is degraded at a rate which is higher than desired”. None of Alphapharm’s witnesses suggested that the omeprazole salts patent disclosed a sub‑coat. A suggestion that one of the examples in the patent did disclose a sub‑coat was put to Professor Rees. Cross‑examiner and witness were, I think, at cross purposes during at least part of the series of questions; Professor Rees denied, however, that the example disclosed a sub‑coat. There is a question, in relation to the omeprazole salts patent, of exactly what was published in Australia before the priority date of the patent in suit. The document in evidence indicates that the application in respect of the omeprazole salts patent was open for public inspection on 6 September 1984, the date of advertisement of the accepted application being 23 July 1987. Curiously, the date of the specification, appearing immediately below the claims, is 3 June 1987. It is not, therefore, entirely clear in what form the application was open for public inspection in 1984. Although in the end nothing may turn on it, I think I can and should infer (given the scheme of the 1952 Act as to the way in which applications were dealt with) that the substance of the document in evidence was published in Australia before the priority date.
(C) Shin‑Etsu H‑17
This is what is described as a technical information sheet, No. H‑17, of the Shin‑Etsu Chemical Co. It is dated March 1975 and entitled “Enteric Coating on Tablets Containing Alkaline Matter”. It was published in Australia before the priority date. It states a particular problem and proposes a solution:
“Enteric coated tablets containing alkaline matter such as ammonium chloride, lithium carbonate or sodium‑salicylate might lose the stability when storing at higher temperature, it has been some times experienced.
It has been found to be improved by putting stearic acid in the intermediate film which is considered to work as some buffer to imaginable ion‑exchange reaction between alkaline and enteric material.”
There is then set out a report of a series of experiments, comparatively testing two formulations for absorption rate in gastric fluid and disintegration time and intestinal fluid: first, two enteric coated tablets with an intermediate coat of, principally, a product known as Pharmacoat 606 and, secondly, enteric coated tablets with an undercoat of Pharmacoat 606 to which stearic acid had been added. Pharmacoat is a Shin‑Etsu brand of hydroxypropylmethylcellulose (HPMC): the evidence established that that is a form of water soluble coating, and that if stearic acid is added it becomes substantially insoluble in water.
(D) Shin‑Etsu P‑30
This is another technical information sheet of Shin‑Etsu, dated April 1980 and entitled “Stability of Methyl‑dopa Tablet Coated with Pharmacoat 606”. Despite the date of that document, it is not proved that anyone in Australia actually had it, or that it was published here, before the priority date. Particularly, it is not included in a folder of Shin‑Etsu documents which Dr Thiel kept. It was, however, referred to by Alphapharm’s witnesses. It deals with a problem apparently caused by a reaction between a drug, which was unstable under alkaline conditions, and Pharmacoat 606. The solution proposed was the addition of acidic material to the core tablet or to the coat.
(E) FMC–Aquateric case history
This is another manufacturer’s document. It dealt with a problem identified as follows:
“When film coatings comprised of enteric polymer with phthalyl groups were applied to a customer’s tablets containing alkaline drug, the functional polymer groups would solubilise on the tablet surface. That is, an alkali‑phthalate salt was formed which was acid soluble.”
The solution proposed was to “seal coat the tablets first with HPMC”. That document, however, is dated simply “1986”. There was no evidence that it was published at all, let alone in Australia, before the priority date.
(F) Röhm Pharma practical course
This document, published in 1983 (and received in Australia at least by Dr Thiel) comprises notes of a course conducted by Röhm Pharma on the coating of tablets. The notes teach, among other things, the layering of coats on a tablet, including for instance the inclusion of an “interspersion layer” beneath an enteric coat. Under the heading “Coating Agents” there was discussion of “formulation aids”, all said to have one thing in common:
“they disintegrate or dissolve within a short time on exposure to water alone, independently of their location in the alimentary canal; the enveloped drug is generally released very rapidly and it is only in exceptional cases that release is delayed even slightly. …
In developing dosage forms with delayed drug release, special attention must be directed to see that:
(1) the availability of the drug is not impaired;
(2)therapeutic blood levels are reached and maintained over the requisite period of time;
(3)release of the drug from the dosage form is assured, notwithstanding individual variations in the conditions within the digestive tract.”
(G) British patent No. 760403: the Abbott patent
This is a 1953 patent relating to improvements in or relating to enteric coatings. What it is principally about appears in the consistory clause:
“The invention consists in an enteric coating composition comprising an enteric film‑forming substance having uniformly dispersed therein a finely divided mineral solid which is inert to the film‑forming substance, the mineral solid being in amount sufficient to render satisfactory coatings substantially free from cracking and crazing upon ageing.”
However, the specification contemplates several coats:
“While the invention is described as residing in the use of a film‑forming substance having an inert mineral solid uniformly suspended therein, it should be pointed out that the invention also contemplates the use of portions of this enteric coating composition with other known enteric coatings. For example it is contemplated that a number of coats of other coating compositions may be applied to the medicament either before or after the application of a coating or film of the composition of this invention.”
And particularly:
“A slurry of the mineral solid should not be so highly alkaline as to attack the film‑forming substance itself and it is desirable that the pH of the filler not exceed about 8. The nature and characteristic of the medicament must also be considered in selecting a film‑forming substance for an enteric coating thereof. A medicament which has a highly alkaline pH may conceivably attack and weaken or destroy the film‑forming substance. By special handling it will still be possible to coat such incompatible drugs, as for example, by sub‑coating with a compatible material and then applying an outer coating of the desired enteric coating composition.”
(H) The Clymer and MacDonnell patent: US patent No. 2,540,979
This is a yet earlier patent: the application date is 24 April 1948. It also relates to an improved enteric coating for medicaments. The perceived problem was that prior enteric coatings had proved less than satisfactory, principally because material which resisted attack by gastric juice but was nevertheless soluble in intestinal fluids was to some extent soluble in gastric juice, so that the medicament, if soluble in gastric juice itself, was “largely leached out through the coating”; if, on the other hand, the enteric coat was fully resistant to attack and impermeable by the “fluids of the stomach” it became “ruptured by the agitation in the stomach, thus allowing the stomach fluids to attack the medicament”.
The solution proposed by the claimed invention was to add a wax coating either beneath or over the enteric coat. Thus, the Clymer and MacDonnell patent claimed:
“1.A new article of manufacture comprising a medicament, and a coating comprising a layer of a cellulose derivative containing free carboxyl groups substantially insoluble in the stomach fluids and soluble in the intestinal fluids, and a layer of wax, said wax layer being characterised by the fact that its integrity will be maintained in the stomach and will be lost in the intestines … .”
(iii) The evidence of Dr Rowe, Dr Story and Dr Marshall
With that by way of somewhat extended background, I can return to the expert witnesses: first, Dr Rowe. Dr Rowe described the steps which, he said, he would have taken to formulate a dosage form of omeprazole before the priority date using only the knowledge and materials that he had, or to which he would have had access, before the priority date. He was asked also to give his opinion of what he believed formulators in Australia would have done if faced with that task. His first step, he said, would have been an extensive literature search, in order to ascertain as much as he could about the physico‑chemical characteristics of the drug. The search would have included a review of textbooks, searches of various databases and manual searches of literature held by local university libraries. Additionally, he would have reviewed the technical literature made available by product manufacturers, a quantity of which he kept in his personal library. He would also have conducted – or someone would have conducted for him – patent searches. By that process he would have found, he says, each of the items which I have described (including the FMC‑Aquateric document, not proved to have been published before the priority date) and a great number of others. He would have read them all. He would have relied particularly on several of them, including Pilbrant and Cederberg, Shin‑Etsu H‑17 and Shin‑Etsu P‑30. He would then have conducted pre‑formulation studies on omeprazole.
Dr Rowe’s evidence was that he would have learnt from Pilbrant and Cederberg (or by standard laboratory testing) that omeprazole degrades rapidly in acidic solutions, is only slightly soluble in water but rapidly soluble in alkaline solutions. That would have meant that an enteric coated dosage form would have been ideal because, once it had passed through the stomach, the omeprazole would dissolve rapidly and be bioavailable. Formulators had, before the priority date, experience in enteric coating acid labile drugs (that is, drugs which degrade or decompose in an acidic environment): in this respect, to work with omeprazole, though different in detail and degree, would be similar to working with any other acid labile compound. The learning – for example in relation to the antibiotic erythromycin – was that an enteric coat could be applied directly to such a compound. The dosage form might be either an enteric coated tablet or enteric coated pellets filled into a hard gelatin capsule. Numerous enteric coating materials were available: as well as standard texts, Dr Rowe would have consulted manufacturers’ literature for the purpose of making a selection.
The next step, according to Dr Rowe, would have been to test the product for stability. A standard test would be to store two batches at a minimum of two temperatures, usually 30°C and 40°C. At appropriate time intervals, the product would be tested for content of the drug “together with appropriate physical tests” including “dissolution, disintegration, appearance, odour, hardness, friability and moisture content”. If the tests revealed diminution in potency, it would have been obvious either that the drug was unstable in the solid state on its own or that it was interacting with something in the formulation. Further tests would have been conducted; and Dr Rowe would have considered reaction with the enteric coated film, containing acidic groups, the most likely cause of the problem. The obvious answer, Dr Rowe said, would have been “to coat the core material with a water soluble film which would protect the drug from the enteric coat and also act as a protective film against moisture and oxygen, which are the common causes of drug instability”. Stability studies would also have revealed whether a low level of moisture was important to protect the drug from decomposition in storage. Knowing that the drug was most stable in an alkaline environment, Dr Rowe would have considered the addition of a basic (alkaline) compound to the core before coating. The use of a sub‑coat to improve stability was well established before the priority date: examples could be seen in manufacturers’ literature as well as general scientific literature; Dr Rowe referred particularly to Shin‑Etsu H‑17 (he referred also to the FMC‑Aquateric document and to Shin‑Etsu P‑30). He observed also that, in his opinion, each of the main features of the formulation claimed in the patent was to be found in the Abbott patent, which would have been revealed by the patent search made in the initial stages of the formulation.
Dr Rowe prepared a further affidavit in response to the evidence of Professor Rhodes, Professor Rees, Dr Pilbrant and Dr Cederberg. It is sufficient to say at present that he maintained his position, expounding some aspects of it in greater detail.
Dr Story, apparently, was given somewhat different instructions. Principally he was asked to review in detail the specification and claims of the patent, not to describe how he would have gone about the task of formulating omeprazole. He did, however, review the patent in detail and he reviewed also a number of documents to which Alphapharm’s solicitors had drawn his attention. His conclusions may (without at this stage commenting on whether they are justified by what precedes them) be quoted in full:
“182Both my initial reading of the Formulation Patent, and my further consideration of it, lead me to conclude that there is nothing new in it. In relation to individual matters described in the Formulation Patent, my view is reinforced by individual publications referred to above. When I take into account these publications in combination, there is no doubt in my mind that there is simply nothing new disclosed in the Formulation Patent, and this reinforces my view that this opinion would be shared by other formulation chemists in Australia before the Priority Date.
183.What is described in the Formulation Patent is simply a collection of known and commonly used ways of formulating an acid labile compound to provide it to its site of action in the body in an effective form and to ensure that it remains in that form over prolonged storage. These requirements were standard to formulation chemists well before the Priority Date. The need to take into account the physico‑chemical characteristics of the active compound, and the ‘problems’ encountered in developing the formulation described in the Formulation Patent, were standard issues that were routinely and successfully dealt with in the manner described in the Formulation Patent.”
In evidence in reply Dr Story described his approach to formulation (and the approach which he said he would have adopted in formulating omeprazole) in terms which closely correspond with the opinion expressed Dr Rowe. I shall return to some of the controversial details. For the present, however, it is worth noting that Dr Story’s evidence supports that of Dr Rowe about the practice of making literature searches and the importance attached by formulators to manufacturers’ literature and patents:
“To my knowledge, and based on my experience, every ‘hands on’ formulator refers to literature provided by suppliers of raw materials and excipients. Peer–reviewed papers in scientific journals do not always cover issues or particular aspects of interest to the formulator. Personally, I would always put more reliance on the information and technical data given in technical literature provided by reputable suppliers of raw materials and equipment. In my experience, the information and data provided by the suppliers has been researched, collated, and put into a technical document with the intention of providing useful hands‑on information to users of such products. … Distribution of unreliable information would compromise the supplier’s reputation. On the other hand, although I read relevant published papers, I regard them often as being of less use in preparing formulations. In many instances I treat the content with a grain of salt because they often take an academic approach rather than a practical, industrial approach.”
That brings me to the evidence of Dr Marshall. It will be recalled that he had not seen the patent. Nor did Alphapharm’s solicitors draw his attention to any particular literature. On instructions from Alphapharm’s solicitors he prepared six reports. Astra objected to the last two of the reports which, they submitted, though annexed to what was purportedly an affidavit in reply, in fact amounted to further evidence in chief. That may be so; as was the case in relation to the other objections there was no particular argument about it. No argument was put that Astra was not in a position to deal with the reports or that it would suffer any particular prejudice as a result of their admission. I have no doubt that they are properly to be accepted as evidence in Alphapharm’s case.
It is necessary to consider in some detail both the instructions given to Dr Marshall and his response to them. Dr Marshall’s initial instructions were to formulate an appropriate dosage form of omeprazole for use by adults. He was specifically informed that he might refer to the compound patent. His first report, in response to those instructions, was of a somewhat general and preliminary kind. Certainly, Dr Marshall did not proceed immediately to suggest any, let alone all, of the integers in the claims of the patent. He discussed the selection of an appropriate dosage form, a consideration of the characteristics of omeprazole, the possible use of controlled release technology, likely reference of the formulator to literature (it may be noted that Dr Marshall did not specifically refer to manufacturers’ literature) and concluded that:
“Preformulation experimentation with excipients should include the following basic steps:
1.Physical characterisation of the active ingredient – particle size distribution, polymorphism, solubilities at varying pH values and buffer systems, flow densities, compressibility etc.,
2.Challenge/stress studies under differing conditions (temperature, humidity) to evaluate solid‑state stability, degradation product profile.
3.Compatibility studies in the presence of excipients.
4.Organoleptic properties (taste, colour, appearance).”
As a possible “starting formulation” Dr Marshall suggested a tablet made by a granulation process. He added:
“Given the literature indications … that bioavailability could be unpredictable due to the acid lability of omeprazole, the formulation may not be straightforward and the physico‑chemical characteristics would need to be addressed. Similarly the product would require analytical support to fully characterise the dissolution and disintegration properties under a number of buffer conditions.”
For the purposes of his second report, Dr Marshall searched the database “MedLine” using the key words “omeprazole bioavailability pharmacokinetics”; only abstracts of articles published prior to 30 April 1996 were reviewed. That led him to, among other things, Pilbrant and Cederberg. He noted that “omeprazole has low water solubility and is chemically labile in an acid environment” and that, in formulating an oral dosage form of omeprazole, the “possibilities of dissolution rate limited absorption and pre‑absorption degradation must be kept in mind”. He concluded that consideration needed to be given to controlled release formulation and the study of prototypes by in vitro dissolution studies.
Dr Marshall was then given some further written instructions. They included the following passage:
“We note that in your second report you conclude that:
‘Consideration needs to be given to controlled release formulation and the prototypes studied by in vitro dissolution studies.’
From your telephone conversation …, we understand that:
1.by ‘controlled release formulation’ you mean an enteric coated formulation; and
2.the ‘in vitro dissolution studies’ that you refer to would include dissolution and acid resistance studies of samples of the prototype formulation that had been subjected to accelerated stability conditions.”
On that footing Dr Marshall was asked to report further on matters which would be of concern to him in preparing a prototype formulation for in vitro testing, an appropriate prototype formulation (with an overview of reasons for selecting it) and the types of in vitro testing which would be carried out. Cross‑examination of Dr Marshall elicited his opinion that “controlled release” was a category which included, but was substantially wider than, an enteric coated dosage form. The following exchange speaks for itself:
“Q.Well, I thought you were telling us, Dr Marshall, that when you wrote your report number 2 you were talking about controlled release formulation; you were using that expression to cover a variety of different possibilities?
A.That’s certainly true. But, I mean, it is quite obvious to a formulator if something is acid‑labile then an enteric coating or some sort of enteric system is going to be implicit in the formulation design.”
The task at hand is, of course, to construe the claims. The relevant rules of construction were summarised by Sheppard J in Decor Corporation Pty Ltd v Dart Industries Inc (1988) 13 IPR 385 at 400 as follows:
“(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 comprehensible 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.”
The expert witnesses called by Alphapharm, notably Dr Ashley, expressed considerable uncertainty as to the meaning which a skilled reader would attribute to a number of the expressions used in the claims. The phrases said to give rise to difficulty included “alkaline reacting compound” (claims 1 and 13), “inert reacting subcoating layer(s)” (claim 1), “pH-buffering, alkaline compounds” (claims 1 and 5), “alkaline compound” (claim 6) and “microenvironment of omeprazole” (claim 5). Though there were other concerns (for example that “comprise” appears to be used in the claims in some places to mean “include among other things” and in others to be used in an exhaustive sense) those were said to be the principal causes of doubt and ambiguity.
There is an apparent tension where witnesses maintain simultaneously the twin propositions, “we do not understand the claims” and “had we been set the task of formulating omeprazole, this is the result at which we would, or very likely would, have arrived”. The concerns expressed by the expert witnesses are not to be so lightly dismissed; but the tension does, I think, suggest that, to an extent, the experts’ complaint is really not so much that they do not understand what is claimed but that terms are used in ways which they have not previously encountered and which might be regarded as scientifically incorrect or inappropriate and that, perhaps confusingly, in some instances a variety of terms is used to denote a single concept. Thus, while all the expert witnesses (those called by Astra as well as those called by Alphapharm) were well acquainted with terms such as “alkali” and “alkaline compound”, none, I think, suggested that he had ever previously encountered the expression “alkaline reacting compound”. Dr Rowe said that he had never previously seen it, Dr Ashley said that it was unusual and Dr Thiel included it among a list of what he regarded as obscure terms some of which he had not previously encountered. There was considerable discussion of whether “reacting” added anything to “alkaline”, and if so, what it added.
Similarly, there was no lack of consensus as to what was meant by “buffering” or “pH-buffering”; but some confusion was expressed as to whether there was a difference between “alkaline reacting compound” and “pH‑buffering alkaline compound” as used, particularly, in claim 5 and also, in relation to the sub‑coating layer(s), in claim 1. Again, “inert” emerged as a well understood term but “inert reacting” as unusual at least: Dr Ashley went so far as to describe it as an oxymoron. “Microenvironment” gave rise to a slightly different issue: there was, as I understood it, no lack of agreement that it meant the immediate (and “micro” indeed) environment of the individual omeprazole particles, the controversial question being whether its pH could be measured. (The term “micro‑pH”, which does not appear in the claim but is used in the specification, was the subject, perhaps fairly, of some disapproving comment but there seemed, in the end, to be general agreement that it should be taken as a contraction of “pH of the microenvironment”).
The expert witnesses could and did assist by elucidating technical terms (it may truly be said of the patent, however, that it is liberal in its use of apparently technical terms which in fact are not terms of art), but the construction of the claims is, of course, a question of law for the Court, applying the principles summarised by Sheppard J in Decor Corporation.
Undoubtedly it would have been better had those who prepared the specification and, particularly, the claims taken greater care than they did to use consistent terminology, at least to the extent of using, upon each occasion where a particular concept was to be referred to, the same words to describe it. That would have eliminated the possibility of such questions being asked as whether a “pH‑buffering alkaline compound” (referred to in claim 5) is simply another phrase used to refer to an “alkaline reacting compound” (claim 1) or whether, on the other hand, it is a subset of “alkaline reacting compound” so that not every alkaline reacting compound may be used if the preparation is to fall within claim 5 (no doubt the “alkaline compound” of claim 6 is the “pH‑buffering alkaline compound” referred to in claim 5), and whether the “inert, alkaline compound” of claim 8 is a subset of the category “alkaline reacting compound” referred to in claim 1.
But the specification must be read as a whole and what is said about the invention in the body of it may shed light on the sense in which terms are used in the claims (Decor Corporation at 403). Particularly relevant, in my view, is what is said under the heading “Cores”:
“Omeprazole is mixed with inert, preferably water soluble, conventional pharmaceutical constituents to obtain the preferred concentration of omeprazole in the final mixture and with an alkaline reacting, otherwise inert, pharmaceutically acceptable substance (or substances), which creates a ‘micro‑pH’ around each omeprazole particle of not less than pH=7, preferably not less than pH=8, when water is absorbed to the particles of the mixture or when water is added in small amounts to the mixture. Such substances can be chosen among, but are not restricted to substances such as the sodium, potassium, calcium, magnesium and aluminium salts of phosphoric acid, carbonic acid, citric acid or other suitable weak inorganic or organic acids; substances normally used in antacid preparations such as aluminium, calcium and magnesium hydroxides; magnesium oxide or composite substances, such as A12O3.6MgO.CO2.12H2O, (Mg6A12(OH)16CO3.4H2O), MgO.A12O3. 2SiO2.nH2O or similar compounds; organic pH‑buffering substances such as trihydroxymethylaminomethane or other similar, pharmaceutically acceptable pH‑buffering substances. Creation of a microenvironment of omeprazole between pH 7 and 12 is preferred. The stabilizing, high pH‑value in the powder mixture can also be achieved by using an alkaline reacting salt of omeprazole such as the sodium, potassium, magnesium, calcium etc. salts of omeprazole, which are described in e.g. EP‑A2‑124 495, either alone or in combination with a conventional buffering substance as previously described.”
That passage, I think, casts considerable light on a number of the matters in controversy. First, however much the somewhat loose use of terminology may be regretted, I do not think there can be any serious doubt that the “alkaline reacting compound” of claim 1 is the “alkaline reacting, otherwise inert, pharmaceutically acceptable substance (or substances)” referred to in the body of the specification. Plainly, the function to be performed by the alkaline reacting compound, mixed in the core, is that of stabilising the omeprazole, which is, the specification tells us, “susceptible to degradation/transformation in acid reacting and neutral media”. As the passage quoted says, the point of adding the alkaline reacting compound is that it will create a “micro‑pH” around each omeprazole particle of not less than the stated level “when water is absorbed to the particles of the mixture or when water is added in small amounts to the mixture”. It is to provide, to put the matter in another way, an environment in which the omeprazole will not degrade.
That being so, it is not easy to see why it is not the only required characteristic of “alkaline reacting compound” that when it is mixed with water the resulting pH will be greater than seven. That is substantially the meaning given to the term by Professors Rees and Brown and, I think, by Professor Rhodes whose forthright exposition was:
“I have no difficulty with this term, nor do I think any competent formulator would. The term plainly means a substance that is capable of reacting as an alkali (i.e. a molecule with basic functional groups. such that it can act as a proton acceptor) and therefore reduce the degree of acidity of the core and may buffer the core against the decrease in pH should hydrogen ions enter the core.” (emphasis added)
It is also apparently, at least in his initial affidavit, the meaning given it by Dr Thiel. (It was also the initial reaction of Dr Story, though further reflection caused him to change his view, so as to give greater significance to the word “reacting”). The other expert witnesses expressed the view that to read the expression in that way does not give sufficient weight to the word “reacting”: thus, for instance, Dr Rowe said:
“I think the word ‘reacting’ is important, as it implies to me more than just the pH value of a solution or suspension of a compound in water. It implies that the requisite compound reacts. In the context of an ‘alkaline reacting compound’ I understand the word ‘reacting’ to mean ‘actively reacts as an alkali with an acid’. Such a reaction would normally produce a salt and water.”
It may well be that, in practical terms, most compounds within the definition preferred by Professors Rees and Brown would also have the characteristics required by Dr Rowe’s definition: but possibly not all of them. I think the passage I have quoted supports the view taken by Professors Rees and Brown; it is also, I think, supported by an earlier passage under the heading “Background of the Invention”, to part of which I have already referred:
“Omeprazole is susceptible to degradation/transformation in acid reacting and neutral media. The half‑life of omeprazole in water solutions at pH‑values less than four is shorter than ten minutes. Also at neutral pH‑values the [degradation] reaction proceeds rapidly. The stability profile is similar in the solid phase.”
The significance of that is, of course, that the term “acid reacting” media appears simply to include “water solutions at pH‑values less than four”: no doubt it was contemplated that certain water solutions at pH values greater than four might also constitute “acid reacting” media, but the important point for present purposes is that what characterises the media as acid reacting is the pH level of the water solution. It follows, I think, that the “pH‑buffering alkaline compound” of claim 5 is a subset of the “alkaline reacting compound” of claim 1: the claim 5 compound is one which will not only produce the requisite pH‑level when mixed with water but will also have a buffering effect: that is, will resist, for example, a lowering of the pH level if acid is added or, in Professor Rees’ terminology, “encroaches”.
A number of the witnesses said that there was no known way of measuring the pH of the “microenvironment” of a particle of omeprazole in a solid dosage form. I do not doubt that, strictly speaking, that is correct. Once again, however, the language of the patent is, I think, less than precise. The patent, in the passage quoted, speaks of “micro‑pH” … “when water is absorbed to the particles of the mixture or when water is added in small amounts to the mixture”. Professors Rees and Brown suggested, no doubt correctly, that the pH level of the resulting mixture could be measured and that should, I think, be taken as what the patent intends.
Ambiguities were said also to arise from the description, in claim 1, of the sub‑coat. It is described as “inert reacting” and it optionally contains pH‑buffering, alkaline compounds. There is no need to say more about the latter point: as in relation to the compound (included in the core material) referred to in claim 5, “pH‑buffering, alkaline compounds” are, I think, a subset of “alkaline reacting compounds”. The expression “inert reacting” was criticised: however, there can be little doubt, in my view, that it means, in context, that the sub‑coating layer will react neither with the material in the core nor with the enteric coat. Similarly, although yet again the looseness of language is to be regretted, I do not think that the expression “an inert, alkaline compound” in claim 8 is simply to be regarded as a contradiction in terms. What is intended may, I think, be gathered from the passage quoted from the specification: an “alkaline reacting, otherwise inert, pharmaceutically acceptable substance …”. The “alkaline compound” is the same as an “alkaline reacting compound” and it is “inert” in the sense that it will not, if mixed in the core material, react otherwise than as an alkali.
Thus, in my view, expressions whose meanings in the claim are not clear may be defined or clarified by a resort to the body of the specification (Decor Corporation at 391 per Lockhart J) so that the patent is not invalid for ambiguity. In my view, Alphapharm has not made good the ground of lack of sufficiency.
(j) Lack of utility
It was not suggested that there is any substantial difference between s 100(1)(h) of the 1952 Act and the combined effect of s 138(3)(b) and s 18(1)(c) of the 1990 Act. A patent may be revoked on the ground that the invention, so far as claimed in any claim, is not useful. To a large extent the particulars of this ground, in the amended particulars of invalidity, cover what is now familiar territory. The particulars include an assertion that ambiguity in the terms used means that a skilled addressee is not enabled to perform the invention. It is not entirely easy to see what that has to do with inutility, and in any case those matters have already been sufficiently dealt with. Apart from those matters, the particulars of inutility may be summarised broadly by saying that they all relate to various respects in which it is said that the scope of the claims is so wide that they encompass, as well as formulations which may “achieve the promises … in the specification”, formulations which will not: for instance, because the quantity of alkaline reacting compound is insufficient, because the water content is too great or because the pH level of the microenvironment of the omeprazole particles is too low.
This ground of invalidity was dealt with in brief written submissions and touched on hardly at all in oral argument. In Coopers Animal Health Australia Ltd v Western Stock Distributors Ltd (1986) 6 IPR 545 at 572 Wilcox J said:
“If a claim exceeds what is useful, it is invalid. It does not matter that no skilled worker would seek to apply the patent to that wider purpose.”
His Honour cited with approval the well known passage from the judgment of Lord Greene MR in Norton and Gregory Ltd v Jacobs (1937) 54 RPC 271 at 276, 277. A degree of caution, however, is required. The following passage from Blanco White, Patents For Inventions, 4th Ed, § 4‑408 was quoted and applied by Gummow J in Rehm at 98, 99:
“It follows from what has been said that it is often a convenient test of the utility of the invention contained in a claim to consider whether the claim includes forms of the invention which are not useful, but that this test must be applied with very great caution. The function of a claim is to delimit the monopoly given by the patent, not to give instructions for the working of the invention, and it is consequently not necessary that the claim should contain these instructions; even the body of the specification is required to contain only those instructions that the reader cannot supply for himself. It would be unreasonable to expect the claims to contain more. A distinction should accordingly be drawn between cases in which the invention claimed is not useful unless an additional feature or features be added to those claimed (the claim then being invalid), and cases where the qualifications and expedients necessary to make the article claimed work can be, and on a true construction of the claim are, left to the reader to supply for himself. Since in cases where the reader can make the thing work the courts tend wherever possible to construe claims as requiring him to do so, it is not in practice enough to ask whether the claim includes things that are not useful; it is necessary to ask also whether there is anything in the language of the claim positively pointing to some useless construction. The successful utility attacks are nearly always in cases of that sort. Examples are: where a claim specifies two alternative processes or constructions of mechanism, of which only one is useful; or the claim specifies the use of any of a group of chemical compounds, and it is not substantially true that all will work; or the claim includes a series of constructions, and only certain members of the series are useful; or more generally, the claim contains a limitation directed to a particular feature and further limitation of that same feature is needed for utility; or the feature needed for effective working is expressly made optional - as when it is added by a subsidiary claim.”
Likewise in the NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1993) 44 FCR 239 at 267, Lockhart J, with the agreement of Jenkinson J and, on this aspect of the case, also of Burchett J said:
“It was argued that where the claim is for a class of chemical substances, specified in chemical terms, there can normally be no room for a construction that would exclude any of them, however obviously useless. Accordingly, if any of them is proved to be useless for the patentee’s purposes, the claim is invalid. The duty of the patentee is to formulate his claim in such a way as to define with clarity the area of his monopoly. Counsel for the respondent argued that in the patent in suit many phosphors would satisfy the STD and e.n measurements which would not be useful for the purposes stated and that the patent does not teach any methods of preparation of phosphors, which may affect the STD measurements …
His Honour expressed the view that the specification in suit sufficiently described the invention and he approached the question of utility on the basis that an issue as to utility does not arise unless the patent is formally valid which means, amongst other things, that it sufficiently describes the invention and describes something that is in truth an invention and a manner of new manufacture. His Honour found that a skilled addressee would know which phosphors, amongst the range of known phosphors, have the necessary qualities, sufficient luminescence and appropriate visual spectrum, to make them worth testing and would appreciate the necessity for proper preparation. In view of these conclusions his Honour rejected the argument that the invention lacked utility.
In my opinion his Honour’s findings have not been shown to be incorrect and should not be disturbed.”
What particularly emerges from the cases – Coopers Animal Health is a good example – is the importance of evidence as to the lack of utility, to achieve the promise of the invention, of particular matters within the scope of the claims. Counsel for Astra pointed, rightly in my view, to a dearth of such evidence in this case. Certainly none was referred to in submissions for Alphapharm. The submissions on behalf of Alphapharm mention a passage in Dr Story’s evidence, but that passage deals only with what Dr Story considered to be unsatisfactory aspects of the examples in the patent: it is not evidence that a particular formulation, falling for example within the terms of claim 1, will not achieve the promise of the invention. Additionally, in my view, counsel for Astra were correct when they submitted that the specification does not promise that any specific criteria will be met: the “Field of the Invention” is described as follows:
“The present invention is related to a new stable pharmaceutical preparation containing omeprazole for oral use, to a method for the manufacture of such a preparation and to a method of affecting gastric acid secretion when using them.”
The specification also makes it clear that omeprazole must be protected from contact with gastric juice and must be released rapidly in the upper part of the small intestine; and that the invention provides an oral pharmaceutical preparation “in order to meet these requirements”. In that state of affairs, in my view, what Lockhart J said in Philips is equally applicable here, and the ground of inutility is not made out.
Conclusion on cross‑claim
Although the other grounds of invalidity have not been made out, the consequence of my conclusion that the ground of obviousness is established is that the cross‑claim succeeds and there should be an order revoking the patent.
Infringement
As I have heard evidence and full argument on the question of infringement, it is desirable that I should express my views about it. Because, however, much of the evidence on infringement was highly confidential, I shall do so in separate reasons which, at least for the present, will not be published except to those employed by, or advising, each party who have entered into confidentiality undertakings or are subject to orders protecting the confidentiality of certain of the evidence.
The conclusion reached in those separate reasons is that, assuming validity (that is, contrary to my conclusion on the question of obviousness), that which is threatened by Alphapharm would constitute infringement of several of the claims of the patent.
Conclusion
My conclusion on obviousness has the consequence that Alphapharm succeeds on its cross‑claim and there should be an order for revocation. Because that is so, Astra’s claim for infringement fails. I have heard no argument about costs. Alphapharm should file and serve short minutes of the orders which it considers should be made. That should be done not later than fourteen days after publication of these reasons. If the form of the orders is not agreed, then the matter can be set down, by arrangement with my associate, for any necessary argument.
I certify that the preceding two hundred and thirty-four (234) numbered paragraphs are a true copy of the Reasons for Judgment herein of the Honourable Justice Lehane. Associate:
Dated: 12 May 1999
Counsel for the First and Second Applicants: Dr J McL Emmerson QC with
Mr D M Yates SC and Ms K J HowardSolicitor for the First and Second Applicants: Minter Ellison Counsel for the Respondent: Dr A C Bennett SC with Mr S C G Burley Solicitor for the Respondent: Mallesons Stephen Jaques Date of Hearing: 8-12, 15-19, 22-26 March 1999 Date of Judgment: 12 May 1999
Key Legal Topics
Areas of Law
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Patent Law
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Intellectual Property Law
Legal Concepts
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Patent Validity
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Infringement
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Obviousness
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