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Federal Court of Australia |
Last Updated: 28 February 2006
FEDERAL COURT OF AUSTRALIA
Aktiebolaget Hässle v Alphapharm Pty Ltd
INTELLECTUAL 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
3.14
NV Philips Gloeilampenfabrieken v Mirabella International Pty
Ltd [1993] FCA 404; (1993) 44 FCR 239 applied
Winner v Ammar Holdings Pty Ltd
[1993] FCA 93; (1993) 41 FCR 205 cited
Wellcome Foundation Ltd v V.R. Laboratories (Aust)
Pty Ltd [1981] HCA 12; (1981) 148 CLR 262 applied
Minnesota Mining and Manufacturing
Co v Beiersdorf (Australia) Ltd [1980] HCA 9; (1980) 144 CLR 253 applied
WR Grace
& Co v Asahi Kasei Kogyo Kabushiki Kaisha [1993] FCA 84; (1993) 25 IPR 481
applied
Allsop Inc v Bintang Ltd [1989] FCA 297; (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] HCA 61; (1978)
141 CLR 305 cited
Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19; (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] HCA 15; (1995) 183 CLR 655 cited
Advanced Building Systems Pty Ltd v Ramset
Fasteners (Aust) Pty Ltd [1998] HCA 19; (1998) 152 ALR 604 referred to
Commissioner
of Patents v Microcell Ltd [1959] HCA 71; (1959) 102 CLR 232 referred to
May v
Higgins [1916] HCA 8; (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] HCA 65; (1968) 119 CLR 156
cited
National Research Development Corporation v Commissioner of Patents
[1959] HCA 67; (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] FCA 1065; (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] HCA 23; (1977) 180 CLR 236
distinguished
CCOM Pty Ltd v Jiejing Pty Ltd [1994] FCA 1168; (1994) 51 FCR 260
cited
Société des Usines Chimiques Rhone-Poulenc v
Commissioner of Patents [1958] HCA 27; (1958) 100 CLR 5 cited
F. Hoffman-La Roche
& Co AG v Commissioner of Patents [1971] HCA 3; (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] FCA 556; (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 cited
AKTIEBOLAGET HÄSSLE AND
ASTRA PHARMACEUTICALS PTY LIMITED v ALPHAPHARM PTY LIMITED
NG 884 OF 1998
LEHANE
J
SYDNEY
12 MAY 1999
|
AKTIEBOLAGET HÄSSLE
First Applicant |
|
|
|
ASTRA PHARMACEUTICALS PTY LIMITED
(ACN 009 682 311) Second Applicant |
|
AND:
|
ALPHAPHARM PTY LIMITED
(ACN 002 359 739) Respondent ALPHAPHARM PTY LIMITED (ACN 002 359 739) Cross Claimant AKTIEBOLAGET HÄSSLE First Cross Respondent ASTRA PHARMACEUTICALS PTY LIMITED (ACN 009 682 311) Second Cross Respondent |
|
DATE OF ORDER:
|
|
|
WHERE MADE:
|
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.
|
AKTIEBOLAGET HÄSSLE
First Applicant |
|
|
|
ASTRA PHARMACEUTICALS PTY LIMITED
(ACN 009 682 311) Second Applicant |
|
AND:
|
ALPHAPHARM PTY LIMITED
(ACN 002 359 739) Respondent ALPHAPHARM PTY LIMITED (ACN 002 359 739) Cross Claimant AKTIEBOLAGET HÄSSLE First Cross Respondent ASTRA PHARMACEUTICALS PTY LIMITED (ACN 009 682 311) Second Cross Respondent |
REASONS FOR JUDGMENT
1 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.
2 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.
3 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).
4 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
5 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.
6 It is necessary to describe the specification in considerable detail and to quote substantial portions of it.
7 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."
8 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."
9 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.
10 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."
11 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."
12 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".
13 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."
14 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.
15 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."
16 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.
17 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.
18 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."
19 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".
20 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."
21 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
22 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
23 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."
24 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] FCA 404; (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] FCA 93; (1993) 41 FCR 205 at 206, 208 per Davies J).
25 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
26 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.
27 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; ..."
28 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; ..."
29 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."
30 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; ..."
31 "Prior art information" is information that is part of the prior art base.
32 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; ..."
33 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.
34 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] HCA 12; (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."
35 Equally well known is his Honour’s discussion, in Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; (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."
36 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] FCA 84; (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] FCA 297; (1989) 15 IPR 686 at 700 and the authorities there cited.
37 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."
38 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."
39 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."
40 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."
41 And, in a very different context, Aickin J said in Graham Hart (1971) Pty Ltd v S W Hart & Co Pty Ltd [1978] HCA 61; (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."
42 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".
43 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
44 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.
45 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.
46 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.
47 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.
48 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.
49 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.
50 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
51 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
52 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
53 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
54 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."
55 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
56 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
57 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."
58 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
59 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
60 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."
61 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
62 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".
63 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
64 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.
65 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.
66 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 30deg.C and 40deg.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.
67 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.
68 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:
"182 Both 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."
69 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."
70 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.
71 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)."
72 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."
73 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.
74 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."
75 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."
76 In his third report, Dr Marshall referred to what was disclosed in Pilbrant and Cederberg (a full copy of which had been provided to him by Alphapharm’s solicitors). Given the characteristics of omeprazole, Dr Marshall suggested that it was a "candidate for controlled release (enteric coat) formulation". He proceeded to describe in some detail the possible methods of manufacturing and coating pellets. He then set out "three basic options ... as a starting point for core formulation", assuming that "the enteric-coated spheres are to be encapsulated in a gelatin capsule ...". He suggested three possible formulations of the core granules, each including sodium phosphate (tribasic) to perform the function of "pH adjustment". He added:
"Given the requirement to avoid acidic components, sodium phosphate is included to absorb moisture and keep the pH alkaline."
77 Dr Marshall proceeded to discuss various enteric coats (and methods of application of enteric coats) which might be tried and to discuss problems which might be encountered in the process. His conclusions and recommendations were summarised as follows:
"1. Literature information to April 30, 1986 on the physico-chemical and pharmaco-kinetic properties of omeprazole strongly suggests an enteric-coat formulation be required to overcome varied bioavailability.
2. It is suggested the formulation be based on enteric coating of spherical cores or granules, formulated to minimise contact with moisture, particularly at low pH values.
3. The use of alkaline excipient such as sodium phosphate is suggested to reduce omeprazole acid catalysed hydrolysis.
4. Hydroxypropylmethylcellulose phthalate (HPMCP) in grades ‘HP50’ and/or ‘HP55’ with a suitable plasticiser such as diethyl phthalate is suggested as the enteric coat."
78 Dr Marshall was then given further written instructions. He was asked to assume three successive "scenarios" and to report on possible causes of them, on further tests which might be required as a result and on steps which might be taken in developing the formulations. The three scenarios were these:
"1. Scenario A
Assume that pellets manufactured according to each of your formulations show unsatisfactory acid resistance at manufacture.
2. Scenario B
Assume that pellets manufactured according to each of your formulations appear satisfactory upon physical examination at manufacture, but discolour after storage for seven days at 40oC/75% RH.
3. Scenario C
Assume that pellets manufactured according to each of your formulations appear discoloured upon physical examination at manufacture."
79 Dr Marshall suggested four possible causes of scenario A: that the coat was too thin, that the characteristics of the coat were unsatisfactory, that insufficient time had been allowed for the coat to age and, fourthly, "Interaction between the Core and Film/Coat". The most likely cause was, Dr Marshall thought, a combination of the first two. It is worth, however, noting what he said about the fourth possible cause:
"On stability there may be migration of water molecules within the core to the interface. In the alkaline micro-environment at the interface partial neutralisation of the film could occur resulting in a ‘leaky’ coat and thus allowing acid to penetrate and effect degradation. This could perhaps be overcome by the use of an additional layer of ‘sealant’ such as ethylcellulose to act as a barrier between the core and enteric coat."
80 There were three possible causes of scenario B: moisture in the core, interaction between core and coat and decomposition of residual methanol. That last was regarded as the least likely cause, and one which could be eliminated by a simple test. Dr Marshall did not say which of the first two causes was the more likely but repeated his comments as to the mechanism by which the problem might occur and as to a possible solution. The possible causes of scenario C were moisture content in the core and, again, interaction between the core and the coating solution. If the problem were interaction between core and coat and if the interaction were between the alkaline core and the methanol in the coating solution, a possible solution was to change the coating solvent or modify the pH of the core. Again, and additionally, Dr Marshall suggested an "additional intermediate layer", as before.
81 Dr Marshall was then asked to say why he suggested ethylcellulose for use in the possible additional layer and to specify any alternative materials which might be used. Those instructions provoked some interesting comments. First:
"The rationale for application of a sealant layer is largely learned from the readily available literature on sugar coating of tablets where the application of sub-coats and sealants is common knowledge and detailed in reference texts. The effect is essentially to provide a ‘sandwich’ of layers."
Secondly:
"The technique of ‘sealing’ has historically been applied to the process of tablet and granule sugar coating and is common practice to those skilled in the art. A sealing coat is applied directly to the tablet or pill for the purpose of providing a moisture barrier by separating the tablet ingredients (e.g. the drug or active ingredient) and water. An additional benefit is the strengthening the tablet for further processing, transport, storage etc.
Historically, sealing coats usually consisted of alcoholic solutions of shellac or shellac with a quantity of povidone, although other sealants such as: cellulose acetate phthalate, hydroxypropylmethyl cellulose (HPMC) and zein applied as solutions in organic solvents have been used. Note that because these polymers also have enteric properties, care must be taken not to apply more coating than is required."
82 After discussing purposes for which sub-coating had been used as "the actual start of the sugar coating process" and of methods of coating, Dr Marshall gave this explanation for his choice of ethyl cellulose:
"Ethyl cellulose is practically insoluble in water because of its high degree of substitution. Assuming the discolouration is facilitated by the interaction between the omeprazole in the granule and the aqueous coating solution the aqueous insoluble property of the ethyl cellulose sealant would presumably provide a sufficient moisture barrier during aqueous enteric film coating."
83 Dr Marshall suggested that the evaluation of other sealants should not be excluded: including shellac, polyvinylpyrrolidone, HPMC and hydroxypropylcellulose (HPC).
84 Finally, Dr Marshall was asked to say what he would do if his formulation showed unsatisfactory bioavailability. He responded in a sixth (and final) report. He listed as the possible causes "unsatisfactory acid resistance", "acid resistance satisfactory but in vivo dissolution too slow at pH5.5" (approximately the level encountered in the small intestine) and "the application of the ethyl cellulose sealant layer". In relation to the third cause, he identified two possibilities: the ethyl cellulose coat was too thick or ethyl cellulose was an inappropriate selection of polymer. He concluded with the following recommendation:
"1. Reduce level of ethyl cellulose.
2. If unsuccessful use alternative polymer sealant:
• Ethylcellulose/hydroxypropylmethyl cellulose dispersion
• Shellac
• Gelatin/acacia
The objective is to produce a ‘leaky’ coat of the ethylcellulose layer to allow water penetration/diffusion in the gastrointestinal tract with resultant core disintegration and omeprazole dissolution."
85 Astra submitted that Dr Marshall’s evidence should not be regarded as particularly helpful to Alphapharm. Though a skilled practitioner in the relevant field, he did not in fact arrive at the solution disclosed in the patent and he came as close as he did only because he was prompted or "nudged" in the right direction. Criticisms were made also of the evidence of Dr Rowe and Dr Story: for example, that they showed (it was said) a tendency to engage in advocacy; that their evidence was based on an illegitimate use of hindsight (a criticism not available, of course, against Dr Marshall); and in certain respects, particularly their opinion as to the kinds of literature searches which would be made and the use which might be made of the results, unrealistic. For the present, I merely record those submissions; I shall return to them after discussing the evidence given on behalf of Astra.
(iv) The Astra team evidence: Dr Pilbrant and Dr Cederberg
86 The evidence of Dr Pilbrant and Dr Cederberg, particularly the former, dealt in detail with the process, within Astra, leading to the development of the formulation claimed in the patent. Dr Pilbrant gave evidence of the work of an Astra team, of which he was a member, known as the Omeprazole Project Group, the purpose of whose activity was to bring omeprazole to the market. The development of an oral dosage form began in 1980. It was discovered that omeprazole had a low solubility in water and was highly unstable, being sensitive to acid conditions, water, solvents, high temperature and light. Acid-sensitive compounds were not unknown, but "the acid sensitivity of omeprazole proved to be particularly problematic". Particularly, the degradation products were highly coloured. Because omeprazole was known to be sensitive to acids and moisture it occurred to the Project Group to try to protect it during manufacture by adding an alkaline substance; to protect the compound against the acid of the stomach they considered it probably useful to try enteric coated pellets (an oil formulation had been tried previously, but found unsatisfactory). Dissolution tests in vitro were made, with results which were not particularly good; but bioavailability in humans could only be ascertained by in vivo studies. Those studies were made. These confirmed poor bioavailability results with enteric coated pellets. Improvements to the enteric coat were considered: particularly, ways to make the coat less permeable. A number of possibilities were tried between April and November 1981. On 10 December 1981 a "brainstorming" meeting was held. A range of possibilities was proposed, including a further investigation of salts, two possibilities for the development of omeprazole tablets (a buffered, uncoated tablet and a "rapidly dissolving core containing omeprazole and an alkaline reacting compound or an alkaline salt of omeprazole, press coated with a neutral coating and then enteric coated – in other words, a subcoated and enteric coated tablet") and various other investigations and tests of pellets for enteric coating, one aspect of which was "studying the possibility of using a subcoat". Dr Pilbrant’s comment about the position reached in December 1981 was:
"The range of ideas suggested reflected the fact that we could see no clear way forward, and there was no way that we could predict that any of the possibilities which had been suggested would solve the problems we had with omeprazole."
87 It had been noticed in in vitro testing of enteric coated formulations that they initially showed gastric resistance but that, at some point during immersion, the enteric coat on some of the samples disappeared. Whether that happened or not appeared to depend upon the amount of alkaline reacting compound in the cores. That suggested that "something unusual might be happening with the enteric coat": some water might be penetrating to the core, there dissolving some of the alkaline material, the alkaline solution then attacking the enteric coat from within. A possible solution was to increase the thickness of the enteric coat; but that might affect bioavailability. The other possible solution that occurred to the team was the introduction of a sub-coat. However, whereas a water insoluble sub-coat might have impeded the dissolution of omeprazole, a water soluble sub-coat might not have prevented water permeation. Because the team believed that they could not afford to reduce bioavailability, they tried a water soluble sub-coat. Further experiments resulted, by March 1982, in a sub-coated pellet, tests of which for degradation, acid resistance and dissolution proved "promising". Work with tablets so far had produced less promising results. According to Dr Pilbrant:
"The position at May 1982 was that, despite two years of work using a considerable part of the company’s pharmaceutical development resources, we still had no functioning Phase III dosage form of omeprazole [i.e. a dosage form for use in the third and final phase of clinical trials, required to obtain regulatory approval to market the drug]. The difficulties encountered made the research management consider other alternatives to omeprazole to be investigated. Other compounds were indeed eventually tested."
88 But Dr Pilbrant believed that, with further work, they could develop a functional formulation. Early in 1983 a formulation, substantially the same as that which was ultimately marketed, was arrived at and could be subjected to long term stability studies: "It was not until we had the results of the long term stability studies in 1985 that we could be sure the invention did solve the problems".
89 Dr Pilbrant commented that the evidence of the Alphapharm witnesses indicated that none of them had ever worked on omeprazole, none appreciated its complexities and none had given an example of a drug which had the characteristics of omeprazole; further, none had given evidence that he had worked on, or thought of, a formulation similar to that disclosed in the patent at any time, before or since publication of the specification.
90 On this aspect of the case, Dr Cederberg’s evidence, I think, takes matters little further: his evidence concerned the series of clinical trials with which he was particularly concerned. His summary was:
"In summary, the development of the formulation involved a very long process of developing ideas and testing those ideas. My role was to conduct trials in humans to see if the various proposed formulations actually worked in the body. It was simply not possible to predict whether a particular formulation would work on the basis of studies conducted in the laboratory. It was only when I could give the results of the trials to the formulation team that we could be sure that a formulation worked. In this way, the trials were integral to the development of the formulation. There were many trials conducted over a period of almost four years. It is impossible to estimate the time and effort devoted to this project by me and by the other members of my team. Of course, the team of formulators and analytical chemists led by Dr Pilbrant were also dedicated solely to this project."
91 Before passing to the expert evidence, it should be said in passing that, in general terms, the evidence of Dr Pilbrant and Dr Cederberg was clearly admissible: Wellcome Foundation at 287 per Aickin J; see also his Honour’s discussion at 280, 281.
(v) The Astra experts
92 Two of the expert witnesses called by Astra, Professor Rees and Professor Rhodes, live and work overseas, and have always done so. It is, therefore, highly unlikely – though perhaps not theoretically impossible – that they could give evidence as to common general knowledge in Australia. At all events, it was not suggested that their evidence is relevant to that question. Alphapharm suggests that, that being so, logically they can say nothing of relevance as to obviousness, since the necessary starting point is common general knowledge in Australia. In my view, however, that submission should not be accepted. If appropriately qualified (as they plainly are) they can express opinions as to matters relating to the formulation claimed in the patent which will assist the Court in deciding the question whether, having regard to the state of common general knowledge in Australia, what is claimed was obvious or did not involve an inventive step.
93 Professor Rees has recently retired from the University of Bath where, since 1981, he has been successively Professor of Pharmaceutics and Professor of Pharmacy Practice. Between 1984 and 1987 he was also Head of the School of Pharmacy and Pharmacology. He is the author, or joint author, of a very large number of scientific publications including several on various aspects of formulation. He has been a member of several learned societies and of numerous academic, professional and public bodies. He has had experience in industry: between 1969 and 1973 he worked in the pharmaceutical research and development department at the headquarters of Sandoz AG in Switzerland where he undertook studies of the polymer film coating of solid dosage forms; between 1978 and 1981 he directed the International Division Development Centre of Abbott Laboratories in the United Kingdom. The Centre undertook formulation, process and analytical development work for Abbott, including projects relating to coated tablets. One of these, Professor Rees said, related to the formulation of enteric coated tablets of the acid labile and alkaline drug, erythromycin. There is no doubt that Professor Rees is very highly qualified and eminent in his field. He also is experienced in giving expert evidence; particularly, he has previously given such evidence for Astra, in proceedings relating to corresponding patents both in Israel and in the European Patent Office. In the Israeli proceedings he prepared a joint statement with Professor Rhodes, a copy of which was tendered by Alphapharm: with some verbal changes, a good deal of what appears in Professor Rees’ affidavit on the validity issues is to be found also in the joint Israeli statement. That is a matter to which counsel for Alphapharm referred in submissions, as going to the weight to be attributed to Professor Rees’ evidence. I do not regard that by itself as a matter of any particular significance. It was also submitted that Professor Rees took the role of an advocate. I do not think, however, that he did so, at least in any inappropriate sense of the term. Undoubtedly he has come to know Astra, and particularly its omeprazole products and patents, very well and I think it is also clear that he has a degree of admiration for the achievement of the Astra team in arriving at the formulation claimed in the patent. But that, in my view, is all.
94 What follows is by no means a complete summary of a very long and detailed affidavit: I shall simply note some of Professor Rees’ principal points. Omeprazole was a new compound which, as it turned out, posed an unusual variety of challenges to the formulator. No witness had given evidence of having ever, previously or since, had to formulate a compound presenting a similar combination of challenges. At the outset, the formulator would have no reason to suppose that a simple enteric coated dosage form would not suffice. Enteric coats had been successfully applied directly to a number of acid labile drugs; in the absence of "free" water (which would as a matter of course be substantially eliminated), and given the chemical characteristics of modern enteric coats, there was no reason in theory, and none which had emerged in practice, to expect a reaction between coat and core. Because of the substantially "dry" methods used to apply enteric coats, degradation during manufacture would not be expected. Nor would it be expected that gastric juice would diffuse through a properly applied enteric coat so as to react with the core material. Given those considerations, discolouration would not be expected; if it appeared, Professor Rees would first suspect the solvents used in the preparation of the cores or in the coating, and would have adjusted the types or quantities of solvents; he would also have studied the conditions under which the coat was applied. He would have considered any gastric resistance problem to be attributable to deficiencies in the enteric coat and would have sought to improve the coat – for instance by making the coat thicker or by varying the choice of components. Having discovered that none of these attempted solutions solved either problem, he would have considered that "one attractive approach aimed at avoiding both of the problems would have been to vary the composition of the core material", by adding alkaline material. That, however, he would have found, would have led him between Scylla and Charybdis: if one added sufficient alkaline material to solve the discolouration problem, the gastric resistance problem was exacerbated; if the amount were reduced so as to solve that problem, then discolouration (indicating degradation, if only slight degradation) occurred. That was demonstrated by the examples in the patent. He would not have expected a sub-coat to solve the problems. A water insoluble sub-coat would have impeded bioavailability; a water soluble sub-coat would not have dealt with the gastric resistance problem, because:
"If any moisture should penetrate the enteric film during residence in the stomach then the subcoat might swell and, in doing so, ‘blow off’ the enteric coat, so that the whole dose would be lost by rapid degradation in gastric acid. Even without swelling, it is likely that there would be loss of adhesion of the enteric coat, leading to detachment of the enteric film and resulting, again, in the rapid and total loss of the drug."
Thus:
"The success of a water soluble subcoat, far from being predictable in advance, is quite unexpected. Indeed, even with the benefit of hindsight and after much deliberation, I can only formulate hypotheses as to why such a subcoat might be effective, and it would require a programme of experimental studies to establish the veracity of those hypotheses."
95 Professor Rees then dealt with a number of the prior publications, none of which, in his opinion, taught or would suggest the patent’s solution to the problems posed by omeprazole. He discussed some of the opinions expressed by the Alphapharm witnesses. He concluded as follows:
"391. I find it impossible to reason how the route to the formulation of the invention could have followed the kind of straightforward progression which Alphapharm’s witnesses (except for Dr Marshall) believe, with the benefit of hindsight, that they would have accomplished. On the other hand, Dr Marshall apparently considered the formulation requirements without knowing the nature of the formulation which had been patented. Dr Marshall recognised that he would have been faced with numerous uncertainties which would have taken him down various blind alleys as I have suggested above; such deviations would have incurred considerable wasted time and effort in experimental work.
392. As I mentioned in my introduction, and as I believe to be demonstrated by the explanations I have given, the ‘inventive step’ of the patent might better be characterised as an ‘inventive journey’. But this expression, referring to the multiplicity of steps or leaps involved, should not be taken to imply that the route could have been mapped in advance. There was a maze of possibilities and choices which lay between the prior art and the claimed invention, in which the competent formulator could have wandered indefinitely. Nonetheless, I will attempt to summarise the matter succinctly:
393. The prior art in relation to omeprazole suggested that a satisfactory drug delivery system could be prepared by applying a conventional enteric coating film directly to an omeprazole core containing alkaline material. There was no expectation of any problems arising with this formulation in practice.
394. The invention involved the discovery of unexpected and conflicting problems, as well as the complex task of tracing their causes to unexpected sources.
395. The invention provided a means of overcoming these conflicting problems by an unusual combination of features, which was far from being the obvious solution to try and, indeed, bearing in mind the problem of permeation by water or gastric juice, was a combination which would not have been considered as a possible solution.
396. One of the beauties of the invention is that it provides an unexpected but simple solution to the complicated formulation problems presented by this troublesome drug, ensuring stability and adequate gastric resistance without prejudicing bioavailability."
96 Professor Rhodes is Professor of Applied Pharmaceutical Studies at the University of Rhode Island. He has held that position since 1975. He is a joint editor of leading texts and author, or joint author, of a great number of publications. He has conducted extensive research on the design and evaluation of drug delivery and systems. He has acted as a consultant to pharmaceutical companies. He is a member of the Committee of Revision of the United States Pharmacopoeia and has served on two subcommittees of that committee, dealing respectively with dissolution and bioavailability and with stability and distribution. As I have mentioned, Professor Rhodes gave evidence, in collaboration with Professor Rees, in the Israeli infringement proceedings. In connection with those proceedings he visited Astra’s facilities in Sweden:
"While at the Astra facility, I reviewed data pertinent to the development of the Astra formulation the subject of the patent. This information, which concerned the stability of omeprazole, was given to me by Astra personnel as background. After reading this material, I formed the firm opinion that had I been in charge of the development of the omeprazole product to be marketed, I would not have found the solution taught by the patent to the stability problems posed by omeprazole. I remember thinking that, had I been faced with these problems, I would have tried radically different approaches to solving them."
97 Professor Rhodes describes the distinction between "research based" companies, like Astra, which develop new chemical entities, and "generic" companies (such as Alphapharm) which, once a patent on a drug substance has expired, produce generic versions. In order to obtain regulatory approval to market a new drug, the developer needs to conduct toxicological and pharmacological tests for safety and efficacy; such studies are not usually required to obtain approval, later, of a generic version. Similarly, a research-based company working on the formulation of a new drug does not have access to published information about it: it must, therefore, conduct extensive, pioneering studies of the physico-chemical and biological properties of the drug, which affect its formulation. Those are not difficulties faced by generic manufacturers.
98 After discussing in general terms the issues of stability and bioavailability, Professor Rhodes proceeds to a discussion of the particular difficulties posed by omeprazole, with which he deals in terms which are not different in substance from the opinion expressed by Professors Rees. Particularly, he expresses the view that the cause of the twin problems with the directly enteric coated formulations, degradation and lack of gastric resistance, would at the priority date have been by no means clear:
"Thus, when it became apparent that the formulation had the problems I have referred to, one might have considered the cause(s) of the problems to have been one or more of the following: the drug, drug impurities, core excipient, excipient impurities, organic solvents, water, solvent impurities, or the choice of coating materials (e.g. film formers (polymers), monomers or initiators, plasticisers or other additives, and impurities). These problems could have been exacerbated by any one or more of the following: process conditions (such as temperature, wetness, humidity, process duration, spray conditions, drying methods and conditions), or storage conditions (i.e. temperature, humidity and light)."
99 Obvious changes which might have improved gastric resistance might well have been expected adversely to affect bioavailability: because at pH values below 9 omeprazole has a relatively low solubility, it is important that the entire surface of the core be exposed as rapidly as possible to the intestinal juices (as soon as the dosage form passes to the intestine) so that the drug can dissolve rapidly and completely. Professor Rhodes would not have thought that a water soluble sub-coat would work:
"First, I would have rejected the idea of using a sub-coat which is water soluble or rapidly disintegrating in water on the ground that such a coat was unnecessary, because the enteric coat, to all practical intents and purposes, would be impervious to water. Even if the enteric coat were permeable, using a sub-coat which contained functional groups capable of interacting with water would merely act as a ‘sink’ for water, attracting water into the dosage form. The enteric coat might then ‘blow off’ while the product was still in the stomach. ...
The teachings of the patent present a brilliant solution to uniquely difficult stability problems. The concept of using a water soluble sub-coat under an enteric film coat together with an alkaline core is not, as far as I am aware, used commercially for other products available on the US market. This is a very rare type of formulation designed in response to a difficult stability challenge."
100 Professor Rhodes then discusses the evidence given by the experts called by Alphapharm, other than Dr Marshall. He discusses also some of the literature relied on, particularly the manufacturers’ literature which he regards, to summarise rather boldly and broadly, as teaching different solutions to different problems and not, therefore, likely to suggest to the competent formulator the solution described in the patent to the particular problems of omeprazole. Particularly, Professor Rhodes disagrees with the following thesis which he described as a common thread running through the opinions expressed by Drs Rowe, Ashley, Thiel and Story:
"The patent contains no truly inventive step. There was nothing novel or non-obvious about the invention in the patent. The obvious answer to the problem of the formulation of omeprazole was that described in the patent. The formulation problems associated with omeprazole were routine. In 1986, there already existed reliable, public literature directly pertinent to the particular formulation challenges presented by omeprazole."
101 Professor Rhodes then sets out four options which might have been considered as solutions to the problems, all entirely different from the solution arrived at by Astra, which might have been adopted either separately or in combination. A formulator would not know at the outset whether any of them, or any combination of them, would actually work. Certainly, the ultimately successful formulation "could not reasonably have been predicted as the solution to all of the problems". Even today, many formulations are not, Professor Rhodes says, readily amenable to a standard, entirely rational approach; that was even more the case in 1986:
"Contrary to the picture painted in [the Alphapharm experts’ affidavits], the invention was not merely a logical progression from problem to solution. Clearly, the development of the invention must have relied upon inspiration, intuition and a lot of hard work.
Even today, we do not know exactly how the invention works. This confirms my view that the discovery that this formulation solved all the problems associated with omeprazole was a truly unexpected and surprising one."
102 Professor Brown was, between 1969 and 1988, lecturer and senior lecturer in Pharmaceutics in the University of Sydney; since 1992 he has been Professor of Pharmaceutics. Between 1988 and 1992 he was Medical and Technical Director of 3M Pharmaceuticals. In that position he was responsible for such matters as laboratory product development, clinical research, medical affairs and quality assurance for new and marketed products. During his employment, 3M Pharmaceuticals was extensively involved in the development of controlled release preparations, among other research and development activities. Professor Brown also draws the distinction between "innovator" and "generic" companies and says (there is no dispute about this) that in 1986 a good deal of generic formulation, but no formulation of new drugs, was carried on in Australia. Professor Brown doubts that a formulator in 1986 would have found all the documents relied on by Alphapharm’s witnesses. Nor, in his opinion, similarly to Professor Rhodes, was an enteric coated dosage form the only choice. Other options were available. If an enteric coated form were chosen, and if problems such as those described in the patent were found to exist, then it was by no means clear that the problem would be solved by adding alkaline material to the core and including a sub-coat. Particularly, it was not known that enteric coats might be incompatible with alkaline core ingredients; and if degradation occurred, it would have been thought likely to be caused by the presence of free water rather than by a reaction between a dry core and an enteric coat.
"In the pharmaceutical context there are numerous examples of acids and bases remaining together and not reacting whilst in a dry state, but which then react upon the addition of water. Specific examples include effervescent aspirin (such as Aspro Clear), antacids (such as Alka Seltzer tablets) and effervescent vitamin preparations (such as Berocca)."
103 Professor Brown comments at length on the assumptions made, and conclusions reached, by the Alphapharm witnesses; he also comments, to similar effect as Professors Rees and Rhodes, on a number of the "prior art documents".
(vi) Discussion
104 "It is trite law that a ‘scintilla of inventiveness’ is sufficient and that ‘no smallness or simplicity will prevent a patent being good’ ... ." (Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19; (1977) 137 CLR 228 at 249). Meyers Taylor is authority also for the proposition, perhaps equally trite, that "subsequent analysis of the invention – ‘the dissection of the invention’ – is not often helpful in resolving the question of obviousness" (at 242). Astra placed some reliance on the former of those propositions; but it is not, I think, one which assists much in this case. There is hardly room, on the evidence, for a finding that there is, in the claims of the patent, a scintilla of invention. The competing possibilities are that there was a very significant inventive step and that there was no inventive step at all. The evidence also leaves no room for doubt that formulators working in Australia before the priority date knew that a compound which tended to degrade in acid or neutral media might be stabilised by the addition of a substance, an aqueous solution of which had an alkaline pH; equally they knew about enteric coats; and they knew of the existence, properties and some uses of coats made of substances such as ethylcellulose and HPMC. That, however, does not advance matters far, because the question is, was the claimed combination obvious? And I think there is a real difficulty in this case, as I have already indicated, about the extent of relevant common general knowledge outside the boundaries of the three general areas to which I have referred.
105 No doubt I may take it that the competent formulator would have had to hand a number of the major pharmaceutical textbooks which were referred to, would have had a good working knowledge of their contents and would have been well able to make full use of them as tools of their trade. But what of patents? It may well be – but there is no evidence of it - that competent formulators would be aware of a number of important patents relevant to their profession. Dr Story’s evidence was to the effect that patents were often mines of useful and practical information. But no witness gave evidence that at the priority date he knew, as part of his general background knowledge, anything taught by, for example, the Abbott patent or the Clymer and MacDonnell patent. And what of manufacturer’s literature? Here there was a distinct divergence between those witnesses whose experience was primarily academic and those who had primarily been engaged in industry. The former (Dr Thiel was an exception) tended to dismiss manufacturers’ literature as of lesser quality and utility than peer reviewed writings; Dr Ashley had not heard of Shin-Etsu (it is not clear whether he knew of FMC) and Professor Brown knew neither of Shin-Etsu nor of FMC. On the other hand, Dr Story knew the manufacturers well, was accustomed to receiving their literature and had a quantity of it to hand; that was true also of Dr Rowe and of Dr Thiel. But it does not of course follow that what was is in a particular item of a manufacturer’s literature, though that item may have been held in a library readily accessible to a particular formulator, formed part of the common general knowledge of formulators in Australia before the priority date. Dr Thiel had Shin-Etsu H-17 in a folder of Shin-Etsu literature, but there was no evidence that what was in it had, before the priority date, entered the stock of common general knowledge.
106 The matter may be approached from a somewhat different direction. Dr Ashley gave evidence that:
"The physical separation of incompatible substances was a well-known tool of formulators before the Priority Date. It would have been obvious to me and to the skilled formulator that this interaction could be prevented by physical separation of the omeprazole from the enteric coat by use of an inert subcoat between the omeprazole-containing core and the enteric coating layer. Before the Priority Date this was a known use of coating materials."
Dr Ashley also said that "[the] potential for interaction between the acidic enteric coat and the acid labile omeprazole would have been apparent to me, and to any skilled formulator, before the Priority Date". Dr Thiel put the same point even more strongly:
"The potential for a basic drug (e.g. omeprazole) to interact with an enteric polymer film is discussed in [the Röhm Pharma course notes, a similar, later (April 1986) set of course notes and Shin-Etsu H-17]. Each of these references discusses the potential for a reaction between a basic drug and an enteric film and recommends the use of an intermediate film to isolate the drug-containing core from the enteric film coating. I would expect an Australian undergraduate pharmacy student as at the Priority Date to appreciate that such an interaction could occur."
107 If that is so, it may not be unfair to comment that a large scientific team at Astra spent prodigally both time and resources in stumbling towards, and finally upon, what should have been an Australian undergraduate’s first thought. But, more importantly, why should it have been thought that the core and the enteric coat were incompatible? No one gave evidence that he had previously, or since, encountered such a problem; there was no evidence of any product manufactured or marketed, before the Priority Date, in the making of which such a problem had had to be dealt with; there was evidence that other drugs which were both acid labile and alkaline (particularly erythromycin) had been successfully, and directly, enteric coated; each of the Alphapharm witnesses who gave evidence of the approach he would have followed in formulating omeprazole would have first tried a directly enteric coated formulation and (as senior counsel for Astra pointed out) Dr Marshall had no hesitation in applying an enteric coat directly to a core containing a significant quantity of a highly alkaline excipient; and, as the witnesses called by Astra said, there was a perfectly sound scientific explanation: in summary, that interaction should not occur in the absence of any significant quantity of free water.
108 I shall return to the question of the relevance of certain of the documents, including those relied on by Dr Thiel in the passage I have quoted. For the present, however, it is worth noting that Shin-Etsu H-17 refers to a loss of stability of enteric coated tablets containing alkaline matter "when storing at higher temperature", that problem being alleviated by "putting stearic acid in the intermediate film": the examples given suggest that (water soluble) Pharmacoat 606 (HPMC) does not by any means solve the problem if no stearic acid is added. Certainly it is true that the Röhm Pharma documents teach the use of an insulating coat if there is an "interaction on drugs coming into direct contact with the lacquer [enteric] coating". However, it does not suggest that such a reaction might be expected in the case of a drug having the characteristics of omeprazole or of such a drug mixed with an "alkaline reacting compound"; and the particular "insulating layer" suggested is one which comprises a Röhm Pharma product which itself is an enteric coating material which has free carboxylic acid groups.
109 In short, the strength of Astra’s case on obviousness may be summarised in this way. The combination ultimately found to work was by no means obvious to a highly qualified team within Astra but, on the contrary, was the unexpected outcome of a great deal of experimentation and "brainstorming". Secondly, though it became apparent early in the process that an enteric coated dosage form was likely to be appropriate, omeprazole presented difficulties in the formulation of such a dosage form, which no other drug, sharing any of its characteristics, had previously presented; and the problem had several possible causes. Thirdly, if the hypothesis that poor acid resistance was due to the leaching of liquid through the enteric coat, then a water soluble sub-coat was an unlikely solution. Fourthly, the particular combination arrived at had never been used in the manufacture of any marketed drug.
110 Certainly, considered at the commencement of a hypothetical attempt, immediately before the priority date, to formulate omeprazole, the combination claimed in the patent was not obvious. The question is whether the hypothetical, not particularly imaginative skilled formulator, equipped with common general knowledge and embarking on the task at that time, would be likely to have arrived at the combination by taking routine steps which such a formulator would take for the purpose of formulating a drug. The test is whether the hypothetical addressee, faced with the same problem, would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not: Wellcome Foundation at 286. In my view, each of the expert witnesses sought conscientiously to fulfil the proper role of such a witness. Thus, for instance, I accept the general descriptions given by Dr Story and Dr Rowe of the way in which they would go about the formulation of a new drug. Nor do I see any reason to doubt the evidence of Dr Story, Dr Rowe and Dr Thiel about the importance of the role played by manufacturers’ literature or the evidence of Dr Story and Dr Rowe about the significance, to formulators in Australia, of patent searches. That was evidence of factual matters within the knowledge and experience of the witnesses and which no one, with experience of the practice of formulators in Australia, was called to contradict.
111 Submissions were made by Astra concerning aspects of the evidence of witnesses called by Alphapharm which, it was said, ought to suggest caution in evaluating their evidence and, in particular instances where that evidence conflicted with evidence given by witnesses called by Astra, to require a preference for the latter. Certainly there are in the evidence some mistakes and inaccuracies, which may be attributable, in part, to shortness of time, and, in some instances, to a degree of carelessness. For example, Dr Story said in his initial affidavit, and repeated in his affidavit in reply, that the use of an alkaline compound to stabilise omeprazole had been suggested in Pilbrant and Cederberg, but it is not. Similarly, in commenting on the specification, Dr Story suggested – incorrectly, as he conceded in cross-examination – that the specification mentioned the use of sodium, aluminium and potassium oxides or hydroxides as buffers. The extent to which Dr Rowe would actually at the outset have read much of the material to which he referred was qualified, and narrowed, by his evidence in cross-examination; and in his initial affidavit he plainly misunderstood the extent to which, according to Pilbrant and Cederberg, omeprazole would be soluble at the pH levels found in the small intestine. Some inaccuracies were found in Dr Thiel’s list of documents which he had, or could have had access to, as at 30 April 1986. Indeed, Dr Story and Dr Rowe also placed some reliance on the FMC Aquateric document which, though dated 1986, was not proved to have been published before 30 April.
112 What is important, however, is the steps which the hypothetical formulator would have taken and where those steps would have led. I have no difficulty with the proposition that a formulator asked, in April 1986, to formulate omeprazole would have done a literature search at least in order to discover what learning there was about omeprazole itself and its characteristics. Clearly enough such a search would have uncovered the compound patent, the omeprazole salts patent and Pilbrant and Cederberg. Pilbrant and Cederberg both indicated a number of the characteristics of omeprazole and pointed the formulator in a particular direction: an enteric coated dosage form seemed most likely to be the best possibility. That being so, there can be no surprise that the witnesses would have first tried directly enteric coating an omeprazole core, or that the particular "controlled release" dosage form that Dr Marshall would have tried was an enteric coated one. I accept that that is what the hypothetical formulator would have done. I accept also that the process which would then have followed would have been a complex, detailed and laborious one, involving a good deal of trial and error, dead ends and the retracing of steps; and it is easy to fall into the twin traps of hindsight and over simplification. But there is no reason to doubt that the hypothetical formulator would, having tried the first simple formulation, have done substantially what Astra did: submitted it to appropriate tests, including tests for stability on manufacture and on storage and for acid resistance.
113 It is difficult then to resist the force of Dr Story’s observation that it is irrational to suppose that the hypothetical formulator’s tests would have produced results substantially different from those of Astra’s tests. The Astra tests showed immediate discolouration, on coating, of a core to which no "alkaline reacting" substance had been added; there was no suggestion that the core was formulated or made in any other than a well known way, that is a way in which the hypothetical skilled formulator might well have chosen. Dr Rowe’s evidence (and similarly to Dr Ashley’s) was that there was nothing unusual about the use of an alkaline substance to stabilise an acid labile drug; and, as I have mentioned, Dr Marshall included an alkali in his formulation of the cores.
114 If that also is accepted, as I think it should be, as a step which the hypothetical formulator was likely to take, there is no reason to suppose that further testing would not have identified the "Scylla and Charybdis" identified by the Astra tests: either inadequate stability on storage or inadequate gastric resistance, depending on the quantity and character of the alkaline material included in the core. Whether a formulator would have concluded that either or both of the problems was due to an interaction between the enteric coat and alkaline material in the core was a matter of great controversy between the parties and between the expert witnesses. There can be no doubt that the twin problems would have been unexpected: so much is common ground. But whereas Professors Rhodes and Rees, particularly, strongly expressed the view that such an interaction was so contrary to experience and to well understood science that the formulator would have thought of other causes and would therefore have pursued solutions other than the one which Astra found, Dr Story and Dr Rowe (and Dr Ashley and Dr Thiel as well) expressed the view that a formulator would have suspected interaction between core and enteric coat as a likely cause of what was seen to be happening.
115 It must be borne in mind that the cause of the gastric resistance problem suggested by the patent, "diffusion" of "water of [sic] gastric juice" was hypothesis, not established fact. In judging whether the interposition of a water soluble sub-coat involved an inventive step, what the hypothetical formulator would have thought, or surmised, is of greater significance than Astra’s hypotheses. The experts called by Alphapharm all gave evidence that they would have regarded the problem as resulting, not from permeation of water or acid through a properly applied and intact enteric coat, but because the enteric coat was undermined by interaction, which they would have taken to be occurring, between coat and core.
116 To a considerable extent that proposition relied on the use that the witnesses said they would have made of the manufacturers’ literature and, to a lesser extent, earlier patents. But I find nothing improbable in their assertions that, once problems were identified resulting from applying an enteric coat directly to the core, the formulator would have consulted manufacturers’ literature and would have found, if not FMC Aquateric, then at least the Röhm Pharma course notes (1983) and Shin-Etsu H-17. It is true that Shin-Etsu H-17 deals with a somewhat different situation in which "imaginable ion exchange" might occur and suggests that, whereas in that situation a water-soluble sub-coat (HPMC) will not work, a water insoluble sub-coat will (and, of course, a water insoluble sub-coat was likely to present serious difficulties with a drug that was only slightly soluble and had to be released in the upper part of the small intestine). And the particular sub-coat suggested by the Röhm Pharma document is a second enteric coat: one, therefore, hardly likely to solve a problem of interaction between an alkaline core and enteric coat.
117 More generally, there is apparent force in the comment made in submissions for Astra that, as at the priority date, references to sub-coats included for the purpose of separating incompatible substances were few and scattered among some obscure publications. Nevertheless, if one accepts, as I do, that it was generally known by Australian formulators that there was commonly to be found in manufacturers’ literature information relevant to the use of their products in formulations, and that the particular publications were likely to have been found by the formulator as a result of routine steps taken in the course of the formulation process, the force of the comment is significantly weakened; and if one accepts also, as again I do, the evidence, particularly of Dr Story, that one does not look at documents only for the purpose of finding precise directions but that one reads them for more general ideas, and that one would first try the simpler solutions rather than the more complex, then it is not difficult finally to accept that the element of a water soluble sub-coat, in combination with the other elements (a core of omeprazole with which alkaline substance has been mixed and an enteric coat) of the combination, might have been arrived at by the skilled, though not particularly imaginative, formulator.
118 To look at the matter in that way is not, I think, to ask the irrelevant question, were the individual integers of the combination obvious, rather than the relevant question, was the combination obvious. That which is obvious, or non-inventive, in this context is that at which the skilled, but not particularly imaginative or inventive, formulator might have arrived by following the routine processes of the craft. Of course, the particular process would not have been a simple or quick one and numerous possibilities might have been tried. But, given Pilbrant and Cederberg and all the expert evidence, an enteric coated dosage form was the highly likely starting point (as it was for Astra) and, to a large extent, the likelihood that particular subsequent steps would be taken must depend on the firmness with which the view was maintained that the selected starting point was appropriate. The evidence of the formulators suggests, and Astra’s experience confirms, that that view was likely to have been maintained with considerable firmness.
119 I am fortified in that way of viewing the matter by the evidence of Dr Marshall. Astra took comfort of a number of aspects of his evidence: that he accepted that the task formulating omeprazole was likely to be a difficult and complex one; that he did not arrive at the precise combination of the patent; and (as it was submitted) that the instructions he was given from time to time directed him along a path towards the combination. I have already described his evidence in some detail. Of course, the exercise undertaken by Dr Marshall was not an actual formulation of a substance which he had but a theoretical or hypothetical one, and that presented difficulties and (as he commented) frustrations. It was conducted in 1998 not 1986, though it was not suggested that that fact particularly affected the value of his evidence as he was effectively blinkered (I do not think that it is of any consequence that he obtained his copy of Pilbrant and Cederberg from Alphapharm’s solicitors: he found the abstract by his own researches). But, despite the limitations of the exercise, several aspects of his report are striking. He, like all the other witnesses, thought that an enteric coated dosage form was an appropriate. He moved quickly to that position following his initial general comments about the formulation process and about sustained and controlled release; I do not doubt that it was his own independent idea to opt for an enteric coat, not merely the product of a suggestion to him by someone else. His formulation of the core included, apparently as a matter of course calling for no particular comment, a strongly alkaline substance (as I have mentioned, he thought it probable that he could successfully apply an enteric coat directly to that core). When presented with scenarios, which had to take the place of actual tests but were, I think, a reasonable reflection of the Astra experience, one of the things which he thought might be occurring was an interaction between core and coat and one of the steps which he suggested was the incorporation of a sub-coat, initially of (water insoluble) ethylcellulose. Perhaps the question he was then asked, "why ethylcellulose?", was a "nudge" but, more importantly, when asked to consider what he would do if tests showed poor bioavailability, he suggested changes to the sub-coat. Certainly, his preferred (theoretical) solution was a "leaky" sub-coat comprising a mixture of ethylcellulose and HPMC; but HPMC was among a number of alternative sub-coating materials which, he suggested, would be considered.
120 Cumulatively and allowing as best I can for the insidious effects of hindsight, the evidence persuades me that the combination claimed in claim 1 of the patent did not, having regard to common general knowledge at the priority date, involve an inventive step. That being so, the same conclusion must apply equally, I think, in relation to each of the claims (certainly there was no suggestion that any of them might be considered independently in this context). The consequence is that, on the ground of obviousness, Alphapharm succeeds on its cross-claim.
121 Before proceeding to the topic of novelty, I should mention that, in its amended particulars of invalidity, Alphapharm relied on "admissions made in the specification and the Original Specification". The alleged admissions comprise, principally at least, a number of references to prior art, and to matters that were known, in the specification of the unamended patent and removed by the amendment. But, whatever importance those references may have elsewhere, they have in my view little significance here. Their origin is in the British patent, from which the patent in suit derived its priority date. They cannot, I think, be taken as admissions as to common general knowledge in Australia, and certainly not as establishing that any particular matter formed part of that body of knowledge.
(c) Novelty
122 It was common ground that because the 1990 Act provides a broader test for determining the content of the relevant prior art, the 1952 Act provided the test to be applied. Section 100(1)(g) of the 1952 Act provides:
"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: ...
(g) that the invention, so far as claimed in any claim of the complete specification ..., was not novel in Australia on the priority date of that claim."
123 There was no dispute that, in general terms, the test to be applied is the "reverse infringement test", that is, "whether the alleged anticipation would, if the patent were valid, constitute an infringement" (Meyers Taylor at 235: see also General Tire & Rubber Co v Firestone Tire & Rubber Co Ltd [1972] RPC 457 at 485, 486). If a paper anticipation is to deprive a patent of novelty, it must disclose each essential integer of the invention, though it may do so if it substitutes "mechanical equivalents" for any inessential integers (as to the use of that term, see Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 at 527, 528 per Gummow J and his Honour’s discussion of the concept in Prestige Group (Australia) Pty Ltd v Dart Industries Inc (1990) 26 FCR 197 at 208, 209. The alleged anticipation is taken to be read by a skilled addressee. After discussing in some detail the English authorities on the extent to which a literal disclosure is required, Gummow J said in Nicaro at 531:
"It follows from the English authorities as they have been applied in Australia that, whilst Hill v Evans does not require a literal disclosure and something less may suffice, and whilst an alleged paper anticipation is to be treated as read by a skilled addressee, a disclosure will fall short of an anticipation by description of an effective means by which the combination claimed in the patent in suit might be produced, if what is required of the skilled addressee is the exercise of any inventive ingenuity and the taking of any inventive step."
124 It is important, however, to note that his Honour continued at 531, 532:
"Any references in this context to workshop improvements or variations should not be understood as importing into this field of novelty concepts of obviousness. There may be room for disagreement upon the English authorities as to what degree of activity by the skilled addressee may be called for in respect of an alleged anticipation for it still to suffice to destroy novelty. In my view, the way in which the English authorities have been treated by the High Court supports the position as stated by Lord Reid in [Van der Lely NV v Bamfords Ltd [1963] RPC 61 at 71, 72]. It is also to be borne in mind that the notional addressee of the alleged anticipation is a skilled addressee with common general knowledge of the art. But his Lordship was not saying that an alleged anticipation of a combination claim, which did not include an integer thereof, nevertheless would constitute an effective disclosure if what was required of a skilled addressee to produce that claimed combination was the taking of an obvious and non-inventive step by way of workshop improvement."
The same point was made by Sundberg J in MJA Scientifics International Pty Ltd v SC Johnson & Son Pty Ltd (Federal Court of Australia, 24 July 1998, unreported) at 18:
"Where the alleged anticipation does not disclose all the essential integers of the patent in suit, the fact that the skilled addressee could come from the alleged anticipation to the patent in suit without the exercise of inventive ingenuity in the light of common general knowledge does not establish lack of novelty."
125 It was submitted on behalf of Alphapharm that it was unnecessary, in order to establish lack of novelty, that a prior publication refer to omeprazole: "the skilled reader would simply regard omeprazole as ‘compound A’; that is, an acid labile compound which when stabilised with an alkaline and put into an enteric coated core needed to be manufactured with a separating layer between the core and the enteric coating." (There may be an element of circularity in that proposition). Thus, any acid labile compound was to be regarded as a mechanical equivalent of an inessential integer. Alphapharm relied on the circumstance that Astra is the proprietor of Australian Patent No. 603568, the priority date of which is the same as that of the patent in suit, for "Coated oral formulations of acid labile compounds" (the acid labile patent). The claims and specifications of the two patents are strikingly similar. But I do not think it is as simple as that. Omeprazole, on the evidence, is not simply an acid labile compound. It has several other significant characteristics as well. And, in any event, the patent in suit is specifically directed to a formulation of omeprazole: it would be a startling conclusion indeed, given the terms of the claims, that anything would infringe the patent which was not a formulation of omeprazole.
126 It is sufficient to consider the list of prior publications on which, in final submissions, Alphapharm placed reliance.
127 Pilbrant and Cederberg. Plainly, in my view, this article is not an anticipation. I do not think that, on a fair reading, it discloses the addition to the core of an alkaline reacting substance. Certainly it does not disclose any sub-coat, and beyond question that is an essential integer of claim 1.
128 The omeprazole salts patent. This was an anticipation only if it is to be read as conveying to the skilled addressee the idea of a water soluble sub-coat. One of the claims of the patent is for an enteric coated tablet. To the untutored lawyer, the example to which the claim refers does not look like a sub-coated tablet: there is a tablet core to which an enteric coat is directly applied. The core, however, comprises omeprazole magnesium salt, lactose, methylcellulose, polyvinylpyrrolidone cross-linked, magnesium stearate, and distilled water. The evidence relied upon by Alphapharm for its suggestion that that core includes a sub-coat, or its mechanical equivalent, occurred only in the cross-examination of Professor Rees: the suggestion being that the polyvinylpyrrolidone cross-linked might form a "matrix with a water soluble material which would enclose the product", a matrix which would rapidly disintegrate in water. I do not think, however, that the passages in Professor Rees’ cross-examination referred to can properly be taken as a concession that polyvinylpyrrolidone cross-linked, mixed in the core, performs the same function as the water soluble sub-coat in the invention claimed in the patent. Whether a "matrix" might be formed was "quantity dependent"; the quantities given in the example were insufficient; and the magnesium stearate in the mixture was hydrophobic.
129 The specification of the omeprazole salts patent also includes the following:
"Soft gelatine capsules may be prepared with capsules containing a mixture of the active compound or compounds of the invention, vegetable oil, fat, or other suitable vehicle for soft gelatine capsules. Soft gelatine capsules are preferably enteric coated as described above. Hard gelatine capsules may contain enteric-coated granules of the active compound. Hard gelatine capsules may also contain the active compound in combination with a solid powdered carrier e.g. lactose, saccharose, sorbitol, mannitol, potato starch ...; the hard gelatine capsules are preferably enteric coated as described above."
130 Alphapharm relied on evidence of Dr Rolf Oscar Jörgen Lindquist, an analytical chemist employed by Astra, in which he accepted that a hard gelatin capsule is soluble in water. I do not think, however, that it is open to me to find, simply on the basis of that evidence, that the disclosure in that context of the use of a hard gelatin capsule preferably enteric coated (and containing a mixture incorporating the active compound) points with sufficient clarity to the three integers of the invention claimed in the patent in suit. It is not insignificant that none of the expert witnesses suggested that it did. Perhaps that is not surprising: the patent (in this respect narrower in its claims than the unamended patent) claims only a dosage form "in the form of a tablet or pellet".
131 Shin-Etsu H-17. This document discloses a solution for a problem said to arise by way of interaction between a tablet core containing alkaline matter and an enteric coat "when storing at higher temperature". What the document discloses is that, in those circumstances, a water soluble sub-coat (Pharmacoat 606) will not work; stearic acid should be added (resulting in the sub-coat losing its solubility in water). A tablet prepared in accordance with the teaching of this document would not infringe the patent; the document is not an anticipation.
132 FMC–Aquateric. This document teaches substantially the process claimed in the patent as to a sub-coat (of HPMC) beneath an enteric coat, applied to "a customer’s tablets containing alkaline drug". The document, however, was not proved to have been published in Australia before the priority date.
133 Röhm Pharma (1983). What this document relevantly teaches is summed up in the following paragraph:
"An insulating coat against penetrating water, formed from Eudragit L solution in isopropyl alcohol/acetone, is desirable when the subsequent processes involve the use of the aqueous dispersion Eudragit L 30D. This insulating coat may frequently be dispensed with on using rapid drying application processes. Other insulating coats may be necessary if there is any interaction on drugs coming into direct contact with the lacquer coating. An enteric lacquer is intended to form a non-porous sealing layer which is largely stable to gastric juice and to mechanical stress."
134 But whatever it teaches, it says nothing about the stabilising of omeprazole (or any acid labile drug) by mixing an alkaline reacting compound in the core or by using an alkaline salt of the active drug. It is not an anticipation.
135 The Abbott patent. I do not think that this patent amounts to an anticipation. It is principally about a claimed method of improving enteric coating material. The specification says this:
"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."
136 That, no doubt, teaches the use of a sub-coat. But it does not, apparently, teach the use of a water soluble sub-coat.
137 I was referred, however, to an earlier passage in the specification:
"The film-forming substance should be one which will disintegrate or dissolve in a pH range between about 6 and 8. The lower limit of this range is desirable because the coating will then disintegrate higher up in the small intestine where the medicament may be more effectively absorbed."
138 But the specification is there speaking of the enteric coat, in my view, not a sub-coat. There may be an implication, perhaps, that any sub-coat must necessarily be water soluble, but it is not said. In any event, even if it teaches the use of a sub-coat in the case of a "highly alkaline" medicament which is to be enteric coated, it does not teach the first integer of claim 1 of the patent.
139 The Clymer and MacDonnell patent. This patent taught that enteric coats of kinds known in 1948 had proved unsatisfactory for use directly on medicaments which were soluble in stomach fluids, since they were permeable by stomach fluids unless applied so thickly as to prevent release of the medicament where it ought to be released, in the intestine. The coat being permeable, the fluids were "thus enabled to leach out or extract the medicament variously to a greater or less extent depending upon the conditions existing in the stomach at the time of ingestion, the period of retention in the stomach and the solubility of the medication in the stomach juices".
140 The suggested solution was the application of a wax coating either over the enteric coat or between the core and the enteric coat. The former of those possibilities is, of course, irrelevant for present purposes. The wax coating, whether an outer coat or a sub-coat, was to be such "that its integrity will be maintained in the stomach and will be lost in the intestines" (Professor Rhodes gave vigorous evidence to the effect that this was substantially impossible). However that may be, what is certain is that, once again, this document does not teach the first integer of claim 1. For that reason it, also, is not in my view an anticipation.
141 Those being the documents relied on by Alphapharm in relation to lack of novelty, that ground of attack on the validity of the patent fails.
(d) Manner of manufacture
142 Once again, the effect of transitional provisions is that the relevant test is that provided in the 1952 Act:
"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: ...
(d) that the invention, so far as claimed in any claim of the complete specification ..., is not an invention within the meaning of this Act; ..."
143 "Invention" is defined in s 6:
" ‘invention’ means any manner of new manufacture the subject of letters patent and grant of privilege within section 6 of the Statute of Monopolies, and includes an alleged invention."
144 Alphapharm submitted that there is no material difference between the test under the 1952 Act and the corresponding test under s 18 of the 1990 Act. It is by no means clear, however, that that is right. In the course of distinguishing NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1995] HCA 15; (1995) 183 CLR 655, the majority of the High Court in Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd [1998] HCA 19; (1998) 152 ALR 604 at 614, 615, said this:
"In that case, revocation was sought under s 138(3)(b) of the 1990 Act. This is significantly different in structure from s 100 of the 1952 statute. The grounds of revocation in s 138(3) of the 1990 Act do not distinguish obviousness and novelty as the 1952 Act does by creating particular grounds to which the special qualification in s 100(2) applies. Rather, s 138(3)(b) of the 1990 Act, by incorporating the definitions of invention in s 18(1) and of patentable invention in Sch 1 of that Act, imports the elements which are found separately in s 100(1) of the 1952 Act. Again, the ‘prior art base’ specified in s 18 is a concept not found in the 1952 Act and is defined in Sch 1 as including information in a publicly available document."
For reasons which will appear, this question need not be pursued further.
145 Alphapharm relied particularly on a number of statements in Commissioner of Patents v Microcell Ltd [1959] HCA 71; (1959) 102 CLR 232: for instance (at 247) "... the mere discovery of a new use of a particular known product is not what is meant by invention within the meaning of the Patents Acts ..."; (also at 247) "once a substance is known, its methods of production ascertained, its characteristics and its constituents well defined, you cannot patent the use of that for a purpose which was hitherto unknown"; and (at 249) "But it is not an inventive idea for which a monopoly can be claimed to take a substance which is known and used for the making of various articles, and to make out of it an article for which its known properties make it suitable, although it has not in fact been used to make that article before". Alphapharm relied also on the proposition, as stated by Griffith CJ in May v Higgins [1916] HCA 8; (1916) 21 CLR 119 at 121, that "a combination is not an invention unless the combination is substantially a new thing". I was referred also to a number of authorities in which May had been cited, for instance Fallshaw Holdings Pty Ltd v Flexello Castors and Wheels Plc (1993) 26 IPR 565 and Sami S Svendsen Inc v Independent Products Canada Ltd [1968] HCA 65; (1968) 119 CLR 156. It is important to recognise, however, that both those cases concerned lack of subject matter, not manner of manufacture; and it is important also to heed the warning in National Research Development Corporation v Commissioner of Patents [1959] HCA 67; (1959) 102 CLR 252 at 262:
"But, as the Microcell Case emphasizes, it must always be remembered how much is wrapped up in the ‘nothing but’. Lord Buckmaster did not use the words without explanation: - ‘... when once a substance is known,’ he said, ‘its methods of production ascertained, its characteristics and its constituents well defined, you cannot patent the use of that for a purpose which was hitherto unknown’ ... And why? Because in the postulated state of knowledge the new purpose is no more than analogous to the purposes for which the utility of the substance is already known, and therefore your suggestion of the new purpose lacks the quality of inventiveness: ... . Unless invention is found in some new method of using the material or some new adaptation of it so as to serve the new purpose, no valid patent can be granted ... . If, however, the new use that is proposed consists in taking advantage of a hitherto unknown or unsuspected property of the material, the situation is not that to which Lord Buckmaster's language refers. In that case there may be invention in the suggestion that the substance may be used to serve the new purpose; and then, provided that a practical method of so using it is disclosed and that the process comes within the concept of patent law ultimately traceable to the use in the Statute of Monopolies of the words ‘manner of manufacture’, all the elements of a patentable invention are present ... . It is not necessary that in addition the proposed method should itself be novel or involve any inventive step ..."
146 Alphapharm relied on a series of statements of prior art in the unamended patent for the proposition that its specification incorporates an admission that each was known at the priority date. As to some of the integers, or aspects of them, that may not be beyond argument. Let it be assumed, however, that each separate integer of the claimed invention was known. It by no means follows that this case is "in that category of cases, considered in Philips, where the lack of an inventive step appears on the face of the specification" (Advanced Building Systems at 616). I do not think it is possible to hold, in this case, that a lack of inventiveness in the combination is apparent on the face of the specification (or was apparent on the face of the specification of the unamended patent); indeed, Alphapharm’s submissions appear to assume that the route to a finding of lack of inventiveness on the face of the specification is via (among other things) the evidence of what was known to skilled formulators in Australia at the priority date and the methods by which such formulators practised their art. It was submitted for Astra that, under the 1952 Act, Advanced Building Systems should be taken as excluding from consideration under "manner of manufacture" anything to do with the concept of "invention", that being a matter exclusively for the ground of obviousness. In view of the conclusion to which I have come, that argument does not require consideration here.
147 Two additional arguments were put by Alphapharm on the question of manner of manufacture. One was that, within the terms of s 6 of the Statute of Monopolies, the existence of the patent was "contrary to the law [or] mischievous to the State, by raising prices of commodities at home or hurt of trade, or generally inconvenient". This is not, I think, the occasion for a consideration of the part that such a principle plays in the modern law. The evidence on which Alphapharm relied was that going to the extent of public funds expended each year on Losec under the National Health Act 1953 (Cth). A continuation of the monopoly would necessarily result, it was said, in a continuation of expenditure at that level. Confidential evidence was given as to the likely effect on Commonwealth expenditure of removal of the monopoly. But, on any view of the matter, the evidence does not go far enough. A patent grants a monopoly over whatever falls within its claims. That necessarily, to that extent, eliminates the possibility of competition and whatever effect competition might have had on the price of the patented product. In any case, once the compound patent expires, Alphapharm, and any other generic drug manufacturer, will be free to market formulations of omeprazole which (assuming the validity of the patent) do not infringe. The evidence does not in my view go so far as to establish that there is only one formulation – that claimed in the patent – which will work. Indeed, Alphapharm claims that its own product does not infringe.
148 Finally, Alphapharm submitted that so far as the patent makes a claim for a method of treatment of the human body, it is invalid. Heerey J concluded in Bristol-Myers Squibb Company v FH Faulding & Co Ltd (1998) 41 IPR 467 that claims to a method of treating the human body did not constitute patentable subject matter; his Honour, in so holding, preferred the views of Sheppard J in Anaesthetic Supplies Pty Ltd v Rescare Ltd [1994] FCA 1065; (1994) 50 FCR 1 to those of Lockhart and Wilcox JJ. The majority judgment in Advanced Building Systems, in the course of considering "the doctrinal content of para (d)" mentioned, as a manner of new manufacture which might be regarded as "contrary to the Law" or "generally inconvenient" within s 6 of the Statute of Monopolies, "the classification of certain methods of treatment of the human body as an inappropriate subject for grants under the Act" (at 614). Again, however, it is unnecessary for me to enter this territory. Claim 17 alone is for a method of treatment of the human body. If the patent were otherwise valid, Alphapharm would obtain no apparent benefit from the revocation of claim 17 alone. That, no doubt, explains why no extended argument was directed to it. If, on the other hand, I am right in thinking that the patent should be entirely revoked, it is unnecessary to consider the separate issue relating solely to claim 17.
(e) Amendment
149 Two quite separate submissions were made about the amendment of the patent. One was that its effect was that the priority date of the patent is not 30 April 1986 but 30 May 1997. The second was that the patent should be revoked because leave to make the amendment was obtained by fraud, false suggestion or misrepresentation. I shall deal with that second submission in the next section of these reasons.
150 The former of the two submissions is based on s 114(1) of the 1990 Act. It provides:
"Where a claim of a complete specification claims matter that was in substance disclosed as a result of amending the specification, the priority date of the claim must be determined under the regulations."
151 Regulation 3.14 of the Patents Regulations 1991 (Cth) provides:
"If subsection 114(1) of the Act ... applies to a claim of a specification, the priority date of the claim is: ...
(b) ... the date of filing of the statement of proposed amendments that resulted in the disclosure referred to in subsection 114(1) of the Act."
152 Those provisions of the 1990 Act and the Regulations apply to the patent by reason of s 233(1) of the 1990 Act. To the extent that those provisions define the priority date, subs (4) does not (nor does any other provision) require reference to the 1952 Act.
153 Section 114 requires a comparison of the claims of the unamended patent and the claims following the amendment. It is common ground that the significant amendments, for present purposes, are those made to claim 1. The effect of the amendments appears in the following composite version of claim 1; words appearing in bold were added by the amendment and words appearing in square brackets were omitted:
"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 [the alkaline reacting] 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."
154 Thus, the claim was narrowed to limit the preparation claimed to one "in the form of a tablet or pellet" and the expression "said core material" replaced "the alkaline reacting core". Corresponding changes were made to claims 5, 7 and 8. For example, a composite version of claim 5 (adopting the same conventions) is:
"5. A preparation according to any one of claims 1 to 4 wherein said [the alkaline] core material comprises omeprazole and pH-buffering alkaline compound rendering to the micro-environment of omeprazole a pH of 7-12."
155 Alphapharm’s submission was straightforward. The claim of the unamended patent required the core to be alkaline reacting; though the amended claims continue to require that the core material contain omeprazole together with an alkaline reacting compound (or an alkaline salt of omeprazole optionally together with an alkaline reacting compound) they do not require that the core be alkaline reacting. Thus, the effect of the amendment is that the claims are wider than previously. Astra submits that the amendment amounts merely to "tidying up" and does not affect the width of the claims.
156 A number of references to "alkaline reacting cores" or "alkaline cores" have been omitted from the body of the specification. The most significant of the changes occurs fairly early in the background to the invention, as described in the unamended patent. Once again, I shall set out the relevant passage using the same conventions to indicate amendments:
"It has been found that in order to enhance the storage stability, the cores which contain omeprazole [must] should also contain alkaline reacting constituents. When such a [an alkaline] core is enteric coated with an amount of 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 water of gastric juice ..."
157 The question is one of construction of the claims before amendment. Literally read, integer (A) of claim 1 does not contain any ambiguity which is relevant for present purposes: it says nothing as to the character or quantity of the alkaline reacting compound to be included in the core material, only that the core material contain omeprazole "together with" an alkaline reacting compound, or an alkaline salt of omeprazole optionally together with an alkaline reacting compound. The words "alkaline reacting core" occur only in the description of integer (C), the sub-coat, and only for the purpose of describing (in itself, in context, a work of supererogation) where the sub-coat is to be applied: "... said inert subcoating layer(s) between the alkaline reacting core and said outer layer ...".
158 To use the expression "alkaline reacting" in that context would be a rather odd way of limiting the extent of integer (A); and it is important, I think, that claim 5 (before amendment) is for a preparation according to any one of claims 1 to 4 "wherein the alkaline core comprises omeprazole and pH-buffering alkaline compound rendering to the micro-environment of omeprazole a pH of 7-12". (The effect of clause 5 was not changed by the amendment). The evidence established that a pH of 7 is neutral and that (subject to a degree of controversy as to a possible "neutral range") a pH above 7 is alkaline. It may be – I do not think that the evidence can be said to exclude the possibility – that the core (as a whole) might be regarded as "alkaline reacting" in circumstances where, assuming the possibility of accurate measurement, the "micro-environment of omeprazole" had nevertheless a pH less than 7. But the presence of claim 5 does, I think, give some support to a literal reading of claim 1.
159 The body of the specification of the unamended patent also, I think, on the whole supports that view. I have referred to the passage early in the section describing the background of the invention which reads, unamended:
"In order to enhance the storage stability the cores which contain omeprazole must also contain alkaline reacting constituents. When such an alkaline core is enteric coated with an amount of a conventional enteric coated polymer ..."
160 In other words, those who drew the specification appear to have proceeded on the footing that a core which contains alkaline reacting constituents (and no more) may be described as "an alkaline core" or "an alkaline reacting core". That impression is again confirmed in the outline of the invention provided in the unamended patent:
"The object of the present invention is to provide an enteric coated dosage form of omeprazole, which is resistant to dissolution in acid media and which dissolves rapidly in neutral to alkaline media and which has a good stability during long-term storage. The new dosage form is characterised in the following way. Cores containing omeprazole mixed with alkaline compounds or an alkaline salt of omeprazole optionally mixed with an alkaline compound are coated with two or more layers ... . This/these first layer/layers separates/separate the alkaline core material from the outer layer, which is an enteric coating."
161 Once again, the only requirement is that the omeprazole be mixed with alkaline compounds. To speak in that context of separating the "alkaline core material" from the outer layer need not be taken to introduce any uncertainty: there is "alkaline core material"; another component of the core material is omeprazole.
162 No doubt, in this respect as perhaps in others, the drafting of the patent is by no means ideal. Nevertheless, in my view, the meaning of claim 1, unamended, requires alkaline material as a component of the core; it does not require that the core, regarded as a whole, be alkaline or alkaline reacting. That being so, the patent is entitled to the priority date claimed.
(f) The amendment: false suggestion or fraud
163 Alphapharm claims, in its amended particulars of invalidity, that the amendment "was obtained by false suggestions or misrepresentations contained in the application for amendment"; particulars of certain representations are then given. Fraud is not expressly pleaded. There arises a further question of the application of the transitional provisions in the 1990 Act. It is a ground of revocation under s 138 of the 1990 Act:
"(3) ...
(e) that an amendment of the patent request or the complete specification was made or obtained by fraud, false suggestion or misrepresentation ..."
164 The corresponding ground in the 1952 Act is to be found in s 100(1)(o):
"that leave to amend, or a direction to amend, the complete specification ... under Part VIII was obtained by fraud."
165 The grounds of revocation in pars (m), (n) and (o) of s 100(1), all relating to amendments, require that fraud (nothing less) be established. By contrast, par (k), dealing with the circumstances in which the patent was obtained, requires that it be established "that the patent was obtained on a false suggestion or representation". I was referred to discussions in the authorities of the meaning of the words "false suggestion", for example the following passage in the judgment of Lockhart J in Prestige Group at 201:
"Although s 100(1)(k) uses the words ‘false suggestion’ I derive no principle from the authorities to support the proposition that fraud in the sense of deliberate intent to deceive is necessarily involved. Indeed, quite the contrary, as the cases speak of the relevant conduct in terms akin to equitable fraud ..."
166 But ground (o) uses different terminology. It requires "fraud". I can see no reason to hold that it means anything less than it says.
167 Alphapharm, however, submitted that the 1990 Act applies to the amendment and submitted, explicitly, that the patent should be revoked because (among other things) the representations of Astra in obtaining the amendment amounted to fraud, false suggestion or misrepresentation.
168 While it is true, in my opinion, that the 1990 Act applied to the amendment, in the sense that the amendment was required to be made in accordance with the provisions of the 1990 Act and the 1990 Act determined the effect of the amendment on the priority date, what is sought to be revoked is nonetheless a patent granted under the 1952 Act. It is, therefore, by force of s 233(4) of the 1990 Act, not invalid on any ground that would not have been available against it under the 1952 Act. It was not a ground of invalidity under the 1952 Act that the amendment was obtained by false suggestion or misrepresentation.
169 For that reason, fraud not having been pleaded, this ground of attack on the patent must fail.
170 There is, however, one matter relied upon by Alphapharm to which I should refer briefly. A particular representation relied upon by Alphapharm was one made by Astra’s patent attorneys in correspondence with the Patent Office in July 1997. In response to a suggestion by the examiner that by the removal from claim 1 of the words "the alkaline reacting core" (replaced by the words "said core material") Astra sought to expand the scope of the claims, the patent attorneys wrote:
"The claims before amendment and the claims as amended simply define the order of the layers A, B and C ... . There is nothing which would amount to an infringement of the claim as amended that would not have been an infringement of the claim before amendment."
171 I have referred to the acid labile patent, which has the same priority date as the patent in suit. As I have mentioned there are considerable similarities in the two patents; and the inventors named in each are the same. Dr Pilbrant, one of the inventors, gave the following evidence;
"Q. Was the work that you did, that went towards this patent [viz, the acid labile patent], the work that you did on omeprazole?
A. Most of the work we did on omeprazole. We did some experiments for sampling [sic] the patent application."
172 Claim 1 of the acid labile patent, however, differs somewhat from the corresponding claim of the omeprazole patent. Particularly, integer (A) in claim 1 is "an alkaline-reacting core material containing the acid-labile oral-use pharmaceutical compound"; and the claim continues, after describing the three layers:
"... the core material being such that an aqueous suspension or solution of the core material has a pH higher than that of a solution in which the enteric coating is just soluble."
173 In correspondence with the Patent Office in 1990, concerning an amendment of the acid labile patent, Astra’s patent attorneys clearly communicated with the Patent Office a view that the "primary feature" of claim 1 was "an innermost or core component consisting of the acid labile pharmaceutical compound in an alkaline environment" and "the alkaline nature of the core material".
174 On the basis of those two sets of correspondence it was submitted that Astra chose to take contrasting approaches in representing to the Patent Office the effect of claim 1 in virtually identical patents and that the description, by the patent attorney, of the effect of the 1997 amendment was one which Astra knew to be incorrect. The material, however, in my view does not support the conclusion. There are considerable similarities between the two patents, but there are also very obvious differences. Even if that were not so, it would be a considerable leap from the fact that Astra’s patent attorney said one thing in 1990 about the acid labile patent to the suggested conclusion that Astra knew that what was said on its behalf in 1997 was wrong. I have, of course, held that what was said in 1997 was in fact correct. If I were wrong in that, then the patent would necessarily be invalid; but not on the ground that the amendment was obtained by fraud.
(g) Obtaining the patent: false suggestion or representation
175 The representations pleaded in the amended particulars of invalidity are that the claims of the specification of the unamended patent were fairly based on matter described in that specification, that the invention was novel, that the invention involved an inventive step and that the invention was useful. It is then said that each of those representations was false for the reasons set out by Alphapharm in its particulars to the corresponding grounds of invalidity. In Prestige Group, Gummow J discussed at length the history of the concept of "false suggestion". His Honour continued, at 218:
"What follows from this review of the long history of the concept of ‘false suggestion’? First, the inclusion in the present Act of a number of grounds of invalidity, including non-compliance with s 40 (s 100(1)(c)), inutility (s 100(1)(h)), prior claiming (s 100(1)(f)) and lack of title in the applicant (s 100(1)(a)), may well leave s 100(1)(k) with much less work to do than was performed by the principles dealing with false suggestion in the past ... . Secondly, that does not mean that circumstances may not still arise where the paragraph does have work to do."
176 Gummow J added:
"It would be a most unusual case where the alleged false suggestion or representation was relied upon as having been made only in the specification, yet reliance was placed upon s 100(1)(k), rather than a ground of failure to observe the various requirements of s 40."
177 On the view I have taken as to the effect of the amendment, and assuming, without deciding, that the specification of the unamended patent incorporated representations to the effect that the invention was novel, involved an inventive step or was useful (there is no evidence or allegation that such representations were made separately) and the representation was false, then the separate grounds of want of novelty, obviousness and inutility would have prevailed or not in the same way as they prevail or do not prevail following the amendment. Consequently, in those respects, ground (k) has no separate work to do. Equally, at least on the view I have taken as to the effect of the amendment, the specification of the unamended statement was no more susceptible to attack on the ground of lack of fair basis than the present specification; if that is so, equally in that respect ground (k) would have no work to do.
178 For reasons to which I shall now turn, it is, I think, not necessary or appropriate that I take the matter any further.
179 In written submissions handed up on the last day of the trial (in the circumstances of the trial no criticism can be offered on that account) Alphapharm alleged two particular misrepresentations in the specification of the unamended patent. One related to the reference in the specification to the Clymer and MacDonnell patent, a reference removed, with other references to prior art, by the amendment. The specification said of the Clymer and MacDonnell patent that it:
"... describes an enteric coated oral dosage form, where the enteric coating is combined with a second and/or first coating of a water insoluble ‘wax’ layer."
180 The specification continued:
"This method of preparation is not applicable on cores containing omeprazole since direct contact between substances such as cellulose acetate pthalate (CAP) and omeprazole causes degradation and discolouration of omeprazole."
181 That is obviously somewhat puzzling, because one might reasonably suppose that if there were a "first coating" of wax there would be no such direct contact. The misrepresentation on which Alphapharm sought to rely, however, was in the reference to "water insoluble ‘wax’ ". As has been seen, the Clymer and MacDonnell patent suggested that the desired wax coat might be "rapidly soluble or dispersible in the intestinal fluids" (Professor Rhodes gave evidence that that was impossible, and cited recent writings of his to that effect, but nevertheless that is what the Clymer and MacDonnell patent claims).
182 At the time when Alphapharm’s written submissions were filed in Court, senior counsel for Astra said:
"So far as the written submissions are concerned, I received those just under one minute ago and, pretty clearly, I am not going to be able to deal with those at all during this morning. I would propose to address on the footing that we already understand what the issues are, but clearly, if there [turn] out to be some issues raised in the written submissions which we haven’t dealt with then it might be necessary to make some arrangements to deal with them."
183 That observation passed without comment. On 22 April (rather more than three weeks after the conclusion of the trial) Astra delivered further written submissions including, among other things, a contention that in some respects (the claim that the reference to the Clymer and MacDonnell patent was a false suggestion being one of them), Alphapharm’s written submissions went beyond anything that had been pleaded or raised in the course of the trial. To that, Alphapharm responded that Astra’s submissions were too late and ought not to be taken into account and, in relation to the Clymer and MacDonnell patent point, that Astra’s submission in any event was incorrect because the paragraphs of the particulars of invalidity dealing with false suggestion "clearly raised the issue that by its representations as to the prior art ... the first applicant falsely represented, inter alia, that the claimed invention was novel and involved an inventive step". That may be true so far as it goes; however, the pleading does not assert, as I read it, that any of the references to the prior art included a false suggestion or representation as to its effect. Nor, so far as I can see, was such a suggestion made either in opening or in closing oral submissions.
184 The other matter relates to the long term stability of omeprazole. This was a point on which Dr Pilbrant was cross-examined at some length. Particularly, he was asked questions about an internal Astra document dated 30 June 1983 which might be taken to suggest that no long stability problem arose if the omeprazole core were directly enteric coated:
"In stability report No. 213-806 a satisfactory stability was shown for omeprazole enteric-coated granulate with no subcoat stored at room temperature for 12 months in folded paper capsules and for 10 months in gelatine capsules. The addition of a subcoat is not expected to give a less stable product which is indicated in the results presented in this report."
185 That founded a suggestion that Astra deliberately withheld stability testing information from the Patent Office in applying for the patent. The examples in the patent omit any reference to long term stability testing. The explanation, it was suggested, was that to reveal the results of tests would have involved demonstrating that the addition of a sub-coat made no difference to long term stability.
186 Again, in its somewhat delayed written submissions, Astra pointed out (correctly) that this particular representation was not pleaded or suggested in opening or oral closing submissions. Certainly the cross-examination raised the question in a general sense and in closing submissions it was put that the material indicated clearly that there was no long term stability problem which required a sub-coat for its solution. What was missing, however, I think, was any linking of that proposition to a suggestion that failure to disclose long term stability studies in the patent amounted to a false suggestion or representation.
187 In that state of the pleadings and submissions I could not, in my view, properly hold, on the basis of either the Clymer and MacDonnell patent representation or the long term stability representation, that the false suggestion ground was made out. Given my conclusion on the ground of obviousness, I think it is appropriate to leave this ground at that.
(h) Fair basis
188 In this respect there is no substantial difference between the 1952 Act and the 1990 Act. This aspect of the matter may be considered by reference to the ground stated in s 100(1)(c) of the 1952 Act, as follows:
"that the complete specification ... does not comply with the requirements of section 40."
189 Section 40(2) provides:
"The claim or claims shall be clear and succinct and shall be fairly based on the matter described in the specification."
190 The amended particulars of invalidity give voluminous particulars of alleged failures of the specification to comply with s 40(2) (or s 40(3) of the 1990 Act). Some of the particulars clearly relate to "fair basing"; of a number of others it may fairly be said that it is not immediately clear whether they relate to that or to other elements of s 40(2). Given that circumstance, and given the voluminous nature of the particulars, several of which were not referred to in argument or written submissions, I shall confine myself to those matters which Alphapharm pressed in closing submissions.
191 The first was that "the entire thrust" of the specification was that the claimed invention was the production of a dosage form of omeprazole which was stable on long term storage; but the claims are not limited to stable preparations. Secondly, it was said that the claims, so far as they relate to tablets, are not fairly based because "there is no disclosure in the specification which demonstrates that tablets according to the formulation are suitable pharmaceutical preparations". Thirdly, it was said that the specification makes it clear that what is contemplated is the manufacture of cores by a process in which a wet mass is "pressed through an extruder and spheronized to pellets" or is dried in a fluidised bed and then forced through a sieve; thus, to the extent that the claims were construed to encompass a "core" produced by any other process, or any other kind of core, they were not fairly based. Fourthly, it was said that the term "alkaline reacting compound" was one the precise meaning of which was demonstrated by the evidence to be far from obvious; if the proper construction of the term was that it meant any substance which "raises the pH of an aqueous solution" then each claim referring to that expression was not fairly based (alternatively, if the proper construction were one which treated the term as meaning a compound which would "raise the pH above neutral pH values" then, while the claims might be fairly based, "the majority of substances to which this reference is made in the specification are demonstrated in the examples not to work": it is not entirely easy to see the relevance of that to "fair basing").
192 The fifth submission related to the sub-coat. Claim 1, it was said, correctly, was, as to the second integer, for one or more "inert reacting subcoating layer(s) ... optionally containing pH buffering, alkaline compounds". But the examples in the specification included only one containing two sub-coats and that example made it clear (it was said) that where a sub-coat contains a "pH-buffering alkaline compound" it is required to be separated from the core by a second sub-coat, not containing such a compound. Thus, claim 1 was not fairly based on the specification "because it is not limited to claiming a second subcoat which is absent a pH buffering alkaline compound where the first subcoat does contain one". It was also said, perhaps somewhat cryptically, that the patent provides no fair basis for the nature of the sub-coat itself, on the footing that the sub-coat appears to perform the same function as the water soluble sub-coat in Shin-Etsu H-17: "preventing acid-base reaction breakdown". Sixthly, it was said that, to the extent that the claims were for a dosage form with water content greater than 1.5 per cent by weight, they were not fairly based on the specification; and, further, even claim 10, for a dosage form the water content of which did not exceed 1.5 per cent by weight, was not fairly based because the specification demonstrated only that whereas a 1 per cent water content was satisfactory, 2 per cent was thoroughly unsatisfactory, so that a claim for a dosage form the water content of which exceeded 1 per cent was not fairly based. Seventhly, it was said that because the specification asserts that omeprazole degrades rapidly at "neutral pH values", those claims which contemplated a "micro-environment" of omeprazole the pH of which was 7 or less were not fairly based; neither was claim 5 fairly based, in requiring a "micro-pH" of 7-12: 7 was too low for the reason already given, and there was no basis given in the specification for the upper limit of 12. Eighthly, and finally, it was said that the specification made it clear that a high amount of buffer salt (as a component of the core) was needed to achieve the aims of the invention, but the claims do not specify a level: hence, it was said, they are not fairly based.
193 Fair basing, more than any other element of the case, demonstrates the difficulties inherent in attempting to deal with a case of the size and complexity of this, on a final basis, in the time which was allotted. Very little attention was given to fair basing in oral submissions. Counsel for Astra, when they prepared their submissions (written and oral), had not seen Alphapharm’s written submissions. As a result, they appear simply to have made a selection of some of the more obvious candidates among the particulars and dealt with them. In consequence, of the matters argued by Alphapharm in written submissions, Astra has dealt only with the first (in part), the sixth and the eighth. In its somewhat delayed further submissions in response, Astra has argued that that part of the first matter not dealt with in its submissions and the second, the third, the fourth and the fifth all were unheralded (particularly, unpleaded) and should not be taken into account on the question of validity. Alphapharm, in reply to those submissions by Astra, says that the fact that matters had not been earlier argued is of no consequence because the hearing was conducted on the basis that opening and final submissions would be limited in time in order to ensure that the hearing was completed within the time available. Alphapharm says also that all of the matters complained of were pleaded and gives two examples by way of demonstration of that argument.
194 I must say that, making all allowance for the time constraints, I find the examples unconvincing. The first relates to Alphapharm’s submissions about stability. Certainly it is true that particular 10(b) of the amended particulars of invalidity clearly states that claims 1 to 12 are not fairly based on the description of the invention in the specification as the invention is directed to a new stable pharmaceutical preparation but the claims are not restricted to stable preparations of omeprazole. I am by no means sure that Astra should have been led by that to expect that they would have to deal with an argument based on a suggestion in Pilbrant and Cederberg that a tablet or dosage must be so stabilised by mixture with alkaline compounds as to ensure stability (in the stomach) for fourteen hours (that is the particular argument of which Astra complains). The second example relates to the fourth submission, concerning "alkaline reacting compound". Astra says that particular 10(a), under the heading "Not Clear, Succinct or Fairly Based", repeats certain of the particulars given in relation to lack of sufficiency: those particulars refer, among other things, to an alleged lack of clarity of the term "alkaline reacting compound" throughout the specification. That might reasonably be supposed to have alerted Astra to a possibility that that matter might be relied upon in relation to an assertion that the claims were not "clear". But it is not at all clear how Astra should have supposed that the lack of clarity might be said to relate to a claim of lack of fair basis. There is, so far as I can see, no pleading of fair basis specifically in relation to Alphapharm’s second submission (tablets); nor have I found a pleading supporting the third argument (method of manufacturing cores); similarly Alphapharm’s fifth submission (sub-coat containing pH-buffering material). Astra made no complaint about the seventh submission (micro-environment or micro-pH), that being clearly enough pleaded; but they have addressed no argument to it.
195 "Fair basing" is a topic of some complexity. As I have come to a conclusion in favour of Alphapharm on the issue of obviousness, it is unnecessary for me to come to a conclusion on fair basis in order to decide the case, and in my view it would be inappropriate to deal with any aspects of fair basis other than those to which both parties have addressed argument.
196 I was referred to the "three-fold investigation" suggested by Lloyd Jacob J in Re Mond Nickel Co Ltd’s Application [1956] RPC 189; but it is necessary to remember that a case such as the present, involving a question of "fair basing" of a claim upon the body of a complete specification, is not altogether analogous to the question of "fair basing" of claims upon earlier documents, such as a provisional specification: Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 at 93 per Gummow J. It is necessary also to bear in mind the warning given by Barwick CJ in Olin Corporation v Super Cartridge Co Pty Ltd [1977] HCA 23; (1977) 180 CLR 236 at 240:
"The question whether the claim is fairly based is not to be resolved, in my opinion, by considering whether a monopoly in the product would be an undue reward for the disclosure. Rather, the question is a narrow one, namely whether the claim to the product being new, useful, and inventive, that is to say, the claim as expressed, travels beyond the matter disclosed in the specification."
197 That warning was reinforced by the Full Court in CCOM Pty Ltd v Jiejing Pty Ltd [1994] FCA 1168; (1994) 51 FCR 260 at 279, 280. If there is a general description of what is meant in the statute by "fair basing" which has found favour in Australian law, it seems to be:
"... whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification."
(Rehm at 95; the principal source is Société des Usines Chimiques Rhone-Poulenc v Commissioner of Patents [1958] HCA 27; (1958) 100 CLR 5 at 11; see also F. Hoffman-La Roche & Co AG v Commissioner of Patents [1971] HCA 3; (1971) 123 CLR 529 at 539; CCOM at 281, 282.)
198 The first and eighth of Alphapharm’s submissions may be taken together. Both deal with stability during storage and both (including that part of the first submission of which Astra complains) make the point that claims 1-12 do not (in the light of the disclosures in the specification) require a sufficiently high level of alkalinity in the core – or a sufficiently large quantity of an alkaline reacting compound – to achieve stability, given the disclosure, for example, that omeprazole degrades rapidly "at neutral pH values". The specification outlines the invention as one "related to a new stable pharmaceutical preparation containing omeprazole for oral use" and, in the background to the invention, says that it "has been found that in order to enhance the storage stability, the cores which contain omeprazole should also contain alkaline reacting constituents". Furthermore, a high amount of buffer salt is needed (so the comparative examples are said to suggest) in order to obtain a long shelf life for the product. Certainly claim 1, for example, does not require a "high amount of buffer salt", all it requires is that there be "core material containing omeprazole together with an alkaline reacting compound, or an alkaline salt of omeprazole optionally together with an alkaline reacting compound".
199 The essence of the question is whether a claim of that width is not fairly based because, in the words of Barwick CJ in Olin Corporation at 240, it "travels beyond the matter disclosed in the specification"; or whether, on the other hand, it is fairly based having regard to the principles stated by Gummow J in Rehm at 95:
"The circumstance that something is a requirement for the best method of performing an invention does not make it necessarily a requirement for all claims; likewise the circumstance that material is part of the description of the invention does not mean that it must be included as an integer of each claim. Rather, the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification."
200 Olin Corporation, I think, provides a useful illustration. The patent there in suit was for an invention concerning a novel process for manufacturing a product in a form in which it had not previously been manufactured. The patent included claims for the process and a claim also for the product. The majority (Barwick CJ dissented) held that the product claim was not fairly based because the invention described in the specification concerned only the particular process by which, the inventor had discovered, the product could be made. The product claim, if valid, would exclude others, if they could find means to do so, from manufacturing the same product by a different process. Thus it could be said that the claim for the product travelled beyond the matter disclosed in the specification.
201 The present case, it seems to me, is very different. The essence of the claimed invention is that the core of the dosage form comprise or contain an alkaline reacting compound and that it be separated from the enteric coat, which is necessary to ensure its safe passage through the stomach, by a water soluble sub-coat. That is what is claimed. The authorities do not, in my view, support a proposition that a claim will be fairly based on a specification only if every way of performing the invention, within the terms of the claim, will produce the result claimed for the invention. There may be questions of degree; but it cannot be right that a claim of the patent in suit would be fairly based only if it claimed particular compounds, particular quantities and particular combinations which the specification disclosed as effective to produce (to some extent, though not necessarily to the extent achieved by the inventor’s best method) the purpose of the invention.
202 The same principles require, in my view, the same result in relation to the submissions concerning water content. In the light of my comments on the other submissions, perhaps it is sufficient simply to say that I do not accept that a claim would be fairly based only if it included, as an essential integer, the maximum water content shown, by the experiments reported in the specification, to work.
(i) Sufficiency; ambiguity
203 As to sufficiency, the parties agreed that, there being no material difference between the provisions of the 1952 Act and the 1990 Act, it was appropriate to refer to s 40(2)(a) of the 1990 Act. It provides:
"A complete specification must:
(a) describe the invention fully, including the best method known to the applicant of performing the invention ..."
204 Section 40(3) provides (in substantially identical terms to s 40(2) of the 1952 Act), that the claim or claims must not only be fairly based on the matter described in the specification but also must be "clear and succinct".
205 There are three distinct strands in the argument on behalf of Alphapharm on this issue. The first is, in effect, a repetition of some of the matters put on the ground of lack of fair basis. For instance, it is said that to the extent that the claims are not limited to stable preparations, they include preparations which will not achieve "the promises or objects of the invention outlined in the specification"; similarly where the claims are not limited to a defined amount of alkaline reacting compound; similarly in relation to water content; similarly as to the pH level required in the environment of the omeprazole particles; and similarly as to the failure to limit the class of omeprazole salts which may be used as core material to those which will "achieve the promises or objects of the invention". But the ordinary understanding of "sufficiency" is as it was succinctly stated by Carr J (with whom Jenkinson and Sackville JJ agreed) in Patent Gesellschaft AG v Saudi Livestock Transport and Trading Company (1997) 37 IPR 523 at 530:
"The specification contains a full description if it makes the nature of the invention plain to persons having reasonably competent knowledge of the subject and also makes it plain, to persons having reasonable skill, how to perform the invention."
206 I do not think that the matters referred to have the consequence that the specification fails to meet that test. To the extent that they were advanced in support of an argument that the claims were not fairly based on the specification, then the principles which I have discussed above would be relevant, but it is unnecessary to say more about that.
207 The second strand relates to the examples given in the patent. The submission was that the examples are "hopelessly inadequate and clearly do not meet the promise of page 2.18 [of the specification] that the invention is ‘described in detail’ in them". There was a good deal of evidence and argument about the examples and about tables summarising the results of storage stability tests applied to cores formulated with various alkaline reacting compounds and of tests, applied to various formulations with and without sub-coats, for acid resistance and for rates of dissolution in a solution having a pH similar to that found in the small intestine.
208 The complaints about the examples and summary tables included the following. No one formulation was tested for long term stability on storage and also for acid resistance and dissolution, so that there was no formulation demonstrated to the skilled addressee as one which would solve all the stated problems; no dissolution studies were reported for non-sub-coated formulations (though there was evidence of Dr Pilbrant that such studies were performed); the accelerated storage stability tests were unsatisfactory in that all formulations were not subjected to precisely the same tests; and there was no teaching as to precisely what ingredients were required, in precisely what amounts, to achieve a satisfactory formulation. The result was that a person skilled in the art could not, by reference to the specification, prepare a stable oral pharmaceutical preparation containing omeprazole without further experimentation and, possibly, modification of the examples.
209 But the criticism largely, I think, rests on a misapprehension as to what is required of a specification. There is no requirement that there be examples. The specification must disclose the best method of performing the invention which is known to the applicant (I shall return to that proposition). But otherwise the test of sufficiency is that which I have quoted. I am unpersuaded by the evidence led by Alphapharm that it is not met. Indeed, and I shall return to this also, there is a tension between the evidence led by Alphapharm in relation to obviousness and the evidence of the same witnesses relevant to sufficiency and ambiguity.
210 There is a discussion of "best method" in Rescare Ltd v Anaesthetic Supplies Pty Ltd (1992) 111 ALR 205 at 220-223, in which the history of the term and a number of earlier authorities are considered. It is not necessary that the specification itself state, in so many words, which of a number of embodiments the applicant regards as the best, if a number of embodiments are described. What is required is that one of those (if there are more than one) be the "best method" known to the applicant. There is no evidence that that requirement was not met. Indeed, the evidence suggests that it was: Dr Pilbrant’s evidence was that what is described in the specification as example 2 (shown in the specification to have performed very satisfactorily in the acid resistance and dissolution studies, though no results are given of its performance under long term storage testing) was the formulation used by Astra in the Phase III clinical trials and that that formulation, in turn, is substantially the formulation of the product Losec.
211 The third strand related to what were claimed to be a number of ambiguities and uncertainties in the use, in the specification and the claims of the patent, of certain expressions. In Elconnex Pty Ltd v Gerard Industries Pty Ltd [1992] FCA 556; (1992) 25 IPR 173 Lockhart J said at 187:
"It is the function of the claims in a patent to define the invention and the specification to fully describe it. The claims must be defined clearly and precisely so that persons who read it may know the precise extent of the monopoly claimed. If a claim is cast in ambiguous language ambiguity may sometimes be resolved by resort to the words in the body of the specification. But if this does not resolve the ambiguity then the claim is bad and the patent avoided."
212 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."
213 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.
214 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.
215 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").
216 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.
217 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.
218 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."
219 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.
220 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)
221 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."
222 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".
223 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.
224 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.
225 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
226 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.
227 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, SS 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."
228 Likewise in the NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1993] FCA 404; (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."
229 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."
230 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
231 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
232 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.
233 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
234 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.
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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.
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Associate:
Dated: 12 May 1999
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Counsel for the First and Second Applicants:
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Dr J McL Emmerson QC with
Mr D M Yates SC and Ms K J Howard |
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Solicitor for the First and Second Applicants:
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Minter Ellison
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Counsel for the Respondent:
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Dr A C Bennett SC with Mr S C G Burley
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Solicitor for the Respondent:
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Mallesons Stephen Jaques
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Date of Hearing:
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8-12, 15-19, 22-26 March 1999
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Date of Judgment:
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12 May 1999
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URL: http://www.austlii.edu.au/au/cases/cth/FCA/1999/628.html