The issues on appeal
19 The appeal was conducted upon the basis that should it become necessary to determine the question of lack of inventive step or 'obviousness' (as it is sometimes called) the matter would need to be remitted to the primary judge for further consideration. The argument on the appeal was thus confined to the questions of whether the primary judge erred in finding that the invention was not a patentable invention as the claims do not constitute an invention or a manner of manufacture or because of lack of novelty having regard to the disclosures in the publications of Lunar News.
MANNER OF NEW MANUFACTURE
20 Section 18(1)(a) of the Act relevantly provides:
'… an invention is a patentable invention for the purposes of a standard patent if the invention, so far as claimed in any claim:
(a) is a manner of manufacture within the meaning of s 6 of the Statute of Monopolies…'
21 'Invention' is defined in sch 1 to mean:
'… 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.'
22 The threshold issue is whether an invention appears on the face of the specification: Philips at 664. The critical steps in his Honour's reasoning on this issue were as follows:
'81. The relevant claims of this patent will stand or fall by the so-called method claims. The disclosures in the specification include the following. It was known that alendronate monosodium trihydrate on an alendronic acid active basis was effective in preventing and treating osteoporosis in a human. It was known that it could be orally administered, that is, taken by mouth in various amounts and at various time intervals. It was known that oral administration of the compound had the potential to give rise to GI side effects in a small but significant proportion of the population. It was known that there could be problems of compliance with a daily dosage regime of the type described in the specification. Thus, in substance, each claim relates to the use of a known substance with known properties for a known purpose in a known manner. There is no claim of any new process or method of administration as such. There is no claim of discovery of new physical properties in the compound.
82. It is trite law that a mere new use for an old thing is not patentable. However, a discovery that an old substance may be so used as to produce a new result may possibly give rise to a patentable invention. The old substance in that case is treated as if it were new, the previously unknown or unsuspected qualities of it being revealed by the discovery if the discovery in question is a consequence of scientific ingenuity. The principle extends to a process that results in a new and useful effect that is an artificially created state of affairs of economic utility (National Research Development Corporation v Commissioner of Patents (1959) 102 CLR 252 (NRDC) at 265, 277; Wellcome Foundation Ltd v Commissioner of Patents (1980) 145 CLR 520 at 528).
83. However, a process claim cannot lead to a monopoly in a substance limited to its use in the process. The process makes no contribution to the substance - it takes advantage of its properties. The substance is merely an ingredient in that process (Wellcome Foundation Ltd v Commissioner of Patents at 529-530). As Parker J said in Adhesive Dry Mounting Co Ltd v Trapp & Co (1910) 27 RPC 341 (at 353):
"The idea of using an old material for an entirely new purpose, not being analogous to purposes for which it has theretofore been used, may be good subject matter, but such idea, however ingenious, can hardly justify a claim for the material itself."
84. As was said in Commissioner of Patents v Microcell Ltd (1959) 102 CLR 232 (at 249):
"Many valid patents are for new uses of old things. 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 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."
85. The authorities which were analysed in Commissioner of Patents v Microcell Ltd at 247-249 including Re B.A.'s Application (1915) 32 RPC 348 in which it was said (at 349):
"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." '
23 After referring to Philips and Advanced Building Systems Pty Ltd at 191-192 his Honour continued:
'87. Guided by those authorities, and having regard only to the disclosures in the specification itself, I would hold that each of the so-called method claims was one way of utilising alendronate and its known qualities for the known purpose of preventing or treating osteoporosis by a known method of oral administration. They are in the nature of directions for use. That does not constitute an invention or a manner of manufacture.'
24 At a later stage his Honour considered the decision of the Full Court in Faulding, a case which dealt with a patent for a method of administration of taxol in the treatment of ovarian cancer. After quoting passages from the joint judgment of Black CJ and Lehane J at [31] and [43]-[44] his Honour said:
'95. It does seem to follow that it was held that a mere dosage regime of a known chemical compound for a known therapeutic use based upon known properties and involving no new method of administration was patentable. As will be apparent from the foregoing, I regard that conclusion as being difficult to reconcile with prior and binding authority if applied to the present circumstances. My reservations are underlined by considering the decision of the United Kingdom Court of Appeal in relation to taxol - Bristol-Myers Squibb Co v Baker Norton Pharmaceuticals Inc [2001] RPC 1 (Bristol-Myers). As pointed out by the High Court in Aktiebolaget Hassle v Alphapharm Pty Ltd (2002) 212 CLR 411, great care needs to be taken in reading United Kingdom cases in this field because of the significant differences which have developed. However, Aldous LJ analysed the claim (at [34]) as being:
"for the use of two known products to produce a medicament with the novelty relied on being provided by the alleged new application."
It was clear that, even under the extended European Community rules, novelty could only lie in a new therapeutic use. Aldous LJ said (at [42]):
"… I turn to claim 1. The judge was right to conclude there was not a claim for a second therapeutic use. The medicaments in question were known to be suitable for treating cancer. The remainder of the claim relates to the way such a medicament was to be used. A similar conclusion was reached by the Dutch Court of Appeal in Bristol-Myers Squibb v Yew Trew of 25 June 1998."
96. I have been referred to the English decisions corresponding to this case (Merck & Co., Inc's Patents [2003] EWHC 5 (Pat); [2003] FSR 29 at first instance; and Merck & Co., Inc's Patents [2003] EWCA Civ 1545; [2004] FSR 16 in the Court of Appeal) and to the corresponding United States decision (Merck & Co., Inc. v Teva Pharmaceuticals USA, Inc. 288 F. Supp. 2d 601). It is accepted by counsel that the law in each place is sufficiently different from our present law to distinguish those decisions and limit their utility for present purposes. However, a revealing exercise in the decision at first instance in the United Kingdom was counsel's redrafting of some statements from Holman J at para [111] in the English decision in Bristol-Myers substituting alendronate for taxol, osteoporosis for ovarian cancer, adverse GI effects for neutropenia and 'the new and old alendronate dosing regimes' for 'the new and old taxol dosing regimes'. The result is as follows (at 519):
"In the present case, however, the drug alendronate is exactly the same; the method of administration, orally, is exactly the same; and the therapeutic application or purpose, namely the attempt to treat osteoporosis, is exactly the same. The only difference is the discovery that if the drug is administered in a unit dosage form of 70mg once weekly rather than 10mg once daily an undesirable side-effect, adverse GI effects, is less than it otherwise would be, whilst the therapeutic effect remains. No previously unrecognized advantageous properties in the chemical compound have been discovered … All that has been discovered … is that if the compound is administered once a week rather than daily, one of its disadvantageous side effects will be less than it otherwise would be."
As Jacob J said, counsel for Merck found no answer to that. That analysis is consistent with that of Heerey J at first instance in Faulding (1998) 41 IPR 467 and with my analysis in this case.'
25 His Honour then (at [97]) distinguished Faulding on the grounds that:
· Taxol was a naturally occurring substance with known beneficial properties which could not be utilised without the invention. The dosage regime was, in his Honour's words, 'the key that unlocked the door to utility', and was arguably akin to a first therapeutic cure;
· Arguably the dosage regime was the result of a newly discovered technical effect, namely the reduction of neutropenia.
Neither of these elements was, in his Honour's view, present in the instant case.
26 We consider that the correctness or otherwise of his Honour's reasoning depends upon an examination of the Patent specification in light of the decision of the High Court in Philips to determine whether the subject matter of the claims was a manner of new manufacture for the purposes of s 6 of the Statute of Monopolies 1623 (Imp). That question requires us to construe the specification.
27 The specification describes the 'background'of the invention, including the occurrence of abnormal bone resorption in human beings and various aspects of the treatment thereof. Numerous publications on the subject, including some patents, are incorporated by reference into the body of the specification. The following propositions emerge:
· Numerous disorders in human beings and other mammals involve, or are associated with abnormal bone resorption including, in particular, osteoporosis and Paget's Disease.
· Osteoporosis most frequently manifests itself in post-menopausal women.
· Osteoporosis leads to low bone mass and deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture.
· Because osteoporosis, as well as other disorders associated with bone loss, are chronic conditions, appropriate therapy will generally require chronic treatment. In this context, 'chronic' seems to mean 'of indefinite duration', 'long term' or, in some cases, 'for the rest of the patient's life'.
· Bisphosphonates are selective inhibitors of bone resorption and are therefore important therapeutic agents in the treatment or prevention of such disorder.
· One such bisphosphonate is alendronate.
· Bisphosphonates may be administered either orally or by subcutaneous or intravenous injection.
· Bisphosphonates are poorly absorbed from the gastro-intestinal tract, thus reducing the efficacy of oral administration.
· Intravenous administration has been used to overcome this problem.
· Intravenous administration is costly and inconvenient.
· Oral administration must be in relatively high dosages (compared with intravenous administration) to compensate for low bio-availability.
· To achieve the required effect it is generally recommended that a patient take bisphosphonates on an empty stomach and fast for at least thirty minutes afterwards. This is inconvenient for many patients.
· Oral administration of bisphosphonates has been associated with adverse GI effects, especially in connection with the oesophagus, apparently because bisphosphonates tend to irritate it, which irritation is possibly exacerbated by the presence of refluxed gastric acid.
· Adverse GI effects increase with increases in dosage.
· These adverse effects are more prevalent in patients who fail to take the bisphosphonate with adequate amounts of liquid or who lie down shortly after administration.
· Oral administration is generally either by a continuous daily treatment regime or a 'cyclic' regimen of treatment involving periods of treatment and rest periods.
· Continuous daily treatment normally involves 'chronic administration of relatively low doses', the objective being delivery of the desired cumulative therapeutic dose over the course of the treatment period.
· Continuous daily dosing has the potential disadvantage of causing adverse GI effects due to repetitive, continuous and additive irritation to the GI tract.
· Daily dosing is burdensome because of the requirements that the medication be taken on an empty stomach and that administration be followed by a period of fasting and maintenance of an upright posture.
· Daily dosing of some bisphosphonates has a further disadvantage in that it can cause decline in bone mineralization. It is not suggested that this disadvantage occurs with alendronate.
· Cyclic regimens are generally intermittent, as opposed to continuous, having treatment periods during which the medication is administered, and non-treatment periods, to 'permit the systemic level of the bisphosphonate to return to base line'.
· Cyclic regimens, as compared to continuous dosing, 'appear to result in a decreased therapeutic antiresorptive efficacy'. It seems that this has not been specifically demonstrated with respect to alendronate.
· Cyclic regimens do not eliminate or minimize adverse GI effects because such regimens typically utilize periods of multiple daily dosing.
· Cyclic regimes are cumbersome to administer and have the disadvantage of low patient compliance, resulting in compromised therapeutic efficacy.
· US Patent No 5,366,956 ('Strein') addresses the problem of adverse GI effects by teaching the administration of a polyphosphonate compound, either orally, subcutaneously or intravenously, according to an intermittent dosing schedule, having both a bone resorption inhibition period and a 'no treatment' rest period.
· That regimen has the disadvantage of not being continuous and regular and requiring nontreatment periods ranging from 20 - 120 days.
· PCT Application Number WO 95/30421 ('Goodship') discloses methods for preventing prosthesis loosening and migration using various bisphosphonate compounds, including administration of a once-weekly partial dose. However it does not address the issue of adverse GI effects or disclose administration of larger or multiple dosages.
28 Against this background, Merck claims that:
'It is seen from the current teachings that both daily and cyclic treatment regimens have shortcomings, and that there is a need for development of a dosing regimen to overcome these shortcomings.'
29 The specification then continues:
'In the present invention, it is found that the adverse gastrointestinal effects that can be associated with daily or cyclic dosing regimens can be minimized by administering the bisphosphonate at a relatively high unit dosage according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing. In other words, it is found that the administration of a bisphosphonate at a high relative dosage at a low relative dosing frequency causes less adverse gastrointestinal effects, particularly esophageal effects, compared to the administration of a low relative dosage at a high relative dosing frequency. This result is surprising in view of the teachings suggesting that adverse gastrointestinal effects would be expected to increase as a function of increasing bisphosphonate dosage.
Such administration methods of the present invention would be especially beneficial in treating patients that have been identified as suffering from or are susceptible to upper gastrointestinal disorders, e.g. gastrointestinal reflux disease (i.e. 'GERD'), esophagitis, dyspepsia (i.e. heartburn), ulcers, and other related disorders. In such patients conventional bisphosphonate therapy could potentially exacerbate or induce such upper gastrointestinal disorders.
From a patient lifestyle standpoint, the method of the present invention would also be more convenient than daily or cyclic dosing regimens. Patients would be subjected less frequently to the inconvenience of having to take the drug on an empty stomach and having to fast for at least 30 minutes after dosing. Also, patients would not need to keep track of the complex dosing regimen. The methods of the present invention are likely to have the advantage of promoting better patient compliance, which in turn can translate into better therapeutic efficacy.'
30 The specification describes the invention as follows:
'The present invention relates to a method, preferably an oral method, for inhibiting bone resorption in a mammal in need thereof, while minimizing the occurrence of or potential for adverse gastrointestinal effects. The present invention relates to methods of treating or preventing abnormal bone resorption in a mammal in need of such treatment or prevention. The methods of the present invention comprise orally administering to a mammal a pharmaceutically effective amount of a bisphosphonate as a unit dosage, wherein said dosage is administered according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing. In other embodiments, the present invention relates to methods comprising a continuous dosing schedule having a dosing periodicity ranging from about once every 3 days to about once every 16 days. Typically, the continuous dosing schedule is maintained until the desired therapeutic effect is achieved for the mammal.
The present invention utilizes higher unit dosages of the bisphosphonate at each dosing point than has heretofore been typically administered, yet because of the dosing schedule chosen, the potential for adverse gastrointestinal effects are minimized. Moreover, the method is more convenient because the disadvantages associated with daily dosing are minimized.'
31 A number of terms are then defined, including the following:
'The term "pharmaceutically effective amount", as used herein, means that amount of the bisphosphonate compound, that will elicit the desired therapeutic effect or response when administered in accordance with the desired treatment regimen. A preferred pharmaceutically effective amount of the bisphosphonate is a bone resorption inhibiting amount.'
'The term "minimize the occurrence of or potential for adverse gastrointestinal effects", as used herein, means reducing, preventing, decreasing or lessening the occurrence of or the potential for incurring unwanted side effects in the gastrointestinal tract … .'
'The terms "continuous schedule" or "continuous dosing schedule", as used herein, mean that the dosing regimen is repeated until the desired therapeutic effect is achieved. The continuous schedule or continuous dosing schedule is distinguished from cyclical or intermittent administration.'
'The term "until the desired therapeutic effect is achieved", as used herein, means that the bisphosphonate compound is continuously administered, according to the dosing schedule chosen, up to the time that the clinical or medical effects sought for the disease or condition is observed by the clinician or researcher. … Nonlimiting examples of administration periods can range from about 2 weeks to the remaining lifespan of the mammal. For humans, administration periods can range from about 2 weeks to the remaining lifespan of the human, preferably from about 2 weeks to about 20 years, more preferably from about 1 month to about 20 years, more preferably from about 6 months to about 10 years, and most preferably from about 1 year to about 10 years.'
32 Under the heading 'Methods of the Present Invention', it is said that:
'The methods of the present invention do not have the disadvantages of current methods of treatment which can cause or increase the potential for adverse gastrointestinal effects or which require cumbersome, irregular or complicated dosing regimens.'
The present invention comprises a continuous dosing schedule whereby a unit dosage of the bisphosphonate is regularly administered according to a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing.
By once-weekly dosing is meant that a unit dosage of the bisphosphonate is administered once a week, i.e. one time during a seven day period, preferably on the same day of each week. In the once-weekly dosing regimen, the unit dosage is generally administered about every seven days. A nonlimiting example of a once-weekly dosing regimen would entail the administration of a unit dosage of the bisphosphonate every Sunday. It is preferred that the unit dosage is not administered on consecutive days, but the once-weekly dosing regimen can include a dosing regimen in which unit dosages are administered on two consecutive days falling within two different weekly periods.'
33 This seems to mean that the once-weekly dosing regimen permits administration of weekly doses on, say, the Sunday at the end of one week and the Monday at the commencement of the next. However this is not a preferred method.
34 The specification provides that:
'The methods of the present invention are intended to specifically exclude methods for the treatment and/or prevention of prosthesis loosening and prosthesis migration in mammals as described in …[Goodship], published November 16, 1995, which is incorporated by reference herein in its entirety.'
We have previously referred to Goodship and will return to it at a later stage. Under the heading 'Pharmaceutical Compositions' in the specification of the Patent, there is a discussion of available bisphosphonate preparations. There is then a discussion of dosage as follows:
'The precise dosage of the bisphonate will vary with the dosing schedule, the oral potency of the particular bisphosphonate chosen, the age, size, sex and condition of the mammal or human, the nature and severity of the disorder to be treated, and other relevant medical and physical factors. Thus, a precise pharmaceutically effective amount cannot be specified in advance and can be readily determined by the caregiver or clinician. Appropriate amounts can be determined by routine experimentation from animal models and human clinical studies. Generally, an appropriate amount of bisphosphonate is chosen to obtain a bone resorption inhibiting effect, i.e. a bone resorption inhibiting amount of the bisphosphonate is administered. For humans, an effective oral dose of bisphosphonate is typically from about 1.5 to about 6000 μg/kg body weight and preferably about 10 to about 2000 μg/kg of body weight.
For human oral compositions comprising alendronate, pharmaceutically acceptable salts thereof, or pharmaceutically acceptable derivatives thereof, a unit dosage typically comprises from about 8.75 mg to about 140 mg of the alendronate compound, on an alendronic acid active weight base, i.e. on the basis of the corresponding acid.'
35 We do not understand the specification to be teaching new information concerning dosing levels but rather reflecting earlier learning. The specification also provides that:
'For once-weekly dosing, an oral unit dosage comprises from about 17.5 mg to about 70 mg of the alendronate compound, on an alendronic acid active weight basis. Examples of weekly oral dosages include a unit dosage which is useful for osteoporosis prevention comprising about 35 mg of the alendronate compound, and a unit dosage which is useful for treating osteoporosis comprising about 70 mg of the alendronate compound.'
These are the dosing levels identified in claims 1 and 2.
36 Experiments on dogs are then described, concluding with the following observations:
'These experiments demonstrate that considerably less esophageal irritation … is observed from the administration of a single high concentration dosage of alendronate … versus administration of low concentration dosages on consecutive days … . These experiments also demonstrate considerably less esophageal irritation is observed from the administration of a single high concentration of alendronate on a weekly basis … versus administration of low concentration dosages on consecutive days … .'
37 In effect, the specification teaches weekly, rather than daily administration of the relevant dose of alendronate. The size of the dose will vary, depending upon potency of the drug and age, size, sex and condition of the patient, including severity of the disorder, and "other relevant medical and physical factors". The dosages of 35 mg and 70 mg identified in claims 1 and 2 seem to be examples only. We do not understand there to be any claimed invention in their selection. Each quantity is described in the relevant claim as "a pharmaceutically effective amount", but that will be so only if the identified dosage is that deemed by the "care giver or clinician" to be appropriate for the particular patient. It seems that claim 3 comprehensively identifies the claimed invention, whilst claims 1 and 2 are specific examples of it. (See Patent at p 18 ll 26-31.)
38 We should also say something about the use in the specification of the terms "cyclic" and "intermittent". The specification asserts that the expression "cyclic regimen" generally involves intermittent, rather than continuous treatment regimens. We infer that cyclic regimens involve periods of treatment and periods of rest from treatment, whereas continuous dosing involves administration of fixed dosages at regular intervals. It is said that cyclic regimens do not eliminate or minimize adverse gastro-intestinal effects 'because such regimens typically utilize periods of multiple daily dosing.' The term 'multiple daily dosing' seems to mean dosing on consecutive days. As cyclic regimes are said generally to involve intermittent treatment regimes, it is implied that intermittent regimes involve daily dosing. It is also asserted that Strein involves an intermittent, rather than a continuous, treatment regime, perhaps inviting the inference that Strein teaches multiple daily dosing as opposed to weekly dosing. Such an inference would be incorrect. Strein teaches (amongst other things) weekly administration of alendronate for the treatment of osteoporosis, although with rest periods. Similarly, Goodship teaches weekly administration of alendronate in doses which include those specified in claims 1 and 2 of the Patent (and, by inference, claim 3), but for a different medical condition. However Goodship asserts that such treatment involves dosages similar to those used in treating osteoporosis. Both Strein and Goodship are expressly incorporated into the Patent. As we have observed the primary judge effectively concluded that the claimed invention was merely a use of alendronate which was analogous to known uses and that:
'All that has been discovered … is that if the compound is administered once a week rather than daily, one of its disadvantageous side effects will be less than it otherwise would be.'
39 In construing the specification we will refer in some detail to Strein and Goodship which are incorporated into it. Those documents support his Honour's conclusion.