Invention; "manner of new manufacture"; inventive step
19 A "patentable invention" must be an "invention" as defined, and thus a "manner of new manufacture the subject of letters patent and grant of privilege within section 6 of the Statute of Monopolies". The primary judge held, following NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1995) 183 CLR 655, that the opening words of s 18(1) impose a threshold requirement of inventiveness: a requirement independent of the specific provisions of s 18(1)(b) as to novelty and an inventive step, judged by comparison with the prior art base as it existed before the priority date. His Honour held that the claimed invention (we use that expression to refer to the invention claimed in each of the petty patents in suit) did not meet that threshold requirement. He held also that it did not involve an inventive step when compared with the prior art base. His Honour's conclusions were based upon two findings. One of them involved an application of the well known principle which denies patentability to a claimed invention which is "nothing but a claim for the use of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable": Commissioner of Patents v Microcell Ltd (1959) 102 CLR 232 at 251. His Honour said at 477:
"At the priority date the material (taxol) had been known for many years. It is a naturally‑occurring compound and thus in itself unpatentable. In the words of the specification, taxol had 'shown great promise as an anti‑cancer drug' and 'been found to be an active agent against drug‑refractory ovarian cancer' … . The properties which made taxol effective against cancer, that is to say its biological mechanism, were well known. They had been discussed in the articles referred to in the specification which were 'incorporated by reference as if reproduced in full below' … . Thus the specification is not merely a claim of a 'new use of an old substance' (Re BA's Application (1915) 32 RPC 348 at 349, Mirabella, 183 CLR at 661) but a claim for the same use of an old substance."
The primary judge, at 477, expressed his other finding as follows:
"Further, the specifications disclose that the claimed inventions were the product of routine testing which merely verified a hypothesis arising from analysis of reports of earlier trials: see WR Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) 25 IPR 481 at 497-498.
By using the term 'routine' I do not wish to be taken as in any way disparaging the skill and effort which obviously went into [the study leading to the claimed inventions]. But the petty patents in suit do not claim any method of scientific investigation or analysis. On their face they claim a particular dosage over a particular period of a substance known to be effective, in a known way, for the treatment of cancer, a dosage and a period arrived at by the 'ordinary methods of trial and error which involve no inventive step …': Van der Lely NV v Bamfords Ltd [1963] RPC 61 at 71 per Lord Reid, cited with approval in Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 at 530 per Gummow J (with whom Jenkinson J agreed)."
20 Nothing in the more recent decision of the High Court in Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd (1998) 194 CLR 171 detracts from the binding effect, in this Court, of the decision in Philips. Ramset fell to be decided under the Patents Act 1952 (Cth) (the "1952 Act"); the Court distinguished Philips on the basis that there were significant differences between the 1990 Act and its predecessor, so that Philips was not determinative of a question arising under s 100 of the 1952 Act. It is necessary, therefore, to ascertain precisely what was decided in Philips. The essence of the decision is, we think, to be found in the following passage in the judgment of the majority, at 663, 664 (omitting citations of authority):
"The effect of those opening words of s 18(1) is that the primary or threshold requirement of a 'patentable invention' is that it be an 'invention'. Read in the context of s 18(1) as a whole and the definition of 'invention' in the Dictionary in Sch 1, that clearly means 'an alleged invention', that is to say, an 'alleged' 'manner of new manufacture the subject of letters patent and grant of privilege within s 6 of the Statute of Monopolies'. In the light of what has been said above about what is involved in an alleged manner of new manufacture, that threshold requirement of 'an alleged invention' will, notwithstanding an assertion of 'newness', remain unsatisfied if it is apparent on the face of the relevant specification that the subject matter of the claim is, by reason of absence of the necessary quality of inventiveness, not a manner of new manufacture for the purpose of the Statute of Monopolies. That does not mean that the threshold requirement of 'an alleged invention' corresponds with or renders otiose the more specific requirements of novelty and inventive step (when compared with the prior art base) contained in s 18(1)(b). It simply means that, if it is apparent on the face of the specification that the quality of the inventiveness necessary for there to be a proper subject of letters patent under the Statute of Monopolies is absent, one need go no further."
The majority, at 663, rejected an argument:
"… that the fact that a claimed use is 'nothing but … a new use of an old substance' and therefore 'outside the whole scope of what is known as an invention' under traditional principles of patent law will not of itself preclude it from being a proper subject of letters patent under the Act."
21 Secondly, at 664, 665, the majority said:
"It is true that it can be argued that there is internal tension in an overall legislative scheme which imposes a threshold requirement of inventiveness reflecting the effect of the saving clause in s 6 of the Statute of Monopolies and then proceeds, if that threshold requirement be satisfied, to impose more specific requirements of novelty and inventive step. It seems to us, however, that there are several answers to that argument. One is that there is no construction of s 18(1) of the Act which is not susceptible of some legitimate criticism. Another is that traditional patents law under s 6 of the Statute of Monopolies long recognised cumulative requirements of an element of invention (as distinct, from, eg, mere discovery or analogous use) in the subject matter as described by the specification and novelty or newness as disclosed by comparison with a prior art base. The distinctive requirements of novelty and inventive step required by s 18 of the Act are emphasised by their elaboration in s 7. In that regard it may be noted that in the 1952 Act one of the grounds for revocation of a patent was that the invention 'was obvious and did not involve an inventive step, having regard to what was known or used in Australia' (s 100(1)(e)). More important, it seems to us to be highly unlikely that it was the legislative intent that there should be a significant alteration of the law as explained in Microcell by extending the ambit of a patentable invention so as to include what is 'nothing more' than 'the use of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable'. In that regard, we do not accept the argument on behalf of Philips that Microcell was decided on the question of newness and not on manner of manufacture."
22 Thirdly, their Honours observed, at 667, that "… it would border upon the irrational if a process which was in fact but a new use of an old substance could be a 'patentable invention' under s 18 if, but only if, that fact were not disclosed by the specification". But, as the majority explicitly acknowledged, at 666, that observation was unnecessary to their decision. Fourthly, and finally, special leave to appeal had been granted on the basis that the sole issue on the appeal was the true construction of s 18(1)(a), including the opening words of s 18(1). Thus, the Court was not called upon to consider the correctness of the finding of the Full Court of this Court, that the claims of the patent in suit were indeed for nothing but a use of a known product for a purpose for which its known properties made it suitable.
23 It is important also to remember that the effect of the decision of the High Court in Philips was to affirm the decision of the Full Court (NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1993) 44 FCR 239). There is no doubt that the majority of the Full Court (Lockhart J, with whom Northrop J agreed) drew what they perceived to be a clear distinction between obviousness or want of inventive step (s 18(1)(b)(ii)) and want of inventiveness sufficient to characterise the subject matter of a patent as a manner of new manufacture. So, at 263, Lockhart J said:
"Although grounds of objection in patent law sometimes overlap, objections of want of novelty and obviousness are nevertheless essentially distinct from each other. Likewise, the requirement that a patentable invention be a manner of new manufacture is inherently distinct from the requirements of novelty, lack of obviousness, involving an inventive step and utility as required by s 18 of the 1990 Act."
And the point emerges clearly from the following observation of Lockhart J at 265:
"Many of the submissions made by counsel for the appellants on this point blurred the distinction between the requirement that the invention be a manner of new manufacture and obviousness. The respondent did not press its case at the trial (nor therefore on appeal) on obviousness, no doubt, at least in part, because the respondent could not establish that what is described in the evidence as the Vrenken Article was common general knowledge in Australia."
In other words, what cannot be established not to involve an inventive step, by reference to common general knowledge in Australia at the priority date, may nevertheless exhibit a want of the quality of inventiveness which is part of the concept of manner of new manufacture.
24 Four comments may be made. First, the proposition that "inventiveness" means in one context something quite distinct from the connotation, in the other, of "inventive step" (or lack of obviousness) is not easy to reconcile with the analysis of Gummow J, with whom Jenkinson J agreed, in R D Werner & Co Inc v Bailey Aluminium Products Pty Ltd (1989) 25 FCR 565 at 593, 599-601. Secondly, so far as the reasoning of Lockhart J depended (see at 263) upon regarding the 1990 Act as having made no relevant change in the law (a view with which it is easy to sympathise, given s 100(d) of the 1952 Act), the distinction between the two aspects of inventiveness having existed under the 1952 Act, that foundation appears to have been removed by Ramset. Thirdly, Lockhart J (upholding the primary judge) appeared to have looked solely at the specification in order to ascertain what was "known", for the purposes of the Microcell principle, though his Honour appears to have relied on other evidence as to aspects of the quality of inventiveness. Fourthly, and perhaps most importantly, little guidance is offered as to how one ascertains whether a claimed invention has the quality of inventiveness necessary to characterise it as a manner of new manufacture.
25 Just as it is not easy to see how one can describe something as new or novel except by reference to what has previously been made, done or published, we cannot see how inventiveness can be judged except by reference to a body of prior knowledge and from the standpoint of someone who has that knowledge. The question, then, is what knowledge, in whose possession, is relevant to the question whether the "inventiveness" component of "manner of new manufacture" is present?
26 It is important, we think, to recognise that the present separate requirements of novelty and an inventive step (s 18(1)(b)(i) and (ii)) themselves result from a process of development, both through the cases and in successive statutes, of the language of the Statute of Monopolies. The history is traced by Gummow J in R D Werner at 594-601 and need not be repeated. The ground of revocation, and now of opposition to grant, encapsulated in the terms "want of subject matter", "obviousness" and "lack of inventive step", is itself a development and refinement of the language of the Statute of Monopolies. If one were still to apply the language used by Lord Esher MR in 1894 - "when you consider it, you come to the conclusion that it is so easy, so palpable, that everybody who thought for a moment would come to the same conclusion; or, in more homely language, hardly judicial, but rather business like, it comes to this, it is so easy that any fool could do it" (Edison-Bell Phonograph Corp Ltd v Smith (1894) 11 RPC 389 at 398) - the question would remain, what is the prior body of knowledge which makes it so easy? In Philips, Lockhart J said at 265:
"As mentioned earlier the expressions 'manner of new manufacture' and 'manner of manufacture' in this branch of law under the 1990 Act mean the same thing and involve the same concepts as they have been understood and developed since 1623 when the Statute of Monopolies was passed."
But, with respect, that begs the question, which are the developments referred to? The modern notions of novelty and obviousness represent, as we have said, developments of the concepts in the Statute. Is there a tertium quid? If so, what precisely is it? It might, perhaps, be supposed that, by preserving the requirement of inventiveness incorporated in "manner of new manufacture", Parliament intended that there be two cumulative requirements, one reflecting the law as it had developed up to some statutory intervention - perhaps in 1952, perhaps in 1990 - the other reflected in the elaborate provisions of s 7(2) and s 7(3), read with the dictionary in Sch 1, of the 1990 Act. Where, however, the judicial and statutory development of the law are as interwoven as they have been in patent law, such a suggestion encounters great difficulty.
27 Philips, as we read it, does not provide a comprehensive answer to the question, by reference to what body of knowledge is that inventiveness judged? It holds, clearly, that the requirement of inventiveness is not satisfied in a case where the claims are for nothing more than the use of a known material in the manufacture of known articles for a purpose for which that material's known properties make it suitable. The majority judgment of the High Court in Ramset points out, at 192, two aspects of that proposition which are, we think, relevant to the present case. One is that the principle that "a claim for 'nothing but' a new use of an old substance lacked the quality of inventiveness" had emerged in the course of the development, during the nineteenth century, of "the doctrine with respect to obviousness and lack of inventive step"; the other is that, if an application for a patent claiming nothing but a new use of an old substance (to adopt the majority's shorthand) proceeded to grant, the grant - under the 1952 Act - would have been liable to revocation under s 100(e) (obviousness) not s 100(d) (not an invention: that is, not a manner of new manufacture). In other words, the relevant ground of revocation being obviousness, the relevant body of knowledge was "what was known or used in Australia on or before the priority date of [the] claim": that is, common general knowledge, in the relevant field of endeavour, in Australia: Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 at 295.
28 Microcell was an appeal from a refusal by the Commissioner of Patents to accept an application and complete a specification. The Court held, at 246, that "[it] must be enough to warrant rejection that it should be clear on its face that the specification discloses no inventive step". Their Honours proceeded to hold that the specification in suit disclosed no such step. It is interesting to note, in passing, that their Honours used the phrase "inventive step", the terminology both of s 100(e) of the 1952 Act (which did not apply to the application before the Court: it was required to be considered under the Patents Act 1903 (Cth)) and s 18(1)(b)(ii) of the 1990 Act. The claims were for the manufacture of self‑propelled rocket projectors, using synthetic resinous plastic material reinforced with mineral fibres. The Court's conclusion was expressed at 251 as follows:
"We have in truth nothing but a claim for the use of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable. A claim for nothing more than that cannot be subject matter for a patent, and the position cannot be affected either by the fact that nobody thought of doing the thing before, or by the fact that, when somebody did think of doing it, it was found to be a good thing to do."
The foundation of that conclusion, however, appears in the following paragraph, at 250:
"Here the specification does not on its face disclose more than a new use of a particular known product. To use Lord Buckmaster's words, no new product is obtained, and there is no new method of manufacture suggested or an old one improved. Tubular self‑propelled‑rocket projectors were at the relevant time well‑known articles of manufacture. Synthetic resinous plastics reinforced with mineral fibres, and in particular polyester plastics reinforced with glass or asbestos fibres, were well‑known materials. These things are to be gathered from the specification itself, which contains no suggestion of novelty in relation to the article to be manufactured or the material to be used. It further appears from matter published in Australia as early as 1946 that the reinforced plastic materials referred to in the specification had been used in the manufacture of a wide variety of articles. The properties of those materials were known generally, and in particular it was well known that they possessed that combination of great strength and lightness wherein, according to the specification itself, lies their virtue for the purpose in hand. The matter published in 1946 refers to their 'extraordinary strength in relation to weight' - they are 'stronger for their weight than steel' - and to their high tensile strength - another quality which the specification regards as a virtue for the purpose in hand. It was well known too that they possessed high impact strength and high resistance to heat. In these circumstances we do not think it can be said, merely because it does not seem previously to have occurred to anyone to make a rocket projector out of reinforced plastic, that any inventive idea is disclosed by the specification."
29 That passage makes it quite clear that the lack of inventive step appeared on the face of the specification. It makes it clear also that the conclusion that there was no inventive step was reinforced by a consideration of material earlier published in Australia, information in which was "well‑known" and "known generally". Although the language used by the Court differs somewhat from the formulation adopted by Aickin J in the Minnesota case, the substance of the Court's finding was that what was apparent on the face of the specification was reinforced by proof that particular information had passed into common general knowledge, in the relevant field, in Australia.
30 The majority of the High Court in Philips explicitly say that their observations about a case where want of the threshold requirement of inventiveness is not apparent on the face of the specification are not necessary to their decision. And, in discussing the commencement point (what is "known") of the inquiry about inventiveness, their Honours refer only to the Microcell principle. In our view, in the light of the authorities to which we have referred, Philips stands for the proposition (as a matter of construction of the 1990 Act) that if, on the basis of what was known, as revealed on the face of the specification, the invention claimed was obvious or did not involve an inventive step - that is, would be obvious to the hypothetical non‑inventive and unimaginative skilled worker in the field (Minnesota at 260 per Barwick CJ) - then the threshold requirement of inventiveness is not met. Some elaboration, however, is required in relation to what the specification reveals as "known". If a patent application, lodged in Australia, refers to information derived from a number of prior publications referred to in the specification or, generally, to matters which are known, in our view the Court - or the Commissioner - would ordinarily proceed upon the basis that the knowledge thus described is, in the language of s 7(2) of the 1990 Act, part of "the common general knowledge as it existed in the patent area". In other words, what is disclosed in such terms may be taken as an admission to that effect. In substance, we think, that is what happened, both in Microcell and in Philips. If, however, the body of prior knowledge disclosed by the specification is insufficient to deprive what is claimed of the quality of inventiveness, then the only additional knowledge or information which will be taken into account is knowledge or information of a kind described in s 7(2) of the 1990 Act. That again, in our view, is consistent with the approach taken in Microcell. It is also, with respect, the only approach which does not, in practical terms, render s 18(1)(b)(ii) otiose. Of course, once that additional knowledge is taken into account, one is applying s 18(1)(b)(ii), not the opening words of s 18(1) - unless, perhaps, one might apply either, there being, in this respect, no difference between them.
31 The findings of the trial judge as to the failure of the claims to meet the threshold requirement of inventiveness relied, as to what was known and as to the studies leading to the claimed invention, only upon what is disclosed in the specifications. The specifications reveal, as his Honour pointed out, that both the efficacy of taxol as an anti‑carcinogenic (particularly in relation to drug‑refractory ovarian cancer) and the mechanism of its action were known. His Honour found, accordingly, that the claimed invention was not merely a claim for a new use for an old substance (his Honour's shorthand) but a claim for the same use of an old substance, thus failing the Microcell test. In our opinion, however, that formulation overlooks two things. One is that the claim is for a method, not a product; the other is the importance of the phrase "nothing but" in the Microcell principle: as to both points, see National Research Development Corporation v Commissioner of Patents (1959) 102 CLR 252, especially at 262. Taxol may, if used in accordance with the claimed invention, be used for a purpose for which its known properties make it suitable; it does not follow that the method claimed does not involve an inventive step. Nor, if the method was proved to be efficacious by a routine process of trial and error (the authorities cited by his Honour have to do with how much, in order to destroy novelty, an anticipation must reveal), does it follow that the claimed invention is obvious or does not involve an inventive step: what matters is whether, to the skilled but unimaginative worker in the field, the claimed method was obvious in the sense that the worker, not necessarily seeing that the method was likely to be safe and efficacious, would have seen that it was one which justified investigation.
32 Because, for the reasons we have given, we respectfully disagree with the primary judge's approach to this part of the case, it is now necessary that we consider the specifications for ourselves. The section entitled "background of the invention" begins as follows:
"Taxol is a naturally occurring compound which has shown great promise as an anti‑cancer drug. For example, taxol has been found to be an active agent against drug‑refractory ovarian cancer by McGuire et al. See 'Taxol: A Unique Anti‑Neoplastic Agent With Significant Activity Against Advanced Ovarian Epithelial Neoplasms,' Ann. Int. Med., 111, 273- 279 (1989). All patents, scientific articles, and other documents mentioned herein are incorporated by reference as if reproduced in full below.
Unfortunately, taxol has extremely low solubility in water, which makes it difficult to provide a suitable dosage form. In fact, in Phase I clinical trials, severe allergic reactions were caused by the emulsifiers administered in conjunction with taxol to compensate for taxol's low water solubility; at least one patient's death was caused by an allergic reaction induced by the emulsifiers. Dose limiting toxicities include neutropenia, peripheral neuropathy, and hypersensitivity reactions."
33 The article by McGuire and others, referred to in the first paragraph, describes also taxol's "unique" mechanism of action. The specifications proceed to discuss a good deal of literature concerning taxol, particularly a number of reports of Phase I and Phase II clinical trials (the purpose of a Phase I trial is to ascertain a safe dose limit; a Phase II trial tests for efficacy under particular treatment regimes, within the safe limit established by Phase I trials). What the specifications say is not altogether easy to follow, because their account of the teaching of the various articles quoted is, in many cases, somewhat abbreviated and the writings are not discussed in chronological order, so that it is difficult to see the way in which expert thinking about the administration of taxol evolved during the period covered by the writings, from 1986 to 1991. For example, the specifications report this:
"Since early trials using a bolus injection or short (1‑3 hour) infusions induced anaphylactic reactions or other hypersensitivity responses, further studies were carried out in which taxol was administered only after premedication with steroids (such as dexamethasone), antihistamines (such as diphenhydramine), and H2-antagonists (such as cimetidine or ranitidine), and the infusion time was extended to 24 hours in an attempt to eliminate the most serious allergic reactions. Various Phase I and Phase II study results have been published utilising 24‑hour infusions of taxol with maximum total dosages of 250 mg/m2, generally with the course being repeated every three weeks."
34 Nevertheless, one of the most recent of the trials referred to, a Phase I trial reported in a July 1991 article by Brown and others, was one in which taxol was provided by a six‑hour infusion every twenty‑one days without premedication. The authors reported that the incidence of hypersensitivity reaction was "schedule‑dependent, 6 to 24-hour infusions of drug having a 0% to 8% incidence of hypersensitivity reactions". The specifications paraphrase the authors as reporting also "that hypersensitivity reactions persist with or without premedication despite prolongation of infusion times".
35 Among the matters which emerge from the writings quoted are that the toxicity of the drug limited the dose which could safely be administered, the maximum tolerated dose being about 275mg/m2 ("m2" refers to the surface area of the skin of the patient); the incidence of hypersensitivity reactions appeared to be substantially reduced by a combination of premedication and prolongation of the infusion period to six hours or longer; but none of the material reported the administration of the drug over a period of less than six hours with premedication; however it was unclear whether those reactions were caused by the taxol or the vehicle in which it was administered; and, because hypersensitivity reactions frequently occurred within a short period after the commencement of infusion, the proposition that lengthening infusion time minimised the likelihood of reaction was uncertain; and because of the relatively high number of the trials which had used a twenty‑four hour infusion schedule, there was a lack of data as to the efficacy of infusion over a shorter period. The specifications continue:
"The conflicting recommendations in the prior art concerning whether premedication should be used to avoid hypersensitivity reactions when using prolonged infusion durations, and the lack of efficacy data for infusions done over a six hour period has led to the use of a 24‑hour infusion of high doses (above 170 mg/m2) of taxol in a Cremophor EL emulsion as an accepted cancer treatment protocol.
Although it appears possible to minimise the side effects of administering taxol in an emulsion by use of a long infusion duration, the long infusion duration is inconvenient for patients, and is expensive due to the need to monitor the patients for the entire 6 to 24‑hour infusion duration; further, the long infusion duration requires that patients spend at least one night in a hospital or treatment clinic."
36 The matters, therefore, requiring to be addressed were the need to reduce the infusion period sufficiently so that both premedication and infusion could be completed during the course of a day, so that patients could be treated as outpatients; the consequent desirability of limiting infusions to a maximum of six hours while nevertheless providing sufficient taxol to have the desired therapeutic effect, at the same time avoiding toxicity; the desirability of minimising premedication, to reduce both patient discomfort and the expense and duration of treatment; and the desirability of reducing doses, if possible, not only to reduce side effects but also to "extend the supply of taxol".
37 The objects of the invention are stated as follows:
"Therefore, it is a primary object of the present invention to provide a new method for administering taxol over a shorter period of time than the present 6 to 24‑hour infusion protocols, while minimising toxic effects induced by the administration of taxol.
It is another object of the present invention to provide a new method for administration of taxol which reduces the amount of taxol administered to a patient, without sacrificing the anti‑neoplastic effects desired by administering taxol.
It is yet a further object of the present invention to provide a new method for administration of taxol which utilizes both lower dosages of taxol and shorter infusion periods, without sacrificing the anti‑neoplastic benefits of the administration of taxol."
38 There follows a detailed description of the invention which, although it is lengthy, we think it is desirable to set out in full:
"Despite the conventional understanding that it is necessary to infuse patients over a 24‑hour period with high dosages of taxol (greater than 170 mg/m2) following premedication to minimize or eliminate hypersensitivity responses, while obtaining the desired anti‑neoplastic effect, it has been surprisingly discovered that taxol can be safely administered to cancer patients via infusions lasting less than 6 hours at dosages of about 135 mg/m2 to about 175 mg/m2. In a preferred embodiment, taxol is administered via an infusion having a duration of about three hours, with a taxol dosage of about 135 mg/m2 or about 175 mg/m2. Of great significance is a surprising discovery that the short term infusion causes less myelosuppression, which leads to a lower incidence of infections and fever episodes (e.g., febrile neutropenia). Following the preferred infusion schedules of the present invention provides an objective response rate of greater than 10% for patients suffering from epithelial ovarian carcinoma, and preferably an objective response rate of 14% or greater for groups of at least 150 patients suffering from ovarian carcinoma.
The surprising discovery that taxol could be safely administered via a short infusion (e.g., less than six hours and preferably over about 3 hours) means that it will now be possible to administer taxol on an out‑patient basis, saving patients the time and expense of yet another hospitalization while improving patient quality of life.
It has also been surprisingly discovered that lower taxol dosages, such as about 135 mg/m2 can be administered via infusions lasting about 3‑hours to about 28‑hours, and still be antineoplastically effective."
39 The specifications proceed to discuss the study from which the applications for the petty patents resulted. It was a randomised comparative study, conducted in a number of centres in Canada and Europe, of treatment with taxol of patients suffering from ovarian carcinoma who had previously been treated with platinum‑based drugs. Each patient was assigned to one of four "arms". Those in Arm A were treated with infusions of 175mg/m2 over twenty‑four hours; those in Arm B with infusions of 175mg/m2 over three hours; those in Arm C with infusions of 135mg/m2 over twenty‑four hours; and those in Arm D with infusions of 135mg/m2 over three hours. All patients were premedicated to minimise acute hypersensitivity reactions.
40 What, then, was the outcome? As to response, complete or partial (reduction in tumour size), the specifications say:
"Thus, use of the present method for administration of taxol produces at least a 14% overall objective response rate for 157 patients. This is an astonishing result, since all of the patients were considered drug refractory. It is also remarkable that 3 out of 46 (7%) of these patients who had progressed on previous platinum containing chemotherapy responded to taxol. Overall, responses to taxol occurred in 13% of patients (14/114) who were considered resistant to platinum therapy … . Further, 52% of patients (24/46) with disease truly refractory to platinum, and 53% of patients (16-36) with an early relapse after platinum, achieved a stabilization of their disease."
41 It may be noted in passing that the specifications do not distribute those results among the various treatment "arms". As for toxicity, the specifications record that serious neutropenia was five times more frequent among those patients infused over twenty‑four hours than those treated with a three hour infusion; severe neutropenia was somewhat more prevalent in the high dose arms than in the low dose arms. Thus, we are told:
"… it is clear that both reducing the dosage and the infusion time will lower hematologic toxicity; however, reducing the infusion to 3 hours from 24 hours appears to have a greater impact on reducing toxicity than reducing the taxol dosage from about 175mg/m2 to 135mg/m2."
Peripheral neuropathy occurred more frequently in the high dose than in the lower dose arm, and somewhat more frequently in patients who received the 3 hour infusion than in those who were infused over 24 hours. Two patients suffered hypersensitivity reactions "which required acute therapeutic intervention". One was treated with 135mg/m2 of taxol infused over twenty‑four hours. It is not stated in which arm the other patient was treated. Less significant hypersensitivity reactions were experienced by some patients in all arms.
42 The results are summarised as follows:
"The success of the use of the new taxol infusion protocol of the present invention in the treatment of ovarian cancer makes it readily apparent that anti‑neoplastically effective dosages of taxol can be infused over much shorter time periods than was previously believed possible, without inducing severe hypersensitivity reactions or inducing fatal anaphylactic shock. Thus, it is contemplated that the infusion protocol of the present invention may be utilized to treat solid tumors and leukemias, such as but not limited to lung cancer, breast cancers, and ovarian cancers. It is to be understood that treatment of different forms of cancer may require the adjustment of the taxol dosage to have optimal efficacy.
The foregoing clearly establishes that taxol is both safe and effective in the treatment of cancer, such as ovarian cancer, when administered according to the protocol of the present invention. In particular, by use of a 3‑hour infusion of about 135 mg/m2 taxol, following premedication, a substantial reduction results in the frequency of myelotoxicity and neuropathy associated with the administration of taxol to patients suffering from cancer. Further, patients who exhibit severe hypersensitivity reactions can be rechallenged with taxol after treating the HSR symptoms by use of an infusion of about 24 hours or greater, preferably using a dosage of about 135 mg/m2 to about 175 mg/m2. Preferably, colony stimulation factors are administered to assist in ameliorating myelosuppression.
The use of lower dosages of taxol to achieve antineoplastic results will allow for more patients to be treated with the present limited supply of taxol. Further, depending upon the toxicities noted in a patient during treatment with taxol according to the present protocol, the duration of infusion can be extended or shortened, or the taxol dosage can be reduced or increased, thus providing more flexibility in treating cancer with taxol. Further, patients capable of handling higher doses of taxol can be administered up to about 275 mg/m2; should the patient encounter severe toxicity, such as a severe neuropathy, the protocol of the present invention allows for reducing the dosage.
From the above teachings, it is readily apparent that many modifications and variations of the present invention are possible. It is to be therefore understood that the invention may be practiced [sic] than as otherwise specifically described."
43 In order to determine whether the claimed invention had the necessary quality of inventiveness what must be asked, in our view, is whether in the light of the prior body of knowledge discussed in the specification, and given the desirability of treating patients as outpatients rather than admitting them overnight and, generally, of reducing cost and inconvenience, the skilled but non‑inventive worker in the field would have seen that infusion over a period less than six hours (particularly, over three hours) with premedication, of approximately the doses actually selected for the trial, was worth trying. In answering that question, it must be borne in mind that "trying" was plainly a process which would involve considerable effort on the part of a large number of people, much expense and the subjection of patients, already very ill, to a form of treatment which, while it might in some cases produce some remission, was known to have the potential to cause very unpleasant, and sometimes life‑threatening, side effects: the circumstances by no means resemble the example of the stainless steel sink referred to in Microcell at 248.
44 What can be gathered from the specification is that the previous teaching encouraged longer infusions (usually twenty-four hours, but certainly not less than six), doses at the upper end of, or above, the range claimed in the petty patents and premedication. Infusions of shorter duration had been tried, without premedication, and had been found unsatisfactory. Given that, frequently, hypersensitivity reactions occurred shortly after the commencement of an infusion, there was some doubt as to whether the infusion period was actually of much significance in relation to reactions of that kind. Nevertheless, it could not be said that there was anything in the teaching referred to which particularly encouraged a view that a three hour infusion of dosages within the range claimed would be safe and would work. The position was simply that the administration of taxol in that way had not (so far as the material referred to goes) been tried, with premedication, and there were several practical reasons why it was desirable to reduce infusion times if possible. Is the Court, armed with that knowledge, equipped with the hindsight against which authority warns (see Minnesota at 293) but otherwise on the basis of its own untutored understanding (particularly, without the benefit of expert evidence), to say that the claimed invention lacks inventiveness (would have been obvious to the skilled worker in the field)? In our view, we should be very slow to do so. If one puts aside the benefit of hindsight, how is the Court to know whether experts would have found what was tried obvious or, for reasons of which we know nothing, counter‑intuitive? It is important to remember warnings (see, for instance, CCOM Pty Ltd v Jiejing Pty Ltd (1994) 51 FCR 260 at 285) that "[the] Court should be careful to avoid assuming a technical expertise it does not have". We are not prepared to hold, on the material before us, that the quality of inventiveness was lacking.
45 Indeed, there is in our view an element of unreality, in a case such as the present, even in posing the question in that form. Although Philips suggests that there may be such cases (it does not decide the question, because obviousness was not pressed), it is not easy to envisage circumstances in which a claimed invention may lack the threshold requirement of inventiveness, but yet involve (for the purposes of s 18(1)(b)(ii)) an inventive step. This is not a case, like Philips, where there was no attack on the patents on the ground of obviousness. It was, instead, a case where expert evidence, including evidence as to common general knowledge, was available (and was given). Where the Court has evidence on the basis of which it can make a finding about common general knowledge, and the other information referred to in s 7(2) and s 7(3), and about what would or would not have been obvious to persons skilled in the relevant art, it must be only rarely that it will be appropriate to find (by resort to a "threshold test") lack of inventiveness on the face of a specification. In our opinion this is not a case where such a finding is justified.
46 We turn to the ground of obviousness. The trial judge's finding (at 484) on this issue was straightforward:
"There is a considerable, perhaps entire, overlap between the evidence on this issue and that on the issue of invention. Comparison with the prior art base referred to in the specifications discloses a lack of an inventive step, for the reasons already discussed."
47 We accept that ordinarily, at least, it would follow that if there were no invention there would be no inventive step. Because, however, we respectfully disagree with his Honour's conclusions on the question of invention, inventive step, or obviousness, requires further consideration.
48 We have already referred several times, in passing, to s 7. It is desirable to set out sub‑sections (2) and (3) in full:
"(2) 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."
49 The respondent sought to support his Honour's conclusion on obviousness by reference to an editorial by Rowinsky and Donehower published in the Journal of the National Cancer Institute in December 1991 (before the priority date). His Honour found that the editorial was an important review article, as it plainly is, written by respected authors. His Honour found that "[it] would have been read with interest by the hypothetical skilled addressee in early 1992 and regarded as reliable". The importance of the editorial was that it revealed the existence and nature of the trials which led to the claimed invention. Heerey J quoted, at 474, 475, the following passages from the editorial:
"Both addition of the pre‑medication regimen and the scheduled change, however, were carried out at the same time. Therefore, the relative merits of each manoeuvre [in reducing hypersensitivity reactions] are not entirely known. Further clinical trials should examine whether the 24-hour infusion which mandates hospitalisation, is necessary when the pre‑medication regimen is given. This is one of the questions being evaluated in a European‑Canadian study with a bifactorial design which is comparing 3‑ and 24‑hour infusions at doses of 135 and 175mg/m2 in patients with ovarian cancer. …
Nevertheless we are still in the dark at this juncture regarding the optimal therapeutic doses and the importance of a dose‑response effect for taxol. The pivotal European‑Canadian study mentioned above with a bifactorial design is currently attempting to address this issue in ovarian cancer by randomly assigning patients who have received previous platinum therapy to one of two different taxol doses (135 and 175mg/m2) and one of two different schedules (24‑ and 3- hour infusions). Still, the discrepancy between the two doses used in this trial may not be wide enough to detect a significant dose‑response effect in a heavily pre‑treated and overall drug refractory patient population."
50 His Honour's finding about that editorial must be read with an earlier finding, at 471, to which senior counsel for the respondent referred us also:
"The field of cancer medicine is a global one. A number of eminent Australian specialists gave evidence in this case. It is apparent from their evidence that they travel regularly to attend overseas conferences and have access to overseas journals."
51 It should be noted also that his Honour referred specifically to certain passages in the evidence, including oral evidence, in support of the proposition that the editorial would, at the relevant time, have been known to the hypothetical skilled addressee.
52 Senior counsel for the appellant submitted that the findings to which we have referred do not "go so far as to show that it is being held by his Honour to be part of the common general knowledge in the sense that it's known to persons working in the art and is treated by them as part of their basic common general knowledge". In our view, however, it is difficult to read his Honour's findings in any other way. If Australians working in the field customarily read major overseas literature (and it would be very surprising if they did not) and if, before the priority date, they read the editorial (as his Honour held that they would have) and believed it to be reliable (as, again, his Honour held that they would have) it is not easy to see what element is lacking without which it would not be right to describe the information in the editorial as being, from early 1992, part of the relevant common general knowledge. No such element was referred to in argument; we do not think there is one; and, consequently, we accept the submission made on behalf of the respondent.
53 Our difficulty, however, is that this is, as we have mentioned, a case in which there was a great deal of expert evidence. Some of that evidence was referred to in submissions, written and oral, but we have not considered all the evidence and do not think it would be appropriate for us to attempt to do so. Particularly in a case concerning a complex and specialised field of knowledge, we do not think it would be appropriate to make a finding that no inventive step was involved without an appreciation of the expert evidence - particularly the totality of the evidence as to common general knowledge - as a whole. For that reason, if the trial judge's finding of invalidity could not be supported on other grounds, we would reluctantly conclude that the matter should be remitted to his Honour for further consideration of the ground of obviousness.