'Potential uses were perceived to be as bronchodilators in asthma or spasmolytics in IBS provided sufficient selectivity for these effects over general vascular effects could be achieved. Other possibilities (not explored) were urinary incontinence and impotence.'
IBS refers to irritable bowel syndrome. The focus of SKF's research was in this area because it already had relevant existing expertise and knowledge. However, according to Dr Warrington, other potential therapeutic applications for PDE V inhibitors were kept in mind including male penile erectile dysfunction.
156 In another paper which he prepared in July 1992, Dr Warrington discussed PDE VA inhibitory activity for the purpose of assisting the SKF Patent Department in the preparation of a patent specification. In the course of that paper he said, referring to the PDE VA inhibitors:
'The compounds have smooth muscle relaxant activity and may be useful in the treatment of urinary incontinence or impotence. In such treatment, the compound may be administered by any suitable route, eg by the oral, respiratory tract, parenteral or topical routes, in manner known per se.'
157 In September 1992, SmithKline Beecham, as SKF had become, decided to cease all gastrointestinal work throughout the company. The entire PDE V program was categorised for management as being gastrointestinal despite its potential application to conditions outside that therapeutic area.
The Pfizer Witnesses - (i) Peter Ellis
158 Doctor Ellis is Executive Director of Exploratory Development in Pfizer. He holds a doctorate in pharmacology from the University of Edinburgh. He was employed from 1981 to 1984 as a Deputy Team Leader in Discovery Biology of Pfizer at its premises in Sandwich. From 1985 he was a Team Leader and from 1992 to 1994 a Section Head overseeing several teams.
159 He described the progress of the project which led to the discovery of the compound, sildenafil monocitrate, known within Pfizer as UK-92,480. The project began in 1986. At the outset it was directed to finding an anti-hypertensive drug that relaxed blood vessels and increased renal excretion of fluid and sodium. In late 1998 it changed direction and involved investigation of a possible agent for the treatment of stable and unstable angina. In 1993 when the angina project was about to be closed as a consequence of limited efficacy and report of lower back pains experienced by patients and volunteers, the compound UK-92,480 was tested on a small scale patient trial as a treatment for male erectile dysfunction. Following the success of that trial the project changed focus again to the development of a treatment for male erectile dysfunction. Dr Ellis set out the progress of the project in some detail in his affidavit. It is not necessary to reproduce that detail here.
160 By July 1990 Dr Ellis and his co-workers knew that UK-92,480 was a cGMP PDEV inhibitor. They also knew that it was orally bioavailable in rats and dogs. It had a predicted oral bioavailability in man of 70% and a half life of five hours. In late 1989, according to Dr Ellis, they knew that UK-92,480 enhanced EDRF-dependent vascular smooth muscle relaxation in blood vessels. The potential of EDRF in mediating erection was not yet elucidated.
161 In or around mid to late December 1991, Per Andersson of the Pfizer Urogenitals group arranged for UK-92,480 to be sent to test its erectile activity under the Gorm Wagner monkey model in Copenhagen. This model for erectile response involved intracavernosal injection of a drug into the penis of an anesthetised monkey. A ligature was placed around the penis prior to injection. A short time after injection the ligature was released to see whether or not the drug had produced an erection.
162 In January 1992 the hypertension task force of which Dr Ellis was a member reported to the Discovery Leadership on new approaches to the treatment of hypertension. One of those approaches involved the identification of an orally delivered NO releasor. There was a brief reference, in the appendix to the report, to the potential for an NO releasor to be of assistance in the treatment of impotence. The report set out the team's understanding of the physiological explanation of impotence as a failure to produce adequate quantities of NO in the penis. The hypertension task force recommended that NO releasing agents be tested in animal models of impotence. At that time UK-92,480 was still awaiting evaluation in the Gorm Wagner monkey model.
163 Dr Ellis received a copy of the Rajfer paper in January 1992. He did not recall whether he had seen it prior to its circulation by Dr Ringrose. Its circulation did not cause a stir within the project team as Dr Ringrose frequently circulated literature. However Dr Brown, the Manager of Pfizer's Chemistry Group at the time, wrote on a yellow Post-it note attached to the Rajfer article:
'UK-92,480 is going to Wagner for ic dosing to his monkeys - scheduled for next week I believe. No 'beneficial S/E's' were reported to the ECMT but I'll check again with Clinical.'
164 At the time Dr Ellis was aware from other papers that penile erection required relaxation of the corpus cavernosum and that smooth muscle contained NO synthase which produced NO which in turn produced cGMP. He knew this to be true for a variety of smooth muscles, including the corpus cavernosum from animal species. He said that what Rajfer reported was evidence for the presence of one pathway only, NANC (NO as neurotransmitter), but provided no data to suggest an intervention in that pathway would overcome the other pathways operating and have any effect on erection in an intact physiological system if there were a defect in another pathway.
165 In March 1992 Per Andersson informed Dr Ellis that the results of the testing in the Gorm Wagner monkey model were negative. UK-92,480 did not elicit a significant erectile response. From this testing Dr Ellis and his team concluded that further investigation of UK-92,480 as a potential treatment for erectile dysfunction was not warranted.
166 In March 1992 Pfizer commenced a double blind placebo controlled multiple dose study of UK-92,480 in 36 healthy male volunteers, designated 'Study 207'. It was carried out by Simbec, a clinical research organisation under the supervision of Dr Allen. On 14 and 15 May 1992 a report was prepared of a monitoring list including a list of adverse events. It was reported that some volunteers had suffered miscellaneous aches and muscle pain (myalgia), some had suffered headaches and there were reports of spontaneous erections. Subsequent discussion of the drug focussed on the myalgia problem. A later study, 'Study 211', which was commenced in October 1992, reported spontaneous erections in five out of seven subjects.
167 Dr Ellis discussed pursuing UK-92,480 for the treatment of erectile dysfunction as he believed it was worthwhile. The drug was first formally considered as a potential treatment for impotence at a meeting held on 26 June 1992. It was followed up by Dr Allen on 4 August 1992. He prepared a planning document proposing clinical studies necessary to evaluate the drug as a treatment for impotence. Study 350 was commenced in July 1993 after being twice postponed. Sixteen impotent patients with no known organic cause for their impotence were studied. They were dosed three times a day. They were admitted to a private hospital and were connected to a device used to measure the rigidity and duration of penile erection (Rigiscan). They were shown a pornographic video before they retired to bed. In November 1993 Dr Allen reported that efficacy against impotence was shown through the patients' diaries and with the Rigiscan measurements. There was some evidence that an improvement in erectile dysfunction was noted on the first day of dosing. This raised the possibility that UK-92,480 might be effective when administered in single doses.
168 In February 1994 Dr Ellis moved from Pfizer's Biology Group to Clinical and at the same time the UK-92,480 program was passed to the Urogenital Group. Dr Ellis said that by June 1993 they understood that UK-92,480 was effecting an erection through inhibition of a high affinity cGMP metabolising enzyme, either PDEI or PDEV. He asked Mr Burslem to determine the mechanism that was at work. Mr Burslem reported his preliminary results on 1 March 1994. He reported three PDEs present in the corpus cavernosum with the greatest activity being that of PDEV. Mr Burslem found that UK-92,480 was a potent inhibitor of PDEV. It was more than 10,000 times more selective for PDEV than for other PDEs present in the human corpus cavernosum. His memo noted that PDEV inhibition most likely represented the mechanism of action underlying the efficacy of UK-92,480 in impotence.
169 A further study was carried out in February 1994 using twelve patients given three escalating doses of the drug and the placebo in random order with at least three days in between each dose. They were subject to visual sexual stimulation while being monitored by a Rigiscan device for periods of three hours. Initial reports in May 1994 indicated that there may have been a dose related increase in rigidity at 10mg, 25mg and 50mg. However the erectile response was modest and only of short duration. A complete patent specification was lodged on 13 May 1994. At that time Dr Ellis believed that the data available and properly tested supported chronic three times a day dosing as the most effective in providing treatment for erectile dysfunction.
170 In a second affidavit Dr Ellis reviewed the Korenman paper. He pointed out that pentoxifylline was not described as a PDEV inhibitor in that study. He attacked its reliability noting that more than half (53 out of 90) of the successful episode data reported in the study related to one patient. To achieve IC50 for pentoxifylline against PDEV the dose would have to be at least 100 times higher than the dose administered in Korenman. It would not be possible to administer that amount as the highest reported dose of pentoxifylline in a man, which was 80mg/kg (about 5.6 grams to a 70 kg man), produced severe side affects including convulsions and loss of consciousness. Pentoxifylline was ineffective as an inhibitor of PDEV at clinical concentrations and did not even approach the required threshold for activity demonstrated by other PDEV inhibitors.
The Pfizer Witnesses - (ii) Michael Allen
171 Dr Allen is Vice President of Pfizer Global Research and Development and Head of Exploratory Development at the Sandwich Laboratories. Since July 2003 he has been the Genitourinary and Gastrointestinal Therapeutic Area Leader for Worldwide Development. He first became aware that the Pfizer Discovery Group was developing a compound UK-92,480 as a possible agent for the treatment of angina in July or August 1989. This was shortly after he joined Pfizer. He described the history of the project relating to the UK-92,480. Much of it was as covered in Dr Ellis' evidence. In late July 1992 Dr Allen had his first discussion with Mr Gingell, a consultant urologist, about the possible trial of UK-92,480 as a treatment for erectile dysfunction. In early August 1992 he attended an Early Candidate Management Team (ECMT) meeting and reported on the ongoing clinical trials for the drug. The meeting was losing its enthusiasm for the angina project at that stage. A well tolerated dose could not be found that reached the target plasma concentration without accompanying incidents of myalgia.
172 In August 1992 Dr Allen was given approval to conduct a small clinical trial to assess UK-92,480 as a potential oral treatment for impotence. The trial was scheduled for January 1993. On 18 August 1992 he contributed to a status report to the ECMT. He reported on spontaneous erections experienced by volunteers in Study 207 following his report on dose related myalgia. He referred to Study 211 in October 1992 in which spontaneous erections were recorded. This Study was related to determination of the operation of a slow release preparation and its effect on the incidence of myalgia.
173 The first erectile dysfunction trial of UK-92,480 was Study 350. The protocol was developed by Dr Allen and Mr Gingell in 1993. The study commenced in July 1993 involving sixteen patients with erectile dysfunction. At the conclusion of the Study it appeared that UK-92,480 taken as a three times a day dose of 25mg improved erectile function. At a meeting held in August 1993 it was decided to put all studies involving the drug for angina indication on hold. Clinical work continued on the drug in relation to its possible effects on impotence.
174 A second erectile dysfunction trial, Study 351, was commenced in March 1994. The early results were encouraging. They were reported to the ECMT on 10 May 1994 by a Dr Boolell.
175 In a second affidavit, Dr Allen offered a critique of the Korenman paper to substantially the same effect as that offered by Dr Ellis.
The Pfizer Witnesses - (iii) Martyn Burslem
176 Mr Burslem is Executive Director, Discovery Biology of Pfizer. He generally verified Dr Ellis' affidavit so far as it related to things he had done. He was aware, early in 1988, of mixed reports in the literature on whether PDEI was the only PDE enzyme in vascular smooth muscle. There were reports of both PDEI and PDEV. Zaprinast, which was weakly selective for PDEV over PDEI, was commonly used to test for cGMP PDE activity. Its weak selectivity explained the mixed reports in the early literature. He hypothesised that PDEV were present in smooth muscle and proposed to isolate it to compare the potency of Pfizer's inhibitors against it and their activity in vascular smooth muscle.
177 In pursuit of this proposal Mr Burslem studied PDE enzymes in rabbit platelet cells. At this time the project with which he was concerned sought to potentiate antral natriuretic factors (ANF) in the kidney with a view to treatment for hypertension and heart failure. The emphasis of the inquiry in so far as it related to therapeutic applications of cGMP PDE inhibitors shifted to the treatment of angina early in 1989. UK-92,480 was screened, apparently for the first time in May 1989, and found to be '… the most potent and selective PDEV inhibitor of the compounds tested in that screening round'.
178 Mr Burslem was involved with studies of the operation of UK-92,480 until January 1992 when he became Team Leader of the Pfizer Cardiovascular Biology Group. He continued as an ad hoc member of the ECMT until mid 1993. He was asked by Dr Ellis in February 1994 to isolate and characterise the PDE isoenzymes in the human corpus cavernosum. He was not aware then of any reported investigations on that question. In a memorandum written in March 1994 about the preliminary results of his isolation and characterisation work, he reported three PDE isoenzymes in human corpus cavernosum tissue. cGMP specific PDEV was predominant. He was surprised to find that PDEV was the peak PDE.
179 As at 1992 the reports of erectile responses to orally administered UK-92,480 were unexpected so far as Mr Burslem was concerned. He thought that any vasodilator given systematically would give rise to major hemodynamic changes well before any erectile response was detected. He said:
'It was surprising and unexpected to me to discover subsequently in 1994 that the human corpus cavernosum was rich in PDEV when compared with other smooth muscle. This explains how, upon generation of nitric oxide as a consequence of sexual stimulation, a PDEV inhibitor present at a concentration which is sufficiently low that it does not cause any major hemodynamic effect can nevertheless lead to an improvement in erectile response.'
The Pfizer Witnesses - (iv) Richard Palmer
180 Dr Palmer is Chief Executive Officer of Alizyme plc, a drug development company based in Cambridge in the United Kingdom. He has held senior positions in pharmacological research in Wellcome Foundation and Glaxo Wellcome. Alizyme plc of which he is now Chief Executive Officer, is a speciality pharmaceutical development company.
181 After reviewing the history of developing understanding of the function of NO in smooth muscle relaxation he made the point that it is one thing to know that NO is an important mediator which contributes to a particular physiological effect. However, translating this into a potential target and getting a therapeutic agent out of it is an entirely different matter. He thought it 'worth a try' in the late 1980s and early 1990s to use highly selective PDE inhibitors as therapeutic drugs to lower blood pressure. But:
'To be able to use one to treat a specific problem in a specific tissue, as is the case with erectile dysfunction, without creating masses of other undesirable side effects is a surprise.'
It seemed to like 'serendipity' that sildenafil, developed for the treatment of angina, happened to favourably affect men with erectile dysfunction without other effects.
182 Dr Palmer reviewed a number of articles including the Rajfer paper. He noted that the paper left unanswered the question whether increasing relaxation by a high concentration of zaprinast would be capable of facilitating a usable erection. In his opinion the data in the paper would not lead one to attempt to treat impotence with zaprinast or to develop another cGMP PDE inhibitor for this indication by first intent. He took issue with different conclusions offered by other witnesses. He made the point that Rajfer was oriented to show that the L-arginine/NO/cGMP pathway was involved in NANC relaxation. The cGMP PDE inhibitor was 'merely another tool, together with L-nitroarginine and methylene blue, to support the conclusion that NO is the NANC transmitter responsible for relaxation of this tissue preparation'.
183 The Murray paper suggested there was potential for selective PDEVA inhibition. However it was not possible to predict from it whether there would be any therapeutic use assuming that new inhibitors could be created based on that rationale.
The Pfizer Witnesses - (v) Rodolphe Fischmeister
184 Dr Fischmeister is Director of Research of INSERM in France and Head of the Cellular and Molecular Cardiology Laboratory in the Faculty of Pharmacy of the University of Paris-Sud.
185 Dr Fischmeister said that the term cGMP PDEV inhibitor conveyed to him that the inhibitor was more selective for a PDEV than for any other known inhibitor.
186 In reviewing the state of scientific knowledge in 1993/94 Dr Fischmeister said that in 1994 as an experienced scientist in the PDE field he would not have understood Rajfer to be referring in any way to the use of PDE inhibitors to treat erectile dysfunction orally or otherwise. The results of the experiments conducted by Rajfer gave good grounds for the view that NO was involved in the relaxation of corpus cavernosum tissue.
187 Dr Fischmeister did not find support in the Rajfer paper for the inference drawn by Murray that zaprinast alone caused a relaxation and enhanced that caused by NO or electrical stimulation. After reviewing a number of papers he said that the concept of using a cGMP PDEV inhibitor as a therapeutic agent for erectile dysfunction was not straightforward in 1993. The possibility that such an inhibitor could achieve an effect as an accelerator like NO required consideration of the possibility that muscle cells in the corpus cavernosum had a significant basal production of cGMP. This was '…certainly not an obvious issue'.
The Pfizer Witnesses - (vi) Alan Robertson
188 Dr Alan Robertson of New South Wales was the Chief Executive Officer of Pharmaxis Ltd. He did his doctorate in synthetic organic chemistry. He described himself as a 'medicinal chemist' which is 'a scientist who conceives new molecules with a view to achieving a given therapeutic effect'. He expressed the view that in 1992 there was simply not the same kind of depth of pharmaceutical research in Australia as in the Northern Hemisphere. There was no research in Australia at a high level of scientific knowledge in the area of EDRF and NO relevant to the present case.
189 Dr Robertson gave extensive evidence about how he would put the Patent into effect based upon the specification and claims in it. In so doing he responded to difficulties raised by some other witnesses. He also undertook a review of the prior art. He observed that the Rajfer paper did not disclose where the problem (if there were one) in the NO pathway, occurred in the case of erectile dysfunction. The Murray article did not suggest how a drug might be developed for relaxing a specific smooth muscle in a specific organ without affecting other smooth muscle in the body. For a scientist reading the Murray article prior to the Pfizer invention, impotence would simply be one of the possible therapeutic targets mentioned, with a lot more research to be done on them.
The Pfizer Witnesses - (vii) Donald Moss
190 Donald Moss is a Urologist working in Ballarat. He was President of the Urological Society of Australia in 1998 and 1999. He said that before the Viagra mode of action was publicised, neither he nor anyone with whom he spoke connected PDEs or PDE inhibitors with a treatment for erectile dysfunction. In 1994 it was clear that NO had an important role in the corpus cavernosum, but even as late as September 1994, at a meeting of the Societie International D'Urologie (SIU) in Sydney there was no consensus on the specifics of the mechanisms for erection. His first awareness of the possible clinical relevance of PDE and PDEV inhibitors was at a meeting he attended in Paris in 1996. He did not recall reading the Rajfer paper. He thought he might have consigned it to the 'yes that's interesting but of no import to me' bin.
191 Dr Moss was of the view, contrary to that of Dr Pryor, that as far as he and other Australian urologists were concerned in the early to mid 1990s they did not have the knowledge of theoretical concepts and research disclosed in Dr Pryor's affidavits.
The Pfizer Witnesses - (viii) Zdzisilaw Wisniewski
192 Dr Wisniewski is a Clinical Urologist. He describes his expertise as that of 'a surgeon providing a clinical practice for patients and frequently surgical intervention for erectile dysfunction and other penile disorders'. Referring to Rajfer's paper and other publications in 1991 and 1992 he said that he understood from them that NO was accepted as a neurotransmitter for erectile tissue and part of the NANC pathway. He also remembered reading that smooth muscle relaxation was mediated through an increase in cGMP. Neither he nor anyone he spoke to in Australian urology circles made the connection between the NO/cGMP pathway and the possible oral treatment for erectile dysfunction. He also disagreed with Dr Pryor's evidence about the knowledge of Australian urologists at the time.
193 Rajfer's paper did not talk about PDEV inhibition to the level of saying there was an oral therapy that might work. He did not see Viagra as having stemmed from Rajfer's work.
The Pfizer Witness - (ix) Steven Pittler
194 Dr Pittler is a Professor in the Department of Physiological Optics and the Department of Ophthalmology at the University of Alabama in Birmingham. His particular interest lay in the role of PDEs in retinal tissue. He said that the term cGMP PDE inhibitor in claim 10 of the Patent indicated a greater selectivity for inhibiting cGMP PDEV than for inhibiting any other cGMP PDE known at the time. He also reviewed the evidence of a number of other witnesses.
The Pfizer Witnesses - (x) Ciara McKenna
195 Ciara McKenna is the Marketing Manager for Endocrinology/Gastroenterology/Urology/Ophthalmology for Pfizer. At the time of the trial she had held that position for over 18 months.
196 She said that Viagra had been granted regulatory approval in the USA on 27 March 1998. In the week ending 24 April 1998, which was its fourth week of release in the USA, it was reported that around 206,246 prescriptions had been filled for it.
197 In 1998 more than 200,000 physicians wrote more than 7 million prescriptions for more than 50 million tablets of Viagra for more than 3 million patients. On 1 May 1998. Viagra had taken a 94% share of all dispensed new prescriptions for erectile dysfunction products. That year gross sales in the USA amounted to $US718 million. She set out a table showing sales in subsequent years. In 2004 to July, the gross sales were $US0.549 billion. Since the grant of marketing authorisation for Viagra in the European Union in September 1998 it enjoyed similar commercial success. It has since obtained marketing approval in over 100 countries.
198 Viagras annual sales of $US1.7 billion comprised 92% of the $US1.8 billion worldwide market for erectile dysfunction therapies in 2002. It was the 25th highest selling prescription drug by worldwide sales in 2002. Ms McKenna also set out worldwide sales figures.
199 Viagra was given marketing approval in Australia in September 1998. Its gross sales were $28.9 million in 2003 and were forecast to be $26.3 million in 2004.
The Reasons for Judgment at First Instance
200 The learned primary judge reviewed the physiological and biochemical processes involved in the erectile functioning of the penis as discussed in the Pfizer and Lilly primers. He set out the relevant terms of the Patent and summarised the contents of the Rajfer, Murray and Korenman articles. His Honour then dealt with the issues before him by formulating and discussing a series of questions which he had to decide.
201 The first of the questions was constructional, namely the meaning of 'cGMP PDEV inhibitor' in claim 10. Pfizer contended that the term referred to a PDEV inhibitor which was selective for PDEV. Lilly's submission was that it referred to any inhibitor that had any activity against PDEV regardless of whether it was more or less selective for that PDE than any of the other known PDEs.
202 His Honour observed that as a matter of ordinary language the term 'cGMP PDEV inhibitor' in claim 10 conveys the concept of a substance identified only by the presence of a particular function or capacity, namely that it inhibits cGMP PDEV. Pfizer's construction involved reading a limitation or qualification into the ordinary language so that the reader would understand that the author of the document was intending to convey a narrower meaning. He referred to Herbert Adams Pty Ltd v Federal Commissioner of Taxation (1932) 47 CLR 222and cited Dixon J at 228-229:
'… it is always less difficult to show that a word has a wider meaning than it is to establish a specialized use. For an extension of meaning involves no abandonment of the use in respect of things to which it would in any case apply; but a uniformly restricted application among any class of persons is necessary in order to establish that it has among them a narrower meaning and that meaning only.'
His Honour regarded the 'linguistic logic' of the passage as compelling particularly once it appeared that the suggested narrower meaning was not a matter of uniform expert opinion or usage and not consistent with the language of the document as a whole.
203 His Honour referred to expert evidence relied upon by Pfizer noting that evidence as to the meaning of technical terms is admissible although the construction of the specification is a matter of law and belongs to the Court. There was evidence of usage supporting Lilly's view. The word 'selective' was commonly used to identify the PDE against which an inhibitor has the most activity. If Pfizer's strictly were correct, the term 'selective PDEV inhibitor' would be tautologous. There was evidence that the term was often used if context required it. Indeed Pfizer had done so in its Canadian Viagra patent in which claim 25, corresponding to claim 10 in the Patent, claimed 'The use of an effective amount of a cGMP PDE inhibitor … wherein the cGMP PDE inhibitor is a selective inhibitor of cGMP-specific PDEv.' Similarly, claim 24 of the Pfizer US patent spoke of 'an effective amount of a selective cGMP PDEV inhibitor'. His Honour concluded that where the context was appropriate the qualifier 'selective' could be used in conjunction with 'cGMP PDEV inhibitor'. He also found support for Lilly's contention in the context of the Patent. He concluded that while sometimes 'cGMP PDEV inhibitor' may, without more, connote an inhibitor selective for PDEV in claim 10, when read in the context of the Patent as a whole it did not.
204 The next question was as to the priority date of claim 10. It was accepted by Pfizer that the priority date was 13 May 1994, which was the date of filing of the PCT application.
205 His Honour then turned to the attack on claim 10 based on want of novelty. He referred to s 138(3)(b) and s 18(1)(b)(i) of the Act as well as the statutory definitions of the concepts of novelty and prior art base found in s 7(1) and the Dictionary in Sch 1 of the Act. He referred to the discussion of the authorities on novelty by Black CJ and Lehane J in Bristol-Myers Squibb Company v FH Faulding & Co Limited (2000) 97 FCR 524 and observed (at 24 [90]):
'For present purposes it is sufficient to say that the question is whether the alleged anticipation would, if the patent were valid, constitute an infringement (the "reverse infringement test"). Where the alleged anticipation takes the form of a publication (a "paper anticipation"), the hypothetical infringement does not arise because of the publication per se; rather one asks whether the publication teaches, in the sense of directing, recommending or suggesting, the invention under consideration.'
He cited a passage from the judgment of the Privy Council in Canadian General Electric Co Limited v Fada Radio Limited [1930] AC 97 at 104:
'… it is not enough to prove that an apparatus described in an earlier specification could have been used to produce this or that result. It must also be shown that the specifications contain clear and unmistakable directions so to use it.'
His Honour then set out a number of questions and answers relevant to the novelty issue. It is not necessary to set out all of those questions here but rather the conclusions at which he arrived in responding to them.
206 His Honour found that the Murray paper did not teach the use of a cGMP PDEV inhibitor to treat impotence. Its pervading tone was hypothetical, cautious, abstract and speculative. It gave no particular prominence to the treatment of impotence among potential users of cGMP PDEV inhibitors. If, contrary to his conclusion, Murray taught the method of claim 10, that teaching would be taken to include oral administration.
207 It was common ground that the Korenman paper was publicly available before the priority date of claim 10, which was 13 May 1994. The Korenman study was carried out to test the possibility that pentoxifylline would be effective in improving blood flow through the penis thereby facilitating the erectile process. It taught away from the pith and substance of claim 10 of the Patent which was the use of a substance identifiable by a particular function, namely the inhibition of cGMP PDEV. There was no reference to pentoxifylline as such an inhibitor. Nor was there in the relevant product information leaflet. Footnotes to the paper referring to two 1989 papers dealing with the effect of pentoxifylline in rabbit pulmonary circulation and in canine arteries and veins did not teach the method of claim 10. The tentative terms in which the footnoted papers were couched and the fact that they dealt with animal rather than human studies and with conditions other than impotence, confirmed the conclusion that Korenman, read as a whole, did not contain clear and unmistakeable directions to use the method of claim 10. In any event, pentoxifylline did not, it seemed, act via a cGMP PDEV inhibitory mechanism of action.
208 Because he had rejected Pfizer's construction claim that claim 10 referred to a selective cGMP PDEV inhibitor, it was not necessary for his Honour to discuss an experiment which Lilly had conducted designed to show that pentoxifylline was in fact a selective cGMP PDEV inhibitor. Had that been so then Korenman could have been treated as in anticipation of claim 10. In any event he was not persuaded that at the relevant time pentoxifylline would have been identified as a selective cGMP PDEV inhibitor. Korenman would have needed to disclose PDEV inhibitory activity to be an anticipation. Otherwise there would not have been disclosure of 'specific details necessary for the practical working and real utility of the alleged invention' - citing Hill v Evans (1862) 4 De G F & J 288 at 301, 45 ER 1195 at 1199. His Honour concluded that claim 10 was not liable to be revoked for want of novelty. He then turned to the question of obviousness.
209 His Honour referred to s 7 of the Act and the criteria of obviousness set out in ss 7(2) and (3). The test for obviousness, as his Honour stated it, was whether a hypothetical skilled person, constituted by a research team or group would, in all the circumstances, including a knowledge of all the relevant prior art, directly be led as a matter of course to try something in the expectation that it might well produce a useful result. He cited Aktiebolaget Hassle v Alphapharm Pty Ltd (2002) 212 CLR 411. If it could be said that upon doing so the group would arrive at the alleged invention then obviousness would be made out. To become part of common general knowledge in the relevant field a publication would need to be not just accessible but to have been assimilated into the consciousness of the hypothetical skilled worker or team.
210 It was common ground before his Honour that the notional team would include a pharmacologist and a chemist with experience in drug discovery and development. He also accepted Lilly's submission that the team would include a medical practitioner experienced in the treatment of impotence.
211 It was not easy to isolate what facts were disputed as within common general knowledge or otherwise. He accepted that the Rajfer and Murray publications formed part of the common general knowledge. He rejected Pfizer's assertion that as at 13 May 1994 there was an incomplete and inaccurate knowledge of the presence of PDEs and their types in corpus cavernosum.
212 His Honour then considered whether the hypothetical skilled person constituted by a research team would, on reading Rajfer, be led directly as a matter of course to try an oral PDEV inhibitor to cure or prevent impotence in the expectation that it might well produce a useful alternative to existing methods of treatment. He referred to evidence of what Rajfer conveyed to various witnesses. He noted that immediately after publication of Rajfer, Dr Ringrose, the Head of Discovery at Pfizer UK, circulated a copy to his management team with a comment written on it:
'Should we not try out UK-92,480 in impotence? Have we seen any beneficial s/e's [side effects]?'
UK-92,480 which was Pfizer's internal designation for sildenafil monocitrate was then being considered as a potential angina treatment. He saw this as a contemporaneous actual reaction by a skilled reader to the Rajfer paper. He mentioned in this context also a paper by Dr Gristwood. Dr Gristwood read Rajfer no later than February 1993 and gave a paper at a conference in Nice in which he referred to Rajfer saying:
'Since PDEV is specific for the metabolism of cGMP, it can be expected that the inhibitors of PDEV will potentiate the relaxant effect of the endothelium-derived relaxing factor EDRF (nitric oxide), which acts by stimulating guanylate cyclase. In fact some studies have demonstrated that zaprinast augments the responses which are dependent on nitric oxide.'
Dr Gristwood had given evidence that on reading Rajfer he appreciated that impotence was a new therapeutic possibility for PDEV inhibitors in light of the fact that zaprinast, a known selective PDEV inhibitor, was shown to enhance smooth muscle relaxation of human corpus cavernosum tissue. Were he looking for a new treatment for impotence Rajfer would have 'strongly suggested' the use of PDEV inhibitors.
213 His Honour said that Dr Gristwood's Nice paper and Dr Ringrose's note were strong indications that Rajfer would, when published, have taught a skilled reader that compounds that inhibit cGMP PDEV were likely to be useful in the treatment of impotence. He held that Rajfer conveyed not certainty, which was not required, but a well-founded expectation that further testing of cGMP PDEV inhibitors might well provide a treatment for impotence or be likely to have that effect.
214 His Honour then dealt with and rejected a number of arguments against obviousness advanced by Pfizer. He concluded that Rajfer could be relied upon to establish a lack of inventive step. He also concluded that Murray formed part of the common general knowledge of the addressee in Australia at the priority date. Pfizer's main answer to Murray was that it did not state that cGMP PDEV inhibitors should be administered orally. His Honour had already observed in rejecting this argument in connection with Rajfer, that oral administration would self-evidently be the preferred route. He concluded that Murray also could be relied upon to establish a lack of inventive step.
215 His Honour then considered whether there were secondary indicia establishing inventive step. He referred to the enormous commercial success of Viagra but found that Pfizer's change of direction with UK-92,480 from angina to impotence was due not to serendipity but to the impact of Rajfer. He referred to Study 207 which Pfizer commenced on UK-92,480 for angina in March 1992. This was a study using healthy volunteers designed to test dosage levels for angina treatment. There were reports of spontaneous erections at higher dose levels. Dr Ellis had given evidence that this was the first occasion upon which spontaneous erections had been reported to him as an adverse effect during clinical trials of UK-92,480. The results of the Study were formally reported within Pfizer on 26 June 1992. It was then said that UK-92,480 would be 'considered for the treatment of impotence on the basis of the spontaneous erection seen in Phase I multiple dose study'.
216 Dr Ellis and Dr Terrett of Pfizer made a Request for Patent Application within Pfizer on 18 January 1993 in relation to the use of cGMP PDE inhibitors for impotence. The request referred to 'recent literature disclosures' which had proposed that NO was an important mediator of penile erection. His Honour found that the reference to 'recent literature disclosures' was an obvious reference to Rajfer, notwithstanding Dr Ellis' reluctance to concede as much. Dr Ellis and Dr Terrett signed a Record of Inventorship on 22 June 1993.
217 This history demonstrated how intimately the ideas conveyed by Rajfer were bound up in Pfizer's work which led to the alleged invention. Pfizer was lucky in having its existing angina project which could be steered in the new direction of impotence treatment. The headstart it was thereby given helped to explain its commercial success. But the story of stumbling by chance on a solution which fulfilled a long-felt want did not fit the historical facts. Nor did the story take into account the rapid developments in scientific knowledge in the area.
218 His Honour considered whether claim 10 was fairly based on the matters described in the specification. He referred to Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (2004) 212 ALR 1. The relevant inquiry is what the body of the specification as a whole discloses as the invention. He observed that claim 10 was an awkward fit in the specification. The Patent in its body and in claims 1 to 8 deals with the use of compounds identified by their chemical structure. There is a detailed hierarchy of compounds.
219 His Honour found it to be common ground that claim 10 is not confined to 'compounds of the invention' or 'compounds of formula (I)'. When in the body of the specification there is an account of the 'preliminary investigation' and the recording of a finding of 'potent and selective' inhibition of the cGMP-specific PDEV it is 'compounds of the invention' that is referred to. In the six components of the consistory clause the only reference to compounds defined not by chemical structure but by inhibitory function is to the inhibition of cGMP PDE, not cGMP PDEV. That reference was written to support the subsequently abandoned claim 9. His Honour observed (at [174]):
'Mere coincidence of language between a claim and part of the body of a specification does not establish fair basing if that part of the language of the specification does not reflect the description of the invention in the light of the specification as a whole … In the present case however there is not even coincidence of language.'
He concluded that claim 10 was not fairly based on the matter described in the body of the specification.
220 He next considered sufficiency and the requirement under s 40(2)(a) of the Act that a complete specification must 'describe the invention fully, including the best method known to the applicant of performing the invention …'. He held that the earliest date for determining sufficiency was the date of grant. Claims 6, 7 and 8 and the other amendments made on 6 January 1997 were therefore to be taken into consideration. The common general knowledge and prior art which could be taken into account by the skilled addressee was that at that date for determining sufficiency. The relevant question then was whether the specification provided sufficient information to enable a skilled addressee to use a single embodiment of a cGMP PDEV inhibitor in applying the method claimed in claim 10. His Honour accepted the evidence of Pfizer's witness, the medicinal chemist, Dr Robertson. He accepted Dr Robertson's evidence that the skilled addressee reading the Patent as a whole and noting the progressive narrowing of claims would be likely to focus on claim 8. If the embodiment selected by the addressee for working came within claim 10, it did not matter that it also might fall within claim 8. There was no justification for requiring the one embodiment of claim 10 relied on to be outside the compounds of formula (I). His Honour concluded that Lilly's ground of insufficiency was not made out.
221 His Honour then considered whether the description of the invention included the best method known to the applicant of performing the invention. The first issue to be determined under that heading was the relevant date for determining whether the best method had been disclosed. His Honour concluded that the relevant date was, at the earliest, the date of grant. Lilly had contended that the date was the date of filing of the PCT application on 13 May 1994. His conclusion was based upon his construction of the requirements of s 40(2)(a) and the definition of 'complete specification' in the Dictionary in Sch 1 of the Act. He identified the best method known to Pfizer to be the use of sildenafil monocitrate. He concluded, based on Dr Robertson's evidence, that to a skilled reader the Patent does disclose the freebase and salt of the especially preferred compound.
222 The next question was whether the claimed invention was 'a manner of new manufacture' within the meaning of s 6 of the Statute of Monopolies (UK). He rejected the proposition advanced by Lilly that claim 10 claimed a 'mere desideratum'. The Patent specification told the reader the manner in which the desired object was to be achieved, namely by use of an orally effective cGMP PDEV inhibitor. This could not be characterised as a 'bare idea'. He noted that in the Bell patents, which were referred to in the complete specification, Pfizer disclosed a number of compounds including formula (I) compounds, suggested to be useful for a number of indications including the treatment of angina within a particular dosage range. They were disclosed in those two patents as potent and selective inhibitors of PDEI and PDEV. The Patent therefore disclosed patentable subject matter.
223 The next question was whether there had been a false suggestion which materially contributed to the decision to grant the Patent. Lilly submitted that the specification gave the false impression that one of the nine 'especially preferred individual compounds' had been tested and worked and that the patentee was disclosing its best method. This was based on the statement in the Patent:
'Moreover patient studies conducted thus far have confirmed that one of the especially preferred compounds induces penile erection in impotent males.'
His Honour acknowledged that the compound which achieved the experimental result referred to in that passage was not a freebase compound as were the 'especially preferred individual compounds'. However Dr Robertson's evidence established that a skilled addressee would not draw a distinction between a compound in its freebase form and the same compound in its salt form. There was no false suggestion.
224 His Honour then considered whether the Lilly product, Cialis, infringed Pfizer's Patent. Certain formal admissions had been made for the purposes of the case. They were the following:
(a) Cialis is an inhibitor of cGMP PDEV;
(b) Cialis tablets are intended to be prescribed by doctors in Australia as a treatment to be taken orally for the treatment of erectile dysfunction in men;
(c) Cialis (in 10mg and 20mg tablet form) has been approved by the Australian Therapeutic Goods Administration (TGA);
(d) Lilly imports, sells, offers for sale or otherwise disposes of Cialis tablets in Australia; and
(e) Cialis:
(i) inhibits PDEV;
(ii) is >10,000-fold more potent for PDEv than for PDEI, PDEII, PDEIII and PDEIV;
(iii) is approximately 700-fold more potent for PDEV than for PDEVI.
225 Lilly argued that Cialis does not 'cure or prevent erectile dysfunction' because it treats such dysfunction on an ad hoc basis for a limited period of up to 36 hours. This, it was said, is not a 'cure' because the person treated is not restored to health in the sense that he no longer has the disease. His Honour however held that claim 10 was concerned with a 'performance problem'. Cialis would treat that problem and thus 'cure' or 'prevent' it in the sense that a man taking Cialis would not have the problem for 36 hours. Cialis therefore cured or prevented impotence within the meaning of claim 10. His Honour also rejected Lilly's argument that 'mere sale or importation' did not infringe a method claimed. He concluded that if claim 10 of the Patent were valid, Lilly's conduct would have constituted an infringement of it.
The Orders at First Instance
226 The learned primary judge delivered judgment on 10 February 2005 and directed counsel to submit minutes of proposed orders. On 11 March 2005 he made orders in the following terms:
'The Court declares that:
1. Claim 10 of Australian Patent No 676571 is and always has been invalid.
The Court orders that:
2. Australian Patent No 676571, so far as it relates to claim 10, be revoked.
3. The Cross-Claim be dismissed.
4. The Respondents/Cross-Claimants pay 72.5% of the Applicants/Cross-Respondents' costs of and incidental to these proceedings, including all costs reserved in these proceedings or to be dealt with in these proceedings, such costs to be taxed in default of agreement.
5. The time within which the Respondents/Cross-Claimants may file and serve a Notice of Appeal be extended to 14 April 2005.
6. Order 2 be stayed:
(a) initially until 14 April 2005; and
(b) if an appeal is lodged within that period, until the determination of that appeal, or further Order.'
227 The Court also noted undertakings by Pfizer to prosecute any appeal expeditiously and to serve a copy of the relevant orders on the Commissioner of Patents and not to threaten any person with proceedings or commence proceedings for infringement of claim 10 of the Patent during the period of the stay. The Court also noted Pfizer's undertaking not to seek to amend the Patent otherwise than in the course of or in connection with the proceedings.
The Grounds of the Appeal
228 The grounds of the appeal were set out in some detail and it is not necessary to reproduce them in full here. It is sufficient to say that Pfizer asserted in the grounds that the learned primary judge erred in finding:
1. that in claim 10, in the context of the Patent as a whole, the term 'cGMP PDEV inhibitor' does not connote an inhibitor which is selective for PDEV (grounds 20 to 23);
2. that claim 10 was not fairly based on matter described in the specification in the Patent (grounds 24 to 28);
3. that claim 10 of the Patent was invalid because it was obvious (grounds 1 to 19).
The issues are set out in the order in which they will be dealt with in the reasons that follow.
The Notice of Contention
229 In its notice of contention Lilly asserted that the learned primary judge:
1. should have held that claim 10 of the Patent was not novel when compared with the prior art base as it existed before the priority date of the claim, as required by s 18(1)(b)(i) of the Act;
2. should have held that the date for determining whether the best method known to the patentee of performing the invention is described in the specification of the Patent, is the date of filing of the complete specification (namely, in the case of the Patent, the date of filing the PCT application on 13 May 1994);
3. should have held that the specification of the Patent did not describe the best method known to the patentee of performing the invention claimed in claim 10 of the Patent at 13 May 1994;
4. erred in his findings as to sufficiency in relation to the relevant date for determining sufficiency, the construction of claim 10, and the test applied to determining sufficiency;
5. assuming that the specification of the Patent did not describe the best method, should have held that there was a false suggestion made by the patentee which materially contributed to the decision to grant the Patent;
6. should have held that the importation or sale of Cialis by the respondents would not infringe claim 10 of the Patent if that claim was valid because it does not 'cure or prevent' male erectile dysfunction within the meaning of claim 10 of the Patent. If he were correct in so construing claim 10, then it was not open to find that the importation and sale of Cialis by the respondents would infringe claim 10 of the Patent as Pfizer did not lead evidence that Cialis cures or prevents erectile dysfunction by cGMP PDEV inhibition.
Statutory Framework - The Patents Act 1990 (Cth)
230 The Patents Act 1990 which is the statute applicable to this appeal repealed the Patents Act 1952 (Cth). The 1990 Act commenced on 30 April 1991. Some of the provisions of that Act which are relevant to this appeal have been amended by subsequent legislation. Textual alterations to accommodate the innovation patent system were introduced by the Patents Amendment (Innovation Patents) Act 2000 (Cth). They came into effect on 24 May 2001. Significant amendments relating to novelty and inventive step were introduced by the Patents Amendment Act 2001 (Cth). These amendments apply to the making of complete applications and to patents for which the complete applications are made on or after the day on which Schedule 1 to that Act commenced. Schedule 1 commenced on 1 April 2002 - see s 13 Patents Amendment Act 2001.
231 The Court is concerned with the Patents Act 1990 as it stood prior to the amendments introduced by the amending Acts of 2000 and 2001. Other earlier amendments are not material for present purposes.
232 A patent for an invention confers upon the patentee the exclusive rights, during the term of the patent, to exploit the invention and to authorise another person to exploit the invention (s 13(1)). The relevant rights are personal property capable of assignment and devolution by law (s 13(2)). A patent for an invention may only be granted to a person who is the inventor or a person who derives or is entitled to derive title to the patent from the inventor (s 15(1)).
233 The class of inventions which are patentable inventions under the Act is described in s 18. Section 18 as it stood prior to the amending Act of 2000 was as follows:
'(1) Subject to subsection (2), a patentable invention is an invention that, so far as claimed in any claim:
(a) is a manner of manufacture within the meaning of section 6 of the Statute of Monopolies; and
(b) when compared with the prior art base as it existed before the priority date of that claim:
(i) is novel; and
(ii) involves an inventive step; and
(c) is useful; and
(d) was not secretly used in the patent area before the priority date of that claim by, or on behalf of, or with the authority of, the patentee or nominated person or the patentee's or nominated person's predecessor in title to the invention.
(2) Human beings, and the biological processes for their generation, are not patentable inventions.'
234 Nothing done under the Act guarantees the granting of a patent or that a patent is valid in Australia or anywhere else (s 20(1)). The invalidity of a patent in relation to a claim does not affect its validity in relation to any other claim (s 22).
235 Section 40 of the Act sets out the requirements for specifications for patents thus:
'(1) A provisional specification must describe the invention.
(2) A complete specification must:
(a) describe the invention fully, including the best method known to the applicant of performing the invention; and
(b) where it relates to an application for a standard patent - end with a claim or claims defining the invention; and
(c) where it relates to an application for a petty patent - end with a single claim, or a single independent claim and not more than 2 dependent claims, defining the invention.
(3) The claim or claims must be clear and succinct and fairly based on the matter described in the specification.
(4) The claim or claims must relate to one invention only.'
236 Section 43(1) requires that each claim of a specification have a priority date. By s 43(2) the priority date of a claim is the date of filing of the specification or a different date determined under the Regulations where they so provide. Section 43(4) provides that the priority date of a claim of a specification may be different from the priority date of any other claim of the specification.
237 Schedule 1 to the Act sets out a dictionary of expressions which, by virtue of s 3 of the Act, are defined for the purposes of the Act or of a particular chapter of the Act. The definitions contained in the dictionary include the following:
'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.
prior art base means:
(a) in relation to deciding whether an invention does or does not involve an inventive step::
(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;
(b) in relation to deciding whether an invention is or is not novel:
(i) information of a kind mentioned in paragraph (a); and
(ii) information contained in a published specification filed in respect of a complete application where:
(A) if the information is, or were to be, the subject of a claim of the specification, the claim has, or would have, a priority date earlier than that of the claim under consideration; and
(B) the specification was published after the priority date of the claim under consideration; and
(C) the information was contained in the specification on its filing date and when it was published.'
'prior art information means:
(a) for the purposes of subsection 7(1) - information that is part of the prior art base in relation to deciding whether an invention is or is not novel; and
(b) for the purposes of subsection 7(3) - information that is part of the prior art base in relation to deciding whether an invention does or does not involve an inventive step.'
238 Section 7 of the Act as it stood at the relevant time provided:
'(1) For the purposes of this Act, an invention is to be taken to be novel when compared with the prior art base unless it is not novel in the light of any one of the following kinds of information, each of which must be considered separately:
(a) prior art information (other than that mentioned in paragraph (c)) made publicly available in a single document or through doing a single act;
(b) prior art information (other than that mentioned in paragraph (c)) 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;
(c) prior art information contained in a single specification of the kind mentioned in subparagraph (b)(ii) of the definition of prior art base in Schedule 1.
(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.'
239 Section 138 of the Act provides for revocation of patents and in particular s 138(3) provides that the court may by order revoke a 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:
'(a) that the patentee is not entitled to the patent;
(b) that the invention is not a patentable invention;
(c) that the patentee has contravened a condition in the patent;
(d) that the patent was obtained by fraud, false suggestion or misrepresentation;
(e) that an amendment of the patent request or the complete specification was made or obtained by fraud, false suggestion or misrepresentation;
(f) that the specification does not comply with subsection 40(2) or (3).'
Constructional Questions
240 The construction of the Patent is logically antecedent to all other issues. In this case however, the constructional debate was narrowly focussed on two questions:
1. Whether the term 'cGMP PDEV inhibitor' in claim 10 refers only to inhibitors which are selective for PDEV (grounds 20 to 25).
2. Whether the term 'cure or prevent' in claim 10 covers a method of treatment which temporarily overcomes the effects of erectile dysfunction.
241 The first question was raised by Pfizer in its attack upon the finding by the learned trial judge that the term 'cGMP PDEV inhibitor' covers PDEV inhibitors which are not selective for that enzyme as well as inhibitors which are. Pfizer submitted in effect that the wide construction adopted by his Honour underpinned his finding that claim 10 was not fairly based on the matter described in the body of the specification. It did not demonstrate how his Honour's construction impinged upon his fair basis conclusion. Lilly submitted that there was no connection. The fair basing question depended solely on whether the specification read as a whole disclosed as the invention the use of the compounds of the invention, that is the compounds of formula (I).
242 In his reasons for judgment the learned trial judge observed that much of the discussion on the construction point was relevant to the issue of fair basing - [170]. Part of that discussion, at [85] and [86], did turn upon the proposition that claim 10 was not limited to the compounds of the invention or compounds of formula (I). His Honour's reasons, however, did not otherwise make any connection between the construction of claim 10 and the fair basis holding.
243 On novelty, Lilly relied upon an experiment designed to show that pentoxifylline was a selective cGMP PDEV inhibitor and thus that Korenman anticipated claim 10. Because of the broader construction of claim 10 which his Honour had adopted he found it unnecessary to discuss the Lilly experiment - [90]. He was, in any event, not persuaded that at the relevant time pentoxifylline would have been identified as a selective cGMP PDEV inhibitor.
244 It may be seen from the foregoing that the question whether claim 10 covered non-selective cGMP PDEV inhibitors played virtually no part in the outcome of the case.
245 The second constructional question was relevant to the asserted infringement of claim 10 by the Lilly product in the event that claim 10 were valid. Lilly argued that its product, Cialis, did not 'cure or prevent erectile dysfunction in man in need of such treatment' within the meaning of claim 10 because it treated such dysfunction 'on an ad hoc basis for a limited period of up to 36 hours'. This was not a 'cure' because even after using Cialis the person treated still had the disease. Similarly it was argued that the word 'prevent' in the context of claim 10 meant to forestall the onset of the disease so as to keep it from occurring. His Honour held, however, that the Patent defined 'impotence' by reference to the inability to achieve penile erection or ejaculation. Cialis treated that problem and thus cured or prevented it in the sense that a man taking Cialis would not have the problem for 36 hours. On that basis his Honour held that Cialis would 'cure or prevent' impotence within the meaning of claim 10.
246 Notwithstanding the marginal relevance of the first constructional question, it is desirable to deal with both as they were fully argued. This requires a consideration of some general principles.
247 Underlying any approach to the construction of a patent is its character as a document conferring a public monopoly not to be construed merely as a written document inter partes. This requires '… a description which is not reasonably capable of misunderstanding' - Martin v Scribal Pty Ltd (1954) 92 CLR 17 at 59 (Dixon CJ); Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588 at 610 (Dixon CJ, Kitto and Windeyer JJ). Plain language is to be given its plain meaning. The clear words of a claim are not to be distorted by importing passages from the specification - Martin v Scribal at 97 (Taylor J). It was put thus in the joint judgment in Welch Perrin (at 610):
'Nevertheless, it is to be remembered that any purely verbal or grammatical question that can be resolved according to ordinary rules for the construction of written documents, does not, once it has been resolved, leave uncertain the ambit of the monopoly claimed.'
So when a claim is clear it is not to be glossed or obscured by reference to the specification. Barwick CJ and Mason J reiterated the rule in Interlego AG v Toltoys Pty Ltd (1972) 130 CLR 461 at 478:
'… the settled rule is that in ascertaining the width of a particular claim it is not permissible to vary or qualify the plain and unambiguous meaning of the claim by reference to the body of the specification.'
248 Construction should not be unduly narrow (Martin v Scribal (at 97)):
'… it is right to construe a claim with an eye benevolent to the inventor and with a view to making the invention work - this is an application of the old doctrine ut res magis valeat quam pereat - and it is illustrated in Nobel's Case [(1894) 11 RPC at 524]; and, where the language of a claim is obscure or doubtful, the doubt may sometimes be resolved by referring to words in the body of the document to explain it. This is known as the dictionary principle.'
A re-statement of the latter part of that proposition may be found in the joint judgment of Barwick CJ and Mason J in Interlego (at 479):
'If the expression is not clear it is then permissible to resort to the body of the specification to define or clarify the meaning of words used in the claim without infringing the rule that clear and unambiguous words in the claim cannot be varied or qualified by reference to the body of the specification.'
249 In Décor Corp Pty Ltd v Dart Industries Inc (1988) 13 IPR 385, Sheppard J reviewed the authorities and set out ten principles of construction:
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.
In Nesbit Evans Group Australia Pty Ltd v Impro Ltd (1997) 39 IPR 56, Lindgren J cited the ten principles with evident approval. Hill J, in a separate judgment, agreed. Wilcox J differed on one point not related to the relevant principles of construction and otherwise agreed with Lindgren J's reasons.
250 Lindgren J added the following to the propositions enunciated by Sheppard J in Décor Corp:
1. There is a danger in considering the integers of a claim individually and in isolation. This could yield a literal rather than a purposive construction - see Catnic Components Ltd v Hill & Smith Ltd [1982] RPC 183 at 243 (Lord Diplock).
2. The Court should avoid too technical or narrow a construction of claims.
3. A construction according to which the invention will work is to be preferred to one according to which it may not do so.
251 The learned trial judge in the present case was of the opinion that, as a matter of ordinary language, the term 'cGMP PDEV inhibitor' in claim 10 conveys to the reader the concept of a substance identified only by the presence of a particular function or capacity, namely that it inhibits cGMP PDEV. On that view the proposition that it describes only selective inhibitors of cGMP PDEV would impose a limitation or qualification upon the ordinary language.
252 His Honour referred to expert evidence on either side of the constructional debate. He also found evidence of usage contrary to the Pfizer contention. In Pfizer's Canadian Viagra Patent claim 25 referred to:
'The use of an effective amount of a cGMP PDEV inhibitor … where the cGMP PDEV inhibitor is a selective inhibitor of cGMP-specific PDEV.'
Claim 24 of the Pfizer US Patent also referred to 'an effective amount of a selective cGMP PDEV inhibitor.
253 The specification refers to 'selective enzyme inhibition' by the compounds of the invention but the selectivity there identified relates to the effect of the inhibitor on cGMP PDEs by way of contrast with its effect on cAMP PDEs. However later in the specification it is said:
'The compounds of the invention have been tested in vitro and found to be potent and selective inhibitors of the cGMP-specific PDEV. For example, one of the especially preferred compounds of the invention has an IC50 = 6.8nM v the PDEV enzyme, but demonstrates only weak inhibitory activity against the PDEII and PDEIII enzymes….'
It may be seen from these passages in the specification that selectivity against cGMP PDEVs is said to be a demonstrated feature of the compounds of the invention. Its importance, as it emerged from the evidence, was that administration of a selective inhibitor would not unduly affect the functioning of smooth muscle in organs other than the penis. Minimising the risk of adverse smooth muscle effects in cardiac, respiratory, bowel and retinal tissue was an important purpose of the invention.
254 Reading claim 10 in a way that is consistent with the terms of the specification to which reference has been made and the state of common general knowledge at the time and with an eye to its utility yields the narrower construction advanced by Pfizer. In this respect it may be said that his Honour erred. However, as already noted, if there were an error, it was not one which was shown to have had any affect upon his overall conclusions.
255 The second constructional question related to the term 'cure or prevent' in claim 10.
256 On the appeal Lilly contended that his Honour erred on the infringement issue by wrongly holding that its product, Cialis, did 'cure or prevent erectile dysfunction in men in need of such treatment' within the meaning of claim 10. Lilly submits that by the use of the expression 'cure or prevent', claim 10 claims more than Cialis achieves. Cialis treats erectile dysfunction 'on an ad hoc basis for a limited period of up to about 36 hours', whereas, according to Lilly's submission, to 'cure' is to produce the result that a man no longer has the underlying disease and ceases to be an impotent man, while to 'prevent' is to forestall the onset of the disease.
257 We were taken to dictionary definitions of 'cure' and 'prevent' but we do not find them particularly helpful. For example, the word 'remedy' is given as one synonym for 'cure', but the question simply becomes whether claim 10 claims a once and for all remedy.
258 We take as our staring point that which his Honour took: the Patent's definition of impotence (page 1, lines 6-11):
'… a lack of power, in the male, to copulate and may involve an inability to achieve penile erection or ejaculation, or both. More specifically, erectile impotence or dysfunction may be defined as an inability to obtain or sustain an erection adequate for intercourse.'
His Honour's reasoning is succinctly expressed in the following passage which follows his quoting of this definition ([230]):
'This would accord with the understanding of the term "impotence" (or its more scientific sounding synonym "erectile dysfunction") in ordinary speech. Accordingly claim 10 is not referring to some underlying physiological or psychological condition. In the vernacular, it is concerned with a performance problem. Cialis will treat that problem and thus "cure" or "prevent" it in the sense that a man taking Cialis will not have the problem for 36 hours. This question must be answered in the affirmative.'
259 We agree that impotence, as defined in the Patent and as commonly understood, is an inability to 'perform' from time to time when desired. Intervening periods do not give rise to any problem, even though the underlying condition exists during them too.
260 In our opinion, an 'inability to obtain or sustain an erection adequate for intercourse' is 'cured or prevented' not only by a once and for all remedy which is directed to the underlying condition, but also by the maintenance of an ongoing dosing regimen which is directed to the condition's manifestations from time to time. The words 'cure or prevent' in claim 10 are not limited to the former. It is no reason to limit them in that way that a once and for all treatment is preferable to a treatment which must be regularly repeated. Of course, the body of the specification makes it clear that the latter is the treatment method to which claim 10 refers: 'A preferred dosing regimen for a typical man is 5 to 75 mg of compound three times daily' (page 10, lines 28-30). If the meaning of the expression 'cure or prevent' in claim 10 were unclear (we do not think it is) it would be permissible to look to those words in the body of the specification to resolve the ambiguity: Interlego AG at 479; Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1at 12 [15].
261 Lilly submits that the draftsperson should be treated as having chosen the words and syntax of claim 10 with skill and care (Lilly cited Sachtler GmbH & Co KG v RE Miller Pty Ltd [2005] FCA 788 at [61]), and that if intermittent relief from impotence dependent on a course of treatment had been intended, some words such as 'A method of orally treating men for erectile dysfunction' would have been used. Lilly also refers to the fact that the corresponding claim in Pfizer's US Patent No 6,469,012 has been rewritten to refer to 'a method of treating erectile dysfunction in a male human'.
262 The fact that claim 10 might have been expressed in a way which, it might be suggested, more clearly excludes a claim of a once and for all remedy is not determinative of the present question. Nor is the different formulation of the corresponding claim in Pfizer's US patent.
263 Lilly refers to the disjunctive form, 'cure or prevent', in claim 10 (and to the disjunctive curative or prophylactic treatment at pp 4 and 11 of the Patent). But Lilly's submission that in claim 10, 'cure' means 'treat an existing disease so that the person treated no longer has the disease', and 'prevent' means 'forestall the onset of the disease to keep it from occurring', erroneously treats claim 10 as stating what it does not state: 'A method of orally treating men to cure to prevent the disease which gives rise to erectile dysfunction'.
264 Importantly, claim 10 states that it is concerned with 'men in need of [treatment to cure or prevent erectile dysfunction]'. Thus, the claim is concerned with men who already have the underlying disease. It follows that claim 10 can not be construed as a claim of a method of forestalling the onset of the disease at all. Since 'prevent' cannot be read as relating to the underlying disease, why should 'cure' be?
265 Lilly's submission does not give due weight to the word 'dysfunction'. Claim 10 is directed to inability to function, operate or perform from time to time when desired, not to the underlying disease which is the cause of that inability.
266 The draftsperson may have chosen the expression 'cure or prevent' in an attempt to focus attention on both the course of successive occasions of dysfunction ('cure') and the individual occasion of dysfunction ('prevent').
Infringement
267 For the purpose of the proceedings before the learned primary judge, Lilly made a number of formal admissions about the operation of its product Cialis in the treatment of erectile dysfunction. Those admissions have been summarised earlier in the discussion of his Honour's reasons for judgment. Given the admissions and his Honour's correct construction of the term 'cure or prevent erectile dysfunction' in claim 10, it follows that Lilly's product would infringe that claim if the claim were to be found valid.
Fair Basing
268 It is a requirement for the specification of a patent that the claim or claims made in it must be 'fairly based on the matter described in the specification' (s 40(3)). The history and content of the term 'fairly based' was discussed at some length in the judgment of the Full Court in CCOM Pty Ltd v Jiejing Pty Ltd (1994) 122 ALR 417 at 432-437 (Spender, Gummow and Heerey JJ). It became part of Australian patent law with the enactment of ss 40 and 45 of the Patents Act 1952 (Cth). As the Full Court said in CCOM (at 496):
'It was used to describe the relationship between the claims defining the invention and the matter described in the complete specification …, and as a criterion for fixing the priority date of the claim of a complete specification fairly based on matter disclosed in the preceding provisional specification….'
It is only the former sense which is relevant for present purposes. It has been carried over into the 1990 Act.
269 The question whether an invention as claimed in any claim is fairly based on the matter described in the specification is a distinct question and not to be conflated with other issues going to validity, such as novelty, utility or obviousness:
'A patent can be successfully challenged on the ground that the claims are not fairly based even though ever other possible ground of challenge fails.'
Lockwood Security Products Pty Ltd at 13 [48].
The process of assessment of fair basing mandated by the judgment in Lockwood Security lends emphasis to the proposition that it stands alone as a ground going to validity (at 14 [49]):
'… when assessing whether there is fair basing within the meaning of s 40(3), it is necessary to split the patent into the claims and the body of the specification in order to see whether the former are fairly based on the matter described in the latter.'
270 The question posed by the fair basing requirement is that formulated by Barwick CJ in Olin Corporation v Super Cartridge Co Pty Ltd (1977) 180 CLR 236 at 240:
'… 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.'
That is to say, assuming novelty, utility and inventive step, does the claim travel beyond the specification. That statement of the question was approved by the High Court in Kimberly-Clark at 12 [15]. The Court put it thus:
'… where the issue is one under a 40(3) of "fair basing" of a claim, what the 1990 Act requires is a comparison between the matter described in the specification and the claim which defines the scope of the monopoly.'
271 In Lockwood Security the court said that the comparison called for by s 40(3) is not analogous to that between a claim and an alleged anticipation or infringement. It is wrong to apply an 'over meticulous verbal analysis' or isolate in the body of the specification essential integers or features of an invention and inquire whether they correspond with the essential integers of a claim - at 20 [69]. What is required is 'a real and reasonably clear disclosure', words taken from the judgment of Fullagar J in Société Des Usines Chimiques Rhône-Poulenc v Commissioner of Patents (1958) 100 CLR 5 at 11. The court in Lockwood Security quoted with approval a passage taken from the judgment of Gummow J in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 (at 95), where his Honour said, inter alia:
'… 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.'
272 The learned primary judge found that claim 10 was not fairly based on the specification. That finding appears largely to have been grounded in his opinion that the specification dealt only with the compounds of the invention or compounds of formula (I), whereas claim 10 was not so limited. Applying the words from the judgment of Gummow J in Rehm he said that the issue of fair basing required a focus on the 'text of the patent'. He found the Patent to direct 'the reader away from further investigation and testing because what it does disclose are the specified "compounds of the invention".' It was the generality of claim 10 extending to substances outside the group defined as the 'compounds of the invention' which appears to have underpinned the fair basing finding in this case.
273 Pfizer's submissions on fair basing involved the following propositions:
1. The learned trial judge's conclusion on fair basis was tied to his construction of the term 'cGMP PDEV inhibitor'. He should have found that that term connoted selectivity.
2. The learned trial judge wrongly concluded that the compounds of the invention were confined to the compounds of formula (I).
3. Whether or not proposition 2 is correct, the principle claimed in claim 10 was broadly described in the specification.
274 As to the first proposition Lilly correctly submitted that it bore no relationship to his Honour's reasons for his finding on fair basis. That is the conclusion already reached earlier in these reasons in the section relating to the construction of claim 10. Lilly further submitted that the basis of his Honour's reasoning was that the Patent does not contain a real and reasonably clear description of the use of cGMP PDEV inhibitors outside the compounds of formula (I). What it does disclose as the invention is the use of the specified compounds of the invention.
275 The specification opens with the statement that the invention relates to '… the use of a series of a pyrazolo [4,3-d] pyrimidin - 7 - ones for the treatment of impotence'. In so doing it makes clear that the invention relates to a defined class of drugs. It does not, on those words, extend to any class of drugs which inhibits cGMP PDEV activity selectively or otherwise. The broad identification of the class of drugs to which the invention relates is linked to the reference on page 2 of the specification to 'The compounds of the invention …' which are said to be 'potent inhibitors of cyclic guanosine 3, 5-monophosphate phosphodiesterases (cGMP PDEs) in contrast to their inhibition of cyclic adenosine 3, 5-monophosphate phosphodiesterases (cAMP PDEs)'. Reference follows in the next paragraph to '… these disclosed compounds …'. There follows the statement that 'the present invention concerns the use of a compound of formula (I):'. That is then elaborated by various molecular substitutional possibilities. It is also widened to incorporate '… a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity …'. There follow repeated references to compounds of formula (I). The term 'compounds of the invention' reappears later in the specification. It is clear however that his Honour was correct in finding, on the proper construction of the specification, that the compounds of the invention are referred to interchangeably with the compounds of formula (I). There is no basis disclosed, upon a reasonable reading of the specification, for any distinction to be drawn between those two terms. Pfizer's second proposition fails.
276 The third proposition depends upon finding in the specification a broad statement of a range of cGMP PDEV inhibitors which can accommodate the range claimed in claim 10. Such a range of compounds is not to be found in the specification. Indeed the whole of its text may be read as limited by the class of compounds referred to in the opening sentence. Any limitation in the specification upon the class of compounds comprising the invention (other than by reference to their effects as cGMP PDEV inhibitors) is fatal to claim 10. For on its face, claim 10 applies to any compound, however defined, which is 'a cGMP PDEV inhibitor'. It makes no difference to that reasoning whether the term 'cGMP PDEV inhibitor' is read as referring only to selective inhibitors. The claim, read as a whole, travels well beyond the range of compounds, large as it may be, which is disclosed in the body of the specification. Pfizer's third proposition fails.
277 His Honour was right to conclude that the invention as claimed in claim 10 is not fairly based on the matter described in the specification.
Lack of Inventive Step - Obviousness
278 It is a necessary condition of patentability that an invention, so far as claimed in any claim, is one which, when compared with the prior art base as it existed before the priority date of the claim, involved an inventive step (s 18(1)(b)(ii)). Section 7(2) has the effect that a claimed invention lacks an inventive step compared with the prior art base only if '… 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'.
279 The term 'common general knowledge' is not defined in the Act but has been the subject of judicial exegesis reflecting:
'… 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.'
Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 at 292 (Aickin J)
Or as the Federal Court put it in WR Grace v Asahi Kasei (1993) AIPC 90-974 at 39,271:
'The common general knowledge of the art or science represents the matters that the skilled person will have at the back of his or her mind when coming to consider the prior art, so that each document alleged to constitute the prior art is to be regarded as the addressee would regard it in the light of common general knowledge. Common general knowledge is relevant as distinct from mere public knowledge.'
280 In addition to the state of common general knowledge, s 7(2) and (3) requires consideration to be given to prior art information publicly available through one document or act or one or more related documents or acts which the skilled addressee could 'be reasonably expected to have ascertained, understood and regarded as relevant to the work in the relevant art in the patent area'. The hypothetical skilled person will not confine himself or herself to the common general knowledge in considering the question answered by the allegedly inventive step. He or she can be expected to carry out literature searches using relevant contemporary search facilities including on-line data bases.
281 The effect of the 1990 amendments was discussed in the context of obviousness in Firebelt Pty Ltd v Brambles Pty Ltd (2002) 188 ALR 280. Under the 1952 Act, as expounded in Minnesota Mining, a prior disclosure 'did not provide a basis for a conclusion as to obviousness without evidence that the disclosure in question was part of the common general knowledge at the relevant priority date - Firebelt at [35]. The report of the Industrial Property Advisory Committee dated August 1984 entitled 'Patents Innovation and Competition in Australia' recommended that:
'For the purpose of determining inventiveness, any single prior disclosure or use should be capable of being considered against the background of all that is common general knowledge in the relevant field of art. On this basis the requirement of inventiveness will not be fulfilled if the knowledge imputed by the disclosure or use, combined with what is common general knowledge in the art would render the claimed invention obvious to a person reasonably skilled in the art.'
The Committee recommended that it not be possible to combine two disclosures or uses when neither lay within the common general knowledge unless one of the disclosures referred to another disclosure or use. The Committee further said:
'On the other hand we see as being treated within the common general knowledge of the art, not merely information which is generally known and used in the art but information publicly available or recorded from anywhere in the world which a skilled person working in the art at the relevant time should reasonably have been expected to find, understand, and regard as relevant.'
The Court in Firebelt noted that the latter recommendation was accepted for standard patents albeit not for petty patents which it was considering in that case.
282 Their Honours quoted with approval (at [36]) an observation by Burchett J in Tidy Tea Ltd v Unilever Australia Ltd (1995) 32 IPR 405 at 414 that:
'The new provisions are limited by the words "being information that the skilled person … could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood and regarded as relevant to work the relevant art in the patent area". And if a prior [disclosure] passes those tests, it must still be able to be said that, if that [disclosure] had been considered by the hypothetical skilled person together with the common general knowledge at the relevant time, "the invention would have been obvious".'
283 In Alphapharm a revocation claim on the ground of obviousness fell for consideration under the 1952 Act. The joint judgment of the majority referred in passing to the 1990 Act as providing relaxation of the rules forbidding the use of prior disclosures which, while publicly available, were not part of the common general knowledge at the priority date (at 422). This, of course, was the relaxation effected by s 7(2) and (3). The prior position reflected in the Minnesota Mining case would not, for example, allow obviousness to be established by an online search of the Patent Office library. The issue would not have been, was it obvious to search there, but whether 'what a search would have disclosed had entered the body of common general knowledge' (Alphapharm at 430).
284 The language of s 7(2) 'indicates that the onus to establish the absence of an inventive step rests upon the party challenging validity' (Firebelt at [31]).
285 The content of the concept of 'inventive step' was not changed by the 1990 amendments. The class of things that might be relied upon to prove its absence were widened, as already discussed, to include a prior disclosure or use or related disclosures or uses considered in the light of common general knowledge before the priority date.
286 The point of departure for determining whether a claimed invention was obvious at the priority date is the statement by Aickin J in Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd (1981) 148 CLR 262 at 286 that:
'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.'
The idea of 'routine' in this passage was elaborated in Alphapharm by reference to an earlier passage of Aickin J's judgment in Wellcome Foundation which was extracted at [51]. That passage referred to:
'… experiments were of a routine character which the uninventive worker in the field would try as a matter of course.'
WellcomeFoundation at 281
287 The Alphapharm majority saw an affinity between the approach adopted by Aickin J and the so-called Cripps Question posed by Graham J in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157. The approach enunciated by Graham J in the passage that follows was expressly approved by the majority in Alphapharm:
'Would the notional research group at the relevant date, in all the circumstances, which include a knowledge of all the relevant prior art and of the facts of the nature and success of chlorpromazine, directly be led as a matter of course to try the -CF3 substitution in the "2" position in place of the - CI atom in chlorpromazine or in any other body which, apart from the - CF3 substitution, has the other characteristics of the formula of claim 1, in the expectation that it might well produce a useful alternative to or better drug than chlorpromazine or a body useful for any other purpose?'
The approval of this passage in Alphapharm did not involve any acceptance of the proposition that a claimed invention is obvious if the steps that led to it would have been seen by a skilled addressee as 'worth while to try' in the light of common general knowledge at the priority date. The majority expressly rejected that criterion. They regarded the decisions of the United States' courts, which also rejected that approach, as reflecting an approach closer to that adopted in the Minnesota Mining and Wellcome Foundation decisions.
288 There was no dispute in Alphapharm that the hypothetical non-inventive worker in the field could be represented by a team of persons experienced in the practical work of formulating drugs for pharmaceutical use. Such persons would be highly qualified chemists usually with a demonstrated capacity for original research. Assuming, as seems to have been common ground in the present case, that a PhD qualification would be an entry level requirement for participation in the notional team of skilled addressees, that would certainly be correct. The majority in Alphapharm paraphrased the approach taken by the learned trial judge in that case (at [30]):
'The hypothesis which the case law required fixed upon members of that class who were not "particularly imaginative or inventive". There are conceptual difficulties in applying what is said in some of the older authorities respecting "workmen" and the like to modern conditions in the pharmaceutical and other industries. But the employment of highly skilled research teams as a matter of course, was noted over seventy years ago, well before the 1952 Act.'
The Court noted that there was no challenge to the approach of the trial judge. It was therefore not required to pass upon that approach but did not criticise it in any way.
289 The essential steps in the reasoning of the learned trial judge in the present case involved the following steps:
1. The notional team of skilled addressees would include a pharmacologist, a medical chemist and a medical practitioner experienced in the treatment of impotence.
2. Rajfer and Murray formed part of the common general knowledge at the priority date.
3. Rajfer could be relied upon to establish a lack of inventive step. It provided an unusually powerful indication that further examination of the PDEV inhibitor possibility was 'worth trying and that the expectation that such examination might produce a worthwhile result was a very reasonable one'.
4. Murray formed part of the common general knowledge of the priority date but also qualified as a s 7(3) document.
5. Murray could be relied upon to establish a lack of inventive step.
290 As Lilly observed in its submissions on the question of inventive step, Pfizer's submissions related almost entirely to evidentiary matters. Pfizer contended that there was no evidence at trial justifying the conclusion that the invention as claimed in claim 10 was obvious. There was no evidence as to the state of common general knowledge of skilled addressees within Australia. If it were proper to rely upon evidence of the knowledge of persons overseas, that did not establish that a skilled addressee, by taking routine steps, would have been led directly to the invention. Moreover, it was submitted, that the evidence of widespread demand for an oral treatment for erectile dysfunction and the failure of anybody to disclose the use of a cGMP PDEV inhibitor in an oral treatment for erectile dysfunction until after the publication of Pfizer's Patent spoke strongly against the trial judge's conclusions.
291 Pfizer identified what it said were a number of incorrect factual findings on the part of the learned trial judge. It summarised its position thus:
(a) Each of Dr Cherry, Dr McMahon and Dr Cartmill, was not capable of giving relevant and admissible evidence of the state of common general knowledge of the skilled addressee working in the field in Australia in 1993/94.
(b) Each of the overseas witnesses, Dr Gristwood, Dr Kruse and Mr Pryor, was not capable of giving relevant and admissible evidence of the state of common general knowledge of the skilled addressee working in the field in Australia in 1993/94.
(c) Murray was not part of the common general knowledge of the skilled addressee in Australia as at 1993/94.
(d) It was not an overstatement to say that as at the relevant priority date each of cGMP PDEV and PDEI 'were known to be located in tissues situated throughout the body, including in the smooth muscle of the vasculature platelets and lung tissue'.
(e) As at 13 May 1994 there was not a complete and accurate knowledge of the presence of PDEs and their types in corpus cavernosum.
(f) The Pfizer team's discovery of the invention claimed in claim 10 was:
(i) not due to the impact of Rajfer; and
(ii) serendipitous.
(g) As at 1993/94 the skilled addressee (overseas, there being no evidence from Australian addressees) was concerned about potential dangerous effects from an orally administered PDEV inhibitor; and
(h) The term 'compounds of formula (I)' is not synonymous with the term 'compounds of the invention'.
292 Pfizer's submissions involved the contention that the learned trial judge should not have had regard to the evidence of expert witnesses from outside Australia as proxies for people who worked in the relevant field in Australia. That submission is not accepted. But it was open to his Honour to have regard to such evidence in assessing the state of common general knowledge of an hypothetical skilled team in Australia at the priority date. He could also have regard to such evidence in assessing the significance of prior art information in Australia. The linkage to be made between the evidence of overseas witnesses and the position in Australia was a matter of fact and inference.
293 There was ample evidence before his Honour of the international character of research in the field of erectile dysfunction. By way of example, Dr Gristwood gave evidence of matters known to him and which he believed would have been known to other pharmacologists in the United Kingdom and elsewhere, including Australia, in 1993. Evidence as to the global nature of a particular field of scientific inquiry can properly be given by one who is an expert in the field. It is the kind of thing which, in the ordinary course of his research and communication with other scientists, he could be expected to know. Whether or not it is to be accepted, is a matter for the trial judge.
294 Mr Pryor was based in the United Kingdom, but gave evidence of contacts with urologists in Australia before 1993 and the close links that existed between the British and Australian Urological Associations. It is not necessary to multiply examples of the evidence which has already been summarised in these reasons. It is sufficient to say that it supported the inference of a global pool of common general knowledge on issues relevant to the invention which would have been known to the skilled hypothetical addressee in Australia and that Rajfer and Murray were, as found by his Honour, part of that common general knowledge.
295 The present case is not to be decided by niceties of the location of particular expert witnesses. That kind of approach would place the fields of pharmacology, medicinal chemistry and urology in Australia in a rather unreal state of isolation from the rest of the world.
296 As to the evidence of clinical urologists, which it was suggested should not have been accepted as they were not properly part of any hypothetical team of skilled addressees, that submission is not accepted. Dr Cherry, who is a Perth urologist, gave evidence of his knowledge of the field which of itself was a good indicator of the common general knowledge that other relevant skilled addressees on the hypothetical team would have. The Pfizer submissions would have excluded relevant clinicians from the team looking for a mode of treatment for impotence. But clinicians and, in particular, urologists, were in a position to offer a practical, clinical perspective, albeit rooted in the necessary theoretical learning which was necessary for the development of an effective treatment.
297 So much having been said, the critical question in this case was whether Rajfer and Murray regarded as part of the common general knowledge or as s 7(3) documents, jointly or severally, rendered the development of the claimed invention obvious. For it was on the foundation of those two works that his Honour held the claimed invention to lack the necessary inventive step.
298 The learned trial judge reviewed, in his reasons for judgment, what Rajfer conveyed to various expert witnesses. His findings in this respect may be summarised as follows:
1. Dr McMahon saw Rajfer as clarifying the role of NO as part of a cascade of neurotransmitters in the development of penile erection. Beyond that the main conclusion he drew was that there may be a role for zaprinast and perhaps for PDEV drugs as a treatment for men with erectile dysfunction.
2. Dr Cherry concluded from Rajfer that the NO/cGMP pathway was responsible for the human erectile response and that, at an in vivo level, the pathway could be manipulated by potentiating NO formation or by the use of a cGMP PDE inhibitor such as zaprinast.
3. Mr Pryor saw the paper as demonstrating that zaprinast was potentially useful in the treatment of erectile dysfunction because it elicited the immediate physiological response, ie smooth muscle relaxation in penile tissue taken from impotent human patients.
4. Dr Gristwood said that on reading Rajfer he appreciated that impotence was a new therapeutic possibility for PDEV inhibitors in light of the fact that zaprinast, a known selective PDEV inhibitor, was shown to enhance smooth muscle relaxation of human corpus cavernosum tissue. Rajfer would have strongly suggested to him the use of PDEV inhibitors as a new treatment for impotence.
5. Dr Kruse did not recall reading Rajfer at the time of its publication. He thought Rajfer completely elucidated the NANC pathway leading to erection. Smooth muscle relaxation induced by NO was mediated through an increase in the cGMP PDE inhibitor, zaprinast, which he knew was a selective inhibitor of PDEV. Because Rajfer used actual human penile muscle tissue from men suffering from erectile dysfunction he would have had a 'high level of confidence' that Rajfer's results would have been directly transferable in vivo.
6. Dr Ellis said that all Rajfer did was to confirm early animal results and demonstrate that NO was a neurotransmitter in the NANC pathway. He agreed in cross-examination that Rajfer showed that zaprinast used as a tool potentiated or augmented or enhanced the effect of electrical field stimulation and NO under experimental conditions defined.
7. Dr Palmer had not read Rajfer before the present proceedings. Its whole thrust was consistent with a focus on confirming the features of the NANC/L-arginine/NO/cGMP pathway. It did not disclose a logical therapeutic use of PDE inhibitors for the treatment of impotence.
8. Dr Robertson said that Rajfer proved to him that NO was the key mediator and that something which mimicked it or supplied it to the penis would be likely to give an erection.
299 His Honour did not refer to that part of Dr McMahon's evidence in which he described the Rajfer paper as a 'proof of concept' type paper which suggested a 'potential role' for zaprinast in the treatment of erectile dysfunction. Dr McMahon also pointed out that the level of relaxation demonstrated in the paper could not be translated to the level of relaxation or the concentration of zaprinast necessary in vivo.
300 Dr Kruse had said in cross-examination that there was no case in which one could take an in vitro experiment and leap to an efficacious dose in man. What could be done was to take the reasonable step of going forward with a PDEV inhibitor and doing appropriate clinical trials.
301 His Honour did not refer to the Bayer witness, Dr Brown. Dr Brown said in his evidence that the obvious pharmacological approach in the light of Rajfer was to use a PDEV inhibitor as an orally active direct acting vasodilator interfering with the L-arginine NO pathway to relax the smooth muscle. However he agreed in cross-examination that it was not possible from Rajfer to draw the conclusion that the reported effect of the PDEV inhibitor in that case would be greater in penile tissue than in any other tissue in the body.
302 His Honour did not canvass Professor Goldie's evidence which was that the overall message from the Rajfer paper was that NO released by NANC nerves is essential to penile erection. It also set the scene for 'clinical intervention to treat impotence with substances which act on the NO pathway either as an NO donor or as a cGMP PDE inhibitor'. Dr Goldie accepted in cross-examination that in learning about the paper some people would say that in addition what they ought to be doing is looking at the potential for PDEV inhibitors as a potential therapy. He was not saying that that was his reaction.
303 Dr Cartmill, another Bayer witness, had not read the Rajfer paper before his preparation for the present proceedings. He said that the use of cGMP PDE inhibitors to treat impotence stood out from Rajfer as an obvious thing to do from a urological perspective.
304 His Honour made the global statement that he accepted the evidence of Lilly and Bayer witnesses as to what Rajfer would have conveyed. However, with respect to his Honour, it cannot be said that the message conveyed by the Lilly and Bayer witnesses was consistent and unambiguous as to what Rajfer would have conveyed to them. It must of course be acknowledged that his Honour made the point that scientific papers have a 'cautious tone of voice' with a 'liberal sprinkling of qualifications' and that (at [135]):
'In a discourse in that style and tone Rajfer conveys, not certainty, for that is not required, but a well-founded expectation that further testing of cGMP PDEV inhibitors might well provide a treatment for impotence or, in Dr Robertson's words, would be likely to have that effect.'
305 In concluding that Rajfer could be relied upon to establish a lack of inventive step, his Honour came close to adopting the 'worthwhile to try' approach eschewed by the High Court in Alphapharm. For he said that Rajfer provided an unusually powerful indication that further examination of the PDEV inhibitor possibility was 'worth trying and that the expectation that such examination might produce a worthwhile result was a very reasonable one'.
306 So far as Murray was concerned, his Honour accepted, correctly, that it was probably unnecessary and artificial to consider Murray without Rajfer as the former specifically referred to the latter. Murray, of course, was a review article, not one reporting research in its own right. Murray really stands or falls with Rajfer in this connection.
307 Rajfer was an in vitro organ bath experiment using strips of penile tissue subjected to electrical stimulation and exposure to different chemicals including methylene blue and zaprinast. Its principal objective was clarification of the NANC L-arginine NO pathway in erectile function. While the evidence of the expert witnesses might well support a conclusion from Rajfer that investigation of the effects of a cGMP PDEV inhibitor on erectile function was worth a try, it could not be said, given the uncertainties attending such further investigation, that it would be routine or 'a matter of course'. The same is true of Murray.
308 The fact that Dr Ringrose suggested to his management team that they 'try out UK-92,480, in impotence' does not of itself establish that any such try out would have been a matter of routine or of course. It might well be, as his Honour said, that the ideas conveyed by Rajfer were intimately bound up in Pfizer's work which led to the alleged invention the subject of the Patent. But the facts as found by his Honour do not, with respect, support the notion of a mere routine process of investigation leading to the invention claimed in claim 10.
309 In a recent essay, Sir Hugh Laddie criticised the concept of 'obvious to try' as the criterion of want of inventive step expounded by the English Courts. He said:
'On its face, this produces an unworkable or irrational test. If the reward for finding a solution to a problem and securing a monopoly for that solution is very high, then it may well be worthwhile for large players to examine all potential avenues to see if one gives the right result, even though the prospects of any one of them succeeding are much less than 50/50. What makes something worth trying is the outcome of a simple risk to reward calculation. Yet, if the reward is very large, the avenues worth trying will be expanded accordingly. So, the more commercially attractive the solution and the more pressing the public clamour for it, the harder it will be to avoid an obviousness attack. In those circumstances a solution which is quite low down a list of alternatives, all of which are more or less worth trying, will fail for obviousness; a consequence which is consistent with the decision in Brugger v Medic-Aid [1996] RPC 635'.
Laddie, 'Patents - what's invention got to do with it?' In Vaver and Bently (eds) Intellectual Property in the New Millennium, Cambridge University Press (2004) 91 at 93.
310 As a more general critique of the obviousness requirement he observed (at 95):
'For example, in the world of medicine and genetics, not only do we now have great understanding of how chemicals and genes work but there are now new disciplines which allow the technician to determine what shape of molecule exhibits a particular beneficial property and how to make molecules of that shape.
It is this type of technology which will be used to tackle diseases in the future, yet in many cases it may be said that the application of such technology to solve known problems is not inventive. It appears that the field of pharmaceuticals, the example which is most often used to demonstrate the necessity of patent protection to delivery of new and valuable products to the public, also illustrates how ill-suited the law is for achieving that goal.
It has been said that patents are not granted simply for coming first in the race to achieve an obvious product or process. Yet in many cases, absent the commercial incentive of a patent, there will not be a race at all.
In this case, on accepted tests of obviousness as enunciated most recently in Alphapharm, his Honour erred in reaching the conclusion that he did. The evidence did not disclose lack of an inventive step in relation to the invention claimed in claim 10. On that point Pfizer succeeds.