Common General Knowledge at the Priority Date
176 The Opposed Application does not expressly refer to acridines, or to particular types of acridines, such as acriflavine or euflavine. They are not identified by name as preferred antiseptics. The respondent contends that they would not be understood by the skilled addressee as preferred antiseptics because they are not named. Alternatively, the respondent contends that they would not be understood by the skilled addressee as preferred antiseptics unless it was common general knowledge that they had one or more of the preferred properties identified in the first passage on page 12 or were, or at least some of them were, ionised antiseptics or QACs. If that was not common general knowledge, then, on the respondent's case, acridines are not preferred antiseptics within the terms of the Opposed Application.
177 It is necessary to identify the common general knowledge shortly before the prior date which the skilled addressee would have for the purposes of construing the Opposed Application. In determining the content of common general knowledge, it is necessary to examine the position shortly before the priority date. That is because it is possible for information to have been common general knowledge at a point in time before the priority date, but to have ceased to have been so at the priority date. By the time of the priority date, the information may "have been discredited or forgotten or merely ignored" (Birss C (ed), Terrell on the Law of Patents (19th ed, Sweet & Maxwell, 2020) at [8-77]; Martin Engineering Co v Trison Holdings Pty Ltd [1989] FCA 64; (1989) 14 IPR 330 (Martin Engineering) at 350 per Burchett J; Technological Resources Pty Ltd v Tettman [2019] FCA 1889; (2019) 375 ALR 185 at [48]-[49] per Jagot J).
178 The starting point in terms of the identification of information which constitutes common general knowledge is the description of the concept in the reasons for judgment of Aickin J in Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; (1980) 144 CLR 253 (at 292):
[T]hat 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.
179 A critical feature of common general knowledge is that it is known to, and accepted by all or the bulk of those in the trade (British Acoustic Films Ltd v Nettlefold Productions Ltd (1935) 53 RPC 221 (British Acoustic Films) at 250 per Luxmoore J; Graham Hart (1971) Pty Ltd v S W Hart & Co Pty Ltd [1978] HCA 61; (1978) 141 CLR 305 at 329 per Aickin J (with whom Barwick CJ agreed); Aktiebolaget Hässle v Alphapharm Pty Ltd [1999] FCA 628; (1999) 44 IPR 593 at [39] per Lehane J; Ranbaxy Laboratories Ltd v AstraZeneca AB [2013] FCA 368; (2013) 101 IPR 11 at [217] per Middleton J). With respect, a clear statement of this feature of common general knowledge was made by the Full Court of this Court in Idenix as follows (at [192]):
It is necessary for us to observe at this point that common general knowledge is background knowledge and experience which is available to all in the trade. It must be generally accepted and assimilated by persons skilled in the art and known and accepted without question by the bulk of those who are engaged in the particular art. Information is not common general knowledge merely because it might be found in a journal, even if widely read. In that conceptual framework, the primary judge correctly found that the hypothetical skilled addressee should not be treated as having available, as part of the common general knowledge, all of the very specific expertise and experience in the fluorination of nucleosides or carbocyclic compounds that Professor Meier and Dr Borthwick possessed by reason of their involvement in particular projects …
180 It follows that the fact that a witness, or even a number of witnesses, had knowledge at the priority date does not of itself establish that the knowledge was common knowledge. The witness may be an expert who has specialised expertise and knowledge (British Acoustic Films at 250 per Luxmoore J; Idenix at [192]). At the same time, as the respondent pointed out, evidence that an expert, or a number of experts, were not aware of certain information may be evidence, possibly powerful evidence depending on the circumstances, that the information was not common general knowledge (Martin Engineering at 350 per Burchett J).
181 Common general knowledge and public knowledge are not the same. The requirement that information be accepted or assimilated by all or the bulk of those engaged in the relevant art before it can be considered to be common general knowledge means that proof that an article or journal has been widely circulated, or even widely read, is not of itself sufficient to establish that it is common general knowledge. In British Acoustic Films, Luxmoore J said (at 250):
In my judgment it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates. A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in a particular art; in other words, when it becomes part of their common stock of knowledge relating to the art.
182 I turn now to identify the matters of common general knowledge shortly before the priority date of 17 September 2008 established by the evidence in this case.
183 As a general proposition, I bear in mind, as the appellant pointed out, that, in assessing the evidence of the experts about acridines and their properties, substantial parts of the evidence of Professors Cook and Huxley and Associate Professor Bunt was based on information and knowledge they acquired after the priority date.
184 As I have said, in the substantive opposition proceeding, the delegate found that it was part of the common general knowledge at the priority date that acriflavine had an antiseptic property and was a dye (at [198] and [207]). The respondent did not appeal against the delegate's decision in the substantive opposition proceeding. Instead, it chose to make an application to amend the claims. The appellant submits that there is clear authority that, in those circumstances, it is not open to the respondent in subsequent opposition proceeding to challenge a final decision on issues arising in the first opposition proceeding and the position must be even stronger in the case where the subsequent proceeding is an application to amend the specification.
185 In support of its argument, the appellant relied on the decision of Rares J in Merck, Sharpe & Dohme (Australia) Pty Ltd v Genentech Inc [2016] FCA 324; (2016) 118 IPR 498 (at [55] and [70]) and, in particular, his Honour's reference to R v Smith; Ex parte Mole Engineering Pty Ltd [1981] HCA 25; (1981) 147 CLR 340 (Mole Engineering) (at 348 per Mason J (as his Honour then was); at 358 per Wilson J). Rares J said (at [70]):
Merck's challenge to the second decision asserting lack of novelty and inventive step was in reality an attack on the first decision that allowed Genetech [sic] to amend claims 1, 4, 5, 15 and 28 to overcome the delegate's findings that they lacked novelty. The attack in the notice of appeal had to be made against the first decision. It could not be made against the second decision by reason of the principle in Mole Engineering and, accordingly, the appeal is incompetent. The delegate's reasoning in the second decision (assuming she had power to make it) was correct.
(Citation omitted.)
The principle in Mole Engineering is that there is to be one substantive opposition proceeding leading to one decision and it is not possible to have potentially two conflicting decisions with no statutory provision to indicate which decision prevails.
186 In the alternative, the appellant submits that the finding of the delegate was legally indispensable and necessary to his decision and there is an issue estoppel between the parties of the type identified by Dixon J (as his Honour then was) in Blair v Curran [1939] HCA 23; (1939) 62 CLR 464 (at 532) and by Barwick CJ in Ramsay v Pigram [1968] HCA 34; (1968) 118 CLR 271 (at 276). The appellant submits that an issue estoppel arises because, although the delegate is not a court, he had jurisdiction to decide finally a question arising between the parties (Kuligowski v Metrobus [2004] HCA 34; (2004) 220 CLR 363 at [22]).
187 The respondent's response to the appellant's submissions is as follows. First, it accepts that when the substantive opposition proceeding resumes after the determination of the amendment application, the findings in the first proceeding will be binding as between the parties. However, there is no authority to the effect that they are binding in this proceeding which is a hearing de novo. Secondly, it submits that there is doubt in the case law as to whether an issue estoppel arises in administrative proceedings dealing with patent validity (SNF (Australia) Pty Ltd v Ciba Speciality Chemicals Water Treatments Ltd [2016] APO 8 at [33]-[46]).
188 The respondent's acceptance that the delegate's finding in the substantive opposition proceeding (in respect of which there was no appeal) is binding on the parties when the matter is returned to the delegate for finalisation of those proceedings is important because it is difficult to conceive of a reason why it is not binding at the intermediate stage (i.e., the amendment application). In my opinion, the finding is binding on the parties and it is not to the point that this proceeding is a rehearing before the Court. The point is that it is not an appeal from the substantive opposition decision.
189 I turn now to describe, in summary form, the respective cases of the parties as to the information which comprised common general knowledge at the priority date. I will then set out my conclusions.
190 The appellant conveniently divided its analysis into six topics.
191 First, the appellant identified common general knowledge with respect to antibiotics and antiseptics shortly before the priority date. It referred to the definition of "antiseptic compound" adopted by the experts in the joint expert report. An "antiseptic compound" is a single chemical moiety or a mixture of closely-related chemical moieties which singly and/or together fit the definition of "antiseptic". A chemical compound can be referred to as an antiseptic if either it kills microorganisms or if its activity inhibits the replication of microorganisms, when it is safely applied topically to living tissue. I accept that these matters were common general knowledge shortly before the priority date.
192 Secondly, the appellant identified its case as to common general knowledge with respect to Gram-positive and Gram-negative bacteria and broad spectrum antiseptics. Bacteria are generally classified as Gram-positive or Gram-negative. The strict definition of the term "broad spectrum" is that it refers to an antimicrobial compound which is effective against some species of both Gram-positive and Gram-negative bacteria. The term "broad spectrum" is commonly used to describe an antimicrobial compound that is effective against a wide range of disease causing bacteria, while "narrow spectrum" is commonly used to describe an antimicrobial compound which is effective against only a specific group of bacteria. I accept that these matters were common general knowledge shortly before the priority date.
193 Thirdly, the appellant identified its case as to common general knowledge with respect to QACs as follows. A QAC is a permanently positively charged organic nitrogen compound in which the nitrogen atom makes four covalent bonds. Such a compound is an ionised compound. I accept that these matters were common general knowledge shortly before the priority date.
194 Fourthly, the appellant identified its case as to common general knowledge with respect to particular antiseptics that were known shortly before the priority date as follows. Before September 2008, known antiseptics included BZK, cetrimide, chlorhexidine, iodophors, triclosan and antiseptic acridines. The MIMS New Zealand 2008 IVS Annual contains a list of chemotherapeutic agents used in veterinary pharmacology. The term "chemotherapeutic agent" refers to any chemical used for the treatment of disease. The list of antiseptics and disinfectants in MIMS New Zealand includes acriflavine, aminacrine (also known as 9-aminoacridine), chlorhexidine and iodophorm (also referred to as iodophors).
195 I accept that known antiseptics shortly before the priority date included BZK, cetrimide, chlorhexidine, iodophors and triclosan. I will return to the issue of the extent to which antiseptic acridines were known antiseptics. MIMS New Zealand contains the matters identified by the appellant.
196 Fifthly, the appellant's case as to the extent of common general knowledge shortly before the priority date with respect to acridines is as follows.
197 Professor Wainwright gave evidence that acridines comprise a central pyridine ring fused to two benzene rings. He gave evidence that the term "acridines" includes acridine derivatives, which are acridines that have substituted, that is, at least one hydrogen atom bonded to a carbon atom on the acridine ring has been replaced by a different atom or group. Not all acridine derivatives are antiseptics. The antiseptic activity of an acridine derivative is dictated by the position and nature of the substituted group(s) on the acridine core.
198 It was agreed in the joint expert report that antiseptic acridines exist in a highly positively ionised (cationic) state and it is the cationic state of antiseptic acridines which allows antiseptic activity. Further, there is a correlation between the degree of ionisation and antiseptic action.
199 Professor Wainwright gave evidence that the ionisation of acridines at physiological pH was well understood and that the ionisation of acridine derivatives was able to be predicted easily using well-known principles of chemistry before the priority date. He gave evidence that euflavine, proflavine, sinflavin and 9-aminoacridine are examples of antiseptic acridines. Acriflavine is also an acridine. Acriflavine is a mixture of euflavine chloride and a minor amount of proflavine hydrochloride.
200 It was agreed in the joint expert report that antiseptic acridines such as euflavine chloride, the purified form of acriflavine, are QACs, which comprise antiseptic acridines where the ring nitrogen makes four covalent bonds. In addition, all acridines which are QACs are permanently positively charged and so are 100% ionised as cations at all pH values.
201 Professor Wainwright said that euflavine, proflavine and aminacrine have broad spectrum activity in that they have activity against both Gram-positive and Gram-negative bacteria. Acriflavine also has broad spectrum activity, being bactericidal against both Gram-positive staphylococcus aureus and Gram-negative escherichia coli.
202 The appellant's case is that the evidence establishes that antiseptic acridines have been used in veterinary products and it referred to the following.
203 The first item of evidence is evidence of Professor Wainwright to the effect that ethacridine, euflavine and acriflavine have been used in the treatment of streptococcal mastitis in cows by injection of a solution into the teat canals of cows. To support that proposition, Professor Wainwright referred to the textbook, Albert A, The Acridines: Their Preparation, Physical, Chemical, and Biological Properties and Uses (2nd ed, Edward Arnold, 1966) (Albert). An extract from Albert was in evidence and it contains the following passage:
Nevertheless, ethacridine has been found useful in streptococcal mammitis and mastitis in cows, a solution being injected into the teat-canals either alone (Bugge, 1924) or mixed with a nitroacrdine (14.3) to form 'Entozon' Compound Granules (Gerke, 1935; Trautwein, et al., 1934; Schalm, 1942) (for the chemistry of 'Entozon' see Section 14.2). However, Steck (1934, 1937) who compared 'Rivanol' with euflavine, preferred the latter for bovine mastitis.
204 The second item of evidence is evidence of Professor Whittem to the effect that acriflavine has been used to treat the very delicate gill tissues of fish which are sensitive to irritation. Professor Whittem said:
Finally, with respect to the acriflavines in particular and the question of how irritants would I expect them to be, as a pharmacologist, I've used these products in treating fish. They're marketed in Australia for that purpose. They're used for treating fungal infections on - or fin rot on fish. So you add the acriflavine to the fish water, and that's in - in the tank, and they swim around in the tank. The very - one of the very most sensitive tissues of fish are their gills. These are very, very delicate tissues which are where the oxygen and other gases are exchanged with the water. The gills are particularly sensitive to irritation, particularly sensitive to irritation from ammonium ions. In fact, if your fish filter, fish tank filter fails, it's very often the ammonium ions that cause the fish to die, and yet we use acriflavine in fish tanks.
205 The third item of evidence is also evidence of Professor Whittem. He said that acriflavine has also been used in wound dressing, against staphylococcus aureus, which is one of the pathogens implicated in mastitis:
MR HEEREY: Yes. And there's description of acriflavine that continues for the rest of that page, and then there's a heading which says Actions and Uses. And it says that acriflavine is often preferred for wound dressing. And, simply, you would accept that wound dressing is a very different application to the use of an antiseptic for an internal teat seal. Do you accept that, Professor Whittem?
PROF WHITTEM: No, I don't, because you use an antiseptic, a disinfectant, or an antimicrobial compound, no matter what you want to call it, against the pathogens that you're targeting. The most common pathogen that infects wounds is staphylococcus aureus, which is a commensal of the skin and, in my mind, one of the target bacteria for treating dry cow mastitis, or preventing dry cow mastitis, is the same organism, staphylococcus aureus. So, in my mind, we're choosing an antiseptic on the basis of a known ability to target the pathogen of interest.
206 The fourth item of evidence relates to two products containing acridines which were listed in the MIMS Australia 2008 IVS Annual. They are Yellow Lotion and Septicide Cream.
207 MIMS Australia identifies the registered name of Yellow Lotion as Ranvet's Yellow Lotion Antiseptic Astringent Wound Lotion. The composition contains acriflavine. The indications are stated as follows:
Promotes healing in granulating wounds and helps stop the formation of proud flesh. It promotes a dry surface, resistant to infection without forming an undesirable hard crust on the wound. Has a sedative effect on nerve ends making it a suitable treatment for wounds, cuts and abrasions. Yellow Lotion has a soothing astringent action for treating sprains and bruises, especially for tendons.
208 Professor Whittem gave evidence that he was aware that Yellow Lotion had been used for the treatment of wounds on the udder. He agreed in the course of his evidence that there was nothing in MIMS Australia to indicate that the Yellow Lotion product or acriflavine was suitable for use in the treatment of mastitis.
209 Septicide Cream is referred to in MIMS Australia as being produced by Virbac (Australia) Pty Limited and it is stated that its composition includes proflavine hemisulfate. In another publication in evidence, Septicide Cream is indicated for insect repellent and an antiseptic cream for use on wounds in dogs and horses. Professor Huxley agreed in the course of his evidence that Septicide Cream was approved for use in animals and that could include animals (i.e., horses) that were intended to enter the food chain, subject to a requirement that there be a withholding period of 28 days.
210 The appellant also referred to the fact that in the substantive opposition proceeding, the delegate found that the prior art disclosed veterinary compositions for treating mastitis in dry cows that included acriflavine. That is correct. The appellant submitted that that was consistent with the evidence of the veterinary scientists in the proceeding and it referred to the evidence of Professors Laven and Whittem and Associate Professor Bunt.
211 Professor Laven said that his main exposure to acriflavines in veterinary medicine was their use as a disinfectant or a pigment or a preservative in a teat sealing product. He said that the very first teat sealing product had both bismuth and acriflavine listed as active ingredients. He was asked whether he was referring to a paper published by Dr WJ Meaney in 1977. He said that it was a "bit before" the paper by Dr Meaney because Dr Meaney had just used a product that was commercially available. Dr Meaney had taken a teat seal which had been developed as a method for controlling mastitis and he tested it. Prior to 2008, the only disinfectant that had been used in a bismuth-based teat sealant was acriflavine. Professor Laven said that he had never used it for the prevention of mastitis, but he knew it to be effective, at least as a teat sealant.
212 The paper by Dr Meaney in 1977 was published in the Irish Journal of Agricultural Research (Vol 16, No 3, 1977) and it reported on Dr Meaney's observations of experiments concerning intramammary teat seals used during the dry period. One seal involved a composition of bismuth subnitrate 25% (w/w) and acriflavine 0.075% (w/w). Professor Laven said that there were three potential reasons why a person might use acriflavine. They are first, as an antiseptic, secondly, as a preservative, and thirdly, because it is orange in colour. Professor Laven said that he did not know, and he did not make any inquiries in 2001, which was at about the time he first read Dr Meaney's 1977 paper, as to why acriflavine was present in the teat seal. Professor Laven said:
However, it does show that if you make a teat sealant with bismuth and acriflavine it does not cause the cow significant harm or discomfort. So, yes, so to me it shows that you can have a teat sealant with bismuth and acriflavine.
213 Professor Whittem made a statutory declaration in the opposition filed by Pfizer, Inc to New Zealand Patent Application No 571347 on 13 December 2011 and in that document he identified what he considered to be common general knowledge before the priority date. He agreed that he did not expressly identify acridines or acriflavine as part of the common general knowledge. However, he did identify the Meaney 1977 paper as part of the common general knowledge and in his evidence he identified a history of acriflavine being incorporated in a teat seal and not causing toxicity issues. In that connection, he referred to a study in evidence "which showed that acriflavine when incorporated in teat seal at 0.1 per cent was able to leach out of the formulation and kill mastitis causing bacteria".
214 Associate Professor Bunt was aware of the use of acriflavine in teat seals because he was aware of a UK Patent Application GB2,273,441 (published on 22 June 1999).
215 The appellant's case as to common general knowledge with respect to mastitis before the priority date is based on the joint expert report. Mastitis is the bacterial infection of a cow's mammary gland. During the dry period, that is, when they are not milked, cows may suffer sub-clinical and clinical forms of mastitis. Typically, infections are thought to be acquired during the period at the beginning and end of the dry period. Clinical mastitis caused by bacteria acquired during the dry period most commonly occurs shortly after calving, but can occur up to a number of months later. There is evidence that some of the bacteria causing mastitis in early lactation have entered the mammary gland earlier during the dry period. Finally, some sub-clinical intramammary infections acquired during the previous lactation can be carried into the dry period. In Australia and New Zealand, where cow milking and calving are seasonal and pasture-based, streptococcus uberis and staphylococcus aureus are the most frequent and dominant causes of mastitis reported in the dry period. In countries with a barn-based season (such as the United States or Europe), streptococcus uberis and coliform bacteria are the dominant groups of mastitis-causing bacteria. Both streptococcus uberis and staphylococcus aureus are Gram-positive bacteria.
216 I turn now to the respondent's case as to the content of common general knowledge shortly before the priority date. It is quite different from the appellant's case.
217 Acridines were not common general knowledge. If they had been at one point in time, they were forgotten and obsolete by the priority date. The antiseptic properties of at least some acridines were not common general knowledge, nor were their characteristics common general knowledge such that they would be identified as ionised antiseptics or QACs. The use of acriflavine in a teat seal was not part of common general knowledge.
218 Each of chlorhexidine, cetrimide, BZK and povidone-iodine were well-known and widely-used antiseptics. The evidence did not establish that it was common general knowledge at the priority date that any acridines were ionised antiseptics or QACs. Professor Huxley is not familiar with acridines or what they are used for. He does not know whether acridines are ionised compounds and whether acridines are QACs without consulting appropriate reference materials. Associate Professor Bunt said that before the priority date, he did not know whether or not acridines were ionised antiseptics. Professor Cook was aware of a single ionised acridine (acridine orange), but he did not consider it to be an antiseptic.
219 As I have said, with respect to knowledge of acridines, the respondent's case is that before the priority date, acridines were a class of largely forgotten and rarely used antiseptics. The characteristics and potential suitability of acridines did not form any part of the common general knowledge of the notional skilled team and the appellant has failed (so the respondent contends) to identify any expert in Australia with expertise in acridines, far less that any such expert who would have formed any part of the notional skilled team.
220 Professor Cook gave evidence to the following effect. He had never used or considered the use of any acridine as an antiseptic and it would not have occurred to him to use an acridine as an antiseptic in the claimed invention. He was not familiar with acriflavine. In his 27 years as a microbiologist, he has never used any acridine for any purpose and, in particular, he has never used, or considered using, any acridine as an antimicrobial. Before the priority date, he would have regarded antiseptic acridines as peripheral to the claimed invention, if not completely irrelevant, because there were many superior antiseptics available. At the priority date, antiseptic acridines were chiefly of historical interest.
221 Professor Huxley gave evidence to the following effect. He did not know what an acridine is. He would not have thought of acridines when reading "antiseptic" in the claim before amendment. He was not aware of any studies which have used acridines in cattle since 1942 and acridines have not commonly been used as antiseptics in the veterinary field in more recent times. In oral evidence, Professor Huxley said that he had never heard of acriflavine being used in dairy cows anywhere in the world. He had not come across any products containing acriflavine being commonly used in dairy cattle at the priority date. Professor Huxley described the field of the invention as dairy cow veterinary medicine (with aspects of pharmacology) and, more particularly, the prevention of bovine mastitis. He produced eight common veterinary textbooks pertinent to the field prior to 17 September 2008 and said that he was unable to identify in those publications any listing for acridines, acriflavine or proflavine for use in a therapeutic context. Both Professors Laven and Whittem agreed in cross-examination that many of the textbooks produced by Professor Huxley were commonly used textbooks in the field of veterinary medicine and mastitis control. The conclusion that Professor Huxley drew from the absence of a listing for acridines, acriflavine or proflavine for use in a therapeutic context in these textbooks is that they are not and were not, prior to 17 September 2008, widely used or known by those working in the field.
222 Associate Professor Bunt gave evidence to the following effect. In his experience, acridines are not and were not, prior to 17 September 2008, commonly used in the field and especially not internally as antiseptics. The field is the prevention of mastitis in cows and, in particular, internal teat seals. Acriflavine is not commonly found as an antiseptic agent in commercial veterinary antiseptic solutions and the use of antiseptic acridines was very uncommon in the field. It was widely accepted in the field prior to 17 September 2008 that acridines have very limited practical utility as antibacterial agents and that acridines were rarely used as antiseptics after the "mid-twentieth century". Associate Professor Bunt said the following:
… I have formulated dozens of antimicrobial formulations. In the entire course of my career, I have never made, tried to make, considered making, or been asked to make any formulation containing an acridine, nor do I recall any reference to any formulation of an acridine antiseptic at any of the numerous conferences which I have attended, or in any conference abstracts I have seen. I do not and have not used acridines for any purpose in my laboratory. I am aware that acridines are used as dyes and stains.
223 Associate Professor Bunt said that if he had been asked to make a formulation described in the Opposed Application prior to 17 September 2008 and it had been suggested to him that he use an acridine as an antiseptic, he would have regarded acridines "as unsuitable for use in the formulations due, in part, to the irritancy issues" and that, in light of those issues, he would not have regarded acridines as physiologically acceptable, that is to say, tolerated and non-toxic at the concentration or dosage at which they would need to be used. He identified the irritancy issues and said that acriflavine was known to cause irritancy and, in some cases, extreme irritancy when used internally in various applications. Associate Professor Bunt said that, in his experience, irritancy is a particularly significant consideration when formulating a means to prevent mastitis in a dairy herd over the dry period.
224 Professor Laven's qualifications are referred to earlier in these reasons. He has published over 150 peer-reviewed articles, over 25 of which related to mastitis, and over 200 non-peer reviewed articles, many of which have focused on mastitis. He has conducted extensive work in relation to teat seals. He said that he had never used acriflavine as a disinfectant in treating dairy cows or any other animal. He accepted that irritation was one factor against the use of acridines as antiseptics in the field of dairy cows.
225 Professor Wainwright said that antiseptics such as chlorhexidine, BZK, cetrimide, cetylpyridinium chloride and triclosan were in widespread use during the decades immediately prior to 2008, whereas the use of antiseptic acridines was less widespread. Under cross-examination, he agreed that persons in his field assumed that acridines were obsolete and he agreed that the title of his article, Wainwright M, "Acridine - a neglected antimicrobial chromophore", Journal of Antimicrobial Chemotherapy (2001) 47, 1-13, was accurate. He agreed that his object in publishing the various articles to which he was referred was to remind the scientific community "of these forgotten antiseptics". Under cross-examination, he agreed that the potential use of acridines is limited to anti-malarial and trypanocidal work, neither of which has anything to do with the treatment or prevention of mastitis.
226 Professor Whittem said that acridines "became less frequently used as a result of the discovery of the penicillin and aminoglycoside classes of microbial compounds, which overtook acridines in popularity". The respondent points to the fact that when first asked to identify the common general knowledge in the field before the priority date, Professor Whittem made no reference to acridines, although he did refer to the Meaney 1977 paper. Professor Whittem agreed the following was a correct statement as at 1991:
These dyes were of considerable importance as bacteriostatic antiseptics but, as with the other non-specific bacteriostats, their importance has waned.
227 This then is the evidence given by the experts. The respondent also addressed the publications referred to by the appellant's experts.
228 Professor Wainwright referred to Albert's textbook. He described it as the leading textbook dealing with the class of antimicrobial chromophores and the pre-eminent textbook on the class of acridine compounds to this day.
229 The respondent made the following points about Albert. The second edition of Albert was published in 1966 which is more than 40 years before the priority date. There has never been a third edition. There is no evidence that any person in Australia ever read Albert, and Associate Professor Bunt said in his affidavit that he had never heard of Albert prior to his involvement in the opposition proceedings. There is no evidence as to the availability of Albert in Australia and there is no evidence as to the extent to which, if at all, Albert continues to be used by any person in Australia. There is no evidence as to the extent to which the contents of Albert were generally accepted in Australia in 1966 and in 2008. Under cross-examination, Professor Wainwright said that he did not know to what extent anyone in Australia read Albert in the four decades between its publication and the priority date. The respondent's case is that, in those circumstances, the appellant has not established that the contents of Albert were common general knowledge shortly before the priority date, even in the field of antimicrobial chemotherapy.
230 The respondent produced a further page from Albert and submitted that, in any event, there are clear disadvantages with acriflavine as indicated in the following passage:
Acriflavine has been widely used as a local antibacterial from 1917 onwards. From 1940 onwards clinicians began to realize that it was a much more damaging substance than proflavine, thanks largely to the work of Russell and Falconer (1940, 1941), mentioned above. Garrod (1940) ably marshalled the evidence, and recommended that proflavine should replace acriflavine. More recently the tendency is to replace these yellow-staining acridines by the non-staining types (see above).
Acriflavine has no advantages over aminacrine, and has the following disadvantages: (a) it is highly acid, (b) it is highly toxic to tissues even when neutralized, (c) it causes disfiguring stains. As relatively little acriflavine is used clinically, and that from traditional rather than from scientific motives, little space need be given it here.
An excellent review of the history of acriflavine as a local antiseptic has been published (Browning, 1943), and the experiences obtained with it in the First World War are on record (War Office, 1922).
Allergic idiosyncrasy to acriflavine has sometimes been recorded after repeated applications of the solution to wounds or ulcers (Young and Hawking, 1938; Sneddon, 1946). Such cases have usually acquired no sensitivity to another acridine, such as ethacridine (Young, 1939).
231 The respondent submitted that if the contents of Albert were common general knowledge shortly before the priority date, "it must follow that acriflavine was known and generally accepted to be wholly unsuitable for use in the invention claimed in the Application". Under cross-examination, Professor Wainwright agreed that Albert was an authoritative text explaining 42 years before the date of the Opposed Application that acriflavine is damaging, it is highly toxic and it is relatively little used and that it was "potentially" saying that it would be "a waste of space" to say anything more about acriflavine. Professor Wainwright also agreed that acriflavine was being superseded as early as 1940.
232 Professor Wainwright referred to Patrick and Thomas as two leading textbooks used to teach undergraduate medicinal chemistry subjects. The reference to Patrick is a reference to Patrick G, An Introduction to Medical Chemistry (2nd ed, Oxford University Press, 2001). It contains the following statement:
Aminoacridine agents such as proflavine (Fig. 7.9) are topical antibacterial agents which were used particularly in the Second World War to treat surface wounds.
233 In the course of his evidence, Professor Wainwright agreed that there is no reference to the ongoing use of aminoacridine agents and nor is there any suggestion that they could be used, other than to treat surface wounds, or in veterinary science. There is no evidence that Patrick is available in Australia, or that the contents of it were generally known and accepted by those working in the field.
234 The reference to Thomas is a reference to Thomas G, Fundamentals of Medicinal Chemistry (John Wiley & Sons, 2000). As the respondent pointed out, the term "acridine" is not even used and the acridine class of compounds is not identified. Professor Wainwright agreed that the word "acridine" is not referred to on the pages he extracted other than in figure 7.13 where there is a depiction of the chemical structure of proflavine. This is the closest the entire book gets to a reference to acridines and none of the text of the book contains any information regarding the manner in which proflavine is being used, or is currently being used. There is no evidence that Thomas is available in Australia, and no evidence that the whole of the contents of this textbook was generally known and accepted by those working in the field.
235 Professor Wainwright (following Associate Professor Bunt's reference) referred to an article by Russell AD in the Journal of Applied Microbiology Symposium Supplement 2002 entitled "Introduction of biocides into clinical practice and the impact on antibiotic-resistant bacteria". The article contains the following statement:
In the early part of the twentieth century, other chlorine-releasing agents (CRAs), and acridine and other dyes were introduced, as were some quaternary ammonium compounds (QACs, although these were only used as biocides from the 1930s).
236 Table 3 in the publication indicates that acridines, including acriflavine and proflavine, were "now little used". There is no evidence that the article is available in Australia. The respondent contends that there is no evidence that the whole of its contents was generally known and accepted by those working in the field.
237 Professor Wainwright said the following under cross-examination:
So, can I put it to you that none of these three text books, Albert, Patrick or Thomas, establish any continuing use of acridines around 2008?---That would be correct, yes.
…
Well, can I put it to you that even in your field of synthetic chemistry, very little reference was made to acridines and that reference was largely confined to comments on their historical use during World War II. Do you accept that?---In the two undergraduate text books that we just discussed, yes, I agree with that. In Albert's book, of course, the whole thing is about acridines. But, as you say, that is a book from 1966.
Yes. So - well you refer to these books now as "undergraduate text books", but these are the books that you have cited under the heading in your affidavit where you wish to make a point that antiseptic acridines are not merely historical. Can I put it to you, Professor Wainwright, that these very text books demonstrate quite how historical antiseptic acridines are. Do you accept that, Professor Wainwright?---I - I guess you - you could read it that way, yes.
238 Professor Wainwright also referred to various journal articles he had authored or previously cited. He agreed that none of them were concerned with veterinary science or, more particularly, mastitis. He agreed that a person reading his article titled "Acridine - a neglected antimicrobial chromophore" would reasonably conclude that as at 2002, acridines were, in fact, little used and generally neglected by people in his field.
239 In his first affidavit, Professor Wainwright discussed QACs and, in the course of that discussion, he referred to a chemistry reference text which he regularly consulted in the course of his work, namely, Kirk-Othmer's Concise Encyclopaedia of Chemical Technology (4th ed, John Wiley & Sons, 2001). Professor Wainwright accepted that there is no reference in Kirk-Othmer's textbook to acridines, acriflavine or euflavine in the chapter dealing with disinfectants and antiseptics. Under cross-examination he agreed that the absence of a reference was consistent with the fact that as far as Kirk-Othmer is concerned, antimicrobial chemotherapy acridines were forgotten and obsolete.
240 Professor Laven identified a small number of journal articles which made reference to acridines. The first was a paper published in The Australian Veterinary Journal in October 1946 entitled "Clinical Bovine Mastitis, Its Treatment and Control". The respondent submitted that there is no evidence as to the extent to which any reference was ever made to that article in the intervening 70 years before the priority date and that the appellant has failed to establish that it formed any part of the common general knowledge.
241 As far as Dr Meaney's papers (1977: "Effect of a Dry Period Teat Seal on Bovine Udder Infection"; 2001: "The Use of a Bismuth Based Teat Seal and the Bacteriocin Lacticin 3147 to Prevent Dry Period Mastitis in Dairy Cows") are concerned, the respondent submits that neither of these papers establishes that the existence or use of acriflavine as an antiseptic was common general knowledge at the priority date. The first paper was published in 1977 and contains a reference in a footnote to acriflavine being part of the composition of a teat seal. Professor Huxley said that he read this article on a number of occasions in the course of writing his PhD thesis. He had no recollection "whatsoever" of acriflavine being mentioned in this article. Professor Laven could not tell from the paper whether the acriflavine had been used as an antiseptic, preservative or dye and he considered that acriflavine was not there for its antibacterial activity. Under cross-examination, Professor Wainwright agreed that the Meaney 1977 paper did not provide any support for a conclusion that acridines continued to be used as at 2008 in veterinary science.
242 The Meaney 2001 paper referred to the use of an internal sealer comprising bismuth subnitrate and acriflavine, but states that further work is required. The paper also contained the following statement:
A significant outcome of our trials was the in vivo evidence of the ability of lacticin 3147 to retain activity against Str. dysgalactiae in the teat and prevent the onset of clinical mastitis during the 8-day trial period. This trial provided convincing evidence that the bismuth-based teat seal and lacticin 3147 combination offered very effective protection against a significant challenge with an important mastitis-causing pathogen.
Lacticin is a bacteriocin which is not an acridine. The paper did not outline any further work in relation to the internal sealer comprising bismuth subnitrate and acriflavine.
243 Professor Whittem referred to four general veterinary textbooks and reference manuals that he consulted before the priority date. He said that he considered any antiseptic compounds included in general veterinary textbooks and reference manuals to be generally known and used prior to 17 September 2008.
244 The first work that Professor Whittem referred to is Greig J (ed), Hoare's Veterinary Materia Medica & Therapeutics (5th ed, Baillière, Tindall and Cox, 1936). The fifth edition of this textbook was published in 1939 and, as the respondent pointed out, there is no evidence that a sixth edition was ever published. There is a short reference to acriflavine in the work. It is not described as an acridine. As the respondent also pointed out, there is no evidence as to the extent to which, if at all, any person in Australia was aware of the six line reference to acriflavine in a text published approximately 70 years before the priority date.
245 The second work is Jenkins, which I have referred to above. This text was published 17 years before the priority date. It contains a small number of paragraphs dealing with acridine derivatives, including acriflavine. It is stated that acridine derivatives, which are dyes, were of considerable importance as bacteriostatic antiseptics but, as with other nonspecific bacteriostats, their importance has waned. They are said to possess little activity against Gram-negative organisms.
246 The third work is Kahn C (ed), The Merck Veterinary Manual (9th ed, Merck & Co., 2005). That is a publication of over 2,158 pages and, as the respondent pointed out, there is no evidence as to the extent to which any persons in the field read or generally accepted the information appearing on page 2,158. The relevant passage appears under the heading "Other Antibacterial Agents" and is as follows:
Acridine dyes (eg, acriflavine, proflavine, aminacrine) are more active against grampositive bacteria. Their activity is enhanced in alkaline medium and antagonized by hypochlorites. Impregnated bandages and gauze and acriflavine jelly have been used extensively for treatment of burns.
Under cross-examination, Professor Whittem agreed that this passage was saying that acridine dyes were more active against Gram-positive bacteria than Gram-negative bacteria and that they have been used extensively for the treatment of burns. He agreed that the reference to acriflavine is brief. Professor Whittem agreed that none of the texts to which he referred state that acriflavine is commonly used as an antiseptic in veterinary medicine.
247 The fourth work is the MIMS IVS Annual for both Australia and New Zealand, 2008. Professor Whittem said that he regularly consulted these texts before 17 September 2008. He agreed that neither MIMS discloses that acriflavine could be used for the prevention of mastitis. MIMS Australia identifies various antiseptic sprays, wipes and teat dips to prevent bovine mastitis. They include Hibitane Teat Dip and Spray which contains chlorhexidine and controls mastitis-causing organisms on cows' teats. It discloses Idedex Teat Dip and Spray which contains iodine and is described as "Post milking teat sanitiser with emollient". It contains directions as to the application of the spray to the udder of the cow. I have already referred to the reference to Yellow Lotion which is stated to contain acriflavine. Professor Huxley said the term "proud flesh" is most commonly used in relation to horses as horses are most prone to the condition described and that, in his view, in light of the description, indications and directions for use, "this product has nothing to do with mastitis prevention or treatment in dairy cows". In his oral evidence, Professor Whittem said that the Yellow Lotion product is not designed for treating mastitis.
248 In his second affidavit, Professor Whittem said that he disagreed with Professor Cook's statement that the use of acridine antiseptics was largely historical. However, he was able to identify two products as being the subject of ongoing use. First, Yellow Lotion was targeted at horses and, in addition, no witness gave evidence that they had ever used Yellow Lotion before the priority date. The second, Septicide Cream, is a product registered to be used in Australia on dogs and horses and the listing in MIMS describes it as an "Insect repellent and antiseptic cream for use on the wounds of dogs and horses". Professor Huxley said that Septicide Cream was utterly irrelevant for mastitis.
249 The respondent submits that the continuing existence of two products never used by any of the six experts in this proceeding which might be used to treat cuts and repel insects on dogs and horses, and which are described as containing acriflavine and proflavine respectively, falls a long way short of refuting the proposition that the use of acridines "was largely historical". It certainly does not establish that it was common general knowledge that acridines had any characteristics which might render them suitable for use as antiseptics in teat seals.
250 My conclusions and reasons as to matters of common general knowledge shortly before the priority date with respect to acridines, their properties and their uses are as follows:
(1) It was common general knowledge shortly before the priority date that acriflavine had an antiseptic property;
(2) The characteristics of antiseptic acridines and, in particular, that some of them are ionised antiseptics and/or QACs were not common general knowledge shortly before the priority date; and
(3) The use of acriflavine or, indeed, any antiseptic acridines in a teat seal was not common general knowledge shortly before the priority date.
251 With respect to acriflavine having an antiseptic property, the finding of the delegate in the substantive opposition proceeding is binding on the parties. In any event, the evidence before the Court supports the conclusion that it was common general knowledge shortly before the priority date that acriflavine had an antiseptic property. Although I consider Professor Cook's evidence that acridines were largely of historical interest to be a fair summary of the position established by the evidence and Professor Wainwright's assumption that, as far as his colleagues are concerned, acridines were largely forgotten and obsolete to be accurate, there is sufficient support for the finding in Professor Whittem's evidence that he was aware of and had used certain antiseptics, including acriflavine before the priority date, based on MIMS Australia and the two products listed in MIMS Australia, including Yellow Lotion.
252 I turn to the characteristics of antiseptic acridines and, in particular, that some of them are ionised antiseptics and/or QACs.
253 Professor Cook said that acridine orange was not a QAC and he was not aware whether other acridines were QACs. Professor Huxley was not familiar with acridines or what they are used for and he gave evidence that, without consulting reference materials, he did not know whether acridines were ionised antiseptics or QACs. Associate Professor Bunt gave evidence that he did not know whether acridines were ionised antiseptics. Professor Laven did not give evidence that he was aware shortly before the priority date that acridines were ionised antiseptics or QACS. Professor Whittem gave evidence that he did not know whether acriflavine, which he had identified as an acridine of which he was aware of before the priority date, was a QAC. Professor Wainwright knew shortly before the priority date that some acridines are ionised antiseptics and/or QACs, but it is clear that his knowledge of acridines was exceptional and beyond that of the ordinarily skilled expert in antimicrobial compounds or antiseptics. I refer to my earlier discussion of his expertise (at [169]-[172]). I have identified various publications referred to by the parties in the course of summarising the respondent's submissions as to common general knowledge. They do not support a conclusion on the balance of probabilities that the characteristics of some acridines as ionised antiseptics and/or QACs was a matter of common general knowledge shortly before the priority date.
254 I turn to the use of acriflavine or, indeed, any antiseptic acridine in a teat seal.
255 There is the finding of the delegate in the substantive opposition proceeding that the evidence did not establish that teat seal formulations containing acriflavine was part of common general knowledge. In any event, the evidence in this case does not establish that the use of acriflavine or, indeed, any antiseptic acridines in a teat seal was common general knowledge shortly before the priority date.
256 The appellant relied on the evidence of Professors Whittem and Laven. As I have said, Professor Whittem made a statutory declaration in the opposition filed by Pfizer, Inc to New Zealand Patent Application No 571347 on 13 December 2011 in which he outlined his opinion as to the state of common general knowledge of skilled workers in the field shortly before the priority date. He referred to patent disclosures of internal teat seal formulations and, in that context, he referred, without further comment, to the Meaney 1977 paper. In oral evidence, he said that there was a history of acriflavine being incorporated in a teat seal and not causing toxicity issues and referred to a study in evidence. Professor Laven agreed. This, it seems, is a reference to the Meaney 1977 paper and Professor Laven had earlier said in his oral evidence that Dr Meaney had "just used a product that was commercially available". Professor Laven described how he became aware of both of Dr Meaney's papers and he said that Dr Meaney was a world-renowned researcher in the field.
257 The appellant submits that Associate Professor Bunt and Professor Huxley were also aware of acriflavine being used in teat seals before the priority date.
258 Associate Professor Bunt referred to GB2,273,441 in his affidavit. In his oral evidence, he said that he was aware of that Patent Application before the priority date. That Patent Application relates to a composition for treating mastitis in dry cows comprising "an antibacterial and a seal comprising a gel base containing a heavy metal salt". He recalled that there was a compound called acriflavine in it as a pigment. He did not know then that it was an antiseptic.
259 Professor Huxley recalls reading the Meaney 1977 paper on several occasions prior to the priority date, but had no recollection "whatsoever" of acriflavine being mentioned in this article.
260 In determining this issue, it is to be borne in mind that information or knowledge is common general knowledge only if it is accepted and assimilated into the knowledge of all, or the bulk, of those in the relevant field, and the fact that information appears in a publication read, even widely read by those in the field, does not of itself establish that the information was common general knowledge at the relevant date. Although the evidence advanced by the appellant establishes that some in the field knew of the use of acriflavine in a teat seal, it does not satisfy the requirements to which I have referred.