(d) DAST was within common general knowledge (grounds 5, 6 and 7)
189 The primary judge stated at [206]:
… If the skilled addressee "is not an avatar for expert witnesses whose testimony is accepted by the court" but a tool for analysis (AstraZeneca AB v Apotex Pty Ltd (Matter No S54/2015) (2015) 323 ALR 605; 114 IPR 445; [2015] HCA 30 at [23]) then it cannot be correct to focus on whether one or other expert witness can be taken to represent the skilled addressee. The relevant issue is the common general knowledge that should be attributed to the skilled addressee given the area of discourse to which the relevant documents relate.
190 Undaunted by what her Honour said, Idenix contends that the primary judge erred in treating Gilead's experts, Professor Furneaux and Dr Lambert, as representatives of the skilled addressee and in accepting that their knowledge both constituted the common general knowledge and represented its outer bounds. Relatedly, Idenix contends that her Honour erred in rejecting "every aspect" of the evidence of Idenix's experts, Professor Meier and Dr Borthwick, as demonstrating additional knowledge beyond the common general knowledge. Idenix submits that the primary judge's key finding to the effect that for a skilled addressee to use DAST to fluorinate with inversion a tertiary hydroxyl involved invention (at [612] and [615]), could not be supported in the evidence. It says that her Honour was required to undertake a careful balanced consideration of the evidence as a whole for the purpose of constructing, as a tool for analysis, an objective skilled addressee with no more human characteristics of volitional and purposive action than necessary. But accepting that to be so, that is what in our view her Honour did. None of Idenix's criticisms of her Honour's approach have merit.
191 In our opinion the primary judge correctly rejected Idenix's contention that the Idenix patent was sufficient because the "DAST route" approach was a matter of common general knowledge. As her Honour rightly found, once one appreciates the scientific complexity, using the term "DAST route" disguises what was at the relevant date complex and uncertain chemistry, particularly for tertiary fluorinations with the correct stereochemistry at the 2' position of a nucleoside.
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 (at [218] to [225]). For example, Dr Borthwick relied substantially on his own experience and numerous non-common general knowledge publications in devising his target syntheses. In that regard, he was dependent upon his own experience in fluorinating a tertiary hydroxyl group at the 4' position of a carbocyclic compound. That work followed five years of research that he had already conducted, in which he had attempted and performed various different fluorination reactions and consulted the literature on the subject.
193 It is convenient to elaborate on some of Idenix's specific arguments in respect of the expert evidence.
194 Idenix submits that before the priority date, Dr Borthwick used DAST as his first choice to fluorinate a tertiary hydroxyl on a nucleoside and achieved fluorination with inversion. It says that contrary to the primary judge's analysis at [535], Dr Borthwick's evidence could not be rejected as irrelevant and being "after the event" and "in wholly hypothetical circumstances". It is said that his experience could not be dismissed as "unique" experience (at [207]) or involving "very particular knowledge" (at [554]) given that his work on the fluorination of two carbocyclic nucleoside analogues having a tertiary hydroxyl at the 4' position was reported in two peer-reviewed publications and was not suggested to be anything other than routine.
195 Further, Idenix submits that the Middleton paper and the March textbook formed part of the common general knowledge and that both disclosed the use of DAST to fluorinate tertiary alcohols. Idenix says that in the light of these texts, the idea of using or trying DAST to fluorinate a tertiary alcohol such as the precursor compound under present discussion could not be "inventive". Further, Idenix criticises the primary judge's finding that the skilled addressee "would know that the teachings of the Middleton Paper could not be applied to the compounds of" the Idenix patent (at [557]), with the apparent basis for that knowledge of the skilled addressee being the evidence of Dr Borthwick. But Idenix contends that that finding was erroneous because Dr Borthwick in 1990 did "exactly what the primary judge found he 'knew' he could not do". Idenix submits that there was no basis for such a finding of "knowledge" of either Dr Borthwick or the skilled addressee. Further, it says that the primary judge also erroneously dismissed the Middleton paper by accepting Gilead's submission that Dr Borthwick did not use the Middleton paper, but used the Matsuda paper (at [559]). Idenix contends that the Matsuda paper was a paper dealing with a specific form of the precursor and was available as part of the teaching of the Idenix patent; in any event it says that Matsuda said nothing about using DAST on the precursor compound. In any event it says that Dr Borthwick did not need to refer to either the Matsuda paper or the Middleton paper for the "common general knowledge idea" of using DAST on the precursor compound. Idenix further contends that the primary judge also dismissed the Middleton paper on the basis that none of Professor Meier, Professor Furneaux, Dr Lambert or the Idenix scientists relied on it (at [559]). But Idenix contends that the Idenix scientists did use the DAST analogue, Deoxo-Fluor, on the precursor compound in the only work Professor Furneaux identified as work he expected a skilled addressee to undertake. We would note at this point that Professor Furneaux's evidence did not precisely say that this was the only work he would have identified, but that he did acknowledge under cross-examination that the Deoxo-Fluor route eventually undertaken by Idenix's scientists was consistent with what he expected an ordinary skilled chemist to do (see the complete transcript of his cross-examination from T238 line 9 to T239 line 11). Further, Idenix contends that Professor Meier thought of using DAST. It was also contended that Dr Lambert was not a skilled addressee and could not assist on the question of what knowledge the skilled addressee could be taken to have possessed. Further, Idenix contends that the fact that the Idenix scientists thought of the method without having to refer specifically to the Middleton paper reinforces rather than detracts from its contention that using DAST on a tertiary alcohol was part of the common general knowledge.
196 We would reject Idenix's submissions.
197 First, as Gilead points out, Dr Borthwick accepted that the material upon which he relied in developing his target syntheses included all of the material listed in Exhibit 39. But this included 19 journal publications for target synthesis 1 and those publications with additions for target synthesis 2. As part thereof, it involved a review by him of the Matsuda references to identify the state of the art in the synthesis of the desired precursor compound. With the exception of the Middleton paper, it would seem that none of the material listed in Exhibit 39 was common general knowledge at the priority date.
198 Further, Idenix has misdescribed the primary judge's findings at [612] and [615] concerning "invention" in using DAST to fluorinate with inversion a tertiary hydroxyl. First, the primary judge's findings were made with reference to the Kimberly-Clark test. The relevant question was not whether the idea of using DAST was inventive. Second, Idenix's criticism of the primary judge's reasons in relation to the Middleton paper does not pay proper regard to what her Honour reasoned at [557]. A similar error is made by Idenix with respect to the March textbook (at [559]) (see [187] and [188] of these reasons above). Third, Idenix's assertion that Dr Borthwick did not need to refer to the Matsuda or Middleton papers is not supported by the evidence. He did so when asked whether he could develop a synthesis of a claim 7 compound. As we have said, he relied upon all of the material in Exhibit 39. Further, contrary to Idenix's submission, the Matsuda paper was not part of the teaching of the Idenix patent. It was not common general knowledge. The reference to it was contained within the footnotes to the Harry-O'kuru paper which itself in any event was only part of the teaching in the Idenix patent for Scheme 9 therein.
199 Second, Idenix contends that the primary judge erred in treating as irrelevant Professor Meier's evidence, who worked on two fluorination reactions on which he reported in 1999, that he would have adopted the DAST route. Idenix says that the primary judge at [207] wrongly "rejected" the evidence of Dr Borthwick and Professor Meier who were directly engaged in the field of the Idenix patent based on their unique or specialised experience. Idenix contends that such evidence was relevant to common general knowledge. Moreover, it is said that Professor Furneaux also had expertise and experience (albeit limited) in the fluorination of nucleoside analogues. Idenix contends that the distinction between Professor Furneaux's expertise and that of Idenix's experts and why the former but not the latter was relevant to the common general knowledge, was not explained by the primary judge. But in our opinion the primary judge correctly found that Professor Meier's knowledge extended well beyond the common general knowledge. As her Honour correctly found, it was based on his own specific experience in relation to fluorination and literature searches he had conducted for the purposes of earlier Norwegian proceedings (at [218] to [219] and [548]).
200 Third, Idenix asserts that the primary judge erred in finding that Dr Lambert was representative of the skilled addressee. It submits that such a finding was inconsistent with her Honour's finding that the skilled addressee would have some familiarity with fluorination reactions (at [219]). It is said that Dr Lambert did not have such familiarity and left such matters to synthetic chemists or nucleoside chemists engaged in the necessary synthesis. But we see no difficulty with her Honour's conclusion that Dr Lambert was the kind of expert to whom the Idenix patent was addressed. Moreover, once again Idenix has not correctly described her Honour's reasons; her Honour said at [219] that some familiarity with fluorination reactions might be imputed to the skilled addressee; further, as she explained, the 350 application and the Idenix patent were not "directed towards such a narrow topic as the fluorination of nucleosides".
201 Fourth, Idenix submits that Professor Furneaux's first thought when approached by Gilead's lawyers to give evidence was to use DAST to fluorinate a precursor. It is said that he gave evidence that the use of DAST (or a two-step agent) on the precursor was "the first thing I would have conceived of" and "conceptually it would have been the obvious thing to conceive first … it was the first thing I thought of". In the light of this evidence, Idenix contends that Professor Furneaux's thoughts about perceived difficulties with using DAST in such a context could not detract from the fact that his first thought was to use DAST (or a two-step agent) on a precursor. Now the primary judge referred to evidence that Professor Furneaux thought that the DAST route had a high chance of not succeeding and "[b]ecause of this it was not his first thought in fact to use DAST on a precursor compound" (at [570]) Idenix contends that if her Honour's finding is that it was not his first thought to use DAST, it was against the evidence. Further, Idenix contends that if it was found that he thought the chances of success were low, and therefore his view was that he would need to undertake further research, then such evidence or finding is "harmless but irrelevant". Idenix submits that the important point is that it cannot rationally be "inventive" to try DAST on the precursor in the light of his evidence. It is said that the fact that Professor Furneaux might have had doubts as to success is not to the point. It is accepted by Idenix that any product of research he might have pursued may not have been part of the common general knowledge, but that it was common general knowledge to use or try the DAST route.
202 Before proceeding further it is worth us setting out what Professor Furneaux actually said (T252 line 31):
But just so we understand the sequence, you accept, don't you, that your plan A, your first plan, would have been to apply DAST to an appropriately protected compound 6 in exhibit 8? --- It would have been the quickest concept to come up with, I accept that.
And that would be the first one you would try, but you would have a plan B ready to go? --- Not necessarily. As I think I explained, sir, the starting material required for that requires it to be made from - in a multistep process with selections for protection and possibly deciding the reaction conditions to get the compound with the right stereochemistry from something like a Grignard reagent. So it's easy to write it on paper, but the chemistry still requires a number of steps.
I understand? --- So intellectually I would have planned out alternative routes and then considered which to undertake.
But doing the best you can, plan A was what you have identified? --- Yes, sir.
Namely, you applied DAST to an appropriately protected claim 6 - I'll start again. Plan A would have been - taking into account everything you said, doing the best you can - would have been to apply DAST or the two-step, or both perhaps - I'll start again. I'll do it as clearly as I can. Is this right, doing the best you can, your plan A would have been to apply, with all the qualifications you've mentioned, DAST to an appropriately protected compound 6 that we see in exhibit 8? --- I will say yes, with one qualification.
Yes? --- And that is that plan A is not necessarily better than plan B or in sans C, it is simply named plan A.
Yes, but when you were answering this question yesterday you were understanding plan A to be the first thing you would try? --- Certainly that is what I've said here, sir, so I will correct, it would been the first thing I would have conceived of, but starting material wouldn't have been something - or unlikely to have been something available in my laboratory. It would have required synthesis, it would have required a retrosynthesis plan to make it and I would have been at the same time considering other alternatives. So the step in deciding what to conduct first would have been on a rational basis of comparing alternatives and doing literature search and ---
But taking it step by step, do you agree that you were intending to convey in that answer at 230 that plan A, in the sense of DAST applied to a compound 6 precursor, was the first thing you'd likely try? --- No, sir.
Isn't that what it says? --- I believe I've just said that I'm correcting that. I believe that's correct, that's what it says, sir, and I'm correcting that.
Yes. The answer you gave we're looking at there which you wish to correct was that the first thing you would most likely have done, with all the qualifications, is to use DAST on a compound 6 exhibit 8 precursor. That's what it says there, isn't it? --- It says no, that I wouldn't have necessarily considered DAST first. That I would have considered both reagents.
Sorry, but subject to that you agree with me? --- So conceptually it would have been the obvious thing to conceive first, but it was also the first thing - it was the first thing I thought of - but also I foresaw that it was, in my opinion, had a high chance of not working.
203 Further, Idenix submits that Professor Furneaux's doubts as to the likely success of the DAST route related to potentially competing reactions. Idenix contends that before conducting searches of the Red Books (the Journal of Carbohydrate Chemistry) and the Pankiewicz Review, he thought it would be complicated chemistry and that there would be competing reactions, but that it would likely produce a range of reactions, one of which could reasonably include fluorination with inversion. Idenix contends that this evidence was quite consistent with his other evidence that inversion was not the only likely outcome of an attempted fluorination reaction of a tertiary hydroxy group in a sugar or nucleoside. It is also said that further oral evidence did not affect the import of that evidence. Idenix contends that the primary judge's attempt to grapple with the ebbs and flows of his evidence does not detract from Professor Furneaux's evidence that he thought that a reasonable possible outcome of the reaction would be the target compound. Idenix further submits that Professor Furneaux had claimed in a US patent application before the priority date a compound with a tertiary fluorine in the 2' down position on the basis that it could be made by methods analogous to known methods.
204 In our opinion, the primary judge correctly found that Professor Furneaux's evidence did not support a finding of sufficiency (see [566] to [582] and especially [566] and [574]). Professor Furneaux was highly doubtful as to the utility of attempting to use DAST to obtain a claim 7 compound (at [570]). He thought DAST was highly unlikely to work, which led him to express the view, as her Honour found, that "several retrosynthetic steps would be required, including a literature search and experimentation, and that the chemistry would be complicated and unpredictable". As Gilead correctly submitted, scepticism can inhibit recognition of the utility of applying a concept or idea. Moreover, Professor Furneaux in his evidence distinguished between what one may conceive of and what one may actually try. Although he conceived of the possibility of using the DAST approach, he thought it unlikely to work. Further, we have perused for ourselves US patent no. 5,047,518 (columns 9, 14, 33, 58 and 59) and the international PCT application WO 99/19338 (pages 16, 18 and 33) which in each case have Professor Furneaux as one of the inventors. Her Honour took these into account and in our view fairly dealt with them at [575(10)]. In any event, they were only a small part of the evidence considered on sufficiency.
205 Fifth and more generally, Idenix contends that common to the evidence of Dr Borthwick, Professor Meier and Professor Furneaux was their knowledge of DAST and Deoxo-Fluor and the use of such methods to fluorinate secondary alcohols, familiarity with that mechanism including inversion, and (as their first thought) the use of DAST to fluorinate a tertiary hydroxyl. Idenix also says that in 2002, DAST and Deoxo-Fluor were the most commonly known means of fluorinating a secondary hydroxyl in the relevant art. It points out that this was made clear in the Middleton paper and the March textbook. It is said that the primary judge erred in finding that there were other well-known means (at [605]). It is said that such other means were not specifically identified and that the evidence did not support such a conclusion.
206 Sixth, Idenix contends that contrary to the primary judge's findings at [543], [577], [610] and [612], the evidence did not support a conclusion that the precursor could not be made by the skilled addressee with the benefit of the Idenix patent and the common general knowledge. It is said that Idenix so succeeded. Idenix asserts that it is "inconceivable" that there would have been a sufficiency attack if the compound in suit was the precursor. It is said that the primary judge failed to pay sufficient regard to the principles she herself expounded at [438(8)].
207 We disagree with both of these contentions. The generality at which Idenix puts these submissions, citing selective references from the extensive evidence, does not in our view do justice to the detailed and careful reasons of the primary judge. The primary judge correctly rejected Idenix's case concerning the evidence of Dr Borthwick, Professor Meier and Professor Furneaux and the precursor. Her Honour's factual findings on this issue have not been shown to be in error.
208 Finally, Idenix has contended that Gilead failed to demonstrate that if the skilled addressee had adopted the DAST route, they would not have obtained the target compound. It is said that the AMRI experiments and Mr Clark's work prove that the skilled addressee would have. Now the AMRI experiments were conducted in 2014 and involved using the Deoxo-Fluor route. The product isolated in the AMRI experiments contained a compound having the same structure as the Clark compound 9, although the AMRI product was not completely pure. Idenix has contended that based upon the AMRI experiments, it could be inferred that Dr Griffon of Idenix created the target compound in February 2003 using the Deoxo-Fluor route. Further, Idenix has contended that it could also be inferred from the AMRI experiments that the reason the target compound was not isolated and identified was that Dr Griffon failed to analyse all of the reaction products. It is said that a skilled addressee would have done so and that such analysis of all the reaction products would have identified the target compound.
209 We agree with the primary judge (at [600]) that the AMRI experiments did not assist Idenix. Her Honour found that the AMRI experiments used more sophisticated techniques than those used by Dr Griffon. The evidence before her Honour well demonstrated such a finding. The AMRI techniques maximised the likelihood of the target compound being isolated and purified. Further, Dr Clemens used LC-MS, which is more sophisticated than TLC, as well as TLC to monitor the reaction. Further, Dr Clemens used HPLC, which is more sophisticated than column chromatography, which is what Dr Griffon used. In contrast, Dr Griffon used standard methods for the day. More generally, the AMRI techniques were neither reflective of the steps the skilled addressee would have taken at the time or that Dr Griffon in fact took. As such, her Honour correctly concluded that it could not be inferred that Dr Griffon would have found the target compound if he had tested all reaction products (assuming he had not) by the methods he in fact used. Further, we also see no difficulty with her Honour's conclusion at [603] that she could not conclude that Dr Griffon had in fact made the target compound in any event. In that paragraph her Honour said:
… In this regard it must be recognised that Professors Furneaux and Barrett were drawing inferences. They were not expressing conclusions or opinions about facts they knew. Ultimately the drawing of any inference about whether Dr Griffon in fact obtained the target compound is a matter for the Court on the whole of the evidence and taking into account all circumstances including that Idenix chose not to call Dr Griffon to explain anything about what he did or did not do and why. There are so many imponderables in this regard and in the unexplained differences between the AMRI experiments and what Dr Griffon did, that I am not prepared to infer that Dr Griffon in fact obtained the target compound but just did not realise it. Even if this is incorrect, I am not prepared to infer that Dr Griffon would have been able to isolate and identify the target compound using the techniques that a person skilled in the art would have used in 2003 in the circumstances in which Dr Griffon was in at that time.
210 Idenix has submitted that the primary judge's failure to find that those experiments obtained the target compound involved error and that her Honour preferred a judicial inference over unanimous expert scientific evidence to the contrary. But we reject that criticism for the reasons given. In any event the relevant and key question is whether the disclosure of the Idenix patent enabled the skilled addressee to make a claim 7 compound within what may informally be described as the Kimberly-Clark parameters taking into account common general knowledge at the relevant time. In that context the primary judge correctly considered the AMRI experiments not to be of much assistance (at [600] to [603]). In light of the significant differences between those experiments and the work of Dr Griffon, in particular the use by AMRI of more sophisticated techniques, and the absence of Dr Griffon as a witness, the primary judge has not been shown to be in error by finding that experimental and opinion evidence offered years later was insufficient to throw doubt on Idenix's own documents, which we will discuss in a moment, disclosing and reporting at some length Dr Griffon's failures.