7.6.5 Professor Furneaux
562 A significant plank in Idenix's approach to Professor Furneaux's evidence about the fluorination of a tertiary hydroxyl (involved in the synthesis proposed by Professor Meier and Dr Borthwick) depended on para 23(d) of his second affidavit where Professor Furneaux said this:
Mechanism of action of DAST: Dr Borthwick's Target Syntheses are also premised on his view that DAST invariably fluorinated with inversion, irrespective of whether the fluorination was performed at a primary, secondary or tertiary hydroxy group. However, Annexure AB-48 to the Borthwick Affidavit (which is co-authored by Dr Borthwick) identifies at page 549 the likelihood of neighbouring group participation reactions occurring when the substrate is more complex than a primary or secondary alcohol. It states 'For simple secondary alcohols the reaction proceeds with inversion of configuration, but in more complex substrates neighbouring-group participation can lead to partial or complete retention of configuration at the reacting carbon centre'. This accords with my understanding as at June 2002 and June 2003 that inversion was not the only likely outcome of an attempted fluorination reaction of a tertiary hydroxy group in a sugar or nucleoside.
563 Professor Furneaux was cross-examined about this statement, particularly the last sentence as follows:
Would you read to yourself the paragraph (d)? Yes, sir.
You made the statement in the last sentence of (d) after carefully considering what you understood was a reasonable approach to the science, didn't you? Yes, sir.
That reflects your view, that sentence, namely:
This accords with my understanding as at June 2002 and June 2003 that inversion was not the only likely outcome of an attempted fluorination reaction of a tertiary hydroxy group in a sugar or nucleoside.
Do you agree? Yes, sir.
What you are saying there is it's a likely outcome, but not the only likely outcome. Do you agree? Yes, sir.
564 When this topic was raised later in the cross-examination this evidence was given by Professor Furneaux:
May we take it you still stand by paragraph 23(d) of your affidavit, which is your second affidavit, page 1134? Yes, sir. Just let me reread that again. I see no reason to disagree with you, I'm just making sure.
The last sentence? Yes, sir, I understand the subtlety of the language.
You agreed, when I asked you, that you accepted that inversion was a likely outcome but not the only likely outcome? So I understand the language and I did not mean to imply that it was a likely outcome and I understand that that language could be interpreted as saying that. Clearly, my evidence to date has suggested that my view was that it was an unlikely outcome.
And, Professor, I asked you, the first question this morning, whether you agreed that what you were intending to convey there was that inversion was a likely outcome but not the only likely outcome and you said yes, didn't you? Sir, I will correct that, sir, because that's not
But that's what you said, wasn't it, Professor? It may be, sir. I
No, there is no maybes here, Professor. You know perfectly well that that's what you said.
…
MR BANNON: Do you agree I asked you, almost the first question this morning, that what you were intending to convey in paragraph 20(d) was that inversion in the last three lines was a likely outcome, but not the only likely outcome. I asked you that question and you said, "Yes." Do you agree that that's what you said? I thank you for providing me with an opportunity to correct myself. I obviously did not think carefully enough about the English language in that sentence and in line with
my other evidence, which has suggested that I thought that the fluorination of a tertiary hydroxy group in a nucleoside or sugar by attempting to undertake a displacement reaction was unlikely to give a fluorinated product. I need to make that correction.
…
I'll start at line 19 of 197 of the live transcript:
That reflects your view, that sentence, namely: "This accords with my understanding as at June 2002 and June 2003 that inversion was not the only likely outcome of an attempted fluorination reaction of a tertiary hydroxy group in a sugar or nucleoside." Do you agree? Yes, sir.
What you are saying there is it's a likely outcome, but not the only likely outcome. Do you agree?
You said, "Yes." Do you accept that that is an accurate transcription of questions I asked and answers you gave? Yes, sir.
Do you accept that I asked you those questions after I asked this question at line 15:
You made that statement in the last sentence of (d) after carefully considering what you understood was a reasonable approach to the science, didn't you? Yes, sir.
Do you accept that that is an accurate transcription of that question I asked and that answer that you gave? Yes, sir.
Those answers you gave to those questions I asked were honest answers, weren't they? They were what I thought were honest answers, yes, sir.
You don't seek to retract them as an honest, independent witness of this court, do you? I do seek to clarify that I had made a mistake in giving those answers because I had misunderstood the English language in that sentence.
Did you make a mistake when you swore to the last sentence of 23(d)? I think that in rereading it now, sir, I had not considered the contrary - the flip side of not the only likely outcome.
Drafts of this affidavit were provided to Australian lawyers. Correct? You provided drafts - the preparation of this affidavit was in consultation with Australian lawyers? I didn't provide drafts, sir, no. My evidence was taken orally and the drafts were provided for me to correct.
Yes? And so that they are my words, they are definitely my words.
Yes? But I have expressed it poorly.
I wasn't seeking to ask the physical process, perhaps it came out that way, but they were prepared in consultation with lawyers? They are my words, sir.
Yes, I wasn't suggesting otherwise. American lawyers were involved as well, as far as you know? Sir, I have no knowledge of that.
You have an understanding that the American client was receiving considerations of drafts which you'd corrected? No, sir, I was unaware of that.
See, you wrote that sentence or provided that sentence after you had considered not only what you had written in your first affidavit, but after you had considered what matters had been pointed out to you by Doctor Borthwick? Yes, sir.
That sentence was written, trying to assist the court, taking into account not only what you had said, but taking heed of what had been pointed out to you or said by one of your peers, namely, Doctor Borthwick. Do you agree? Yes, sir.
You were under no misapprehension as to what that sentence meant in 23(d) when you swore the affidavit, were you? So, sir, I must have been because it doesn't correlate with the other evidence I have provided and my understanding of the situation as what my view at 2002-2003 is.
565 Idenix said this in submissions:
Critically, in paragraph 23(d) of his reply affidavit, Professor Furneaux indicated that his understanding as at 2003 was that inversion was not the only likely outcome of an attempted fluorination reaction of a tertiary hydroxyl group in a sugar or nucleoside. As a matter of ordinary English that is an acceptance that inversion was a likely outcome. It is consistent with his other affidavit evidence. He initially accepted in cross-examination that by [23(d)] he intended to convey that inversion was one of the likely outcomes, but not the only likely outcome. Then, he attempted to retreat from it and from his affidavit [23(d)], in an effort to defend the more extreme position he adopted at times in cross-examination to the effect that fluorination may not occur at all (as opposed to not being favoured (i.e. not being the major product) which was his affidavit evidence).
566 I do not accept this submission. Contrary to what Idenix proposes, the effect of Professor Furneaux's evidence on a fair view is not that inversion was a likely outcome of an attempted fluorination reaction of a tertiary hydroxyl group in a sugar or nucleoside. Professor Furneaux's position at all times was that he considered that to introduce a fluoro substituent at the 2' position in the down orientation with a methyl substituent up in such a compound would be complicated chemistry. He said in his first affidavit (and thereafter) that the chemistry would be unpredictable. He said it was "unlikely that a displacement reaction at a tertiary carbon would be favoured". Again, contrary to Idenix's submissions, it is apparent on a fair review of all of Professor Furneaux's evidence that he used the concept of a reaction being "favoured" inconsistently. From the context of each use it is apparent that he sometimes meant that he expected or thought it likely a reaction would occur but not be the predominant reaction and other times meant that he expected or thought it likely that a reaction would not occur at all. It is not possible to understand Professor Furneaux's evidence to be that he expected or thought that inversion was a likely outcome of an attempted fluorination reaction of a tertiary hydroxy group in a sugar or nucleoside. If that were so, the balance of his evidence, right from his first affidavit, would make no sense. When he uses "favoured" the context of each reference must be considered. When dealing with the fluorination of a tertiary hydroxyl, by "favoured" Professor Furneaux means that in his view as at 2002/2003 he believed it unlikely that fluorination would occur at all; instead there would be an elimination reaction.
567 It is convenient (again) to adopt Gilead's submissions which I consider disclose why Professor Furneaux used a formula of words in para 23(d) of his second affidavit which, read literally, conflict with the balance of his evidence. Gilead said, and I accept, the following:
In para 23(d), Professor Furneaux was responding specifically to Dr Borthwick's view that "DAST invariably fluorinated with inversion" - a fair characterisation of the impression given in the statements in Dr Borthwick's affidavit. In saying that inversion was not "the only likely outcome of an attempted fluorination reaction of a tertiary hydroxy group", it is apparent that Professor Furneaux was merely intending to disagree with Dr Borthwick's view that this was the only likely outcome. Having regard to the evidence he had previously given as outlined above, Gilead respectfully submits that the Court would not take Professor Furneaux to be expressing a different view, and now accepting that fluorination with inversion was a likely outcome, albeit one of several likely outcomes.
568 In other words, it is readily understandable that when a person (not being a lawyer) is presented with a proposition to the effect "fluorination with inversion is the only likely outcome of this reaction" and is asked whether or not they agree the person might respond with a statement that "fluorination with inversion is not the only likely outcome of this reaction" without meaning to convey that fluorination is a (in distinction from the only) likely outcome. Nor is it surprising that Professor Furneaux, knowing that he had expressed his views clearly and consistently otherwise, might read his statement in the witness box and yet not appreciate that, divorced from the overall context of his evidence, his statement, read literally, conveyed that fluorination with inversion is a (in distinction from the only) likely outcome. The notion that para 23(d) in fact captured Professor Furneaux's true opinion, the rest of his evidence being obfuscation or worse, is untenable. Professor Furneaux was a frank, open and highly engaging expert (as, indeed, were all of the experts who gave oral evidence in this case) who had a clear opinion which, but for one paragraph, he consistently expressed.
569 As a result, I do not accept any of Idenix's criticisms of Professor Furneaux based on para 23(d) of his second affidavit.
570 Another significant plank in Idenix's case is that Professor Furneaux never disclosed until cross-examination that he had in mind at all times the same precursor compound as Professor Meier and Dr Borthwick, and that this compound would be subjected to DAST. Again, a fair view of Professor Furneaux's evidence indicates that the criticism is not warranted. The content of his affidavits (specifically the first affidavit) was a result of the questions he had been asked. He was asked about the Idenix patent providing information about synthesising a compound within claim 7 and concluded it gave him no real assistance (a conclusion I consider reflects the position the skilled addressee would have reached). As noted, he considered that complicated and unpredictable chemistry would be involved in such a synthesis and mentioned the possibilities of adding the methyl group with the fluorine already present and fluorinating a tertiary hydroxyl group. Because he did not think either route would necessarily work, he believed that he would have had to undertake further research in order to investigate the route which should be adopted. He was then asked how he would fluorinate a tertiary hydroxyl group (that is, how he would go about one of the possible routes he had thought of). His initial reaction to this, he said in oral evidence, was to think about the possibility of using DAST (a so-called "one pot" or "one step" reaction) or TBAF (tetrabutylammonium fluoride) (a so-called "two pot" or "two step" reaction) but, at the same time, to characterise this possible route as having a "high chance" of not working; his state of mind when he thought of fluorinating a tertiary hydroxyl with inversion by the one or two step processes was immediately "[w]hoa, that's going to be difficult" or "[w]ow, that's going to be tough". Because of this it was not his first thought in fact to use DAST on a precursor compound. As such, it cannot be said that he thought DAST was the first thing he should try. In fact he thought DAST was highly unlikely to work which is what led him to express the opinions he did in both his affidavits and oral evidence - that several retrosynthetic steps would be required, including a literature search and experimentation, and that the chemistry would be complicated and unpredictable.
571 Idenix's submissions about Professor Furneaux do not take into account these important matters. They undermine Idenix's submission that:
Professor Furneaux's alleged doubts in relation to tertiary hydroxyl groups, crucially, did not prevent him from arriving at the obvious synthesis route of obtaining the Precursor Compound and reacting it with DAST - i.e. assuming that a tertiary hydroxyl group may well react with DAST to give replacement with inversion, even if he had some doubts about whether that reaction be "favoured". This was implicit in all of Dr Furneaux's affidavit evidence where he sought to explain why he had some doubts as to whether reaction of a tertiary hydroxyl group on a nucleoside would proceed with replacement with inversion, or whether elimination would be "favoured", i.e. be the major product. In his first affidavit, he did so with reference to a synthesis route which he did not articulate, but referred to as "the chemistry". That was before Dr Borthwick or anyone else had suggested the Exhibit 8 synthesis route. That unarticulated route was plainly applying DAST to the Precursor Compound.
572 Certain parts of Professor Furneaux's cross-examination may appear to support Idenix's characterisation of his evidence but only when taken out of context. Professor Furneaux was asked and answered numerous questions based on an assumption that he was "going to go down the fluorination route" (that is, fluorinating a tertiary hydroxyl group). Much of the evidence on which Idenix relies is evidence qualified by this assumption - an assumption which is contrary to the overall effect of Professor Furneaux's evidence. For example, I note the following:
(1) His evidence that "DAST is an obvious reagent to be considered" was in response to questions which assumed that he was going to "go down the fluorination route".
(2) His evidence about "Plan A" was in the same context - it was premised on the assumption of "if you'd done the fluorination reaction in 2002". On that premise, Professor Furneaux said:
I suppose what I was thinking, that you would certainly want a plan B because I didn't think that plan A would be guaranteed to be successful.
…
What I am saying is that no fluorination could be a result, you might not get the product you desire, and my corollary to that is that you may have to have a plan B, another alternative method of approaching it.
…
So I expected that, in my words, that you may well expect not to get it as one of the products.
…
So I suggest what you are taking out of me, that plan A would have been favoured over plan B, and that's just - I have chosen those letters. They are not intended to indicate that I would have chosen plan A first rather than plan B.
…
But let's leave aside whether plan A was plan A or plan B, at least one of the plans - and we'll come back to whether it was plan A or plan B - was to fluorinate. Correct? That was certainly a consideration as to whether that would be an approach.
…
I think what I may have said straight off the bat was, "Whoa, that's going to be difficult."
In any event, I thought you said, and you will correct me and we can check the transcript, I thought you said that if you'd been asked to look at the matter in 2002, you would have suggested fluorinating in the expectation you'd likely get a range of reactions, one of which would include, but not necessarily include, the successful displaced fluorination reaction. Isn't that the effect of what you said before? It is not how I've said it.
But you agree that would have been your approach, wouldn't it? I agree that it would have been one consideration as an approach to making a compound with a methyl up and a fluorine down.
The submission that this evidence supports the proposition that "[d]espite later qualifications, it is clear "plan A" was being referred to as a first course of action" by Professor Furneaux is difficult to accept. His evidence as follows, on which Idenix relies, also has to be understood in this context - the initial premise on which he was answering questions - and that at most he considered the fluorination of a precursor compound with DAST or TBAF but, at the same time as that consideration, thought "[w]hoa, that's going to be difficult" or "[w]ow, that's going to be tough". The exchange in cross-examination was this:
Let us assume someone comes to you and says, "I want you to make this target compound," in 2002, okay? Secondly, they also say, "I'm not concerned about the yield, I'm not concerned about it being the most favoured reaction, I just want you to make it." All right?---Yes, sir.
So they are your instructions. Do you agree that plan A, as you mentioned this morning, trying to assist this court, the most likely thing you would say is you would proceed as plan A with fluorinating a precursor compound of one of the types which we've looked at, do you agree, with DAST?---So yes to the bit before you got to DAST and I would say I would have equally considered the two-step process in which I activated the tertiary hydroxyl with a sulfonate leaving group and used a source of fluorine in a secondary reaction in an attempt to achieve a fluorination reaction, so those would have both been in my mind.
For the reasons given I do not accept Idenix's submission that this evidence "is clearly an answer that he would "proceed as plan A with fluorinating a precursor compound with DAST" or, he added, a two-step agent. It was not simply a "consideration" but it was an action".
573 Nor do I consider that Idenix's criticisms of Professor Furneaux which led to the submission that "Professor Furneaux was eventually forced to concede that the reference to "the chemistry" in the first affidavit was the transformation of a tertiary hydroxyl group to a tertiary fluoride using DAST" should be accepted. In a lengthy cross-examination about three affidavits and more besides Professor Furneaux at one point wrongly thought he was addressing Dr Borthwick's proposed synthesis in his first affidavit when in fact he was addressing the question he had been asked about how he would fluorinate a tertiary hydroxyl. This exchange occurred:
The statement, "The chemistry may look simple on paper," was a reference to what you envisaged would be the likely route that you would have taken in 2002. Do you agree? So it refers to that transformation of a tertiary hydroxyl group to a tertiary fluoride using DAST, yes, that would be the chemistry I'm referring to as looking simple on paper.
…
The reference there to, "The chemistry may look simple on paper," do you agree that what you are referring to there was the use of DAST on a precursor to produce an inversion reaction? I don't think I was specifically referring to DAST, but to the replacing a hydroxyl group using a displacement reaction to get to a tertiary fluoride and as I commented on before, I did think there were two ways that you could do it and one was using DAST and another was using a sulfonation activation step followed by a fluoride displacing reaction in a separate vessel.
…
So that you hadn't seen the Clark patent when you suggested as one approach to getting the compound was to use DAST on a precursor compound. That's correct? So when you say I suggested that approach, I considered that approach and considered that it was going to be difficult, so I don't wish to convey, by agreeing with your statement, that I settled on this as an approach to take.
You described it earlier as plan A, didn't you? So this is at the start of the paper chemistry and clearly I would have considered that as a piece of paper chemistry and also would have needed to consider other approaches because my perspective was that it was not simple chemistry, it was complicated chemistry and could take some experimentation before I could figure out whether it would work or not because of the need to, in protecting group chemistry, find the right protecting groups make the starting materials and with not a high expectation that it would work.
Whether you described it as paper chemistry, I think you've told the court that you were likely to perform to make the product in 2002 using a DAST reaction on a precursor I think and now you've added or a two-step sulfonate process. Is that right? That I would have considered those.
Considered and would have done one of them? I haven't agreed to your second point, that I would have done, would carry out that.
574 The mistake Professor Furneaux made does not suggest that he was trying to conceal that he had considered the fluorination of a precursor compound in response to the question he had been required to answer by his instructions. Beyond that, his evidence was consistently that while he considered fluorination by DAST or TBAF he thought at the same time how difficult those reactions were going to be because "it was complicated chemistry and could take some experimentation before I could figure out whether it would work or not because of the need to, in protecting group chemistry, find the right protecting groups make the starting materials and with not a high expectation that it would work". This cannot be reduced to Idenix's proposition that "Professor Furneaux's first reaction as to how to best achieve the synthesis of a compound of claims 7 and 8 was to obtain the Precursor Compound and apply DAST to it, or perhaps do a similar thing in two-stage reaction using TBAF".
575 Accordingly, on the basis of the whole of Professor Furneaux's evidence, I do not accept Idenix's propositions that:
(1) "Professor Furneaux's doubts expressed in his affidavit about whether the tertiary hydroxyl group, when reacted with DAST, would proceed with replacement and inversion, were not doubts as to whether that reaction would proceed at all, but were doubts as to whether that reaction would be "favoured", i.e. would be the reaction yielding the largest amount of reaction product". In fact, Professor Furneaux did not expect the desired reaction to occur at all.
(2) "Professor Furneaux does not say that very specific reactions would be required to produce a product with fluorine introduced in the 2'-position - but only that very specific reaction conditions would be required to favour it - i.e. for it to be the major reaction product". In context, it is apparent that Professor Furneaux did think very specific reaction conditions would be required for there to be a fluorination reaction at all.
(3) "…his understanding as at 2003 was that inversion was not the only likely outcome of an attempted fluorination reaction of a tertiary hydroxyl group in a sugar or nucleoside. As a matter of ordinary English that is an acceptance that inversion was a likely outcome". This is not so - see above.
(4) "Professor Furneaux's reticence to accept in cross examination that at least one of the expected reactions would have been successful fluorination coincided with him having to concede that the route he first thought of and regarded as obvious was the DAST fluorination reaction with inversion". I am unable to see anything in Professor Furneaux's evidence to support the view that he was being anything less than frank at all times.
(5) "…even in cross examination, his position was inconsistent" as to whether fluorination with inversion was likely to occur. I disagree. His answers must be read in context and as a whole. When this is done any perceived inconsistency disappears.
(6) "Professor Furneaux's alleged doubts as to whether applying DAST or a similar reagent to the precursor would result in a fluorination reaction being "favoured" were formed after he specifically searched the Red Books, and did searches on both Google and Google Scholar, for matters disclosing complications with fluorination reactions on secondary hydroxyl groups". In fact, his expectation that the reaction would not work existed from the outset and he then did searches to confirm his views.
(7) "…he accepted that the reaction normally proceeded with replacement with inversion". Professor Furneaux accepted that fluorination with inversion of a secondary hydroxyl could be expected, albeit along with other reactions. He never accepted that fluorination with inversion of a tertiary hydroxyl could be expected - a point contrary to the whole thrust of his evidence. Hence, care is required in identifying "the reaction" to which reference is being made by Professor Furneaux.
(8) Professor Furneaux searched for problems to support his "mantra of "complicated chemistry"". In fact, Professor Furneaux knew that the fluorination with inversion of a secondary hydroxyl often involved competing reactions so when confronted with the question of fluorination of a tertiary hydroxyl, which he considered would be complicated chemistry, he reminded himself of literature which disclosed competing reactions in respect of secondary hydroxyls. I do not see this as some form of illegitimate search for problems to support a "mantra". Professor Furneaux already knew about complications associated with fluorination of secondary hydroxyls. He already thought that fluorination of a tertiary hydroxyl was unlikely to succeed.
(9) "Professor Furneaux did not have any clear or consistent scientific rationale as to why he considered an elimination reaction would be "favoured"". To the contrary Professor Furneaux explained that his views took into account steric hindrance, crowding by other groups and neighbouring group participation.
(10) "…when considering the Patent, Professor Furneaux requires detailed exemplification of all reaction conditions to fluorinate a tertiary hydroxyl group on the sugar ring of a nucleoside, but when making representations to the US Patent and Trade Mark Office he is content to say that fluorinating a tertiary hydroxyl group at the 2 position on a sugar ring is within the ordinary skill of the addressee". This is a reference to a patent naming Professor Furneaux as an inventor in which some of the formulas show methyl-"up" and fluoro-"down" groups at the 2'-position which are said to be able to be made by methods analogous to those known in the art. As Professor Furneaux said, these compounds were never specifically exemplified in the patent naming him as an inventor. Moreover, he did not "require" anything from the Idenix patent. He was giving his opinion on specific issues as requested and no more.
(11) "A fair characterisation of the approach taken by Professor Furneaux was that he was not looking to succeed, as the sufficiency addressee ought to be. Rather, he was operating outside his comfort zone of expertise, and accordingly became unduly anxious about theoretical reasons which he considered might result in failure. He then deliberately sought out complications in the literature to justify his doubts". As discussed, I do not accept any of the contentions which underlie this characterisation.
(12) Professor Furneaux's evidence "is contradicted in terms by the common general knowledge in the Middleton Paper and March. His later attempts to distinguish the Middleton Paper in his affidavit in reply need to be viewed in that light - i.e. as a rearguard defence of an uninformed original opinion". As noted, irrespective of whether he specifically had in mind the Middleton Paper or March textbook when he prepared his first affidavit, Professor Furneaux's view that those papers dealt with only a couple of very simple tertiary hydroxyls and were of little relevance to the task of fluorinating the tertiary hydroxyl of a compound such as that involved in claim 7, in my view, would have reflected the approach of the skilled addressee armed with the Idenix patent and the common general knowledge in 2002 and 2003.
576 I accept Gilead's submissions that:
(1) "The import of Professor Furneaux's evidence is that he would have investigated other possible approaches and would have had to engage in a retrosynthetic analysis and research project in order to attempt to make a compound within claim 7. That is entirely consistent with the objective evidence" (that is, the Idenix documents).
(2) "…the effect of Professor Furneaux's evidence was that he immediately considered fluorination with DAST only to be an approach that was problematic, and which he did not expect to produce a successful result. He did not give evidence that he would have adopted that approach. The answers on which Idenix relies were given in response to questions that required him to make multiple assumptions which in effect determined the result".
(3) "…there can be no doubt that Professor Furneaux's opinion is that the fluorination of a tertiary alcohol with DAST appeared to him to involve complex chemistry and he was not satisfied that that was a synthetic route he would pursue. That is the relevant level of the debate, not whether using DAST had occurred to him".
(4) "Professor Furneaux was very clear to distinguish between what one may conceive of as opposed to what one may actually try because upon conceiving of the possibility of using the DAST approach, he thought it unlikely to work… There was no reason for him, in light of the questions he was answering in his affidavit and his opinion about the likely utility of the DAST approach, to identify in his affidavit only to dismiss it immediately".
(5) "…the sincerity of Professor Furneaux's views in this respect was readily apparent in his cross-examination and that the Court would accept that he was giving his evidence honestly, including that this was his view before undertaking the Red Book review and reading Pankiewicz 2000".
577 Insofar as capacity to make the required precursor compound is concerned, Professor Furneaux expected he would be able to make the precursor but not, as Idenix would have it, by resorting only to the common general knowledge. Professor Furneaux said that this would be "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" for which he would "have planned out alternative routes and then considered which to undertake" recognising that he "would have to go to the literature, look up the methods, but with the expectation that that information would be present". An expectation that he would find the information he needed is not the same as knowing specific information exists and merely looking it up to confirm the details (which I accept may fall within the rubric of the common general knowledge).
578 I also do not accept Idenix's submissions that because the issue is whether the skilled addressee could make something within claim 7 and not whether the addressee would do so, Professor Furneaux's evidence about what he expected is irrelevant. This identification of the issue is an over-simplification of the test which is concerned with whether the disclosure in the specification (construed in the light of common general knowledge) provides the relevant enablement.
579 Further, as Gilead said:
…where reliance is placed on the common general knowledge as the source of the information required to enable the skilled person to produce something within the claim, as opposed to any instruction or direction in the Patent, the question whether a skilled person would or would not adopt a particular course of action is highly relevant. If the skilled person would not in fact take a step that is available in common general knowledge, for example because it would not occur to them to do so, or because it appears to them to be too complicated or unlikely to succeed, it is a fiction to say that "the disclosure" in the specification has enabled that person to take that step without new inventions or additions or prolonged study of matters presenting initial difficulty.
580 If Idenix's submission were correct then it also would follow that the expectations of every other expert, including Professor Meier and Dr Borthwick, were irrelevant. Yet it is those expectations which, in each case, led them to express opinions about what they would have done in 2002 and 2003. Without their expectations it is unclear what, if anything, they say they would have done. Gilead said this:
A person's expectation as to whether or not a particular course of action would or would not lead to the invention will plainly be relevant to whether or not he or she would undertake it, and thus whether he or she would be put in possession of the invention.
This is particularly so where, as in this case, the specification admittedly provides no instruction on how to produce the invention, so that the skilled person has to resort to common general knowledge in order to attempt to produce it. If there were directions given in the specification for how to make a compound within claim 7, then the question of the skilled person's expectation would not arise in practical terms, as the instructions could simply be followed in order to make it. But where it is the common general knowledge is relied on as the source of the method of synthesis, the question of that person's expectation is highly relevant.
The common general knowledge is a general body of knowledge used by persons in the field; it is not a set of instructions to be followed for doing any particular thing. In order to extract from it a pathway to making the invention, if one indeed exists, and without any direction in the Patent, the skilled person relies on his or her expectation that adopting that particular course will in fact lead to the invention. That expectation necessarily informs such a person's decision as to whether, in the absence of any instruction to do so, he or she would use the common general knowledge to take the relevant steps. If he or she would not, then there has been no enablement to produce something by that route.
Similarly, in the absence of any direction in the Patent, if a skilled person's expectation is that he or she would need to research non-common general knowledge methods in order to attempt to devise a way to produce something within the claim, that evidence cannot simply be ignored. That is what Idenix would have the Court do in relation to Professor Furneaux's evidence. By inviting the Court to take that course, Idenix in effect treats the Patent as though it contains instructions to the skilled person to adopt a different approach - a method of synthesis involving fluorination with DAST - being something Idenix admits the Patent simply does not provide.
581 I agree. Professor Furneaux's expectations were no different from those of Professor Meier and Dr Borthwick. Idenix would have it that the expectations of Professor Meier and Dr Borthwick are legitimate but those of Professor Furneaux irrelevant. In fact, the expectations of Professor Meier and Dr Borthwick were based on highly specific knowledge which, as discussed, did not form part of the common general knowledge. Professor Furneaux's expectations were based on common general knowledge. He went to literature only to confirm what he already knew. Further, Professor Furneaux's view that to ascertain if he could make a compound within claim 7 he would need to formulate a retro-synthesis, undertake research and experimentation (that is, go beyond the common general knowledge) was itself based on the common general knowledge.
582 Gilead's characterisation of Idenix's submissions about the irrelevance of expectation and of what a skilled addressee would do is persuasive. Gilead said these submissions involved an approach in which "the skilled person is forced into adopting a course of action he or she would not have adopted, disregarding his or her expectation as to whether or not it would work and whether or not he or she would in reality have taken it, and being precluded from conducting research and inquiry into other matters that he or she would in fact have sought to conduct", which is an artificial and inappropriate way to try to determine sufficiency.