6.6 Analysis
184 Claim 1 of the patent application provides:
A method of controlling lice on an animal, characterised by the step of administering by backlining a pharmaceutically effective amount of thiacloprid, wherein the amount of thiacloprid administered to the animal is from 10 to 30 mg/kg by weight of the animal, wherein the thiacloprid is administered in a composition containing 0.5%-2% w/v of thiacloprid, and wherein the animal is a sheep or a goat.
185 Abbey submits that in testing whether or not there is an inventive step on the facts, the Cripps question can be modified to read as follows:
Whether the skilled team would have been directly led as a matter of course to try dosages within the claimed dosage range/concentration in the expectation that this might well produce a better or useful alternative to the existing sheep lice treatments or some other useful result.
186 It submits that this must be answered in the affirmative, but in any event submits that the inventive step question may be answered separately by reference to the test set out in Wellcome Foundation at 287 (set out in section 6.2 above), namely whether the hypothetical addressee, faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not. Elanco disputes this, submitting that the skilled team would not have been directly led as a matter of course to try thiacloprid in the ranges claimed.
187 In the course of its argument, Elanco submits that it would not be sufficient for the hypothetical skilled team to arrive at a dosage of thiacloprid in a pour-on formulation to treat lice in sheep that was within the range of dosage and concentration claimed in claim 1 of the patent application. It submitted that the range itself would need to be determined.
188 I do not consider this proposition to be supported by the authorities. In my view, it is sufficient for Abbey to establish that it was obvious to achieve something that falls within the range claimed to invalidate the entirety of the claim for want of inventive step. As the Full Court said in AstraZeneca AB v Apotex Pty Ltd [2014] FCAFC 99; (2014) 226 FCR 324 (Besanko, Foster, Nicholas and Yates JJ) at [195] (Jessup J agreeing at [447]):
In assessing novelty or obviousness, the focus is on the claim as construed in light of the complete specification read as a whole and the common general knowledge as it stood at the priority date of the claim. In particular, in assessing whether or not an invention was obvious and, consequently, lacking an inventive step, the relevant inquiry is whether anything within the claim (not merely embodiments described in the complete specification) would have been obvious to the hypothetical person skilled in the art: Blanco White TA, Patents for Inventions (5th ed, Stevens & Sons, 1983) at [4-201]; see also Grove Hill Pty Ltd v Great Western Corporation Pty Ltd (2002) 55 IPR 257 at [364] per Gyles J. The position in Australia and United Kingdom is no different in this respect. It is the claimed invention that must involve an inventive step: Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] RPC 28 at [17] to [19] per Lord Hoffman.
(Emphasis added)
189 Just as the novelty of the claim would be defeated by a disclosure within the range, so too is the inventive step.
190 In this regard, I note that whilst claim 1 identifies a range, nowhere in the specification is there any suggestion that the inventive step is in the selection of the range. Indeed, as a review of the patent application demonstrates, the broadest statements of the invention involve assertions that the method may be characterised by the step of topically administering a composition containing from 0001% to 3.5% w/v of thiacloprid (see [52] above). Trial Example 10, which is the only example referring to the backlining method, does not purport to show a range. Indeed, the results of the four trials conducted report efficacy in pour-on treatments with dosage levels of 15 mg/kg, 10 mg/kg and 5 mg/kg, all of which are said to have resulted in an absence of live lice on the sheep tested. The dose of 5 mg/kg is outside the dose range of claim 1. Accordingly, whilst claim 1 is for a method of treatment within a range, there is no basis upon which it may be said that the range, rather than a dose within the range, forms part of the inventive step.
191 Abbey submits that the skilled team would, as a matter of routine, have conducted the solubility, proof of concept and dose determination studies leading from the Trade Advice Notice to the claimed invention in the expectation that they might well succeed in finding a dose within the claimed range, citing Merck Sharp & Dohme Corporation v Wyeth LLC [2020] FCA 1477; (2020) 155 IPR 1 (MSD v Wyeth) at [255] and [822] and the cases there cited.
192 Elanco contends that the evidence demonstrates that it was not routine to develop the minimum effective dose of the active ingredient. It disputes that the formulation of a pour-on dosage form of thiacloprid would be straightforward, identifying two difficulties facing the skilled team, first the question of solubility and secondly the question of dosage amount.
193 I have addressed the evidence concerning questions of formulation in sections 6.5.1 and 6.5.2 above. It is not in dispute that the present patent application is not for a formulation, but rather for a dose range for use in a method of treatment. I have concluded in section 6.5.2 that no inventive step lay in finding a suitable solvent for thiacloprid.
194 The question of dosage amount, or as some of Elanco's submissions suggested, a "starting dosage" was, to some extent, a distraction. This was perhaps generated by the manner in which the evidence of Ms Mahashabde was presented. However, neither Ms Mahashabde nor any other expert stands as a proxy for the notional skilled team. The task of the Court is to assimilate the evidence and determine whether the invention claimed lacks an inventive step.
195 The distinction between characterising steps taken as a matter of routine that would invalidate a claim (Wellcome Foundation at 286; AstraZeneca (HC) at [15]) and steps taken because the skilled team regards them to be "worth a try" but would not invalidate a claim (AB Hässle at [72]; AstraZeneca (HC) at [15]) is not always clear. In Generic Health, the Full Court explained at [71] that one way of distinguishing the two is by reference to the expectation of the skilled team that it may succeed in its endeavour:
… It is difficult to think of a case where an expectation that an experiment might well succeed is not implicit in the characterisation of steps as routine and to be tried as a matter of course. On the other hand, we think a test formulated in terms of worthwhile to try was firmly rejected by the High Court in [AB Hässle] …
196 As I have noted in section 6.2 above, in Nichia the Full Court observed that the relevant test for expectation will be satisfied if the Court finds that the hypothetical skilled team expects that the steps may well work, rather than knowing that steps will or would or even may well work (at [99]).
197 Elanco relies on the analysis by Besanko J in ICOS Corporation to demonstrate that in the present case the evidence does not rise to the level required. In that case, after a thorough examination of the authorities, many of which have been referred to above, his Honour found, in relation to the 946 patent that although the development team would as a matter of course, be directly led to try the compound tadalafil with the required expectation of success, he was not satisfied that the team would, as a matter of course, be directly led to the claimed doses with such an expectation (at [465]). The factual matrix that led his Honour to that conclusion is quite different to the present case. The skilled team here, in possession of the Trade Advice Notice, has been provided with a template for the use of a potent active ingredient that has been shown to be efficacious and safe in a dip formulation. There is no obstacle to its use in proof of concept studies. The only task is for the skilled team to identify dosage amounts to be applied.
198 In this regard, the evidence of the veterinarian experts to which I have referred in section 6.5.4.1 above persuades me that the conduct of proof of concept studies forms a basic tool for the skilled team to ascertain an effective dose to thiacloprid in a pour-on product. I am not persuaded that there was any relevant obstacle to the skilled team in developing such a dose. Indeed, the evidence was that there were before the priority date several pour-on formulations within the common general knowledge used for backlining treatments that were also formulated for use in dips. Armed with the Trade Advice Notice the skilled team had every reason to expect that an efficacious dosage would be achieved.
199 Furthermore, I accept that the skilled team would work to ascertain an efficacious dosage amount of active ingredient that sat in the lower end of the range. I have concluded in section 6.5.4.1 that this was the routine approach.
200 Within the skilled team, the formulator would work in conjunction with other members to determine appropriate dosage amounts. Ms Mahashabde determined that she would take the dose amount from Trade Advice Notice by estimating the amount used in the dip formulation and then applying that estimate to several proof of concept studies. Mr Pippia, if using the Trade Advice Notice to select a starting point, would have taken much the same approach. Both would use those studies to check for efficacy using multiples of the dosage range identified. I do not accept that this approach is arbitrary - that there was nothing scientifically rigorous about the selection of a starting dose, at the early stage, or that it simply involved guesswork.
201 I accept that at the outset the skilled team would not know the dosage amount that would be ultimately selected. But that is precisely why the tests are required. Such tests are, however, in my view in the nature of tests for checking and verifying of the type referred to in Wellcome Foundation at 280-281. The plurality in AB Hässle considered at [51] what Aickin J had in mind by his use of "routine" by referring to an earlier passage of Wellcome Foundation (at 280-281):
Evidence of what he did by way of experiment may be another matter. It might show that the experiments devised for the purpose were part of an inventive step. Alternatively it might show that the experiments were of a routine character which the uninventive worker in the field would try as a matter of course. The latter could be relevant though not decisive in every case. It may be that the perception of the true nature of the problem was the inventive step which, once taken, revealed that straightforward experiments will provide the solution. It will always be necessary to distinguish between experiments leading to an invention and subsequent experiments for checking and testing the product or process the subject of the invention. The latter would not be material to obviousness but might be material to the question of utility.
202 In the present case, no inventiveness lies in the perception of the true nature of the problem. Once armed with the Trade Advice Notice the skilled team immediately perceives the desirability of moving to a backlining method using thiacloprid. The question remaining is whether the process of arriving at a formulation within the claimed range was an inventive step.
203 In my view the hypothetical skilled veterinarian in the team would be robust about the likelihood that an efficacious dose of thiacloprid for use in a pour-on product would be ascertained. Dr Agnew held the view that it would be a straightforward step to determine the dose range of a pour-on product, including where information is available about a dip product using the same active. He explained that in his career he had never experienced a circumstance where an active ingredient that was administered as a dip was not able to be adapted to be used as a pour-on. In cross examination he explained that when he saw the Trade Advice Notice he automatically assumed that it would work for a pour-on formulation. In this regard, he gave an example of his own experience:
MR FOX: Yes, yes. But you don't - you don't look at, for example, the trade advice notice and see it referring to thiacloprid being useful for dipping and then automatically assume that it will work for pour-on formulation, do you?
DR AGNEW: Actually, I did. And so the reason - the reason for that is, again, based on my experience from the Spinosad work where we started with a concentrate, a suspension concentrate product. We then moved to a suspension concentrate, a same formulation but much less concentrated for the sheep dip. And because the efficacy of Spinosad against sheep lice was fantastic, then the step of deciding to develop a pour-on was quite straightforward because we had information based on the species; so sheep were the same. We had information that the dip was efficacious against sheep lice. So that was the parasite we were going after. And so the biggest challenges in terms of assessing are that you've got a reasonable chance of success with a product. So - so when I - when I see a trade advice notice with a product where the active that I'm thinking of developing as a pour-on and I see it's used on sheep and against lice, I actually would be very confident that you could backline formulation with that active.
204 Professor Whittem noted that one could not make assumptions about dose when moving from a dip to a pour-on product, but that one would have, from the dip formulation, evidence that efficacy in a pour-on product is possible if one got the distribution right.
205 To the extent that there is variance in their approach, I accept the evidence of Dr Agnew as more persuasive.
206 In relation to dose, I have accepted at [172] above that proof of concept studies would typically aim to determine a range, with the focus being to establish a minimum effective dose. The evidence of Ms Mahashabde and Mr Pippia focussed on the starting doses to be tried in proof of concept studies, although it is apparent from their evidence, and I accept, that the skilled team would broaden the range of the doses used in proof of concept studies as results came in. As Mr Pippia said, he would be "guided by the data". Although I accept that the process of determining the dosage amounts would be time consuming and expensive, and would possibly take the team a long time to achieve, I am satisfied that their conduct is well within the range of the skills of the skilled team and falls within the range of conduct described in the authorities as "routine steps". On the basis of their approach, as set out in the evidence considered in section 6.5.4.2 above, I am satisfied that even their starting ranges would include dosage amounts within the range claimed in claim 1.
207 In my view, the present facts are analogous to those in AstraZeneca (HC). In that case, the Watanabe Article did not disclose dosage amounts. French CJ relevantly said at [42] - [44]:
Jessup J concluded that the primary judge had not erred in concluding that a person skilled in the art would have been led directly and as a matter of course to try rosuvastatin at a dosage of 5-10 mg/daily in the expectation that it might well be an efficacious treatment for a patient suffering from hypercholesterolemia. The evidence of Professor O'Brien and of Dr Reece was sufficient to sustain the conclusion that the skilled person, having read the Watanabe Article in the light of the common general knowledge, would have entertained the expectation that rosuvastatin might well be at least as efficacious a treatment as atorvastatin. No error was involved in that reasoning. In the light of the evidence it would be a routine step to test rosuvastatin at the lowest efficacious dose.
Jessup J rejected a submission by AstraZeneca that the primary judge's conclusion that the skilled person would have proceeded to try rosuvastatin at any dose, let alone a 5 or 10 mg dose, with any reasonable expectation of success was not open on the evidence before her. That rejection was plainly correct. As his Honour said (91): "Whether an invention is obvious is a question to be answered by the Court." The question posed by this Court in Wellcome Foundation Ltd and AB Hässle does not require that, in order to sustain an obviousness case, a party has to lead evidence which echoes the terms of that question. A similar conclusion was open, as the primary judge found, on Patent 471.
AstraZeneca submitted in this Court that the "claimed invention" is a treatment using a once daily, 5-10 mg dosage of rosuvastatin. The only dosage expert, Dr Reece, confirmed that neither the Watanabe Article nor Patent 471 contained animal or human trial safety data. He had given evidence that such data were essential to determining what dosage should be tested in clinical trials. The person skilled in the art would never have chosen the dose to be tested simply by trying the doses that worked for other statins. That evidence was referred to by Jessup J, who said (92):
"But that evidence also made it quite clear that such trials would conventionally be carried out. They would fall within the concept of working towards the invention with an expectation of success referred to in AB Hässle."
No error is disclosed in that reasoning.
208 Justice Kiefel said at [93] - [95]:
The final submission was that, armed with the Watanabe article and the common general knowledge, the skilled person would not have been led directly to the invention because the starting dosages are an essential element of the invention and were not revealed by that article or by any other prior art document.
This may be accepted. The dosages were revealed to AstraZeneca by clinical trials on humans, as inevitably they would be if undertaken. The point is that the Watanabe article contained sufficient information, including as to the results of the pre-clinical trials on animals, for Professor O'Brien to consider that clinical trials were warranted. Dr Reece was of the same view.
Professor O'Brien's evidence about what the right dosages might be, although accurate, was largely speculative and this was not his area of expertise. However, Dr Reece, who has a background in clinical pharmacology and research, gave evidence that dose sizes which would be trialled could be expected to start from 5 mg, 10 mg and 20 mg. I do not understand AstraZeneca to contend that the starting dosages disclosed in the Patent would not be identified by normal clinical trials, which utilise certain standards and procedures. The evidence therefore shows that the skilled person would be led to the invention.
209 Justices Gageler and Keane said at [116]:
It is also wrong to suggest, as AstraZeneca did, that the need for further testing of human subjects was an obstacle to a conclusion that rosuvastatin would have been tried as a matter of course in the expectation of a solution to the problem in the common general knowledge. Section 7(2) does not invite a consideration of the notional addressee's motivation to carry out any tests that would need to be done. In particular, it does not contemplate consideration of whether the skilled addressee would be sufficiently encouraged by the available information to undertake the expense and inconvenience of further tests necessary to bring the solution to the stage of implementation.
210 Justice Nettle said at [123]:
In fact, however, there is no basis in the objection. Both the primary judge and the Full Court approached the matter in accordance with that requirement. As Jessup J said, although Dr Reece's evidence was that the Watanabe article contained no safety data the result of either animal or human trials, the evidence also disclosed that trials of that kind would conventionally be carried out. Accordingly, carrying out the trials fell within the concept of working towards an invention with an expectation of success and that was consistent with the conclusion that the invention was obvious.
(Footnote omitted)
211 In my view, that team would be confident, in commencing its proof of concept studies, that it would obtain an efficacious backlining treatment using thiacloprid. It would not know the dosage amounts, but adopting routine testing of the type described and with the approach identified for the selection of a dosage range in 6.5.4.2 in my view the skilled team would have arrived at a dosage amount that falls within the claims. Indeed, although on my analysis it was not necessary for it to do so, the results set out in the table in section 6.5.4.2, where the approach to commencing proof of concept studies would lead to a dose amount within the range, support this conclusion. Such results were not necessary because in my view, on the basis of the promising information in the Trade Advice Notice, the skilled team would, if it did not find an efficacious dose in initial proof of concept studies, vary the range until they did.
212 As a footnote, I observe that there is a degree of arbitrariness about the range claimed in claim 1. Trial Example 10 demonstrates that the administration of 5 mg/kg (0.5 ml/kg) was effective. This is half the minimum amount claimed. No evidence suggests that there was any rational basis for excluding the lower dose from the claim. For present purposes it is not necessary to dwell on the consequences of that exclusion for the validity of the claim. However, in light of the matters to which I have referred, no invention will lie in arbitrarily limiting an effective range.