The Role of the Inventive Concept in an Obvious to Try Analysis

Eli Lilly Canada Inc v Apotex Inc 2023 FCA 125 Rivoalen JA: de Montigny, Gleason JJA affg 2020 FC 816 St-Louis J

2,371,684 / tadalafil / CIALIS ADCIRCA / FC Selection / FC Anticipation

This case is ultimately a straightforward example of the asserted claims being invalid on an obvious-to-try analysis, but because of the way it was argued it also sheds some light on the role of the inventive concept in the obviousness analysis.

The asserted claims of the 684 patent are to dosage forms of tadalafil for treating ED, namely doses from 1 to about 20 mg, as well as specific doses within that range, including 2.5, 5, 10 and 20 mg doses [FC 197-213]. The question in this case was whether the 684 patent is valid over the prior art 2,226,784 patent, which claims tadalafil for the treatment of ED, and disclosed a dose range from 0.2 to 400 mg [12]. At trial, St-Louis J held on the facts that starting from the knowledge that doses from .02 to 400 mg were useful, it would be routine for the skilled team to carry out the trials necessary to narrow that down to the range providing the best balance between efficacy, and safety and tolerability, and they would be motivated to do so [FC 325–28]. The claimed invention was therefore obvious to try [FC 323, 330]. The FCA has now affirmed on that basis [65]–[80].

Lilly’s challenge on appeal was to find a question of law to attack in St-Louis J’s essentially factual finding. Lilly argued that St-Louis J had erred in her construction of the inventive concept, a question of law [48] arising at step 3 of the Windsurfing test for obviousness, which was adopted in Sanofi 2008 SCC 61 [67]. Lilly waffled in its argument as to what constituted the specific inventive concept, before settling on the position that the inventive concept is that the claimed dose remains effective in treating ED, with a reduced flushing side-effect as compared to larger doses of tadalafil [20]–[27], [61]. (As an aside, getting an extra four years of exclusivity on a popular drug on the basis of reduced flushing would be grist for the mill for critics of evergreening practices. From a PR perspective, it is probably a good thing for Lilly that this patent was invalidated.)

There has been a debate as to the role of inventive concept in assessing obviousness, which came to the fore in Shire 2021 FCA 52. One central issue is whether the inventive concept is the “end point” of the obviousness inquiry (Shire [65]), or is rather a “distraction” that can be avoided if it is unhelpful Ciba 2017 FCA 225 [76]–[77]: see here. Rivoalen JA held that in this case, it did not matter whether Lilly was right as to the nature of the inventive concept; the claims were invalid for obviousness in any event [49].

As noted, St-Louis J used an obvious-to-try analysis, which was endorsed by Rivoalen JA [65]. (So far as I can tell, Lilly did not dispute that the obvious-to-try test was appropriate.) St-Louis J found that carrying out a drug dosing study is typically done in Phase II clinical trials, and it is normally routine work [FC 325]. Such studies aim to identify the dosage that provides the best balance of efficacy, safety and tolerability [69]. In reviewing the factors relevant to an obvious-to-try analysis, Rivoalen JA pointed out that the reduced flushing that was eventually identified as an advantage of the optimal dose does not change the aim of identifying the dose range that offers the best balance [72]. Further, on the facts that the dosing study in this case was routine; again, this conclusion is not affected by the fact that reduced flushing turned out to be one of the advantages of the optimal dose [73]–[77]. After carrying out this routine dosing study, the skilled person would be motivated to identify and commercialize the optimal dose [79]. Consequently, the claimed dosage range was obvious [80].

To summarize, there was nothing inventive about carrying out the dosing study and identifying the optimal dose—and that conclusion does not depend on the precise properties of the final dose. While minimizing the flushing side effect was one goal of the dosing study, it is possible that the optimal dose would not have reduced flushing significantly; while flushing was a side effect of interest, it is a relatively minor side-effect, certainly compared to other side-effects such as passing out from low blood pressure. So, before carrying out the trials, the skilled person might not have predicted that the optimal dose would have reduced flushing. Nonetheless, there was nothing inventive about the dosing studies, even though not all the specific properties of the optimal dose could not have been predicted ex ante. This is really the whole point of the obvious-to-try analysis: when something is obvious to try (finding the optimal dose) and the trials themselves are routine, the resulting product is obvious, even if not all of its properties could have been predicted in advance.

In other words, apart from the distraction of the inventive concept debate, this was a perfectly ordinary application of the obvious-to-try test, and the patent was invalidated on that basis both at trial and on appeal.

What does this tell us about the role of the inventive concept? Rivoalen JA was very explicit that she was accepting Lilly’s construction of the inventive concept only for the sake of argument, and her conclusion did not turn on whether that was the true inventive concept [49], [61]. On its face, this implies that it is not always necessary to identify the inventive concept in order to assess obviousness.

But there is also a debate as to how to define the inventive concept. In this case, Lilly seemed to be using it to mean new information that was disclosed in the patent and embodied in the claimed subject-matter. But the inventive concept has also been equated to “the solution taught by the patent” (Bristol-Myers 2017 FCA 76 [65]). In a previous post, I argued that the focus on the obviousness inquiry should be on whether the subject-matter defined by the claim is the solution to the objective problem that would have faced the skilled person. This is consistent with Rivoalen JA’s analysis in this case. In a dosage study, the problem is to find the dose that best balances efficacy against side-effects. In this case, the solution to that problem was a dose from 1 to about 20 mg. On the facts, that solution was obvious on an obvious-to-try analysis.

So perhaps the underlying issue is how to define the inventive concept. If we define it as the solution to the objective problem, then perhaps it is the proper focus of the obviousness inquiry; that view is at least consistent with the result and analysis in this case. On that view, the real lesson of this case is that if we are going to use the inventive concept as part of the obviousness analysis, we cannot allow the patentee free rein in defining it.

Finally, St-Louis J had also held that that the 684 patent was anticipated by the prior art 784, and she had an extended discussion of whether the 684 patent was a selection patent, evidently on the view that this had important consequences for validity. I had criticized her analysis of both these points: see here and here. In light of her holding that the patent was invalid for obviousness, Rivoalen JA found it unnecessary to address these issues; she added that “[t]hese reasons, however, should not be viewed as endorsing the Judge’s findings or reasons in respect of these issues” [82].

Accounting Elected in the Alternative

UPL NA Inc v AgraCity Crop & Nutrition Ltd 2022 FC 1422 Aylen J

2,346,021 / flucarbazone sodium herbicide / EVEREST / SIERRA / HIMALAYA

I am finally starting to catch up on some of the cases I missed during my blogging break, but the end of term is busy and my blogging will continue to be erratic until late May.

In this decision, released last November, Aylen J found Arysta’s 021 patent to be valid in the face of obviousness and anticipation attacks. (The headline plaintiff, UPL, is a related company.) Infringement by AgraCity was conceded [3], [82]. Aylen J awarded $227k on an accounting of AgraCity’s profits. Relatively little infringing product was sold because an interim injunction had been granted soon after AgraCity had launched: see 2019 FC 530, blogged here and here. The decision turned largely on the facts, but there is an interesting point on the limits of inducement. The trial was not bifurcated, and, unusually, AgraCity was permitted to elect an accounting if its damages award did not meet a certain threshold. This seems to be inconsistent with the rule set out in AlliedSignal (1995), 61 CPR (3d) 417 (FCA), but the point does not appear to have been contested.

The 021 patent relates to a selective herbicide, namely flucarbazone sodium, and its use in weed control. Herbicides may be total herbicides, which kill all plants, or selective herbicides, which kill weeds with minimal injury to crops [118].

The key prior art was US Patent 5534486 and the corresponding Canadian Patent 2,064,636; like the 021 patent, both were originally granted to Bayer [30], [39], and the 486/636 and 021 patents had several overlapping inventors. There was not much difference between the 486 and 636 patents, and Aylen J focused her analysis on the 486 patent [157].

The 486 patent claimed a large genus of compounds and set out 327 preparation examples [33]. Eleven compounds were specifically claimed, including Claim 10 to flucarbazone and its salts [38]. Claim 10 was simply to the compound as such, not to any use. The 486 patent also disclosed that the claimed compounds are herbicides, but it was ambiguous as to whether they were total or selective herbicides [161], [182]. The 486 patent disclosed that some compounds had been tested and found to be effective herbicides, but there were few details: “No specific test results were included. For the tests that were conducted, the 486 Patent does not disclose which weeds were tested or which crops were tested, nor was flucarbazone or flucarbazone sodium included among the compounds that were tested” [182]; and see similarly [34]–[37].

Claim 1 of the 021 patent is to a selective-herbicidal composition, comprising an effective amount of flucarbazone sodium [57]. So, the point of novelty of Claim 1 over Claim 10 of the 486 patent was the identification of flucarbazone as being specifically a selective herbicide. Claim 10 of the 021 patent was to a method of controlling a variety of grassy weeds, including wild oats, in a cereal crop, such as wheat [57]. The point of novelty over Claim 10 of the 486 patent was the identification of flucarbazone as being a selective herbicide for the control of wild oats in crops of wheat [178].

The thrust of the obviousness attack was that in light of the disclosure in the 486 patent that flucarbazone was a herbicide, it would have been obvious to test it to see if it was a selective herbicide. The obvious-to-try argument failed on the facts. In large part this was because Aylen J found that the evidence did not disclose any reason that a skilled person would pick flucarbazone sodium out of the 327 specifically disclosed compounds for further testing as a selective herbicide: the fact that it was specifically claimed was not enough [190]–[192]. Moreover, at the relevant time, “sulfonylurea herbicides [which includes flucarbazone] were not generally known for the control of grassy weeds. Rather, they were known for controlling broadleaf weeds and demonstrating little activity on grassy weeds” [193]. Thus, the CGK would have steered the Skilled Person away from selecting flucarbazone sodium as the candidate compound for further testing [193]. This goes more directly to Claim 10 than to Claim 1, but as I understand it, the skilled person would have been interested in developing selective herbicides for commercially important grassy weeds, such as wild oats, and the fact that flucarbazone was unlikely to be good for that purpose made it unlikely that it would be selected as a candidate compound for further investigation.

This was a key determination. It might have been routine to determine if flucarbazone was a selective herbicide starting with flucarbazone itself as the candidate compound, but once it was determined that the proper field of candidates was all 327 disclosed compounds, the finding on the facts that it would have required prolonged and arduous effort to identify flucarbazone in particular as a selective herbicide, followed [203]–[209]. The same conclusion would have followed even if it could be said that the skilled person would have started with just the eleven claimed compounds [203].

It would be interesting to know specifics about the test data that underpinned the 486. I get the feeling that the drafters of the 486 patent may have been careful not to disclose the specifics of the testing, precisely in order to allow a follow-on patent to be filed on the most promising compounds. That would raise an interesting question as to whether the 486 was insufficient for not making full disclosure, and how that might be proven.

The findings relating to obviousness were fatal to the anticipation attack [224]. A broad disclosure does not anticipate a subsequent more specific claim [220], and in this case there was nothing in the prior art patents providing the requisite “clear and unmistakeable direction” that flucarbazone sodium was a selective herbicide for the control of wild oats in wheat [219], [224].

Inducement

AgraCity is a distributor of generic crop protection products, including a generic flucarbazone sodium herbicide which it sold under the name HIMALAYA. The flucarbazone sold by AgraCity was manufactured abroad by a third party and imported into Canada by AgraCity [243]. AgraCity conceded infringement and inducement [3], [83].

There was, however, an interesting issue regarding the liability of NewAgco. Pursuant to the Pest Control Products Act, companies seeking to market and sell herbicides in Canada must register the proposed herbicide with the Health Canada’s Pest Management Regulatory Agency and obtain approval of the herbicide’s proposed label, which outlines who can use the herbicide and under what circumstances it can be used [11]. NewAgco held the registration for HIMALAYA with the PMRA and its name appears on the end-use label [243]. Other than that, it appears that NewAgco has nothing to do with the manufacture, importation, or sale of HIMALAYA [240]–[246]. Aylen J held that that was not sufficient for NewAgco to be liable for inducement [246].

Remedies

Turning to remedies, Arysta sought damages only if the award would hit a specified target, defined by “displaced sales”:

[254] The Plaintiffs seek damages in the form of lost profits due to the Defendants’ sales of HIMALAYA on the basis that 90% of HIMALAYA sales displaced sales of EVEREST 3.0 AG or SIERRA 3.0 AG. In the alternative, if the Court finds that the evidence does not support a 90% capture rate, then the Plaintiffs elect a disgorgement of the Defendants’ profits on 100% of the HIMALAYA sales.

That is, Arysta sought damages, but only if they could establish on the facts that at least 90% of the sales of the infringing product by AgraCity would have been made by Arysta. This affects the quantum, as Arysta would be entitled to lost profit damages on displaced sales, but only reasonable royalty damages on other infringing sales.

Permitting Arysta to seek an accounting in the alternative in this manner appears to be contrary to AlliedSignal (1995), 61 CPR (3d) 417 (FCA) 444:

While courts of law have, for some time, given the successful party a right to elect one or the other of these two recourses, it seems clear from recent experience that the choice between the two remedies cannot be left entirely to the successful plaintiff. Moreover, it certainly cannot depend on whichever amount would turn out, on inquiry, to be more profitable. An accounting of profits is an equitable remedy which ought to be allowed by the Court in the exercise of its equitable jurisdiction when the circumstances so warrant.

The point does not appear to have been contested, so permitting Arysta to elect an accounting in the alternative is not strictly inconsistent with AlliedSignal as a matter of law. It does, however, illustrate the point that it had become routine to allow the patentee to elect an accounting, almost as a matter of right. This practice will be tested in cases involving patent assertion entities, such as Rovi Guides v BCE 2022 FC 1388, discussed here. Further, in my article on Nova v Dow 2022 SCC 43, forthcoming in the IPJ, I argue that the new approach to an accounting set out in Nova v Dow implies that the courts should take a more restrictive approach to allowing the plaintiff to elect an accounting, to ensure that it is awarded only when necessary in light of the deterrence rationale for an accounting emphasized by Rowe J.

On the facts, Arysta could not establish a 90% capture rate, and so was permitted to elect an accounting.

Obvious-to-Try Clarified

Apotex Inc v Janssen Inc 2021 FCA 45 Locke JA: Webb, Boivin JJA affg Janssen Inc v Apotex Inc 2019 FC 1355 Phelan J

            2,661,422 / abiraterone acetate & prednisone / ZYTIGA / old NOC

The invention at issue in this case relates to the use of the combination of abiraterone acetate (AA) & prednisone for the treatment of prostate cancer. Wednesday’s post provides an outline of the facts and a discussion of patentable subject-matter. This post discusses the obviousness analysis, where the main point of interest is a clarification of the obvious-to-try analysis set out in Sanofi 2008 SCC 61.

Apotex argued that Phelan J had not applied the obvious-to-try analysis correctly because he had focused unduly on the question of whether it is “more or less self-evident that what is being tried ought to work” and had erroneously considered that question to be a requirement rather than merely a factor to be considered [30]. Locke JA agreed that that question is merely a factor, not a requirement, and noted that there were passages which gave the impression that Phelan J had indeed considered this to be the overarching requirement [33]. However, on a reading of the decision as a whole, Locke JA concluded that Phelan J had properly considered all of the relevant factors [34] and he therefore affirmed Phelan J’s holding that the invention was not obvious.

Locke JA noted that some confusion was understandable, as the SCC had given “mixed signals” on the issue [36]. He pointed out that the SCC in Sanofi at [65] stated that “I am of the opinion that the ‘obvious to try’ test will work only where it is […] more or less self-evident that what is being tested ought to work.” This makes it seem that being self-evident that what is being tested ought to work is a requirement, such that if the answer is no, the invention is not obvious [36]. But the SCC at [69]–[70] clearly listed the same consideration as being simply one factor among several, which is not in itself determinative. In this decision, Locke JA reaffirmed his view, previously expressed in Hospira 2020 FCA 30 [88]–[90], that read as a whole, the SCC in Sanofi intended that whether it is self-evident that what is being tried ought to work should be considered as a factor, and not a requirement [36].

I agree with Locke JA’s analysis, which strikes me as being consistent both with the purpose of the obvious-to-try analysis and with a contextual analysis of the text. In a passage in Hospira, quoted at [31], Locke JA had pointed out that the SCC in Sanofi [66] had stated that whether it is “more or less self-evident to try to obtain the invention”—as distinct from whether it is self-evident that it will work—is a requirement. If the particular solution arrived at by the inventor was not obvious to try, then it cannot have been obvious, as the inventive step lay in the very decision to try pursuing a line of research that would not have occurred to a skilled person.

If the inventor’s solution was obvious to try, things get more complicated. One might suppose that even if the solution was obvious to try, if it was not self-evident that it ought to work, the invention would therefore be non-obvious, as there is a non-obvious step along the path from the problem to the solution. That logic supports the view that being self-evident that it ought to work is a requirement. But that logic is wrong, as is illustrated by Johns-Manville’s Patent [1967] RPC 479 (CA). The claimed invention was the use of a particular compound, polyacrylamide, as a flocculating agent for filtration of cement. Flocculating agents were well known as being useful in filtration processes generally and the possibility of using such an agent to improve filtration of cement had long been appreciated, but all those previously tried had decreased the quality of the final cement product. Polyacrylamide had been recently developed by a third party as a general flocculating agent and its use in cement filtration had been suggested. Because it was particularly effective and could be used at low concentrations, there was reason to think that it would prove useful for cement where other agents had not. However, the nature of cement making is such that nothing is certain until it is tried. It was therefore self-evident to try polyacrylamide as a flocculating agent in cement, but it was not more or less self-evident that it would work. The patentee tried polyacrylamide and found that it did indeed work without difficulty.* The Court of Appeal held the invention to be obvious: there was no invention in the decision to try, and there was no invention in getting it to work. This illustrates why being “more or less self-evident that what is being tested ought to work,” should not be a requirement; and given that Johns-Manville’s was cited with approval in Sanofi [59], [61], this reinforces Locke JA’s point that read as a whole, the SCC did not intend it to be a requirement. The flaw in the logic set out at the beginning of the paragraph lies in supposing that there must be an inventive step in carrying out an experiment, simply because the outcome cannot be predicted in advance. Johns-Mansville illustrates why that assumption is not correct.

While not a requirement, whether it is self-evident that the solution ought to work is nonetheless a factor; if the invention was obvious to try, and it was self-evident that it would work, then it is almost certainly obvious. But the converse is not true; if the invention was obvious to try, and not self-evident that it would work, the other factors come into play. If it is tried and works readily with routine methods, as in Johns-Manville, or in a routine salt-screen, then it will be obvious, even if the outcome was not predictable in advance; if it is tried and eventually works, but only after long and arduous trials, or after unforeseen hurdles are overcome, then it may not be obvious. (And because being obvious to try is a requirement, if it was not obvious to try in the first place, it will not be obvious, even if it was self-evident that it would work once the idea was conceived of.)

I must say that I have always found the discussion of the obvious-to-try analysis in Sanofi to be oddly elusive; it makes sense at first, but then the more you try to pin it down to a structured test, the less sense it makes. Locke JA’s decision is very helpful in pinning down one source of the of the confusion, and properly laying it to rest.

*In fact, polyacrylamide had not worked when the patentee had initially tried it, but it was held that it would have worked had a person skilled in the art tried it, and it was the patentee’s incompetence that had led to the initial failure. The patentee was obliged to accept this position, as the patent did not disclose the particular procedure the patentee had successfully implemented and if the procedure was not obvious then the patent would have been void for insufficiency.

Reasonable Expectation of Success: Between Boston College Doug Flutie “Hail Mary” and Wayne Gretsky “Open Net Shot”

Janssen Inc v Apotex Inc 2021 FC 7 Phelan J

            2,661,422 / abiraterone acetate & prednisone / ZYTIGA / NOC

In this decision Phelan J held Janssen’s 422 patent to be invalid for obviousness in a textbook example of the obvious-to-try analysis [198]. He held that it was not invalid for lack of utility, and that it would have been infringed by inducement if it had been valid.

The main argument was focused on obviousness and specifically the obvious-to-try analysis. The 422 patent related to the combination of abiraterone acetate (AA) and prednisone (PN) for the treatment of a prostate cancer. Both of these were known to be useful in treating prostate cancer (with PN being used for palliation rather than treatment as such) [27], [28], and the key question was whether it would have been obvious to try the combination. Phelan J held that it was obvious to try [161] and the effort needed to achieve success did not rise to the level of inventiveness [193]. Consequently, the 422 patent was invalid for obviousness [198].

In a prior decision under the old NOC regulations, 2019 FC 1355 (see here and here) rejected the invalidity attacks and granted an order of prohibition. Phelan J noted that in this action, brought under new Regulations, he had new and better evidence, and consequently his findings and analysis in that decision were irrelevant to this action: [9]–[11] and see eg [123], [161].

Phelan J’s holding turned largely on the facts, with a particularly nice application of the obvious-to-try analysis, so I’ll just note a few points that caught my eye.

Obvious to try is a factor, not the test

In the obvious-to-try analysis [134]:

whereas being “more or less self-evident to try to obtain the invention” is a requirement for obviousness to try, being “more or less self-evident that what is being tried ought to work” is not a requirement but a factor to be considered.

That is, the claims are not non-obvious merely because success was not self-evident. That is because the obvious-to-try analysis is used precisely in areas where advances are won by experiment, so that success cannot be guaranteed before trying. This point is now well-established, but it is good to see it reaffirmed.

Reasonable expectation of success is somewhere between Doug Flutie and Wayne Gretsky

In particular, the fact that clinical trials are necessary to establish that the invention will work is not determinative.

[191] It would be a concern to courts if the normal work of a clinical trial was held out to be the effort that would bar an “obvious to try” analysis. It would mean that no pharmaceutical treatment which would otherwise be obvious to try would ever meet the Supreme Court of Canada’s fourth step because regulatory approval would trump patent law.

On the expectation of success, Phelan J remarked:

[135] As to “ought to work”, it is clear that certainty of success is not required otherwise there would be no point in describing it as something “to try”. “Trying” implies the possibility of failure but with the expectation of success. While never easy to define on a spectrum of likely success, it is neither a Boston College Doug Flutie “Hail Mary” pass nor a Wayne Gretsky “open net shot”. Some limited experimentation is permitted in the context of the second factor. It is not to be arduous, inventive or unusual.

Not new law, but a fun way to state the test.

Golden bonus

The “golden bonus” principle was also raised, albeit indirectly. The ultimate goal of any cancer treatment is to improve survival, but that is difficult to measure directly in research because the only way to determine survival benefit is for the patient to die [23]. Presumably, gathering statistics on that basis would take too long. So a surrogate in the form of some anti-tumour or anti-cancer activity is used. Janssen argued that the combination of AA and PN was not obvious because there was no evidence of survival benefit for either individually. Phelan J rejected this in part because (my emphasis):

[179] If the search for survival benefits was as important as suggested, the positive anti-cancer effects of each drug outlined above in conjunction with O’Donnell 2004 provided good reason for a POS to combine AA and PN. The inventors do not have to be seeking the same solution as the eventual patent discloses (Hospira FCA [2020 FCA 30], para 94).

I take it that this is related to the “golden bonus” point noted in last Friday’s post: if an invention is obvious to try for one reason, it does not become less obvious because it turns out to have some unexpected advantage.

Apotex got caught in a squeeze in its utility attack, as “much of the evidence on which it relies for Obvious to Try supports the utility of the Patent” [203]. That’s not a bad squeeze to be in, given that they succeeded on obviousness. In holding the invention to be useful Phelan J noted that “ For purposes of utility, it is not necessary to meet Guidelines or FDA approvals. Utility is met if some patients, even if only those in dire circumstances, respond” [209].

Courts should be cautious on patentability of methods of medical treatment

Apotex also raised an attack based on patentable subject matter. Phelan J noted that “The arguments of both parties on this issue of unpatentable subject matters are confusing and difficult to consider” [216]. Perhaps this is because the law itself is confusing, as the FCA recently recognized in Hospira. Accordingly, Phelan J noted that “The issue of method of medical treatment is not a settled one and therefore a court should be cautious in striking down claims on this basis” [223]. This strikes me as salutary advice.

Product Monograph important in establishing inducement

Given his holding on validity, it was unnecessary for Phelan J to consider infringement, but he did so nonetheless, in order to facilitate the inevitable appeal [19]. He found that if the patent were valid, Apotex would infringe by inducement by the sale of their AA product “indicated in combination with prednisone for the treatment of metastatic prostate cancer” [246]. This finding was based in large part on Apotex’s draft Product Monograph, which directed use in a manner consistent with the asserted claims [245]–[260]. This is consistent with many prior cases, but it is nonetheless worth reiterating the importance of the PM in respect of inducement.

Do physicians read the PM?

Apotex apparently tried to get around this by arguing that their product would not be used for anti-cancer treatment, as specified in some of the asserted claims, but for other purposes, such as controlling side effects. Phelan J rejected this, in part because (my emphasis):

[250] In their draft Product Monographs the Defendants cite a number of References (publications such as de Bono 2011, the Attard Reports) which address PN contributing to anti-cancer effects of the combination with AA. PN’s role in mitigating side effects is also contained in the References. It is no answer to say that although the Defendants put the References in the Product Monograph, they do not expect the doctors or pharmacists to consider them.

Despite Phelan J’s apparently rhetorical point, I’ll note that there are a number of cases calling into doubt whether doctors or pharmacists consider the PM itself, particularly the generic PM, much less the references found in it: see Solvay 2008 FC 308 [192]; Aventis 2006 FC 861 [44]; Abbot 2006 FC 1411 [40] affd 2007 FCA 251 [26]; Allergan 2011 FC 1316 [161]. Of course, these cases can be distinguished because there was evidence on this issue, and there does not appear to have been similar evidence in this case. Nonetheless, Phelan J’s remark does make the point that it is very counter-intuitive to argue that while the PM directs infringement, that’s permissible, because no one reads it anyway. On that note, I’ll plug my draft article “Is 'But For' Causation Necessary to Establish Inducement?” which argues that the way to resolve this difficulty is to recognize that “but for” causation is not required in the second stage of the inducement test. This article has been on the back burner for too long, and I hope to return to it soon. Here’s the abstract:

The established Weatherford test for inducing patent infringement requires, as its second branch, that inducement by the indirect party be the “but for” cause of the direct infringement. This article shows that such a requirement of “but for” causation leads to problematic results, particularly when the evidence indicates that the direct infringers do not heed the encouragement provided by the indirect party. The article argues that while the “but for” causation requirement is often stated, it has rarely actually been applied, and there are several cases which suggest a less stringent requirement. This article argues that the best way to reconcile the cases is to recognize that causation in the second branch of the inducement test may be established on the basis of material contribution, rather than “but for” causation, while also recognizing that “but for” causation remains necessary for an award of any monetary remedy. This approach, combining material contribution as the substantive causation requirement at the second stage of the inducement test, with “but for” causation in awarding monetary remedies, also appropriately balances the policy concerns of ensuring effective enforcement of the patentee’s rights while avoiding the problem of overbroad enforcement.

Open question whether claim of invalidity can be consolidated with a NOC action

Finally, Phelan J noted an unsettled procedural point. Apotex has alleged in a counterclaim that claims that were not asserted by Janssen were also invalid. Section 6(3)(a) of the Regulations allows the second person to bring a counterclaim for a declaration of invalidity “in respect of any patent claim asserted in the action.” A counterclaim is a separate action, and while s 6(3) “allows a party the convenience of bringing a challenge to a patent in the context of an NOC action in respect of asserted claims,” it is restricted to the claims asserted in the action [234]. “Whether a separate claim of invalidity could be consolidated with a NOC action remains an open question” [234].

The Limits of Anticipation by Speculation

Teva Canada Innovation v Pharmascience Inc 2020 FC 1158 Kane J

2,702,437 / 2,760,802 / glatiramer acetate / Copaxone / Glatect / NOC

The patents at issue in this case relate to the use of glatiramer acetate for the treatment of multiple sclerosis [MS]. Glatiramer acetate was known to be effective in treating MS, with a standard dose of 20mg daily, administered by subcutaneous injection. The 437 patent claims the early use of glatiramer acetate for the purpose of delaying the development of MS, while the 802 patent claims a dosing regime of 40mg three times a week. The decision turned largely on the facts (to the tune of 936 paragraphs!), but a few points of interest were raised, particularly in the discussion of the 437 patent, which Kane J held to be novel, but invalid for obviousness. Kane J's holding that the 802 patent was not invalid for obviousness or lack of utility, and that it would be infringed by Pharmascience's 40mg product, turned on the facts.

MS is a disease of the central nervous system in which the patient’s own immune system attacks the myelin of the CNS. The early course of the disease is characterized by intermittent attacks, which include episodes of numbness, muscle weakness and spasticity, etc [73]. The disease also gives rise to lesions on the CNS resulting from destruction of the myelin sheath [71]. Patients who present with a single clinical attack having features typical of MS were considered to have a “clinically isolated syndrome” (CIS) [77]. CIS patients are at elevated risk for MS itself (also referred to as “clinically definite MS” or CDMS), but not all CIS is caused by MS, so CIS patients are not considered to actually have MS.

The inventive concept of the 437 patent is that glatiramer acetate could be used to delay the onset of clinically definite MS in CIS patents at risk of developing MS [569]. Accordingly, Claim 1 was to glatiramer acetate “for use in delaying the onset of clinically definite multiple sclerosis,” in a patient who presents with at least one lesion “suggestive of multiple sclerosis” and who is “at risk of developing” clinically definite MS, and “prior to development of clinically definite multiple sclerosis” [251].

The claim construction debate turned on the fact that around the time of filing, in 2007, the criteria for diagnosing MS were changing. The older Poser criteria relied on clinical signs, ie two clinical attacks. The new McDonald criteria were developed to take advantage of the use of MRI for diagnosis using direct detection of lesions characteristic of MS with less reliance on clinical signs. The result is that some patients who would not have been diagnosed as actually having MS using the Poser criteria, would be diagnosed as having it using the McDonald criteria. The 437 patent was apparently developed with the Poser criteria in mind and there was a long and involved argument as to whether the patients with MS according to the McDonald criteria would be included in the claim; if so, the claim would not be novel, as the use of glatiramer acetate for treating MS was known [305].

I must admit that I was having trouble following the argument and its significance, and I was relieved when Kane J stated that “In my view, far too much time and effort was devoted to debating the meaning of the terms, the evolving diagnostic criteria and the scope of the patients covered by the claims” [306] . All the experts construed the claims in accordance with their plain language, which did not specifically refer to either set of criteria by name, and “the claims mean what they say” [307]. Kane J held that on a plain reading of the claims they were directed to a patient who did not already have a confirmed diagnosis of MS, and so did not include patients who already met the McDonald criteria [329]. This reading seems eminently sensible to me. The result of this claim construction holding was to negate both anticipation based on the Pinchasi 2007 prior art [454] as well as the Gillette defence [396], [403].

In light of this conclusion on claim construction, the more interesting anticipation argument was based on the Karussis 2006 prior art. This was a report of an International Working Group for Treatment Optimization in MS [458]. The report suggested the use of therapies approved for treatment of MS itself, which prominently includes glatiramer acetate, as a possible treatment for patients at risk of developing MS (ie, those with CIS), but acknowledged that this was an inference and was not based on evidence [464], [465]. So, the Working Group concluded that “as [other therapies] and glatiramer acetate have been shown to be effective in [the most common form of diagnosed MS], and a patient with a CIS is highly likely to progress to MS, it is reasonable to propose early treatment with [therapies approved for treatment of MS] at the doses approved for MS, even though there is not yet evidence to support this approach” [465]. The question is whether this and similar statements anticipated the claims of the 437 patent.

This raises the issue of what I have called “anticipation by speculation,” as raised in Hospira 2020 FCA 30 and Biogen v Taro 2020 FC 621, which held that similarly speculative statements were anticipatory. As discussed here and here, my view is that Hospira and Biogen v Taro stretched anticipation to the very limit, and perhaps beyond. In this case, Kane J held that Karussis 2006 was not anticipatory. This is not to say that Kane J’s holding is necessarily inconsistent with Hospira and Biogen v Taro, which Kane J considered and distinguished on the facts: [479]–[482]. I won’t go through all the particular grounds, though I will say that the distinctions she draw struck me as generally reasonable; as always in borderline cases, some of the distinctions to be drawn will necessarily be fine and turn on the particular facts. The broader point is that Kane J’s holding illustrates that anticipation by speculation can only be pushed so far and the line is somewhere in this general vicinity.

One general observation made by Kane J is worth pointing out (my emphasis):

[484] In my view, if Karussis 2006 is anticipatory art, what would prevent a group of experts in any field from having discussions and speculating on the positive outcome of a clinical trial in progress, developed and implemented by others, in order to later argue that their speculation that the trial in progress would be successful anticipated the claims of a patent that are based on such clinical trials. This approach seems to be inconsistent with the objectives of the experimental use exemption established in the common law.

[485] As noted by Teva, the law recognizes that there is no disclosure for the purposes of anticipation where a prior use is experimental. If a patent cannot be anticipated by its own clinical study, in my view, it cannot be anticipated by the speculative recommendations of a group of experts who discuss the state of MS treatment, note the lack of evidence, and note that trials are underway.

Kane J then went on to hold that Karussis 2006 did not in any event satisfy the enablement branch of anticipation: [486]–[493].

All that was for nought, so far as Allergan is concerned, as Kane J then went on to find the 437 patent invalid for obviousness on an obvious-to-try analysis. This is likely to be common in cases where a clear suggestion to try the invention can be found in the prior art, especially since the holding in Hospira 2020 FCA 30 that the state of the art for purposes of an obviousness attack includes all prior art. Exactly where we draw the line on anticipation is now less important, because if an obscure piece of prior art does not quite reach the level of anticipation, it can still be used as the basis for an obviousness attack. With that said, it does not appear that the Hospira rule made any difference in this case; while Karussis 2006 was not common general knowledge, it reflected several studies that were [573].

I’ll finish with two quick points on obviousness.

First, Kane J clearly stated that the mere fact that it is not self-evident that the invention will work, before any experiments are undertaken, does not mean that it is not obvious.

[593] Dr. Selchen’s opinion that the invention was not self-evident appears to conflate the obvious to try test with the factor or consideration that informs the test, i.e., whether it was self-evident that it would work, in the sense of being effective for CIS patients to delay the onset of MS and achieve the other claimed benefits.

I entirely agree with Kane J on this, but it is a point that continues to pop up and cause confusion, as it did for Dr Selchen in this case.

Second, Kane J recognized and applied the “golden bonus” rule, usually traced back to Hallen v Brabantia [1991] RPC 195, 216 (CA), which says that if an invention is obvious for one reason, it does not become non-obvious merely because it has some non-obvious benefits (the "golden bonus"):

[594] Teva’s submission – that the therapeutic benefits or outcomes of the ‘437 Patent were not obvious or expected – does not diminish that the invention was obvious to try. In Janssen [2015 FC 184] at para 100 [see here], the Court explained, that “if a patentee obtains a workable formulation, the later discovery of one of its inherent characteristics does not add anything inventive to what had already been discovered: see Alcon Canada Inc. v Apotex Inc., 2012 FC 410 at para 45, [2012] FCJ No 1707 (QL).” In the present circumstances, once the POSITA pursued the use of glatiramer acetate for CIS patients, the claimed benefits would follow.

As Kane J notes, this is not an entirely new development in Canadian law, but it is nonetheless welcome to see the point expressly recognized and affirmed. I believe that this is the first time that the phrase “golden bonus” has actually been used in a Canadian case [510].

Filgrastim Patent Obviousness Upheld on the Facts

Amgen Inc v Pfizer Canada ULC 2020 FCA 188 Stratas JA: Gleason, Laskin JJA aff’g 2020 FC 522 Southcott J

1,341,537 / filgrastim / NEUPOGEN / NIVESTYM

Southcott J at first instance in this NOC decision found Amgen’s 537 patent to be obvious on an obvious-to-try analysis in a decision that turned almost entirely on the facts. The FCA has now upheld that the decision, largely on the usual basis that read holistically, there was no overriding error, and it is not the FCA’s role to re-weigh the evidence [12]. The FCA then went further and specifically approved Southcott J’s decision, saying that even if it had reviewed the evidence de novo, it would have come to the same conclusion [13]. The FCA commended Southcott J’s analysis, saying “we consider the Federal Court’s reasons worthy of recognition for their attention to detail, their careful analysis of the rival experts and the thorough analysis throughout.

“Obvious-to-try” and “Obvious to Try”

Amgen Inc v Pfizer Canada ULC 2020 FC 522 Southcott J
            1,341,537 / filgrastim / NEUPOGEN / NIVESTYM

In this NOC action, Southcott J found Amgen’s 537 patent to be obvious on an obvious-to-try analysis in a decision that turned almost entirely on the facts. The patent at issue is governed by the old Act [10]; it was filed in 1986, claiming priority from an August 1985 US application, and was issued in 2007 – more than twenty years after its priority date. This in itself illustrates a glaring deficiency of the old Act; if the 537 had been valid, it would be unconscionable if a 35 year old invention could be used to impede current drug development.

The patent relates to a filgrastim, a hematopoietic growth factor, which stimulates the growth of white blood cells [11]. It is used to boost the immune system in cancer patients whose natural immune system has been compromised by chemotherapy [149]. Filgrastim is a recombinant DNA version of the naturally occurring “granulocyte colony-stimulating factor” or “G-CSF” [12]. The key moment in the development of filgrastim was the discovery by scientists at the Sloan-Kettering Institute that a protein secreted by a certain human bladder carcinoma cell line had a stimulatory effect on blood cell precursors. This work was published by Welte in March 1985 [24]. The Amgen scientists built on Welte by identifying and sequencing the associated gene and using recombinant DNA technology to express it in a host cell to allow production of clinically useful quantities of G-CSF [25]. It was largely uncontested that it was obvious to try making a recombinant G-CSF in light of Welte, and the real question was whether there was any inventive step required to actually do so. Southcott J ultimately held that the path forward was known at the time, and there were no hurdles that required inventive ingenuity to surmount.

I have little doubt that if, instead of publishing, Welte et al had developed their discovery into a recombinant G-CSF, their invention would have been patentable, with the inventive step lying in the identification of the naturally occurring protein and its properties. On the other hand, while the work done by Amgen was, in one sense, routine, it may be doubtful whether any institution would have actually carried it out without the lure of a patent. Thus the broad underlying issue strikes me as a version of the problem addressed by the Bayh-Dole Act; even if the true inventive step is undertaken at a university research lab, or some similar institution, and introduced into the public domain, some kind of IP rights may nonetheless be needed to incentivise the additional steps needed for commercialization. In principle that incentive may be provided by data exclusivity; in any event, a monopoly on products produced 35 years later is clearly not the right solution.

Doctrinally, Southcott J’s decision strikes me as a careful application of the obvious-to-try analysis. At the risk of sounding like a broken record, I’ll recapitulate my views on the obvious-to-try test, and show how Southcott J’s analysis is a good example. It’s a bit unfortunate that “obvious-to-try” has become the name of a doctrine, as opposed to a string of words with their ordinary meaning. I will distinguish “obvious-to-try” as the doctrine, from “obvious to try” as words with the ordinary meaning that it was obvious to try whatever it was, without any implication that the invention was obvious or not.

While “inventive step” and “obvious” are two sides of the same coin, the analysis is much easier if we approach it in terms of inventiveness. There are two questions: (1) Was it inventive to think of even trying the claimed invention as a solution to the problem at hand? If yes, then it was inventive, regardless of how easy it was to implement the solution: see eg Tye-Sil (1991) 35 CPR(3d) 350 (FCA). If the answer to (1) is no (ie it was obvious to try), then (2) was there an inventive step in achieving success? If the answer to (2) is yes, then invention is not obvious, regardless of how easy it was to think of trying it in the first place. If the answer to both these questions is no — it was not inventive to try and there was no invention in achieving success — then there was no inventive step anywhere along the path, which is to say that the invention was obvious. I acknowledge that this is not the way the “test” was laid out in Sanofi 2008 SCC 61, [69], but I suggest it is consistent with Sanofi.

Southcott J identified three “factors” from Sanofi [69]: namely Motive [291ff]; whether it was self-evident that what being tried ought to work (Self-Evident Factor) [296ff]; and Extent of the Effort [367ff]. The Motive factor goes to the first question, whether it was obvious to try the invention. It was not really contested that there was specific motivation in 1985 to make a recombinant G-CSF in light of Welte. While Southcott J remarked that “the Motive Factor is only one factor and is not determinative” [296], he later [322] invoked the statement by the FCA in Hospira FCA, 2020 FCA 30 [90] that (my emphasis):

It should be noted that, whereas being “more or less self-evident to try to obtain the invention” (per Sanofi at para. 66) is a requirement for obviousness to try, being “more or less self-evident that what is being tried ought to work” (per Sanofi at para. 69) is not a requirement but merely a factor to be considered.

I have to admit that I overlooked this paragraph in my post on Hospira, but I now see its importance in establishing that the three factors — Motive, Self-Evident and Extent of the Effort — should not be seen as three factors going into the same hopper to be blended together: Motive is a requirement, while Self-Evident is not.

This makes sense in light of the two-step approach outlined above. The first phrase in the statement by the FCA is to the effect that if it is not “more or less self-evident to try to obtain the invention,” then the invention is not obvious. This goes to question (1): if there was an inventive step involved in the decision to try the claimed invention, then the invention is not obvious; that is why being more or less self-evident to try is a requirement for obviousness. So, keeping in mind the distinction between “obvious-to-try” and “obvious to try,” we can say that if the invention is not obvious to try, then it is not obvious-to-try, which means it is not obvious.

But the converse is not true; simply because an invention is obvious to try, does not mean it is obvious-to-try; we have to go on to question (2) and look at the other factors to see whether there was an inventive step involved in achieving success. This is why, as the FCA noted, the Self-Evident factor is not a requirement. Accordingly, Southcott J treated the Self-Evident Factor and the Extent of Effort Factor as distinct factors, neither of which is determinative. It may be that it is more or less self-evident that what is being tried ought to work, given expenditure of sufficient effort and resources, and yet at the same time, “the experimentation prolonged and arduous, such that the trials would not be considered routine” Sanofi [69]; and see similarly Halocarbon [1979] 2 SCR 929, 944: "A patient searcher is as much entitled to the benefits of a monopoly as someone who hits upon an invention by some lucky chance or inspiration".

On the facts, Southcott J’s conclusion on the Self-Evident factor is that it would be self-evident that the steps leading to the claimed invention polypeptide ought to work [366]. On the Extent of Effort, he concluded that “Any potential challenges [the skilled person] would encounter could be addressed with skill and did not require inventiveness” [425]. I like this way of putting it because he phrases it in terms of inventiveness, which I find more intuitive in this context. Putting these together, (1) there was no inventive step in the decision to try the claimed invention — it was obvious to try; and (2) there was no inventiveness required in achieving success — it was (i) self-evident that it would work (ii) without undue effort; and therefore the invention was obvious-to-try and therefore obvious.

Obvious to Try Does Not Require That it Is Obvious That What Is Being Tested Will Work

Hospira Healthcare Corporation v. Kennedy Trust for Rheumatology Research 2020 FCA 30 Locke JA: Rivoalen, Nadon JJA var’g 2018 FC 259 Phelan J
            2,261,630 / infliximab / INFLECTRA

There is some confusion in the obvious-to-try test as discussed in Sanofi 2008 SCC 61. At one point the SCC stated that

[65] I am of the opinion that the “obvious to try” test will work only where it is very plain or, to use the words of Jacob L.J., more or less self-evident that what is being tested ought to work.

This lends itself to the view that it must be self-evident, prior to any experimentation, that the claimed invention will solve the problem at hand. But there is a second understanding of the obvious-to-try test that emerges from the very next paragraph, where the SCC went on to say (my emphasis):

[66] For a finding that an invention was “obvious to try”, there must be evidence to convince a judge on a balance of probabilities that it was more or less self-evident to try to obtain the invention. Mere possibility that something might turn up is not enough.

This implies that it must be more or less self-evident to try, not more or less self-evident that what is being tried will work.

In my view, the latter interpretation is preferable. As the SCC noted at [68], the obvious to try test is appropriate “[i]n areas of endeavour where advances are often won by experimentation.” In such fields, a test requiring that it is very plain, prior to any experimentation, that the invention would work, would mean almost nothing would be obvious. On the second interpretation of Sanofi, if something is obvious to try, and when tried, it works without difficulty, there is no inventive ingenuity involved in arriving at the invention, even though the result could not have been predicted in advance. So, if a routine salt screen discloses that the maleate salt of a new pharmaceutical has good manufacturability, that might not support a patent to the maleate, even though it could not have been predicted in advance that the maleate would be better than any other pharmaceutically acceptable salt.

As I have discussed in previous posts (here and generally here), the Federal Court has quite consistently applied the second approach to the obvious-to-try test, under which an invention might be considered obvious even though a successful outcome could not have been predicted in advance.

In this case, Phelan J appeared at some points to apply the first approach, saying that “Although the POSITA may have had “good reason” to pursue the combination of anti-TNF-α and MTX, it was not self-evident that this combination would work to solve the problem identified in the prior art” [226] (and see similarly 228].) The FCA disapproved of this statement, with Locke JA saying at [94]:

[T]his factor is not determinative. The other factors also required consideration. In my view, the Judge’s analysis of the second factor (concerning the extent, nature and amount of effort required to achieve the invention) was inadequate.

This means that the mere fact that a successful outcome could not have been predicted in advance does not mean that the invention is not obvious under the obvious-to-try test. This is a welcome affirmation from the FCA that the second approach to the obvious-to-try test that I have outlined above is indeed preferable.

However, the FCA went on to say (my emphasis) that:

[95] The determinative test on this issue is whether it was more or less self-evident to try to obtain the invention, including co-administration of an anti-TNF-α antibody and MTX to treat RA in MTX IRs.

This implies that if an invention was obvious to try, it will necessarily be obvious under the obvious to try test. The statement that this is the "definitive test" is difficult to reconcile with the SCC’s statement in Sanofi at [64] that ”the ‘obvious to try’ test must be approached cautiously. It is only one factor to assist in the obviousness inquiry.” Similarly, the SCC remarked that "obvious to try” is “not a mandatory test,” but rather “one factor of a number that should be considered, having regard to the context and the nature of the invention” [62]. So, I would suggest that if a particular avenue is obvious to try, and it eventually succeeds, but only after prolonged and difficult experimentation, it may well be inventive even though it was obvious to try. [Update: On re-reading, I think that Locke JA meant only that this was the determinative test on the facts of this case, not that it is the determinative test generally.] 

On the facts, I would note that while at places Phelan J did indicate that the invention was not obvious to try simply because it was not self-evident that it would succeed, other statements can be taken to imply it was not obvious even to try (see esp [223]).

Both Phelan J [24] and Locke JA [15] remarked on the vast array of issues raised by Hospira, to the extent that Locke JA stated that “it will not be practical to address each one specifically” [15]. I can only suppose that as a consequence, the submissions weren’t as fully prepared as they would have been if the arguments had been more carefully focused, and I can’t help but feel that this is reflected in the reasons.

Arginine Salt Obvious to Try

Les Laboratoires Servier v Apotex Inc 2019 FC 616 Roy J
            2,423,825 / perindopril arginine / VIACORAM / NOC

The most interesting aspect of this decision concerns overbreadth, which was also raised in another decision released last week, Aux Sable 2019 FC 581. I’ll deal with overbreadth in a subsequent post. This post provides an overview and deals with the finding that the invention was obvious.

Perindopril is used for treating hypertension and related cardiovascular disorders. Servier invented perindopril in the early 1980s, and ultimately received Canadian patent 1,341,196 for the compound per se [9], which it marketed as the erbumine salt under the brand name COVERSYL [10]. The 196 patent expired in March of 2018. The erbumine salt had stability problems, particularly in hot and humid conditions, that adversely affected shelf life [15], [34]. These problems had been raised early on in the development of perindopril. At that time one of the inventors of the 825 patent had suggested pursuing alternative salt forms and did some preliminary experiments with the arginine salt. However, pursuing a different salt form was not a priority for Servier, which initially dealt with the stability problem by using “tropicalized” packaging for some countries [31], and accepting a limited 2 year shelf life. Eventually though, in the late 1990s, Servier decided to pursue a new salt form, and returned to further development of the arginine salt. In 2002 Servier filed the application which matured to the 825 patent. Claim 1 is to the arginine salt of perindopril and its hydrates (“Sel d'arginine de périndopril ainsi que ses hydrates”). Servier markets the arginine salt as VIACORAM. Apotex, wishing to sell a generic version of perindopril arginine, which it concedes will infringe the 825 patent, attacked the validity on a variety of grounds, including obviousness and overbreadth [5]-[6].

The obviousness attack succeeded, on a fairly straightforward application of the obvious-to-try test. There was no real difficulty in testing and making the arginine salt, so the real question was whether selecting it to try involved inventive ingenuity. At the time the inventors had initially suggested the arginine salt, they had never heard of it being used to to form a salt of an active ingredient [31], and Roy J remarked that the decision, at the time, may have involved a spark of ingenuity [244], [252]. However, that was in the early 1980s and salt screen methods had moved on by the claim date in 2002. Roy J accepted the evidence of Apotex’s expert that a routine structured salt screen would have succeeded in identifying perindopril arginine as a suitable salt. In particular, the expert  identified arginine as one of only nine salt formers that would be selected for the initial structured salt screen [286].

One point that I found a bit confusing is that Roy J referred to Apotex’s expert as having been “blinded” [140], [290], and “truly blind” [292], but his expert report appears to take into account the particular properties of perindopril in identifying suitable salt formers for the initial screen [286]. In any event, it appears that by 2002 arginine was fairly commonly used as a salt former [292], [294].

I would also note that Roy J interpreted the principle that it should be “more or less evident that what is being tried ought to work,” as meaning that there should be a high expectation that a salt screen would identify a suitable salt, and not that there should be a high expectation that the arginine salt itself would work [285].

UKSC Weighs in on Obvious to Try and Golden Bonus

Actavis v ICOS [2019] UKSC 15 (27 March 2019) Lord Hodge: Lady Hale, Lords Kerr, Sumption, Briggs aff’g [2017] EWCA Civ 1671 Kitchin LJ: Lewison, Floyd LLJ rev’g [2016] EWHC 1955 (Pat) Birss J

EP (UK) 1,173,181 / tadalafil dosage / CIALIS

In Actavis v ICOS the UKSC has affirmed the decision of the EWCA holding ICOS’s dosage patent for tadalafil to be obvious on an obvious-to-try analysis. As discussed here, the EWCA decision was consistent with the way the obvious-to-try analysis has consistently been applied by the Federal Courts. The decision of the UKSC provides further reassurance, if any was needed, that the Canadian approach is sound. Along the way, the UKSC expressly affirmed the “golden bonus” rule: if a particular invention is obvious for one reason, it does not become non-obvious simply because it had additional unexpected or non-obvious advantages.

The obvious-to-try analysis was endorsed by the SCC in Sanofi 2008 SCC 61, where the Court stated that:

[65] I am of the opinion that the “obvious to try” test will work only where it is very plain or, to use the words of Jacob L.J., more or less self-evident that what is being tested ought to work.

This might lend itself to the view that it must be self-evident, prior to any experimentation, that the claimed invention will solve the problem at hand. But the Court immediately went on to say that for an invention to be “obvious to try”, there must be evidence that it was “more or less self-evident to try to obtain the invention” [66]. That is, it is trying that must be self-evident, not that that the specific claimed invention would work. In Actavis v ICOS, the UKSC addressed exactly this question.

The facts in Actavis v ICOS are simple, and raise a paradigmatic version of the obvious-to-try analysis. The key claim was to a 5mg daily dose of tadalafil for the treatment of ED.^* Tadalafil was known to be an effective oral treatment for ED, but the optimal dosage was not part of the the prior art [23]. It was obvious to carry out a dose-ranging study to determine the appropriate dose. The initial dose ranging study would be of on demand dosing using 25, 50 and 100mg doses. This study would have revealed a therapeutic plateau in that range [35]-[36]. Birss J held that it was “very likely” that a skilled team would then investigate lower doses. Both the EWCA and the UKSC treated this “very likely” finding as meaning that it would have been obvious to do so; ie, that it would have been obvious to try lower doses. Birss J held that if they had done so they would have discovered that a 5mg dose tadalafil was efficacious and had reduced side effects; that is, the posita would have discovered the invention. There would, however, have been no prior expectation that a dose of 5mg would have been efficacious; on the contrary, it would have been surprising that such a low dose would be effective [37]. It would have doubly surprising that the 5mg dose also had reduced side-effects [37].

Birss J held that claims at issue to be non-obvious, essentially because “the claimants failed to prove that efficacy at 5mg tadalafil was predictable or worth considering by the skilled team based on the properties of tadalafil as compared to sildenafil,” and “[a]ssuming a 5mg/day dose of tadalafil was tested, it would not be tested with a reasonable expectation of success” [38]. In other words, Birss J held that the 5mg dose was not obvious because, if the skilled team had been asked, prior to testing, whether a 5mg dose would have been efficacious, the answer would have be "probably not". In Birss J's view, the conclusion of non-obviousness followed notwithstanding that the entire course of research leading to the invention would have been obvious to try. The EWCA reversed, and Lilly (the exclusive licensee), appealed.

The key question was summarized in Lilly’s central submission [50]:

the question which the Court of Appeal should have asked was whether at the priority date, before the skilled team embarked on its investigation, it was obvious in the light of [the knowledge that tadalafil is effective for treating ED], and without knowledge of the alleged invention, that a 5mg per day dose of tadalafil would be a safe and effective treatment, with minimal side effects, for sexual dysfunction.

That is, the invention is not obvious unless there would be a reasonable expectation, prior to undertaking the dose-ranging study, that the 5mg dose would work. A reasonable expectation that some minimum dose would be safe and effective, and that the minimum could be determined from a dose-ranging study, would not suffice, unless there was a reasonable expectation that the 5mg dose in particular would work.

The UKSC rejected this submission [52]: “uninventive steps which the skilled team would take after the priority date to implement the [knowledge that tadalafil is effective in treating ED] are not excluded from consideration in assessing the obviousness of the alleged invention at the priority date” [59]. On the facts, the UKSC affirmed the EWCA in holding the patent to be obvious [105]. This is a clear holding that the mere fact that there would be no reasonable prior expectation that the particular claimed invention – the 5mg dose – would work, does not in itself mean the invention is non-obvious.

The UKSC elaborated with nine points.

First, “it is relevant to consider whether at the priority date something was ‘obvious to try’” [65]. I take this to mean the same as the SCC meant in Sanofi when it held at [64] that the “obvious to try” inquiry is one factor to be considered in the obviousness inquiry. An invention which is obvious to try is not necessarily obvious for that reason alone, as there may be invention in getting it to work.

The second point was that “the routine nature of the research and any established practice of following such research through to a particular point may be a relevant consideration” [66]. Even if it was not obvious in advance that the invention would work, it may nonetheless be obvious, if the route to success was obvious to try, and there were no difficulties along the way requiring invention. The Court continued by saying that this is “weighed against the consideration that the claimed process or product was not obvious to try at the outset of a research programme” [66]. This is a bit obscure to me. The point appears to be that the fact that the particular claimed product – the 5mg daily dose – was not obvious to try at the outset is a consideration. I’m not sure why that should be a consideration, as the premise here is that the specific claim product would not have been predicted in advance, even though it was the outcome of a routine investigation.

“Thirdly, the burden and cost of the research programme is relevant” [67]. The parallels the Sanofi factor asking as to the “extent, nature and amount of effort required to achieve the invention? Are routine trials carried out or is the experimentation prolonged and arduous, such that the trials would not be considered routine?” [69] Even trials that are technically routine might nonetheless rise to the level of invention if sufficiently arduous: “A patient searcher is as much entitled to the benefits of a monopoly as someone who hits upon an invention by some lucky chance or an inspiration” (Halocarbon [1979] 2 SCR 929).

“Fourthly, the necessity for and the nature of the value judgments which the skilled team” [68]. Routine work is no longer routine if it requires extensive exercise of judgment.

“Fifthly, the existence of alternative or multiple paths of research will often be an indicator that the invention contained in the claim or claims was not obvious” [69]. Again, this corresponds to Sanofi (by coincidence also at [69]): “Are there a finite number of identified predictable solutions known to persons skilled in the art?”

“Sixthly, the motive of the skilled person is a relevant consideration. The notional skilled person is not assumed to undertake technical trials for the sake of doing so but rather because he or she has some end in mind. It is not sufficient that a skilled person could undertake a particular trial; one may wish to ask whether in the circumstances he or she would be motivated to do so” [70]. The invention may lie in the decision to try a pursue a particular line of investigation, even if the inquiry is routine after that decision is made. Put another way, an invention that is not obvious to try, is not obvious under the obvious to try test. The invention may lie either in the decision to pursue a particular line of inquiry, or in overcoming obstacles along the way.

“Seventhly, the fact that the results of research which the inventor actually carried out are unexpected or surprising is a relevant consideration as it may point to an inventive step, at least in so far as it suggests that a test was not obvious to try or otherwise the absence of a known target of the research which would make it less likely that the skilled person would conduct a test” [71]. I take this to be related to the previous point. Mere unexpected results – as on the facts, the unexpectedly low effective dosage – does not establish non-obviousness, but the unexpected nature of the results may be relevant to the extent that it supports a finding that the inquiry was not obvious to try in the first place.

“Eighthly, the courts have repeatedly emphasised that one must not use hindsight, which includes knowledge of the invention, in addressing the statutory question of obviousness” [72]. This point is very well recognized by the Canadian courts.

The ninth point is particularly significant, as it is the first time, to my knowledge, that the UKSC has expressly affirmed the “golden bonus” rule. If a particular invention is obvious for one reason, it does not become non-obvious simply because it had additional unexpected or non-obvious advantages. The leading case is Hallen & Co v Brabantia (UK) Ltd [1991] RPC 195 (EWCA), in which it was obvious to coat a corkscrew with slippery PTFE in order to aid its penetration into the cork. The EWCA held that the invention did not become non-obvious simply because it turns out that it also had a non-obvious benefit of improving extraction of the cork. That holding has now been approved in principle by the UKSC [73], and also apparently applied it on the facts, as the 5mg dosage had a surprising beneficial property of minimal side effects, which nonetheless did not make that dosage regime an invention [31].

While the UKSC held the claims at issue to be obvious, the Court took pains to say that dosage patents are not suspect per se, approving the view that: “there [is] no policy reason why a novel non-obvious dosage regime, which was the product of expensive and unpredictable research, should not be rewarded with a patent of a Swiss-form claim” [76], [103]. Moreover, there is no general rule “that the product of well-established or routine enquiries cannot be inventive” [103]. 

It should not be very surprising that the SCC and UKSC jurisprudence on obvious-to-try are consistent, given that the SCC in Sanofi relied heavily on the prior UK case law. It is nonetheless reassuring that a consistent body of jurisprudence has developed, as this indicates that the charted path was the right one.

*The representative claim was Claim 7, which was effectively to a dosage form of tadalafil suitable for oral administration up to a maximum total dose of 5 mg per day, for the treatment of sexual dysfunction.

Crystalline Form Not Obvious to Try

Apotex Inc v Pfizer Canada Inc 2019 FCA 16 Boivin JA: Webb, de Montigny JJA aff’g 2017 FC 774 Brown J
Teva Canada Ltd v Pfizer Canada Inc 2019 FCA 15 Boivin JA: Webb, de Montigny JJA aff’g 2017 FC 777 Brown J

2,436,668 / desvenlafaxine (ODV) / PRISTIQ / NOC

In ODV the FCA has affirmed Brown J’s finding that Claims 8 and 9 of the ‘668 patent, to Form I ODV succinate (a particular crystal form of a particular salt of the compound ODV), were not obvious. The decision turns on the obvious-to-try analysis: see here for a review of the facts. The FCA decision does not apply new law, but it is another helpful discussion of the obvious-to-try analysis applied to the particular facts. It is useful to contrast this case, in which the crystalline form was found not to be obvious on an obvious-to-try analysis, with Dasatinib 2017 FCA 190 aff’g 2017 FC 296, holding the claims at issue to be obvious-to-try: see here for a discussion. These are companion cases, and the reasons are largely the same. This discussion will refer primarily to the Apotex decisions, simply because it is the one I happened to read first.

As the FCA discussed in Atazanavir 2017 FCA 76 (see here), as well as in Ciba v SNF 2017 FCA 225 (see here), the role of the inventive concept in an obviousness analysis has been problematic. In this case, it was uncontested that the inventive concept of the relevant claims is Form I ODV succinate. Apotex’s main argument was that “the Federal Court Judge erred when he made reference to the properties of ODV succinate – and specifically Form I – in his reasons as they are not part of the inventive concept” [37]. This is an important point. An obvious to try analysis is likely to be appropriate “where advances are often won by experimentation” (Sanofi [68]). In such a case, the detailed properties of the invention normally cannot be predicted in advance. If the detailed properties are part of the inventive concept, then the claimed invention would never be obvious, even though it was obvious to try and succeeded without the need for inventive ingenuity, as, for example, in Dasatinib. The FCA acknowledged this concern:

[38] I am mindful that our Court cautioned in Atazanavir to not implicitly adopt a definition of the inventive concept that focuses on properties if the properties are not part of the inventive concept (Atazanavir at para. 74).

In the Teva appeal, the Court noted that there was no dispute between the parties that the inventive concept does not include properties [32]. (This is not to say that the properties can never be part of the inventive concept, as the Court indicated in [38].)

Apotex’s complaint did have some basis in Brown J's reasons; in places, he did discuss the properties of ODV in a way that could be taken to imply that it would have been necessary to be able to predict its properties from the prior art: see eg the passages quoted at [38]. However, when read as a whole:

the Federal Court Judge did not find non-obviousness on the basis that the properties were not predictable in the manner seemingly suggested by Apotex. Indeed, although the Federal Court Judge discusses properties in various parts of his reasons, his conclusion that Form I ODV succinate is not obvious does not rest solely on the unpredictability of the properties of a salt form. Rather, the Federal Court Judge relied on evidence that demonstrated that a skilled person could not have known or predicted that the Form I ODV succinate – i.e., the crystal form itself – could be made or even existed:

So, Brown J found that “the number of experiments required to move from the acceptable pharmaceutical salts to the Form I ODV succinate was extremely large, as Dr. Myerson deposes at para 102 of his affidavit, and in the nature of a research program, not routine experimentation” [FC 230] quoted at [38]. So, on the facts, actually making the crystal form required inventive ingenuity, quite aside from whether the properties are part of the inventive concept, or could have been predicted.

The FCA also affirmed that the jurisprudence “does not establish any “hard and fast rules” on obviousness when it comes to evaluating whether or not a salt screen or any other form of experimentation is obvious or not” [42]. Whether salt forms, polymorphs or crystalline forms are obvious will turn on the facts of the case.