Wednesday, August 17, 2022

Is it Necessary to Disclose the Special Advantage of a Selection Patent?

Pharmascience Inc v Bristol-Myers Squibb Canada Co 2022 FCA 142 Locke JA: de Montigny, Monaghan JJA affg 2021 FC 1 Zinn J FC Selection

2,461,202 / 2,791,171 / apixaban / ELIQUIS

This decision raises some issues related to selection patents and the date for assessing sufficiency. I’ll deal with these in separate posts, starting with selection patents.

The patents in suit relate to the anticoagulant compound apixaban which is used in treating thromboembolic disorders, including stroke. The 202 patent claims the compound apixaban as such, as well as its use in the treatment of thromboembolic disorders [4]. The 171 patent claims various formulations of apixaban. Only validity was at issue. Four related actions, two each involving Pharmascience and Sandoz as defendants, were tried “on a coordinated basis” at first instance. Only Pharmascience pursued its appeal [1].

The more interesting issues relate to the 202 patent and its validity over the prior art patent 2,349,330. Apixaban is a selective inhibitor of the enzyme Factor Xa (FXa) and it works by blocking certain clotting proteins in the blood. The 330 patent disclosed and claimed a large class of compounds which were disclosed as FXa inhibitors and so potentially useful in the treatment and prevention of thromboembolic disorders [FC 79]. The class is extremely large: “more possibilities than stars in the universe” [FC 80]. On the evidence provided by Sandoz’s experts, the class encompassed apixaban [FC 77], but did not specifically disclose it, or describe how to make it [FC 82]. Thus, the 202 patent is what would traditionally be called a selection patent over the 330 patent. A three-part test for the validity of selection patents was set out in IG Farbenindustrie (1930) 47 RPC 289 (Ch) 322-23 and endorsed in Sanofi 2008 SCC 61 [9]-[11]. The factors, in summary, are: (1) a valid selection must possess some substantive advantage over the genus; (2) all of the selected members must possess the advantage; (3) the advantage must be peculiar to the selected group.

There has been considerable debate as to the role of the IG Farbenindustrie factors and their relationship to the standard grounds of invalidity. In Olanzapine 2010 FCA 197 [33] the FCA stated that an assessment of whether the IG Farbenindustrie conditions have been met “does not constitute an independent basis upon which to attack the validity of a patent,” and “A selection patent is the same as any other patent. Its validity is vulnerable to attack on any of the grounds set out in the Act.” This implies that the IG Farbenindustrie factors are a reflection of one or more of the standard grounds of invalidity. As discussed in my post on Zinn J’s decision, he was quite skeptical of the IG Farbenindustrie factors. He stated that failure to meet those requirements is not a stand-alone basis to find a selection patent invalid [FC 104], and he rejected anticipation [FC 83] and obviousness [FC 88] attacks without reference to the factors, though he did go on to hold that if compliance with the IG Farbenindustrie factors were required, the 202 Patent meets that test [FC 106–08].

So, the continued vitality of the IG Farbenindustrie factors and their relationship to the standard grounds of invalidity remains unclear. The FCA will no doubt clarify that relationship in due course, but chose not to do so in this decision. On appeal, Pharmascience argued that Zinn J erred because he never made a clear finding that the 202 patent is a selection patent. Locke JA noted that Zinn J had nonetheless clearly held that the 202 patent satisfied the IG Farbenindustrie criteria and in particular that it disclosed the special advantages of apixaban (the first factor, and typically the most important) [12]. The FCA then went on to separately affirm Zinn J on anticipation and obviousness, without reference to the IG Farbenindustrie factors as such [16]–[21]. Thus, it is not clear whether Locke JA considered it necessary for Zinn J to address the IG Farbenindustrie factors.

Requirement to disclose the special advantage

The most commonly applied IG Farbenindustrie factor is the first, requiring that “There must be a substantial advantage to be secured or disadvantage to be avoided by the use of the selected member” Sanofi [10.1]. This is readily seen as a reflection of the non-obviousness requirement in the context of selection patents. If the prior art discloses a large genus of compounds and discloses that all members of the genus possess a certain property, eg all the compounds treat cancer, then it is not inventive to select one species from that genus and show that it treats cancer, since we already knew that all members of the genus treat cancer. To select one species from a genus is an “arbitrary selection” discussed here and here. A selection must therefore have some special advantage—it cures cancer with fewer side effects, or with higher efficacy—compared with what was known about the genus as a whole.

In this case, Pharmascience argued that Zinn J “erred in failing to recognize (i) that the 202 Patent did not indicate a special advantage, and (ii) the requirement that a selection patent disclose the special advantage of the selection (because the special advantage is the invention, and a patent must disclose its invention” [11]. That is, the argument is not just that apixaban must have a special advantage over the compounds of the 330 patent, but that the special advantage must be disclosed in the 202 patent. This argument seems to be ultimately derived from Sanofi-Aventis v Apotex 2013 FCA 186 [51] (though that case was not cited), where the FCA said “In the case of selection patents, as we have seen, the novelty of the selection and its advantages (including disadvantages to be avoided) are the invention and must be described in the patent,” relying at [45] on Sanofi 2008 SCC 61 [114] (and also Olanzapine 2010 FCA 197 [78], which cited the same paragraph of Sanofi.) Sanofi in turn stated

[114] While double patenting requires a comparison of the claims of a genus and selection patent, it is necessary that the specification of the selection patent define in clear terms the nature of the characteristic which the patentee alleges to be possessed by the selection for which he claims a monopoly. See I. G. Farbenindustrie, at p. 323.

The SCC was evidently referring to the following passage from IG Farbenindustrie:

It should be obvious, after what I have said as to the essence of the inventive step, that it is necessary for the patentee to define in clear terms the nature of the characteristic which he alleges to be possessed by the selection for which he claims a monopoly. He has in truth disclosed no invention whatever if he merely says that the selected group possesses advantages. Apart altogether from the question of what is called sufficiency, he must disclose an invention; he fails to do this in the ease of a selection for special characteristics, if he does not adequately define them. The cautions repeatedly expressed in the House of Lords as regards ambiguity have, I think, special weight in relation to selection patents.

This all looks like good authority for the proposition that a valid selection patent must disclose the special advantages. (Though the reference to ambiguity is a bit mystifying.)

The difficulty with this proposition is that it is well-established that the inventive concept that renders the invention non-obvious need not be disclosed: see Raleigh v Miller (1948) 65 RPC 141 (HL) 161 (Lord MacDermott) stating “a patentee is not bound to include in his specification a statement of the inventive step”; Consolboard [1981] 1 SCR 504, 532-33; BUSM v Fussell (1908) 25 RPC 631 (CA) 649-653. The specification must disclose an invention—which is to say, subject-matter that is in fact new, useful, and non-obvious—but it is not necessary for the specification to disclose what makes it an invention. There has been some confusion on this point because it was at one time necessary in English law that the patent should distinguish what is new from what is old, on the view that the specification ought to inform the public of the bounds of the monopoly. But that function is now served by the claims, which serve that purpose by defining the scope of the monopoly directly, rather than by distinguishing old from new: see BUSM v Fussell (1908) 25 RPC 631 (CA) 650-51, explaining that the rule became outdated with the advent of claims. So, it is now well-established that it is not necessary to describe in what respect the invention is new. So long as the claimed invention is in fact novel and sufficiently disclosed, “There is no obligation to go further, and to state why it is novel, or what in it is novel”: Consolboard [1981] 1 SCR 504, 531-32, quoting with approval BUSM v Fussell (1908) 25 RPC 631 (CA) 651. The same principle applies to obviousness.

Given that there is no general requirement to disclose the inventive concept, either there is no requirement to disclose the special advantage of a selection, or there is some special rule that applies only to selection patents, and the latter is contrary to the Olanzapine principle that “A selection patent is the same as any other patent. Its validity is vulnerable to attack on any of the grounds set out in the Act.”

As the SCC pointed out in Consolboard at 532, a contrary rule would “impose[] an impossible burden on the patentee. Suppose he was not aware of another invention that was very similar to his own. If he failed to specify the differences between the two inventions, the patent would be invalid notwithstanding that his invention was new and different.” It would be “grossly unjust” to require the inventor to keep abreast of every development in her field, nor would such a requirement benefit the public: BUSM at 652, quoted in Consolboard at 532. So, suppose that the inventor in this case was not aware of the 330 patent, notwithstanding that it was prior art; it would then be impossible for the patent to specify the special advantages of apixaban over the compounds disclosed in the 330 patent.

In any event, Locke JA did not have to address these issues because he held that the patent did in fact disclose special advantages of apixaban [12], though he did state that “There was no need for the 202 Patent to provide an explicit comparison of apixaban to any other particular compound falling within the scope of the 330 Patent” [14]. He also stated that “There is no requirement for a selection patent to discuss the special advantages of the selection over the genus in any particular way” [38]. This is ambiguous, as it is consistent with the view that it is necessary to disclose the special advantages, just not in a particular way, such as explicit comparison with the genus compounds.

Usefulness as the special advantage

The decision also raises a different issue. Locke JA noted that the special advantage of apixaban is that “it was useful” [12, quoting FC 107, original emphasis]. The fact that apixaban is useful is a special advantage over the compounds of the 330 patent because “the skilled person reading the 330 Patent would understand that not all of the claimed compounds would be useful in treating and preventing thromboembolic disorders” [12, quoting FC 107]. This is consistent with the view that the first IG Farbenindustrie factor is a reflection of the non-obviousness requirement, as Locke JA made the same point in the context of the obviousness discussion. He noted that Zinn J identified the inventive concept as the selection of apixaban from the other compounds of the 330 patent, and that the difference between the inventive concept and the state of the art, reflected in the 330 patent, was that apixaban was “effective” in treating thromboembolic disorders, as opposed to the compounds of the 330 patent, which merely had the “potential” to be useful [20].

This is a bit odd on its face. If the 330 patent were valid, then we would know that the compounds encompassed by it, including apixaban, are sufficiently useful to satisfy the utility requirement. If the genus is useful and we pick a species out and say it’s useful too, isn’t that just arbitrary selection? As the defendants argued “It is obvious that apixaban can be used to treat thromboembolic disorders as the 330 Patent states that the bicyclic compounds claimed therein (which include apixaban) are effective FXa inhibitors and are useful for the treatment of a thromboembolic disorder” [FC 85]. This may be a reference to the statement in the 330 disclosure that “These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that the presently claimed bicyclic compounds, or pharmaceutically acceptable salt or prodrug forms thereof, are effective factor Xa inhibitors.”

There are a couple of answers. First, assuming the 330 patent is valid, the bar for patentable utility is low, requiring merely a sound prediction of utility for the claimed compounds. Selecting a compound that is actually useful from among many that are merely predicted to be useful is arguably inventive, assuming, as Zinn J found at [FC 87], that the search is difficult enough. This is not very different from the advantages of the selected compound in Sanofi, which had “greater therapeutic effect and less toxicity” [78] than the other compounds of the genus. (It seems clear that there is nothing special about lower toxicity; no doubt greater therapeutic effect alone would suffice.) While the 330 compounds and apixaban both satisfy the utility requirement, maybe the 330 compounds barely clear the hurdle and apixaban cleared it easily. That is the thrust of both Zinn J and Locke JA’s reasoning on this point, though the point might perhaps have been made more clearly. Zinn J did not draw a direct comparison between the utility of the genus and apixaban, and while he did find that apixaban was useful, he did not state explicitly that it surpassed the standard easily. With that said, the evidence he accepted that the studies “really leaves no doubt” that it would be therapeutically useful in humans certainly indicates that it substantially surpassed the relatively low bar for patentable utility.

In any event, even if we don’t know whether the 330 patent is valid. We know that many granted patents are invalid, and it is possible that most of the compounds are actually not useful at all, even on the basis of sound prediction. In that case, selecting a truly useful compound could well be a special advantage. One way or the other, the bottom line is that just because the 330 patent says the disclosed compounds are effective, there is no particular reason to believe that statement.

The apparent puzzle largely disappears if we simply ignore the fact that the patent is a selection and treat the genus patent as prior art with no special status. If the genus patent in fact establishes that all compounds withing its scope will actually be effective, then selecting one from the group will be obvious. But if it simply indicates a direction to be explored, and actually finding a useful compound is arduous, then there should be no objection to granting a patent to the successful explorer. On that view, the key aspect of the decision is Zinn J’s statement that the invention was “the result of hard work, innovative thinking and a bit of good luck” [87], though that is somewhat conclusory; see also the evidence, accepted by Zinn J in the context of anticipation, to the effect that it would be only a small percentage of the genus compounds that would be safe and effective in treating thromboembolic disorders [FC 81]. I wonder if the question of whether apixaban had unexpected utility over the genus patent might have been addressed more explicitly if the genus patent had simply been treated as part of the prior art, rather than framing the issue in terms of a selection patent.

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