Monday, July 29, 2013

Restrictive Interpretation of the Obvious to Try Test

Sanofi-Aventis v Apotex Inc / clopidogrel 2013 FCA 186 Pelletier JA, concurred in by Noël, Gauthier JJA; separate concurring reasons by Gauthier JA, rev’g 2011 FC 1486 Boivin J
            1,336,777 – PLAVIX

There is a great deal packed into this FCA decision holding Sanofi’s clopidogrel patent to be valid and infringed. The NOC proceedings respecting clopidogrel had culminated in Sanofi 2008 SCC 61 (referred to by the FCA as Plavix), in which the SCC had held that the ‘777 patent was neither anticipated nor obvious. Apotex subsequently sought a declaration of invalidity, which was consolidated with Sanofi’s infringement action. In the FC, Boivin J held the patent invalid for lack of utility and as being obvious. The FCA has now reversed on both these points. The FCA decision raises all of the most difficult doctrines in Canadian pharmaceutical patent law; the promise of the patent, selection patents, and the “obvious to try” analysis are all discussed at length, and the requirement that the factual basis for sound prediction be disclosed in the patent is touched on in Gauthier J’s concurrence. This post deals with the obviousness issue.

The ‘777 patent is a selection patent from the genus claimed in 1,194,875. In particular, Claim 1 of the ‘777 patent claims clopidogrel, which is the dextro-rotatory enantiomer of a racemic compound referred to as PCR 4099. (The remaining claims are to certain of its salts, a process for making clopidogrel and pharmaceutical compositions.) The ‘875 patent, which was conceded to be part of the common general knowledge [FC 608], claimed a genus encompassing PCR 4099, which was also specifically disclosed in Example 1 [FC 611]. The obviousness question was therefore simply whether the enantiomer was obvious over the racemate.

Boivin J found that the properties of clopidogrel, and in particular that the dextro-rotatory isomer was both more pharmacologically active and better tolerated than the levo-rotatory enantiomer (and hence also than the racemate), could not have been known prior to separation and testing [676]. Thus this was an “area[] of endeavour where advances are often won by experimentation" (Sanofi 2008 SCC 61, [68]), and so an "obvious to try" analysis was appropriate.

In my post on Boivin J’s decision, I suggested that the obvious to try analysis can be separated into two parts:

We might therefore say that in order to be obvious, the invention must be both obvious to try and obvious to succeed, with the understanding that “obvious to succeed” does not mean that success can be predicted in advance, but only that success followed on “routine trials” [SCC 69]. Conversely, we might say that the necessary inventive step may lie in either the decision to undertake the experiment, or in carrying the experiment to success. Either is sufficient: if it was very clever to even think of conducting the experiment, it does not matter that it succeeded easily; and if successfully carrying it out required great ingenuity, it does not matter that anyone might have conceived of the attempt.

In this case, the evidence indicated that once a decision to separate the enantiomers was made, separation by the “classic” method was reasonably straightforward. The real issue was whether it was obvious to attempt to separate them. (I would have said “obvious to try,” except that has become a term of art.) As Boivin J put it, “While there were undoubtedly discussions on the issue of separating enantiomers in the scientific community in the mid-1980’s, the real question is whether these discussions had reached such a level that the person of ordinary skill in the art working in the field in 1987 would have been motivated to separate the enantiomers” [FC 723]. Boivin J reviewed a number of general motivations, such as the thalidomide disaster, and increased regulatory pressure, and concluded that “the person of ordinary skill in the art would therefore have had the motivation to separate the enantiomers of PCR 4099" [FC 750]. In my previous post, I suggested that a shortcoming of this analysis, and the reason that Boivin J did not reach the same conclusion as the SCC, was that he did not consider Sanofi’s actual course of conduct in making the decision to attempt separation. While he did consider the actual course of conduct, it was the course of conduct in achieving separation, not the course of conduct in deciding whether to make the attempt [FC 752ff]. 

In her concurring reasons, Gauthier J focused on exactly this point: “in my view, the analysis of the Trial Judge is incomplete because it only focused on the resolution of PCR 4099" [136], and in Sanofi “Rothstein J. made it clear . . . that whether the separation or resolution of the enantiomers was routine or involved arduous work would assume small significance in this case when one considers the whole course of conduct that led to the decision to separate” [137, my emphasis]. Moreover, “It appears to me that the Trial Judge did not really weigh the extent, nature, and amount of efforts required to arrive at a decision to actually develop PCR 4099" [138], and

[139] The Trial Judge did not find that the person skilled in the art would obviously start a development project based on the ‘875 Patent compound with PCR 4099 as opposed to any other compound, including the 21 compounds expressly used in the examples. In fact, Sanofi’s actual course of action militates against such a conclusion.

Some of Pelletier J’s opinion is to the same effect. So, he noted that “[the Supreme Court in Sanofi] held that just because the methods of separating a racemate into its isomers are known, it does not follow that a person skilled in the art would necessarily apply them” [73]. But the thrust of Pelletier J's opinion focuses on a different analysis of Sanofi:

[74] What emerges from this review of the Supreme Court’s decision in Plavix, cited above, is that the key factor in its “obvious to try” analysis was the lack of knowledge of the properties of the enantiomers of the compounds of the ‘875 Patent, including the racemate from which clopidogrel was obtained. Absent that knowledge, it was not obvious to try to resolve the racemate, or any other compound, so as to obtain the enantiomer having those advantageous properties.

[79] The reasons of the Trial Judge make it clear that, as was the case in Plavix, it was not possible to predict the properties of the separated enantiomers: Reasons, at paragraphs 673 and 676. The lack of knowledge as to these properties is precisely what led the Supreme Court in Plavix, cited above, to hold that it was not self-evident that what was being tried ought to work (Plavix, at paragraph 92, quoted above). Simply put, the person skilled in the art would not think of separating PCR 4099 and testing its enantiomers in order to obtain the benefit of its properties when the existence and nature of those properties were unknown.

[81] Put another way, the distance between the common general knowledge and the inventive concept of the ‘777 Patent could not be bridged by routine experimentation since the results to be obtained were unknown.

I have quoted substantial passages, because I am not entirely confident of my interpretation, but this seems to me to say that the invention was not obvious because the properties of the enantiomer could not be predicted in advance: see similarly [76], [78]. In my view, this is an overly restrictive interpretation of the doctrine. The point of the obvious to try doctrine, originally developed in Johns-Manville's Patent [1967] RPC 479, is that in some areas it is very difficult to predict the results of an experiment in advance, yet if the state of the art points directly to trying a certain experiment, and that experiment works without difficulty once tried, there was no invention in achieving success: see IPKat post on Omnipharm Ltd v Merial [2011] EWHC 3393 (Pat), and my case comment “Restricted application of ‘obvious to try’” JIPLP 2012; doi: 10.1093/jiplp/jps030 expanding on that post. Pelletier J's analysis implies that, on the contrary, an invention will never be obvious in areas where advances are won by experimentation, because in those areas, by definition, and the outcome of experiments cannot be predicted in advance. 

My view is that the best reading of Sanofi as a whole is that an invention may be obvious even if the properties of the claimed compound could not be predicted in advance, so long as the experiments were obvious to try and succeeded without undue difficulty. However, I must acknowledge Sanofi is not entirely clear on the issue, and Pelletier J's analysis does have considerable support in the decision, particularly in Rothstein J’s statement that “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" [65]. And after all, as Pelletier J rightly points out, the SCC held that clopidogrel was not obvious to try. Pelletier J's analysis is also much the same as that of Floyd J in Omnipharm. (Omnipharm was appealed, [2013] EWCA Civ 2, but obviousness was not raised, perhaps because it was thought that Floyd J has stated the law correctly.)

While I prefer the focus in Gauthier J’s opinion, her observations were additional comments, and she also concurred with Pelletier J's reasons [122]. This means that the FCA Clopidogrel decision has established a restrictive interpretation of the obvious to try test. In last Thursday's post on Kane J's valganciclovir decision I stated that Apotex's position on the obvious to try test was preferable to that of Roche; it seems now that the FCA has adopted a position much closer to that of Roche.

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