Wednesday, September 23, 2020

Does a Range Anticipate a Point Within the Range?

 Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC 2020 FC 816 St-Louis J

            2,371,684 / tadalafil / CIALIS ADCIRCA

Lilly markets 2.5mg, 5mg, 10mg and 20mg strengths of tadalafil for the treatment of erectile dysfunction [11]. The defendants in this action are various generics that want to sell tadalfil in those dosage forms [13] The asserted claims of the 684 patent were 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 [197-213].

The question in this case was whether the 684 patent is valid over the prior art 2,226,784 application, which claims tadalafil for the treatment of ED, and discloses unit doses of tadalafil from 0.2 to 400 mg. 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 [325-28]. The claimed invention was therefore obvious to try [323, 330].

So far, so good, and I wish I could stop the post here. However, St-Louis J also held that the 784 application anticipated the 684 patent, which, with due respect, is clearly wrong. I’ll address that issue in this post. There is also some problematic discussion of selection patents, which I will discuss in the next post. And there are some difficulties with the discussion of the role of the inventive concept in the obviousness analysis, which I won’t address, as it did not seem to impact the obvious-to-try conclusion. St-Louis J, and the parties, appear to have been guided by the decision of de Montigny J in NOC proceedings involving the same patent, Lilly v Mylan 2015 FC 125, which has similar problems, though again the basic obvious-to-try analysis was not affected.

Anticipation requires an enabling disclosure of the claimed subject-matter: Sanofi 2008 SCC 61 at [24]–[28]. On the disclosure branch, St-Louis J held that the essential elements were disclosed, which is to say that the 10mg dose was disclosed, because “[a]ccording to the 784 Application, the dose should generally range in between 0.5–500mg daily for a 70kg adult patient, except for individual instances. This range is wider than the 2.5–20mg dose range in the asserted Claims.” In other words, a range anticipates a point within that range. With respect, that is clearly wrong.

It is of course abundantly clear that disclosure of a genus does not anticipate a species. This was established in Sanofi as an application of the general principles of the law of anticipation:

If. . . the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee’s claim will not have been anticipated, although it may fail on the ground of obviousness.

Sanofi [21], quoting General Tire [1972] RPC 457 at 486 (CA) and describing the law as stated therein as “being accepted in Canada without reservation” [22]. Now, the prior art that discloses the genus may also specifically disclose the species, eg as a preferred embodiment, in which case the species will be disclosed (and anticipated if the disclosure is enabling). But even in that case, it is the specific disclosure of the species that anticipates, not the disclosure of the genus. So, if the prior art discloses a genus of 100 related compounds, and the subsequent species patent claims one of those compounds, then practising the prior art would be at least as likely as not (much more likely, in this example) to be carried out in a way which would not infringe. Exactly the same is true for a range and a point within the range: if the prior art discloses a range of 0.2 to 400 mg, and the subsequent patent claims 10 mg, carrying out the prior art would be at least as likely as not to be carried out in a way which would not infringe (eg the prior art might be carried out with a dose of 392 mg, or 0.7 mg or 128 mg etc).

Similarly with the test from Beloit (1986), 8 CPR(3d) 289 (FCA) at 297, quoted in Sanofi at [20]:

The prior publication must contain so clear a direction that a skilled person reading and following it would in every case and without possibility of error be led to the claimed invention.

If the prior art discloses a genus of 100 related compounds, and the subsequent species patent claims one of those compounds, then the skilled person would not, “in every case” be led to the claimed invention, as there would be many cases (99 out of a hundred) that would not lead to the claimed invention. The same is true for a range and a point within the range: if the prior art discloses a range of 0.2 to 400 mg, and the subsequent patent claims about 10 mg, the skilled person would not, “in every case” be led to the claimed invention, as there would be many cases in which carrying out the prior art would not lead to the claimed invention (eg 392 mg, or 0.7 mg or 128 mg etc).

Similarly with the test from Synthon [2005] UKHL 59 at [22], quoted in Sanofi at [25]:

the matter relied upon as prior art must disclose subject matter which, if performed, would necessarily result in an infringement of the patent.

If the prior art discloses a genus of 100 related compounds, and the subsequent species patent claims one of those compounds, then performing the prior art would not necessarily result in infringement of the patent, because there are 99 ways out of a hundred of performing the prior art that that would not infringe. The same is true for a range and a point within the range: if the prior art discloses a range of 0.2 to 400 mg, and the subsequent patent claims about 10 mg, there would be many cases in which carrying out the prior art would not infringe (eg 392 mg, or 0.7 mg or 128 mg etc).

A prior art range does raise some distinct issues in the application of the general principles. As noted, a genus patent will anticipate the species if the species is specifically disclosed in the genus patent, eg as a preferred embodiment. In the case of a species, the question of whether it is specifically disclosed is binary—it is, or it is not. In the case of a range, there is a question of what constitutes a specific disclosure; so, if the prior patent discloses a range from 0.2 to 400 mg, but then discloses a smaller range, from 1–20 mg as especially preferred, does this anticipate a claim to 10 mg? What about 5–15 mg? 9–11 mg? But this issue does not appear to have arisen on the facts in this case.

This all seems clear, so where did St-Louis J go astray? I think the key point was her reliance at [257] on the decision of Hughes J in Merck / finasteride 2010 FC 510 at [167] as holding that a range anticipated a point within the range because “it would be within the expected skill of a person skilled in the art, as the ‘457 Patent itself acknowledges, to determine an appropriate dosage for a given person.” With respect, this is an error which conflates the anticipation and enablement branches of the anticipation requirement: at the disclosure stage “there is no room for trial and error or experimentation by the skilled person” Sanofi [25]. As Lord Hoffmann explained in Synthon at [30] (emphasis added):

in deciding whether there has been anticipation, there is a serious risk of confusion if the two requirements are not kept distinct. For example, I have explained that for the purpose of disclosure, the prior art must disclose an invention which, if performed, would necessarily infringe the patent. It is not enough to say that, given the prior art, the person skilled in the art would without undue burden be able to come up with an invention which infringed the patent.

Trial and error is permitted only at the enablement stage; Hughes J and St-Louis J have made exactly the error Lord Hoffmann cautioned against.

St-Louis J at [257] stated that “[i]n general, dosing a drug itself does not bring anything novel, subject to exceptional circumstances, which means that a dosage patent will almost always be anticipated.” With respect, this statement conflates anticipation and obviousness, as direct a result of conflating the two steps of the anticipation analysis.

So, in Synthon at [23] Lord Hoffmann explained that for the disclosure requirement to be satisfied

[T]he infringement must be not merely a possible or even likely consequence of performing the invention disclosed by the prior disclosure. It must be necessarily entailed. If there is more than one possible consequence, one cannot say that performing the disclosed invention will infringe. The flag has not been planted on the patented invention, although a person performing the invention disclosed by the prior art may carry it there by accident or (if he is aware of the patented invention) by design. Indeed, it may be obvious to do so.

We can throw in some US law for good measure: in EI DuPont v Synvina 904 F3d 996 at 1006 (Fed Cir 2019), the Fed Cir noted, in the context of obviouisness, that

For decades, this court and its predecessor have recognized that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."

So, it may well be obvious to determine the optimum dosage by routine experimentation, but this does not mean the dosage is anticipated by the disclosure of a range.

de Montigny J's decision on this point in NOC proceedings involving the same patent, 2015 FC 125, [148–49] was much the same. I acknowledge that we now have three FC decisions holding that a range can anticipate a point within that range, even where the range is not specifically disclosed. I would also note that Grammond J appears to have made a similar error in conflating the enablement and disclosure aspects of anticipation, in Seedlings Life Science 2020 FC 1, as discussed here. As an academic, I recognize that there is a difference between what I think the law should be and what the law actually is. But it is perfectly clear that a genus does not anticipate a species and I am unable to see any difference in principle between a prior range and point within it, as compared with a prior genus and a species within it; and the leading statements of the law of anticipation quoted above seem quite clear, whether applied to a genus or a range. It also perfectly clear that no trial and experimentation is permitted at the enablement stage of the anticipation inquiry. For now, I am going to go with the SCC in Sanofi and the UKHL in Synthon as stating the law.

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