Sunday, September 30, 2012

Use Claims and Choice in Construction of the Promise

Bristol-Myers Squibb Co v Mylan / efavirenz (NOC) 2012 FC 1142 Barnes J
            2,101,572 – 2,279,198 – efavirenz – SUSTIVA

Efavirenz is an anti-retroviral drug used to treat HIV infection, typically in combination with other anti-retroviral agents. Two patents related to efavirenz were at issue in this case: the ‘572 patent, expiring in July 2013,which claimed efavirenz; and the ‘198 patent, expiring in 2018, which claims a particular crystalline form of efavirenz (Form I) and a process for producing it. BMS was successful in obtaining an order of prohibition in respect of the ‘572 patent, but not in respect of the ‘198 patent. This post will focus on the ‘572 patent. The interesting question of how to construe the promise of the patent in the context of a use claim, where the utility is specified in the patent itself, was raised but avoided. The most interesting statement in the decision hints in dicta at a return to the older view that “. . it is sufficient utility to support a patent that the invention . . . affords the public a useful choice.”

Infringement was conceded [78] and the sole validity attack was based on utility. As is now common in Canadian cases, this turned entirely on the construction of the promise of the patent. An important class of HIV drugs, including both AZT and efavirenz, operates by inhibiting HIV reverse transcriptase. Mutations in the HIV reverse transcriptase gene can cause it to become resistant to standard drugs. The particular advantage of efavirenz is that it is very effective against the so-called 103 and 181 mutations [26]. Tests demonstrating its efficacy against these strains were disclosed in the patent. It is also active against the unmutated wild-type (WT) virus [26]. It’s efficacy in this respect was not contested.

The thrust of Mylan’s argument was that the patent promised that efavirenz would also be effective against the 188 mutation. Efavirenz had never been tested against this strain, so there was no evidence of its efficacy in this respect. Construction of the promise was therefore crucial. Unusually, Mylan lost this point on the basis that this argument was insufficiently specified in the NOA. Mylan’s allegation was that patent promised efavirenz's utility “against all known HIV RT resistant strains” [58], [60]. Because HIV mutates at a very high rate, so that new strains resistant strains are emerging constantly, this was conceded to be overly broad if literally understood [55], [84]. Mylan argued that the allegation should be read down to include what it characterized as all material resistant strains [60]. Barnes J accepted evidence of BMS’s experts that the 103 and 181 strains were of particular interest at the time, and he held that Mylan’s allegation failed to inform BMS that the case would focus on the 188 strain. Consequently, BMS met its burden and was entitled to an order of prohibition [63].

Barnes J nonetheless dealt with Mylan’s inutility allegation on the merits. There were really three different possible constructions at issue:

1) Efficacy against all major resistant strains of HIV reverse transcriptase
2) Efficacy against the specific strains referred to in the patent.
3) Efficacy against at least some forms of HIV reverse transcriptase

The broad construction is supported by passages from the disclosure, which had several broad statements to the effect that “The particular advantages of the present compounds are their demonstrated inhibition of resistant HIV reverse transcriptase” [76]. Based on these statements, Mylan argued that the patent should be construed as promising effectiveness against major resistant strains, which arguably included the 188 strain.

The narrowest reading is based on the claims at issue, which were essentially as follows:

            28        Efavirenz.

            29        A pharmaceutical composition useful for inhibiting HIV reverse transcriptase, comprising [efavirenz].

            30        A pharmaceutical composition useful for treating infection of HIV or for treating AIDS [], comprising [efavirenz].

BMS argued that “the 572 Patent promises only that efavirenz inhibits HIV [reverse transcriptase] thereby inhibiting HIV infection and rendering it useful to treat AIDS. . . in humans” [81]. The efficacy against specified strains was “an advantage” and “not part of the promise of its claims” [81]. In effect, the argument is that in the case of a use claim, the promise of the patent was defined by the claims. Though it was not cited, this in effect adopts the position expressed by Zinn J in Fournier / fenofibrate (NOC) 2012 FC 741 [126] (blogged here):

Where that promise - that claimed utility - is clearly and unequivocally expressed by the inventor in the claims of the patent, then that expression ought to be viewed as the promise of the patent. Any statement found elsewhere should be presumed to be a mere statement of advantage unless the inventor clearly and unequivocally states that it is part of the promised utility. . .

Despite BMS’s position, BMS’s experts adopted the middle ground, that efavirenz would be effective against “the specific resistant strains referred to and tested in the patent” [85(73)].

Ultimately Barnes J held that it was unnecessary for him to decide as between the two narrower alternatives [81], as he rejected Mylan’s broad reading, and utility was clearly established on either of the narrow constructions. Barnes J rejected Mylan’s construction in part because “Nowhere in the 572 Patent is there a statement that efavirenz is effective against any resistant mutant strains of HIV RT beyond those that were tested” [89] – except, of course the broad statements relied on by Mylan – and in part because there was no logical limit to Mylan’s position. Mylan conceded that the promise could not reasonably be understood by a skilled person as literally promising efficacy against all resistant strains, but if a literal reading were rejected, there is no logical reason to draw the line to include strains that are not referred to in the specification [92].

To my mind, the most interesting part of Barnes J’s decision is his statement that “I do not accept, however, that testing the efficacy of an HIV RT inhibitor against the 188 mutation or, indeed, against any particular mutation would have been seen by a person of skill to be a prerequisite for establishing a level of utility. On the evidence before me, the development of a novel compound that inhibited only the WT virus would have been seen as inventive and useful” [96]. Though strictly dicta, this comes very close to rejecting the promise of the patent doctrine entirely. It is suggests a return to the traditional position, expressed in Consolboard [1981] 1 SCR 504 at 525 that “. . it is sufficient utility to support a patent that the invention . . . affords the public a useful choice.”

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