Friday, May 15, 2020

Split in Inducement Case-law Recognized

Janssen Inc v Teva Canada Ltd 2020 FC 593 Manson J
             2,655,335 / paliperidone palmitate / INVEGA SUSTENNA

In this NOC action, Manson J held that Janssen’s 335 patent, relating to dosing regimens for long acting injectable paliperidone palmitate formulations for treatment of schizophrenia, was not invalid for obviousness. He also held certain product claims would be infringed by the sale of Teva’s paliperidone palmitate product, though Teva would neither infringe nor induce infringement of the parallel use claims. He accordingly enjoined the sale of Teva’s product until the expiry of the 335 patent. The obviousness analysis turned on the facts. The most interesting part of the decision is Manson J’s analysis of inducement. Manson J acknowledged the apparent split in the case law on the second step of the Corlac test, which I identified in my paper “Is 'But For' Causation Necessary to Establish Inducement?” (available on SSRN). I’m not entirely persuaded by Manson J’s explanation of the split, but recognizing its existence is certainly a step in the right direction. The practical take-away is that product claims are crucial to effective enforcement of a dosage regimen invention.

Schizophrenia is a debilitating and incurable disease [4]. Antipsychotic drugs are the cornerstone of treatment and management [8]. A leading cause of relapse is non-adherence, where patients do not take their antipsychotic medication as prescribed [11]. “One strategy to ensure treatment adherence is the use of long acting formulations of antipsychotics. One type of long acting formulation is intramuscular injections of antipsychotic drugs, known as ‘depot formulations’ or ‘long acting injectables’. Once injected, the drug releases from the injection site slowly, providing the patient with a prolonged dose of the drug” [12]. Paliperidone was known in the prior art to be a useful antipsychotic, and it was available as an extended release tablet for oral administration [121]. The invention at issue relates to a dosage regimen for a depot formulation of paliperidone palmitate [15]. Specifically, the regimen consists of a first loading dose of 150 mg-eq of paliperidone palmitate administered into the deltoid muscle on day 1; a second loading dose of 100 mg-eq of paliperidone palmitate administered into the deltoid on day 8 + 2 days; and subsequent maintenance doses of 75 mg-eq of paliperidone palmitate administered into the deltoid or gluteal muscle monthly + 7 days after the second injection [19].

As paliperidone palmitate was a known antipsychotic and the use of long-acting depot formulations was also known, the validity of all the claims turned on the inventiveness of the dosing regimens itself [174]. Obviousness turned on a fairly straightforward application of the obvious-to-try analysis [198]. Manson J noted in particular that in order to design the regimen, it would be necessary to first determine the pharmacokinetic profile of paliperidone depot formulation, which was not disclosed in the prior art [201], [203], [208], and that in order to arrive at the appropriate regimen, the POSITA would have had to carry out prolonged and arduous experimentation in the form of clinical trials to evaluate the safety and efficacy of a large number of variables including fixed doses, variable doses, and injection sites [203], [218]. Consequently, he held that the dosage regimen was inventive and the asserted claims were therefore not obvious [224].

Turning to infringement, the 335 patent has three sets of claims. Claims 1 to 16 are to prefilled syringes adapted for administration according to the claimed dosing regimen (“product” claims); claims 17 to 32 mirror the first sixteen claims, except that they are directed towards “use of a dosage form of paliperidone as paliperidone palmitate” rather than prefilled syringes [148] (“use” claims); and the final set of claims are the “use of paliperidone as paliperidone palmitate for the preparation [or manufacture] of a medicament” (Swiss-type claims).

The parties agreed that Teva would not directly infringe the “use” claims [153], [235], and infringement of those claims therefore turned on inducement. In my paper on Is 'But For' Causation Necessary to Establish Inducement? (available on SSRN), I noted that while the test for inducement set out in Corlac 2011 FCA 228 [162] requires at its second stage that the influence of the indirect party be the “but for” cause of direct infringement, there are a number of other cases that endorse a less stringent test. For example, Abbott v Novopharm 2007 FCA 251 [26] inducement was found on the basis that the proposed product monograph would be “an encouragement to infringe.”

In his decision, Manson J expressly acknowledged the divergence between these lines of cases, [259-64]. I am pleased to see the Federal Court recognize explicitly that there is an apparent split in the cases, as confronting the issue directly will help clarify the law. However, I am not entirely persuaded by Manson J’s analysis of the divergence. In Manson J’s view, the split is between the “earlier cases” [264], and the “more recent cases” [262]. The earlier cases only required “some nexus” to the generic company (the cases reviewed by Manson J were all NOC cases) [261], while “in more recent cases,” the Court has “scrupulously” applied the Corlac test, “with particular focus on the second prong” [262]. Manson J stated expressly that “The ‘but for’ influence required in the second prong of the Corlac test requires a higher threshold for establishing inducement than was applied in the earlier cases” [264].

Thus, if I understand correctly, Manson J is of the view that the law has changed, presumably in light of Corlac; or alternatively, the law has not changed, but since Corlac the courts have become more careful in applying what was always existing law. So, he says that in the earlier cases “the second and third prongs of the inducement test, influence by the generic on the infringing party and knowledge that this influence will result in infringement, appear not to have been fully considered” [261]. I have great difficulty with the view that the law has changed; as I discuss in my paper, Corlac cited a line of prior cases articulating the requirement in the same way, through Dableh [1996] 3 FC 751 (FCA) and Warner-Lambert (1988), 19 FTR 198, all the way back to Slater Steel (1968), 55 CPR 61 (Ex Ct).

I also have difficulty accepting the suggestion that the Court of Appeal in Abbott, for example, was simply careless in its application of the test, with the implication that the result would have been different had the Court been more careful. Manson J recognized that there was a line of cases that “are fairly consistent” than inducement can be established simply by making reference to the “new” infringing use, in cases involving a new use for a known compound ([259]), including three decisions by, or affirmed by, the FCA. One case might be carelessness, but a series of cases to the same effect is precedent.

My view, as discussed in my paper, is that the cases are consistent in the result, as the stringent “but for” nature of the second branch was not determinative in any decision except Slater Steel, while there are cases which apply the more relaxed standard, which would have gone the other way had a but for test been used. In my view, there is no split, but rather a single outlier, namely Slater Steel.

While Manson J clearly endorsed the application of a strict “but for” causation requirement at the second branch of the Corlac test, it is not clear to me whether his holding on this point was determinative. Whatever legal test is used, the facts are obviously crucial to the outcome of any particular case. As Manson J pointed out “[a]n important factor in all of these cases is the wording of the claims themselves” [266], along with the instructions in the product monograph, which is “a key document in the inducement analysis” [276]. Unfortunately, Manson J’s analysis of Teva’s product monograph is so heavily redacted that I cannot tell whether his application of a strict “but for” test was crucial to the outcome, or whether the inducement test failed primarily because the statements in the PM were too indirect, even on a more relaxed standard. My suspicion is that the “but for” element was crucial, but I really am not sure.

There is a related point that I found puzzling, probably because of the redactions. In arriving at his conclusion on inducement, Manson J emphasized evidence that physicians’ prescribing practices would be individualized based upon clinical symptoms and that psychiatric medical professionals are very familiar with using paliperidone palmitate in their practice [285-89]. Consequently, medical professionals would not “eschew good clinical practice in favour of a general recommendation in a PM” [286], and would instead “consider individual patient characteristics when prescribing and dispensing depot formulations of paliperidone palmitate rather than blindly following a number in a PM” [289]. For this reason he concluded that while some infringement would occur, “this infringement is the result of prescribing physicians’ skill and judgment applied to specific patient characteristics, rather than influence exercised by Teva via its PM” [290]. My puzzle with all of this is that Manson J had concluded that the dosage regimen was non-obvious and indeed was the result of a great deal of experimentation and research. If that is the case, it’s not clear to me why medical practitioners are not influenced by the PM, which apparently instructs use of the claimed regimen (again, this is not entirely clear because of the redactions). Is it that the claimed regimen, though inventive, is really not that good, and a skilled medical practitioner would have no difficulty coming up with something better on a case by case basis? In any event, I won’t speculate further. No doubt the point would be clear from the unredacted decision, or to someone with more familiarity with the facts.

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