Tuesday, May 17, 2011

Exact Matching Required in PM(NOC) Listing of Dosage Claims

Purdue Pharma v Canada (Attorney General) / TARGIN 2011 FCA 132 Layden-Stevenson JA: Blais CJ, Stratas JA aff’g 2010 FC 738 Crampton J

As described in the previous post, Purdue Pharma sought to list 2,098,738 against TARGIN. TARGIN is a controlled release combination of two active ingredients, oxycodone and naloxone. The ‘738 patent claims a controlled release oxycodone formulation “comprising” oxycodone in a matrix. None of the claims expressly mention naloxone. Yesterday's post critiqued the FCA’s suggestion that the ‘738 patent was restricted to drugs containing only oxycodone, so that TARGIN could not infringe. If TARGIN could not infringe, the ‘738 patent would not be eligible for listing. However, even if TARGIN might fall within the scope of the ‘738 patent, it does not follow that the ‘738 patent can be listed. Since the 2006 amendments it is clear that list eligibility and infringement do not exactly coincide: it is not true that any patent that would be infringed by production of a particular drug is therefore eligible for listing against that drug (RIAS to SOR/2006-242 at 1512). Even if TARGIN potentially infringes, listing eligibility is a distinct question. This is the issue of “product specificity.” Is the match between the product and the patent sufficiently close?

The Canada Health Guidance Document respecting the PM(NOC) Regulations accepts at 8, that under section 4(2)(a), relating to medicinal ingredients, a patent claiming a single medicinal ingredient as a compound “will be eligible for listing with respect to a drug that contains the said medicinal ingredient in combination with other medicinal ingredients, notwithstanding that the medicinal ingredient on the NOC is the combination of medicinal ingredients.” However, in Bayer Inc v Canada (Health) / YAZ, 2009 FC 1171 affm'd 2010 FCA 161 the Court held that in the case of a formulation claim, under section 4(2)(b), there must be an exact match between the claim and the appproved drug. YAZ is a combination oral contraceptive, containing drospirenone and ethinyl estradiol. The patent at issue, 2,194,979 claimed the use of β-cyclodextrin to reduce the oxidative degradation of 17α-ethinyl estradiol. The listing was refused on the basis that a claim that refers to only one medicinal ingredient does not match an approved formulation containing two medicinal ingredients [FC 69]. In TARGIN the FCA held that similarly, in the case of a dosage claim under section 4(2)(c), a claim that expressly includes only one medicinal ingredient does not encompass a dosage form that includes two medicinal ingredients. The claims dosage form and the approved dosage form must be “the very same” [43].

This is not entirely satisfactory. In either a formulation or dosage claim it is possible that the additional of non-named medicinal ingredients will not affect the operation of the claimed invention. There was evidence to this effect in YAZ [FC 33], for example. Indeed, we may expect this will normally be the case; otherwise, a broad claim comprising the specified formulation or dosage would be invalid for insufficiency. That means that in general, in addition to claiming a product comprising the specified formulation or dosage form, the patent could also explicitly claim the formulation or dosage form in combination with an arbitrarily long list of specific additional ingredients. If that were done, and one of the named ingredients matched the approved formulation or dosage, then there would be an exact match and listing would be permitted. So the listing is permissible, and the only question is whether the extra ingredients must be explicitly named in the patent. It is not clear what policy goal is achieved by requiring explicit listing..

The cases turn primarily on the interpretation of the relevant regulations. The main principled argument raised in favour of the narrow interpretation is that “the detailed product-specificity (or relevance) requirements exist to limit the application of the NOC Regulations to ‘that which the innovator has invested time and money to test and have approved for sale’” (YAZ [FC 48]. This is not persuasive. In a medicinal ingredient case under section 4(2)(a) it is clear that a patent for the compound can be listed against a combination, even though it was the combination which “the innovator has invested time and money to test and have approved for sale” in respect of that particular NOC. As the RIAS to the 2006 amendments states at 1510, the basic policy goal is to “to balance effective patent enforcement over new and innovative drugs with the timely market entry of their lower priced generic competitors.” It is now clear that the mere possibility of infringement does not justify a listing; and rightly so. I entirely agree with the basic point of the 2006 amendments, that an innovator should not be able to trigger the NOC procedure with patents that have only a tenuous connection to the approved drug. But even if a tighter linkage there mere possibility of infringement is required, it nonetheless remains true that the main concern weighing in the balance is protection for the innovator’s investment in invention, not their investment in the approval for sale.

With that said, I am not sure that the listing was justified in either YAZ or TARGIN. In YAZ the NOC was for a combination drug, and the patent was for a particular method of preventing degradation of one of the components. A generic would face the same problem of degradation, but I do not see anything in the NOC listing or the product monograph that specifies that the patented method must be used to solve that problem. It is therefore not evident that the generic would be required to use the patented method of preventing degradation in order to use YAZ as a reference product in its ANDS. A similar point can be made with respect to TARGIN. While TARGIN is a controlled release product, it is not clear to me that the generic would be required to use the patented controlled release method. (I am not an expert in the Food and Drug Regulations, so I may be missing something here – I would appreciate it if any reader could clarify this point.) If I am wrong on this point, and the generic is in fact legally required to use the patented method, then I find it difficult to see why these patents would not have sufficient product specificity, regardless of whether the expressly claimed compounds match exactly. But if the generic is not legally required to use the patented methods, the problem of product specificity becomes a difficult question of fact. If there are other solutions to the problems of degradation and controlled release which could easily be adopted by the generic, then it would be entirely appropriate to refuse the listing on the basis that this linkage is not sufficiently tight. On the other hand, if as a practical matter the generic would have to use the patented method, the argument that there is sufficient specificity is strong. This approach raises a difficult question as to exactly how tight that linkage has to be. Also, this kind of inquiry would be difficult and fact intensive: see for example the analysis of the linkage in Solvay Pharma Inc v Apotex Inc. 2008 FC 308. It would be understandable if the Minister of Health viewed this approach to specificity as too administratively complex to form the basis for the listing decision. But the strict matching requirement affirmed in TARGIN does not solve that problem, which will arise even in those cases where the medicinal ingredients match exactly. While the product specificity problem is difficult, I doubt that the strict matching requirement addresses the right question.

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