Patent Infringement provisions of Section 271 are not effective to prevent potential “off-label” sale of drug covered by method claims reciting approved use.

Once a drug has been approved by the Food and Drug Administration (FDA) for sale for one purpose, doctors can legally prescribe it for any purpose for which they deem it effective and safe, including for non-FDA-approved indications. This “off-label” prescribing accounts for an estimated one-fifth of all prescriptions in the US (Radley et al., “Off-label Prescribing Among Office-Based Physicians” Archives of Internal Medicine 166 (9): 1021-1026, 2006), diverting multi-billion dollar “off-label” sales from brand name drug manufacturers to generic manufacturers.

The Federal Circuit held in AstraZeneca Pharmaceuticals v. Apotex Corp, that 35 U.S.C. § 271(e)(2) does not provide basis for an infringement claim against a generic pharmaceutical manufacturer who filed an Abbreviated New Drug Application (ANDA) with the FDA for uses other than those recited in the claims of two unexpired patents listed in the Orange book.

One of the listed patents claims methods of using CRESTOR® to treat heterozygous familial hypercholesterolemia (HeFH), and the other claims methods of using CRESTOR® to lower the cardiovascular disease risk for individuals who have normal cholesterol levels but demonstrate elevated circulating C-reactive protein (CRP).

AstraZeneca’s approved New Drug Application (NDA) and corresponding CRESTOR® labeling cover several indications, including treatment of HeFH in pediatric patients and preventative use in high-risk patients with elevated CRP. While the above indications fall under AstraZeneca’s unexpired listed patents, the FDA also approved CRESTOR® for treating homozygous familial hypercholesterolemia (HoFH) and hypertriglyceridemia, uses not claimed by either unexpired Orange book listed patent.

Apotex requested approval of their ANDA to offer their generic version of the CRESTOR® formulation for treating only HoFH and hypertriglyceridemia while omitting the patented indications HeFH and elevated CRP. Apotex, in accord with 21 U.S.C. § 355(j)(2)(A)(viii), submitted a statement that the ANDA excludes all uses claimed in the patent (section viii statement).

AstraZeneca filed suit and alleged that Apotex’s ANDA filings infringed and would cause infringement of the method patents on the theory that the approval of the ANDA would result in unlicensed sales of CRESTOR®, which has FDA-approved patent-protected uses. Such sales would inevitably infringe AstraZeneca’s method patents allegedly contrary to the plain language and legislative aims of 35 U.S.C. §271(e)(2).

Section 271(e)(2) provides as follows:

It shall be an act of infringement to submit-(A) an application [i.e., an ANDA] under section 505(j) of the Federal Food, Drug, and Cosmetic Act [codified at 21 U.S.C. § 355(j)] for a drug claimed in a patent or the use of which is claimed in a patent . . . if the purpose of such submission is to obtain approval under such Act to engage in the commercial manufacture, use, or sale of a drug claimed in a patent or the use of which is claimed in a patent before the expiration of such patent.

The Federal Circuit construed the above section consistently with its holding in Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 65 USPQ2d 1481 (Fed. Cir. 2003), that infringement of method claims under § 271(e)(2) requires filing an ANDA wherein at least one “use” listed in the ANDA is claimed in a patent, especially in view of section viii, which allows generic manufacturers to limit the scope of regulatory approval by excluding patented indications from their ANDAs. Allowing an infringement suit in these circumstances would vitiate section viii; and as such, would be contrary to the statutory scheme.

AstraZeneca also alleged that section viii ignores market realities because, even if a generic drug is formally approved only for unpatented uses, pharmacists and doctors will nonetheless substitute the generic for all indications once it becomes available. The Federal Circuit found this argument unpersuasive. Again consistent with Warner-Lambert, they found that, by adopting AstraZeneca’s views, a pioneer drug manufacturer would be able to maintain de facto indefinite exclusivity over a pharmaceutical compound by obtaining serial patents for approved methods of using the compound and then wielding § 271(e)(2) “as a sword against any competitor’s ANDA seeking approval to market an off-patent drug for an approved use not covered by the patent. Generic manufacturers would effectively be barred altogether from entering the market.” See Warner-Lambert.


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