In an effort to bring generic drugs to market in a timely manner while maintaining patent protection for innovator drugs, Congress enacted a specialized infringement provision, 35 U.S.C. § 271(e)(2). In connection with that provision, a panel of the United States Court of Appeals for the Federal Circuit (“Federal Circuit”) recently held that innovator drug companies cannot maintain a suit for infringement against generics where the generics seek marketing approval only for uses of the innovator drug that do not fall under the explicit terms of the innovator patent(s).

The patent statute contains provisions specifically directed to infringement based on a generic drug company’s submission of an Abbreviated New Drug Application (“ANDA”) to the U.S. Food and Drug Administration (“FDA”) in order to obtain approval to market a generic equivalent of a brand name drug. Specifically, 35 U.S.C. § 271(e)(2) provides in relevant part: “It shall be an act of infringement to submit - (A) an application under section 505(j) of the Federal Food, Drug, and Cosmetic Act or described in section 505(b)(2) of such Act for a drug claimed in a patent or the use of which is claimed in a patent . . . .” This provision allows holders of New Drug Applications (“NDA”) to bring infringement actions against ANDA filers at the time the ANDA is submitted to the FDA.

In considering the scope of § 271(e)(2) in the context of method of use patents, a panel of the Federal Circuit in AstraZeneca Pharm. LP v. Apotex Corp., 669 F.3d 1370 (Fed. Cir. 2012) (“AstraZeneca”) held for the first time that ANDA applicants can “carve-out” patented methods of use from their ANDAs (and thereby insulate themselves from an infringement suit under § 271(e)(2) based on those methods) by excluding patented indications from their ANDAs.

Some NDA holders have argued that this result will allow generic drug makers to “carve-out” patented drug indications on paper, but that doctors and pharmacists will prescribe the drugs in an infringing manner—in effect allowing generics to induce infringement without consequence. On the other hand, ANDA filers argue that such speculative arguments, if accepted, would allow NDA holders to improperly extend their exclusivity over pharmaceutical compounds.

This article addresses the relevant statutory framework, the fact pattern presented by AstraZeneca and the Federal Circuit’s analysis of the reach of § 271(e)(2).

Underlying Statutory Framework

Pursuant to the Hatch-Waxman Act, a generic drug manufacturer may seek FDA approval by submitting an ANDA demonstrating that its generic drug formulation is bioequivalent to the pioneer drug of interest. See 21 U.S.C. § 355(j)(2)(A). According to the statutory scheme, which seeks to strike a balance between protecting innovation and bringing affordable drugs to market, see Teva Pharm. USA, Inc. v. Pfizer, Inc., 395 F.3d 1324, 1327 (Fed. Cir. 2005), the pioneer drug maker must provide a list to the FDA of all patents covering its drug or a method of use for which “a claim of patent infringement could reasonably be asserted” against a generic drug maker. 21 U.S.C. § 355(b)(1). A list of all such patents is published in what is known as the FDA’s “Orange Book.” See U.S. Dep’t of Health & Human Servs., Food and Drug Administration, Approved Drug Products with Therapeutic Equivalence Evaluations (32d ed. 2012). An ANDA may be submitted prior to the expiration of listed patents covering the pioneer drug, as long as the ANDA is accompanied by a proper certification indicating that: (I) there is no listed patent covering the drug; (II) the patent has expired; (III) the patent will expire on a specified date; or (IV) the patent is invalid or would not be infringed by the filer’s drug product. 21 U.S.C. § 355(j)(2)(A). The submission of an ANDA with a paragraph IV certification is a technical act of infringement, 35 U.S.C. § 271(e)(2)(A), and the patent holder must be provided with proper notice of the filing. See 21 U.S.C. § 355 (j)(2)(B). As an alternative to one of the four above-listed certifications, an ANDA applicant may also submit a section viii statement certifying that the ANDA does not seek approval for any indications claimed by relevant patents listed in the Orange Book. 21 U.S.C. § 355(j)(2)(A)(viii). “A section viii statement ‘indicates that a patent poses no bar to approval of an ANDA because the applicant seeks to market the drug for a use other than the one encompassed by the patent.’” AstraZeneca Pharm. LP v. Apotex Corp., No. 10-338, 2010 WL 5376310, at *2 (D. Del. Dec. 22, 2010) (citation omitted).

Where a patent holder is notified of a paragraph IV certification, it may sue the ANDA filer within 45 days. 21 U.S.C. § 355(j)(5)(B)(iii). 35 U.S.C. § 271(e)(2) creates an artificial cause of action for patent infringement in this situation—making the filing of an ANDA “for a drug claimed in a patent or the use of which is claimed in a patent” an act of infringement so that NDA holders can sue to enforce their patents before the FDA approves the ANDA. See, e.g., AstraZeneca, 2010 WL 5376310, at *3.

The AstraZeneca Case

The litigation at issue in AstraZeneca related to the drug rosuvastatin calcium, developed and marketed by AstraZeneca as CRESTOR®. AstraZeneca, 669 F.3d at 1373. AstraZeneca holds a patent claiming the compound and two patents claiming methods of using the drug to treat specific cholesterol related issues. Id. The compound patent expires several years earlier than the two method of use patents. Id.

The FDA approved AstraZeneca’s NDA for rosuvastatin calcium to treat certain uses claimed in AstraZeneca’s two method of use patents and additional non-patented uses. Id. Defendants were several generic pharmaceutical manufacturers who filed ANDAs seeking approval to make and market rosuvastatin calcium for uses that were approved by FDA, but not claimed in AstraZeneca’s two method of use patents. Id. at 1374.

Previous to suit AstraZeneca listed certain patents in the Orange Book, including the three patents described above. Id. at 1373. Defendants filed paragraph IV certifications for the compound patent, but submitted section viii statements for the two method of use patents because the ANDAs only sought approval for non-patented methods of use. Id. at 1374. AstraZeneca sued for infringement of the three patents under § 271(e)(2) in various actions. Id. at 1374-1375. Defendants challenged AstraZeneca’s ability to sustain a cause of action under § 271(e)(2) for the method of use patents on several grounds. Id. at 1375. The district court dismissed AstraZeneca’s complaints relating to the method of use patents for lack of jurisdiction. Id. at 1376.

Federal Circuit Ruling That ANDAs Claiming Unpatented, But FDA-Approved, Uses Cannot Form The Basis Of An Action Under § 271(e)(2)(A)

On appeal, the Federal Circuit determined that a viable cause of action based on a method of use patent listed in the Orange Book cannot be sustained pursuant to § 271(e)(2) where the alleged infringer does not seek approval for the use covered by the patent at issue. The Federal Circuit reached this conclusion on different grounds than that of the district court. The district court had dismissed the actions based on lack of subject matter jurisdiction. The Federal Circuit disagreed with the district court’s decision in this regard, but affirmed on other grounds—specifically that AstraZeneca failed to state a viable claim for relief under § 271(e)(2). AstraZeneca, 669 F.3d at 1377.

Put simply, “the Act allows generic manufacturers to limit the scope of regulatory approval they seek—and thereby forego Paragraph IV certification and a § 271(e)(2) infringement suit—by excluding patented indications from their ANDAs.” Id. at 1379.

In reaching this conclusion, the Federal Circuit observed that the Hatch-Waxman Act “only allows ANDA filers to obtain approval for marketing drugs for uses that have been approved under a preexisting NDA. [Here, Defendants] further restricted their ANDAs, . . . ‘carving out’ patented indications.” Id. at 1374. The Federal Circuit rejected AstraZeneca’s argument that Defendants’ “ANDA filings infringed and would cause infringement of the . . . method patents, even though [they] had not requested approval for any patented indications and had filed Section viii statements to that effect.” Id. at 1375. AstraZeneca’s two main arguments were: (1) approval of the ANDAs would infringe the method patents because approval would result in unlicensed sales of a product having FDA-approved patent protected uses; and (2) the FDA would eventually require amendments to the ANDAs to include all approved indications (negating any attempt at a carve-out). Id. at 1376.

With respect to AstraZeneca’s first argument, the Federal Circuit agreed with AstraZeneca that the claims were within the district court’s jurisdiction, but found that AstraZeneca failed to state a viable claim for relief under § 271(e)(2) based on the language of the statute: “It shall be an act of infringement to submit . . . [an ANDA] for a drug claimed in a patent or the use of which is claimed in a patent . . . .” 35 U.S.C. § 271(e)(2)(A) (emphasis added).

The italicized language—the use of which—had been interpreted previously by the Federal Circuit to mean “the use listed in the ANDA.” Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1356 (Fed. Cir. 2003). Thus, the Federal Circuit there held 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.” AstraZeneca, 669 F.3d at 1378 (citing Warner-Lambert, 316 F.3d at 1358-59). AstraZeneca attempted to distinguish Warner-Lambert on its facts because there the asserted patent claimed an unapproved use. Id. at 1379. The Federal Circuit found that to be a distinction irrelevant for purposes of § 271(e)(2). Id. Overall, claims under § 271(e)(2) are precluded when “based on method of use patents where the ANDA does not expressly recite a patented method.” Id.

Finally, the Federal Circuit rejected AstraZeneca’s argument based on its claim that the FDA will, in the future, require the label for Defendants’ rosuvastatin calcium to include information relating to the uses in AstraZeneca’s method patents as unripe for adjudication because that claim rested on “contingent future events that may never occur.” Id. at 1380.


Although the law is likely to further evolve, the AstraZeneca decision presently provides that a labeling carve-out with a section viii statement is a permissible route for generic drug makers to avoid litigation under § 271(e)(2) and seek FDA approval. In the event that NDA holders have a basis to bring an action for induced infringement under 35 U.S.C. § 271(b) after a generic formulation is on the market, they may do so at that time. Necessarily, however, the NDA holders will not be afforded the 30 month stay they would otherwise get under the Hatch-Waxman statute and will typically face higher evidentiary burdens as they will likely have to prove that doctors are prescribing the generic drug for the patented use.

*This article initially appeared in the January/February 2012 IP Litigator.