March 2012

ANDA Seeking to Market a Drug for Unpatented Uses Cannot Infringe Method of Use Patents Under 35 U.S.C. § 271(e)(2)
Angela Y. Dai

In AstraZeneca Pharmaceuticals LP v. Apotex Corp., Nos. 11-1182, -1183, -1184, -1185, -1186, -1187,
-1188, -1189, -1190 (Fed. Cir. Feb. 9, 2012), the Federal Circuit affirmed the district court’s dismissal of AstraZeneca Pharmaceuticals LP, AstraZeneca AB, IPR Pharmaceuticals, Inc., and The Brigham and Women’s Hospital, Inc.’s (collectively “AstraZeneca”) 35 U.S.C. § 271(e)(2) patent infringement claims for infringement of two method of use patents.

AstraZeneca markets a cholesterol-lowering drug, rosuvastatin calcium, under the brand name CRESTOR® and holds rights to two method patents, U.S. Patent Nos. 6,858,618 (“the ’618 patent”) and 7,030,152 (“the ’152 patent”), which are at issue in this appeal, and a compound patent which was the subject of a separate ANDA litigation and appeal.  Collectively, the two patents-at-issue claim methods of using rosuvastatin compounds to treat heterozygous familial hypercholesterolemia (“HeFH”) and to lower the cardiovascular disease risk for individuals with elevated circulating C-reactive protein (“CRP”).  Each patent is listed in the FDA’s Orange Book and covers an approved indication for use of CRESTOR®.

In addition to the two treatment indications claimed in the patents-at-issue, rosuvastatin calcium is also approved for uses not claimed by either of these patents, including the treatment of patients with homozygous familial hypercholesterolemia (“HoFH”) or hypertriglyceridemia.  The defendant generic pharmaceutical companies (collectively “the generic manufacturers”) filed ANDAs seeking to market generic rosuvastatin calcium for treating HoFH and hypertriglyceridemia while carving out the patented indications directed toward HeFH and elevated CRP.  To do so, the generic manufacturers filed statements under 21 U.S.C. § 355(j)(2)(A)(viii) (“Section viii statement”) averring that their ANDAs excluded all uses claimed in the ’618 and ’152 patents.

In prior litigation, AstraZeneca sued several generic manufacturers for infringement of its compound patent, which the district court found valid, enforceable, and infringed, conferring exclusivity until 2016.  Those determinations are the subject of a separate appeal.  While that litigation was pending, AstraZeneca brought suit for infringement of its method of use patents, asserting that the ANDA filings infringed and would cause infringement of the method of use patents under § 271(e)(2).  AstraZeneca alleged that (1) the ANDAs violated § 271(e)(2) as applications for a drug, the use of which is claimed in the ’618 and ’512 patents; (2) if approved by the FDA, the generic manufacturers’ proposed activities will induce infringement of the ’618 and ’152 patents; and (3) the FDA will require labeling amendments explicitly incorporating the indications covered by the ’618 and ’152 patents.  The district court dismissed AstraZeneca’s infringement claims for lack of subject matter jurisdiction, finding that AstraZeneca had not presented a valid § 271(e)(2) claim based on the ANDA filings.  The district court also held that AstraZeneca’s claims were unripe to the extent they relied on presumptive future labeling amendments.  AstraZeneca appealed.

On appeal, the Federal Circuit first addressed the issue of subject matter jurisdiction.  The Court rejected the district court’s determination that subject matter jurisdiction did not exist, explaining that, under 28 U.S.C. § 1338(a), the district courts have original jurisdiction over any civil action arising under any Act of Congress relating to patents.  And by enacting § 271(e)(2), Congress established a specialized new cause of action for patent infringement.  The Court explained:  “When patentees pursue this route, their claims necessarily arise under an Act of Congress relating to patents.”  Slip op. at 13.  Thus, “the requirements for jurisdiction in the district courts are met once a patent owner alleges that another’s filing of an ANDA infringes its patent under § 271(e)(2), and this threshold jurisdictional determination does not depend on the ultimate merits of the claims.”  Id.  Accordingly, AstraZeneca met the requirements for subject matter jurisdiction under § 1338(a) when it alleged that the ANDA filings infringed its listed patents under § 271(e)(2).

The Federal Circuit, however, agreed with the district court’s underlying determination that AstraZeneca failed to state a viable claim for relief under § 271(e)(2).  The Court first rejected AstraZeneca’s interpretation of § 271(e)(2), finding 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.  “Thus, an ANDA seeking to market a drug not covered by a composition patent for unpatented methods of treatment cannot infringe under § 271(e)(2).”  Id. at 17.

Second, the Court also disagreed with AstraZeneca’s attempt to distinguish Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348 (Fed. Cir. 2003), as involving a patent that claimed an unapproved or
“off-label” use for which no generic could be approved through the ANDA process.  The Federal Circuit found the distinction between patents claiming unapproved and approved uses irrelevant for purposes of § 271(e)(2), explaining that when considering allegations that an ANDA filing infringes a patented method, § 271(e)(2) directs the analysis to the scope of approval sought in the ANDA.  The Court noted that the Hatch-Waxman 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 with a Section viii statement.  The Court held that is what occurred here.

The Federal Circuit was not convinced by AstraZeneca’s practical argument that pharmacists and doctors can substitute the generic product for all indications once the product becomes available regardless of the uses expressly sought in an ANDA.  The Court stated that finding infringement under § 271(e)(2) based on such speculative prescribing practices would, in practice, vitiate § 355(j)(2)(A)(viii) by enabling § 271(e)(2) infringement claims despite a Section viii statement and corresponding proposed labeling that explicitly and undisputedly carves out all patented indications for a particular product.  Moreover, the Court expressed concern that a pioneer drug manufacturer could 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.

Finally, the Federal Circuit found that AstraZeneca’s allegation that the FDA would require future labeling amendments to include all FDA-approved indications for rosuvastatin calcium were insufficiently ripe for adjudication to the extent they relied on prospective labeling amendments.  Here, the ANDAs affirmatively carved out the patented indications, were limited to unpatented methods for using rosuvastatin calcium, and the Court stated that nothing in the record indicated that the FDA required or would require the labeling amendments asserted by AstraZeneca.

Accordingly, the Federal Circuit affirmed the district court’s dismissal of AstraZeneca’s complaint despite the existence of subject matter jurisdiction.