In a closely watched case challenging FDA’s recent rulings on claims to pediatric exclusivity and 180-day generic exclusivity for Pfizer’s popular hypertension drug Norvasc® (amlodipine), the U.S. District Court for the District of Columbia has denied motions by three generic manufacturers to block FDA from implementing those rulings while the Court more fully considers the parties’ conflicting claims. Mylan Labs., Inc. v. Leavitt, 2007 WL 1241884 (D.D.C. April 30, 2007). Even if appealed, this preliminary decision may well stand as the last word on the matter, as it will be difficult to get a Court of Appeals ruling before the case becomes moot.

Norvasc has been Pfizer’s second-biggest product for the treatment of high blood pressure and angina, with U.S. sales of $2.7 billion last year. Several generic firms with pending ANDAs for amlodipine are eager to secure a piece of the market. The current dispute stems from the interplay of two near-simultaneous events – the recent invalidation of three claims in Pfizer’s controlling patent on amlodipine by the U.S. Court of Appeals for the Federal Circuit (Pfizer Inc. v. Apotex, Inc., 2007 WL 851203 (March 22, 2007)), and the expiration of the same patent only three days later, on March 25, 2007.

The District Court decision in Mylan v. Leavitt upholds, for the time being at least, FDA’s rulings that (1) by virtue of Pfizer’s six-month pediatric exclusivity for Norvasc, no ANDAs for generic amlodipine can be approved until September 25, 2007 – with two exceptions; (2) the two exceptions are Apotex, the only amlodipine ANDA applicant to win its challenge to Pfizer’s patent, and Mylan, which thus far has lost its own challenge to Pfizer’s amlodipine patent but which is the only applicant whose ANDA had previously received final approval from FDA; (3) FDA nonetheless remains barred from granting final approval even of Apotex’s amlodipine ANDA until the Federal Circuit issues its formal mandate in the patent litigation (which may be some time away because of Pfizer’s pending petition for rehearing), leaving Mylan as the only approved manufacturer of generic amlodipine; and (4) Mylan’s right to 180-day generic exclusivity, as the first to file an ANDA challenging the Pfizer patent, was extinguished when the patent expired.

Although this perhaps incongruous outcome is to some extent the result of an unusual combination of facts, the District Court’s legal rationales are sure to be invoked by future litigants as instructive, if not controlling, in subsequent controversies.


The last of Pfizer’s two Orange-Book-listed patents on amlodipine (U.S. Patent No. 4,879,303) expired on March 25, 2007, but in 2001 FDA granted six-month pediatric exclusivity to Pfizer, thus potentially precluding approval of ANDAs for amlodipine from the date of patent expiration until September 25, 2007. Mylan, however, which was the first of several generic firms to file a Paragraph IV ANDA for amlodipine, had already received final approval of its ANDA in October 2005. Still embroiled in the infringement litigation brought against it by Pfizer, Mylan held off marketing; but on March 22, 2007, three days before the ‘303 patent was to expire, the Federal Circuit held in Pfizer’s patent infringement suit against another amlodipine Paragraph IV ANDA applicant (Apotex) that claims 1-3 of the ‘303 patent (the only claims on which Apotex had been sued) were invalid for “obviousness.” Even though by this time the district court in Pfizer’s separate infringement suit against Mylan on the same claims had rejected Mylan’s challenge and enjoined approval of Mylan’s ANDA, on March 23 Mylan obtained a stay of the injunction from the Federal Circuit (presumably on the strength of the Circuit panel’s Apotex decision) and commenced marketing the very same day, thus triggering the start of its statutory 180-day generic exclusivity period as first Paragraph IV ANDA filer.

On March 26, the day after the ‘303 patent expired, Mylan sued FDA in U.S. District Court for the District of Columbia, seeking to enjoin the agency from approving any other ANDAs for amlodipine until Mylan’s 180-day generic exclusivity period had fully run. Apotex and Teva (as well as another generic firm) intervened, opposing Mylan and seeking to compel FDA to approve their respective amlodipine ANDAs immediately. Thus far, Pfizer has not joined the litigation.

At the District Court’s request, FDA notified interested parties and the Court that the agency “has decided not to approve ANDAs other than Mylan’s at this time.” FDA determined that (1) “under the literal terms of the statute,” Pfizer’s pediatric exclusivity does not alter the continuing effectiveness of the final approval previously granted to Mylan’s amlodipine ANDA, and because the district court order enjoining approval of the ANDA was stayed pending appeal, that injunction provides no basis for FDA to take any action; (2) all the unapproved ANDAs are currently blocked by Pfizer’s pediatric exclusivity; (3) ordinarily, “if in paragraph IV litigation a court determines that a patent is invalid or not infringed, pediatric exclusivity will not bar approval of that applicant’s ANDA” (emphasis by FDA); (4) if and when the Federal Circuit issues its mandate effectuating the panel’s March 22 decision in the Apotex case invalidating the ‘303 amlodipine patent, Apotex’s ANDA will no longer be blocked by Pfizer’s pediatric exclusivity; (5) because there were claims in the ‘303 patent not addressed by the Federal Circuit in Apotex, “in the absence of further judicial or other action clarifying the status of the patent, FDA will assume the ‘303 patent remains validly listed” in the Orange Book, which will block approval of other ANDAs, such as Teva’s, until Pfizer’s pediatric exclusivity expires; and (6) Mylan’s 180-day marketing exclusivity terminated when the patent expired.

The District Court’s Decision

The Court found that neither Mylan, Apotex, nor Teva had demonstrated “a substantial likelihood of success on the merits” so as to justify a preliminary injunction against FDA’s implementation of its rulings. In addition, the Court found that none of them had shown the “irreparable injury” necessary to justify issuing a preliminary injunction, as they had not even argued that loss of the “millions of dollars” at stake for each firm, even if irretrievable, “would threaten the continued existence of their businesses” as preliminary-injunction principles require. Nor did any “balancing of equities” or public interest considerations support preliminary injunctive relief.

1. Because Pfizer was awarded pediatric exclusivity for amlodipine, FDA is precluded by statute from approving amlodipine Paragraph IV ANDAs such as Apotex’s and Teva’s until September 25, 2007 if “in the patent infringement litigation resulting from the [Paragraph IV] certification the court determines that the patent is valid and would be infringed” (21 U.S.C. § 355a(c)(2)(B)). Although the Court did not articulate any analysis of the issue, it endorsed FDA’s ruling that “[b]ased on this language, … the converse must also be true –” a “determin[ation]” of patent invalidity forecloses pediatric exclusivity based on the invalidated patent, at least as to the successful Paragraph IV litigant. This is a significant addition to pediatric-exclusivity doctrine.

The Court acknowledged, as had FDA, that this result “clearly marks a departure” from established principles relating to the effect of patent expiration on pending ANDA certifications (discussed below). But it deemed the inconsistency “reasonable,” “not contrary to the language in Hatch-Waxman,” and “well within the agency’s discretion” in light of its conclusion that the statute “manifests a clear Congressional intent that pediatric exclusivity not block [a Paragraph IV] ANDA applicant [that] has prevailed in [its] patent infringement litigation.”

2. The Court nevertheless noted that § 355a(c)(2)(B) is “silen[t] as to the particular court which may determine the patent dispute,” and concluded that under the terms of that provision, the ruling of the district court in Pfizer’s infringement suit against Apotex that the patent was valid and infringed had triggered Pfizer’s pediatric exclusivity. (This is consistent with previous court decisions, including one obtained, ironically, by Apotex, interpreting similar language in other Hatch-Waxman provisions.) Quoting D.C. Circuit authority, the Court further reasoned that “‘the vitality of [the district court] judgment is undiminished by pendency of the appeal. Unless a stay is granted either by the court rendering the judgment or by the court to which the appeal is taken,’ … the pediatric exclusivity period, triggered by the district court’s ruling, remains effective until it is formally stayed or reversed.” Accordingly, the Court concluded that Apotex had failed to demonstrate a substantial likelihood of showing that FDA acted contrary to law in its decision to await the Federal Circuit mandate before approving Apotex’s ANDA.

That mandate may be a while in coming. On April 5, Pfizer filed a motion in the Federal Circuit Apotex patent case for rehearing and/or rehearing en banc, which automatically stays the issuance of mandate. The likelihood of the motion being granted may have been substantially diminished by the Supreme Court’s fortuitously-timed decision in KSR Int’l Co. v. Teleflex Inc., 2007 WL 1237837 (U.S. April 30, 2007), endorsing a broad application of the “obviousness” defense on which Apotex prevailed. But the Federal Circuit may feel constrained at least to review the panel’s Apotex decision for consistency with KSR (and indeed may conclude that it has been instructed by the Supreme Court to do so, see KSR at 16).

3. The District Court in Mylan v. Leavitt also declined to interfere with FDA’s determination that other generic amlodipine manufacturers, including Teva, will continue to be blocked from ANDA approval even if and when the Federal Circuit mandate in Apotex issues. Because the Federal Circuit invalidated only three claims of Pfizer’s ‘303 amlodipine patent, the Court stated, the patent remains valid as to the remaining claims. Whether the remaining claims justify the continued listing of the patent, the Court ruled, is something FDA need not attempt to decide. (This too is consistent with previous court decisions, this time including one against Apotex, confirming FDA’s role, or lack of one, in evaluating patents for Hatch-Waxman purposes.) And now that the patent has expired, those other ANDA applicants are deemed (under the established principles mentioned above) to have filed Paragraph II certifications, which under the pediatric exclusivity statute cannot be approved until the six-month pediatric exclusivity period expires. “[U]ntil Teva succeeds in its own patent litigation with Pfizer or until administrative or legal action completely de-lists Pfizer’s patent from the Orange Book,” the Court ruled, FDA’s decision to withhold approval of Teva’s ANDA remains in effect.

4. Finally, the Court addressed Mylan’s claim that its position as the first Paragraph IV ANDA filer bars FDA from approving Apotex’s or any other Paragraph IV amlodipine ANDA until 180 days after Mylan commenced marketing on March 23, 2007. The Court rejected Mylan’s claim, agreeing with FDA that “when Pfizer’s Norvasc patent expired on March 25, 2007, all paragraph IV certifications converted to paragraph II certifications and became eligible for approval.” Because Mylan’s generic exclusivity, by the terms of the statute, operates only to preclude approval of Paragraph IV ANDAs during the 180-day exclusivity period, and as all Paragraph IV certifications cease to exist upon patent expiration, FDA’s decision that Mylan’s 180-day generic exclusivity does not survive patent expiration was deemed a reasonable interpretation of the statute. (This is consistent with the conclusions of other courts on the issue, including a 2006 D.C. Circuit decision involving, among others, Teva.)


For now, Mylan retains its position as the exclusive source of generic amlodipine, other than Pfizer’s “authorized generic” launched the same day as the Mylan product. FDA will not approve any other amlodipine ANDAs unless and until the Federal Circuit issues its mandate under the panel’s March 22, 2007 decision holding Claims 1-3 of the ‘303 patent invalid for “obviousness.” Mylan therefore enjoys de facto generic exclusivity by virtue of Pfizer’s pediatric exclusivity, despite the fact that Mylan’s statutory 180-day generic exclusivity technically ended upon expiration of Pfizer’s ‘303 patent. If and when the Federal Circuit mandate does issue, however, Mylan will have to “share” its de facto exclusivity with Apotex. And for the future, the District Court decision reveals a new exception to pediatric exclusivity.