[author: Kevin E. Noonan]

It is a truism that each case that comes before an appellate court is decided on its own facts and on the court's application of the law to those facts.  The Federal Circuit has the additional burden of establishing consistency to how the law (patent law) is applied to the facts.  But that consistency has been difficult at times to appreciate in recent years, and this case is a good illustration of that difficulty.

The case involved a District Court grant of a preliminary injunction to Momenta in litigation between two ANDA filers.  Momenta entered the marketplace after ANDA litigation with the patent holder, Aventis, over Lovenox (enoxaparin), a specific formulation of heparin.  As explained in the opinion, heparin (unlike most drugs) is not "a single defined molecule" but rather a heterogeneous mixture of molecules that differ in "the length of the polysaccharide chain" and the "component disaccharide units and the corresponding distribution of disaccharide unit sequences in the polysaccharide chains."  This affects its molecular weight distribution as well as the distribution of uronic acid moieties.  Enoxaparin is the result of fragmentation of native heparin into a "diverse set" of oligosaccharides.  Accordingly, FDA approval for ANDA filers required five "criteria" or "standards of identity" to be met, including "[e]quivalence in disaccharide building blocks, fragment mapping, and sequence of oligosaccharide species" identified by specific enzymatic treatment and physical/chemical analyses of the drug product, including separation and spectroscopy.

Although Amphastar filed its ANDA first, Momenta was first to market.  Perhaps tellingly, the Federal Circuit described the genesis of this lawsuit as follows:

Being the only generic version of enoxaparin has it benefits:  its sales generated revenues of $260 million per quarter.  . . .  The approval of Amphastar's version of enoxaparin, and the resultant ruinous competition of another generic version of the drug, threatened this unique market position.  Understandably unwilling to give up a billion dollars in yearly revenue, Momenta initiated the present litigation two days after Amphastar received final FDA approval to market its generic enoxaparin.

The legal basis for the suit was infringement of U.S. Patent No. 7,575,866 assigned to Momenta, which claimed methods for analyzing heparin and specifically low molecular weight heparins such as enoxaparin.  The opinion cited claims 6 and 15 as being "representative" of the '886 patent claims that Momenta asserted against Amphastar:

6.  A method for analyzing an enoxaparin sample for the presence or amount of a non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin that included β-eliminative cleavage with a benzyl ester and depolymerization, comprising: providing an enoxaparin sample that has been exhaustively digested with two or more heparin degrading enzymes; using a separation method to determine, in the enoxaparin sample that has been contacted with two or more heparin degrading enzymes, the presence of a structural signature associated with the non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin that includes .beta.-eliminative cleavage with a benzyl ester and depolymerization; and making a determination about the enoxaparin sample based upon a comparison of the determination of the presence of a structural signature associated with the non naturally occurring sugar associated with peak 9 to a reference standard for enoxaparin, wherein the determination based upon the comparison to the reference standard regards the quality of the sample, to thereby analyze the enoxaparin sample.

15.  A method for analyzing an enoxaparin sample for the presence or amount of a non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin that included β-eliminative cleavage with a benzyl ester and depolymerization, comprising: providing an enoxaparin sample that has been exhaustively digested with two or more heparin degrading enzymes; using a separation method to determine, in the enoxaparin sample that has been contacted with two or more heparin degrading enzymes, the presence of a structural signature associated with the non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin that includes .beta.-eliminative cleavage with a benzyl ester and depolymerization; and making a determination about the enoxaparin sample based upon a comparison of the determination of the presence of a structural signature associated with the non naturally occurring sugar associated with peak 9 to a reference standard for enoxaparin, wherein the level of one or more structural signatures associated with the non naturally occurring sugar associated with peak 9 of FIG. 1 is determined, to thereby analyze the enoxaparin sample.

The Federal Circuit characterized Momenta's complaint as alleging that Amphastar infringed the '886 patent by complying with FDA requirements for testing its enoxaparin product as part of the quality control necessary for making this drug.

Judge Moore joined by Judge Dyk vacated the preliminary injunction and remanded, in an opinion that made it very unlikely that the District Court will be able to grant the injunction.  Chief Judge Rader wrote an extensive and vigorous dissent, once again directing his analysis not only to the specific matter before the Court but also opining more broadly on some of the underlying currents in this Court's, as well as the Supreme Court's, prejudices and presumptions in applying U.S. patent law.  The majority, while noting that review is on an "abuse of discretion" standard curiously then stated that Momenta, as the party seeking the injunction, bore the burden of establishing that it was entitled to the "extraordinary relief" of the injunction.  While true, Momenta presumptively bore that burden before the District Court, and the Federal Circuit (if not engaging in plenary review) should be limited to deciding whether the District Court abused that discretion.

The question here is whether Momenta established a likelihood of (ultimate) success on the merits.  Amphastar's defense in opposing the injunction was that its activities fell within the "safe harbor" of 35 U.S.C. § 271(e)(1):

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention (other than a new animal drug or veterinary biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Act of March 4, 1913) which is primarily manufactured using recombinant DNA, recombinant RNA, hybridoma technology, or other processes involving site specific genetic manipulation techniques) solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

The District Court rejected this contention because the infringing activity occurred after Amphastar received regulatory approval, and interpreted the statute to be limited to otherwise infringing acts that were performed in order to obtain approval (while acknowledging that the information was, ultimately, submitted to the FDA).  According to Judge Moore's opinion, the District Court interpreted the meaning of the statute with reference to its legislative history.

And here, according to the majority, was the source of the District Court's error.  Importantly, Momenta relied in its appellate arguments on the Federal Circuit's recent decision in Classen Immunotherapies, Inc. v. Biogen IDEC, which under analogous circumstances held that post-approval activity does not fall within the § 271(e)(1) safe harbor.  In addition, Momenta argued that the FDA did not specifically require tests falling within the scope of the '886 patent to be performed, and non-infringing alternatives existed.

The majority did not immediately address these arguments, but turned instead to its own independent interpretation of the statute.  In the majority's view, resort to the legislative history was unnecessary if the "plain meaning" of the statutory language was clear.  (Tellingly, the majority cites Supreme Court cases almost exclusively in its analysis.)  Indeed, the panel majority deems any such recourse to the legislative history to be improper, quoting United States v. Ron Pair Enters., Inc., 489 U.S. 235, 240 (1989), for the proposition that the "inquiry must cease if the statutory language is unambiguous and 'the statutory scheme is coherent and consistent.'"  Selectively quoting from portions of the legislative history, the opinion notes that the statute was enacted to "balance the need to stimulate innovation against the goal of furthering the public interest."  H.R. Rep. 98-857, pt. 2, at 2714 (Aug. 1, 1984).  (Note for later reference that the legislative history in the House, rather than the Senate, formed the basis for the majority's understanding of Congressional purpose.)  In citing the statute, the majority highlighted the clause reading that the safe harbor was "solely for uses reasonably related to the development and submission of information under a Federal law."  And this is the end of it, for the majority:  "Congress could not have been clearer in its choice of words," and thus "any activity" included acts taken after approval (provided that there was information submitted under a Federal law).  Moreover, for the majority it is significant that Congress did not limit (expressly) the scope of the safe harbor to the Food, Drug and Cosmetic Act but "broadly" included within the scope of the safe harbor "any federal law" that "regulates the manufacture, use, or sale of drugs."  This interpretation is consistent with the majority's parsing of the rest of the statute, citing portions of the provision that do specifically reference the FDCA (referring to animal drug or veterinary biological product[s]" and by reciting in § 271(e)(2) the specific provisions of the FDCA relating to submission of an ANDA (albeit, to be fair that citation was to provide a definition so that patent law and FDA law would be read consistently).

For the majority, the fact that Congress included express reference to provisions of the FDCA relating to obtaining approval under § 271(e)(2) for infringement made it improper to "import" that limitation into the safe harbor provisions of § 271(e)(1).  Calling theirs the "only coherent and consistent interpretation of" provisions of  § 271(e) (1) relating to "a Federal law which regulates the manufacture, use, or sale of drugs," the majority declares its analysis of the scope of the safe harbor to be "complete":

When the intent of Congress is expressed so clearly and consistently throughout the statute, there is neither the need nor the occasion to refer to the legislative history.  Id.  The scope of the Hatch-Waxman safe harbor does not stop at activities reasonably related to development of information submitted in an ANDA. Instead, the safe harbor applies "to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products."  As long as the allegedly infringing use is "for uses reasonably related" to the development and submission of that information it is not an act of infringement, regardless of where that requirement resides in the law.

The panel majority cites two specific instances where the Supreme Court ruled on the meaning of § 271(e)(1) in a manner consistent with its interpretation:  Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 666 (1990), and Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 202 (2005).  In the Lilly case, the Court interpreted the safe harbor to include testing of medical devices because (despite the "clear and unambiguous language of the statute" that the safe harbor was limited to drugs) in the Court's view regulation of medical devices fell within the ambit of the FDCA.  And in Merck, the Supreme Court "reaffirmed this expansive view" of the safe harbor, holding that infringement of patent claims directed towards activities that were not directly related to obtaining data for submission to the FDA, i.e., clinical trials, but extended to basis compound discovery activities, on the grounds that Congress had used the word "any" in reciting the activities within the scope of the safe harbor.  And the panel also provided a reminder that Merck held that the phrase "reasonably related to the development and submission of information" relating to regulatory approval did not require that the activities actually resulted in information that was submitted for regulatory approval.  Accordingly, but with less than pellucid explication of their reasoning, the panel majority concluded that the Court's Merck decision "explicitly rejected the notion that §271(e)(1) was limited 'to the activities necessary to seek approval of a generic drug'" so long as "the accused infringer 'has a reasonable basis for believing' that the use of the patented invention might yield information that 'would be appropriate to include in a submission to the FDA.'"

Turning to the case before it, the panel majority rejected Momenta's contention that the process and quality control information obtained by Amphastar's infringement was not submitted to the FDA but was retained by defendants; these "batch records" must be maintained "for at least one year after expiration of the batch" of generic enoxaparin and must be "readily available for authorized inspection" by the FDA.  "The fact that the FDA does not in most cases actually inspect the records" does nothing to change the majority's view that the records are produced using the infringing method for producing information that the agency could demand to see.  The panel then based its decision that Amphastar's activities fall within the safe harbor expressly on the Merck decision, and in the process distinguished the Federal Circuit's earlier Classen decision (as it must to come to a contrary conclusion, as it did here).  Classen, the panel majority states, involved voluntary studies "not mandated by the FDA" and that produces "'information that may be routinely reported to the FDA, long after marketing approval has been obtained'" (i.e., adverse event information that is reported as it is obtained).  That is not the case here according to the opinion, because here the information obtained from infringing Momenta's patents is necessary for Amphastar to continue to sell enozaparin (and failure to do so could cause FDA to "suspen[d] or revo[ke] Amphastar's approval."  Accordingly, the opinion states that "[w]e therefore hold that post-approval studies that are "reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs" fall within the scope of the § 271(e)(1) safe harbor."  And under this interpretation of the law, the majority further holds that Momenta is not likely to prevail on the merits below.

The panel majority also rejected Momenta's argument that the existence of non-infringing alternatives should motivate a decision to the contrary.  There is no such requirement in the statutory language, denying the safe harbor in instances where non-infringing alternatives exist.  According to the majority, "the safe harbor expressly allows the submitter the freedom to use an otherwise patented means to develop the necessary information demanded by the 'Federal law,'" which "makes good sense because it eliminates liability for infringement when that act of infringement is, in effect, required by the federal government as part of the continuing safety and efficacy monitoring of an approved drug."  It "also avoids the situation here, where a drug has received approval, but is nevertheless kept from the market based on an FDA mandated testing requirement."  Here, the majority noted that the U.S. Pharmacopoeia requires a determination of the chemical composition of Amphastar's enoxaparin in order to avoid it being rejected as an "adulterated drug," providing yet another rationale for finding Amphastar's activities to fall within the scope of the § 271(e)(1) safe harbor.

And to add insult to injury, the panel majority awarded costs to Appellants (i.e., imposing Amphastar's costs of its appeal on Momenta).

A portion of Judge Rader's dissent has been discussed elsewhere (see "Chief Judge Rader (Not Surprisingly) Gets it Right about Chimerical 'Tragedy of the Anti-Commons'"), and the remainder will be the subject of a subsequent post.  And as preview, and in homage to the late Paul Harvey, that post will consider the rest of the story.

Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc. (Fed. Cir. 2012)
Panel: Chief Judge Rader and Circuit Judges Dyk and Moore
Opinion by Circuit Judge Moore; dissenting opinion by Chief Judge Rader