Limitation On Future Patent Protection For Biosimilars?

On August 3, 2012, the U.S. Court of Appeals for the Federal Circuit issued an opinion vacating a preliminary injunction that had been granted by the U.S. District Court for the District of Massachusetts to Momenta Pharmaceuticals, Inc. and Sandoz, Inc. (collectively, "Momenta"). See Momenta Pharmaceuticals, Inc., et al. v. Amphastar Pharmaceuticals, Inc., et al., Nos. 2012 1062,-1103, -1104 (Fed. Cir. Aug. 3, 2012) ("Momenta Opinion").¹ Click here for the opinion.

Momenta – the sole marketer in the United States of a generic version of sanofi-aventis's branded drug Lovenox® (enoxaparin) until recently – had previously brought suit against Amphastar Pharmaceuticals, Inc., International Medication Systems, Ltd., Watson Pharmaceuticals, Inc. And Watson Pharma, Inc. (collectively, "Amphastar") for infringement of Momenta's patents, which claim quality control methods for generic enoxaparin products. At Momenta's request, the district court issued a preliminary injunction precluding Amphastar from selling its own generic version of Lovenox®, rejecting Amphastar's argument that its use of Momenta's patented methods after FDA approval of Amphastar's generic product could fall within the safe harbor of 35 U.S.C. § 271(e)(1). On appeal, the Federal Circuit vacated the preliminary injunction (over Chief Judge Rader's dissent), holding that in some circumstances, even post-approval manufacturing activities may fall within the § 271(e)(1) safe harbor and be protected from infringement liability.

Background and District Court Litigation Below

Lovenox® (enoxaparin) is a low molecular weight heparin, a complex polysaccharide comprising sugar chains of varying lengths and compositions. In July 2010, in response to a Citizen's Petition, the FDA established five criteria that would be required for a generic enoxaparin product to demonstrate active ingredient "sameness" to Lovenox®. These criteria include, inter alia, evaluating "the nature and arrangement of components that constitute enoxaparin." On the same day that the FDA issued these guidelines, it approved an ANDA for a generic enoxaparin product developed in collaboration between Momenta and Sandoz.

Prior to approval of its generic enoxaparin product, Momenta had obtained U.S. Patent No. 7,575,886 ("the '886 patent"), with claims directed to methods of analyzing a sample of enoxaparin to ensure its conformity with an enoxaparin reference standard. Momenta subsequently asserted these claims against Amphastar, a potential competitor that had filed its own ANDA for a generic version of enoxaparin. In response to Momenta's request for a preliminary injunction, Amphastar asserted, inter alia, that its alleged infringing activities fell within the safe harbor of 35 U.S.C. § 271(e)(1), a statutory provision that protects otherwise infringing activity when used "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." The district court rejected Amphastar's argument, holding that the § 271(e)(1) safe harbor "'does not permit a generic manufacturer to continue in [an] otherwise infringing activity after obtaining [FDA] approval.'"²

Federal Circuit Majority Opinion

In vacating the preliminary injunction, the Federal Circuit found that the district court had adopted an overly narrow interpretation of the safe harbor provided by § 271(e)(1). According to the majority, the § 271(e)(1) safe harbor is not restricted to activities conducted prior to FDA approval for inclusion in an ANDA under 21 U.S.C. § 355(j), and may include post-approval activities conducted to generate information for "submission" pursuant to federal law.³ The court further held that the act of "submission" under § 271(e)(1) may include merely maintaining information in records for possible FDA inspection – even if such inspection is unlikely to actually take place.⁴ Finally, the court held that the safe harbor may apply even in the case where there are potential non-infringing alternatives that could conceivably meet FDA requirements for post-approval submissions.⁵ According to the majority, "[a]s long as the use of [a] patented invention is done to generate information that will be submitted pursuant to a relevant federal law, that use falls within the safe harbor."⁶

The majority acknowledged and distinguished the prior Federal Circuit decision in Classen Immunotherapies, Inc. v. Biogen IDEC,⁷ in which the court held that the safe harbor is notApplicableto "'information that may be routinely reported to the FDA, long after marketing approval has beenobtained.'"⁸ According to the court, Classen merely carved out from the § 271(e)(1) safe harbourcertain "routinely reported" post-approval submissions. Thus, the court held that Amphastar's qualitycontrol records do not qualify as "routinely reported" information under Classen because theirmaintenance is required by FDA and is necessary for Amphastar to "continue its FDA approval for itsANDA and to continue manufacturing and marketing enoxaparin under its ANDA."⁹ In particular, theFederal Circuit pointed to the fact that under FDA statute and regulation, Amphastar could not sell abatch of enoxaparin unless it maintained quality control batch records for inspection by FDA at anytime.¹⁰

Chief Judge Rader's Dissent

In his dissent, Chief Judge Rader took issue with the majority's statutory interpretation of the § 271(e)(1) safe harbor provision in several respects. First, Chief Judge Rader argued that the safe harbor provision cannot be properly interpreted to encompass "post-approval, continuous, commercial use[s]."¹¹ Chief Judge Rader pointed to legislative history that only addressed pre approval activities,¹² and further noted that the term "solely" should exclude post-approval activities used "for the purpose of manufacturing a product to sell on the market in commerce."¹³ Chief Judge Rader also disputed the majority's broad interpretation of the term "submission," finding that it would encompass "almost all activit[ies] by pharmaceutical companies" for which a "record" can be made, in view of law allowing FDA inspection of any drug manufacturer records.¹⁴ Furthermore, Chief Judge Rader argued that Classen did in fact rule that post-approval activities are excluded from the § 271(e)(1) safe harbor, and that the instant decision creates a conflict with Classen perhaps suitable for en banc review.¹⁵ Even under the majority's reading of Classen, Chief Judge Rader disagreed that the patented analytic methods at issue in this case were "mandated" by FDA, arguing that Amphastar conceivably could have invented its own method to meet FDA's requirements, but chose not to do so.¹⁶ Finally, Chief Judge Rader asserted that, as a practical matter, the majority's interpretation of § 271(e)(1) could "essentially render manufacturing method patents worthless," particularly in the scenario where an innovative, patented method is adopted as an FDA standard because of its superiority, and is thereby deprived of its right to effective patent protection.¹⁷

Potential Implications for Biosimilars Litigation

Although the approval of generic equivalents to Lovenox® is regulated under the Hatch-Waxman Act, and not the Biologics Price Competition and Innovation Act of 2009 ("BPCIA"), FDA's "sameness" requirements for generic enoxaparin products bear a resemblance to FDA's current draft guidance for approval of biosimilar products under the BPCIA. Likewise, it can be expected that developers of biosimilars could try to patent their innovative, proprietary methods for meeting the quality control benchmarks required to establish biosimilarity – which may be developed after significant expenditure of time and resources. Under the Federal Circuit's opinion in Momenta, it may be the case that if FDA adopts a patented analytic method as a standard for all biosimilar applications on a particular reference biologic product, the use of such methods by competitors of the patentee may be subject to an argument that it is shielded under the § 271(e)(1) safe harbour provision even when conducted in the course of post-approval manufacturing. Chief Judge Rader's dissent suggested that the rule established by the Momenta majority may undermine the incentives for developers of biosimilars and other researchers to innovate in this challenging, dynamic scientific field.

Moreover, given the breadth of the Momenta majority's statutory constructions regarding what constitutes a "submission" and when an activity is "solely" for uses reasonably relating to such submissions, it is unclear whether the majority's opinion might even extend beyond the field of post-approval analytical testing, and limit patent protection for claims directed to other post approval manufacturing activities. For example, if FDA required all biosimilar applicants for a reference biologic product to perform a particular patented purification step in order to obtain and maintain approval as biosimilar, Momenta might be argued to shield such manufacturing activities from infringement liability, even when conducted for commercial market batches. Given the apparent split between the Momenta and Classen decisions, and Chief Judge Rader's dissent, it is quite possible that these issues will continue to be addressed in subsequent panel decisions or perhaps an en banc review.

Footnotes

^{1 Notably, the Federal Circuit had already stayed the preliminary injunction shortly after hearing oral argument. See Momenta Opinion at 7.}

^{2 See id. at 9.}

^{3 See id. at 17-20, 22 & n.2.}

^{4 See id. at 16-17.}

^{5 See id. at 21-22.}

^{6 Id. at 22.}

^{7 659 F.3d 1057 (Fed. Cir. 2011).}

^{8 See Momenta Opinion at 18 (quoting Classen, 659 F.3d at 1070).}

^{9 See Momenta Opinion at 19.}

^{10 See id. at 22-24.}

^{11 See Momenta Opinion at 2-13 (Rader, J., dissenting).}

^{12 See id. at 3-11.}

^{13 See id. at 11-12.}

^{14 See id. at 12 (citing 21 U.S.C. § 374).}

^{15 See id. at 13-16.}

^{16 See id. at 16-17.}

^{17 See id. at 17-18.}

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