Orange Book Blog

Federal Circuit Hands Mixed Ruling to Momenta on 271(g) and 271(e)(1) Issues

Momenta and Sandoz v. Teva, No. 2014-1274 (Fed. Cir.)

Momenta and Sandoz v. Amphastar, No. 2014-1276 (Fed. Cir.)

    by Aaron F. Barkoff

In a precedential opinion today, in companion cases concerning generic enoxaparin, the Federal Circuit reached two decisions that pharmaceutical companies should take note of:

1.    Teva's enoxaparin is not "made by" a patented process within the meaning of § 271(g) because the process is used merely "to ensure that the intended product or substance has in fact been made."  In other words, the process simply "provides information regarding a substance that has already been made but does not transform it."

2.    The safe harbor of § 271(e)(1) does not apply to Amphastar's "routine quality control testing of each batch of generic enoxaparin as part of the post-approval, commercial production process."

Momenta and Sandoz, which were the first to market a generic version of Sanofi's anticoagulant Lovenox (enoxaparin), asserted U.S. Patent No. 7,575,886 against Teva and Amphastar.  The '886 patent claims methods for analyzing enoxaparin to determine whether it has the appropriate chemical structure.  Momenta alleged that Teva's and Amphastar's enoxaparin manufacturing processes infringe the '886 patent.

The Federal Circuit's decision concerning § 271(g) was a split decision, with Judges Wallach and Moore in the majority and Judge Dyk dissenting.  According to the majority opinion, Momenta argued that its patented method "is used [by Teva] to select and separate batches of intermediate drug substance that conform to USP requirements for enoxaparin from batches that do not," and that selected batches are then used to make the finished drug product.  The majority concluded, "Although Momenta's arguments are not without merit, it is more consonant with the language of the statute, as well as with this court's precedent, to limit § 271(g) to the actual 'ma[king]' of a product, rather than extend its reach to methods of testing a final product or intermediate substance to ensure that the intended product or substance has in fact been made."

Judge Dyk, in dissent, argued that "the quality control testing method of the '886 patent is a necessary intermediate step in the manufacture of enoxaparin."  He warned:

Patents on purification methods or the quality control method at issue here, which may be integral to the regulatory or commercial viability of a product, but which do not create or transform a product, combine components, or confer new properties, could be freely infringed simply by outsourcing those processes abroad.  Congress could not have intended to create this loophole when it sought to protect process patent owners from foreign competitors using U.S. manufacturing processes abroad.

The Federal Circuit's decision concerning the 271(e)(1) safe harbor is especially interesting because the court previously reached the opposite conclusion during the preliminary injunction phase of the case (Momenta I).  There, the court found that Amphastar's testing according to the patented method was protected by the safe harbor because it was "necessary both to the continued approval of the ANDA and to the ability to market the generic drug."  The majority in that case distinguished the facts from those in Classen, where the court held that § 271(e)(1) "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."  In Momenta I, Judge Moore wrote the opinion for the majority, which included Judge Dyk, while Chief Judge Rader vigorously dissented.

This time around, the panel (which again included Judges Dyk and Moore) unanimously held that § 271(e)(1) does not exempt Amphastar's testing.  The court states, "With the benefit of additional briefing in the current appeals, which reflects the full district court record developed by all parties after the preliminary injunction phase, we conclude Amphastar's submissions are appropriately characterized as 'routine.'"  According to the court, "The conclusion in Momenta I that Amphastar's commercial use of Momenta's patented method falls within the safe harbor of § 271(e)(1) would result in manifest injustice.  Amphastar points to no case, until Momenta I, extending immunity under § 271(e)(1) to encompass activities related to ongoing commercial manufacture and sale."  Thus, the court vacated the district court's grant of summary judgment to Amphastar and remanded the case.

Momenta Pharmaceuticals Files Supreme Court Petition in 271(e)(1) Safe Harbor Case

    by Aaron F. Barkoff

Following through on its plan announced earlier this month, Momenta Pharmaceuticals recently filed a petition for a writ of certiorari in Momenta v. Amphastar.  As we reported previously, the Federal Circuit's decision in this case appears to conflict with its 2011 decision in Classen v. Biogen IDEC.  Both cases concern the scope of the "safe harbor" under 35 U.S.C. 271(e)(1), which exempts certain activities that otherwise would amount to patent infringement.

Recapping briefly, in Classen, the patent owner accused its competitors of infringing patents claiming methods of immunization.  Specifically, Classen alleged that the defendants' post-approval studies of vaccines were infringing activities, and the defendants argued that their participation in the vaccine studies was reasonably related to the FDA requirement to report adverse events to FDA, and was therefore encompassed by the safe harbor.  In a 2-1 decision, the Federal Circuit found in favor of Classen, holding that 271(e)(1) "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."

In Momenta, the patent owner accused its competitors of infringing patents claiming methods of analyzing enoxaparin.  More specifically, Momenta argued that the defendants' post-approval testing of commercial batches of enoxaparin infringed its patent.  The defendants, on the other hand, argued that their activities were reasonably related to the FDA requirement to perform quality-control testing on commercial batches of their product, and were therefore protected by the safe harbor.  This time, in another 2-1 decision, the Federal Circuit found in favor of the defendants.  The majority distinguished Classen:

Here, the submissions are not "routine submissions" to the FDA, but instead are submissions that are required to maintain FDA approval.  . . .  Unlike Classen, where the allegedly infringing activity "may" have eventually led to an FDA submission, there is no dispute in this case that Amphastar's allegedly infringing activities are carried out to "satisfy FDA's requirements."

The defendants in Classen petitioned the Supreme Court, and the Court asked the Solicitor General to file a brief setting forth the views of the United States government.  In its brief, the Solicitor General recommended that the Court deny review, stating that the case "would provide a poor vehicle for the Court to consider the application of Section 271(e)(1) to post-approval activities."  On January 14, the Court denied cert in Classen, perhaps with an eye toward taking the Momenta case instead.

In its cert petition, Momenta frames the question presented as follows:

Whether the use of a patented invention in the course of post-approval manufacture of a drug for commercial sale, where the FDA requires that a record of that manufacturing activity be maintained, is exempted from liability for patent infringement under Section 271(e)(1) as "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."

Momenta asserts in its petition that the Federal Circuit's decisions in Classen and Momenta are irreconcilable, and that both are "fundamentally wrong."  Momenta argues, for instance, that "[h]ad Classen been applied in this case, Amphastar's use of Momenta's patented invention would not have been exempted from infringement.  Amphastar uses Momenta's patented method in the course of routine post-approval, commercial manufacturing of its drug, not to obtain pre-marketing approval."  Momenta further argues that both Classen and Momenta are inconsistent with the statutory text and Supreme Court precedents, including the Court's most recent case interpreting the safe harbor, Merck v. Integra.

Finally, Momenta argues the scope of the safe harbor "is an issue of exceptional, immediate importance to the pharmaceutical industry."  According to Momenta, "The Federal Circuit's diametrically opposed interpretations of Section 271(e)(1) have created immense uncertainty in a trillion-dollar industry that develops life-saving and life-enhancing drugs."  Further, Momenta states, "the Federal Circuit's ruling in this case could shield from infringement any approved activity by a pharmaceutical company for which the company must maintain a record for possible future FDA inspection.  This could render numerous method, composition, and packaging patents completely worthless."

Hat tip to Alex MacCormick for the news that Momenta filed its cert petition.

Federal Circuit Continues to be Split Over Scope of 271(e)(1) Safe Harbor

Momenta Pharms. v. Amphastar Pharms., No. 2012-1062 (Fed. Cir.)

    by Aaron F. Barkoff

Last year, in Classen v. Biogen IDEC, a three-judge panel of the Federal Circuit held that the safe harbor of Section 271(e)(1) "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."  The majority opinion was written by Judge Newman, with Chief Judge Rader concurring and providing additional views, and Judge Moore dissenting.  A petition for certiorari in the case is currently pending at the Supreme Court, and the Court recently asked the Solicitor General's office to weigh in with its views.

Last Friday, in Momenta v. Amphastar, a case between two manufacturers of generic Lovenox (enoxaparin), a slightly different three-judge panel of the Federal Circuit held that the safe harbor does apply to certain post-approval activities.  In the case, Judge Moore wrote the majority opinion, joined by Judge Dyk, and Chief Judge Rader wrote a blistering 29-page dissent.  The decisions in the two cases do not seem entirely consistent with each other, which likely raises the odds that the Supreme Court will agree to hear the Classen case.

Momenta is the assignee of U.S. Patent No. 7,575,886, which generally relates "to methods for analyzing heterogeneous populations of sulfated polysaccharides, e.g. heparin [and] . . . LMWH [low molecular weight heparin--e.g., enoxaparin]."  Two days after Amphastar received final FDA approval to market its generic enoxaparin (and more than a year after Momenta received its own approval), Momenta filed suit against Amphastar, accusing Amphastar of "manufacturing generic enoxaparin for commercial sale" and performing "in their process for manufacturing batches of enoxaparin" an analytical method that infringes the '886 patent.  According to the majority opinion, Momenta also alleged that this infringing testing was necessary to "satisfy the FDA's requirements."

The district court granted Momenta a preliminary injunction, concluding that Amphastar's testing falls outside the scope of the safe harbor under Section 271(e)(1):  "although the safe harbor provision permits otherwise infringing activity that is conducted to obtain regulatory approval of a product, it does not permit a generic manufacturer to continue in that otherwise infringing activity after obtaining approval."  Amphastar appealed, contending that the district court adopted an overly restrictive view of the safe harbor.

The Federal Circuit majority opinion began by addressing Momenta's "contention that the information in question was not 'submitted' to the FDA, but rather was retained by the ANDA holder."  Here, the majority concluded that "the fact that the FDA does not in most cases actually inspect [Amphastar's manufacturing test records] does not change the fact that they are for the development and submission of information under a Federal law."  The majority cited the Supreme Court's Merck v. Integra decision for "holding that uses which are not ultimately included in a submission to the FDA are nonetheless exempted by the safe harbor."

The majority then turned to whether Amphastar's submissions are protected by the safe harbor.  Here, the majority took pains to distinguish Classen:

At issue in Classen were [post-marketing] studies to evaluate the association between the timing of childhood vaccinations and the risk of developing certain immune-mediated disorders.  The studies themselves were not mandated by the FDA, but any vaccine license holder was required to report to the FDA "adverse experience information," such as adverse side effects, it acquired as a result of vaccine studies.  We found that the studies conducted by the vaccine license holder according to patented methods were not insulated by the safe harbor because the studies did not facilitate marketing a generic drug by "expediting development of information for regulatory approval."  We, of course, are bound by the Classen decision unless it is overruled en banc or by the Supreme Court.  Accordingly, the scope of the safe harbor provision does not extend to "information that may be routinely reported to the FDA, long after marketing approval has been obtained."

This case, however, fits well within Classen because the information submitted is necessary both to the continued approval of the ANDA and to the ability to market the generic drug.  Here, the submissions are not "routine submissions" to the FDA, but instead are submissions that are required to maintain FDA approval.  . . .  Failure to comply with these requirements could result in suspension or revocation of Amphastar's ANDA approval to market the drug.

We also note that, unlike in Classen where the patented studies performed were not mandated by the FDA, the information here is not generated voluntarily by the manufacturer but is generated by FDA requirements the manufacturer is obligated under penalty of law to follow.  Under such circumstances, the information can be said to have been gathered solely for submission to the FDA and not, as in Classen, primarily for non-FDA purposes.  While Momenta urges us to adopt the pre-/post-approval distinction used by the district court, we cannot:  Classen did not turn on this artificial distinction, and the plain language of the statute is not restricted to pre-approval activities.

Unlike Classen, where the allegedly infringing activity "may" have eventually led to an FDA submission, there is no dispute in this case that Amphastar's allegedly infringing activities are carried out to "satisfy the FDA's requirements."

In a strongly-worded dissent, Chief Judge Rader repeatedly refers to Amphastar as a "trespasser" and "infringer."  He traces the legislative history of Section 271(e)(1)--which is curious given that the Supreme Court has twice minimized the legislative history and based its decisions instead on the plain (and broad) language of the statute.  And he takes great exception to the majority opinion's basis for distinguishing Classen.  Finally, he claims that the majority's "interpretation of 271(e)(1) would essentially render manufacturing method patents worthless."  While this is an exaggeration, the Supreme Court might reply:  "that is a problem for Congress to fix, if they so choose."

Where the scope of the 271(e)(1) safe harbor ends up matters a great deal, particularly as we approach the era of biosimilar patent litigation.  Like enoxaparin, biologics are complex molecules and thus analytical-method patents figure to be in the patent portfolios protecting them.  The sooner the courts can agree on the scope of the safe harbor, the better for everyone.

Federal Circuit Confines 271(e)(1) Safe Harbor to Pre-Approval Activities

Classen Immunotherapies v. Biogen IDEC et al., Nos. 2006-1634, -1649 (Fed. Cir. 2011)

In a 2-1 opinion today, the Federal Circuit held that the Section 271(e)(1) safe harbor "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."

35 U.S.C. § 271(e)(1) states:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States . . . a patented invention . . . 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 law was passed as part of the Hatch-Waxman Act in 1984, and while the purpose of the law was to shield generic drug makers from claims of patent infringement during the generic drug development process, the Supreme Court has interpreted the law much more broadly.

For instance, in Eli Lilly v. Medtronic, 496 U.S. 661 (1990), the Court held that the safe harbor applies not only to pharmaceutical development, but also to medical device development.  More recently, in Merck v. Integra, 545 U.S. 193 (2005), the Court held that the safe harbor applies not only to generic pharmaceutical development, but rather to "all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA."  In addition, the Court stated, "there is simply no room in the statute for excluding certain information from the exemption on the basis of the phase of research in which it is developed or the particular submission in which it could be included."  In both Lilly and Merck, the Supreme Court reached its conclusions based on the plain language of the statute, which is intentionally broad.

In this case, Classen accused Biogen IDEC and GlaxoSmithKline of infringing its patents claiming methods of immunization on the ground that both companies participated in post-approval studies "to evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenza . . . and risk of developing type 1 diabetes; and to determine whether timing of vaccinations influences risk."  The district court granted summary judgment that these activities are within the Section 271(e)(1) safe harbor.

On appeal, Classen argued "that this statute, as enacted and intended, and as judicially interpreted, is limited to activities conducted to obtain pre-marketing approval of generic counterparts of patented inventions, before patent expiration."  Biogen and GSK argued, on the other hand, that their participation in studies evaluating risks associated with different vaccination schedules is reasonably related to their requirement under, e.g., 21 C.F.R. § 601.70 and 21 C.F.R. § 600.80, to review and report adverse events to the FDA.

The majority opinion, authored by J. Newman and joined by J. Rader, found in favor of Classen, stating:

Classen is correct, for § 271(e)(1) provides an exception to the law of infringement in order to expedite development of information for regulatory approval of generic counterparts of patented products.  The statute does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained.

The majority opinion then proceeds to review the legislative history of the Hatch-Waxman Act, which obviously focused on the then-new abbreviated approval process for generic drugs.  While the majority opinion quotes from both Eli Lilly v. Medtronic and Merck v. Integra, it ignores how broadly the Supreme Court interpreted the safe harbor in those cases.  Rather, according to the majority opinion, "every decision examining the statute has appreciated that § 271(e)(1) is directed to premarketing approval of generic counterparts before patent expiration."

But as the dissent by J. Moore notes, regardless of what the statute "is directed to" (whatever that means), there was no dispute in this case that the safe harbor applies to pre-approval activities.  J. Moore wrote:

The majority cites extensively from the legislative history in an attempt to justify its construction.  But these citations miss the point entirely.  There is no dispute that § 271(e)(1) covers pre-approval studies, as the legislative history indicates.  None of the legislative history cited by the majority, nor the cases it references, speak to the question at issue here -- whether the statute as enacted also covers post-approval activities.  The question is not whether Congress intended to protect pre-approval activity -- but whether the enacted legislation covers more than just pre-approval activity.  The language Congress chose to enact and that was signed by the President is plain on its face.  There is no "pre-approval" limitation.

The other main issue addressed in the opinion concerns the patent-eligibility of Classen's claims under 35 U.S.C. § 101.  Patently-O has an excellent discussion of that portion of the opinion.

Federal Circuit Narrows the Scope of the Section 271(e)(1) Research Exemption

Proveris Scientific Corp. v. Innovasystems, No. 2007-1428 (Fed. Cir. 2008)

35 U.S.C. § 271(e)(1) states:

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 . . . 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.

This statute, passed as part of the Hatch-Waxman Act in 1984, provides a "safe harbor" from claims of patent infringement based on activities related to the pursuit of FDA approval of drug products.  For example, it exempts ANDA applicants from allegations of patent infringement based on R&D done for the purpose of establishing bioequivalence.

Proveris Scientific owns U.S. Patent No. 6,785,400, which is directed to a system and apparatus for characterizing aerosol sprays used in drug delivery devices, such as nasal spray pumps and inhalers.  Innova makes and sells a device that, although not itself subject to FDA approval, is used in connection with FDA regulatory submissions.  Specifically, the device is used to measure the physical parameters of aerosol sprays used in nasal drug delivery devices.

Proveris filed suit against Innova, alleging infringement of the '400 patent.  As part of its defense, Innova invoked the safe harbor provision of section 271(e)(1).  Innova argued that its allegedly infringing activities are immunized because its device is used by third parties solely for the development and submission of information to the FDA.  At trial, the district court ruled as a matter of law that Innova could not avail itself of section 271(e)(1).  In an opinion released yesterday, the Federal Circuit affirmed the district court.

Innova argued on appeal that it is entitled to the benefit of section 271(e)(1) because it offered to sell its device only to pharmaceutical companies and the FDA, and that its device was used exclusively in relation to applications for FDA approval.  Proveris responded that the section 271(e)(1) safe harbor is applicable only to products that are subject to patent term extensions under 35 U.S.C. § 156(f)--namely, drug products, medical devices, food additives, and color additives.  According to Proveris, section 271(e)(1) does not immunize infringement of patents on laboratory or manufacturing equipment.

The Federal Circuit framed the issue as this:  "whether section 271(e)(1) immunizes the manufacture, marketing, or sale of Innova's device, which is used in the development of FDA regulatory submissions, but is not itself subject to the FDA premarket approval process."

The court concluded that section 271(e)(1) provides no such immunity, reasoning that Congress did not intend for section 271(e) to apply to parties like Innova, whose device is not subject to FDA premarket approval, and who therefore faces no regulatory barriers to market entry upon patent expiration.

The Federal Circuit explained that its conclusion "achieves the same kind of fit, or symmetry" that the Supreme Court spoke of in the Eli Lilly v. Medtronic case, which also dealt with section 271(e)(1).  According to the court, "Because Proveris's patented product is not subject to a required FDCA approval process, it is not eligible for the benefit of the patent term extension afforded by 35 U.S.C. § 156(f).  At the same time, because Innova's device also is not subject to a required FDCA approval process, it does not need the safe harbor protection afforded by 35 U.S.C. § 271(e)(1)."

RELATED READING:

• Holman's Biotech IP Blog
• Patently-O

Federal Circuit Addresses Effect of 271(e)(1) "Safe Harbor" in ITC Actions

Amgen v. Int'l Trade Comm'n and Roche, No. 2007-1014 (Fed. Cir. 2008)

Amgen holds at least six US patents that relate to erythropoeitin and its derivatives (EPO) and processes for making EPO, protecting the Amgen drugs Aranesp and Epogen.  Sales of Aranesp alone topped $3.6 million last year.  Roche produces EPO in Europe and has been seeking FDA approval for its own EPO drug, Mircera, in the US.

Roche began importing EPO as part of its effort to generate data for its regulatory submissions to the FDA.  Amgen did not object to these acts of importation.  However, Roche continued importing EPO even after its FDA application was complete (though Roche has not yet sold or contracted to sell any of its EPO in the US).  Amgen responded by filing a Section 337 action with the International Trace Commission (ITC), asking the ITC to enjoin Roches further importation and future sale in the US of its European-produced EPO.

The ITC denied Amgens injunction request because (1) the ITC determined that Roches importation of EPO was protected by the FDA safe harbor provision of Section 271(e)(1), which provides that conduct cannot infringe a patent when it is reasonably related to securing FDA approval; and (2) the ITC has no jurisdiction absent a sale or contract for sale of EPO in the US.  In a decision Wednesday, the Federal Circuit affirmed in part, reversed in part, and remanded the case to the ITC.

Amgen made three arguments on appeal: (1) Section 271(e)(1) provides no exemption for the importation of articles made overseas by patented processes in Section 337 actions before the ITC; (2) Section 271(e)(1) does not provide blanket protection for all pre-FDA-approval conduct; and (3) the ITC has jurisdiction whenever sale of the accused article is imminent.  All three Federal Circuit panelists sided with Amgen on the second and third points.  On the first point, however, Judges Newman and Lourie agreed with the ITC, while Judge Linn dissented to express his agreement with Amgen’s argument.

On Amgen’s first point, the majority accepted the ITC’s argument, i.e., that the Section 271(e)(1) safe harbor should operate identically in ITC litigation as in federal district court litigation.  The importation of an article made by an infringing process constitutes an act of infringement under Section 271(g).  But the safe harbor of Section 271(e)(1) holds that certain acts related to gaining regulatory approval are not acts of infringement.  Therefore, 271(e)(1) cuts back on 271(g) by declaring that certain types of conduct do not constitute infringement.  The ITC, however, does not look to Section 271(g) for its authority.  Instead the ITC looks to 19 USC § 337(a)(1)(B)(ii), which declares unlawful the importation of any article “made . . . by means of a process covered by the claims of a valid and enforceable United States patent.”  In contrast, Section 271(g) only forbids the importation of articles made by means of a process that infringes the claims of a valid and enforceable US patent.  Because the safe harbor of Section 271(e)(1) only addresses infringement, Judge Linn (in dissent) argues that the safe harbor applies to infringement liability under Section 271(g) but not to unlawful trade practices under Section 337(a)(1)(B)(ii).  The majority’s holding elects to gloss over these key differences between Section 271(g) and Section 337.

On the other hand, the majority’s holding probably does comport more closely with the policy rationales that support having the regulatory safe harbor.  As the majority notes, the legislative history supports this proposition that the 271(e)(1) safe harbor applies identically to importation under Section 271(g) and to importation under Section 337(a)(1)(B)(ii).  Moreover, the Supreme Court’s broad reading of the scope of the regulatory safe harbor in Integra v. Merck and Eli Lilly v. Medtronic lends further support for the majority’s policy judgment.  Judge Linn even agrees that the majority reaches the policy outcome that makes the most sense.  Nevertheless, the text of Section 337(a)(1)(B)(ii) is clearly at odds with such a policy outcome.

On Amgen’s second point, the Court agreed with Amgen.  The safe harbor of Section 271(e)(1) does not provide blanket protection for all pre-FDA-approval conduct.  For each separate act, the accused party must demonstrate that each act is reasonably related to gaining regulatory approval.  Amgen asserted that Roche continued importing EPO after its FDA application was complete and used the imported EPO to conduct marketing studies.  The Court remanded the case to the ITC for an act-by-act evaluation of whether Roche’s conduct was indeed within the ambit of Section 271(e)(1).

On Amgen’s third point, the Federal Circuit held that the ITC jurisdiction is invoked “[w]hen it has been shown that infringing acts are reasonably likely to occur . . . .”  The court went to great lengths to point out that this standard is not new, and is, in fact, consistent with nearly three decades of ITC precedent.  Because Section 337 provides for a prospective remedy, it makes no sense for the complainant to wait for an actual sale to occur, so long as an actual sale is imminent.

RELATED READING:

• Patently-O
• Reuters

Patent Protection for Research Tools Remains Unclear After Federal Circuit Revisits Integra v. Merck

Integra Lifesciences v. Merck KGaA, No. 2002-1052 (Fed. Cir. 2007)

Last Friday, the Court of Appeals for the Federal Circuit decided Integra v. Merck, on remand from the Supreme Court.  Click here for the opinion.  The case has important implications for owners of "research tools" patents.

In the mid-1990s, Integra sued Merck KGaA (the German company) and Scripps for infringing five patents relating to peptides that contain the RGD sequence of amino acids.  This suite of patents included both patents directed to RGD-containing peptide compounds and patents directed to laboratory methods (i.e., research tools) using the RGD-containing peptides.

Merck and Scripps defended their conduct by relying on the FDA safe harbor of 35 USC § 271(e)(1), which precludes liability for activities "reasonably related to the development and submission of information under [the Food, Drug and Cosmetic Act]."  The FDA safe-harbor was passed as part of the Hatch-Waxman Act to permit "a limited amount of testing so that generic manufacturers can establish the bioequivalency of a generic substitute."  In this sense, the safe harbor encompasses activities that develop information that will normally find its way into an FDA submission.

At the original trial in the district court, Integra argued for a narrow reading of the FDA safe harbor in three respects.  First, Integra argued that the safe harbor includes only studies on the safety of administration to humans, and does not include experiments on mode of action (i.e., ADME and PK studies).  Second, Integra argued that the safe harbor excludes studies on related compounds that were not the subject of any FDA submission.  Third, Integra argued that the safe harbor can only include experiments complying with the FDA’s Good Laboratory Practices (GLP), since only data from GLP-compliant studies qualify for submission to the FDA.

A jury verdict and bench opinion accepted Integra's narrow reading of the safe harbor statute, and found Merck and Scripps liable for infringement.  A divided panel of the Federal Circuit affirmed.  The Supreme Court granted certiorari on the limited question of "whether uses of patented inventions in preclinical research, the results of which are not ultimately included in a submission to the [FDA], are exempted by [the FDA safe harbor]."  The term "patented inventions" presumably included both patented compounds and patented research tools that use those compounds.

Pharma News Briefs

• The Antitrust & Competition Policy Blog reports on a new paper by Prof. Christopher Leslie of Chicago-Kent College of Law advocating the use of antitrust law to challenge the licensing of invalid patents.
• Richard Epstein, my law school Property professor, has a new book out entitled Overdose: How Excessive Government Regulation Stifles Pharmaceutical Innovation.  Judy Chevalier has this review at Slate.  Prof. Epstein wrote two related Op-Ed pieces for the Boston Globe and L.A. Times.
• Via Patent Circle, Abraxis, Orchid, and Sandoz have filed citizen petitions in support of their ANDAs for generic versions of Wyeth's Zosyn.  The Economic Times of India published this article about the petitions.
• Ed Silverman, veteran reporter for The Star-Ledger of New Jersey, recently started Pharmalot, a new blog covering news and trends in the pharmaceutical industry.
• The Voluntary Trade Blog reports that FTC Commissioner William Kovacic, in a recent interview with Dow Jones, harshly critized the Department of Justice for advising the Supreme Court not to take the FTC v. Schering-Plough "reverse payments" case last year.
• Peter Zura's Two-Seventy-One Patent Blog reports on a recent district court decision applying the 271(e)(1) "safe harbor" to research tools.
• The Economist and The Scientist recently published articles on the current "dismal" state of the pharmaceutical industry.

Hoffman-LaRoche's Motion to Dismiss EPO Case On Basis of 271(e)(1) Research Exemption Is Denied

Amgen dodged a bullet last week when Judge William G. Young of the U.S. District Court for the District of Massachusetts denied Hoffman-LaRoche's motion to dismiss Amgen's complaint alleging infringement of its patents on erythropoeitin (EPO).  Hoffman-LaRoche based its motion to dismiss on the assertion that all of the allegedly infringing activities fell under 35 U.S.C. 271(e)(1), which exempts activities reasonably related to the development of information necessary for FDA approval.

Judge Young's opinion explains that the 271(e)(1) research exemption is an affirmative defense to patent infringement, and therefore Amgen was not required to plead that Hoffman-LaRoche's activities were not protected by the exemption.  Amgen's complaint survived the motion to dismiss simply because Amgen pled facts sufficient to establish importation of a patented drug in violation of section 271(a).

In dicta, Judge Young stated that even if Amgen were required to plead acts that fall outside the 271(e)(1) research exemption, the court would conclude that Amgen's complaint supported a claim of infringement.  The court recognized that although many of Hoffman-LaRoche's activities fall within the research exemption, Amgen alleged that Hoffman-LaRoche is importing a drug "which is materially indistinguishable from Amgen's patented invention."  According to Judge Young, "This Court cannot conclude, as a matter of law, that because Roche/Hoffman is in the process of submitting information to the FDA, that this importation of the alleged infringing drug must be solely for uses that reasonably relate to the submission of that information."

This case suggests that because the 271(e)(1) research exemption is an affirmative defense, 271(e)(1) can never be the basis for a motion to dismiss.  Instead, a defendant relying on 271(e)(1) must wait at least until the summary judgment stage to dispose of the case, when it can move for summary judgment of noninfringement based on the research exemption.

RELATED READING:

• Amgen press release
• More on 271(e)(1) at Patent Docs

Merck and Integra Submit Post-Hearing Letters to Federal Circuit, Urging the Court Not to Address Research Tools Issue

As reported in a post last week, the Federal Circuit recently heard oral arguments in Merck KGaA v. Integra LifeSciences following remand from the Supreme Court.  Since the hearing, both Merck and Integra have submitted letters to the Federal Circuit, urging the court not to decide the issue of whether Merck's use of Integra's patented compounds fell outside the 271(e)(1) FDA exemption as "research tools," in which case Merck would be liable for patent infringement.

Merck asserted in its letter that a Federal Circuit decision based on the research tool issue would be improper because Integra never argued--in the district court, Federal Circuit, or Supreme Court--that the jury verdict for Integra should be sustained on the basis that Merck used Integra's patented compounds as research tools.  Integra, in its own letter, agreed with Merck, stating that while the research tool question is extremely important, it should be answered in a case in which the issue has been "squarely raised and thoroughly vetted" in the trial court.

At oral argument, Judge Rader, in particular, seemed gung ho to remand the case to the district court to determine whether Merck used Integra's compounds as research tools and therefore was not entitled to the 271(e)(1) FDA exemption.  If the other two members of the panel, Judges Newman and Prost, follow the parties' advice and ignore that issue, then the Federal Circuit will limit its opinion to the narrower technical question of whether Merck's JMOL motion was properly denied by the district court.

NOTE:  Thanks to Dennis Crouch for providing the parties' letters!