Hatch-Waxman Act Archives

Hatch-Waxman Act

Transparency Is the Best Medicine: Device Parts Don’t Justify Orange Book Listing

by Amit Kumar Saha, PhD | Jan 9, 2025 | Patents

The US Court of Appeals for the Federal Circuit affirmed a district court’s delisting of patents from the Orange Book because the patent claims did not “claim the drug that was approved” or the active ingredient of the drug that was approved. Teva Branded Pharmaceutical Products R&D, Inc., et al. v. Amneal Pharmaceuticals of New York, LLC, et al., Case No. 24-1936 (Fed. Cir. Dec. 20, 2024) (Prost, Taranto, Hughes, JJ.)

Teva owns the product that Amneal sought to delist, ProAir® HFA Inhalation Aerosol. The ProAir® HFA combines albuterol sulfate (the active ingredient) with a propellant and an inhaler device to administer the drug. Although the US Food and Drug Administration (FDA) approved Teva’s ProAir® HFA as a drug, the ProAir® HFA contains both drug and device components (the device components being the physical machinery of the inhaler). Teva lists nine nonexpired patents in the Orange Book for its ProAir® HFA.

Amneal filed an abbreviated new drug application (ANDA) seeking approval to market a generic version of the ProAir® HFA that uses the same active ingredient. Amneal asserted that it did not infringe Teva’s nine patents listed for the ProAir® HFA. Teva sued for infringement of six of those patents. Amneal filed counterclaims for antitrust and for a declaratory judgment of noninfringement and invalidity and sought an order requiring Teva to delist the five patents that it asserted against Amneal. Amneal moved for judgment on the pleadings on the ground that Teva improperly listed the asserted patents. The district court granted Amneal’s motion, concluding that Teva’s patents “do not claim the drug for which the applicant submitted the application.” The district court ordered Teva to delist its patents from the Orange Book. Teva appealed.

On appeal, Teva argued that a patent can be listed in the Orange Book if the claimed invention is found in any part of its new drug application (NDA) product. Teva argued that a patent “claims the drug” if the claim reads on the approved drug (i.e., if the NDA product infringes that claim). Teva also argued that according to the Federal Food, Drug, and Cosmetic Act’s broad definition of the word “drug,” any component of an article that can treat disease meets the statutory definition of a “drug.” With this interpretation, Teva’s patents “claim the drug” as the claim dose counter and canister components of the ProAir® HFA.

The Federal Circuit rejected Teva’s interpretation as overbroad because it would allow the “listing of far more patents than Congress has indicated.” The Court rejected Teva’s argument that a patent claiming any component of a drug is listable, explaining that Teva cannot list its patents just because they claim the dose counter and canister parts of the ProAir® HFA.

The Federal Circuit also rejected Teva’s argument that even if Teva’s statutory arguments were rejected, the Federal Circuit must remand the case to the district court to construe the claims. In doing so, the Court rejected Teva’s interpretation of the word “claims” in the listing and counterclaim/delisting provisions, [...]

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The Devil Is in the Details: Bioequivalence, In Vitro Testing Not Enough to Establish Infringement

by Pete Marston | Dec 19, 2024 | Patents

Addressing for the first time the issue of whether bioequivalence data and in vitro testing can show that an abbreviated new drug application (ANDA) product with different immediate and delayed release portions infringed on a patent, the US Court of Appeals for the Federal Circuit upheld the district court’s finding of noninfringement. Galderma Laboratories, L.P. v. Lupin Inc., Case No. 24-1664 (Fed. Cir. Dec. 6, 2024) (Moore, C.J.; Linn, Prost, JJ.)

Galderma owns and markets Oracea® (doxycycline USP) 40 mg capsules, which are used to treat papules and pustules associated with rosacea. Galderma’s patents cover a unique once-daily oral formulation of doxycycline, combining 30 mg of immediate release (IR) and 10 mg of delayed release (DR) pellets. Lupin filed an ANDA to market a bioequivalent 40 mg doxycycline product, featuring 22 mg IR and 18 mg DR pellets, and using the same enteric polymer for the DR portion as Oracea®. Galderma sued Lupin under the Hatch-Waxman Act, alleging patent infringement.

Despite Lupin’s different pellet composition, Galderma contended that Lupin’s product effectively contained 30 mg IR and 10 mg DR because of a “weak enteric coat” on the DR pellets, causing early release of some doxycycline. Lupin presented two key pieces of evidence:

A two-stage in vitro dissolution test at pH 1.1 and 4.5, showing some DR pellet release at pH 4.5.
Bioequivalence data comparing Oracea® and Lupin’s product.

The district court ultimately ruled in favor of Lupin. Galderma appealed. The issue on appeal was whether Galderma’s evidence of bioequivalence and in vitro testing was indeed insufficient to establish literal infringement or infringement under the doctrine of equivalents (DoE).

The Federal Circuit agreed with the district court: in vitro testing and bioequivalence were not enough to establish literal infringement. Crucially, Galderma’s two-stage in vitro dissolution test didn’t accurately mimic in vivo conditions. The Court highlighted that the pH 4.5 environment used in the test wasn’t physiologically relevant for a fasted stomach, which typically has a pH between 1 and 2. Moreover, the bioequivalence data failed to address the differing proportions of IR and DR pellets. Consequently, the Court found no clear error in the district court’s factual findings.

Nor did the DoE save Galderma. The Federal Circuit applied two different tests: the function-way-result test and the insubstantial differences test. Under the function-way-result test the court is charged with determining whether the accused product performs the same function, in the same way, to achieve the same result as the claimed invention. Under the insubstantial differences test – as its name suggests – the court is charged with determining whether the differences between the claimed invention and the accused product are insubstantial.

Again, Galderma relied on bioequivalence data and its in vitro testing to argue that either DoE test was satisfied. The Federal Circuit was not persuaded, finding no clear error in the district court’s reasoning. As for the function-way-result test, the in vitro testing did not show that Lupin’s ANDA product used the same function or method as the asserted [...]

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If the Label Is Skinny Enough – No Inducement Under Hatch-Waxman

by Ian J. Howard | Dec 14, 2023 | Patents

The US Court of Appeals for the Federal Circuit made explicit what has long been considered implicit based on Warner-Lambert and its progeny, namely, that plaintiffs asserting an induced infringement theory to bar the entry of generic drugs in a Hatch-Waxman suit are subject to higher scrutiny than plaintiffs asserting the same theories outside of the Hatch-Waxman context. H. Lundbeck A/S v. Lupin Ltd., Case No. 22-1194 (Fed. Cir. Dec. 7, 2023) (Dyk, Prost, Hughes, JJ.)

Lundbeck owns the approved new drug application (NDA) for Trintellix®, a drug indicated for the treatment of major depressive disorder (MDD), as well as an expired compound patent for the associated active ingredient vortioxetine. Lundbeck also owns a patent that claims the use of vortioxetine as an antidepressant that can be prescribed in place of a traditional antidepressant to alleviate a patient’s negative sexual side effects, and another patent that claims the use of vortioxetine to treat cognitive impairment symptoms in patients with MDD.

Generic pharmaceutical companies filed abbreviated new drug applications (ANDAs) seeking approval to market generic versions of Trintellix® and asserting that Lundbeck’s unexpired patents listed in its NDA were invalid and would not be infringed by the generic companies. As required by the Hatch-Waxman Act (to prevent the entry of a generic on the market), Lundbeck sued the generic companies. At the district court, the defendants prevailed on the finding of noninfringement but lost on invalidity. Lundbeck appealed.

Lundbeck pressed its induced infringement and contributory infringement theories on appeal. Lundbeck argued that the generics infringed under the plain text of Hatch-Waxman (35 USC 271(e)(2)(A)) because they filed ANDAs seeking approval to market vortioxetine, and that “some uses of vortioxetine—for the treatment of patients that have previously taken other drugs but had to cease or reduce use due to sexually related adverse events and for the treatment of cognitive impairment—are covered by [Lundbeck’s listed] patents; and the labels do not prohibit prescribing vortioxetine for those uses, even though the defendants do not propose to market the drug for those patented uses.” In other words, Lundbeck argued that in terms of its inducement allegation, it made no difference whether a drug would be sold for a use not covered by Lundberg’s NDA-listed patents because the drug could be prescribed for those patented uses.

The Federal Circuit disagreed, explaining that “‘the use’ in § 271(e)(2)(A) refers to the use for which the FDA has granted an NDA” and for which the ANDA was submitted.” The Court emphasized that it is not “an act of infringement under . . . § 271(e)(2)(A) to submit an ANDA for a drug if just any use of that drug were claimed in a patent.” If it were, a brand could “maintain its exclusivity merely by regularly filing a new patent application claiming a narrow method of use not covered by its NDA,” which “would confer substantial additional rights on pioneer drug patent owners that Congress quite clearly did not intend to confer.” As the Court then held, “actions for [...]

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ANDA Filing Alone Insufficient for Induced Infringement of Method Patent

by Tessa Kroll | Jan 5, 2023 | Patents

The US Court of Appeals for the Federal Circuit upheld a district court’s findings of invalidity and noninfringement in a Hatch-Waxman case involving two sets of method patents directed to modulating dosages of pirfenidone, a drug used to treat idiopathic pulmonary fibrosis (IPF). The Court found that the first set of patents were obvious over the prior art and standard medical practice, while the second set were not directly infringed in light of actual physician prescription practice. Genentech, Inc. v. Sandoz Inc., Case No. 22-1595 (Fed. Cir. Dec. 22, 2022) (Newman, Lourie, Prost, JJ.) (Newman, J., dissenting).

Sandoz submitted two abbreviated new drug applications (ANDAs) for approval to market a generic version of pirfenidone, which Genentech sells under the brand name Esbriet®. Genentech sued Sandoz under the Hatch-Waxman Act, asserting that Sandoz’s generic version would induce infringement of two sets of patents: one directed to modifying dosages of pirfenidone in patients with abnormal liver biomarkers (LFT patents), and the other directed to avoiding adverse interactions in patients also taking fluvoxamine (DDI patents).

The LFT patents are directed to methods of administering pirfenidone to a patient who has exhibited Grade 2 abnormalities in liver function biomarkers alanine transaminase (ALT) and/or aspartate transaminase (AST) in response to pirfenidone. The LFT patents generally recite the following administration options:

Temporarily reducing the dose before returning to the full dose
Maintaining the full dose
Reducing the dose
Temporarily discontinuing pirfenidone before returning to the full dose
Temporarily discontinuing pirfenidone before returning to a reduced dose.

Sandoz’s proposed label included a “Dosage Modification due to Elevated Liver Enzymes” section, which stated that if a patient exhibits grade 2 elevations of ALT and/or AST, “[t]he full daily dosage may be maintained, if clinically appropriate, or reduced or interrupted (e.g., until liver chemistry tests are within normal limits) with subsequent re-titration to the full dosage as tolerated.” Genentech argued that these instructions constituted induced infringement of the LFT patents. The district court disagreed and held that the LFT patents were obvious over the prior art and standard medical practice and that the defendant would not induce infringement because the labels “merely described” the infringing uses but did not recommend them.

The DDI patents are directed to methods for avoiding adverse interactions between pirfenidone and fluvoxamine and generally involve the steps of discontinuing fluvoxamine or modifying the dose of pirfenidone and continuing fluvoxamine. Sandoz’s proposed label warned of the adverse interactions between pirfenidone and fluvoxamine and stated that fluvoxamine should be discontinued prior to administering pirfenidone or the dose of pirfenidone should be reduced. Genentech similarly argued that these instructions constituted induced infringement of its DDI patents, but the district court held that there was insufficient evidence for infringement because Genentech had not shown that a patient would actually be prescribed both pirfenidone and fluvoxamine in practice.

Genentech appealed the district court’s holdings with respect to both the LFT and DDI patents.

LFT Patents

The Federal Circuit first observed that “varying doses in response to the occurrence [...]

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An Early Holiday Present for Generics? Legislation Requiring Greater Disclosure by Brands Passes the Senate

by Christopher M. Bruno | Dec 21, 2020 | Patents

Earlier this month, two bills intended to promote generic competitiveness by presenting a clearer idea of the patent landscape covering reference products passed the full Senate, albeit with amendments. These laws, if enacted, will require brand pharmaceutical companies to submit more information about their innovator products.

Potential Changes to Orange Book Listing Requirements for Non-Biologics Drugs

As part of its current obligations, an innovator product manufacturer must submit to the FDA the patent number and expiration date of any patents that claim the drug or a method of using the drug. The FDA then performs the ministerial function of listing the information in the Approved Drug Products with Therapeutic Equivalence Evaluations, known as the Orange Book. The Hatch-Waxman Act permits generic manufacturers to file a counterclaim to delist a patent that they believe is improperly listed. Over the years, FDA has issued technical regulations expanding on the requirements, which under statute, are relatively sparse. However, there has been some uncertainty regarding what patents must be listed—especially in the case of drug products with innovative delivery systems.

The Orange Book Transparency Act of 2020, H.R. 1503, seeks to codify certain existing regulations and bring some certainty to the process. First, the Orange Book Act provides greater clarity on the types of patents a brand company must list. Currently, the relevant statutes require submission of patent information for “any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug” that could be asserted based on the manufacture, use, or sale of the drug. The Orange Book Act would alter that language to require submission of patent information for patents that claim the drug substance (active ingredient), the drug product (formulation or composition), or a method of use that is included in the application (i.e., a method of use that corresponds with an approved indication/use code). All other patents—e.g., patents that cover off-label use—must not be listed.

Second, the FDA would be responsible for “specify[ing] any exclusivity period that is applicable,” including the 180-day exclusivity period for first-to-file applicants.

Finally, the Orange Book Act codifies certain existing agency requirements. Under current FDA regulations, brand manufacturers are required to promptly request delisting if they determine that a patent no longer qualifies or its relevant claims are invalidated, and within 14 days if court-ordered. The Orange Book Act would codify the duty on brand manufacturers to remove listed patents within 14 days—rather than “promptly”—when any claim of a listed patent “has been cancelled or invalidated pursuant to a final decision” by the Patent Trial & Appeal Board or a court once it is unappealable. This quick turnaround time of communicating to the public which patents have been found invalid will be key to giving generics an advantage in developing generic products and patents covering branded drug products invalid. The Orange Book Act includes a 30-day period for a brand manufacturer to list a patent after issuance; this requirement mirrors already existing FDA regulations.

While [...]

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Venue in Hatch-Waxman Cases Limited to District Where ANDA Is Submitted

by Amol Parikh | Nov 11, 2020 | Patents

The US Court of Appeals for the Federal Circuit found that in cases brought under the Hatch-Waxman Act, for purposes of determining venue, infringement occurs only in districts where actions related to the submission of an abbreviated new drug application (ANDA) occur, and not in all locations where future distribution of the generic products specified in the ANDA is contemplated. Valeant Pharmaceuticals North American LLC v. Mylan Pharmaceuticals Inc., Case No. 19-2402 (Fed. Cir. Nov. 5, 2020) (O’Malley, J.).

Valeant holds a new drug application for the brand name drug Jublia®, which is used to treat toenail fungal infections. In 2018, Mylan Pharmaceuticals Inc. (MPI) executed an ANDA seeking approval to market a generic version of Jublia®. MPI sent the ANDA from its West Virginia corporate office to the US Food and Drug Administration, located in White Oak, Maryland. The ANDA included a Paragraph IV certification that the Orange-Book-listed patents for Jublia® were invalid, unenforceable or would not be infringed by the ANDA product. After the ANDA was filed, Valeant filed suit in the District of New Jersey against MPI, Mylan Inc. and Mylan Laboratories Ltd. (MLL) pursuant to the Hatch-Waxman Act, alleging infringement of the Orange-Book-listed patents. Valeant also filed an essentially identical lawsuit in the Northern District of West Virginia against the same three defendants. MPI is a West Virginia corporation with a principal place of business in Morgantown, West Virginia. Mylan Inc. is a Pennsylvania corporation with a principal place of business in Canonsburg, Pennsylvania. MLL is an Indian corporation with a principal place of business in Hyderabad, India.

The Mylan entities moved to dismiss the New Jersey litigation, arguing that venue was improper under 28 USC § 1400(b) because none of the Mylan defendants reside or have a regular and established place of business in New Jersey, and the only alleged act of infringement (submission of the ANDA) did not occur in New Jersey. In response, Valeant argued that it was unduly narrow to limit “act of infringement” to the act of submitting the ANDA, and that the court should consider the Mylan entities’ planned future acts, which included acts of infringement in New Jersey. The district court granted the Mylan entities’ motion based on improper venue, finding that the ANDA was submitted from West Virginia and thus venue was proper there. Valeant appealed.

The two issues presented on appeal were the proper venue in Hatch-Waxman cases after TC Heartland v. Kraft Foods, and the proper venue for patent cases brought against foreign entities. Starting with the first issue, the Federal Circuit explained that determining whether venue is proper under § 1400(b) in a district other than the state in which a defendant is incorporated requires determining where the defendant committed acts of infringement. Under the Hatch-Waxman Act, it is an act of infringement to submit an ANDA for a drug claimed in a patent if the purpose of the submission is to obtain approval to engage in commercial activities related to the drug before [...]

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Inherent Claim Limitation Necessarily Present in the Prior Art Invalidates Patent

by Mandy H. Kim | Jan 29, 2020 | Life Sciences, Patents

Addressing the issue of obviousness, the US Court of Appeals for the Federal Circuit affirmed the district court’s finding that a patent was invalid based on inherency because the claim limitation was necessarily present in the prior art. Hospira, Inc. v. Fresenius Kabi USA, LLC, Case Nos. 19-1329, -1367 (Fed. Cir. Jan. 9, 2020) (Lourie, J).

The patent at-issue is directed to premixed pharmaceutical compositions of dexmedetomidine that do not require reconstitution or dilution prior to administration and remains stable and active after prolonged storage. Hospira makes and sells dexmedetomidine products, including a ready-to-use product called Precedex Premix covered by the patent at-issue. Fresenius filed an Abbreviated New Drug Application (ANDA) seeking approval by the Food and Drug Administration (FDA) to market a generic ready-to-use dexmedetomidine product. Hospira brought suit alleging infringement under the Hatch-Waxman Act.

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