On December 20, 2024, the Federal Circuit issued its ruling in Teva Branded Pharm. Prods. R&D, Inc. v. Amneal Pharms. of N.Y., LLC, No. 24-1936, interpreting the requirements for Orange Book patent listings in the Federal Food, Drug, and Cosmetic Act (FDCA).
The ruling marks a significant development in Hatch-Waxman practice, appearing to assert that all drug-related patents must “claim” at least the active ingredient of the approved drug to be properly listed in the Orange Book.
However, the reasoning behind the Federal Circuit’s opinion in Teva v. Amneal creates many ambiguities regarding what the court means and the practicalities of implementing the ruling.
The Federal Circuit denied Teva’s petition for rehearing en banc and also denied Teva’s motion for an administrative stay pending a petition for certiorari to the Supreme Court. Therefore, absent a grant of certiorari from the Supreme Court, the Federal Circuit’s interpretation of the patent listing requirements will prevail.
Accordingly, both innovator and generic companies should be aware of the potential impact of the Federal Circuit’s opinion on existing and future listings, plus any implications beyond patent listings.
Teva v. Amneal: A Brief Summary
In 2023, Teva sued Amneal Pharmaceuticals, Inc. for infringement of patents listed in the Orange Book for its ProAir® HFA inhaler, a single-entity drug-device combination product (see the text below regarding types of combination products defined in FDA’s regulations) approved through an NDA. Teva’s NDA lists albuterol sulfate as the product’s active ingredient. Teva was notified of the potential infringement after Amneal submitted an ANDA for a generic version of ProAir HFA.
In response to the patent infringement suit, Amneal sought to delist Teva’s inhaler patents, counterclaiming that Teva had improperly submitted the patents for Orange Book listing.
In June 2024, the district court sided with Amneal, reasoning that the statute governing Orange Book listings (21 U.S.C. § 355(b)(1)(A)(viii)) requires that a patent must “claim” the active ingredient of the approved drug product to be listed in the Orange Book.
The claims of Teva’s inhaler patents did not mention or refer to albuterol sulfate. As stated in the district court opinion, “It is undisputed that no claim in any of the Inhaler Patents discloses albuterol sulfate.”
The district court ordered that Teva delist five inhaler patents from the Orange Book because they “do not claim the drug for which the applicant submitted the application.”
Teva appealed the district court decision, arguing that the inhaler patents “claim the drug” because: (1) the patents claim the canister and the dose counter components of the approved drug product; and (2) any component of an article that can treat disease meets the FDCA definition of “drug.”
The Federal Circuit rejected Teva’s argument that the inhaler patents claim the drug, reasoning that “to list a patent in the Orange Book, that patent must, among other things, claim the drug for which the applicant submitted the application and for which the application was approved. And to claim that drug, the patent must claim at least the active ingredient.”
According to the court, “to claim something, a patent must particularly point out and distinctly claim what it purports to be the invention. See 35 U.S.C. § 112(b)). And to qualify for listing, a patent must claim at least the active ingredient in the application and the approved drug product.”
In addition, the court rejected Teva’s assertion that any component of a drug product that can treat disease meets the “drug” definition for Orange Book listing. “While Teva’s argument may have some superficial appeal, its reliance on the FDCA’s definition of drug fails to account for how the FDCA’s other provisions inform and limit what kind of medical products within the FDA’s purview are drugs.”
The court emphasized the distinct approval pathways for drugs versus devices, stating that FDCA defines a device as an instrument “which does not achieve its primary intended purposes through chemical action . . . and which is not dependent upon being metabolized for the achievement of its primary intended purposes.” 21 U.S.C. § 321(h)(1).
In asserting that the device constituent parts were not part of the drug, the opinion cited Genus Med. v. FDA, No. 20-5026 (D.C. Cir. 2021), stating “what distinguishes a drug from a device under the FDCA is that a device excludes a product that achieves its primary intended purposes through either chemical action or metabolization.”
Regulation of Drug-Device Combination Products
Congress revised the Safe Medical Devices Act (SMDA) of 1990 to create a new type of product—the combination product. FDA implemented new regulations at 21 C.F.R. §3.2(e) and defined the following types of combination products:
- “A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity (a single entity combination product, such as a prefilled syringe or drug-eluting stent).”
- “Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products (a co-packaged combination product, such as a surgical or first-aid kit containing bandages and an antiseptic drug).”
- “A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved, individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed (e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose) (a cross-labeled combination product, as might be the case for a light-emitting device and a light-activated drug indicated for use together for treatment of a dermatologic condition).”
- “Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect (also a cross-labeled combination product).”
FDA now uses the term “constituent part” as a succinct way to identify a drug, device, or biological product included in a combination product. Similarly, in the Current Good Manufacturing Practice Requirements for Combination Products Final Rule (78 Fed. Reg. 4307, 4312 (Jan. 22, 2013)), FDA explained that the term “component” as used in the definition for “single-entity combination product” in 21 C.F.R. § 3.2(e) is synonymous with “constituent part” under FDA’s rules and guidance.
The Federal Circuit’s opinion points out that, while Congress defined a new kind of product, it did not establish a new approval pathway. Instead, FDA conducts a premarket review of combination products, determining the appropriate approval pathway (i.e., drug, device, or biological) by the combination product’s primary mode of action (i.e., the single mode of action expected to make the greatest contribution to the therapeutic effect of the combination product).
Therefore, the court concluded that a “combination product being approved with an NDA does not necessarily make every part of the NDA a drug.”
The product at issue in the case was a single-entity drug-device combination product, and the opinion focuses most clearly on such combination products. Accordingly, the applicability of the Teva ruling to patents with claims directed to the device constituent parts of co-packaged and cross-labeled combination products is not clear.
Potential Impact of Teva v. Amneal
Claiming, Mentioning, Reciting
The court ruling creates uncertainty regarding both its reasoning and the practicalities of implementing its decision. For example, the Federal Circuit’s emphasis that “a patent must particularly point out and distinctly claim” suggests that “claiming” an active ingredient requires “mentioning” or “reciting” the active ingredient. In that regard, the ruling suggests that a patent that claims the specific active ingredient could be listed but a patent that claims the genus of molecules that comprises the active ingredient perhaps could not be listed.
Moreover, it is not clear whether mentioning or reciting is sufficient for claiming. Under the Federal Circuit’s opinion, is it possible for a claim to mention or recite an active ingredient without claiming the active ingredient? Or are claiming, mentioning, and reciting identical for purposes of Orange Book patent listing?
Even if we resolve the potential distinction between claiming and mentioning or reciting, the opinion does not describe how mentioning or reciting the active ingredient must occur. Common names and alternatives? Chemical name and alternatives? Chemical structure? What about a class of molecules, drugs defined by function, components of the active ingredient-but not the approved active ingredient, free base versus approved salt form?
Would the Teva ruling permit the listing of a patent with a claim that recited “the active moiety or any metabolite or pharmaceutically acceptable salt thereof” if the active ingredient was a metabolite or a pharmaceutically acceptable salt of the recited active moiety?
Traditional Products
Although Teva v. Amneal was decided in the context of a drug-device combination product, the court’s language is not limited to that context. Similarly, the Orange Book Transparency Act (OBTA) of 2020, the Hatch-Waxman Act, and FDA’s implementing regulations do not draw a distinction in the Orange Book patent listing requirements between traditional (non-combination) drug products and drug-device combination products.
Accordingly, the court appears to interpret the patent listing requirements for all drug products. That is, the ruling in Teva appears to apply equally in the context of traditional products.
Under Teva, patents that “read on” drug products would not be eligible for listing if they did not claim, recite, or mention the active ingredient. As emphasized in Corning Glass Works v. Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1258, (Fed. Cir. 1989), to determine whether a patent claims a product, “the words of the claim must . . . be ‘read on’ the accused structure to determine whether each of the limitations recited in the claim is present in the accused structure.”
The court’s ruling would also have significant implications for drug products that depend on a component other than the active ingredient for safe and effective use. Examples might include products encapsulated by liposomes or microspheres, or products in tablets that depend on coatings or other aspects of tablet structure. For example, patents on the liposome or microsphere technology that do not have claims that specifically mention the active ingredient of the drug product in which the technology is used would not qualify for listing under the court’s test.
Fixed-Combination Drug Products
The implications of the ruling are also uncertain for patents that claim one ingredient in a fixed-combination drug product when the ingredient is not approved for independent use.
As discussed above, FDA has defined combination products as products comprising two or more regulated components that are (1) combined and produced as a single entity, (2) two or more regulated components packaged together or (3) two or more regulated components packaged separately with labelling stating they are intended to be used together.
On the other hand, under 21 CFR 300.50, fixed-combination drug products are defined as two or more drugs combined in a single dosage form where each component makes a contribution to the claimed effects and the dosage of each component (amount, frequency, duration) is such that the combination is safe and effective for a significant patient population.
For example, Gilead’s fixed-combination drug, ATRIPLA, combines efavirenz, emtricitabine, and tenofovir disoproxil fumarate in a tablet to be used alone or in combination with other antiretrovirals in the treatment of HIV-1. Each of the three components is an “active ingredient.”
In the case of fixed-combination drug product patents that claim one ingredient, the patent for the single ingredient might not be considered a patent that claims the combination active ingredients of the approved fixed-combination drug product.
Form FDA 3542
Teva v. Amneal also muddies the waters regarding Form FDA 3542, the form that FDA requires NDA holders to use to submit patent information for Orange Book listings. For example, in Section 2.1, the form asks, “does the patent claim the drug substance that is the active ingredient in the drug product described in the approved NDA or supplement?” And in Section 3.1, the forms asks, “does the patent claim the approved drug product as defined in 21 CFR 314.3?”
FDA statements in the instructional supplement suggest that a patent could claim the drug substance (active ingredient) without claiming the drug product. Likewise, a patent could claim the drug product without claiming the drug substance.
“If the patent is eligible for listing as claiming the drug substance AND section 2 is completed, you do not need to complete section 3 even if the patent also is eligible for listing as claiming the drug product.” and “If the patent is eligible for listing as claiming the drug product AND section 3 is completed, you do not need to complete section 2 even if the patent also is eligible for listing as claiming the drug substance.”
In fact, in the 2016 Final Rule, FDA stated that “an applicant need only satisfy the requirements for patent listing set forth in section 505(b)(1) and (c)(2) of the FD&C Act and, subject to the requirements for submission of method-of-use patent information, need not identify each basis on which the patent claims the drug. . . Accordingly, if a patent is eligible for listing as claiming both the drug substance and the drug product, an applicant only would be required to identify one of these two bases for listing.” 81 FR 69580, at 69596 (October 6, 2016).
Although FDA’s comments in the Final Rule and the statements in the instructional supplement suggest that the questions in section 2 and section 3 of Form FDA 3542 are different, thereby possibly producing different answers, the court’s ruling in Teva appears to require that the answers to these questions always be the same for a patent to be eligible for listing. That is, whether the patent purports to claim the drug substance under section 2.1 or the drug product under section 3.1, the patent must “claim” the active ingredient.
Adding to the confusion, the Federal Circuit focused its opinion on an interpretation of the Orange Book patent listing requirements under the OBTA without addressing previous rulings and pre-OBTA interpretations.* However, during enactment of the OBTA, Congress expressed the view that the statutory language implemented FDA’s current practice.
Even the Federal Circuit noted regarding the OBTA: “Congress adopted this language to ‘codify current [FDA] regulations and practice regarding the types of patent and exclusivity-related information listed in the Orange Book.’ H.R. Rep. No. 116-47, at 6.”
The regulatory provisions that Congress referenced reflect that, since 2003, the FDA has interpreted the class of patents that claim the drug for which the applicant submitted the application to “consist of drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method-of-use patents.” 21 C.F.R. § 314.53(b)(1).
The FDA defines “drug substance” to mean “an active ingredient,” and it defines “drug product” to mean “a finished dosage form . . . that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients.” 21 C.F.R. § 314.3(b).
Thus, despite Congress’s intent to clarify FDA’s then-current practice in the language of the OBTA, it is difficult to reconcile FDA’s previous statements and practices with the court’s ruling.
180-Day Exclusivity
To the extent that the Federal Circuit opinion limits patent listings for traditional (non-combination) drug products, there will be fewer Orange Book listed patents that will be available for challengers with paragraph IV certifications to qualify themselves as first applicants for eligibility to receive 180-day generic drug exclusivity.
For first applicants that are eligible for 180-day exclusivity based on a paragraph IV certification to a patent that meets the Federal Circuit’s test, there is a greater likelihood that the marketing of the follow-on product would infringe unlisted patents that might not have been resolved in the Hatch-Waxman litigation context.
In that regard, a first applicant might not be able to take advantage of the 180-day exclusivity unless the first applicant is willing to market the product during the pendency of patent infringement litigation related to the unlisted patents, thereby risking the possible imposition of substantial infringement damages.
Patent Term Restoration
Teva argued that the inhaler patents claim the drug by asserting that “[t]he scope of what a patent
‘claims’ is effectively coterminous with the products that infringe a patent.” However, the Federal Circuit rejected Teva’s argument, reasoning that to read “claiming to be ‘effectively coterminus’ with infringing”… “would create a stunning example of statutory redundancy.”
A similar issue arose in Hoechst-Roussel Pharmaceuticals, Inc. v. Lehman, 103 F.3d 756 (Fed. Cir. 1997). There, the court considered the meaning of the term “claim” and the term’s relationship to the concept of infringement in the context of the Patent Term Restoration provision of the Hatch-Waxman Act, concluding that a patent claiming a metabolite or the use of a metabolite does not claim the approved drug product and thus does not qualify for patent term restoration.
In practical effect, Hoechst distinguished between claiming and infringement by limiting “claim” for Patent Term Restoration to literal “reads on.”
In Hoechst, the court explained that the Patent Term Restoration provisions of the Hatch-Waxman Act apply to patents that claim the FDA-approved drug product without consideration of equivalents, metabolites, or intermediates.
To reach that result, the Hoechst court adopted the position of the United States Patent and Trademark Office (USPTO) and employed what is known as a literal “reads on” analysis, which requires that the limitations recited in the claim be found “literally” in the accused products—not, for example, by the doctrine of equivalents.
The Hoechst court’s reasoning and conclusion regarding the meaning of the term “claim” seem to be equally applicable to patent listings. Thus, if the Federal Circuit’s current interpretation of “claim the drug” for Orange Book listing purposes would also apply to the same term in the Patent Term Restoration provisions, there could be a substantial impact on the patents that would be eligible for Patent Term Restoration.
Final Takeaways
As mentioned earlier, the Federal Circuit denied Teva’s petition for rehearing en banc and subsequently denied Teva’s motion for an administrative stay pending a petition for certiorari to the Supreme Court. Therefore, absent a grant of certiorari from the Supreme Court, the Federal Circuit’s interpretation of the patent listing requirements will prevail.
The reasoning behind the Federal Circuit’s opinion in Teva v. Amneal creates many ambiguities regarding what the court means and the practicalities of implementing the ruling. Although the Federal Circuit’s ruling has substantially clarified patent listing issues for single-entity drug-device combination products, the greatest impact on the operation of the Hatch-Waxman Act could be on Orange Book patent listings for traditional (non-combination) drug products, where the patent that reads on the approved drug product does not recite the active ingredient by common name, chemical name, or specific structure.
Pharmaceutical companies should consider a careful review of all listed patents. Companies who do not conform their patent listings to the ruling in Teva might be vulnerable to delisting proceedings and allegations of antitrust violations.
*Gregory J. Glover, MD JD, is one of the nation’s leading experts on the complex interaction of food and drug regulation and intellectual property and consults with companies in ongoing matters involving Orange Book patent listing requirements prior to the enactment of the OBTA.