Blog March 31, 2023
Federal Circuit to Consider the Relevance of an Alleged Infringer’s “Intent” in a Hatch-Waxman Safe Harbor Analysis
In February 2020, the U.S. Court of Appeals for the First Circuit found that Sanofi improperly listed U.S. Patent No. 8,556,864 ("the '864 patent") which claims aspects of a drive mechanism of the Lantus® SoloSTAR® insulin glargine injector pen in the Orange Book. In re Lantus Direct Purchaser Antitrust Litigation, 950 F.3d 1 (1st Cir. 2020). This blog summarizes the First Circuit's decision and FDA guidance regarding the listing of patents claiming pre-filled drug delivery devices in the Orange Book.
Lantus® ("Lantus") is Sanofi's insulin glargine product. The U.S. Food and Drug Administration (FDA) first approved Lantus in 2000 as a sterile solution of insulin glargine for use as an injection. As originally approved, Lantus had two package forms vials for use with single-dose syringes, and cartridges for use in an injector pen called OptiPen® One. At that time, Sanofi listed the original patent for insulin glargine (U.S. Patent No. 5,656,722) in the Orange Book. Sanofi later obtained two additional patents relating to the ingredients in the Lantus vial formulation, and listed these patents in the Orange Book as well. In re Lantus Direct Purchaser Antitrust Litigation, 284 F. Supp. 3d 91, 99 (D. Mass. 2018).
In 2007, FDA approved Sanofi's application to sell Lantus in another disposable injector pen called SoloSTAR® ("SoloSTAR"). At that time, Sanofi listed several patents covering the Lantus SoloSTAR, including the '864 patent, in the Orange Book. The '864 patent claims a drive mechanism used in the Lantus SoloSTAR injector pen. However, the '864 patent does not claim Lantus or insulin glargine. The issue in the recent litigation was whether Sanofi appropriately listed the '864 patent in the Orange Book. Id. at 99—100.
The "Orange Book" is the common name for the FDA publication Approved Drug Products with Therapeutic Equivalence Evaluations. The Orange Book identifies FDA-approved drug products and lists related patent and exclusivity information. One of the purposes of the Orange Book "is to provide would-be generic manufacturers with notice of any patent rights that are implicated by a brand-name drug." Lantus, 284 F. Supp. 3d at 103 (quoting United Food & Commercial Workers Unions & Employers Midwest Health Benefits Fund v. Novartis Pharmaceuticals Corp., No. 15-cv-12732, 2017 WL 2837002, at *5 (D. Mass. June 30, 2017)).
Drug manufacturers applying for FDA approval of a new drug or FDA approval of changes to an approved drug are required to submit certain patents for listing in the Orange Book. The Food, Drug & Cosmetic Act (FD&C Act) requires an applicant to file:
[T]he patent number and the expiration date of any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug.
21 U.S.C. § 355(b)(1). FDA regulations further identify which patents should be submitted for Orange Book listing—applicants should list "patent[s] that claim the drug or a method of using the drug ... [which] consist of drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method-of-use patents," but should exclude process patents and patents claiming packaging. 21 C.F.R. § 314.53(b)(1). FDA regulations also require that applicants declare that a patent submitted for Orange Book listing claims the "drug substance," "drug product (composition/formulation)," or "one or more methods of using" the drug for which it is listed. Lantus, 950 F.3d at 4 (quoting 21 C.F.R. § 314.53(c)(2)(i)(M)—(O)).
FDA reviews submissions for completeness and lists the patents in the Orange Book, but FDA does not "review patent information for its accuracy and relevance." Id. at 3 (quoting 59 Fed. Reg. 50,338, 50,343, 50,345 (Oct. 3, 1994)). FDA does not have any processes for "review[ing] the scope of [a submitted Orange Book] patent and its application to the approved drug product" or for delisting patents in the Orange Book. Id. at 4 (quoting 68 Fed. Reg. 36,676, 36,683 (June 18, 2003)).
There is no clear guidance from FDA with respect to the listing of patents covering drug delivery devices, like the Lantus SoloSTAR, in the Orange Book. Several drug manufacturers have submitted requests for advisory opinions to FDA, asking "whether patents directed to drug delivery systems ... that do not recite the approved active ingredient or formulation should be listed in the [Orange Book]." Id. at 9. In response, FDA has only acknowledged that the Orange Book "was not designed to separately address combination product listings or to identify the specific type of drug delivery system" and that it "could benefit from enhanced listing capabilities." Id. In response to one request, FDA also stated that it had "been unable to reach a decision ... due to the need to address other Agency priorities." Id. at 9-10.
In December 2016, consumers who purchased the Lantus SoloSTAR brought a purported class action against Sanofi in the District of Massachusetts, alleging that Sanofi improperly delayed market entry of a competitive insulin glargine product manufactured by Eli Lilly. The plaintiffs asserted claims under the Sherman Act and alleged, inter alia, that Sanofi prolonged its monopoly for insulin glargine by improperly listing six patents related to the Lantus SoloSTAR in the Orange Book. Lantus, 284 F. Supp. 3d at 94.
In January 2018, the district court granted Sanofi's motion to dismiss both counts of the amended complaint pursuant to Rule 12(b)(6) for failure to state a claim upon which relief could be granted. Id. at 95. The plaintiffs argued that the '864 patent was improperly listed in the Orange Book because the patent did not "claim the finished dosage form of the approved drug product," insulin glargine. Id. at 100. Sanofi, however, argued that it was proper to list the '864 patent in the Orange Book because "FDA has expressly interpreted 'drug products' which must be listed in the Orange Book to include 'pre-filled drug delivery systems,'" and the '864 patent relates to the Lantus SoloSTAR, which is an approved "pre-filled drug delivery device." Id. at 100, 104. The district court found "that while the issue of whether the Lantus SoloSTAR patent is appropriately listed in the Orange Book is an open question, Sanofi's interpretation is reasonable and, therefore, defeats the plaintiffs' antitrust claims." Id. at 100, 106. According to the court, it was reasonable for Sanofi to conclude that it was required to list the '864 patent in the Orange Book because, inter alia, FDA has expressly interpreted "drug products" that must be listed in the Orange Book to include "pre-filled drug delivery systems." Indeed, FDA had approved the Lantus SoloSTAR as a drug delivery system, not as a package change; and the Lantus SoloSTAR was, in fact, sold as a pre-filled drug delivery system. Id. at 103—05.
In February 2020, the First Circuit found that Sanofi improperly listed the '864 patent in the Orange Book, reversed the district court's dismissal of the plaintiffs' claims, and remanded for further proceedings consistent with its decision. Lantus, 950 F.3d at 3, 15. The court found that "[t]he statute and regulations clearly require that only patents that claim the drug for which the NDA is submitted should be listed in the Orange Book[, and] [t]he '864 patent, which neither claims nor even mentions insulin glargine or the Lantus SoloSTAR, does not fit the bill." Id. at 10.
First, the court analyzed the relevant statute and FDA regulations and found that the plain text makes clear that only patents that claim the drug for which an NDA is submitted should be listed in the Orange Book. The court found that the plain text of 21 U.S.C. § 355(b)(1) calls for the listing of patents "which claim the drug for which [an application is submitted] or which claim a method of using such drug." Id. at 4 (quoting 21 U.S.C. § 355(b)(1)). And the court found that an FDA regulation "makes it clear that 'only' such patents are to be listed" in the Orange Book. Id. (citing 21 C.F.R. § 314.53(b)(1)). The court noted that these requirements "reflect an attempt to balance two competing interests: promoting competition between âbrand-name' or 'innovator drugs' and 'generic' drugs, and encouraging research and innovation." Id. at 5 (quoting 68 Fed. Reg. at 36,676 (June 18, 2003)) (alterations omitted).
Next, the court found that FDA guidance supported Sanofi's argument that the Lantus SoloSTAR is a "drug product" under 21 C.F.R. § 314.3(b). FDA regulations define "drug product" as "a finished dosage form, e.g., tablet, capsule, or solution, that contains a drug substance, generally, but not necessarily, in association with one or more ingredients." Id. at 7 (quoting 21 C.F.R. § 314.3(b)). Sanofi argued that the Lantus SoloSTAR is a "drug product" because it is a "finished dosage form," which FDA regulations define as "the physical manifestation containing the active and inactive ingredients that delivers a dose of the drug product." Id. The court found that FDA guidance supported this reading of the regulations. FDA guidance has described the Orange Book's appendix as "list[ing] current dosage forms for approved drug products," including "metered aerosols, capsules, metered sprays, gels, and pre-filled drug delivery systems." Id. (quoting 68 Fed. Reg. at 36,680 (June 18, 2003)). And a "Frequently Asked Questions" page on the FDA website lists an "insulin injector pen" as an example of a "prefilled drug delivery system." Id. (alterations omitted).
The court then turned to the '864 patent and found that there was "a vital link missing" in "Sanofi's chain of reasoning"—"the '864 patent does not claim or even mention the Lantus SoloSTAR[;] [i]ndeed, though it claims a device intended for use in an injector pen, it does not claim any injector pen, nor even a method of using a pen." Id. at 8. According to the court's reading of the statute, for the '864 patent to have been properly listed in the Orange Book, the patent would have to "claim the drug (or a method of using the drug) for which the applicant submitted' the sNDA." Id. at 8 (quoting 21 U.S.C. § 355(b)(1)). Because the claims of the '864 patent do not mention the drug for which the sNDA was submitted (insulin glargine), the '864 patent does not "claim the drug." Id. The court therefore concluded that it was improper for Sanofi to have submitted the '864 patent for listing in the Orange Book as a patent claiming either insulin glargine or the Lantus SoloSTAR. Id.
Next, the court rejected Sanofi's argument that the drive mechanism claimed in the '864 patent is an "integral component" of the Lantus SoloSTAR that FDA regulations require listing in the Orange Book. According to Sanofi's reasoning, because the drive mechanism is an integral part of the Lantus SoloSTAR, a patent that claims the drive mechanism claims a part of a drug product, and thus "claims the drug." Id. The court found, however, that "nothing in the statute or regulations  welcomes such a further expansion of the already-stretched statutory terms, whereby an integral part of an injector pen becomes the pen itself, and in turn is a drug." Id.
The court rejected Sanofi's argument "that, because the language of the regulations suggests that multiple patents can be filed with an application, the regulations must contemplate submission of patents claiming components of a drug product," otherwise, "manufacturers would have to claim every part of a drug in a single patent in order to file it, and the plural language in the regulations would be meaningless." Id. The court noted that "Sanofi [did] not explain why multiple patents could not all directly claim a drug product." Id. at 9. The court also contrasted the '864 patent with, for example, the patents for Narcan (U.S. Patent No. 9,211,253) and the EpiPen (U.S. Patent No. 8,870,827), which "claim all the components of a combination drug product." Id.
Finally, the court rejected Sanofi's argument that the drive mechanism claimed by the '864 patent is itself a "drug" under 21 U.S.C. § 321(g)(1). Under this statute, the term "drug" includes, inter alia, "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals," and "articles intended for use as a component of any article specified" in the previous clause. Id. at 10 (quoting 21 U.S.C. § 321(g)(1)). The court found that the "definition of 'drug' in section 321(g)(1) demonstrates that Congress knew that some drugs had 'components'; thus the absence of any mention of 'component'" in the provisions setting out which patents should be filed cuts against any attempt to interpret the statute and its implementing regulations as requiring or allowing listing of patents that claim only components of a proposed drug." Id.
FDA is currently seeking to modernize the Orange Book. On June 1, 2020, FDA established a public docket (Docket No. FDA-2020-N-1127) to solicit comments on the listing of patent information in the Orange Book, including "the types of patents currently listed in the Orange Book and the impact that any change to current patent listing practices may have on drug product development."
In the supplementary information provided with the docket, FDA acknowledged that there is uncertainty among stakeholders regarding whether certain types of device-related patents should be submitted for listing in the Orange Book. As part of "an Agency-wide effort to modernize the Orange Book," FDA is examining whether it should "provide additional clarity regarding the types of patent information listed in the Orange Book," including, inter alia, "[t]he listing of patents that claim a device constituent part of a combination product approved under section 505 of the FD&C Act (e.g., a drug delivery device)."
As of June 26, 2020, FDA has not yet received any comments in response to this docket. The docket will close on August 31, 2020. We will monitor further developments on this issue as they occur. Stay tuned!
 A drug manufacturer seeking FDA approval of a new drug must file an application called a "new drug application," or an "NDA." A drug manufacturer seeking approval of changes to an approved drug must file a supplemental application called a "supplemental new drug application," or an "sNDA." Both NDA and sNDA applicants are required to submit appropriate patents for listing in the Orange Book.
 FDA has only a "limited mechanism for reviewing the âaccuracy or relevance of patent information submitted' for listing in the Orange Book." Lantus, 950 F.3d at 4 n.2 (quoting 21 C.F.R. § 314.53(f)). Anyone may notify FDA in writing about a potential problem, and in response, FDA may require the NDA holder either to "confirm the correctness of the patent information," or "withdraw or amend the patent information." Id. (quoting 21 C.F.R. § 314.53(f)(1)(i)). "Unless the NDA holder withdraws or amends its patent information in response to the patent listing dispute, [FDA] will not change the patent information in the Orange Book." 21 C.F.R. § 314.53(f)(1)(i)(A).
Authors: Kayleigh McGlynn and Brian Coggio
The opinions expressed are those of the authors on the date noted above and do not necessarily reflect the views of Fish & Richardson P.C., any other of its lawyers, its clients, or any of its or their respective affiliates. This post is for general information purposes only and is not intended to be and should not be taken as legal advice. No attorney-client relationship is formed.
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