Update: Orange Book Listing of Drug Delivery Device Patents After In re Lantus, February 2020

Update: Orange Book Listing of Drug Delivery Device Patents After In re Lantus, February 2020¹

Introduction

The U.S. Court of Appeals for the First Circuit recently ruled that Sanofi could potentially be held liable for an antitrust violation for improperly listing an insulin delivery device-related patent in the U.S. Food and Drug Administration’s (“FDA”) Orange Book (“OB”) for LANTUS® soloSTAR®.² LANTUS® soloSTAR® is an insulin self-injection delivery system, sometimes called an insulin pen.

The patent at issue U.S. Patent No. 8,556,864 (the ‘864 patent) claims the drive mechanism within the pen, not the pen itself, and no claim describes the insulin analog or drug formulation delivered with this device. Sanofi submitted the ‘864 patent, for OB listing in 2013. Several companies later submitted 505(b)(2) new drug applications (“NDA”) referencing LANTUS®, with paragraph IV certifications to the ‘864 patent, but resulted in licensing agreements with Sanofi.

The plaintiffs in In Re Lantus allege that Sanofi prolonged its “monopoly for insulin glargine” by improperly listing the ‘864 patent (and other patents). Plaintiffs assert that, because the ‘864 was improperly listed in the OB, patent infringement litigation based on Paragraph IV certifications for this patent was a “sham” initiated to trigger the automatic 30 month stay of FDA approval of the competing product. The District Court dismissed the plaintiff’s antitrust claims for improper listing of the ‘864 patent because of the “ambiguities in the FDA’s listing requirements.” However, on appeal, the First Circuit reversed. The court held that a patent that claims only a component of a drug delivery device, and does not explicitly claim the drug product, cannot be listed in the OB.³ Slip op. at 20.

LANTUS® soloSTAR® is one of several products approved for marketing as drugs in the US that is administered using a device (a drug-device combination product).⁴ Companies that own such products often file at least one U.S. patent to protect the device. The company may also wish to list the device patent in the OB. Listing a patent in the OB patent provides certain benefits to the owner of a drug product.⁵

In the scenario described above, the company may already have or may be seeking patents to cover the active ingredient and/or formulation aspect of the combination product, in which case the device patent adds to the patent barrier protecting the drug product. However, in some cases the active ingredient and formulation are old and no longer protected by patent, or the patent(s) will expire earlier than the device patent(s), as in the Lantus soloSTAR® case.

Determining whether to list a device patent in the FDA’s OB for drug-delivery device combination products can present a quandary. While a company may choose to list such patents, an ANDA filer or 505(b)(2) NDA filer may seek delisting, and/or the NDA owner may risk being accused of an antitrust violation for such a listing, depending on the patent claims. This blog provides some suggestions to strengthen eligibility for listing, and reduce these risks.

Background

The owner of a New Drug Application is required to list in the OB patents that claim “the drug” or a method of using it “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). The FDA defines “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 other ingredients.” 21 C.F.R. § 314.3. A “dosage form” refers to

the physical manifestation containing the active and inactive ingredients that delivers a dose of the drug product. This includes such factors as: (1) The physical appearance of the drug product; (2) The physical form of the drug product prior to dispensing to the patient; (3) The way the product is administered; and (4) The design features that affect frequency of dosing.

Id. Thus, patents that claim the drug should be listed, and the meaning of “drug” includes the “finished dosage form” which is “the physical manifestation” of the product including “the way the product is administered.” The statute and rules relating to patent listing do not explicitly address devices used to administer the drug, but the language above suggests that patents that claim such devices are eligible for listing.

The FDA has identified the following types of delivery devices as part of the drug product, indicating that patents for such devices should be listed in the OB: “metered aerosols, capsules, metered sprays, gels and pre-filled drug delivery systems.” See 68 Federal Register 36,675, 36680 (June 18, 2003).⁶ In each of these examples, performance of the drug-delivery device is critical to proper administration of the approved drug product and clinical efficacy. In contrast, the FDA has prohibited the listing of “process patents, patents claiming packaging, patents claiming metabolites, and patents claiming intermediates.” 21 C.F.R. § 314.53(b)(1).

However, guidance regarding the OB listing requirement is unclear and incomplete regarding patents that claim a drug delivery device.

While FDA guidance regarding OB listing of drug delivery device patents is ambiguous, the FDA has not rejected listing of drug-delivery device patents. The FDA does not review patent content for each patent listing, instead it treats listing as a ministerial function.⁷ Some companies have notified the FDA they intend to list these patents and/or have sought an advisory opinion from the FDA regarding the listing of such patents.⁸ The FDA has not substantively responded to any of these requests for guidance.⁹

Although the FDA appears to have acquiesced to listing drug delivery device patents in the OB, irrespective of what they claim, third parties, such as ANDA or 505(b)(2) NDA filers, may dispute listing by request delisting of a patent. See 21 C.F.R. § 314.53(f)(1). In addition, if sued for patent infringement, the ANDA or 505(b)(2) filer may seek delisting of a patent by filing a delisting counterclaim under 21 USC §355(c)(3)(D)(ii)(I).

Courts have not ruled on the OB listing of drug delivery device patents in the context of Hatch-Waxman patent infringement litigation, although the issue has been raised. See King Pharms., Inc. v. Intelliject, Inc., No. 1:11-cv-00065-UNA (D. Del. Jan. 19, 2011). In this suit, the 505(b)(2) NDA filer filed a counterclaim pursuant to FDC Act §505(c)(3)(D)(ii)(I) to seek the delisting of patent information from the OB for a device-related patent on the ground that the patent did not claim the drug product, EpiPen®. The suit was settled and dismissed before this issue was resolved by the court.

In re Lantus

The First Circuit’s opinion in the In re Lantus antitrust litigation is the first guidance from an appellate court regarding the listing of drug delivery device patents. The court held 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 OB. The ‘864 patent, which neither claims nor even mentions insulin glargine [(the active ingredient)] or the Lantus soloSTAR, does not fit the bill.” In re Lantus, No. 18-2086, slip op. at 20 (1st Cir. Feb. 13, 2020). The opinion does not provide much guidance on the meaning of “drug product.” It is unclear whether, had the patent included a claim to a pen containing the drive mechanism, or a claim to a method of using a pen containing the drive mechanism to administer the active ingredient would have changed the outcome.⁹ What is clear is that a patent that claims only a component of a drug delivery device is not eligible for listing in the OB, at least according to the First Circuit.

How to Improve OB Listing Eligibility

Drafting a patent application and claims that clearly tie the drug delivery device invention to the finished product may reduce risk in listing drug delivery device patents.

The In re Lantus opinion states that even assuming “that the Lantus SoloSTAR is a drug under the statute, there is still a vital link missing: the ‘864 patent does not claim or even mention the Lantus SoloSTAR. Indeed, 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 14. Furthermore, the court stated that “even assuming that the drive mechanism claimed by the ‘864 patent is itself a drug, we still find Sanofi falling short of its goal because the drive mechanism is not the ‘drug for which [Sanofi] submitted’ the sNDA. . . . For that reason alone the patent for the drive mechanism does not qualify for listing in the Orange Book as claiming the Lantus SoloStar.” Id. at 18. Further, in the summary of the facts, the court had noted that “[t]he patent does not mention insulin glargine or the Lantus SoloSTAR at any point. The patent’s specification only briefly mentions diabetes and insulin, the latter as an example of the type of drug the device using the drive mechanism could dispense.” Id. at 10. These statements suggest that, had Sanofi included in the ‘864 patent a claim to the entire pen device containing the drive mechanism, and/or a method of using the pen device, the court’s conclusion would have been different. In addition, the court’s statements regarding the limited description of insulin suggest that including a claim in which the pen contained an insulin glargine formulation or was used to administer such a formulation would have also strengthened the case for patent listing.

In view of In re Lantus, when drafting a drug delivery device patent application, it would be prudent to include disclosure describing (1) the specific drug active ingredient, and formulation containing it, to be administered using the device, and (2) the method of administration using the device. If known, In re Lantus, suggests it may help to include the trade name of at least the drug formulation in the disclosure, although why this would be so is unclear, and often the trade name has not been selected at the time at which the patent application is filed. In addition, the application should claim the device and drug product together, such as a kit or device filled with the drug product, and include claims to a method of using the device to administer the drug product. Including a “picture claim,” i.e., a narrow claim with limitations specific to the drug product, may also be prudent (and can also be useful when facing an invalidity challenge) as some of the statements in In re Lantus,, suggest that linking the device to a specific drug product (“the drug” not just “a drug”) would have helped Sanofi’s case. If the invention is only a component of the device, include claims to the entire device containing the component, to the device (with component) containing the drug active ingredient, and to a method of using the device (with component) to administer this active ingredient. Dependent claims describing the formulation containing the active ingredient should also be included if this information is known.

If the drug aspect of the combination product is still patentable, the patent(s) for the drug should be filed before or on the same date as the device patent application, since the device patent application containing a description of the drug could become prior art to the drug patent (and vice versa if the device is disclosed in the drug patent application).

If the device patent application has already been filed, review the disclosure carefully for mention of the drug product, even a generic description of it, and add claims to the device plus drug and method of administration, if the application disclosure supports such claims.

If it is too late to add claims, e.g., if the patent has issued and there are no pending continuing applications, consider filing a petition for an advisory opinion from the FDA regarding listing of the patent before doing so. In re Lantus held that “the defenses to antitrust liability as a result of such an improper submission [of the ‘864 patent for OB listing] include proving that the submission was the result of a reasonable, good-faith attempt to comply with the Hatch-Waxman scheme” and remanded the case for further discovery. Id. at 30.