One of the most significant obstacles to drug competition is a patent listed in FDA’s “Orange Book.” The mere listing of a patent can delay competition for months, or even years, and drive up expense for competitors. Drug patent owners want to extend the patent protection on their products for as long as they can, including their exclusivity in the market. Competitors want exactly the opposite.
So it is important to understand which patents belong in the Orange Book and, more to the point, which ones don’t. We’ve been watching a controversy over the listing of patents on devices that may be used with drugs, even though the device patents don’t refer to the listed drugs. A pending antitrust class action has challenged the practice, while FDA has avoided taking a clear position on it. See In re Lantus Direct Purchaser Antitrust Litig., No. 16-cv-12652-JGD (D. Mass. filed Dec. 30, 2016).
FDA guidance is clear that applicants may list “drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method-of-use patents.” 21 C.F.R. § 314.53(b)(1). Applicants may not list process patents, patents claiming packaging, patents claiming metabolites, and patents claiming intermediates. Id.
So is it proper to list a drug-delivery device patent in the Orange Book if the patent doesn’t claim the drug? Combination products—for example, pre-filled syringes, inhalers, transdermal patches—are becoming more and more prevalent. New-drug applicants are no doubt eager to add patents covering these products to the Orange Book, as added protection for their approved drugs. Some argue that drug-delivery device patents qualify as “drug product” patents.
What is a drug product in this context? A drug product “is 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. FDA has indicated that certain drug-delivery systems, including “metered aerosols, capsules, metered sprays, gels, and pre-filled drug delivery systems,” are drug products. Applications for FDA Approval to Market a New Drug: Patent Submission and Listing Requirements and Application of 30-Month Stays on Approval of Abbreviated New Drug Applications Certifying That a Patent Claiming a Drug Is Invalid or Will Not Be Infringed, 68 Fed. Reg. 36676, 36680 (June 18, 2003).
But may an applicant list a drug-delivery device patent in the Orange Book when the patent does not claim the drug? FDA has not clearly answered this question. But FDA has said that “[t]he key factor is whether the patent being submitted claims the finished dosage form of the approved drug product.” Id.
Brands have asked FDA for guidance on this issue at least a handful of times. See Comments of the Pharmaceutical Research and Manufacturers of America, Docket No. FDA-2011-N-0830, at 8-9 (June 8, 2015); see also In re Lantus, 2018 U.S. Dist. LEXIS 4503, at *30-31 (D. Mass. Jan. 10, 2018) (“Since at least 2005, drug manufacturers have sought to determine whether patents directed to drug delivery systems that do not recite the approved active ingredients or formulation should be listed in the Orange Book. In the absence of any response to several inquiries to the FDA, in 2007, AstraZeneca informed the FDA that it was going to continue to list in the Orange Book patents for approved pre-filled drug delivery systems even if the patent neither disclosed nor claimed the active ingredient or formulation of the approved drug product.” (citation omitted). The FDA has yet to respond.). Tired of waiting for a response, several brands have announced that they will list patents that claim all or part of an integrated drug-device product, “regardless of whether the approved drug substance is specifically mentioned in the claims of such patents.” Will the Fourth Time be the Charm? FDA is Once Again Asked for Guidance on Drug Delivery Device Patent Orange Book Listing, FDA Law Blog (July 21, 2011). As recently as several months ago, a federal district court acknowledged that the issue remains unresolved. In re Lantus, 2018 U.S. Dist. LEXIS 4503.
So what can an ANDA or § 505(b)(2) applicant do if it believes that a patent owner has improperly listed patents in the Orange Book? The applicant may file a citizen petition and request guidance from FDA. Or if it’s looking for a slightly speedier response, the applicant may file a claim for improper listing in district court. See, e.g., King Pharmas. Inc. v. Intelliject Inc., No. 11-cv-65 (D. Del. filed Jan. 19, 2011). We are watching the In re Lantus Direct Purchaser Antitrust Litigation to see how the issue is treated there.