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The U.S. Patent and Trademark Office (USPTO), in conjunction with the Food and Drug Administration (FDA) and in response to 2022 and 2022 letters from Senator Thom Tillis (R-NC), has published a examining the time from approval of a New Drug Application (NDA) until the first generic launch for 25 drug products, including consideration of patent and regulatory exclusivities. The stated purpose of the report is “to provide a baseline approach that researchers and policymakers can use in future analysis,” but the conclusions drawn from its sample of drug products are interesting for what they do not show. As stated in the conclusion, “The study observes that patent expiration dates, like the number of patents, may not be predictive of the timing of actual launch of competing products.”

The study furthers the Biden Administration’s ongoing policy discussion on balancing the development of innovative medicines and the availability of generic drugs and addresses Senator Tillis’s request for an independent assessment of the actual years of market exclusivity enjoyed by an NDA holder prior to generic launch, in light of assertions of improper extensions of IP rights and protections for drug products made in University of California College of the Law, Evergreen Drug Patent Database (UC Database) and Initiative for Medicines, Access & Knowledge (I-MAK) reports.

The Study Methodology

The study methodology included a review of patents, regulatory exclusivity, and drug approval data found in USPTO databases, the Orange Book, and other public FDA databases for 25 drug products (representing 13 active ingredients or combinations thereof). The 25 drug products were selected based on several factors, including top-grossing products by revenue in 2017, most prescribed branded products in 2017, and being the subject of the reports cited in the Tillis letters. The number of Orange Book-listed patents per product ranged from one to 27. For the drug products in the study with identified generic competition, the market exclusivity ranged from about three years to about 16 years. The report explains that, unlike the UC Database, it did not rely on patent “use codes” listed in the Orange Book as an indication of patent scope, because use codes are only provided by the NDA holder for patents claiming a method of using the drug product and may not prevent generic launch if the use can be carved-out under 21 U.S.C. § 355(j)(2)(A)(viii).

Discussion

The list of studied drug products include top-grossing products in 2017 (e.g., apixaban (ELIQUIS), lenalidomide (REVLIMID), pregabalin (LYRICA), rivaroxaban (XARELTO), ibrutinib (IMBRUVICA) and bictegravir sodium (BIKTARVY)); most prescribed branded products in 2017 (e.g., atorvastatin (LIPITOR), amlodipine besylate (NORVASC), or albuterol sulfate (VENTOLIN HFA)); a fixed dose combination drug (e.g., lopinavir/ritonavir (KALETRA)); a new innovation of well-known active ingredients (e.g., aspirin-containing products (VAZALORE)); and a widely available drug marketed by multiple manufacturers (e.g., zolpidem tartrate (AMBIEN).

As noted above, the report concludes that reliance on the number of patents is an “imprecise way to measure the intellectual property landscape of a drug product.” Instead, the report states that “a comprehensive analysis of all the patents and pending patent application claims that, if issued in a patent, could reasonably be asserted against an ANDA applicant [would] provide a more fulsome picture of the general competitive landscape for a drug product.”

In reaching this conclusion, the USPTO points to specific examples where the number of patents did not tell the whole story:

• In some cases (e.g., MIRAPEX), newer methods of use protected by a patent (e.g., directed to treating restless leg syndrome) may not necessarily prevent a generic launch for other uses for which patent protection has expired (treating Parkinson’s disease)
• For some drugs, such as (LIPITOR (settlement agreement), LYRICA CR (noninfringement judgment), KALETRA (statutory disclaimer), or REVLIMID (settlement agreement), generics were launched before the expiration of all applicable Orange Book-listed patents and exclusivity time periods for that product
• A higher number of patents may not necessarily delay a generic launch (e.g., REVLIMID)
• The doctrine of nonstatutory double patenting prevents multiple patent applications filed by the same patentee to novel but obvious variations of related inventions from issuing with a different patent expiration date (e.g., IMBRUVICA)
• Aspirin is an example of an older active ingredient patented in a new formulation that did not impact the continued availability of other products containing aspirin during the period of the listed patents
• In some cases, no generic has launched despite the expiration of Orange Book-listed patent(s) (e.g., VENTOLIN HFA, AMBIEN, NORVASC, or XARELTO), whereas other products with patent and exclusivity barriers have no competition (e.g., IMBRUVICA or ELIQUIS).

In summary, while the sample size may limit generalizations, the study report illustrates the limitations of simply quantifying raw numbers of patents to draw conclusions about the intellectual property landscape surrounding a drug product. The actual market exclusivity periods for drug products vary widely and are influenced by a complex interplay of patent law, FDA statutes and regulations, and other factors.

Overall, the report illuminates the importance of policymaking based on accurate and transparent data and is particularly timely given the USPTO’s proposed rulemaking on terminal disclaimer practice, which is expressly designed to address the perceived problem of multiple patents directed to obvious variants of an invention potentially deterring competition.

Special thanks for Meyke Kang, a summer associate in �鶹ֱ��’s Washington, D.C. office, for her contributions to this article.