Patent Portfolios Protecting 10 Top-Selling Prescription Drugs.

Importance: Brand-name drugs are sold at high prices in the US during market exclusivity periods protected by patents. Multiple overlapping patents protecting a drug are known as patent thickets and can effectively delay the emergence of price-lowering generic competition for many years. Objective: To evaluate the composition of patent thickets of 10 top-selling prescription drugs in the US and compare the characteristics of drug patents filed during development with those filed on these products after US Food and Drug Administration (FDA) approval. Design and Setting: This cross-sectional study examined US patent thickets of the 10 prescription drugs with the highest US net sales revenue in 2021 using information on issued patents and patent applications as of June 30, 2022, obtained from a public database by the Initiative for Medicines, Access, and Knowledge. Data were analyzed from September 2022 to June 2023. Main Outcomes and Measures: Prevalence of patents filed before and after FDA approval; types of claims present in issued patents (ie, chemical composition, method of use, process or synthesis, formulation, and delivery device); and patent thicket density (number of active patents at a given time). Results: The 10 top-selling prescription drugs in the US for 2021 included 4 small-molecule drugs and 6 biologics. These 10 drugs were linked to 1429 patents and patent applications: 742 (52%) issued patents, 218 (15%) pending applications, and 469 (33%) abandoned applications. Almost three-quarters of patent applications (1028 [72%]) were filed after FDA approval. The postapproval proportion was higher for biologics (80%) than for small-molecule drugs (58%). Postapproval filing of patent applications peaked in the first 5 years after FDA approval for small-molecule drugs and 12 years after FDA approval for biologics. Of 465 patents issued for applications filed after FDA approval, 189 (41%) had method of use claims, 127 (27%) had formulation claims, and 103 (22%) had process or synthesis claims, while 86 (19%) had chemical composition claims and 46 (10%) had device claims. Patent thicket density peaked 13 years after FDA approval, at which time these 10 drugs were protected by a median (IQR) of 42 (18-83) active patents, 66% of which were filed after FDA approval. Conclusions and Relevance: This study found that among the 10 top-selling prescription drugs in the US in 2021, patents filed after FDA approval and containing claims covering aspects other than the active ingredient of the drug contributed to patent thickets. Scrutiny of patent applications and of patents filed after FDA approval is needed to facilitate timely generic or biosimilar competition.

Delivery Device Patents on GLP-1 Receptor Agonists.

This study analyzed the US Food and Drug Administration­listed patents on glucagon-like peptide 1 (GLP-1) receptor agonists to determine their claim characteristics and the potential barriers they pose to generic entry.

Patents on Risk Evaluation and Mitigation Strategies for Prescription Drugs and Generic Competition.

This cross-sectional study identifies the prevalence of patents on risk evaluation and mitigation strategies and their association with delaying generic competition.

Biologic Patent Thickets and Terminal Disclaimers.

This study analyzes the use and timing of terminal disclaimers in all biologic patents involved in litigation from 2010 to 2023.

Preserving Timely Generic Drug Competition with Legislation on "Skinny Labeling".

Patents prevent generic drug entry. Brand firms file new "method of use" patents for old drugs to prevent generic entry. Congress addressed this issue by creating the "skinny label" pathway, which allows generic firms to use the drug label to indicate that the old drug can only be used for non-patented uses. This pathway is now in jeopardy due to a recent court case. This paper outlines the issues and suggests possible legislative solutions.

Ancillary Product Patents to Extend Biologic Patent Life.

This study examines all patents associated with biologic litigation to understand how manufacturers use ancillary product patents to delay biosimilar market entry.

Inequitable Conduct and Invalidation of Patents Related to Food and Drug Administration-Regulated Products.

This study examines the frequency of drug patent invalidations based on inequitable conduct.

Next-Generation Bioprinted Products: Products of Nature or Patentable Innovation?

Bioprinting is an additive manufacturing process used to create architectures that mimic natural living tissues in form and function [1]. It involves the deposition of bioink, which can include a mixture of living cells, nutrients, and extracellular matrix. The bioink is then deposited onto a scaffold to generate 3-D structures that imitate natural tissues and organs. This process has already been used to generate a diverse range of products, including bioprinted human ears for transplant, and 3-D printed bioceramic and modified biopolymer bone implants that received U.S. Food and Drug Administration (FDA) marketing approval [2] Researchers are working on bioprinted versions of a wide range of organs, including liver, kidney, lung, and heart.

Changes in the Number of Continuation Patents on Drugs Approved by the FDA.

This study assesses the frequency of continuation patents on brand-name drugs approved by the US Food and Drug Administration from 2000 to 2015.

Free Speech Challenges to the Inflation Reduction Act.

This Viewpoint looks at the lawsuits brought by pharmaceutical companies to challenge the Inflation Reduction Act of 2022, in particular claims under the First Amendment's protection of free speech.

Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists.

Importance: Glucagon-like peptide 1 (GLP-1) receptor agonists were first approved for the treatment of type 2 diabetes in 2005. Demand for these drugs has increased rapidly in recent years, as indications have expanded, but they remain expensive. Objective: To analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity. Evidence Review: The annual US Food and Drug Administration's (FDA) Approved Drug Products With Therapeutic Equivalence Evaluations was used to identify GLP-1 receptor agonists approved from 2005 to 2021 and to record patents and nonpatent statutory exclusivities listed for each product. Google Patents was used to extract additional data on patents, including whether each was obtained on the delivery device or another aspect of the product. The primary outcome was the duration of expected protection from generic competition, defined as the time elapsed from FDA approval until expiration of the last-to-expire patent or regulatory exclusivity. Findings: On the 10 GLP-1 receptor agonists included in the cohort, drug manufacturers listed with the FDA a median of 19.5 patents (IQR, 9.0-25.8) per product, including a median of 17 patents (IQR, 8.3-22.8) filed before FDA approval and 1.5 (IQR, 0-2.8) filed after FDA approval. Fifty-four percent of all patents listed on GLP-1 receptor agonists were on the delivery devices rather than active ingredients. Manufacturers augmented patent protection with a median of 2 regulatory exclusivities (IQR, 0-3) obtained at approval and 1 (IQR, 0.3-4.3) added after approval. The median total duration of expected protection after FDA approval, when accounting for both preapproval and postapproval patents and regulatory exclusivities, was 18.3 years (IQR, 16.0-19.4). No generic firm has successfully challenged patents on GLP-1 receptor agonists to gain FDA approval. Conclusions and Relevance: Patent and regulatory reform is needed to ensure timely generic entry of GLP-1 receptor agonists to the market.

Five-Year Sales for Newly Marketed Prescription Drugs With and Without Initial Orphan Drug Act Designation.

This study evaluates sales revenue earned in the first 5 years for newly marketed brand-name drugs with and without an initial orphan drug designation.

Patent Challenges And Litigation On Inhalers For Asthma And COPD.

Between 1986 and 2020 the Food and Drug Administration (FDA) approved fifty-three brand-name inhalers for asthma and chronic obstructive pulmonary disease (COPD), but by the end of 2022 only three of those inhalers faced independent generic competition. Manufacturers of brand-name inhalers have created long periods of market exclusivity by obtaining multiple patents, many on the delivery devices rather than the active ingredients, and by introducing new devices that contain old active ingredients. Limited generic competition for inhalers has raised questions about whether the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, for challenging patents is adequately facilitating the entry of complex generic drug-device combinations. For the fifty-three brand-name inhalers approved during the period 1986-2020, generic manufacturers filed challenges authorized by the Hatch-Waxman Act, which are known as paragraph IV certifications, on only seven products (13 percent). The median time from FDA approval to first paragraph IV certification was fourteen years. Paragraph IV certifications resulted in approved generics for only two products, each of which experienced fifteen years of market exclusivity before generic approval. Reform of the generic drug approval system is critical to ensuring the timely availability of competitive markets for generic drug-device combinations such as inhalers.

Broad Patent Claims Come Before the Supreme Court in Amgen v Sanofi.

This Viewpoint discusses a current Supreme Court lawsuit, Amgen v Sanofi, involving Amgen's broad patents on PCSK9 that could effectively prevent other manufacturers from producing similar or even clinically superior antibodies, with important negative consequences for patients.

Patenting Strategies on Inhaler Delivery Devices.

BACKGROUND: Patients with asthma and COPD rely on inhalers to control symptoms. Yet, these products remain expensive, in part because brand-name manufacturers have obtained numerous patents on inhalers, including on their delivery devices. Recent antitrust litigation has raised questions about the boundaries of listing device patents with the US Food and Drug Administration (FDA), particularly when patents do not claim any active ingredients. RESEARCH QUESTION: How have manufacturers relied on device patents to preserve market exclusivity on brand-name inhalers? STUDY DESIGN AND METHODS: We identified patents on brand-name inhalers approved for asthma and COPD between 1986 and 2020 using the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). We extracted information about patents from LexisNexis TotalPatent One and Google Patents and searched device patents for mention of active ingredients or other prespecified features linking the patent to the relevant drug. For each inhaler, we determined the duration of protection added by device patents. RESULTS: The FDA approved 53 brand-name inhalers for asthma and COPD from 1986 through 2020, 39 of which had at least one device patent. One hundred thirty-seven distinct device patents were in the final cohort, representing 49% of all patents listed on inhalers. Seventy-seven percent of device patents made no mention of active ingredients or their molecular structures, and 72% made no mention of any relevant prespecified feature connecting the device patent to the drug product. For the 39 brand-name inhalers with one or more device patents listed in the Orange Book, device patents extended the duration of market protection by a median of 5.5 years (interquartile range, 0.0-10.5 years) beyond the last-to-expire nondevice patent. INTERPRETATION: Patent and regulatory reform is needed to promote generic competition and to ensure that patients with asthma and COPD have access to affordable medications.

Recent Patent Reform Bills and Their Implications for Prescription Drugs.

This Viewpoint discusses 3 bills introduced recently in Congress that focus on patent eligibility, fraud, and quality and that have major implications for clinical medicine and pharmaceutical development.

Manufacturer Revenue on Inhalers After Expiration of Primary Patents, 2000-2021.

This study quantifies the revenue earned on all brand-name inhalers approved by the US Food and Drug Administration from 2000 to 2021 and compared earnings before and after expiration of primary patents on these products.