Use of Public Research and Manufacturing Enterprises to Lower Prescription Drug Prices and Increase Innovation

This article proposes building on the success of publicly funded drug research and development and expanding the model to include the full cycle development, testing, manufacture and distribution of innovative and affordable new drugs

Overqualified and Underrepresented: Gender Inequality in Pharmaceutical Patent Law

Pharmaceutical patents represent some of the most valuable intellectual property assets in the world: they can be worth billions of dollars if courts uphold their validity and find them infringed. But, if invalidated, generic drug manufacturers can get to market earlier, generating billions of dollars of revenue for themselves and creating enormous savings for consumers. Accordingly, drug patents are the product of careful, high-cost prosecution and are associated with high-stakes, bet-the-company litigation. But women lawyers are noticeably absent from pharmaceutical patent practice. This article reports an original empirical study finding that women comprise only one-third of the top pharmaceutical patent litigators and only one-quarter of lawyers who prosecute litigated pharmaceutical patents — numbers far below the share of women in the legal profession overall. The usual explanation for any lack of representation in patent practice is the “pipeline” problem — that is, an insufficient number of women in the technical fields underlying patent law. But our study finds little support for any pipeline problem. Indeed, recent studies indicate that more women law students have scientific undergraduate and graduate degrees than their male counterparts. Interestingly, the gender gap among pharmaceutical patent lawyers does not carry over to public sector work. The U.S. Patent and Trademark Office is the one place where our study finds anything close to parity: 42.3% of pharmaceutical patent examiners are women and 57.7% are men. This finding adds to a nascent literature documenting vast disparities in gender representation in the private versus public sectors, both in patent law and in law practice more generally. It also suggests that the lack of women doing patent law in private practice in the pharmaceutical field probably is not due to any pipeline problem; instead, it likely stems from structural inequalities that permeate the highest levels of corporate law firms. Those firms, as well as their pharmaceutical company clients, all say that diversity is important. But, as our study shows, there is a disconnect between rhetoric and reality. Fully solving structural inequality in law practice is a formidable task, but this article sketches a few ways in which firms and their clients could help create a patent bar that is more diverse and inclusive

Monoclonal antibody humanness score and its applications

BACKGROUND: Monoclonal antibody therapeutics are rapidly gaining in popularity for the treatment of a myriad of diseases, ranging from cancer to autoimmune diseases and neurological diseases. Multiple forms of antibody therapeutics are in use today that differ in the amount of human sequence present in both the constant and variable regions, where antibodies that are more human-like usually have reduced immunogenicity in clinical trials. RESULTS: Here we present a method to quantify the humanness of the variable region of monoclonal antibodies and show that this method is able to clearly distinguish human and non-human antibodies with excellent specificity. After creating and analyzing a database of human antibody sequences, we conducted an in-depth analysis of the humanness of therapeutic antibodies, and found that increased humanness score is correlated with decreased immunogenicity of antibodies. We further discovered a surprisingly similarity in the immunogenicity of fully human antibodies and humanized antibodies that are more human-like based on their humanness score. CONCLUSIONS: Our results reveal that in most cases humanizing an antibody and confirming the humanness of the final form may be sufficient to eliminate immunogenicity issues to the same extent as using fully human antibodies. We created a public website to calculate the humanness score of any input antibody sequence based on our human antibody database. This tool will be of great value during the preclinical drug development process for new monoclonal antibody therapeutics

Product hopping in the drug industry — lessons from Albuterol

Product Hopping in the Drug Industry Product hops to albuterol inhalers containing hydrofluoroalkane rather than chlorofluorocarbons cost payers and patients billions of dollars. Without patent and regulatory reform, this pattern is likely to be repeated

Accelerating biosimilar market access: the case for allowing earlier standing

Biosimilars, which are affordable alternatives to biologic medicines, face delays in market entry due to the current patent litigation framework under the Biologic Price Competition and Innovation Act. Currently, biosimilar manufacturers can only initiate patent litigation to attempt to clear weak and invalid patents after submitting their Biologic License Application to the Food and Drug Administration (FDA), which happens after completing extensive, and costly clinical trials. By contrast, generic drug manufacturers can start litigation earlier due to shorter development times and less stringent clinical requirements, allowing them to launch immediately after the primary patent expires. We propose allowing biosimilars to begin patent litigation at the start of phase 3 clinical trials, the final stage of biosimilar development, where the product and manufacturing process and product profile are largely finalized. This change would enable biosimilar firms to resolve patent issues well before the brand biologic\u27s primary patent expiration date, potentially reducing market entry delays by about 1.8 years. This article examines the issues surrounding initiation of biosimilar litigation and suggests litigation reforms to expedite biosimilar market availability

Manufacturer revenue on inhalers after expiration of primary patents, 2000-2021

Inhalers remain the cornerstone therapy for patients with asthma and chronic obstructive pulmonary disease (COPD). Over the past several decades, brand-name manufacturers have continued to sell most inhalers at high prices without the threat of direct generic competition. They have arranged for long periods of market exclusivity by obtaining patents not just on the active ingredients (primary patents) but also on peripheral aspects of these products, such as the propellants and delivery devices (secondary patents), and by shifting active ingredients to different devices (device hops), thereby adding new secondary patents

Differential legal protections for biologics vs. small-molecule drugs in the US

Importance: Biologics approved by the US Food and Drug Administration (FDA) receive 12 years of guaranteed protection from biosimilar competition compared to 5 years of protection from generic competition for new small-molecule drugs. Under the 2022 Inflation Reduction Act, biologics are exempt from selection for Medicare price negotiation for 11 years compared to 7 years for small-molecule drugs. Congress has chosen to codify these differing legal protections on the premise that biologics require more time and resources to develop and have weaker patent protection, necessitating additional protections for manufacturers to recoup their development costs and generate adequate returns on investment. Objective: To review empirical evidence from the US experience with biologics to determine whether they require longer market exclusivity or protection from price negotiation compared to small-molecule drugs. Evidence Review: Recent data on development times, clinical trial success rates, research and development costs, patent protection, market exclusivity periods, revenues, and treatment costs of biologics vs. small-molecule drugs were analyzed. Findings: The FDA approved 599 new therapeutic agents from 2009-2023, of which 27% (159) were biologics and 73% (440) were small-molecule drugs. Median development times were 12.6 years (interquartile range [IQR]: 10.6-15.3 years) for biologics versus 12.7 years (IQR: 10.2-15.5 years) for small-molecule drugs (P=0.76). Biologics had higher clinical trial success rates at every phase of development. Median development costs were estimated to be $3.0 billion (IQR:$1.3 billion-$5.5 billion) for biologics and$2.1 billion (IQR: $1.3 billion-$3.7 billion) for small-molecule drugs (P=0.39). Biologics were protected by a median of 14 patents (IQR: 5-24 patents) compared to 3 patents (IQR: 2-5 patents) for small-molecule drugs (P<0.001). The median time to biosimilar competition was 20.3 years (IQR: 16.9-21.7 years) compared to 12.6 years (IQR: 12.5-13.5 years) for small-molecule drugs. Biologics achieved higher median peak revenues ($1.1 billion in year 13; IQR:$0.5 billion-$2.9 billion) than small-molecule drugs ($0.5 billion in year 8; IQR: $0.1 billion-$1.2 billion) (P=0.01) and had higher median revenues in each year following FDA approval. The median annual cost of treatment was $92,000 (IQR:$31,000-$357,000) for biologics and$33,000 (IQR: $4,000-$177,000) for small-molecule drugs (P=0.005). Conclusions and Relevance: There is little currently available evidence to support biologics having extended market exclusivity or protection from negotiation. As a result of differential treatment, US law appears to over-reward the development of biologics relative to small-molecule drugs

Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects

INTRODUCTION: Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI). METHODS: We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging. In addition, 170 age-matched replacements were tested for the first time at study wave 2. Group differences were used to calculate practice effects after controlling for attrition effects. MCI diagnoses were generated from practice-adjusted scores. RESULTS: There were significant practice effects on most cognitive domains. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%. Importantly, practice effects were present although there were declines in uncorrected scores. DISCUSSION: Accounting for practice effects is critical to early detection of MCI. Declines, when lower than expected, can still indicate practice effects. Replacement participants are needed for accurately assessing disease progression.Published versio