The data we collected were analyzed to reveal useful trends in therapeutic purpose, safety, developability, PK, and patient convenience of antibody-based biotherapeutic drug products. 60 targets, and the field is still growing! Drug manufacturers are solidifying their choices regarding types of antibodies and their molecular formats. IgG1 kappa continues to be the most common molecular format among marketed antibody-based biotherapeutics. GW-1100 Most antibody-based biotherapeutics approved since 2015 are either humanized or fully human, but the data we collected do not show a direct correlation between humanness and reported incidence of anti-drug antibodies. Furthermore, there have also GW-1100 been improvements in terms of drug product stability and high concentration liquid formulations suitable for subcutaneous route of administration, which are being approved more often in recent years. These improvements, however, have not been uniformly adopted across all therapeutic areas, suggesting that multiple options for drug product development are being used to serve diverse therapeutic purposes. Insights gained from GW-1100 this analysis may help us devise better end-to-end antibody-based biotherapeutic drug discovery and development strategies. KEYWORDS:Antibody, biotherapeutics, developability, drug, formulation, pharmacology == Introduction == Antibody-based biotherapeutics represent one of the fastest-growing segments in the pharmaceutical market (Figure 1(a)) because of their ability to bind with high selectivity along with desirable pharmacological attributes, such as longer half-lives, resulting in safe and effective medicines with convenient dosing GW-1100 schedules.1,2By November 21, 2021, a total of 131 antibody-based biotherapeutics were approved under regulatory review in the United States or European Union.3Moreover, the number of antibodies in clinical development (Phases I-III) grew by over 30% in the past year.4Representation of antibody-based biotherapeutics in the portfolios of large pharmaceutical companies has also grown significantly in recent years.5While monoclonal antibodies (mAbs) have been developed to treat infectious diseases previously,69the coronavirus disease 2019 (COVID-19) pandemic has created renewed interest in using TNFSF10 antibody-based biotherapeutics as a treatment option for infectious diseases.1012In 2021, the global antibody market was valued at 217.3 billion USD and is projected to exhibit an annual growth rate of approximately 15% in the next decade.1315Considering the scale at which antibody-based biotherapeutics are now being discovered and developed, it is apparent that the industrialization of mAbs has come of age. == Figure 1. == (a) Marketed antibody-based biotherapeutics by year. By June 2022, 111 antibody-based biotherapeutic drug products have been approved by the FDA (shown in orange) and 106 have been approved by the EC (shown in green). 19 total antibody-based biotherapeutic drugs have been approved by India (3), Cuba (2), Russia (4), China (9), and Japan (1), but not by the FDA or EC (shown in gray). The total number of unique marketed antibody-based biotherapeutics as of June 2022 is 136 shown in blue with right y-axis showing growth over time. (b) Molecular formats of marketed antibody-based biotherapeutics. Gray regions represent constant regions. Green regions are variable regions. Red regions are a second variable region in the bispecific therapeutics. The purple circles are examples of where a small molecule drug could attach to an antibody and form antibody-drug conjugates (ADCs). Early overviews of marketed antibody-based biotherapeutics were limited because very few products had been granted approvals at the time.1620As more were approved, growing interest in the scientific community led to broader overviews,2123as well as reviews of specific characteristics,2426such as cell culture and immunogenicity of marketed and clinical trials stage mAbs.27,28In 2010, Dr. Janice Reichert started publishing the Antibodies to Watch series, which continues to be released yearly.2941More recent publications on marketed mAbs have looked at deeply specific characteristics,42,43such as glycosylation patterns,44,45or broad concepts like development trajectories.46,47 Given the growth in the field, this is an opportune time to examine how antibody-based biotherapeutics have evolved, since the first approval of muromonab in 1986.48Specifically, we assessed the evolution of crucial aspects of antibody-based biotherapeutics, such as 1) therapeutic purpose, 2) safety and immunogenicity, 3) developability, and 4) patient convenience, by analyzing the trends in their product characteristics (e.g., types and molecular formats, formulation, routes of administration,.