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Tafolecimab, a novel fully human monoclonal antibody targeting PCSK9, has been assessed in Chinese healthy volunteers and patients with hypercholesterolemia. This analysis is to develop and qualify a population pharmacokinetics (PopPKs)/LDL‐C model to characterize tafolecimab PK and LDL‐C profiles, evaluate the impact of potential covariates on tafolecimab, estimate individual predicted exposure, and LDL‐C decreasing, furthermore, explore exposure–response relationship to support clinical use. Data from six clinical trials in China were used to develop the PopPK/LDL‐C model. A Michaelis–Menten approximation of the target‐mediated drug disposition (TMDD) model was used to describe PK data and indirect response (IDR) model was developed to estimate the LDL‐C profile. A stochastic approximation expectation maximization algorithm was applied to estimate PopPK/LDL‐C parameters. The PK/LDL‐C time course data for tafolecimab were well described by TMDD/IDR model. Baseline covariates resulting in statistically significant changes in PK/LDL‐C parameters included: body weight and sex on absorption rate constant; body weight, sex, and unbound PCSK9 on central volume; body weight and sex on clearance; baseline LDL‐C on first‐order rate constants for the removal of an effect); and disease and sex on maximum effect. However, the magnitudes of changes associated with these covariates do not necessitate dose adjustment. Exposure–efficacy relationship indicated that the nadir of LDL‐C reduction achieved with the steady‐state trough plasma concentration (Ctrough) of tafolecimab at 5 μg/mL, and no further LDL‐C decreasing with the increasing Ctrough. There was no exposure dependency observed in exposure‐safety exploration. The PopPK/LDL‐C model was successfully developed, validated, and predicted tafolecimab/LDL‐C concentrations and individual exposures. [ABSTRACT FROM AUTHOR]

During the past decade, metagenomics became a method of choice for the discovery of novel viruses. However, host assignment for uncultured viruses remains challenging, especially for archaeal viruses, which are grossly undersampled compared to viruses of bacteria and eukaryotes. Here, we assessed the utility of CRISPR spacer targeting, tRNA gene matching and homology searches for viral signature proteins, such as major capsid proteins, for the assignment of archaeal hosts and validated these approaches on metaviromes from Yangshan Harbor (YSH). We report 35 new genomes of viruses which could be confidently assigned to hosts representing diverse lineages of marine archaea. We show that the archaeal YSH virome is highly diverse, with some viruses enriching the previously described virus groups, such as magroviruses of Marine Group II Archaea (Poseidoniales), and others representing novel groups of marine archaeal viruses. Metagenomic recruitment of Tara Oceans datasets on the YSH viral genomes demonstrated the presence of YSH Poseidoniales and Nitrososphaeria viruses in the global oceans, but also revealed the endemic YSH‐specific viral lineages. Furthermore, our results highlight the relationship between the soil and marine thaumarchaeal viruses. We propose three new families within the class Caudoviricetes for the classification of the five complete viral genomes predicted to replicate in marine Poseidoniales and Nitrososphaeria, two ecologically important and widespread archaeal groups. This study illustrates the utility of viral metagenomics in exploring the archaeal virome and provides new insights into the diversity, distribution and evolution of marine archaeal viruses. [ABSTRACT FROM AUTHOR]