United Kingdom (UK)
Recombinant monoclonal antibody to PCSK9. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the human B cell clone 508.20.33b (Fab33).
UniProt Accession Number of Target Protein: Q8NBP7
Alternative Name(s) of Target: NARC1; NARC-1; PC9; Proprotein convertase subtilisin/kexin type; Neural apoptosis-regulated convertase 1; Proprotein convertase 9; Subtilisin/kexin-like protease PC9
Immunogen: The original antibody was isolated from a phage display library by panning against biotinylated human PCSK9.
Specificity: This antibody binds human PCSK9. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease enzyme encoded by the PCSK9 gene in humans and it plays a role in regulation of circulating cholesterol. It is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease.
Application Notes: The binding affinity of this antibody towards PCSK9 protein from human, murine, rhesus, and cynomolgus monkey was done using surface plasmon resonance. This antibody was found to inhibit binding of PCSK9 to LDLR in a competition binding ELISA. This antibody plays a role in effective prevention of LDLR downregulation in HepG2 cells in vitro. When administered in vivo, this antibody prevented LDLR downregulation in mouse liver. This antibody showed a reduction in total serum cholesterol levels in mice when a single dose of 10 mg/kg was administered. It was also found that a combination of this antibody and statin results in a greater reduction in total cholesterol level compared to anti-PCSK9 antibody alone or statin alone treatments (US9266961). A randomized, double-blind, placebo-controlled, single and multiple dose study was conducted to evaluate, primarily, the safety and tolerability of single and multiple (four weekly) doses of reformatted IgG1 version of this antibody when administered by subcutaneous (SC) injection to healthy volunteers with elevated serum low-density lipoprotein cholesterol (LDL-c) concentration. It was found that there were no serious or severe adverse events, no discontinuations for adverse events, and no dose-limiting toxicities (US9266961).
Antibody first published in:
Zhang et al. Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists. Nat Struct Mol Biol. 2017 Oct;24(10):848-856. PMID:28825733
Note on publication:
Describes the generation of antagonistic antibodies that encroach on the EGF(A)-binding site and inhibit LDLR binding.