United Kingdom (UK)
Recombinant monoclonal antibody to PCSK9. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the phage display clone PA4.
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; PA4Fab
Immunogen: The original antibody was isolated from a natural human Fab phage display library by panning against recombinant human PCSK9. Later one the Fab antibody was converted to IgG1 format.
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 human IgG1 format of this antibody was reported to bind human PCSK9 with a binding affinity Kd= 1.05 nM. The binding characterization of this antibody to human PCSK9 was done using ELISA and western blot. In an in vitro competition binding ELISA, IgG1-PA4 blocked PCSK9 from binding to LDLR, with an IC50 of approximately 7 nM. In vitro, it also attenuated PCSK9-mediated degradation of LDLR on the HepG2 cell surface in a dose dependent manner. In C57BL/6 mice, administration of IgG1-PA4 at 30 mg/kg increased hepatic LDLR protein levels by as much as 3 fold when compared with control. This antibody has potential for being used as a therapeutic for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs (PMID: 26056005).
Antibody first published in:
Cao et al. Selection and characterization of human PCSK9 antibody from phage displayed antibody library. Biochem Biophys Res Commun. 2015 Aug 7;463(4):712-8. PMID:26056005
Note on publication:
This paper describes the isolation of a Fab antibody that binds human PCSK9. The IgG1 format was generated and characterized.