CloneID: LY2062430 (Solanezumab, hu266)
Antigen Long Description: The parental mouse antibody 266 was generated by immunization of mice with a peptide composed of residues 13-28 of human Aβ peptide. The original humanized version of the antibody was generated by grafting CDRs of the mouse antibody onto human framework regions.
Buffer Composition: PBS only.
Uniprot Accession No.: P05067
Specificity Statement: This antibody recognizes amino acids 13-28 of amyloid beta and only recognized soluble form of the amyloid beta peptide. It functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis.
Application Notes (Clone): The human IgG1 version of this antibody binds amyloid beta peptide Aβ1-42 with a binding affinity of Kd= 4pM in an in vitro BIAcore assay. The binding characterization of this antibody towards Aβ1-42-BSA conjugate was done using ELISA (US8591894). A study in patients with Alzheimer's disease (AD) suggested that a single dose of solanezumab was generally well tolerated, except that mild self-limited symptoms consistent with infusion reactions occurred in few patients when higher doses are given. A dose-dependent change in plasma and CSF Abeta was also observed (PMID: 20375655). The original mouse antibody 266 slowed Aβ accumulation in the brain but failed to deplete Aβ plaques in animal studies (PMID: 11438712). This humanized antibody is likely to have impeded the efflux of soluble Aβ from the brain in patients owing to the formation of Aβ–antibody complexes in the brain interstitial fluid and cerebrospinal fluid, as suggested from animal studies (PMID: 24638135). Phase 1 and 2 studies of solanezumab revealed evidence of target engagement by dose-dependent increases in plasma and CSF total Aβ (PMID: 20375655; 22672770). In the phase 2 study of mild to moderate AD, 12 weeks of solanezumab treatment yielded a dose-dependent increase in CSF-free Aβ42, suggesting a shift in equilibria sufficient to mobilize Aβ42 from plaques (PMID: 22672770). In the first phase III studies, solanezumab did not demonstrate significant benefit for the primary outcomes in either study but showed a favorable safety profile (PMID: 26238576).
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