Anogen-Yes Biotech Laboratories Ltd.




A novel monoclonal antibody against the N-terminus of Aβ 1-42 reduces plaques and improves cognition in a mouse model of Alzheimer’s disease
Senile plaques consisting of Amyloid-beta (Aβ) peptides, in particular Aβ1–42, are the hallmark of Alzheimer’s disease (AD) and have been the primary therapeutic targets. Passive immunotherapy with monoclonal antibodies (mAbs) has shown initial success in mouse models of AD. However, the existing Aβ-directed mAbs mostly were tested on animal models or patients with advanced disease. The effects and mechanisms of mAbs on animals or human trial participants in the prodromal phase of AD are not fully clarified. In the current study, a novel mAb (3F5) directed against the 1–11 amino acids of Aβ1–42 was generated by immunizing mice with an emulsion of full length human Aβ1–42. The mAb (3F5) showed the ability to disrupt Aβ1–42 aggregation and prevent Aβ-mediated neurotoxicity in vitro. In a mouse model of AD, administration with 3F5 for 3 months in 6 months-old mice demonstrated that the mAb specifically bound with Aβ1–42 to promote the depolymerization of Aβ fibrils, facilitated endocytosis of Aβ1–42 by microglia, and attenuated the death and apoptosis of neuronal cells, accompanied by neurite outgrowth. APP/PS1 double-transgenic mice treated with 3F5 mAb showed reduced memory loss, cognitive decline, and decreased levels of amyloid deposits in the brain. Aβ1–42 levels in cerebral tissues were also significantly reduced, whereas serum Aβ1–42 was markedly increased. Interestingly, the concentration of 3F5 in peripheral circulation is much higher than that in the brain. These results indicate that 3F5 is able to cross the blood-brain barrier (BBB) to bind Aβ and initiates the phagocytosis of antibody/Aβ complexes by microglia in the amyloid depositing mice. 3F5 also promotes Aβ efflux from the brain. As a consequence, the antibody reduces plaques in the AD mouse brain, in association with reduction in the pathology of AD.

Research & Development Project Updates: ALZHEILIN – Aβ42 mAb for Early Detection & Targeting Treatment of Alzheimer’s Disease


Anogen News

Anogen’s IL-17A monoclonal antibodies, clone 10F9 and clone 2D11, have been shown to neutralize IL-17A induced IL-6 expression in human dermal fibroblasts. The IC50 was < 0.25mg/ml. (IL-17A is an inflammatory cytokine produced by Th17 cells, a newly characterised group of CD4 T help cells that plays a role in autoimmune diseases and chronic inflammatory diseases. IL-23 is the main inducer of Th17 cell development. Other cytokines such as TGF-beta, IL-6 and IL-21 were also found to contribute to the procedure. IL-17A belongs to the IL-17 family which includes IL-17A, IL-17B, IL-17C, IL-17D and IL-17E. IL-17, like interferon-gamma, is a potent mediator of delayed-type reaction. IL-17 induces the secretion of many other pro-inflammatory cytokines and chemokines such as IL-6, IL-8, GM-CSF, G-CSF, TGF-beta, TNF-alpha, GRO-alpha, and MCP-1. IL-17 stimulates the expression of NF-kappaB, mitogen activated protein kinase, and prostaglandings by many cell types, and enhances the production of nitric oxide). Anogen is providing pre-titrated reagent sets for making ELISA kit.   Anogen hybridoma cell bank ensures excellent product quality and low between lot variations. Anogen has developed 20 hybridomas to human CD47.  High reactivity to human CD47 has been observed in the monoclonal antibodies secreted by these hybridomas.  These antibodies are being evaluated for the function on blockage of CD47-SIRPalpha binding and restoration of phagocytosis to cancer cells.