Out-licensing

Generation of an Anti-polyethylene Glycol Monoclonal Antibody (E11): Use in PEG-modified Therapeutic Protein Analysis

Introduction/Background

Covalent attachment of poly(ethylene glycol) (PEG) molecules to drugs, proteins, nanoparticles and liposomes is a proven technology for improving their bioavailability, safety and activity, and has been approved by the Food and Drug Administration (FDA) for human usage.

Aims/Hypothesis

Therefore, qualitative and quantitative analysis of PEG-derivatized molecules is important for both drug development and clinical applications.

Research

We now describe a new IgG1 monoclonal antibody (E11) that bound the repeating subunits of the PEG backbone and could accelerate the clearance of PEG-modified molecules in vivo and detect free PEG and PEG-modified molecules by ELISA, immunoblotting, and flow cytometry. Detection sensitivity increased with the length and the number of PEG chains on pegylated molecules. Importantly, by combining another previous developed PEG antibody, AGP3, a sandwich ELISA was developed to detect PEG-modified molecules, the ELISA could quantify, in the presence of 10% foetal bovine serum, free methoxy-PEG20,000, PEG5,000-proteins, PEG2,000-quantum dots, and PEG2,000-liposomes at concentrations as low as ng/mL levels. E11 antibody should be generally applicable to the qualitative and quantitative analysis of all PEG derivatized molecules in future.

Up to now, simple methods to measure intact PEG-derivatized molecules are not available. Besides our first generation of anti-PEG antibody, AGP3/ IgM, there is no other PEG antibody that has been reported. Our second generation PEG antibody, E11, is an IgG antibody with high efficiency on clearing PEG modified molecules in vivo and detect free PEG and PEG-modified molecules by ELISA, immunoblotting, and flow cytometry. A sandwich ELISA in which E11/AGP3 was employed as the capture/detection antibodies was developed to detect any PEG-modified molecules.

Conclusion

We have generated an anti-polyethylene glycol monoclonal antibody for use in PEG-modified therapeutic protein analysis, PEG-modified nanoparticles and bio-molecule qualification and quantification.

Relevance/Opportunity

We are currently seeking licensing or codevelopment partnerships. Please enquire quoting reference no. 12T-941125.

Preclinical