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Publication Abstract from PubMed

Monoclonal antibodies are a favorite drug platform of the biopharmaceutical industry. Currently, over 20 Mabs have been approved and several hundred others are in clinical trials. The anti-LINGO-1 Mab Li33 was selected from a large panel of antibodies by Fab phage display technology based on its extraordinary biological activity in promoting oligodendrocyte differentiation and myelination in vitro and in animal models of remyelination. However the Li33 Fab had poor solubility when converted into a full antibody in an IgG1 framework. A detailed analysis of the biochemical and structural features of the antibody revealed several possible reasons for its propensity to aggregate. Here we successfully applied three molecular approaches (isotype switching, targeted mutagenesis of CDR residues, and glycosylation site insertion mutagenesis) to address the solubility problem. Through these efforts we were able to improve the solubility of the Li33 Mab from 0.3 mg/mL to >50 mg/mL and reduce aggregation to an acceptable level. These strategies can be readily applied to other proteins with solubility issues.

Improving the solubility of anti-LINGO-1 monoclonal antibody Li33 by isotype switching and targeted mutagenesis.,Pepinsky RB, Silvian L, Berkowitz SA, Farrington G, Lugovskoy A, Walus L, Eldredge J, Capili A, Mi S, Graff C, Garber E Protein Sci. 2010 Mar 2. PMID:20198683^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.