Affinity Purification of Biologics with Mimetope Peptides

Monoclonal antibodies and other biologicsincluding next generation antibody therapeuticsare the fastest growing segment of the pharmaceutical industryprojected to reach almostB in annual sales byBiologic therapies have had significant impact on the treatment of many cancersautoimmune diseasesand neurological diseases with newer therapies targeting a wider range of serious health conditionsMost of these drugs are produced in mammalian cell culture systemsrequiring extensive downstream purification through multi step processesFor traditional monoclonal antibodiesmAbsthe most expensive of those steps is affinity capture by Protein AProtein A is a bacterial protein that binds to the Fe of most mAb or Fc fusion biologic drugsHoweverit is expensivepoorly reusablerequires harsh acid elution to recover the captured moleculesand does not work for biologics lacking an Fc domainWe propose a novel form of weak affinity chromatography based on the use of mimetope peptides specific for a given biologic drugIn previous workwe have developed these mimetope peptides as capture reagents for immunoassays and have demonstrated that we can robustly generate mimetope peptides specific to almost any mAb through screening phage displayed peptide librariesMimetope Peptide Weak Affinity ChromatographyMPWAChas several advantages over Protein AProducing peptide coupled beads for chromatography is simple as peptides are generally synthesized on bead during solid phase synthesisIndustrial scale peptide synthesis is already routine in the industry and benefits from significant economies of scale that will make it considerably cheaper than production of Protein A mediaImmobilized peptides are robust and reusableand compatible with mixed mode chromatography approachesImportantlythe affinity of a mimetope peptide for its target drug product can be tuned for true isocratic chromatography that avoids damaging elution conditionsThe annual market for Protein A chromatography is rapidly growing and will exceed half a billion dollars in the next few yearsWith the proposed MPWAC technologya broader array of biologic therapies will be manufacturable at reasonable costs to benefit patients in the US and worldwide Biologic therapies are powerful means to treat serious diseasesbut their production requiresexpensive and damaging purification methodsThis project will develop a new method to purifythose types of therapeutics that is much cheaper and does not require harsh chemicals