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Crystallization approach for purification of intact monoclonal antibodies: A review

Author Affiliations

  • 1Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India
  • 2Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India
  • 3Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India
  • 4Department of Biotechnology, Kolhapur Institute of Technology’s College of Engineering, Kolhapur, Maharashtra, India

Res.J.chem.sci., Volume 13, Issue (1), Pages 65-78, February,18 (2023)


Over the 20th century, protein crystallization had been accepted and developed as a powerful purification tool before chromatography. It has also been applied for various biologically important macromolecules for efficacious durability and contracted dosage in the field of drug formulation. Right from the evolution, intact monoclonal antibodies (mAbs) have gained prime importance in the field of therapeutic drug applications, especially in immunotherapies. The fragments of mAbs have also been used for different applications. The purification strategies researched and established for these molecules during the last 20 years are predominantly chromatographies. But considering the process cost limitations, crystallization was found to be effective to purify the intact monoclonal antibodies from a massive number of proteins in culture broth and feasible to use as an alternative platform. This review presents the success rate of crystallization in intact monoclonal antibody purification. Further, the importance of phase behavior studies, the effects of additives on monoclonal antibody crystallization is discussed with the help of case studies. Also, the comparison of different batch versus continuous crystallization methods applied is discussed. In the end, the requirement and prospects of large-scale crystallization studies of intact monoclonal antibodies invoking the accomplishment of high throughput demand are discussed.


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