Bioseparations and Downstream Processing

Mixture of three amino acids as stabilizers replacing albumin in lyophilization of new third generation recombinant factor VIII GreenGene F

  1. Sang Hoon Paik1,2,*,
  2. Yong Jae Kim1,
  3. Sang Kyul Han1,
  4. Jean Man Kim1,
  5. Jae Wook Huh1,
  6. Young In Park2,3,*

Article first published online: 23 OCT 2012

DOI: 10.1002/btpr.1640

Issue

Biotechnology Progress

Biotechnology Progress

Volume 28, Issue 6, pages 1517–1525, November/December 2012

Additional Information

How to Cite

Paik, S. H., Kim, Y. J., Han, S. K., Kim, J. M., Huh, J. W. and Park, Y. I. (2012), Mixture of three amino acids as stabilizers replacing albumin in lyophilization of new third generation recombinant factor VIII GreenGene F. Biotechnol Progress, 28: 1517–1525. doi: 10.1002/btpr.1640

Author Information

  1. 1

    GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea

  2. 2

    College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 136-701, Korea

  3. 3

    College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong, 339-700, Korea

*GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea

Publication History

  1. Issue published online: 4 DEC 2012
  2. Article first published online: 23 OCT 2012
  3. Accepted manuscript online: 26 SEP 2012 05:52AM EST
  4. Manuscript Revised: 31 AUG 2012
  5. Manuscript Received: 5 MAY 2012

Funded by

  • Green Cross Corporation

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (748K)

Keywords:

  • albumin;
  • factor VIII;
  • lyophilization;
  • formulation;
  • protein stabilization

Abstract

A formulation with stabilizers replacing albumin was developed for lyophilization of recombinant factor VIII (FVIII), GreenGene F (WHO INN: beroctocog alfa), to achieve stability and eliminate safety issues of blood-derived albumin. L-Arginine (hydrophilic amino acid, positively charged side chain), L-glutamic acid (hydrophilic amino acid, negatively charged side chain), and L-isoleucine (hydrophobic amino acid, nonpolar) were selected as stabilizers, and the mixture of the three amino acids were optimized. The mixture had results comparative with albumin and other commonly used stabilizers showing good preservation of recombinant FVIII during lyophilization, robust stability with consistently high recovery of FVIIII, very low aggregate formation, and good storage stability without alterations in protein characteristics. In vivo test results showed that the efficacy was maintained and had no signs of toxicity. The study demonstrated that the three amino acid mixture acts as a good stabilizer for lyophilization of recombinant FVIII and as a safe excipient. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012

View Full Article (HTML) Get PDF (748K)