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

Authors

  • Sang Hoon Paik,

    Corresponding author
    1. GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea
    2. College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 136-701, Korea
    • GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea
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  • Yong Jae Kim,

    1. GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea
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  • Sang Kyul Han,

    1. GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea
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  • Jean Man Kim,

    1. GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea
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  • Jae Wook Huh,

    1. GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin 446-799, Korea
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  • Young In Park

    Corresponding author
    1. College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 136-701, Korea
    2. College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong, 339-700, Korea
    • College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 136-701, Korea
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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

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