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Therapeutic antibody fragments with prolonged in vivo half-lives

Nature Biotechnology volume 17, pages 780–783 (1999)Cite this article

Abstract

Antibody fragments can be isolated rapidly using techniques such as phage display and can be expressed to high levels in microbial systems. However, to date such antibody fragments have been of limited use for many therapeutic applications because they are rapidly cleared from the body. We present a strategy for the site-specific chemical modification of antibody fragments with polyethylene glycol, which results in the production of antibody fragments with long in vivo half-lives and full retention of antigen-binding properties. This technology should allow more rapid and economical production of therapeutic antibodies for chronic disease therapy.

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Figure 1: Pharmacokinetics of 125I-labeled Fab' and randomly modified Fab'–PEG conjugates in rats.
Figure 2
Figure 3: Comparison of randomly modified Fab'–PEG at one thiol group per Fab' and site-specific attachment by SDS–PAGE.
Figure 4: Pharmacokinetics of 125I-labeled IgG, Fab', and site-specifically attached Fab'–PEG conjugates in rats.
Figure 5: Pharmacokinetics of 125I-labeled IgG and site-specifically attached Fab'–PEG conjugates in cynomolgus monkeys.

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Author notes

  1. David J. King

    Present address: Coulter Pharmaceutical, 600 Gateway Blvd., South San Francisco, CA, 94080

Authors and Affiliations

  1. Celltech Therapeutics, 216 Bath Rd., Slough, SL1 4EN, Berks, UK

    Andrew P. Chapman, Pari Antoniw, Mariangela Spitali, Shauna West, Sue Stephens & David J. King

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  1. Andrew P. Chapman
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  2. Pari Antoniw
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Correspondence to Andrew P. Chapman.

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Chapman, A., Antoniw, P., Spitali, M. et al. Therapeutic antibody fragments with prolonged in vivo half-lives. Nat Biotechnol 17, 780–783 (1999). https://doi.org/10.1038/11717

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