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. 2022 Jan-Dec;14(1):2123299.
doi: 10.1080/19420862.2022.2123299.

Systematic analysis of the varied designs of 819 therapeutic antibodies and Fc fusion proteins assigned international nonproprietary names

Ian Wilkinson  1 , Geoff Hale  1
Affiliations

Systematic analysis of the varied designs of 819 therapeutic antibodies and Fc fusion proteins assigned international nonproprietary names

Ian Wilkinson et al. MAbs. 2022 Jan-Dec.

Abstract

By combining and cross-checking data from the World Health Organization's lists of international nonproprietary names with three other databases, we assembled a dataset of amino acid sequences of 819 antibody-related therapeutics. This enabled the systematic tabulation of 57 different molecular formats and about 90 different constant-region variants (47 for silencing, 14 for enhancement, 8 for modifying binding to FcRn, 13 for heterodimerization, 4 for site-specific modification and 4 for stabilization), as well as the frequencies of different targets and immunoglobulin allotypes. The curated dataset provides a resource for researchers, giving insights into trends in antibody engineering and a guide to the most frequently tested designs.

Keywords: Allotype; FC receptor; FC region; immunoglobulin fusion protein; immunoglobulin sequence; international nonproprietary name; therapeutic antibody.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Caption: Monospecific antibody formats. Below each image the number of occurrences of this format within the dataset is shown.
Figure 2.
Figure 2.
Caption: Multispecific antibody formats. Below each image the number of occurrences of this format within the dataset is shown.
Figure 3.
Figure 3.
Caption: Analysis of the first reporting date for each INN and molecular format within the multispecific antibodies category. The cumulative number of INNs is shown in Orange and formats in blue.
Figure 4.
Figure 4.
Caption: Fc fusion protein formats. Below each image the number of occurrences of this format within the dataset is shown.
Figure 5.
Figure 5.
Caption: Analysis of the first reporting date for each INN and molecular format within the Fc fusion proteins category. The cumulative number of INNs is shown in Orange and formats in blue.
Figure 6.
Figure 6.
Caption: Antibody fusion protein formats. Below each image the number of occurrences of this format within the dataset is shown.
Figure 7.
Figure 7.
Caption: Analysis of the first reporting date for each INN and molecular format within the antibody fusion proteins category. The cumulative number of INNs is shown in Orange and formats in blue.
Figure 8.
Figure 8.
Caption: Miscellaneous formats. Below each image the number of occurrences of this format within the dataset is shown.
Figure 9.
Figure 9.
Caption: Analysis of cumulative INN listings over time for different categories of design formats.
Figure 10.
Figure 10.
Caption: Comparison of annual INN listings for IgGs, in blue, and all other non-IgG formats, in Orange (data available only till April 2022).
Figure 11.
Figure 11.
Caption: Trend in the number of different antibody-related formats reported in INN listings as a cumulative measure over time.
Figure 12.
Figure 12.
Caption: Cumulative use over time of different groups of variants for Fc silencing.
See this image and copyright information in PMC

References

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