A purification platform for antibodies and derived fragments using a de novo designed affinity adsorbent

Antibody technologies are the most representative success-case in the biopharmaceutical industry. Widely available purification technologies fail in providing a dedicated universal purification platform that can accommodate antibodies structural diversity, namely antibodies from non-human sources, as chicken IgY, and antigen-binding fragments. In this work, we took inspiration from natural and engineered antibody-binding ligands, to rationally design affinity adsorbents able to capture full-length antibodies and fragments. The one-pot Petasis and Ugi combinatorial reactions were sequentially employed to rapidly generate a library of putative solid-phase adsorbents. The best performing adsorbent yielded a single-step recovery, under mild conditions, of human and chicken whole antibodies, antigen-binding fragments and engineered single-domain antibodies from different complex feedstocks. Due to its simple preparation, the lead antibody adsorbent finds broad applicability as a universal purification platform to increase the availability of antibody technologies in research and development.