FIELD: biotechnology; medicine.
SUBSTANCE: immunoglobulin heavy chain single variable domain (ISVD) is a VHH domain, a humanized VHH domain, or an overblown VH domain that is directed against TNF, in which (i) position 112 is either K or Q; or (ii) position 110 is either K or Q and position 11 is V; or (iii) position 89 is T; or (iv) position 89 is L and position 110 is either K or Q; or (v) position 11 is V and position 89 is L; or any suitable combination of (i)–(v). The polypeptide has reduced binding to pre-existing antibodies present in samples from subjects suffering from SLE, compared to a polypeptide containing VHH, humanized VHH or overblown VH without amino acid residues (i) 112 K or Q; (ii) 110 K or Q and 11 V; (iii) 89T; (iv) 89L and 110 K or Q; or (v) 11B and 89L; where the positions of amino acid residues are designated by Kabat numbering.
EFFECT: invention can be used in a pharmaceutical composition directed against TNF.
24 cl, 31 dwg, 37 tbl, 15 ex
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