ENGINEERED ANTIBODY FC VARIANTS

摘要

In some aspects, mutant or variant Fc domains are provided that can exhibit increased affinity or selectivity for FcγRIIB. The variant Fc domain may be a mutant IgG1 Fc domain. In some embodiments, a mutant or variant Fc domain may be present in a therapeutic antibody such as, e.g., an agonistic antibody. Additional methods for using and identifying mutant Fc domains are also provided.

主权项

1. A polypeptide comprising an aglycosylated mutant or variant human IgG Fc domain capable of binding human FcγRIIb; and
at least one of:
(i) substitution mutations of arginine at position 234 (L234R), glutamic acid at position 235 (L235E), glutamic acid at position 236 (G236E), arginine at position 238 (P238R), and glutamine at position 351 (L351Q);(ii) substitution mutations of glutamine at position 246 (K246Q), alanine at position 260 (T260A); glutamine at position (L351Q), arginine at position 386 (Q386R); phenylalanine at position 396 (P396F), and methionine at position 397 (V397M);(iii) substitution mutations of alanine at amino acid 264 (V264A), serine at amino acid 328 (L328S), cysteine at amino acid 329 (P329C), tryptophan at amino acid 330 (A330W), asparagine at amino acid 332 (I332N), glycine at position 333 (E333G), and valine at amino acid position 336 (I336V); or(iv) substitution mutations at the positions of an engineered Fc domain of Table 1.