FIELD: biotechnology.
SUBSTANCE: invention relates to versions of Fc-fragments and methods for recombinant production thereof in milk of transgenic animals and can be used in medicine in treating inflammatory and autoimmune pathologies. Disclosed is a variant of the Fc-fragment of IgG1, having high affinity for the FcRn receptor and high affinity for at least one Fc receptor (FcR) compared to that of the reference IgG1 Fc-fragment, which includes: 334N, 352S, 378, 397M and 434Y mutations or 296W, 334N, 352S, 378, 397M and 434Y mutations, where numbering corresponds to numbering of EU index or equivalent in Kabat. Invention provides obtaining versions of Fc-fragments with improved activity, in particular with improved binding affinity with FcRn, due to which they enable to increase the effectiveness of therapeutic products which contain them.
EFFECT: disclosed Fc fragments enable more effective blocking of the FcRn receptor and thus faster elimination of autoantibodies, and also have better inhibition of complement-dependent cytotoxicity (CDC) than IVIG, which enables to reduce the toxicity of pathogenic autoantibodies, such as those involved in inflammatory and/or autoimmune diseases.
19 cl, 7 dwg, 6 tbl, 7 ex
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Authors
Dates
2024-05-30—Published
2018-12-14—Filed