CONJUGATED IMMUNOGLOBULINS WITH C-TERMINAL LYSINE Russian patent published in 2021 - IPC A61K47/68 C12N9/10 

FIELD: biotechnology.

SUBSTANCE: group of inventions relates to biotechnology, in particular to methods for producing conjugated immunoglobulins using microbial transglutaminase. Immunoglobulin is incubated with microbial transglutaminase and a therapeutic or diagnostic agent containing an acyl-donor substrate, including a glutamine residue, where transglutaminase catalyzes the conjugation of immunoglobulin K447 with the glutamine residue of the acyl-donor substrate. The immunoglobulin contains at least one amino acid residue, but less than 13 amino acid residues after lysine 447 (K447) on the heavy chain according to the EC numbering system. When the immunoglobulin contains one amino acid residue after K447, the specified one amino acid residue is not proline, aspartic acid, glutamic acid, lysine, or arginine. When the immunoglobulin contains more than one amino acid residue after K447, the first amino acid residue is not aspartic acid, glutamic acid, or proline, and the last amino acid residue is selected from the group consisting of phenylalanine, leucine, isoleucine, methionine, valine, serine, proline, threonine, alanine, tyrosine, histidine, glutamine, asparagine, aspartic acid, glutamic acid, cysteine, tryptophan, and glycine. In another embodiment, the immunoglobulin is incubated with a microbial transglutaminase and an acyl-donor substrate containing a glutamine residue and a reactive group, where the microbial transglutaminase catalyzes the conjugation of immunoglobulin K447 with the glutamine residue of the acyl-donor substrate. The therapeutic or diagnostic agent is then conjugated to the reactive group of the acyl donor substrate.

EFFECT: conjugation of C-terminal lysine using microbial transglutaminase leads to site-specific and predictable incorporation of conjugated functional agents.

77 cl, 6 ex, 10 dwg