БАРТ Джон (GB),ГОДВИН Энтони (GB),БАДЕСКУ Джордж (GB)
申请号:
RU2015101333
公开号:
RU2015101333A
申请日:
2013.06.19
申请国别(地区):
RU
年份:
2016
代理人:
摘要:
1. A method for producing an antibody conjugate in which a engineered antibody having a single disulfide bond between heavy chains is reacted with a conjugation reagent that forms a bridge between two cysteine residues derived from a disulfide bond. The method of claim 1, wherein the antibody is an IgG1 or IgG4.3 molecule. A method according to claim 1 or 2, wherein the antibody is obtained by recombinant expression or chemical synthesis. The method of claim 3, wherein the mutation of the nucleic acid sequence encoding the parent antibody is carried out, said mutation leading to the deletion or replacement of one or more cysteine residues between the heavy chains with an amino acid other than cysteine; expression of the nucleic acid in the expression system and isolation of the engineered antibody. . The method of claim 4, wherein site-specific mutagenesis is introduced to introduce replacement nucleotides into the coding sequence of the parent antibody. The method of claim 1, wherein said single disulfide bond between the heavy chains is at position 226 or 229 of the antibody according to the EC index numbering system. The method of claim 1, wherein the antibody contains cysteine at position 226 and an amino acid other than cysteine at position 229 according to the EU index numbering system or an amino acid other than cysteine at position 226 and cysteine at position 229 according to the EU index numbering system. 8. The method of claim 7, wherein the amino acid other than cysteine, in which there is no thiol group, is, for example, a series, threonine, valine, alanine, glycine, leucine or isoleucine, another polar amino acid, another natural amino acid, or1. Способ получения конъюгата антитела, в котором осуществляют реакцию сконструированного антитела, имеющего одинарную дисульфидную связь между тяжелыми цепями, с реагентом для конъюгации, который образует мостиковую связь между двумя остатками цистеина, полученными из дисульфидной связи.2. Способ по п. 1, в кото