摘要 |
PCT No. PCT/EP95/02626 Sec. 371 Date Jan. 14, 1997 Sec. 102(e) Date Jan. 14, 1997 PCT Filed Jul. 5, 1995 PCT Pub. No. WO96/02574 PCT Pub. Date Feb. 1, 1996A process for improving the stability of an antibody or fragment thereof is disclosed. A gene encoding for an amino acid sequence of a variable domain of an antibody or fragment thereof to be modified is provided, and the amino acid sequence of the gene is compared with one of consensus tables 1-6. At least one codon of each pair of codons in the gene, which pair together code for disulfide bridge-forming cysteines, are modified so that all disulfide bridges present in the antibody as produced in a eukaryotic cell are absent from the modified antibody as produced in the method. At least one additional codon in the gene which codes for an amino acid other than a disulfide bridge-forming cysteine is also modified. A prokaryotic microorganism is transformed with the modified gene and additional variable domain DNA, and the modified antibody or fragment thereof is expressed in the prokaryotic microorganism.
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