Development of Fab molecule with the stable scaffold for next generation

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In order to prepare humanized Fab with the stable scaffold for next generation, we tried to stabilize the constant region of humanized Fab. At first, we showed that Asn138 in L chain of the Fab was easy to deamidate to Asp of Asn residues in the Fab. After preparation of the Fab mutants where Asn138 is mutated to Asp or Ala in L chain of the Fab, respectively, we examined their stabilities against guanidine hydrochloride at pH 6.5 and 25℃. As a result, we found that Asp138Fab was more destabilized than the nonmutant Fab while Ala138Fab had a stability similar to the nonmutant Fab. After heating at pH 9, the residual amount of Ala138Fab was higher than that of the nonmutant Fab.