Methods and materials for modulation of the immunosuppressive ac

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Structurally-modified antibody – immunoglobulin – or fragment...

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4241441, 5303873, 53038822, 43524027, A61K 39395

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active

058855734

ABSTRACT:
The binding specificity of the murine OKT3 has been transferred into a human antibody framework in order to reduce its immunogenicity. This "humanized" anti-CD3 mAb (gOKT3-5) was previously shown to retain, in vitro, all the properties of native OKT3, including T cell activation which has been correlated, in vivo, with the severe side-effects observed in transplant recipients after the first administration of the mAb. Disclosed is a single amino acid mutation from a leucine to a glutamic acid at position 235 in the Fc receptor (FcR) binding segment of the gOKT3-5 mAb to produce Glu-235 mAb. Also disclosed is an amino acid mutation from the contiguous phenylalanine at position 234 to a leucine (Leu-234).

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