C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 16/28 (2006.01) A61K 39/395 (2006.01) A61P 37/06 (2006.01) C07K 16/46 (2006.01)
Patent
CA 2163989
The binding specificity of the murine OKT3 has been transferred into a human antibody framework in order to reduce its immunogenicity. "Humanized" anti-CD3 mAbs, such as gOKT3-5 and gOK73-7, have been 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 are modified versions of humanized anti-CD3 mAbs that do not have the property of T cell activation. Further disclosed are methods of using such mAbs.
On a transferré la spécificité de liaison de l'anticorps monoclonal murin OKT3 sur un cadre d'anticorps humain afin de réduire son immunogénécité. On a démontré que les anticorps monoclonaux anti-CD3 adaptés au système humain, tels que gOKT3-5 et gOKT3-7, conservent, in vitro, toutes les propriétés de l'OKT3 natif, y compris l'activation des lymphocytes T que l'on a corrélé, in vivo, avec les effets secondaires importants observés chez des receveurs de greffe, après la première administration de l'anticorps monoclonal. L'invention concerne également des versions modifiées d'anticorps monoclonaux anti-CD3 adaptés au système humain, ne présentant pas la propriété d'activation des lymphocytes T. En outre, l'invention concerne des procédés d'utilisation desdits anticorps monoclonaux.
Bluestone Jeffrey A.
Jolliffe Linda
Zivin Robert A.
Arch Development Corporation
Bereskin & Parr Llp/s.e.n.c.r.l.,s.r.l.
Macrogenics Inc.
Ortho Pharmaceutical Corporation
Ortho-Mcneil Pharmaceutical Inc.
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