Recombinant antibodies specific for tnf-.alpha.

Details Recombinant antibodies specific for tnf-.alpha. Recombinant antibodies specific for tnf-.alpha.

C - Chemistry, Metallurgy

07

K

C07K 16/24 (2006.01) A61K 39/395 (2006.01) C07K 16/46 (2006.01)

Patent

CA 2129554

Recombinant, in particular humanised, e.g. humanised chimeric and CDR-grafted humanised, antibody molecules having specificity for human TNF.alpha., are provided for use in diagnosis and therapy. In particular the antibody molecules have antigen binding sites derived from murine monoclonal antibodies CB0006, CB0010,hTNF3 or 101.4. Preferred CDR-grafted humanised anti-hTNF.alpha. antibodies comprise variable region domains comprising human acceptor framework and donor antigen binding regions and wherein the frameworks comprise donor residues at specific positions. The antibody molecules may be used for therapeutic treatment of human patients suffering from or at risk of disorders associated with undesirably high levels of TNF, in particular for treatment of immunoregulatory and inflammatory disorders of septic, endotoxic or cardiovascular shock.

Recombinant, dans des molécules d'anticorps humanisés particuliers, p. ex. chimère et CDR greffé humanisés, possédant une spécificité pour TNF alpha humain; cela sert à des fins diagnostiques et thérapeutiques. En particulier, les molécules d'anticorps ont des sites de fixation d'antigène dérivé des anticorps monoclonaux de souris CB0006, CB0010,hTNF3 ou 101,4. Les anticorps de premier choix CDR greffés humanisés, anti-hTNF alpha, ont des domaines de région variables comprenant un cadre d'accepteurs humains et des régions d'attachement d'antigène-donneur; dans ces cadres, il y a des résidus- donneur dans des positions spécifiques. Les molécules d'anticorps peuvent servir à des fins thérapeutiques chez les humains exposés à des troubles liés à de hauts niveaux indésirables de TNF, ou victimes de ceux-ci, en particulier pour le traitement de troubles immuno-régulateurs et inflammatoires de choc septique, endotoxique ou cardiovasculaire.

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