Monoclonal antibodies that block ligand binding to the cd22...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 5/12 (2006.01) A61K 39/395 (2006.01) C07K 14/705 (2006.01) C07K 16/28 (2006.01) C12N 5/16 (2006.01) C12P 21/08 (2006.01)

Patent

CA 2140538

The present invention is concerned with a series of novel monoclonal antibodies directed against CD22, a B lineage-restricted member of the Ig-superfamily which serves as an adhesion receptor expressed by mature B lymphocytes and is believed to function in the regulation of B cell activation. The monoclonal antibodies (mAb) specifically block red blood cell and leukocyte adhesion (80-100 %) to COS cells transfected with CD22 cDNA and also identify a region of CD22 distinct from those defined by previously described CD22 mAb. The invention also encompasses therapeutic compositions including therapeutically effective amounts of a polypeptide comprising the CD22 ligand or portion thereof or of a polypeptide comprising the first two amino- terminal Ig-like domains of CD22, or the ligand binding portion thereof. The antibodies and polypeptides of the invention find use in therapeutic methods for treatment of humans to retard or block CD22 adhesive function, particularly in autoimmune disease.

La présente invention concerne une série de nouveaux anticorps monoclonaux dirigés contre le récepteur CD22, un élément restreint par la lignée des lymphocytes B de la superfamille Ig qui sert de récepteur d'adhésion exprimé par les lymphocytes B matures et qui est censé fonctionner dans la régulation de l'activation des lymphocytes B. Les anticorps monoclonaux (mAb) bloquent spécifiquement l'adhésion des érythrocytes et des leucocytes (80-100 %) sur les cellules COS transfectées par l'ADNc de CD22 et identifient également une région du CD22 distincte de celles définies par les anticorps monoclonaux (mAb) de CD22 précédemment décrits. L'invention concerne également des compositions thérapeutiques comprenant des quantités thérapeutiquement efficaces d'un polypeptide renfermant le ligand de CD22 ou une partie de celui-ci, ou des quantités thérapeutiquement efficaces d'un polypeptide comprenant les deux premiers domaines à terminaison amino de type Ig de CD22 ou d'une partie de fixation du ligand de celui-ci. Les anticorps et les polypeptides de l'invention s'appliquent dans des procédés thérapeutiques de traitement chez l'homme afin de retarder ou bloquer la fonction d'adhésion de CD22, notamment dans les maladies autoimmunes.

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