A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 39/395 (2006.01) C07K 16/18 (2006.01) C07K 16/28 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2270922
The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.
La présente invention concerne l'identification d'anticorps qui sont spécifiques de l'antigène B7.1 humain (CD80), qui sont capables d'empêcher la liaison de B7.1 sur un récepteur CD28, et qui ne sont pas capables d'empêcher la liaison du B7.1 sur un récepteur CTLA-4. Deux de ces anticorps, le 16C10 et le 7C10, empêchent sensiblement la production d'IL-2, malgré l'existence d'un second ligand B7.2 activateur (CD86). Il résulte de l'effet antagoniste de ces anticorps, affectant la co-stimulation positive, combiné à l'effet agoniste de ces anticorps, affectant la signalisation négative, un blocage du signal d'activation primaire entre le CD28 et le B7.1 (CD80), tout en autorisant une interaction non entravée ou en coïncidence du CTLA-4 et du B7.1 et/ou B7.2. Ces anticorps conviennent particulièrement comme immunodépresseurs spécifiques, notamment pour le traitement d'affections auto-immunes et pour la prévention du rejet de greffe.
Anderson Darrell R.
Brams Peter
Hanna Nabil
Heard Cheryl
Biogen Idec Inc.
Idec Pharmaceuticals Corporation
Smart & Biggar
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