Peptide analogues of myelin basic protein epitopes in the...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/47 (2006.01) A61K 38/17 (2006.01) A61K 47/48 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2445640

This invention relates to novel linear and cyclic peptide analogues of Myelin Basic Protein epitopes (from guinea pig MBP72-85 and human MBP87-99) and their conjugates with mannan and/or KLH useful in the treatment of Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS). For the first time cyclic analogues of MBP epitopes have been synthesized and shown to prevent the development of EAE. There is gathering evidence that analogues of disease-associated epitopes can be conjugated to mannan and/or KLH and actively generate antigen specific regulatory CD4/CD8 T cells and Th1/Th2 cytokines.

Cette invention concerne des analogues peptidiques linéaires et cycliques d'épitopes de protéines de base de myéline (prélevés sur un cobaye MBP¿72-85? Et sur l'homme MBP¿87-99?) et leur conjugués avec la mannane et/ou KLH qui sont utiles pour les traitement de l'encéphalomyélite auto-immune expérimentale (EAE) et de la sclérose en plaques. Pour la première fois, on a pu synthétiser des analogues cycliques d'épitopes de protéines de base de myéline et démontrer qu'ils empêchaient le développement de l'EAE. Il apparaît de plus en plus que des analogues d'épitopes associés à la maladie peuvent être conjugués à la mannane et/ou à KLH et produisent activement des lymphocytes t CD4/CD8 régulateurs spécifiques de l'antigène et des cytokines Th1/Th2.

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