High affinity human monoclonal antibodies specific for rsv...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/13 (2006.01) A61K 39/42 (2006.01) C07K 16/00 (2006.01) C07K 16/08 (2006.01) C07K 16/10 (2006.01) C12N 5/10 (2006.01) G01N 33/569 (2006.01) G01N 33/577 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2223033

A highly efficient method for generating human antibodies in particular which are specific to be RSV fusion protein which combines in vitro priming of human spleen cells and antigen boosting in SCID mice is taught. This method provides for very high human antibody titers which are predominantly of the IgG isotype which contain antibodies of high specificity and affinity to desired antigens. This method is well suited for generating human monoclonal antibodies for therapeutic and diagnostic applications as well as for rescue for human cells for generation of combinational human antibody gene libraries. Two human monoclonal antibodies, RF-1 and RF-2 which each possess an affinity for RSV-F protein <= 2x10-9 Molar are taught as well as their corresponding amino acid and DNA sequences. These antibodies are to be used therapeutically and prophylactically for treating or preventing RSV infection, as well as for diagnosis of RSV in analytes.

Procédé extrêmement efficace visant à générer des anticorps humains qui sont en particulier spécifiques à la protéine de fusion du virus respiratoire syncytial (RSV) et qui associe l'amorçage in vitro des cellules de la rate chez l'homme et le développement d'antigènes dans la souris DICS (ayant un déficit immunitaire combiné sévère). Ce procédé permet de produire des titres très élevés d'anticorps humains qui sécrètent de manière prédominante l'isotype IgG qui comprend des anticorps ayant une haute spécificité et une haute affinité vis-à-vis des antigènes désirés. Ce procédé est parfaitement approprié à la production d'anticorps monoclonaux humains dans des applications thérapeutiques et diagnostiques ainsi que pour sauver des cellules humaines servant à générer des banques de gènes combinatoires d'anticorps humains. L'invention concerne également deux anticorps humains monoclonaux, RF-1 et RF-3, qui ont chacun une affinité pour la protéine F du virus respiratoire syncytial <= 2x10?-9¿ molaire, ainsi que leurs séquences correspondantes d'acides aminés et d'ADN. Ces anticorps sont destinés à être utilisés de manière thérapeutique et prophylactique dans le traitement ou la prévention des infections dues au virus respiratoire syncytial ainsi que dans le diagnostic de ce virus dans des analytes.

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