Human antibodies that bind lymphocyte activation gene-3...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 16/28 (2006.01) A61K 39/395 (2006.01) A61K 51/10 (2006.01) A61P 31/12 (2006.01) A61P 35/00 (2006.01) A61P 37/04 (2006.01) C12N 15/13 (2006.01) C07K 14/705 (2006.01)

Patent

CA 2734335

The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen- specific T cell responses. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. This disclosure also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which an anti- LAG-3 antibody is co-administered with at least one additional immuno stimulatory antibody, is also provided.

La présente invention porte sur des anticorps monoclonaux isolés qui se lient spécifiquement à LAG-3 avec une affinité élevée, et en particulier sur des anticorps monoclonaux humains. De préférence, les anticorps se lient à LAG-3 humain. Dans certains modes de réalisation, les anticorps se lient à LAG-3 à la fois humain et de singe mais ne se lient pas à LAG-3 de souris. L'invention porte sur des anticorps anti-LAG-3 qui inhibent la liaison de LAG-3 à des molécules du CMH de Classe II et qui peuvent stimuler des réponses de lymphocyte T antigène-spécifique. L'invention porte également sur des molécules d'acides nucléiques codant pour les anticorps de l'invention, sur des vecteurs d'expression, sur des cellules hôtes et sur des procédés pour exprimer les anticorps de l'invention. L'invention porte également sur des immunoconjugués, des molécules bispécifiques et des compositions pharmaceutiques comprenant les anticorps de l'invention. Cette invention porte également sur des procédés de détection de LAG-3, ainsi que sur des procédés pour traiter les réponses immunitaires stimulantes à l'aide d'un anticorps anti-LAG-3 de l'invention. L'invention porte également sur une thérapie de combinaison, dans laquelle un anticorps anti-LAG-3 est co-administré avec au moins un anticorps immunostimulant supplémentaire.

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