Anti-factor xi monoclonal antibodies and methods of use thereof

Details Anti-factor xi monoclonal antibodies and methods of use thereof Anti-factor xi monoclonal antibodies and methods of use thereof

C - Chemistry, Metallurgy

07

K

C07K 16/36 (2006.01)

Patent

CA 2705851

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction. Methods for making an anti-factor XI monoclonal antibody, or epitope-binding fragments, variants, or derivatives thereof, are also provided.

L'invention concerne des compositions et des procédés pour inhiber la thrombose sans hémostase compromettante. Les compositions comprennent des anticorps monoclonaux anti-facteur Xi (aXIMab) capables de se lier à un épitope sur la chaîne lourde du FXI humain, en particulier le domaine A3 de la chaîne lourde du FXI humain. Des compositions comprennent également des fragments de liaison à un épitope, des variantes et des dérivés des anticorps monoclonaux, des lignées cellulaires produisant ces compositions d'anticorps, et des molécules d'acides nucléiques isolées codant les séquences d'acides aminés des anticorps. L'invention comprend en outre des compositions pharmaceutiques comprenant les anticorps monoclonaux anti-facteur XI de l'invention, ou des fragments de liaison à un épitope, des variantes ou leurs dérivés, dans un support pharmaceutiquement acceptable. Des procédés de l'invention comprennent l'administration des compositions décrites ci-dessus à un sujet qui en a besoin dans le but d'inhiber une thrombose, de réduire une dose requise d'un agent anti-thrombotique dans le traitement d'une thrombose, le traitement d'un cancer métastatique, ou le traitement d'une réaction inflammatoire aiguë. Des procédés de préparation d'un anticorps monoclonal anti-facteur XI, ou de fragments de liaison à un épitope, de variantes ou de leurs dérivés, sont également proposés.

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