Engineered anti-alpha v- integrin hybrid antibodies

Details Engineered anti-alpha v- integrin hybrid antibodies Engineered anti-alpha v- integrin hybrid antibodies

C - Chemistry, Metallurgy

07

K

C07K 16/46 (2006.01) A61K 38/16 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01) C07K 16/28 (2006.01) C07K 19/00 (2006.01) C12N 15/13 (2006.01)

Patent

CA 2693863

The invention relates to engineered antibodies which specifically bind to integrin receptors, especially the alpha V integrin receptor subunit. The antibodies comprise the antigen binding sites (CDRs) of a known mouse anti-integrin antibody, as well as hybrid light chain variable sequences, mutated heavy chain variable sequences (Frs) and modified heavy chain constant sequences. The novel antibodies have improved immunogenic and expression properties and elicit excellent anti-angiogenic as well as anti-tumor activities in humans in monotherapy but also and above all in combination with other angiogenesis and tumor inhibiting agents.

L'invention concerne des anticorps modifiés qui se lient spécifiquement à des récepteurs d'intégrine, en particulier à la sous-unité alpha V du récepteur de l'intégrine. Les anticorps précités comprennent les sites de liaison à l'antigène (CDR) d'un anticorps anti-intégrine murin connu, et des séquences variables de la chaîne légère hybrides, des séquences variables de la chaîne lourde mutées (Fr) et des séquences constantes de la chaîne lourde modifiées. Les anticorps de l'invention possèdent des propriétés d'expression et des propriétés immunogènes améliorées et suscitent une excellente activité anti-angiogénique et anti-tumorale chez les humains en monothérapie, mais également et par-dessus tout, lorsqu'ils sont combinés à d'autres agents inhibiteurs de l'angiogenèse et des tumeurs.

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