Improved anti-cd19 antibodies

Details Improved anti-cd19 antibodies Improved anti-cd19 antibodies

C - Chemistry, Metallurgy

07

K

C07K 16/46 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) A61K 49/00 (2006.01) A61K 51/10 (2006.01) C07K 16/28 (2006.01)

Patent

CA 2742254

The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence.

La présente invention porte sur des anticorps anti-CD19 humanisés, chimériques et humains, des protéines de fusion d'anticorps anti-CD19 et des fragments de ceux-ci qui se lient à un marqueur de lymphocyte B humain. De tels anticorps, protéines de fusion et fragments de ceux-ci sont utiles pour le traitement et le diagnostic de divers troubles des lymphocytes B, comprenant des tumeurs de lymphocyte B et des maladies auto-immunes. Dans des modes de réalisation plus particuliers, les anticorps anti-CD19 humanisés peuvent comprendre une ou plusieurs substitutions d'acide aminé de la région d'infrastructure mises au point pour améliorer la stabilité des protéines, la liaison de l'anticorps et/ou les taux d'expression. Dans un mode de réalisation particulièrement préféré, les substitutions comprennent une substitution Ser91Phe dans la séquence hA19 VH.

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