Designed deimmunized monoclonal antibodies for protection...

Details Designed deimmunized monoclonal antibodies for protection... Designed deimmunized monoclonal antibodies for protection...

C - Chemistry, Metallurgy

12

N

C12N 15/13 (2006.01) A61K 39/395 (2006.01) A61P 31/18 (2006.01) A61P 37/02 (2006.01) C07K 16/28 (2006.01) C07K 16/46 (2006.01) C12N 5/10 (2006.01) C12P 21/08 (2006.01)

Patent

CA 2512040

This invention is directed to deimmunized antibodies that are useful as immunotherapeutic drugs against Human Immunodeficiency Virus (HIV) and CD4- mediated autoimmune disorders. More specifically, antibodies expressed by clones, Clone 7 containing the recombinant genes B4DIVHv1/VK1CHO#7, Clone 16 containing the recombinant genes B4DIVHv1/VK1#16, and clone 21 containing the recombinant genes B4DIVHv1/VK1#21, are derived from mouse monoclonal B4 antibody (mAb B4). The antibodies were produced by removing particular murine determinants recognized as foreign by the human immune system. These recombinant antibodies were generated by the chimerization and deimmunization of the Fv region of mouse monoclonal antibody (mAb) B4. For improved safety, the coding sequence may further be mutated to express an aglycosylated IgG1 antibody that is unable to bind complement. The deimmunized antibodies retain the specificity of the murine mAb B4 for a receptor complex involving CD4 on the surface of the host T cells, and retain the characteristic ability of mAb B4 to neutralize primary isolates of HIV.

Cette invention concerne des anticorps désimmunisés qui sont utilisés comme médicaments immunothérapeutiques contre le virus de l'immunodéficience humaine (VIH) et les troubles autoimmuns induits par CD4. De manière plus spécifique, des anticorps exprimés par des clones, à savoir le clone 7 contenant les gènes recombinants B4DIVHv1/VK1CHO#7, le clone 16 contenant les gènes recombinants B4DIVHv1/VK1#16 et le clone 21 contenant les gènes recombinants B4DIVHv1/VK1#21, sont dérivés de l'anticorps B4 monoclonal de souris (mAb B4). Ces anticorps sont produits par la suppression de certains déterminants murins considérés comme étrangers par le système immunitaire humain. Ces anticorps recombinants sont générés par la chimérisation et la désimmunisation de la région Fv de l'anticorps monoclonal de souris (mAb) B4. Pour plus de sécurité, la séquence codante peut également être mutée de façon qu'elle exprime un anticorps IgG¿1? non glycosylé qui est incapable de fixer le complément. Les anticorps désimmunisés conservent la spécificité de l'anticorps mAb B4 murin pour un complexe récepteur impliquant CD4 sur la surface des lymphocytes T hôtes et conservent la capacité caractéristique de l'anticorps mAb B4 à neutraliser les isolats primaires du VIH.

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