DESIGNED DEIMMUNIZED MONOCLONAL ANTIBODIES FOR PROTECTION AGAINST HIV EXPOSURE AND TREATMENT OF HIV INFECTION

摘要

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.