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 IgG1antibody 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.此專利發明為一種可用以對抗Human Immunodeficiency Virus(HIV)感染以及治療CD4媒介(CD4-mediated)的自體免疫(autoimmune)疾病的去免疫性抗體。更進一步而言,抗體是由一些選殖株所表現出來,這些選殖株為含有重組基因B4DIVHv1/VK1CHO#7的7號選殖株、含有重組基因B4DIVHv1/VK1#16的16號選殖株以及含有重組基因B4DIVHv1/VK1#21的21號選殖株,這些選殖株是由鼠源B4單株抗體(mAb)所衍生而來。這些抗體已經被移除了會被人類免疫系統所辨認外來的鼠源序列。這些重組的抗體是由嵌合與去免疫鼠源B4單株抗體的Fv區域所成。為改進安全性,表現序列被更進一步的突變成去醣化的IgG1而使之不會與補體(complement)結合。去免疫性的抗體仍保留著鼠源B4單株抗體對抗寄主T細胞表面CD4的接受器複合體之結合力,並保留了B4單株抗體中和HIV原始病毒分離株的特性。
