The Rockefeller University

Craig Stuart Pace

David D Ho

Yaoxing Huang

David Joon Ho

Ruijiang Song

Qing Fang

The disclosure is directed to a histidine-mutated anti-HIV antibody having one or more mutations at the residue Y53a, D58, K96, D97, N98, or T100a in the heavy chain of ibalizumab, and at the residue S26, L30, L33, Q89, Y92, S93 or Y94 in the light chain of ibalizumab. In addition, the disclosure also is directed to two histidine mutated variants with two mutations, one with mutations at the residues Y53a and Y94, and the other with mutations at the residues D58 and L30 in the heavy and light chains of ibalizumab, respectively.

Engineering pH-dependent antigen binding activity into anti-HIV antibodies with improved pharmacokinetics

Disclosed herein are fusion antibodies created to provide both an antigen-binding site that targets the CD4 receptor and an antigen-binding site that targets the HIV envelope. The fusion antibodies disclosed herein provide improved potency and breadth against HIV as compared to monospecific antibodies, and additionally provide high barrier against viral resistance. Also disclosed are pharmaceutical formulations and therapeutic methods utilizing such fusion proteins.

Growing community of inventors

Pacifica, CA, United States of America

Craig Stuart Pace