	US 12,012,451 B2
	Engineering pH-dependent antigen binding activity into anti-HIV antibodies with improved pharmacokinetics
Craig Stuart Pace, Pacifica, CA (US); and David D. Ho, New York, NY (US)
Assigned to The Rockefeller University, New York, NY (US)
Filed by The Rockefeller University, New York, NY (US)
Filed on Aug. 19, 2020, as Appl. No. 16/997,547.
Claims priority of provisional application 62/888,840, filed on Aug. 19, 2019.
Prior Publication US 2021/0054054 A1, Feb. 25, 2021
Int. Cl. C07K 16/28 (2006.01); A61K 47/68 (2017.01); C07K 16/10 (2006.01); C12N 15/113 (2010.01)

CPC C07K 16/2812 (2013.01) [A61K 47/6839 (2017.08); C07K 16/1045 (2013.01); C07K 2317/41 (2013.01); C07K 2317/565 (2013.01); C07K 2317/76 (2013.01); C07K 2317/94 (2013.01); C12N 15/1132 (2013.01)]

16 Claims

1. A histidine-mutated anti-HIV antibody having one or more of the following mutations in the heavy chain of ibalizumab (amino acids 20-471 of SEQ ID NO: 2): Y73H, D78H, K119H, D120H, N121H, and T124H, or one or more of the following mutations in the light chain of ibalizumab (amino acids 20-238 of SEQ ID NO: 3): S45H, L49H, L58H, Q114H, Y117H, S118H, and Y119H; wherein the ibalizumab is comprises in its light chain an engineered N-linked glycosylation site at the amino acid position selected from the group consisting of positions 54Gln, 77Ser, 78Thr, 79Arg, 85Asp, 90Ser, 92Ser, and 101Ser; wherein the antibody has a pH-dependent CD4-binding activity.