Bispecific HIV-1-neutralizing antibodies
In various embodiments, the present invention relates generally to using bispecific antibodies in the prevention and treatment of HIV.
1. A bispecific antibody in a CrossMab format capable of neutralizing HIV, wherein the antibody comprises a light chain and heavy chain portion of a first antibody 10E8, or a variant thereof, that binds to a HIV envelope protein, and a light chain and heavy chain portion of a second antibody ibalizumab, or a variant thereof, that binds to a cell membrane receptor protein or a cell membrane co-receptor protein, wherein
the light chain portion of the first antibody 10E8 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 46 and the heavy chain portion of the first antibody 10E8 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 47; and
the light chain portion of the second antibody ibalizumab comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 1, and the heavy chain portion of the second antibody ibalizumab comprises an amino acid sequence having at least 97% with SEQ ID NO: 2; and wherein any variations relative to SEQ ID NOs:1, 2, 46 and 47 are outside the variable regions.
2. The bispecific antibody of claim 1 , wherein the antibody comprises a light chain portion of an ibalizumab antibody comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain portion of an ibalizumab antibody comprising the amino acid sequence of SEQ ID NO: 2.
3. The bispecific antibody of claim 1 , wherein the antibody comprises a light chain portion of a 10E8 antibody comprising the amino acid sequence of SEQ ID NO: 46 and a heavy chain portion of a 10E8 antibody comprising the amino acid sequence of SEQ ID NO: 47.
4. A pharmaceutical composition comprising the bispecific antibody of claim 1 , and a pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4 , wherein the composition is formulated for oral, intranasal, pulmonary, intradermal, transdermal, subcutaneous, intramuscular, intraperitoneal, or intravenous delivery.