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: 33, and the heavy chain portion of the first antibody 10E8 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 34; 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 amino acid alterations relative to SEQ ID NOS: 1, 2, 33, and 34 are outside of the variable regions.
2. A pharmaceutical composition comprising the bispecific antibody of claim 1 , and a pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2 , wherein the composition is formulated for oral, intranasal, pulmonary, intradermal, transdermal, subcutaneous, intramuscular, intraperitoneal, or intravenous delivery.
4. 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: 33 and a heavy chain portion of a 10E8 antibody comprising the amino acid sequence of SEQ ID NO: 34.
5. The bispecific antibody of claim 1 , wherein 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.
6. 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 Pro 140, 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 94% identity with SEQ ID NO: 31, and the heavy chain portion of the first antibody 10E8 comprises an amino acid sequence having at least 98% identity with SEQ ID NO: 32;
the light chain portion of the second antibody Pro 140 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 11, and the heavy chain portion of the second antibody Pro 140 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 12; and
wherein any amino acid alterations relative to SEQ ID NOS: 11, 12, 31, and 32 are outside of the variable regions.
7. The bispecific antibody of claim 6 , wherein the antibody comprises a light chain portion of a 10E8 antibody comprising the amino acid sequence of SEQ ID NO: 31 and a heavy chain portion of a 10E8 antibody comprising the amino acid sequence of SEQ ID NO: 32.
8. The bispecific antibody of claim 6 , wherein the antibody comprises a light chain portions of a Pro 140 antibody comprising the amino acid sequence of SEQ ID NO: 11 and a heavy chain portion of a Pro 140 antibody comprising the amino acid sequence of SEQ ID NO: 12.
9. A pharmaceutical composition comprising the bispecific antibody of claim 6 , and a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 9 , wherein the composition is formulated for oral, intranasal, pulmonary, intradermal, transdermal, subcutaneous, intramuscular, intraperitoneal, or intravenous delivery.