High affinity antibodies that neutralize
This invention provides antibodies that specifically bind and neutralize Staphylococcus enterotoxin B. In addition, nucleic acids encoding such antibodies, and cells that express such antibodies are provided. Also provided are methods for treating diseases mediated by, and for neutralizing Staphylococcus enterotoxin B.
1. An isolated human antibody, said antibody comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 68, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 70, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or an antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B with a dissociation constant (K D ) of less than 3×10 −8 M.
2. The antibody of claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 176 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 174, or an antigen-binding fragment thereof.
3. The antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 30 and the light chain comprises the amino acid sequence of SEQ ID NO: 28, or an antigen-binding fragment thereof.
4. An isolated human antibody, said antibody comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 130, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 132, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 106, or an antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B with a dissociation constant (K D ) of less than 3×10 −8 M.
5. The antibody of claim 4 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 204 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 200, or an antigen-binding fragment thereof.
6. The antibody of claim 4 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 232 and the light chain comprises the amino acid sequence of SEQ ID NO: 186, or an antigen-binding fragment thereof.
7. An isolated human antibody, said antibody comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 94, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 82, or an antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B with a dissociation constant (K D ) of less than 3×10 −8 M.
8. The antibody of claim 7 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 160 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 158, or an antigen-binding fragment thereof.
9. The antibody of claim 7 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 251 and the light chain comprises the amino acid sequence of SEQ ID NO: 249, or an antigen-binding fragment thereof.
10. An isolated human antibody, said antibody comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 144, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 148, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140, or an antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B with a dissociation constant (K D ) of less than 3×10 −8 M.
11. The antibody of claim 10 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 230 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 228, or an antigen-binding fragment thereof.
12. The antibody of claim 10 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 216 and the light chain comprises the amino acid sequence of SEQ ID NO: 214, or an antigen-binding fragment thereof.
13. The antibody of claim 1 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 1×10 −9 M.
14. The antibody of claim 1 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 3×10 −10 M.
15. A composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.
16. The antibody of claim 4 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 1×10 −9 M.
17. The antibody of claim 4 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 3×10 −10 M.
18. A composition comprising the antibody or antigen-binding fragment of claim 4 and a pharmaceutically acceptable carrier.
19. The antibody of claim 7 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 1×10 −9 M.
20. The antibody of claim 7 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 3×10 −10 M.
21. A composition comprising the antibody or antigen-binding fragment of claim 7 and a pharmaceutically acceptable carrier.
22. The antibody of claim 10 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 1×10 −9 M.
23. The antibody of claim 10 , or an antigen-binding fragment thereof, wherein the affinity of the antibody is less than about 3×10 −10 M.
24. A composition comprising the antibody or antigen-binding fragment of claim 10 and a pharmaceutically acceptable carrier.