Methods, compositions and kits for treating a subject using a recombinant heteromultimeric neutralizing binding protein
Methods, compositions and kits are provided for treating a subject exposed to or at risk for exposure to a disease agent using a pharmaceutical composition including at least one recombinant heteromultimeric neutralizing binding protein including two or multiple binding regions, such that the binding regions are not identical, and each binding region specifically binds a non-overlapping portion of the disease agent, thereby treating the subject for exposure to the disease agent. In a related embodiment, the heteromultimeric neutralizing binding protein includes two or multiple binding regions that neutralize a plurality of disease agents. In certain embodiments, the disease agent includes a bacterium, a bacterial protein, a virus, a viral protein, a cancer cell, and a protein or molecule produced therefrom. In certain embodiments, the disease agent is a plurality of different disease agents.
1. A composition comprising an isolated recombinant neutralizing binding polypeptide comprising an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, and SEQ ID NO: 76.
2. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 65.
3. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 66.
4. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 67.
5. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 68.
6. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of, SEQ ID NO: 69.
7. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 70.
8. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 71.
9. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 72.
10. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 73.
11. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 74.
12. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 75.
13. The composition according to claim 1 , wherein the recombinant neutralizing binding polypeptide comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from the group consisting of and SEQ ID NO: 76.
14. A composition comprising at least one recombinant neutralizing binding protein, the recombinant neutralizing binding protein including a recombinant camelid heavy chain-only VHH antibody of an amino acid sequence selected from the group consisting of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, and SEQ ID NO: 76.
15. A composition comprising at least one recombinant heteromultimeric neutralizing binding protein comprising two or more specific binding regions, the binding regions being not identical and each of the binding regions specifically binding to a non-overlapping epitope of Clostridium difficile toxin B, and the neutralizing binding protein containing an amino acid sequence selected from the group consisting of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, and SEQ ID NO: 76.
16. The composition according to claim 15 , wherein the binding protein further comprises a peptide linker that is located between the specific binding regions.
17. A kit comprising the composition according to claim 15 , a container, and instructions for use.
18. The composition according to claim 15 , wherein the neutralizing binding protein contains an amino acid sequence selected from SEQ ID NO: 67 or SEQ ID NO: 68.