Antibodies to the PcrV antigen of
View Patent ↗The current invention provides high-affinity antibodies to the Pseudomonas aeruginosa PcrV protein that have reduced immunogenicity when administered to treat Pseudomonas aeruginosa infections.
1. An isolated anti-PcrV antibody that binds to PcrV, comprising:
a V H region that comprises a CDR3 having a sequence NRGDIYYDFTYAMDI (SEQ ID NO:99), a CDR2 sequence VISYDGSEKWYADSVKG (SEQ ID NO:57), and a CDR1 sequence NYPMH (SEQ ID NO:54); and a V L region that comprises a CDR3 having a sequence QHFWGTPYT (SEQ ID NO:110), a CDR2 sequence DASTLQS (SEQ ID NO:73) and a CDR1 sequence RASEGVDRWLA (SEQ ID NO:69).
2. The antibody of claim 1 , wherein the V H region comprises the amino acid sequence of the V-segment region of SEQ ID NO:26.
3. The antibody of claim 2 , wherein the V H region comprises the amino acid sequence set forth in SEQ ID NO:26.
4. The antibody of claim 1 , wherein the V L region comprises the amino acid sequence of the V-segment of SEQ ID NO:24.
5. The antibody of claim 4 , wherein the V L region comprises the amino acid sequence set forth in SEQ ID NO:24.
6. The antibody of claim 1 , wherein the antibody is a Fab′ fragment.
7. The antibody of claim 1 , wherein the antibody is an IgG.
8. The antibody of claim 1 , wherein the antibody is PEGylated.
9. The antibody of claim 8 , wherein the antibody is di-PEGylated.
10. The antibody of claim 1 , wherein the V H region or the V L region, or both the V H and V L region amino acid sequences comprise a methionine at the N-terminus.
11. An isolated anti-PcrV antibody that is an antagonist of the Type III secretion system, comprising: a V H region having the amino acid sequence set forth in SEQ ID NO:26 and a V L region having the amino acid sequence set forth in SEQ ID NO:24.
12. The antibody of claim 11 , wherein the V H region or the V L region, or both the V H and V L regions have a methionine present at the N-terminus.
13. The antibody of claim 11 , wherein the antibody is a di-PEGylated Fab′.
14. A composition comprising the isolated antibody of claim 11 and a pharmaceutically acceptable carrier.
15. A composition comprising the isolated antibody of claim 1 and a pharmaceutically acceptable carrier.