Therapeutic antibodies against flagellated
Improved antibodies are provided selected from human, dual-specific, chimeric or humanized antibodies, wherein said human chimeric and humanized antibodies specifically bind to flagellin type A or type B of P. aeruginosa , and said dual-specific antibodies specifically binds to flagella type A and type B of Pseudomonas aeruginosa , and said antibodies are protective against infection caused by P. aeruginosa . These antibodies as well as pharmaceutical composition comprising them are useful for the treatment of indications caused by P. aeruginosa infection.
1. An antibody that specifically binds to flagella type B of P. aeruginosa , wherein the antibody comprises a VH fragment comprising a complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 6, a CDR2 comprising the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 7, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 8; and a VL fragment comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11, a CDR2 comprising the amino acid sequence of AAS or SEQ ID NO: 12, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 10.
2. The antibody according to claim 1 , which is a human antibody comprising a human IgG constant region fused to human variable regions of an anti- P. aeruginosa monoclonal antibody that specifically binds to flagella type B.
3. The antibody according to claim 2 , wherein said IgG constant region is a human IgG1 constant region.
4. The antibody according to claim 1 , wherein the antibody is covalently linked, optionally via a cleavable linker, to an antibiotic agent.
5. The antibody according to claim 4 , wherein said antibiotic agent is selected from the group consisting of Amikacin, Ampicillin/Sulbactam, Amoxicillin/Calvulanic acid, Aztreonam, Cefepime, Cefotaxime, Ceftazidime, Chloramphenical, Ciprofloxacin, Colistin, Doripenem, Gentamicin, Imipenem, Levofloxacin, Meropenem, Minocycline, Piperacillin, Piperacillin/Tazobactam, Ticracillin, Tigecycline, Tobramycin and Trimethoprim-Sulfamethoxazole.
6. The antibody according to claim 1 , wherein the antibody is covalently linked to a nonproteinaceous polymer, such as polyethyleneglycol.
7. An antigen binding fragment of the antibody according to claim 1 , wherein said fragment binds flagella type B of P. aeruginosa and wherein said fragment comprises a VH fragment comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 6, a CDR2 comprising the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 7, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 8; and a VL fragment comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11, a CDR2 comprising the amino acid sequence of AAS or SEQ ID NO: 12, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 10.
8. A pharmaceutical composition comprising at least one antibody according to claim 1 .
9. A pharmaceutical composition comprising at least one antigen binding fragment according to claim 7 .