Targeting immunological functions to the site of bacterial infections using cell wall targeting domains of bacteriolysins
AssigneeIntegrated Biotherapeutics, Inc.
InventorsMohammad Javad Aman, Rajan Prasad Adhikari
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Abstract
This disclosure provides a comprehensive approach to specifically target various immune functions to the site of infection by a variety of fusion proteins that consist of a bacteriolysin cell wall targeting domain (CWT) and an immune function mediating component (IFMC). The CWT targets the fusion protein to the bacterial surface leading to accumulation at the site of infection. The IFMC mediates various immune functions such as toxin neutralization or recruitment of immune cells that can clear the bacteria.
Claims20
A method for treating a bacterial infection, disease, or disorder, comprising administering to a subject in need of treatment an effective amount of a therapeutic polypeptide comprising a cell wall targeting (CWT) domain of a bacteriolysin fused to an immune function mediating component (IFMC) through a peptide linker:
- wherein the bacteriolysin is a bacteriocin selected from the group consisting of:
- Lysostaphin, Bacteriocin AS-48, Bacteriocin ColE9, adherence binding domain DSL peptides of the pilin protein, an E-colicin, Autolysin, and the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme, or
- wherein the bacteriolysin is a phage encoded lysin selected from the group consisting of:
- Phage phiKZ gp144 lysin, ϕNM3 lysin, ϕ11 lysin, ϕ68 P17 lysin, ϕB30 lysin, OK LysK lysin, ϕ MR11 MV-L lysin, ϕSs2 PlySs2bacteriophage lysin, OBPgp279 endolysin, PVP-SE1gp146 lysin, E201φ2-1gp229 lysin, Endolysin PlyL, Endolysin PlyG, LambdaSa2 cpl-7 lysin, bacteriophage SM1 lysin, Endolysin CD27L, and mycobacteriophage Ms6 lysin,
- wherein the IFMC comprises an antibody or antigen binding fragment thereof to a bacterial toxin or toxoid, or a fragment thereof, wherein the antibody or antigen binding fragment thereof lacks the ability to recognize a bacterial cell wall, and wherein the CWT domain of the therapeutic polypeptide can target the IFMC to a bacterial target.
Dependencies are inferred from the claim text.