Anti-pseudomonas psl binding molecules and uses thereof

Abstract

This disclosure relates to an anti- Pseudomonas Psl binding molecule and uses thereof, in particular in prevention and treatment of Pseudomonas infection. Furthermore, the disclosure provides compositions and methods for preventing and treating Pseudomonas infection.

1 - 71 . (canceled) 
     
     
         72 . A method of producing an antibody or antigen-binding fragment thereof which specifically binds  Pseudomonas  Psl, comprising culturing a host cell comprising a polynucleotide comprising a nucleic acid encoding an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (VH), wherein the VH comprises a VH complementarity determining region-1 (VHCDR1), VHCDR2, and VHCDR3 of amino acid sequences SEQ ID NOs:47, 48, and 75, respectively, and the antibody or antigen-binding fragment comprises a light chain variable region (VL), wherein the VL comprises a VLCDR1, VLCDR2, and VLCDR3 of amino acids SEQ ID NOs: 50, 51, and 52, respectively, and recovering the binding molecule or fragment thereof. 
     
     
         73 - 77 . (canceled) 
     
     
         78 . A method of preventing or treating a  Pseudomonas  infection in a subject in need thereof, comprising administering to the subject an effective amount of an antibody or fragment thereof comprising a set of complementarity determining regions (CDRs) VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3 comprising SEQ ID NOs: 47, 48, 75, 50, 51, and 52. 
     
     
         79 . The method of  claim 78 , wherein the  Pseudomonas  infection is a  Pseudomonas aeruginosa  infection. 
     
     
         80 . The method of  claim 78 , wherein the subject is a human. 
     
     
         81 . The method of  claim 78 , wherein the infection is an ocular infection, a lung infection, a burn infection, a wound infection, a skin infection, a blood infection, a bone infection, or a combination of two or more said infections. 
     
     
         82 . The method of  claim 78 , wherein the subject suffers from acute pneumonia, burn injury, corneal infection, cystic fibrosis, or a combination thereof. 
     
     
         83 . (canceled) 
     
     
         84 . A method of enhancing opsonophagocytic killing (OPK) of  P. aeruginosa  comprising contacting a mixture of phagocytic cells and  P. aeruginosa  with an antibody or fragment thereof comprising a set of complementarity determining regions (CDRs) VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3 comprising SEQ ID NOs: 47, 48, 75, 50, 51, and 52. 
     
     
         85 . The method of  claim 84 , wherein the phagocytic cells are differentiated HL-60 cells. 
     
     
         86 . The method of  claim 72 , wherein the antibody or fragment thereof comprises the VH and VL of SEQ ID NO:74 and SEQ ID NO:12. 
     
     
         87 . The method of  claim 72 , wherein the antibody or fragment thereof comprises a single chain Fv (scFv). 
     
     
         88 . the method of  claim 86 , wherein the antibody or fragment thereof comprises a single chain Fv (scFv). 
     
     
         89 . The method of  claim 72 , wherein the host cell is a COS, CHO, BLK, 293, or 3T3 cell. 
     
     
         90 . An antibody or fragment thereof produced by the method of  claim 72 . 
     
     
         91 . The method of  claim 78 , wherein the antibody or fragment thereof comprises the VH and VL of SEQ ID NO:74 and SEQ ID NO:12. 
     
     
         92 . The method of  claim 78 , wherein the antibody or fragment thereof comprises a single chain Fv (scFv). 
     
     
         93 . The method of  claim 91 , wherein the antibody or fragment thereof comprises a single chain Fv (scFv). 
     
     
         94 . The method of  claim 78 , wherein the antibody or fragment thereof is administered by intravenous, intraarterial, intraperitoneal, intramuscular, or subcutaneous administration. 
     
     
         95 . The method of  claim 84 , wherein the antibody or fragment thereof comprises the VH and VL of SEQ ID NO:74 and SEQ ID NO:12. 
     
     
         96 . The method of  claim 84 , wherein the antibody or fragment thereof comprises a single chain Fv (scFv). 
     
     
         97 . The method of  claim 95 , wherein the antibody or fragment thereof comprises a single chain Fv (scFv).