P. aeruginosa mucoid exopolysaccharide specific binding peptides

Abstract

The present invention relates to peptides, particularly human monoclonal antibodies, that bind specifically to P. aeruginosa mucoid exopolysaccharide. The invention further provides methods for using these peptides in the diagnosis, prophylaxis and therapy of P. aeruginosa infection and related disorders (e.g., cystic fibrosis). Some antibodies of the invention enhance opsonophagocytic killing of multiple mucoid strains of P. aeruginosa . Compositions of these peptides, including pharmaceutical compositions, are also provided, as are functionally equivalent variants of such peptides.

1 - 74 . (canceled)  
     
     
         75 . A composition comprising an isolated antibody or antibody fragment that selectively binds to  P. aeruginosa  mucoid exopolysaccharide (MEP) and comprises at least two MEP-binding CDR amino acid sequences.  
     
     
         76 . The composition of  claim 75 , wherein the at least two MEP-binding CDR amino acid sequences comprise one or two CDR3 amino acid sequences.  
     
     
         77 . The composition of  claim 76 , wherein the one or two CDR3 amino acid sequences are selected from the group consisting of SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29 and SEQ ID NO:32.  
     
     
         78 . The composition of  claim 75 , wherein the at least two MEP-binding CDR amino acid sequences comprise one or two CDR2 amino acid sequences.  
     
     
         79 . The composition of  claim 78 , wherein the one or two CDR2 amino acid sequence are selected from the group consisting of SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:28 and SEQ ID NO:31.  
     
     
         80 . The composition of  claim 75 , wherein the isolated antibody or antibody fragment comprises at least three MEP-binding CDR amino acid sequences.  
     
     
         81 . The composition of  claim 80 , wherein the at least three MEP-binding CDR amino acid sequences comprise a CDR3 amino acid sequence, a CDR2 amino acid sequence and a CDR1 amino acid sequence.  
     
     
         82 . The composition of  claim 81 , wherein the at least three MEP-binding CDR amino acid sequences comprise 
 (a) SEQ ID NOs: 21, 22 and 23; or    (b) SEQ ID NOs: 30, 31 and 32.    
     
     
         83 . The composition of  claim 75 , wherein the isolated antibody or antibody fragment is a human antibody or antibody fragment.  
     
     
         84 . The composition of  claim 75 , wherein the isolated antibody or antibody fragment is a human monoclonal antibody or antibody fragment.  
     
     
         85 . The composition of  claim 75 , further comprising a pharmaceutically acceptable carrier.  
     
     
         86 . The composition of  claim 75 , wherein the isolated antibody or antibody fragment is labeled with a detectable label.  
     
     
         87 . The composition of  claim 75 , wherein the isolated antibody or antibody fragment is an isolated monoclonal antibody fragment selected from the group consisting of an F(ab′) 2  fragment, an Fd fragment, an Fv fragment, and an Fab fragment.  
     
     
         88 . The composition of  claim 75 , wherein the isolated antibody or antibody fragment enhances opsonophagocytosis of  P. aeruginosa.    
     
     
         89 . A method for detecting  P. aeruginosa  in a subject comprising 
 determining a test level of binding of the isolated antibody or antibody fragment of  claim 75  to a sample in or from a subject, and    comparing the test level of binding to a control,    wherein a test level of binding that is greater than the control is indicative of the presence of  P. aeruginosa  in the sample.    
     
     
         90 . A method for treating a subject having, or at risk of developing, a  P. aeruginosa  infection or a  P. aeruginosa  related disorder comprising 
 administering to a subject in need of such treatment the isolated antibody or antibody fragment of  claim 75  in an amount effective to inhibit a  P. aeruginosa  infection or the disorder.