Antibodies to the pcrv antigen of pseudomonas aeruginosa

Abstract

The current invention provides high-affinity antibodies to the Pseudomonas aeruginosa PcrV protein that have reduced immunogenicity when administered to treat Pseudomonas aeruginosa infections.

What is claimed is: 
     
         1 . An isolated anti-PcrV antibody that selectively binds PcrV, wherein the antibody comprises a V L  region that has a CDR3 having a sequence Q(Q/H)FWGTPYT (SEQ ID NO:41) and a V H  region that has a CDR3 having a sequence NRGDIYYDFTYA(M/F)DX 1  (SEQ ID NO:42), wherein X 1  is I, Q, Y, or S. 
     
     
         2 . The isolated anti-PcrV antibody of  claim 1 , wherein the V H  V-segment as at least 80% identity to the human VH1-18 subclass V-segment or to the human VH3-30.3 V segment and the V L  V-segment has at least 80% identity to a human germline Vkappa I or Vkappa III sequence, or at least 80% identity to a human germline Vlambda sequence. 
     
     
         3 . The isolated anti-PcrV antibody of  claim 2 , wherein the V H  region comprises a FR4 that has at least 90% identity to the FR4 region of the human JH3 or human JH6 segment and the V L  region comprises a FR4 that has at least 90% identity to the FR4 region of the human JK2 germline gene segment or at least 90% identity to the JL2 germline sequence. 
     
     
         4 . The isolated anti-PcrV antibody of  claim 3 , wherein the FR4 of the V H  region has the sequence WGQGTX 2 VTVSS (SEQ ID NO:45), wherein X 2  is T or M; and the FR4 of the V L  region has the sequence FGQGTKLEIK (SEQ ID NO:47) or FGGGTKLTVL (SEQ ID NO:48). 
     
     
         5 . The isolated anti-PcrV antibody of  claim 1 , wherein the antibody is a Fab′. 
     
     
         6 . The isolated anti-PcrV antibody of  claim 1 , wherein the antibody is PEGylated. 
     
     
         7 . The isolated anti-PcrV antibody of  claim 1 , wherein the antibody is a di-PEGylated Fab′. 
     
     
         8 . A composition comprising the isolated anti-PcrV antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         9 . An isolated anti-PcrV antibody that selectively binds PcrV, wherein the antibody comprises:
 a V H  region having 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.   
     
     
         10 . The isolated anti-PcrV antibody of  claim 9 , wherein the V H  region comprises the amino acid sequence of the V-segment region of SEQ ID NO:26. 
     
     
         11 . The isolated anti-PcrV antibody of  claim 10 , wherein the V H  region comprises the amino acid sequence of the V-segment region of SEQ ID NO:26. 
     
     
         12 . The isolated anti-PcrV antibody of  claim 9 , wherein the antibody is a Fab′. 
     
     
         13 . The isolated anti-PcrV antibody of  claim 9 , wherein the antibody is PEGylated. 
     
     
         14 . The isolated anti-PcrV antibody of  claim 9 , wherein the antibody is a di-PEGylated Fab′. 
     
     
         15 . A composition comprising the isolated anti-PcrV antibody of  claim 9  and a pharmaceutically acceptable carrier. 
     
     
         16 . An isolated anti-PcrV antibody that selectively binds PcrV, wherein the antibody comprises:
 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); and   a V H  region.   
     
     
         17 . The isolated anti-PcrV antibody of  claim 16 , wherein the V L  region comprises the amino acid sequence of the V-segment of SEQ ID NO:24. 
     
     
         18 . The isolated anti-PcrV antibody of  claim 17 , wherein the V L  region comprises the amino acid sequence set forth in SEQ ID NO:24. 
     
     
         19 . The isolated anti-PcrV antibody of  claim 16 , wherein the antibody is a Fab′ fragment. 
     
     
         20 . The isolated anti-PcrV antibody of  claim 16 , wherein the antibody is a di-PEGylated Fab′.