Monoclonal antibodies to basic fibroblast growth factor

Abstract

The present invention is directed toward a neutralizing monoclonal antibody to basic fibroblast growth factor, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.

What is claimed is: 
     
         1 . A monoclonal antibody (mAb) that binds and neutralizes human basic fibroblast growth factor (FGF2), wherein the mAb is genetically engineered. 
     
     
         2 . The mAb of  claim 1  which is chimeric. 
     
     
         3 . The mAb of  claim 1  which is humanized. 
     
     
         4 . The mAb of  claim 1  which is human. 
     
     
         5 . The mAb of  claim 1  which completely inhibits binding of FGF2 to each of the FGF receptors FGFR1, FGFR2, FGFR3 and FGFR4. 
     
     
         6 . The mAb of  claim 1  which inhibits FGF2-induced proliferation of My 1 Lu cells. 
     
     
         7 . The mAb of  claim 1  which inhibits growth of a human tumor xenograft in a mouse. 
     
     
         8 . The mAb of  claim 1  which is a Fab or F(ab′) 2  fragment or single-chain antibody. 
     
     
         9 . A pharmaceutical composition comprising a mAb of  claim 1 . 
     
     
         10 . A method of treating cancer in a patient comprising administering to the patient a pharmaceutical composition comprising the mAb of  claim 1 . 
     
     
         11 . A monoclonal antibody (mAb) that competes for binding to FGF2 with an antibody produced by hybridoma PTA-8864 and has reduced immunogenicity. 
     
     
         12 . The mAb of  claim 11  which inhibits growth of a human tumor xenograft in a mouse. 
     
     
         13 . The mAb of  claim 11  which is humanized or human. 
     
     
         14 . A pharmaceutical composition comprising a mAb of  claim 11 . 
     
     
         15 . A method of treating cancer in a patient comprising administering to the patient a pharmaceutical composition comprising the mAb of  claim 11 . 
     
     
         16 . The method of  claim 15  wherein said cancer is hepatocellular carcinoma. 
     
     
         17 . A mouse, chimeric or humanized form of a mAb produced by the PTA-8864 hybridoma. 
     
     
         18 . A humanized antibody comprising a humanized light chain comprising CDRs from the sequence in  FIG. 11A  (GAL-F2) (SEQ ID NO:1) and a humanized heavy chain comprising CDRs from the sequence of  FIG. 11B  (GAL-F2) (SEQ ID NO:4). 
     
     
         19 . The humanized antibody of  claim 18 , wherein residues H1, H27, H30, H48, H67, H71 and H94 by Kabat numbering are occupied by the residue occupying the corresponding position of the heavy chain shown in  FIG. 11B  (GAL-F2) (SEQ ID NO:4). 
     
     
         20 . The humanized antibody of  claim 18  wherein the light chain variable region has at least 95% sequence identity to the sequence shown in  FIG. 11A  (HuGAL-F2) (SEQ ID NO:2) and the heavy chain has at least 95% sequence identity to the sequence shown in  FIG. 11B  (HuGAL-F2) (SEQ ID NO:5). 
     
     
         21 . The humanized antibody of  claim 18 , comprising the three light chain CDRs and three heavy chain CDRs shown in  FIGS. 11A  (HuGAL-F2) (SEQ ID NO:2) and  11 B (HuGAL-F2) (SEQ ID NO:5).