Peptides that specifically bind hgf receptor (cmet) and uses thereof

Abstract

A polypeptide or multimeric polypeptide construct having the ability to bind to cMet or a complex comprising cMet and HGF, and methods for use are disclosed.

1 .- 32 . (canceled) 
     
     
         33 . A diagnostic imaging agent comprising:
 a) a polypeptide which binds cMet or which binds a complex comprising cMet and HGF, wherein the polypeptide comprises the amino acid sequence:
   C-X2-C-X3-G-P-P-X4-F-X5-C-X6-C; 
   wherein
 X2=H, Y, N, R, S, D, Q, L or E; 
 X3=S, G, N, I, K or Y; 
 X4=T, W, R, S, A or Q; 
 X5=E or Q; 
 X6=W, Y, F, T or A; and, 
   b) a detectable label for diagnostic imaging.   
     
     
         34 . The diagnostic imaging agent of  claim 33 , wherein the polypeptide comprises the amino acid sequence:
   G-X1-C-X2-C-X3-G-P-P-X4-F-X5-C-X6-C-X7-X8-X9-X10-P;   wherein
 X1=S, N, A, K, F, D, I, R, G or T; 
 X2=H, Y, N, R, S, D, Q, L or E; 
 X3=S, G, N, I or Y; 
 X4=T, W, R, S, A or Q; 
 X5=E or Q; 
 X6=W, Y, F, T or A; 
 X7=Y or F; 
 X8=G, D, A, E, S, R, H, T or V; 
 X9=T, S, V, M, A, L, Q, E or P; and, 
 X10=E, D, A, N, Y or G. 
   
     
     
         35 . The diagnostic imaging agent of  claim 33 , wherein the polypeptide comprises the amino acid sequence:
   S-C-X2-C-X3-G-P-P-X4-F-X5-C-X6-C-X7-X8-X9-X10;   wherein
 X2=N, H or Y; 
 X3=G or S; 
 X4=T; 
 X5=E; 
 X6=W; 
 X7=Y; 
 X8=A, D, E, G or S; 
 X9=S or T; and, 
 X10=D or E. 
   
     
     
         36 . The diagnostic imaging agent of  claim 33 , wherein the polypeptide comprises the amino acid sequence:
   E-X12-G-S-C-H-C-S-G-P-α-T-F-E-C-X6-C-X7;
   wherein
 X12=A, E, G or S; 
 X6=F, W or Y; and, 
 X7=F or Y. 
   
     
     
         37 . The diagnostic imaging agent of  claim 33 , wherein the polypeptide comprises the amino acid sequence: 
       
         
           
                 
               
                   C-Y-C-S-G-P-P-R-F-E-C-W-C 
                 
                   or 
                 
                     
                 
                   S-E-T-R-P-T-E-A-G-S-C-Y-C-S-G-P-P-R-F-E-C-W-C-Y-E- 
                 
                     
                 
                   T-E-P-T-E. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         38 . The diagnostic imaging agent of  claim 33 , wherein the detectable label is an enzyme, a fluorescent compound, a liposome, an optical dye, a paramagnetic metal ion, an ultrasound contrast agent, or a diagnostic radionuclide. 
     
     
         39 . The diagnostic imaging agent of  claim 38 , wherein the paramagnetic metal ion or the diagnostic radionuclide is complexed with a chelator. 
     
     
         40 . The diagnostic imaging agent of  claim 33 , wherein the detectable label is an ultrasound contrast agent or a diagnostic radionuclide, wherein the diagnostic radionuclide is complexed with a chelator. 
     
     
         41 . The diagnostic imaging agent of  claim 33 , wherein the detectable label is detectable by optical imaging, acousto-optical imaging or sonoluminescent imaging. 
     
     
         42 . The diagnostic imaging agent of  claim 41 , wherein the detectable label is a photolabel. 
     
     
         43 . The diagnostic imaging agent of  claim 42 , wherein the photolabel is an optical dye or bioluminescent molecule. 
     
     
         44 . The diagnostic imaging agent of  claim 33 , further comprising a linker. 
     
     
         45 . A method of detecting cMet or a complex comprising cMet and HGF in a subject, the method comprising:
 (a) administering to the subject the diagnostic imaging agent of  claim 33 ; and,   (b) detecting the diagnostic imaging agent in the subject.   
     
     
         46 . The method of  claim 45 , further comprising imaging a portion of the subject. 
     
     
         47 . The method of  claim 46 , further comprising constructing an image. 
     
     
         48 . The method of  claim 47 , wherein the image is constructed using ultrasound energy, radioimaging or light imaging. 
     
     
         49 . The diagnostic imaging agent of  claim 37 , wherein the detectable label is an enzyme, a fluorescent compound, a liposome, an optical dye, a paramagnetic metal ion, an ultrasound contrast agent, or a diagnostic radionuclide. 
     
     
         50 . The diagnostic imaging agent of  claim 49 , wherein the paramagnetic metal ion, or the diagnostic radionuclide is complexed with a chelator. 
     
     
         51 . The diagnostic imaging agent of  claim 37 , wherein the detectable label is an ultrasound contrast agent or a diagnostic radionuclide, wherein the diagnostic radionuclide is complexed with a chelator. 
     
     
         52 . The diagnostic imaging agent of  claim 37 , wherein the detectable label is detectable by optical imaging, acousto-optical imaging or sonoluminescent imaging. 
     
     
         53 . The diagnostic imaging agent of  claim 52 , wherein the detectable label is a photolabel. 
     
     
         54 . The diagnostic imaging agent of  claim 53 , wherein the photolabel is an optical dye or bioluminescent molecule. 
     
     
         55 . The diagnostic imaging agent of  claim 37 , further comprising a linker. 
     
     
         56 . A method of detecting cMet or a complex comprising cMet and HGF in a subject, the method comprising:
 (a) administering to the subject the diagnostic imaging agent of  claim 37 ; and,   (b) detecting the diagnostic imaging agent in the subject.   
     
     
         57 . The method of  claim 56 , further comprising imaging a portion of the subject. 
     
     
         58 . The method of  claim 56 , further comprising constructing an image. 
     
     
         59 . The method of  claim 58 , wherein the image is constructed using ultrasound energy, radioimaging or light imaging.