Anti- egfr conformational single domain antibodies and uses thereof

Abstract

The present invention relates to anti-Epidermal Growth Factor Receptor (EGFR) conformational single domain antibodies and uses thereof in particular in the therapeutic and diagnostic field.

1 - 23 . (canceled) 
     
     
         24 . A nucleic acid encoding for a an anti-Epidermal Growth Factor Receptor (EGFR) single domain antibody, comprising:
 i) a CDR1 having a sequence set forth as SEQ ID NO: 1, a CDR2 having a sequence set forth as SEQ ID NO:2 and a CDR3 having a sequence set forth as SEQ ID NO:3;   ii) a CDR1 having a sequence set forth as SEQ ID NO:5, a CDR2 having a sequence set forth as SEQ ID NO:6 and a CDR3 having a sequence set forth as SEQ ID NO:7; or   iii) a CDR1 having a sequence set forth as SEQ ID NO:9, a CDR2 having a sequence set forth as SEQ ID NO:10 and a CDR3 having a sequence set forth as SEQ ID NO:11.   
     
     
         25 . A vector which comprise the nucleic acid of  claim 24 . 
     
     
         26 . A host cell which is transformed with the nucleic acid sequence of  claim 24 . 
     
     
         27 - 28 . (canceled) 
     
     
         29 . A method of treating a patient suffering from cancer comprising administering the patient with a therapeutically effective amount of
 an anti-Epidermal Growth Factor Receptor (anti-EGFR) single domain antibody comprising
 i) a CDR1 having a sequence set forth as SEQ ID NO: 1, a CDR2 having a sequence set forth as SEQ ID NO:2 and a CDR3 having a sequence set forth as SEQ ID NO:3; 
 ii) a CDR1 having a sequence set forth as SEQ ID NO:5, a CDR2 having a sequence set forth as SEQ ID NO:6 and a CDR3 having a sequence set forth as SEQ ID NO:7; or 
 iii) a CDR1 having a sequence set forth as SEQ ID NO:9, a CDR2 having a sequence set forth as SEQ ID NO:10 and a CDR3 having a sequence set forth as SEQ ID NO:11. 
   
     
     
         30 . The method of  claim 29  wherein the single domain antibody or polypeptide is administered in combination with a HER inhibitor. 
     
     
         31 . The method of  claim 30  wherein the HER inhibitor is cetuximab. 
     
     
         32 . (canceled) 
     
     
         33 . A method of diagnosing a disease, disorder or condition mediated by Epidermal Growth Factor Receptor (EGFR) comprising:
 i) obtaining a sample from the subject,   ii) contacting, in vitro, the sample with an anti-EGFR single domain antibody comprising
 a CDR1 having a sequence set forth as SEQ ID NO: 1, a CDR2 having a sequence set forth as SEQ ID NO:2 and a CDR3 having a sequence set forth as SEQ ID NO:3; 
 a CDR1 having a sequence set forth as SEQ ID NO:5, a CDR2 having a sequence set forth as SEQ ID NO:6 and a CDR3 having a sequence set forth as SEQ ID NO:7; or 
 a CDR1 having a sequence set forth as SEQ ID NO:9, a CDR2 having a sequence set forth as SEQ ID NO:10 and a CDR3 having a sequence set forth as SEQ ID NO:11, or a polypeptide comprising the single domain antibody; 
   iii) detecting binding of said single domain antibody or said polypeptide to said sample, and   iv) comparing the binding detected in step (iii) with a standard, wherein a difference between binding to said sample and said standard is diagnostic of the disease, disorder or condition characterized by EGFR.