Monoclonal antibody capable of binding to anexelekto, and use thereof

Abstract

The present inventors have succeeded in producing anti-AXL antibodies with specific functions. The present inventors also discovered that the antibodies have an angiogenesis-suppressive effect and an antitumor effect, and thereby completed the present invention. The anti-AXL antibodies of the present invention are useful as angiogenesis inhibitors and agents for inducing or inhibiting phosphorylation activity.

1 .- 46 . (canceled) 
     
     
         47 . A monoclonal antibody that binds to fibronectin type III domain 1 (FND1) of human anexelekto (AXL), has cell-growth-suppressive activity, and does not inhibit phosphorylation of AXL. 
     
     
         48 . The antibody according to  claim 47 , wherein the antibody suppresses cancer cell growth. 
     
     
         49 . The antibody according to  claim 47 , wherein the antibody has an activity that reduces AXL expression level. 
     
     
         50 . The antibody according to  claim 47 , wherein the antibody has angiogenesis inhibitory activity. 
     
     
         51 . The antibody of  claim 47 , wherein phosphorylation of AXL is induced by the binding of an AXL ligand to AXL. 
     
     
         52 . The antibody of  claim 48 , wherein phosphorylation of AXL is induced by the binding of an AXL ligand to AXL. 
     
     
         53 . A monoclonal antibody prepared using as an antigen a peptide consisting of the entire amino acid sequence of FND1 of human AXL or an amino acid sequence comprising five or more consecutive amino acids thereof, wherein the antibody has cell-growth-suppressive activity and does not inhibit phosphorylation of AXL. 
     
     
         54 . The antibody according to  claim 53 , wherein the antibody has an activity that reduces AXL expression level. 
     
     
         55 . The antibody according to  claim 53 , wherein the antibody has angiogenesis inhibitory activity. 
     
     
         56 . The antibody of  claim 53 , wherein phosphorylation of AXL is induced by the binding of an AXL ligand to AXL. 
     
     
         57 . A monoclonal anti-AXL antibody that competes for binding to the same epitope bound by either of
 (a) a monoclonal antibody (Ax284) produced from a hybridoma deposited with the IPOD, AIST, and assigned Accession No. FERM BP-10857; or   (b) a monoclonal antibody (Ax225) produced from a hybridoma deposited with the IPOD, AIST, and assigned Accession No. FERM BP-10854,   wherein the anti-AXL antibody blocks the binding of either Ax284 or Ax225 to AXL protein by at least 50% as compared to a control level of binding of either Ax284 or Ax225 to AXL protein in the absence of the anti-AXL antibody.   
     
     
         58 . A method of inhibiting angiogenesis in a subject, the method comprising administering to a subject in need thereof the antibody according to  claim 47 . 
     
     
         59 . A method of suppressing cell-growth in a subject, the method comprising administering to a subject in need thereof the antibody according to  claim 47 . 
     
     
         60 . The method of  claim 59 , wherein the antibody suppresses growth of a cancer cell. 
     
     
         61 . A method of treating cancer in a subject, the method comprising administering to a subject in need thereof the antibody according to  claim 47 . 
     
     
         62 . The method of  claim 61 , wherein the cancer is glioma, gastric cancer, endometrial cancer, or non-small-cell lung cancer. 
     
     
         63 . The method of  claim 61 , wherein the cancer is pancreatic cancer, gastric cancer, lung cancer, osteosarcoma, colon cancer, prostate cancer, melanoma, endometrial cancer, ovarian cancer, uterine leiomyoma, thyroid cancer, cancer stem cell, breast cancer, bladder cancer, renal cancer, glioma, neuroblastoma, or esophageal cancer. 
     
     
         64 . The method of  claim 63 , wherein the cancer is pancreatic adenocarcinoma or breast cancer. 
     
     
         65 . A method for reducing a level of AXL protein expression in a cell, the method comprising contacting a cell that expresses AXL protein with the antibody according to  claim 47 . 
     
     
         66 . The method of  claim 65 , wherein the cell is contacted with the antibody in vitro. 
     
     
         67 . The method of  claim 65 , wherein the cell is contacted with the antibody in vivo.