Anti-axl antibodies

Abstract

Antibodies which specifically bind to the Axl protein are described. Also disclosed are methods for the production and use of the anti-Axl antibodies.

1 - 60 . (canceled) 
     
     
         61 . An antibody that binds Axl and which comprises:
 a. a heavy chain variable region (VH) domain comprising a VH complementarity determining region (VH CDR) 1, a VH CDR2, and a VH CDR3 of SEQ ID NO: 3 as determined by Kabat; and   b. a light chain variable region (VL) domain comprising a VL complementarity determining region (VL CDR) 1, a VL CDR2, and a VL CDR3 of SEQ ID NO: 4 as determined by Kabat.   
     
     
         62 . The antibody according to  claim 61 , wherein the antibody competes for binding to Axl with an Axl binding domain of an antibody comprising a VH domain of SEQ ID NO: 3 and a VL domain of SEQ ID NO: 4. 
     
     
         63 . The antibody according to  claim 61 , comprising the VH domain of SEQ ID NO: 3. 
     
     
         64 . The antibody according to  claim 61 , comprising the VL domain of SEQ ID NO: 4. 
     
     
         65 . The antibody according to  claim 61 , that binds Axl with affinity equal to or better than the affinity of an Axl antigen-binding site formed by a VH domain of SEQ ID NO: 3 and a VL domain of SEQ ID NO: 4, wherein the affinity of the antibody and the affinity of the antigen-binding site being are determined under the same conditions. 
     
     
         66 . The antibody according to  claim 61 , wherein the antibody comprises an antibody constant region. 
     
     
         67 . The antibody according to  claim 61 , wherein the antibody is a whole antibody or an antigen-binding antibody fragment selected from the group consisting of aFv, scFv, dsFv, Fd, Fab, F(ab′)2, minibody, diabody, single-chain diabody, tandem scFv, bi-body, tri-body, and kappa(lambda)-body. 
     
     
         68 . The antibody according to  claim 61 , wherein the antibody is a humanized antibody. 
     
     
         69 . The antibody according to  claim 61 , wherein the antibody is conjugated to a detectable label, enzyme, or toxin, optionally via a peptidyl bond or linker. 
     
     
         70 . The antibody according to  claim 69 , wherein the toxin is MMAE or MMAF, or the detectable label is FITC. 
     
     
         71 . An isolated nucleic acid which comprises a nucleotide sequence encoding an antibody or antibody VH or VL domain of an antibody according to  claim 61 . 
     
     
         72 . A host cell transformed with the isolated nucleic acid according to  claim 71 . 
     
     
         73 . A method of producing an antibody or an antibody VH or VL domain, the method comprising culturing host cells according to  claim 72  under conditions for production of said antibody or antibody VH or VL domain. 
     
     
         74 . A method of treatment of a proliferative disease or disorder, the method comprising administering an antibody according to  claim 61  to a subject in need thereof. 
     
     
         75 . The method of  claim 74 , wherein the proliferative disease is characterized by overexpression of Axl. 
     
     
         76 . The method of  claim 74 , wherein the proliferative disease is cancer. 
     
     
         77 . The method of  claim 74 , wherein the proliferative disease is a cancer that is a lymphoma or a leukemia. 
     
     
         78 . The method of  claim 74 , wherein the proliferative disease is acute myeloid leukemia. 
     
     
         79 . The method of  claim 74 , wherein the proliferative disease is a solid tumour cancer selected from the group consisting of lung, breast, and prostate cancer. 
     
     
         80 . The method of  claim 74 , wherein the method comprises administering a second therapeutic agent.