Lox and loxl2 inhibitors and uses thereof

Abstract

The present application relates to anti-LOX and anti-LOXL2 antibodies and their use in purification, diagnostic and therapeutic methods. Antibodies include monoclonal antibodies, humanized antibodies and functional fragments thereof. Anti-LOX and anti-LOXL2 antibodies can be used to identify and treat conditions such as a fibrotic condition, angiogenesis, or to prevent a transition from an epithelial cell state to a mesenchymal cell state.

1 - 65 . (canceled) 
     
     
         66 . A light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 74. 
     
     
         67 . The light chain polypeptide of  claim 66 , comprising the amino acid sequence of SEQ ID NO:71. 
     
     
         68 . A nucleic acid comprising a coding sequence for the light chain polypeptide of  claim 66 . 
     
     
         69 - 70 . (canceled) 
     
     
         71 . An antibody comprising the light chain polypeptide of  claim 66 . 
     
     
         72 . A heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 79. 
     
     
         73 . The heavy chain polypeptide of  claim 72 , comprising the amino acid sequence of SEQ ID NO:76. 
     
     
         74 . A nucleic acid comprising a sequence coding for the heavy chain polypeptide of  claim 72 . 
     
     
         75 - 76 . (canceled) 
     
     
         77 . An antibody comprising the heavy chain polypeptide of  claim 72 . 
     
     
         78 . An antibody comprising:
 a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 74; and   a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 79.   
     
     
         79 . A polypeptide comprising the amino acid sequence of SEQ ID NO:82. 
     
     
         80 . A cell expressing a polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 71, 74, 76, and 79. 
     
     
         81 . A method of reducing growth of a tumor in a subject, the method comprising:
 administering to the subject an antibody comprising the amino acid sequences of SEQ ID NOs: 74 and 79.   
     
     
         82 . A method of inhibiting angiogenesis in a subject, comprising: administering to the subject an antibody comprising the amino acid sequences of SEQ ID NOs: 74 and 79. 
     
     
         83 . A method of inhibiting a fibrotic disease in a subject, comprising:
 administering to the subject an antibody comprising the amino acid sequences of SEQ ID NOs: 74 and 79.   
     
     
         84 . A diagnostic method, comprising: determining a level of LOX and/or LOXL2 in a sample from a subject by contacting said sample with an antibody comprising the amino acid sequences of SEQ ID NOs: 74 and 79, wherein a difference in level of LOX and/or LOXL2 in the sample in comparison with a reference sample indicates the presence or increase of a tumor or metastasis. 
     
     
         85 . A composition, comprising: an antibody comprising the amino acid sequences of SEQ ID NOs: 74 and 79 and a pharmaceutically acceptable carrier or excipient. 
     
     
         86 . A kit for treating a condition associated with LOX or LOXL2, comprising:
 the composition of  claim 85 .