Substances

Abstract

The present invention provides a homologue to heparanase which is present in three splice variants.

1 . A polypeptide which:
 a) comprises the amino acid sequence of Seq. ID No 2, starting at residue 1, 2, 11, 12 or 43;   b) comprises the amino acid sequence of Seq. ID No 4, starting at residue 1, 2, 11, 12 or 43;   c) comprises the amino acid sequence of Seq. ID No 6, starting at residue 1, 2, 11, 12 or 43;   d) is a derivative of at least 40 amino acids in length having one or more amino acid substitutions, deletions or insertions relative to a polypeptide as defined in a), b) or c) above, said derivative being at least 80% identical to an amino acid sequence of said polypeptide; or   e) is a fragment of a polypeptide as defined in a), b) or c) above, which is at least twenty five amino acids in length, or a fragment of a polypeptide as defined in d) above, which is at least forty amino acids in length.   
     
     
         2 . A fragment of a polypeptide according to  claim 1  comprising the sequence: 
       
         
           
                 
                 
                 
               
                     
                   QPIRIYSRASLYGPNIGRPRKNV; 
                   (Seq. ID No 9) 
                 
                     
                     
                 
                     
                   DTLSDQIRKIQKVVNTYTPGKKIW; 
                   (Seq. ID No 10) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   AVHVAGLQRKPRPGRVIRDKLRIYA. 
                   (Seq. ID No 11) 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . A polypeptide according to  claim 1  or  2  for use in the treatment of a human or non-human animal or for use in diagnosis. 
     
     
         4 . A pharmaceutical composition comprising a polypeptide according to  claim 1  or  2  and a pharmaceutically acceptable carrier. 
     
     
         5 . A kit comprising a composition according to  claim 4 , optionally including instructions for the use of said composition. 
     
     
         6 . An antibody or a derivative thereof which binds to a polypeptide according to  claim 1  or  2 . 
     
     
         7 . An antibody according to  claim 6  which is a monoclonal antibody. 
     
     
         8 . A method for the treatment and/or prophylaxis of a condition/disease associated with abnormal levels of the polypeptide according to  claim 1  comprising administering a therapeutically effective amount of an antibody according to  claim 6  or  7  to a subject in need thereof. 
     
     
         9 . A nucleic acid molecule comprising or consisting of:
 (i) a sequence which codes for a polypeptide of  claim 1  or  2 ; or   (ii) a sequence which is complementary to a sequence of (i).   
     
     
         10 . A nucleic acid molecule according to  claim 9 , the nucleic acid molecule comprising or consisting of a sequence which is a DNA sequence shown at residues 601, 604, 631, 634 or 727 to 2376 of Seq. ID No 1, residues 601, 604, 631, 634 or 727 to 2202 of Seq. ID No 3 or at residues 601, 604, 631, 634 or 727 to 2040 of Seq. ID No 5 or its RNA equivalent, including or excluding all or part of the sequence which is 5′ or 3′ thereto. 
     
     
         11 . A vector comprising a nucleic acid molecule according to  claim 9  or  10 . 
     
     
         12 . A vector according to  claim 11 , further comprising nucleic acid encoding one or more of the following: promoters, enhancers, signal sequences, leader sequences, translation start and stop signals, DNA stability controlling regions, or a fusion partner. 
     
     
         13 . The use of a vector according to  claim 11  or  12  in the transformation or transfection of a prokaryotic or eukaryotic host. 
     
     
         14 . A host cell transformed with a vector according to  claim 11  or  12 . 
     
     
         15 . A method for obtaining a polypeptide according to  claim 1 , comprising incubating a host according to  claim 14  under conditions causing expression of the polypeptide and then purifying said polypeptide. 
     
     
         16 . A method for the identification of an agent that modulates the activity of a polypeptide according to  claim 1 , comprising comparing the activity of said polypeptide in the presence of a test agent with the activity of said polypeptide in the absence of the test agent. 
     
     
         17 . A method for the treatment and/or prophylaxis of a condition/disease associated with abnormal levels of the polypeptide according to  claim 1  comprising administering a therapeutically effective amount of an agent which modulates the activity of a polypeptide according to  claim 1  to a subject in need thereof. 
     
     
         18 . The method according to  claim 8  or  17  where the condition/disease is selected from: cancer, metastasised cancer, CNS and neurodegenerative diseases, inflammation and cardiovascular diseases, autoimmune diseases such as psoriasis, lupus erythematosus and allografts, inflammatory diseases such as arthritis including rheumatoid- and osteoarthritis, asthma, vascular restenosis, atherosclerosis, fibro-proliferative disorders, Alzheimer's Disease, diabetic retinopathy and wound healing.