Human heparanase polypeptide and cDNA

Abstract

This invention relates to identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, a polypeptide of the present invention is “heparanase” obtainable from the human SV40-transformed fibroblast cell line ATCC CCL 75.1. The heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate into 6 to 20 kDa fragments.

1 . A polypeptide showing the biological activity of human heparanase obtainable from SV-40 transformed human fibroblast cell line ATCC CCL 75.1, or a functional derivative, a functional fragment or a functional analogue thereof.  
     
     
         2 . A polypeptide according to  claim 1  having the amino acid sequence of amino acids 158 to 543 set forth in SEQ ID NO 2.  
     
     
         3 . A polypeptide having the amino acid sequence of amino acids 1 to 543 set forth in SEQ ID NO 2:  
     
     
         4 . A polynucleotide comprising a nucleotide sequence encoding a polypeptide as defined in any of claims  1 ,  2  or  3 .  
     
     
         5 . A polynucleotide according to  claim 4  comprising the corresponding coding region contained in SEQ ID NO 1.  
     
     
         6 . A hybrid vector comprising a polynucleotide as defined in any of claims  4  or  5 , said polynucleotide being operably linked to suitable control sequences.  
     
     
         7 . A hybrid vector according to  claim 6 , said hybrid vector being an expression vector.  
     
     
         8 . A host cell transformed with a hybrid vector as defined in  claim 6  or  claim 7 .  
     
     
         9 . A process for the preparation of a polypeptide as defined in any of claims  1 ,  2  or  3 , said process comprising chemical synthesis, recombinant DNA technology or a combination of these methods.  
     
     
         10 . A process according to  claim 9 , said process comprising 
 (i) cultivation of a host cell transformed with a hybrid vector as defined in  claim 7  under conditions suitable for performing expression of the polypeptide, and    (ii) isolation of the thus-expressed polypeptide.    
     
     
         11 . A process for the preparation of a polynucleotide as defined in any of claims  4  or  5 , said process comprising chemical synthesis, recombinant DNA technology, polymerase chain reaction or a combination of these methods.  
     
     
         12 . An antibody which specifically recognizes and binds to a polypeptide as defined in any of claims  1 ,  2  or  3 .  
     
     
         13 . A polypeptide according to any of claims  1 ,  2  or  3  for use in medicine.  
     
     
         14 . Use of a polypeptide according to any of claims  1 ,  2  or  3  in the preparation of a pharmaceutical composition for the treatment of a disease resulting from shortage or lack of said polypeptide.  
     
     
         15 . A pharmaceutical composition suitable for administration to a warm-blooded animal inclusive man suffering from a disease resulting from shortage or lack of a polypeptide as defined in any of claims  1 ,  2  or  3 , said composition comprising a polypeptide as defined in any of claims  1 ,  2  or  3  together with at least one pharmaceutically acceptable carrier and/or excipient.  
     
     
         16 . A pharmaceutical composition suitable for administration to a warm-blooded animal inclusive man suffering from a disease resulting from excessive acitvity or overexpression of a polypeptide as defined in any of claims  1 ,  2  or  3 , said composition comprising an antibody as defined in  claim 12  together with at least one pharmaceutically acceptable carrier and/or excipient.  
     
     
         17 . A method of treatment of a disease resulting from shortage or lack of a polypeptide as defined in any of claims  1 ,  2  or  3 , said method comprising administration of a suitable amount of a polypeptide as defined in  claim 1 ,  2  or  3 .  
     
     
         18 . A method of treatment of a disease resulting from excessive acitvity or overexpression of a polypeptide as defined in any of claims  1 ,  2  or  3 , said method comprising administration of a suitable amount of an antibody as defined in  claim 12 .  
     
     
         19 . A method for identifying a substance capable of modulating the biological activity or expression of a polypeptide as defined in any of claims  1 ,  2  or  3  in a cell, said method comprising contacting a polypeptide as defined in any of claims  1 ,  2  or  3 , or a functional derivative, a functional fragment or a functional analogue thereof, or a cell capable of expressing a polypeptide as defined in any of claims  1 ,  2  or  3 , or a with at least one compound or agent whose ability to modulate the biological activity or expression of said polypeptide, functional derivative, functional fragment or functional analogue is sought to be investigated, and determining the change of the biological activity or the expression of said polypeptide, derivative or fragment caused by the substance.  
     
     
         20 . An assay system for testing a substance for its capability of binding to or having functional effects on a polypeptide as defined in any of claims  1 ,  2  or  3  of, said assay system comprising a polypeptide as defined in any of claims  1 ,  2  or  3 , or a functional derivative, a functional fragment or a functional analogue thereof, or a cell expressing such a polypeptide, functional derivative, functional fragment or functional analogue.  
     
     
         21 . A substance obtainable by a method as defined in  claim 19 , said substance being an agonist or an antagonist of a polypeptide as defined in any of claims  1 ,  2  or  3 .  
     
     
         22 . An oligonucleotide or a derivative thereof, or a salt thereof where salt-forming groups are present, which is specifically hybridizable with the nucleotide sequence set forth in SEQ ID NO 1, said oligonucleotide or derivative thereof comprising nucleoside units or analogues of nucleoside units sufficient in number and identity to allow such hybridization.  
     
     
         23 . Use of a polynucleotide as defined in  claim 4  in gene therapy.  
     
     
         24 . A method of diagnosis of conditions resulting from shortage or lack of a polypeptide as defined in any of claims  1 ,  2  or  3 , or resulting from excessive acitvity or overexpression of a polypeptide as defined in any of claims  1 ,  2  or  3 , said method comprising contacting cells or tissues or body fluids from an animal inclusive man suspected of having such a condition with an antibody as defined in  claim 12  or a substance as defined in claim  21 .