Novel growth factor and a genetic sequence encoding same

Abstract

The present invention relates generally to an isolated molecule having vascular endothelial growth factor-like properties and to a genetic sequence encoding same. The molecule will be useful in the development of a range of therapeutics and diagnostics useful in the treatment, prophylaxis and/or diagnosis of conditions requiring enhanced or diminished vasculature and/or vascular permeability. The molecule of the present invention is also a useful effector of primary and central neurons and is capable of inducing astroglial proliferation.

1 . A biologically isolated proteinaceous molecule having the following characteristics: 
 (i) comprises an amino acid sequence having at least about 15% similarity but at least about 5% dissimilarity to the sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one property in common with vascular endothelial growth factor (VEGF).    
     
     
         2 . A proteinaceous molecule according to  claim 1  wherein the molecule exhibits at least one of the following properties. 
 (i) an ability to induce vascular endothelial cells;  
 (ii) an ability to interact with flt-1/flk-1 family of receptors; and/or  
 (iii) an ability to induce cell migration, cell survival and/or an increase in intracellular lavels of alkaline phosphatase.  
 
     
     
         3 . A proteinaceous molecule according to  claim 1  or  2  wherein said molecule has the capacity to induce astroglial proliferation.  
     
     
         4 . A proteinaceous molecule according to  claim 1  wherein said molecule is of human origin.  
     
     
         5 . A proteinaceous molecule according to  claim 1  wherein said molecule is of non-human origin.  
     
     
         6 . A proteinaceous molecule according to  claim 5  wherein said molecule is of livestock animal, companion animal, laboratory test animal, avian, fish or reptilian origin.  
     
     
         7 . A proteinaceous molecule according to  claim 5  wherein said molecule is encoded by a gene located at chromosome 11q13.  
     
     
         8 . A proteinaceous molecule according to  claim 1  wherein the percentage similarity to SEQ ID NO:2 is at least about 30%.  
     
     
         9 . A proteinaceous molecule according to  claim 1  wherein the percentage similarity to SEQ ID NO:2 is at least about 40%.  
     
     
         10 . A proteinaceous molecule according to  claim 1  wherein the percentage similarity to SEQ ID NO:2 is at least about 60-70%.  
     
     
         11 . A proteinaceous molecule according to  claim 1  comprising a sequence of amino acids as set forth in SEQ ID NO:4 or a part, fragment, derivative or analogue thereof.  
     
     
         12 . A proteinaceous molecule according to  claim 1  comprising an amino acid sequence substantially set forth in SEQ ID NO:6 or a part, fragment, derivative or analogue thereof.  
     
     
         13 . A proteinaceous molecule according to  claim 1  comprising an amino acid sequence substantially set forth in SEQ ID NO:8 or a part, fragment, derivative or analogue thereof.  
     
     
         14 . A proteinaceous molecule according to  claim 1  comprising an amino acid sequence substantially set forth in SEQ ID NO:10 or a part, fragment, derivative or analogue thereof.  
     
     
         15 . A recombinant molecule having the following characteristics: 
 (i) an amino acid sequence substantially as set forth in SEQ ID NO:4 or having at least about 15% similarity to but at least about 5% dissimilarity to the amino acid sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one biological property in common with VEGF.    
     
     
         16 . A recombinant molecule having the following characteristics: 
 (i) an amino acid sequence substantially as set forth in SEQ ID NO:6 or having at least about 15% similarity to but at least about 5% dissimilarity to the amino acid sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one biological property in common with VEGF.    
     
     
         17 . A recombinant molecule having the following characteristics: 
 (i) an amino acid sequence substantially as set forth in SEQ ID NO:8 or having at least about 15% similarity to but at least about 5% dissimilarity to the amino acid sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one biological property in common with VEGF.    
     
     
         18 . A recombinant molecule having the following characteristics: 
 (i) an amino acid sequence substantially as set forth in SEQ ID NO:10 or having at least about 15% similarity to but at least about 5% dissimilarity to the amino acid sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one biological property in common with VEGF.    
     
     
         19 . A recombinant molecule according to  claim 15  or 16 or 17 or 18 having at least one of the following properties: 
 (a) an ability to induce vascular endothelial cells;  
 (b) an ability to interact with ftl1/flki family of receptors;  
 (c) an ability to induce cell migration, cell survival and/or increase intracellular levels of alkaline phosphatase.  
 
     
     
         20 . A recombinant molecule according to  claim 15  or  16  or  17  or  18  having the capacity to induce astroglial proliferation.  
     
     
         21 . A recombinant molecule according to  claim 20  wherein the molecule comprises an amino acid sequence substantially as set forth in SEQ ID NO:6.  
     
     
         22 . A peptide fragment corresponding to a portion of the amino acid sequence set forth in SEQ ID NO:4 or a derivative or chemical equivalent thereof.  
     
     
         23 . A peptide fragment according to  claim 22  having the sequence set forth in SEQ ID NO:6 or a chemical equivalent thereof.  
     
     
         24 . A peptide fragment according to  claim 22  having the sequence set forth in SEQ ID NO:8 or a chemical equivalent thereof.  
     
     
         25 . A peptide fragment according to  claim 22  having the sequence set forth in SEQ ID NO:10 or a chemical equivalent thereof.  
     
     
         26 . A nucleic acid molecule comprising a sequence of nucleotides or complementary to a sequence encoding a proteinaceous molecule having the following characteristics: 
 (i) comprises an amino acid sequence having at least about 15% similarity but at least about 5% dissimilarity to the sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one property in common with vascular endothelial growth factor (VEGF).    
     
     
         27 . A nucleic acid molecule according to  claim 26  wherein the proteinaceous molecule exhibits at least one of the following properties: 
 (i) an ability to induce vascular endothelial cells;  
 (ii) an ability to interact with flt-1/flk-1 family of receptors; and/or  
 (iii) an ability to induce cell migration, cell survival and/or an increase in intracellular lavels of alkaline phosphatase.  
 
     
     
         28 . A nucleic acid molecule according to  claim 27  wherein the proteinaceous molecule has the capacity to induce astroglial proliferation.  
     
     
         29 . A nucleic acid molecule according to  claim 28  wherein said molecule encodes an amino acid sequence substantially as set forth in SEQ ID NO:6.  
     
     
         30 . A nucleic acid molecule according to  claim 1  wherein said molecule is of human origin.  
     
     
         31 . A nucleic acid molecule according to  claim 1  wherein the percentage similarity to SEQ ID NO:2 is at least about 30%.  
     
     
         32 . A nucleic acid molecule according to  claim 26  comprising a nucleotide sequence substantially as set forth in SEQ ID NO:3 or having at least 15% similarity thereto or capable of hybridising under low stringency conditions to a reverse complement of the nucleotide sequence as set forth in SEQ ID NO:3 provided that the nucleotide sequence has at least 15% similarity but at least 30% dissimilarity to the nucleotide sequence set forth in SEQ ID NO:3.  
     
     
         33 . A nucleic acid molecule according to  claim 26  encoding a murine homologue of human VEGF and comprising a nucleotide sequence substantially as set forth in FIG. 9.  
     
     
         34 . A pharmaceutical composition comprising a proteinaceous molecule according to  claim 1  or  2  or  3  or  11  and one or more pharmaceutically acceptable carriers and/or diluents.  
     
     
         35 . A method for preparing a recombinant molecule having the following characteristics: 
 (i) comprises an amino acid sequence having at least about 15% similarity but at least about 5% dissimilarity to the sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one property in common with vascular endothelial growth factor (VEGF),    said method comprising expressing a nucleic acid molecule encoding said recombinant molecule by a suitable host grown under conditions effective to synthesise said. recombinant molecule and then isolating said molecule.    
     
     
         36 . A method according to  claim 35  wherein the nucleic acid molecule comprises a sequence of nucleotides as set forth in SEQ ID NO:3 or having at least 15% similarity thereto or is capable of hybridising under low stringency conditions to a reverse complement of the nucleotide sequence as set forth in SEQ ID NO:3 provided that the nucleotide sequence has at least 15% similarity but at least 30% dissimilarity to the nucleotide sequence set forth in SEQ ID NO:3.  
     
     
         37 . A method of inducing astroglial proliferation in a mammal, said method comprising administering to said mammal an effective amount of a recombinant proteinaceous molecule having the characteristics: 
 (i) comprises an amino acid sequence having at least about 15% similarity but at least about 5% dissimilarity to the sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one property in common with vascular endothelial growth factor (VEGF),    said administration being for a time and under conditions sufficient to induce astroglial proliferation.    
     
     
         38 . A method according to  claim 3   7  wherein the recombinant proteinaceous molecule comprises an amino acid sequence substantially as set forth in SEQ ID NO:3 or is a derivative thereof.  
     
     
         39 . A method according to  claim 37  wherein the recombinant proteinaceous molecule comprises an amino acid sequence substantially as set forth in SEQ ID NO:6 or is a derivative thereof.  
     
     
         40 . A method of promoting neuronal survival and/or proliferation in a mammal, said method comprising administering to said mammal an effective amount of a recombinant proteinaceous molecule having the characteristics: 
 (i) comprises an amino acid sequence having at least about 15% similarity but at least about 5% dissimilarity to the sequence set forth in SEQ ID NO:2;    (ii) exhibits at least one property in common with vascular endothelial growth factor (VEGF),    said administration being for a time and under conditions sufficient to induce astroglial proliferation.    
     
     
         41 . A method according to claim  40  wherein the recombinant proteinaceous molecule comprises an amino acid sequence substantially as set forth in SEQ ID NO:3 or is a derivative thereof.  
     
     
         41 . A method according to claim  40  wherein the recombinant proteinaceous molecule comprises an amino acid sequence substantially as set forth in SEQ ID NO:6 or is a derivative thereof.