Novel hepatoma-derived growth factor-like proteins, polynucleotides encoding them and methods of use

Abstract

The present invention provides HDGFX, a novel isolated polypeptide, as well as a polynucleotide encoding HDGFX and antibodies that immunospecifically bind to HDGFX or any derivative, variant, mutant, or fragment of the HDGFX polypeptide, polynucleotide or antibody. The invention additionally provides methods in which the HDGFX polypeptide, polynucleotide and antibody are used in detection and treatment of a broad range of pathological states, as well as to other uses.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule encoding HDGFX, said molecule comprising a nucleotide sequence encoding a polypeptide having an amino acid sequence that is at least 85% identical to SEQ ID NO:2, or the complement of said nucleic acid molecule.  
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein said nucleotide sequence encodes a polypeptide of SEQ ID NO:2, or the complement of said nucleic acid molecule.  
     
     
         3 - 27 . Canceled.  
     
     
         28 . The isolated nucleic acid molecule of  claim 1  encoding a mature form of the polypeptide having an amino acid sequence of SEQ ID NO:2.  
     
     
         29 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule is naturally occurring.  
     
     
         30 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence of SEQ ID NO1.  
     
     
         31 . The isolated nucleic acid molecule of  claim 1 , said molecule hybridizing under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule comprising the sequence of nucleotides of SEQ ID NO:1, or the complement of said nucleic acid molecule.  
     
     
         32 . The isolated nucleic acid molecule of  claim 1 , said molecule encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence of SEQ ID NO:2.  
     
     
         33 . An oligonucleotide of the nucleic acid molecule of  claim 1 , said nucleic acid molecule less than 100 nucleotides in length and comprising at least 6 contiguous nucleotides of SEQ ID NO:1, or a complement thereof.  
     
     
         34 . A nucleic acid vector comprising the nucleic acid molecule of  claim 1 .  
     
     
         35 . The nucleic acid vector of  claim 34 , wherein said vector is an expression vector.  
     
     
         36 . The vector of  claim 34 , further comprising at least one regulatory element operably linked to said nucleic acid molecule.  
     
     
         37 . A host cell comprising the isolated nucleic acid molecule of  claim 1 .  
     
     
         38 . A host cell comprising the vector of  claim 34 .  
     
     
         39 . A method of producing an isolated polypeptide at least 80% identical to a polypeptide selected from the group consisting of: 
 a) a polypeptide comprising an amino acid sequence of SEQ ID NO:2;    b) a fragment of a polypeptide comprising an amino acid sequence of SEQ ID NO:2,wherein the fragment comprises at least 6 contiguous amino acids of SEQ ID NO:2;    c) a derivative of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;    d) an analog of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;    c) a homolog of a polypeptide comprising an amino acid sequence of SEQ ID NO:2; and    f) a naturally occurring allelic variant of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;    wherein the polypeptide is encoded by a nucleic acid molecule that hybridizes to a nucleic acid molecule of SEQ ID NO:1 under stringent conditions, said method comprising the step of culturing the host cell comprising the isolated nucleic acid molecule of  claim 1  under conditions in which the nucleic acid molecule is expressed.    
     
     
         40 . The method of  claim 39  wherein the cell is a bacterial cell.  
     
     
         41 . The method of  claim 39  wherein the cell is an insect cell.  
     
     
         42 . The method of  claim 39  wherein the cell is a yeast cell.  
     
     
         43 . The method of  claim 39  wherein the cell is a mammalian cell.  
     
     
         44 . A composition comprising a therapeutically or prophylactically effective amount of a composition selected from the group consisting of: 
 a) an isolated nucleic acid molecule encoding HDGFX, said molecule comprising a nucleotide sequence encoding a polypeptide having a sequence that is at least 85% identical to SEQ ID NO:2, or the complement of said nucleic acid molecule;    b) an isolated polypeptide at least 80% identical to a polypeptide selected from the group consisting of: 
 i) a polypeptide comprising an amino acid sequence of SEQ ID NO:2;  
 ii) a fragment of a polypeptide comprising an amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 6 contiguous amino acids of SEQ ID NO:2;  
 iii) a derivative of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;  
 iv) an analog of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;  
 v) a homolog of a polypeptide comprising an amino acid sequence of SEQ ID NO:2; and  
 vi) a naturally occurring allelic variant of a polypeptide comprising an amino acid sequence of SEQ ID NO:2; wherein the polypeptide is encoded by a nucleic acid molecule that hybridizes to a nucleic acid molecule of SEQ ID NO:1 under stringent conditions; and  
   c) an antibody that selectively binds to the polypeptide of step (b), and fragments, homologs, analogs, and derivatives of said antibody;    and a pharmaceutically acceptable carrier.    
     
     
         45 . A kit comprising in one or more containers, a therapeutically or prophylactically effective amount of the composition of claim  19 .  
     
     
         46 . The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a proliferative disorder, a differentiative disorder, and a tumorigenic disorder, wherein said therapeutic is selected from the group consisting of: 
 a) an isolated nucleic acid molecule encoding HDGFX, said molecule comprising a nucleotide sequence encoding a polypeptide having a sequence that is at least 85% identical to SEQ ID NO:2, or the complement of said nucleic acid molecule;    b) an isolated polypeptide at least 80% identical to a polypeptide selected from the group consisting of: 
 i) a polypeptide comprising an amino acid sequence of SEQ ID NO:2;  
 ii) a fragment of a polypeptide comprising an amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 6 contiguous amino acids of SEQ ID NO:2;  
 iii) a derivative of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;  
 iv) an analog of a polypeptide comprising an amino acid sequence of SEQ ID NO:2;  
 v) a homolog of a polypeptide comprising an amino acid sequence of SEQ ID NO:2; and  
 vi) a naturally occurring allelic variant of a polypeptide comprising an amino acid sequence of SEQ ID NO:2; wherein the polypeptide is encoded by a nucleic acid molecule that hybridizes to a nucleic acid molecule of SEQ ID NO:1 under stringent conditions; and  
   c) an antibody that selectively binds to the polypeptide of step (b), and fragments, homologs, analogs, and derivatives of said antibody.