METH1 and METH2 Polynucleotides and Polypeptides

Abstract

The present invention relates to novel anti-angiogenic proteins, related to thrombospondin. More specifically, isolated nucleic acid molecules are provided encoding human METH1 and METH2. METH1 and METH2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic methods for the prognosis of cancer and therapeutic methods for treating individuals in need of an increased amount of METH1 or METH2. Also provided are methods for inhibiting angiogenesis using METH1 or METH2.

1 . An isolated nucleic acid molecule comprising a polynucleotide selected from the group consisting of:
 (a) a polynucleotide encoding amino acids 1 to 950 in SEQ ID NO:2;   (b) a polynucleotide encoding amino acids 2 to 950 in SEQ ID NO:2;   (c) a polynucleotide encoding amino acids 29 to 950 in SEQ ID NO:2;   (d) a polynucleotide encoding amino acids 30 to 950 in SEQ ID NO:2;   (e) a polynucleotide encoding the complete amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209581;   (f) a polynucleotide encoding the mature amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209581;   (g) a polynucleotide encoding amino acids 1 to 968 of SEQ ID NO:125;   (h) a polynucleotide encoding amino acids 235 to 459 in SEQ ID NO:2;   (i) a polynucleotide encoding amino acids 460 to 544 in SEQ ID NO:2;   (j) a polynucleotide encoding amino acids 545 to 598 in SEQ ID NO:2;   (k) a polynucleotide encoding amino acids 841 to 894 in SEQ ID NO:2;   (l) a polynucleotide encoding amino acids 895 to 934 in SEQ ID NO:2;   (m) a polynucleotide encoding amino acids 536 to 613 in SEQ ID NO:2; and   (n) a polynucleotide encoding amino acids 549 to 563 in SEQ ID NO:2.   
     
     
         2 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector in operable linkage to a promoter. 
     
     
         3 . A recombinant vector produced by the method of  claim 2 . 
     
     
         4 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 3  into a host cell. 
     
     
         5 . A recombinant host cell produced by the method of  claim 4 . 
     
     
         6 . A recombinant method for producing a polypeptide, comprising culturing the recombinant host cell of  claim 5  under conditions such that said polypeptide is expressed and recovering said polypeptide. 
     
     
         7 . (canceled) 
     
     
         8 . An isolated nucleic acid molecule comprising a polynucleotide selected from the group consisting of:
 (a) a polynucleotide encoding amino acids 1 to 890 in SEQ ID NO:4;   (b) a polynucleotide encoding amino acids 2 to 890 in SEQ ID NO:4;   (c) a polynucleotide encoding amino acids 24 to 890 in SEQ ID NO:4;   (d) a polynucleotide encoding amino acids 112 to 890 in SEQ ID NO:4;   (e) a polynucleotide encoding the complete amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209582;   (f) a polynucleotide encoding the mature amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209582;   (g) a polynucleotide encoding amino acids 214 to 439 in SEQ ID NO:4;   (h) a polynucleotide encoding amino acids 440 to 529 in SEQ ID NO:4;   (i) a polynucleotide encoding amino acids 530 to 583 in SEQ ID NO:4;   (j) a polynucleotide encoding amino acids 837 to 890 in SEQ ID NO:4;   (k) a polynucleotide encoding amino acids 280 to 606 in SEQ ID NO:4; and   (l) a polynucleotide encoding amino acids 529 to 548 in SEQ ID NO:4.   
     
     
         9 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 8  into a vector in operable linkage to a promoter. 
     
     
         10 . A recombinant vector produced by the method of  claim 9 . 
     
     
         11 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 10  into a host cell. 
     
     
         12 . A recombinant host cell produced by the method of  claim 11 . 
     
     
         13 . A recombinant method for producing a polypeptide, comprising culturing the recombinant host cell of  claim 12  under conditions such that said polypeptide is expressed and recovering said polypeptide. 
     
     
         14 . (canceled) 
     
     
         15 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
 (a) amino acids 1 to 950 in SEQ ID NO:2;   (b) amino acids 2 to 950 in SEQ ID NO:2;   (c) amino acids 29 to 950 in SEQ ID NO:2;   (d) amino acids 30 to 950 in SEQ ID NO:2;   (e) the complete amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209581;   (f) the a mature amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209581;   (g) amino acids 1 to 968 of SEQ ID NO:125;   (h) amino acids 235 to 459 in SEQ ID NO:2;   (i) amino acids 460 to 544 in SEQ ID NO:2;   (j) amino acids 545 to 598 in SEQ ID NO:2;   (k) amino acids 841 to 894 in SEQ ID NO:2;   (l) amino acids 895 to 934 in SEQ ID NO:2;   (m) amino acids 536 to 613 in SEQ ID NO:2; and   (n) amino acids 549 to 563 in SEQ ID NO:2.   
     
     
         16 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
 (a) amino acids 1 to 890 in SEQ ID NO:4;   (b) amino acids 2 to 890 in SEQ ID NO:4;   (c) amino acids 24 to 890 in SEQ ID NO:4;   (d) amino acids 112 to 890 in SEQ ID NO:4;   (e) the complete amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209582;   (f) the mature amino acid sequence encoded by the cDNA clone contained in ATCC™ Deposit No. 209582;   (g) amino acids 214 to 439 in SEQ ID NO:4;   (h) amino acids 440 to 529 in SEQ ID NO:4;   (i) amino acids 530 to 583 in SEQ ID NO:4;   (j) amino acids 837 to 890 in SEQ ID NO:4;   (k) amino acids 280 to 606 in SEQ ID NO:4; and   (l) amino acids 529 to 548 in SEQ ID NO:4.   
     
     
         17 - 18 . (canceled) 
     
     
         19 . A method for inhibiting angiogenesis in an individual, comprising administering an effective amount of METH1 or METH2. 
     
     
         20 . The method of  claim 19 , wherein said method is used to treat cancer, benign tumors, an ocular angiogenic disease, rheumatoid arthritis, psoriasis, delayed wound healing, endometriosis, vasculogenesis, granulations, hypertrophic scars, nonunion fractures, scleroderma, trachoma, vascular adhesions, myocardial angiogenesis, coronary collaterals, cerebral collaterals, arteriovenous malformations, ischemic limb angiogenesis, Osler-Webber Syndrome, plaque neovascularization, telangiectasia, hemophiliac joints, angiofibroma, fibromuscular dysplasia, wound granulation, Crohn's disease or atherosclerosis. 
     
     
         21 . The method of  claim 19 , wherein said method is used in birth control. 
     
     
         22 . The method of  claim 19 , further comprising administering another angiogenic compound. 
     
     
         23 . The method of  claim 19 , wherein said METH1 or METH2 is administered by cell or gene therapy means wherein cells have been modified to produce and secrete METH1 or METH2.