Human aminoacyl-tRNA synthetase polypeptides useful for the regulation of angiogenesis
Pharmaceutical compositions comprising truncated tryptophanyl-tRNA synthetase polypeptides useful for regulating angiogenesis an nucleic acids encoding such tRNA synthetase polypeptides are described. Methods of making and using such compositions are also disclosed.
1. A pharmaceutical composition for inhibiting angiogenesis comprising a pharmaceutically acceptable excipient in combination with (a) an amino-terminal truncated human tryptophanyl-tRNA synthetase polypeptide capable of regulating angiogenesis, wherein the truncated human tryptophanyl-tRNA synthetase polypeptide comprises a Rossmann fold nucleotide binding domain, and does not comprise residues 1 to 47 of SEQ ID NO: 10, or (b) a nucleic acid comprising a polynucleotide sequence encoding the polypeptide of (a).
2. The composition of claim 1 , wherein the polypeptide comprises amino acid residues 71-471 of SEQ ID NO: 10.
3. The composition of claim 1 , wherein the polypeptide comprises amino acid residues 48-471 of SEQ ID NO: 10.
4. The composition of claim 1 , wherein the polypeptide consists of amino acid residues 71-471 of SEQ ID NO: 10.
5. The composition of claim 1 , wherein the polypeptide consists of amino acid residues 48-471 of SEQ ID NO: 10.
6. The composition of claim 1 , wherein the nucleic acid further comprises a leader polynucleotide sequence fused thereto in an open reading frame with the polynucleotide sequence encoding the polypeptide, and the leader polynucleotide sequence encodes a secretory peptide sequence for controlling transport of the polypeptide from a cell.
7. The composition of claim 1 , wherein the nucleic acid is incorporated in a recombinant vector.
8. A method of treating a solid tumor in a subject comprising administering an angiostatically effective amount of the composition of claim 1 to the subject.
9. A method of treating a solid tumor in a subject comprising administering an angiostatically effective amount of the composition of claim 2 to the subject.
10. A method of treating a solid tumor in a subject comprising administering an angiostatically effective amount of the composition of claim 3 to the subject.
11. A method of treating a solid tumor in a subject comprising administering an angiostatically effective amount of the composition of claim 4 to the subject.
12. A method of treating a solid tumor in a subject comprising administering an angiostatically effective amount of the composition of claim 5 to the subject.
13. A method of treating a solid tumor in a subject comprising administering an angiostatically effective amount of the composition of claim 6 to the subject.
14. A composition comprising a pharmaceutically acceptable excipient in combination with (a) an amino-terminal truncated human tryptophanyl-tRNA synthetase polypeptide capable of regulating angiogenesis, wherein the truncated human tryptophanyl-tRNA synthetase polypeptide comprises a Rossmann fold nucleotide binding domain, and does not comprise residues 1 to 47 of SEQ ID NO: 10, or (b) a nucleic acid comprising a polynucleotide sequence encoding the polypeptide of (a).
15. The composition of claim 14 , wherein the polypeptide comprises amino acid residues 71-471 of SEQ ID NO: 10.
16. The composition of claim 14 , wherein the polypeptide comprises amino acid residues 48-471 of SEQ ID NO: 10.
17. The composition of claim 14 , wherein the polypeptide consists of amino acid residues 71-471 of SEQ ID NO: 10.
18. The composition of claim 14 , wherein the polypeptide consists of amino acid residues 48-471 of SEQ ID NO: 10.
19. The composition of claim 14 , wherein the nucleic acid further comprises a leader polynucleotide sequence fused thereto in an open reading frame with the polynucleotide sequence encoding the polypeptide, and the leader polynucleotide sequence encodes a secretory peptide sequence for controlling transport of the polypeptide from a cell.
20. The composition of claim 14 , wherein the nucleic acid is incorporated in a recombinant vector.