tRNA synthetase fragments

Abstract

The present invention relates to compositions and methods for treating conditions associated with angiogenesis. In particular the present invention relates to multi-unit complexes of tRNA synthetase fragments and uses thereof; diverse multi-unit complexes including a tRNA synthetase fragment; compositions and methods for modulating angiogenesis; polynucleotides encoding tRNA synthetase fragments and uses thereof; antibodies and epitopes specific to tRNA synthetase fragments; variants of tRNA synthetase fragments and uses thereof; methods for treating angiogenesis; methods for screening for anti-angiogenic agents; methods of modulating angiogenesis; kits for modulating angiogenesis; and business methods for modulating angiogenesis. Preferably the tRNA synthetase fragments are tryptophanyl tRNA synthetase fragments, and more preferably human tryptophanyl tRNA synthetase fragments.

What is claimed is: 
     
         1 . A method for purifying a tRNA synthetase fragment suitable for ophthalmic administration to a patient, comprising performing an endotoxin-reduction filtration step after performing a clarification step and prior to performing at least one of the steps selected from: a buffer exchange step; a concentration step; and a cation-exchange chromatographic step, wherein said endotoxin-reduction filtration step does not include the use of a detergent. 
     
     
         2 . A method for purifying a tRNA synthetase fragment suitable for ophthalmic administration to a patient, comprising performing an endotoxin-reduction filtration step after performing an anion-exchange chromatographic step, wherein said endotoxin-reduction filtration step does not include the use of a detergent. 
     
     
         3 . The method according to  claim 1 , wherein said tRNA synthetase fragment comprises a first tRNA synthetase fragment and a second tRNA synthetase fragment. 
     
     
         4 . The method according to  claim 3 , wherein said first and said second tRNA synthetase fragments are tryptophanyl tRNA synthetase fragments. 
     
     
         5 . The method according to  claim 4 , wherein said first tRNA synthetase fragment and said second tRNA synthetase fragments are identical. 
     
     
         6 . The method according to  claim 5 , wherein said first tRNA synthetase fragment consists of SEQ ID NO: 27. 
     
     
         7 . The method according to  claim 3 , wherein said first tRNA synthetase fragment consists of SEQ ID NO: 27 and said second tRNA synthetase fragment consists of SEQ ID NO: 24 or SEQ ID NO: 27. 
     
     
         8 . The method according to  claim 3 , wherein said first tRNA synthetase fragment and said second tRNA synthetase fragment are each independently selected from the group consisting of SEQ ID Nos. 24, SEQ ID No. 25, SEQ ID No 26, SEQ ID No 27, SEQ ID No 28, SEQ ID No. 29, SEQ ID No. 36, SEQ ID No. 37, SEQ ID No. 38, SEQ ID No. 39, SEQ ID No. 40, SEQ ID No. 41, SEQ ID No. 48, SEQ ID No. 49, SEQ ID No. 50, SEQ ID No. 51, SEQ ID No. 52 and SEQ ID No. 53, or homologs thereof, and wherein said first and said second fragments are non-covalently dimerized. 
     
     
         9 . The method according to  claim 1 , wherein said tRNA synthetase fragment has greater than 50 angiostatin activity units; an endotoxin concentration of less than 10 endotoxin units per milligram of said tRNA synthetase fragment; and at least 99% level of purity. 
     
     
         10 . The tRNA synthetase fragment obtained by the method according to  claim 1 . 
     
     
         11 . A formulation comprising the tRNA synthetase fragment obtained by the method according to  claim 1 . 
     
     
         12 . A method for treating an individual suffering from an angiogenic condition comprising administering to said individual said tRNA synthetase fragment according to  claim 10 . 
     
     
         13 . The method according to  claim 12 , wherein the angiogenic condition is selected from the group consisting of: age-related macular degeneration, cancer, developmental abnormalities, diabetic retinopathy, endometriosis, ocular neovascularization, psoriasis, rheumatoid arthritis (RA), skin discolorations (hemangioma), and wound healing.