Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of tyrosyl-trna synthetases

Abstract

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

1 - 132 . (canceled) 
     
     
         133 . A therapeutic composition, comprising a pharmaceutically-acceptable carrier and an antibody or antigen-binding fragment thereof that exhibits binding specificity for an isolated aminoacyl-tRNA synthetase (AARS) polypeptide selected from Table(s) 1-3, or Table(s) 4-6, and Table(s) 7-9, wherein the composition has a purity of at least about 90% on a protein basis and less than about 10 EU endotoxin/mg protein. 
     
     
         134 . The therapeutic composition of  claim 133 , wherein the AARS polypeptide is selected from Table E7. 
     
     
         135 . The therapeutic composition of  claim 133 , wherein the antibody or antigen binding fragment thereof is a monoclonal antibody. 
     
     
         136 . The therapeutic composition of  claim 133 , wherein the antibody is a humanized antibody. 
     
     
         137 . The therapeutic composition of  claim 133 , wherein the antibody or antigen-binding fragment thereof is an Fv fragment or a single chain Fv (sFv) polypeptide. 
     
     
         138 . The therapeutic composition of  claim 133 , wherein the composition is a sterile, freeze-dried powder. 
     
     
         139 . The therapeutic composition of  claim 133 , wherein the composition is a sterile injectable solution. 
     
     
         140 . The therapeutic composition of  claim 133 , wherein the composition is buffered and comprises an isotonic agent. 
     
     
         141 . The therapeutic composition of  claim 133 , wherein the composition is suitable for intravenous, intramuscular, subcutaneous, or intraperitoneal administration. 
     
     
         142 . The therapeutic composition of  claim 133 , wherein the composition comprises a surfactant. 
     
     
         143 . The therapeutic composition of  claim 133 , wherein the composition has a purity of at least about 95% on a protein basis. 
     
     
         144 . A method of modulating a cellular activity of a cell, or protein, comprising contacting the cell or protein with a therapeutic composition of  claim 133 . 
     
     
         145 . The method of  claim 144 , wherein the cellular activity is selected from cell proliferation, cell differentiation, cell signaling, gene transcription, angiogenesis, cell binding, metabolism, cytokine production or activity, cytokine receptor activity, and inflammation. 
     
     
         146 . The method of  claim 144 , wherein the cell type is selected from the group consisting of pre-adipocytes, bone marrow, neutrophils, blood cells, hepatocytes, astrocytes, mesenchymal stem cells, and skeletal muscle cells. 
     
     
         147 . The method of  claim 144 , wherein the cell is in a subject. 
     
     
         148 . The method of  claim 147 , comprising treating the subject, wherein the subject has a condition associated with a neoplastic disease, an immune system disease or condition, an inflammatory disorder, an infectious disease, a metabolic disease, neuronal/neurological disease, a muscular/cardiovascular disease, a disease associated with aberrant hematopoiesis, a disease associated with aberrant angiogenesis, or a disease associated with aberrant cell survival. 
     
     
         149 . A method of reducing or ameliorating a symptom of a disease mediated by a mutation, inappropriate subcellular association, over-expression, or subcellular distribution of tyrosyl-tRNA synthetase (TyrRS), comprising administering to a subject a therapeutic composition of  claim 133 .