Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase

Patent metadata

Field	Value
Publication number	US-8980253-B2
Application number	US-201113643755-A
Country	US
Kind code	B2
Filing date	Apr 26, 2011
Priority date	Apr 26, 2010
Publication date	Mar 17, 2015
Grant date	Mar 17, 2015

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.

First claim

We claim:

1. A therapeutic composition, comprising an isolated cysteinyl-tRNA synthetase (CRS) polypeptide of about 100 to 240 amino acids in length that comprises SEQ ID NO:12 or an amino acid sequence that is at least 92% identical to SEQ ID NO:12, wherein the polypeptide has an extracellular signaling activity and a solubility of at least about 5 mg/mL, and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.

2. The therapeutic composition of claim 1 , wherein the CRS polypeptide specifically binds to a binding partner to exert a physiological effect.

3. The therapeutic composition of claim 1 , wherein the CRS polypeptide differs from SEQ ID NO:12 by substitution, deletion, and/or addition of about 0, 1, 2, 3, 4, 5, 6, or 7 amino acids, and wherein the altered CRS polypeptide substantially retains a non-canonical activity of the unaltered polypeptide.

4. The therapeutic composition of claim 1 , wherein the CRS polypeptide is fused to a heterologous polypeptide.

5. The therapeutic composition of claim 1 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.

6. The therapeutic composition of claim 1 , wherein the CRS polypeptide is fused to a pharmokinetic (PK) property modifier.

7. A method of modulating a cellular activity of a cell, or protein, comprising contacting the cell or protein with a therapeutic composition of claim 1 .

8. The method of claim 7 , wherein the cell or protein is in a subject having a disease or disorder mediated by the dysregulation of the expression, activity or spatiotemporal location of a tRNA synthetase, comprising administering the therapeutic composition to the subject.

9. The method of claim 8 , wherein the disease is selected from cancer, neuropathy, diabetes, and inflammatory disorders.

10. The therapeutic composition of claim 3 , wherein the CRS polypeptide differs from SEQ ID NO:12 by substitution, deletion, and/or addition of about 0, 1, 2, 3, 4, or 5 amino acids.

11. The therapeutic composition of claim 1 , wherein the CRS polypeptide is about 100 amino acids in length and comprises SEQ ID NO:12 or a sequence that is at least 95% identical to SEQ ID NO:12.

12. The therapeutic composition of claim 11 , where the CRS polypeptide comprises SEQ ID NO:12.

13. The therapeutic composition of claim 1 , wherein the CRS polypeptide is about 100 to about 140 amino acids in length and comprises SEQ ID NO:12 or a sequence that is at least 92% identical to SEQ ID NO:12.

14. The therapeutic composition of claim 13 , wherein the CRS polypeptide comprises SEQ ID NO:12 or 18.

15. The therapeutic composition of claim 1 , wherein the CRS polypeptide is about 200 to about 240 amino acids in length and comprises SEQ ID NO:12 or a sequence that is at least 92% identical to SEQ ID NO:12.

16. The therapeutic composition of claim 15 , wherein the CRS polypeptide comprises SEQ ID NO:12 or 36.

Assignees

• Greene Leslie Ann
• Chiang Kyle P
• Hong Fei
• Vasserot Alain Philippe
• Lo Wing-Sze
• Watkins Jeffry D
• Quinn Cheryl L
• Mendlein John D
• Atyr Pharma Inc
• Pangu Biopharma Ltd

Inventors

• Greene Leslie Ann
• Chiang Kyle P
• Hong Fei
• Vasserot Alain Philippe
• Lo Wing-Sze
• Watkins Jeffry D
• Quinn Cheryl L
• Mendlein John D

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P35/00

  Antineoplastic agents · CPC title