Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of tryptophanyl-tRNA synthetases

Patent metadata

Field	Value
Publication number	US-9399770-B2
Application number	US-201113877899-A
Country	US
Kind code	B2
Filing date	Oct 6, 2011
Priority date	Oct 6, 2010
Publication date	Jul 26, 2016
Grant date	Jul 26, 2016

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 tryptophanyl-tRNA synthetase (TrpRS) polypeptide of up to 280 amino acids in length that comprises the amino acid sequence of SEQ ID NO: 56 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56, wherein the TrpRS polypeptide has an extracellular signaling activity and has 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 as measured by HPLC and less than about 10 EU endotoxin/mg protein.

2. The therapeutic composition of claim 1 , wherein the TrpRS polypeptide consists of the amino acid sequence of SEQ ID NO: 56 or differs from the amino acid sequence of SEQ ID NO: 56 by substitution, deletion, and/or addition of 1, 2, 3, 4, 5, 6, or 7 amino acids.

3. The therapeutic composition of claim 2 , wherein the TrpRS polypeptide consists of the amino acid sequence of SEQ ID NO: 56 or differs from the amino acid sequence of SEQ ID NO:56 by substitution, deletion, and/or addition of 1, 2, or 3 amino acids.

4. The therapeutic composition of claim 1 or 2 , wherein the TrpRS polypeptide is fused to a heterologous polypeptide and retains the extracellular signaling activity.

5. The therapeutic composition of claim 1 or 2 , wherein the TrpRS polypeptide is fused to a heterologous pharmacokinetic (PK) modifier and retains the extracellular signaling activity.

6. The therapeutic composition of claim 1 , wherein at least one heterologous moiety or a heterologous solid substrate is covalently or non-covalently attached to the TrpRS polypeptide and retains the extracellular signaling activity.

7. The therapeutic composition of claim 1 , wherein the TrpRS polypeptide of up to 280 amino acids in length comprises the amino acid sequence of SEQ ID NO:56, 16, or 48 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56, 16, or 48.

8. The therapeutic composition of claim 7 , wherein the TrpRS polypeptide of up to 280 amino acids in length comprises the amino acid sequence of SEQ ID NO: 56, 16, or 48.

9. The therapeutic composition of claim 1 , wherein the TrpRS polypeptide is up to 260 amino acids in length and comprises the amino acid sequence of SEQ ID NO:56 or 16 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56 or 16.

10. The therapeutic composition of claim 9 , wherein the TrpRS polypeptide of up to 260 amino acids in length comprises the amino acid sequence of SEQ ID NO: 56 or 16.

11. The therapeutic composition of claim 1 , wherein the TrpRS polypeptide is up to 160 amino acids in length and comprises the amino acid sequence of SEQ ID NO: 56 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56.

12. The therapeutic composition of claim 11 , wherein the TrpRS polypeptide of up to 160 amino acids in length comprises the amino acid sequence of SEQ ID NO:56.

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

14. The method of claim 13 , 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 of claim 1 to the subject.

15. The method of claim 14 , wherein the disease or disorder is selected from cancer, neuropathy, diabetes, and inflammatory disorders.

Assignees

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

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title