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

Patent metadata

Field	Value
Publication number	US-9637730-B2
Application number	US-201615179715-A
Country	US
Kind code	B2
Filing date	Jun 10, 2016
Priority date	Jul 12, 2010
Publication date	May 2, 2017
Grant date	May 2, 2017

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 pharmaceutical composition, comprising an isolated polynucleotide that encodes an aminoacyl-tRNA synthetase (AARS) polypeptide fragment of 100-150 amino acids in length that comprises an amino acid sequence which is at least 95% identical to SEQ ID NO:64 or a fragment thereof which is at least 95% identical to SEQ ID NO:83, wherein the polynucleotide is selected from (a) a cDNA polynucleotide and (b) a modified mRNA polynucleotide, wherein the AARS polypeptide fragment has an extracellular signaling activity, and wherein the composition is substantially endotoxin-free.

2. The pharmaceutical composition of claim 1 , wherein the AARS polypeptide fragment comprises the amino acid sequence of SEQ ID NO:64 or a fragment thereof which comprises the amino acid sequence of SEQ ID NO:83.

3. The pharmaceutical composition of claim 1 , wherein the AARS polypeptide fragment is at least 95% identical to SEQ ID NO:64 or 83.

4. The pharmaceutical composition of claim 3 , wherein the AARS polypeptide fragment is at least 95% identical to SEQ ID NO:64.

5. The pharmaceutical composition of claim 3 , wherein the AARS polypeptide fragment is at least 95% identical to SEQ ID NO:83.

6. The pharmaceutical composition of claim 1 , wherein the AARS polypeptide fragment consists of SEQ ID NO:64 or 83 or differs from SEQ ID NO:64 or 83 by substitution, deletion, and/or addition of about 1, 2, 3, 4, or 5 amino acids.

7. The pharmaceutical composition of claim 1 , wherein the AARS polypeptide fragment is fused to a heterologous polypeptide.

8. The pharmaceutical composition of claim 7 , wherein the heterologous polypeptide is selected from the group consisting of purification tags, epitope tags, targeting sequences, signal peptides, membrane translocating sequences, and pharmacokinetic (PK) property modifiers.

9. The pharmaceutical composition of claim 1 , wherein the isolated polynucleotide comprises one or more transcriptional and/or translational control elements.

10. The pharmaceutical composition of claim 1 , wherein the modified mRNA polynucleotide comprises at least one modified base.

11. The pharmaceutical composition of claim 1 , wherein the isolated polynucleotide is formulated for delivery encapsulated in a lipid particle, a liposome, a vesicle, a nanosphere, or a nanoparticle.

12. The pharmaceutical composition of claim 1 , which is suitable for intravenous administration.

Assignees

• Atyr Pharma Inc
• Pangu Biopharma Ltd

Inventors

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

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · 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

• A61P7/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title