Histidyl-tRNA synthetase-Fc conjugates

Patent metadata

Field	Value
Publication number	US-11072787-B2
Application number	US-202016842200-A
Country	US
Kind code	B2
Filing date	Apr 7, 2020
Priority date	Mar 15, 2013
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

The present invention provides histidyl-tRNA synthetase and Fc region conjugate polypeptides (HRS-Fc conjugates), such as HRS-Fc fusion polypeptides, compositions comprising the same, and methods of using such conjugates and compositions for treating or diagnosing a variety of conditions. The HRS-Fc conjugates of the invention have improved controlled release properties, stability, half-life, and other pharmacokinetic and biological properties relative to corresponding, unmodified HRS polypeptides.

First claim

The invention claimed is:

1. A method of reducing a lung inflammatory response in a subject in need thereof, comprising administering to the subject a composition comprising a histidyl-tRNA synthetase (HRS) fusion polypeptide having at least one Fc region (HRS-Fc fusion polypeptide), wherein the HRS-Fc fusion polypeptide has an amino acid sequence that is at least 95% identical to SEQ ID NO:337, wherein the HRS-Fc fusion polypeptide is at least about 95% pure and less than about 5% aggregated, and wherein the composition is substantially endotoxin-free.

2. The method of claim 1 , wherein the HRS-Fc fusion polypeptide reduces immune cell activation and invasion into damaged lung.

3. The method of claim 1 , wherein the HRS-Fc fusion polypeptide increases production of anti-inflammatory cytokines, reduces production or activity of pro-inflammatory cytokines, or both.

4. The method of claim 1 , wherein the HRS fusion polypeptide comprises an amino acid sequence at least 97% identical to SEQ ID NO: 337.

5. The method of claim 4 , wherein the HRS fusion polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 337.

6. The method of claim 1 , wherein the Fc region and the HRS polypeptide are separated by a peptide linker.

7. The method of claim 1 , wherein the HRS-Fc fusion polypeptide is substantially in dimeric form in a physiological solution.

8. The method of claim 1 , wherein the HRS-Fc fusion polypeptide has substantially the same secondary structure as a corresponding unmodified HRS polypeptide, as determined via UV circular dichroism analysis.

9. The method of claim 1 , wherein the HRS-Fc fusion polypeptide has a plasma or sera pharmacokinetic AUC profile at least 5-fold greater than a corresponding, unmodified HRS polypeptide.

10. The method of claim 1 , comprising intravenously administering the composition to the subject.

11. The method of any one of claims 1 - 10 , wherein the subject has problems with breathing.

12. The method of claim 1 , wherein the problems with breathing comprise shortness of breath, a non-productive cough, or both.

Assignees

• Atyr Pharma Inc

Inventors

• Wu Chi-Fang
• Lee Darin
• Watkins Jeffry D
• Piehl Kristi
• Chiang Kyle P
• Thomas Marc
• Do Minh-Ha
• Buechler Ying
• Mendlein John D

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C12N9/93 Primary

  Ligases (6) · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• C12Y601/01021

  Histidine-tRNA ligase (6.1.1.21) · CPC title