Histidyl-tRNA synthetase-Fc conjugates

Patent metadata

Field	Value
Publication number	US-10711260-B2
Application number	US-201916577992-A
Country	US
Kind code	B2
Filing date	Sep 20, 2019
Priority date	Mar 15, 2013
Publication date	Jul 14, 2020
Grant date	Jul 14, 2020

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. An isolated polynucleotide, comprising a nucleotide sequence that encodes a histidyl-tRNA synthetase (HRS) fusion polypeptide having at least one Fc region, where the polypeptide has an amino acid sequence that is at least 95% identical to SEQ ID NO:337.

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

3. The isolated polynucleotide of claim 1 , wherein the HRS fusion polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO: 337.

4. The isolated polynucleotide of claim 1 , wherein the Fc region and the HRS polypeptide are separated by a peptide linker.

5. The isolated polynucleotide of claim 4 , wherein the peptide linker is about 1-10 amino acids, or 1-5 amino acids in length.

6. The isolated polynucleotide of claim 1 , wherein the polynucleotide is a synthetic DNA or RNA.

7. A vector, comprising the isolated polynucleotide of claim 1 , or a host cell comprising the vector comprising the isolated polynucleotide of claim 1 .

8. A method for manufacturing a histidyl-tRNA synthetase (HRS) fusion polypeptide having at least one Fc region, comprising a) culturing the host cell of claim 7 to express the HRS fusion polypeptide; and b) isolating the HRS fusion polypeptide from the host cell.

9. The method of claim 8 , wherein the host cell is E. coli.

10. The method of claim 9 , wherein the E. coli is the K-12 strain.

11. The method of claim 10 , wherein the K-12 strain is selected from W3110 and UT5600.

12. The method of claim 8 , wherein host cell is a bacterium, yeast, or mammalian cell.

13. An isolated RNA polynucleotide, comprising a nucleotide sequence that encodes a histidyl-tRNA synthetase (HRS) fusion polypeptide having at least one Fc region, where the polypeptide has an amino acid sequence that is at least 95% identical to SEQ ID NO:337, wherein the RNA polynucleotide is encapsulated in a nanoparticle or liposome.

14. The isolated RNA polynucleotide of claim 13 , comprising a modified cap or tail structure to enhance stability and translation.

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

• C12N9/93 Primary

  Ligases (6) · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P29/00

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

• C12N9/96

  Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title