Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities

Patent metadata

Field	Value
Publication number	US-9605265-B2
Application number	US-201414262272-A
Country	US
Kind code	B2
Filing date	Apr 25, 2014
Priority date	Mar 16, 2009
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

Isolated histidyl-tRNA synthetase splice variant polynucleotides and polypeptides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

First claim

The invention claimed is:

1. A pharmaceutical composition, comprising an RNA polynucleotide analog that comprises at least one modified base and encodes a HRS splice variant polypeptide of SEQ ID NO:6, 9, or 11 which has a non-canonical activity selected from reduction of inflammation and neuroprotection, or an active variant thereof having at least 95% identity along its length to SEQ ID NO:6, 9, or 11, where the composition is sterile and pyrogen-free.

2. The pharmaceutical composition of claim 1 , where the HRS splice variant polypeptide further comprises a heterologous fusion partner.

3. The pharmaceutical composition of claim 2 , where the heterologous fusion partner comprises an Fc fragment.

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

5. The pharmaceutical composition of claim 1 , where the polynucleotide is selected from coding sequence of SEQ ID NO:5, 8, and 10, or a variant thereof that comprises non-naturally-occurring codon(s).

6. The pharmaceutical composition of claim 1 , where the polynucleotide is selected from the coding sequence of SEQ ID NO:5, 8, and 10.

7. The pharmaceutical composition of claim 1 , where the polynucleotide is operably linked to a translational regulatory element.

8. A pharmaceutical composition, comprising a recombinant vector and a pharmaceutically-acceptable carrier, where the recombinant vector comprises a polynucleotide that encodes a HRS splice variant polypeptide of SEQ ID NO:6, 9, or 11 which has a non-canonical activity selected from reduction of inflammation and neuroprotection, or an active variant thereof having at least 95% identity along its length to SEQ ID NO:6, 9, or 11, wherein the polynucleotide is operably linked to a translational regulatory element, where the composition is sterile and pyrogen-free.

9. The pharmaceutical composition of claim 8 , where the polynucleotide of is selected from the coding sequence of SEQ ID NO:5, 8, and 10, or a variant thereof that comprises non-naturally-occurring codon(s).

10. The pharmaceutical composition of claim 9 , where the polynucleotide is selected from the coding sequence of SEQ ID NO:5, 8, and 10.

11. The pharmaceutical composition of claim 8 , where the FIRS splice variant polypeptide further comprises a heterologous fusion partner.

12. The pharmaceutical composition of claim 11 , where the heterologous fusion partner comprises an Fc fragment.

Assignees

• Atyr Pharma Inc
• Pangu Biopharma Ltd

Inventors

• Zhou Jie
• Lau Ching-Fun
• Xu Zhiwen
• Lo Wing-Sze
• Piehl Kristi Helen
• Greene Leslie Ann

Classifications

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title