Compositions and methods comprising histidyl-TRNA synthetase splice variants having non-canonical biological activities
AssigneeaTyr Pharma, Inc.
InventorsJie Zhou, Ching-Fun Lau, Zhiwen Xu, Wing-Sze Lo, Kristi Helen Piehl, Leslie Ann Greene
Life of this patent
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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.
Claims26
A method for treating an inflammatory or autoimmune condition in a subject in need thereof, comprising administering to the subject a pharmaceutical composition that comprises a pharmaceutically acceptable carrier and a histidyl-tRNA synthetase (HRS) polypeptide splice variant, where the HRS polypeptide is about 50-175 amino acids in length and comprises 50 or more contiguous amino acids of SEQ ID NO:6 or a variant thereof having at least 95% sequence identity to SEQ ID NO:6, and where the HRS polypeptide comprises a WHEP domain and lacks a functional aminoacylation domain.
A method for treating an inflammatory or autoimmune condition in a subject in need thereof, comprising administering to the subject a pharmaceutical composition that comprises a pharmaceutically acceptable carrier and a histidyl-tRNA synthetase (HRS) polypeptide, where the HRS polypeptide is about 212 amino acids in length and comprises 50 or more contiguous amino acids of SEQ ID NO:11 or a variant thereof having at least 95% sequence identity to SEQ ID NO:11, and where the HRS polypeptide comprises a WHEP domain and lacks a functional aminoacylation domain.
An isolated histidyl-tRNA synthetase (HRS) splice variant polypeptide, for use in a method of reducing inflammatory activity wherein the HRS polypeptide comprises the amino acid sequence of SEQ ID NO:
- 11, or a variant thereof having at least 95% sequence identity to SEQ ID NO:
- 11, where the HRS polypeptide comprises a WHEP domain and lacks a functional aminoacylation domain.
A method for treating an inflammatory or autoimmune condition in a subject in need thereof, comprising administering to the subject a pharmaceutical composition that comprises a pharmaceutically acceptable carrier and a histidyl-tRNA synthetase (HRS) polypeptide, where the HRS polypeptide is about 40-80 amino acids in length and comprises about 40 or more contiguous amino acids of SEQ ID NO:6 or a variant thereof having at least 95% sequence identity to SEQ ID NO:6 where the HRS polypeptide comprises a WHEP domain.
A method for treating an inflammatory or autoimmune condition in a subject in need thereof, comprising administering to the subject a pharmaceutical composition that comprises a pharmaceutically acceptable carrier and a histidyl-tRNA synthetase (HRS) polypeptide, where the HRS polypeptide consists essentially of a WHEP domain from human histidyl-tRNA synthetase (HRS).
An isolated recombinant histidyl-tRNA synthetase (HRS) polypeptide, for use in a method of reducing inflammatory activity wherein the HRS polypeptide is 50-175 amino acids in length and comprises at least 50 contiguous amino acids of SEQ ID NO:
- 6, or a variant thereof having at least 95% sequence identity to SEQ ID NO:
- 6, where the HRS polypeptide comprises a WHEP domain and lacks a functional aminoacylation domain.
Dependencies are inferred from the claim text.