Granted Patent
B2
US 12,497,466 · App. 17/355,587 · Granted Dec 16, 2025
Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
Inventors:
Jie Zhou (Hong Kong, CN); Ching-Fun Lau (Hong Kong, CN); Zhiwen Xu (San Diego, CA); Wing-Sze Lo (Hong Kong, CN); Kristi Helen Piehl (San Diego, CA); Leslie Ann Greene (San Diego, CA)
C07K16/40C12N9/93C12N15/1137C12Q1/6876C12Q1/6886C12Y601/01021G01N33/573A61K38/00C07K2317/24C07K2317/56C07K2317/622C07K2317/76C12N2310/11C12N2310/14C12Q2600/136C12Q2600/156G01N2333/9015G01N2500/04G01N2500/10
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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.
Claims (9)
1 . A method for monitoring cytokine production in a subject, comprising the steps of:
(a) administering a fusion polypeptide to the subject, wherein the fusion polypeptide comprises a histidyl-tRNA synthetase (HRS) polypeptide fused to an Fc fragment, wherein the HRS polypeptide consists of a sequence that has at least 95% identity along its length to SEQ ID NO: 6, comprises a WHEP domain, and lacks a functional aminoacylation domain; and
(b) detecting a cytokine mRNA or a cytokine polypeptide in a sample obtained from the subject to measure changes in cytokine production, wherein the cytokine is one or more selected from the group consisting of TNF-«, IFN-γ, MCP-1, IL-6, and combinations thereof, thereby monitoring cytokine production in the subject following treatment with the HRS polypeptide fused to the Fc fragment.
2 . The screening method of claim 1 , wherein the HRS polypeptide consists of a sequence that has at least 98% identity along its length to SEQ ID NO: 6.
3 . The screening method of claim 1 , wherein the N-terminal region of the HRS polypeptide is truncated by 1, 2, or 3 amino acids.
4 . The screening method of claim 1 , comprising detecting the cytokine mRNA by RT-PCR.
5 . The screening method of claim 1 , comprising detecting the cytokine protein by ELISA, ELISpot, or flow cytometry.
6 . The screening method of claim 1 , wherein the subject has an inflammatory lung disease or inflammatory granulomatous disorder.
7 . The screening method of claim 6 , wherein the inflammatory lung disease is selected from the group consisting of scleroderma, asthma, and autoimmune pulmonary inflammation.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 19, 2022
From: ZHOU, JIE; LAU, CHING FUN; XU, ZHIWEN; LO, WING SZE; PIEHL, KRISTI HELEN; GREENE, LESLIE ANN
To: ATYR PHARMA, INC.
Reel/Frame 061472/0369 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 19, 2022
From: ZHOU, JIE; LAU, CHING FUN; XU, ZHIWEN; LO, WING-SZE
To: PANGU BIOPHARMA LIMITED
Reel/Frame 061472/0472 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 19, 2022
From: PANGU BIOPHARMA LIMITED
To: ATYR PHARMA, INC.
Reel/Frame 061472/0531 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 19, 2022
From: ATYR PHARMA, INC.
To: PANGU BIOPHARMA LIMITED
Reel/Frame 061726/0816 →
Continuity (10)
Provisional Application
61239747
· Sep 3, 2009
Provisional Application
61160630
· Mar 16, 2009
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