Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl-tRNA synthetases

Patent metadata

Field	Value
Publication number	US-8993723-B2
Application number	US-201113643753-A
Country	US
Kind code	B2
Filing date	Apr 28, 2011
Priority date	Apr 28, 2010
Publication date	Mar 31, 2015
Grant date	Mar 31, 2015

Abstract

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

First claim

We claim:

1. A therapeutic composition, comprising an isolated alanyl-tRNA synthetase (AlaRS) polypeptide that consists of SEQ ID NO:81 or differs from SEQ ID NO:81 by substitution, deletion, and/or addition of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, wherein the AlaRS polypeptide has an extracellular signaling activity and a solubility of at least about 5 mg/mL, and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.

2. The therapeutic composition of claim 1 , wherein the AlaRS polypeptide specifically binds to a binding partner to exert a physiological effect.

3. The therapeutic composition of claim 1 , wherein the AlaRS polypeptide consists of SEQ ID NO:81 or differs from SEQ ID NO:81 by substitution, deletion, and/or addition of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids.

4. The therapeutic composition of claim 1 , wherein the AlaRS polypeptide is fused to a heterologous polypeptide.

5. The therapeutic composition of claim 1 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to the AlaRS polypeptide.

6. The therapeutic composition of claim 1 , wherein the AlaRS polypeptide is fused to a pharmacokinetic (PK) property modifier.

7. The therapeutic composition of claim 1 , wherein the AlaRS polypeptide consists of SEQ ID NO:81 or differs from SEQ ID NO:81 by substitution, deletion, and/or addition of about 1, 2, 3, 4, or 5 amino acids.

8. The therapeutic composition of claim 1 , wherein the AlaRS polypeptide comprises SEQ ID NO:81 or 142 or a sequence that is at least 95% identical to SEQ ID NO:81 or 142.

9. The therapeutic composition of claim 8 , wherein the AlaRS polypeptide comprises SEQ ID NO:81 or 142.

10. The therapeutic composition of claim 8 , wherein the AlaRS polypeptide comprises SEQ ID NO:81.

11. The therapeutic composition of claim 6 , wherein the PK modifier is selected from human albumin, antibody Fc domains, poly Glu or poly Asp sequences, transferrin, conformationally disordered polypeptide sequences composed of the amino acids Pro, Ala, and Ser, and IgG.

Assignees

• Greene Leslie Ann
• Chiang Kyle P
• Hong Fei
• Vasserot Alain Philippe
• Lo Wing-Sze
• Watkins Jeffry Dean
• Quinn Cheryl L
• Mendlein John D
• Atyr Pharma Inc
• Pangu Biopharma Ltd

Inventors

• Greene Leslie Ann
• Chiang Kyle P
• Hong Fei
• Vasserot Alain Philippe
• Lo Wing-Sze
• Watkins Jeffry Dean
• Quinn Cheryl L
• Mendlein John D

Classifications

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title