Fusion protein comprising glutathione-s-transferase and protein having binding affinity target cell or target protein, and use thereof

Patent metadata

Field	Value
Publication number	US-2021000971-A1
Application number	US-201816767804-A
Country	US
Kind code	A1
Filing date	Nov 28, 2018
Priority date	Nov 28, 2017
Publication date	Jan 7, 2021
Grant date	—

Abstract

Provided are a fusion protein including glutathione-S-transferase and a protein having binding affinity for a target cell or a target protein, and use thereof as a drug delivery carrier and a pharmaceutical composition. The fusion protein and the drug delivery carrier including the same according to an aspect may sustain an in vivo residence time, and may also have improved target cell-targeting ability, and thus may be effectively delivered to target cells. Accordingly, it may be usefully applied to a targeted therapeutic agent.

First claim

1 . A fusion protein comprising:
glutathione-S-transferase (GST); a protein having binding affinity for a target cell or a target protein; and a linker that links the GST with the protein having binding affinity for a target cell or a target protein.

2 . The fusion protein of claim 1 , wherein the protein having binding affinity for a target cell or a target protein is any one selected from the group consisting of an antibody, an antigen-binding fragment, an affibody, a diabody, and an aptamer.

3 . The fusion protein of claim 1 , wherein the protein having binding affinity for a target cell or a target protein specifically binds to receptor tyrosine kinases (RTKs).

4 . The fusion protein of claim 3 , wherein the RTKs are any one selected from the group consisting of epidermal growth factor receptor, insulin receptor, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor, cholecystokinin (CCK) receptor, neurotrophic factor (NGF) receptor, hepatocyte growth factor (HGF) receptor, ephrin (Eph) receptor, angiopoietin receptor, and related to receptor tyrosine kinase (RYK) receptor.

5 . A drug delivery carrier comprising:
glutathione-S-transferase (GST); a protein having binding affinity for a target cell or a target protein; a linker that links the GST with the protein having binding affinity for a target cell or a target protein; and a drug bound with the GST.

6 . The drug delivery carrier of claim 5 , wherein the protein having binding affinity for a target cell or a target protein is any one selected from the group consisting of an antibody, an antigen-binding fragment, an affibody, a diabody, and an aptamer.

7 . The drug delivery carrier of claim 5 , wherein the protein having binding affinity for a target cell or a target protein specifically binds to receptor tyrosine kinases (RTKs).

8 . The drug delivery carrier of claim 5 , wherein the RTKs are any one selected from the group consisting of epidermal growth factor receptor, insulin receptor, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor, cholecystokinin (CCK) receptor, neurotrophic factor (NGF) receptor, hepatocyte growth factor (HGF) receptor, ephrin (Eph) receptor, angiopoietin receptor, and related to receptor tyrosine kinase (RYK) receptor.

9 . The drug delivery carrier of claim 5 , wherein the binding of GST with the drug occurs via glutathione (GSH).

10 . The drug delivery carrier of claim 5 , wherein the drug is a nanoparticle capable of loading a drug.

11 . The drug delivery carrier of claim 5 , wherein the nanoparticle is any one selected from the group consisting of a mesoporous silica nanoparticle (MSN), a gold nanoparticle, a magnetic nanoparticle, a nucleic acid-metal organic framework nanoparticle, and a polymer nanoparticle.

12 . The drug delivery carrier of claim 11 , wherein glutathione (GSH) is bound onto the surface of the nanoparticle.

13 . The drug delivery carrier of claim 5 , wherein the drug is an anticancer agent.

14 . A pharmaceutical composition for preventing or treating cancer, the pharmaceutical composition comprising:
glutathione-S-transferase (GST); a protein having binding affinity for a target cell or a target protein; a linker that links the GST with the protein having binding affinity for a target cell or a target protein; and an anticancer agent bound with the GST.

15 . The pharmaceutical composition for preventing or treating cancer of claim 14 , wherein the protein having binding affinity for a target cell or a target protein is any one selected from the group consisting of an antibody, an antigen-binding fragment, an affibody, a diabody, and an aptamer.

16 . The pharmaceutical composition for preventing or treating cancer of claim 14 , wherein the protein having binding affinity for a target cell or a target protein specifically binds to an epidermal growth factor receptor, an insulin receptor, a platelet-derived growth factor receptor, a vascular endothelial growth factor receptor, or an angiopoietin receptor.

17 . The pharmaceutical composition for preventing or treating cancer of claim 14 , wherein the binding of GST with the anticancer agent occurs via glutathione (GSH).

18 . The pharmaceutical composition for preventing or treating cancer of claim 14 , wherein the anticancer agent is an anticancer agent-loaded nanoparticle.

19 . The pharmaceutical composition for preventing or treating cancer of claim 14 , wherein the anticancer agent is any one selected from the group consisting of camptothecin, doxorubicin, cisplatin, verapamil, fluorouracil, oxaliplatin, daunorubicin, irinotecan, topotecan, paclitaxel, carboplatin, gemcitabine, methotrexalte, docetaxel, and pharmaceutically acceptable salts thereof.

20 . A method of delivering a drug to an individual, the method comprising administering a composition comprising glutathione-S-transferase (GST); a protein having binding affinity for a target cell; a linker that links the GST with the protein having binding affinity for a target cell; and a drug bound with the GST to an individual in need thereof.

21 . A method of preventing or treating cancer, the method comprising administering a composition comprising glutathione-S-transferase (GST); a protein having binding affinity for a target cell; a linker that links the GST with the protein having binding affinity for a target cell; and an anticancer agent bound with the GST to an individual in need thereof.

Assignees

• Ulsan Nat Inst Science & Tech Unist

Inventors

• Ryu Ja Hyoung
• Oh Joon Yong
• Kim Han Sol
• Kim Chae Kyu
• Kang Se Byung

Classifications

• A61K9/5169 Primary

  Proteins, e.g. albumin, gelatin · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K47/6929

  the form being a nanoparticle, e.g. an immuno-nanoparticle · CPC title

• A61K9/5052

  Proteins, e.g. albumin · CPC title

• C07K2319/23

  containing a GST-tag · CPC title