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-11844844-B2
Application number	US-201816767804-A
Country	US
Kind code	B2
Filing date	Nov 28, 2018
Priority date	Nov 28, 2017
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

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

The invention claimed is:

1. A drug delivery carrier comprising:
glutathione-S-transferase (GST);
an affibody, which is 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 via glutathione (GSH).

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

3. The drug delivery carrier of claim 1 , 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.

4. The drug delivery carrier of claim 1 , wherein the drug is a nanoparticle capable of loading a drug.

5. The drug delivery carrier of claim 4 , 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.

6. The drug delivery carrier of claim 5 , wherein the GSH is bound onto the surface of the nanoparticle.

7. The drug delivery carrier of claim 1 , wherein the drug is an anticancer agent.

8. A pharmaceutical composition for preventing or treating cancer, the pharmaceutical composition comprising:
glutathione-S-transferase (GST);
an affibody, which is 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 via glutathione (GSH).

9. The pharmaceutical composition for preventing or treating cancer of claim 8 , 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.

10. The pharmaceutical composition for preventing or treating cancer of claim 8 , wherein the anticancer agent is an anticancer agent-loaded nanoparticle.

11. A method of delivering a drug to an individual, the method comprising administering a composition comprising glutathione-S-transferase (GST); an affibody, which is 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 via glutathione (GSH) to an individual in need thereof.

12. A method of preventing or treating cancer, the method comprising administering a composition comprising glutathione-S-transferase (GST); an affibody, which is 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 via glutathione (GSH) 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

• A61K47/6889 Primary

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · 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

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K47/6929

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