Parvovirus formulation for treating tumors

Patent metadata

Field	Value
Publication number	US-11324788-B2
Application number	US-202016824791-A
Country	US
Kind code	B2
Filing date	Mar 20, 2020
Priority date	Jun 23, 2015
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

Described is a parvovirus formulation which comprises (a) at least 1×109 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus such as LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus or Rat virus (RV) and (b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl2×2 H2O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium. A preferred use is the therapy of a brain tumour by intratumoral injection.

First claim

What is claimed is:

1. A method for treating a tumor comprising intratumoral or intravenous injection of a pharmaceutical composition comprising
(a) at least 2×10 9 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus selected from the group consisting of LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus and Rat virus (RV) and
(b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl 2 ×2 H 2 O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium,
wherein the viscosity of the carrier is between 3.5 to 4.5 mPa·s at 37 to 40° C.

2. The method according to claim 1 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

3. The method of claim 1 , wherein the pharmaceutical acceptable carrier contains 48% Iodixanol (w/v), 0.81 mmol CaCl 2 ×2 H 2 O, 52.80 mmol NaCl, 1.06 mmol KCl, 0.88 mg/ml Tromethamine and 0.07 mg/ml Edetate calcium disodium.

4. The method according to claim 3 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

5. The method of claim 1 , wherein the parvovirus concentration is between 2×10 9 pfu/ml and 1×10 10 pfu/ml.

6. The method according to claim 5 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

7. The method of claim 3 , wherein the parvovirus concentration is between 2×10 9 pfu/ml and 1×10 10 pfu/ml.

8. The method according to claim 7 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

9. A method for treating a tumor comprising intratumoral or intravenous injection of a pharmaceutical composition comprising
(a) at least 2×10 9 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus selected from the group consisting of LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus and Rat virus (RV) and
(b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl 2 ×2 H 2 O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium,
wherein the viscosity of the carrier is between 4 and 5 mPa·s.

10. The method according to claim 9 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

11. The method of claim 9 , wherein the pharmaceutical acceptable carrier contains 48% Iodixanol (w/v), 0.81 mmol CaCl 2 ×2 H 2 O, 52.80 mmol NaCl, 1.06 mmol KCl, 0.88 mg/ml Tromethamine and 0.07 mg/ml Edetate calcium disodium.

12. The method according to claim 11 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

13. The method of claim 9 , wherein the parvovirus concentration is between 2×10 9 pfu/ml and 1×10 10 pfu/ml.

14. The method according to claim 13 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

15. The method of claim 11 , wherein the parvovirus concentration is between 2×10 9 pfu/ml and 1×10 10 pfu/ml.

16. The method according to claim 15 , wherein the tumor is a brain tumor, pancreatic carcinoma, cervical carcinoma, lung cancer, head and neck cancer, breast cancer or colon cancer.

17. The method of claim 9 , wherein the viscosity of the carrier is about 4.5 mPa·s.

Assignees

• Deutsches Krebsforsch
• Univ Heidelberg Ruprecht Karls

Inventors

• Leuchs Barbara
• Geletneky Karsten
• Rommelaere Jean
• Dinsart Christiane
• Dahm Michael
• Krebs Ottheinz

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/0085

  Brain, e.g. brain implants; Spinal cord · CPC title

• A61K35/768 Primary

  Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766 · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title