VIRUS-CONTAINING FORMULATION AND USE THEREOF

• US 20150250869A1
• Filed: 10/02/2013
• Published: 09/10/2015
• Est. Priority Date: 10/02/2012
• Status: Active Grant

• Current Assignee: Transgene S.A. (Compagnie Merieux Alliance SAS)
• Original Assignee: Transgene S.A. (Compagnie Merieux Alliance SAS)
• Inventors: Sene, Claude, Chasle, Mlina
• Granted Patent: US 10,111,947 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 39/285 Vaccinia virus or variola virus
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C12N 2710/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to formulation comprising (i) at least one virus-based material, (ii) at least one polymer selected in the group of polyvinylpyrrolidone and derivatives thereof, (iii) at least one sugar, (iv) at least two different amino acids, (v) at least two pharmaceutical acceptable salts, wherein at least one of said salts is a phosphate salt and, optionally (vi) a pharmaceutical acceptable buffer. Such a formulation is particularly suitable for freeze-drying. The present invention also relates to the corresponding dry product, as well as its preparation process. The present invention also relates to a reconstituted material comprising said dry product, which can be administered to a patient in need thereof. Such formulation and reconstituted material are useful as vaccines, preferably for the treatment and/or the prevention of cancers, infectious diseases and/or autoimmune disorders.

Claims

1. A formulation comprising (i) at least one virus-based material, (ii) at least one polymer selected in the group of polyvinylpyrrolidone and derivatives thereof, (iii) at least one sugar, (iv) at least two different amino acids, (v) at least two pharmaceutical acceptable salts, wherein at least one of said salts is a phosphate salt and, optionally (vi) a pharmaceutical acceptable buffer.

2. The formulation of claim 1, wherein it is an aqueous formulation.

3. The formulation of claim 1, wherein it is a freeze-drying formulation.

4. The formulation of claim 1, wherein said (ii) at least one polymer is selected in the group of polyvinylpyrrolidone and derivatives thereof, and mixture thereof.

5. The formulation of claim 4, wherein said polyvinylpyrrolidone or derivatives thereof have a molecular weight comprised between 10 kDa and 40 kDa, preferably between 15 kDa and 30 kDa and more preferably of 25 kDa.

6. The formulation of claim 4, wherein said formulation comprises between 10 g/L and 50 g/L, preferably between 15 g/L and 40 g/L, and more preferably between 20 g/L and 35 g/L of polyvinylpyrrolidone or derivatives or mixture thereof.

7. The formulation of claim 1, wherein said (iii) at least one sugar is chosen among monosaccharide, disaccharide, trisaccharide and tetrasaccharide and derivatives thereof.

8. The formulation of claim 7, wherein said formulation comprises at least one disaccharide selected from the group consisting in sucrose, lactulose, lactose, maltose, trehalose, cellobiose, isomaltose and maltulose.

9. The formulation of claim 7, wherein said formulation comprises between 20 g/L and 80 g/L, preferably between 30 g/L and 70 g/L and more preferably between 40 g/L and 60 g/L of sugar.

10. The formulation of claim 9, wherein said formulation comprises 50 g/L of sucrose.

11. The formulation of claim 1, wherein said (iv) at least two different amino acids are chosen among alanine, arginine, asparagine, aspartate, cysteine, glutamine, glutamate, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, pyrrolysine, selenocysteine, serine, threonine, tryptophane, tyrosine and valine and derivatives thereof, including both stereoisomers.

12. The formulation of claim 11, wherein said formulation comprises between 5 g/L and 100 g/L and preferably between 5 g/L and 80 g/L of arginine.

13. The formulation of claim 11, wherein said formulation comprises between 1 g/L and 10 g/L and preferably between 1 g/L and 5 g/L of glutamate.

14. The formulation of claim 1, wherein at least one of said salts is a phosphate salt and is selected in the group consisting of sodium and potassium salts, and combination thereof.

15. The formulation of claim 14, wherein said phosphate salt is selected in the group consisting of monobasic phosphate salts, dibasic phosphate salts and tribasic phosphate salts.

16. The formulation of claim 14, wherein it further comprises an additional pharmaceutically acceptable monovalent salt.

17. The formulation of claim 16, wherein said additional pharmaceutically acceptable salt is selected in the group consisting of NaCl and KCl, and is preferably NaCl.

18. The formulation of claim 16, wherein said formulation comprises between 1 g/L and 5 g/L of said additional pharmaceutical acceptable salt.

19. The formulation of claim 1, wherein said (i) virus-based material is a wild type, attenuated or recombinant virus or viral particle.

20. The formulation of claim 19, wherein said virus-based material is a virus or viral particle selected from the group consisting of Vaccinia Virus (W) and modified VACCINIA Virus Ankara (MVA).

21. The formulation of claim 20, wherein said virus-based material is a recombinant MVA selected from the group consisting in a MVA expressing HCV NS3, NS4 and NS5B antigens;

a MVA expressing the MUC-1 antigen and IL-2 and a MVA expressing non oncogenic E6 and E7 antigens of HPV-16 and IL-2.

22. The formulation of claim 20, wherein said virus-based material is a recombinant Vaccinia Virus selected from the group consisting in a thymidine kinase (TK)-inactivated vaccinia virus expressing an immune-stimulating cytokine which is a granulocyte macrophage colony stimulating factor and a doubly thymidine kinase (TK-) and ribonucleotide reductase (I4L-) inactivated vaccinia virus expressing a suicide gene.

23. The formulation of claim 1, wherein the virus titer in said formulation is comprised between 1.10⁶ Pfu/mL and 1.10¹⁰ Pfu/mL.