Title of Invention	"ALPHAVIRUS AND ALPHAVIRUS REPLICON PARTICLE FORMULATIONS AND METHODS"
Abstract	Disclosed are methods for preparing dried (preferably lyophilized) preparations comprising a population of alphaviruses or alphavirus replicon particles, a sugar or polyol, a surfactant and a salt and preparations made by said methods, both in the dried form but also as liquids prior to drying or after reconstituting dried preparations. These preparations may further comprise a plasticizer and/or a bulking agent. These preparations are readily reconstituted, with little or no loss in infectivity of the viruses or replicon particles.

Title of Invention

"ALPHAVIRUS AND ALPHAVIRUS REPLICON PARTICLE FORMULATIONS AND METHODS"

Abstract

Disclosed are methods for preparing dried (preferably lyophilized) preparations comprising a population of alphaviruses or alphavirus replicon particles, a sugar or polyol, a surfactant and a salt and preparations made by said methods, both in the dried form but also as liquids prior to drying or after reconstituting dried preparations. These preparations may further comprise a plasticizer and/or a bulking agent. These preparations are readily reconstituted, with little or no loss in infectivity of the viruses or replicon particles.

Full Text	We Claims :- 1. A dried composition with rehydration and storage stability comprising (1) alphaviruses or aiphavirus replicon particles, (2) a salt, (3) a surfactant, and (4) a hydrogen-bonding sugar, sugar alcohol or other polyol. 2. The composition of claim 1 further comprising a plasticizer. 3. A dried composition with rehydration and storage stability comprising (1) a alphaviruses or aiphavirus replicon particles, (2) a salt, (3) a surfactant, (4) a hydrogen-bonding sugar or sugar alcohol or other poiyol, and (5) a bulking agent. 4. The composition of daim 2 further comprising a plasticizer. 5. The composition of claim 1, wherein the pH of the composition prior to drying is maintained at a pH from about 7 to about 9. 6. The composition of claim 5, wherein boric acid and a pharmaceutically acceptable salt of tetraborate are used to buffer the composition prior to drying. 7. The composition of claim 1, wherein the alphaviruses or aiphavirus replicon particles are produced in Vera cell culture, CHO cell culture, BHK cell culture, or 293 cell culture. 8. The composition of claim 1, wherein tha aiphavirus is Venezuelan Equine Encephalitis Virus (VEE). 9. The composition of claim 1, wherein the salt is provided at an ionic strength sufficient to reduce, minimize or eliminate aggregation in the population of alphaviruses or aiphavirus replicon particles. 10. The composition of claim 9, wherein the salt is sodium sulfate, sodium citrate, sodium glutamate, magnesium sulfate or sodium sucrose octasulfate. 11. The composition of claim 1, wherein the surfactant is a protein, Tween 20 ™ (polyoxyethylene (20) sorbitan monolaurate), Tween 80 ™ (Polyoxyyathylanasorbitan monooleate), Brij 35 ™ (poly(ethaxethylene-23) lauryl ether), polaxamer 188 (triblock copolymer of the form poly(ethylene oxide)-poly(propyiene oxide)-poly(ethylene oxide)) or gelatin. 12. The composition of claim 11, wherein the protein is human serum albumin. 13. The composition of claim 12, wherein the human serum albumin is produced recombinantly. 14. The composition of claim 2 wherein the bulking agent if hydroxyethyl starch, dextran, mannitol, glycine, Ficoll or polyvinylpyrrolidone. 15. The composition of any of claim 1, wherein there is residual moisture content from about 0.5% to about 10%. 16. The composition of olaim 15 wherein the residual moisture content is from about 2 to about 7%. 17. The composition of claim 16, wherein the residual moisture content is from about 3 to about 5%. 18. The composition of claim 2, wherein the plasttcizer is from about 0.05% to about 2% glycerol. 19. A method for preparing the composition of claim 1 which comprises the steps of: (a) preparing an aqueous solution or dispersion comprising an alphavirus or alphavirus replicon particle, a satt, a surfactant, and a hydrogen-bonding sugar or sugar alcohol; and (b) drying the aqueous dispersion to obtain a composition wherein the alphavirus or alphavirus replicon particle is dispersed in an amorphous glassy matrix comprising the surfactant and sugar or sugar alcohol. 20. The method of claim 19 wherein the infectivity titer of the dried composition is no more than one tog less than the infectivity titer of the aqueous solution. 21. The method of claim 19, wherein the aqueous solution or dispersion further comprises a plasticizer. 22. The method of claim 20, wherein the aqueous solution or dispersion further comprises a bulking agent. 23. The method of claim 20, wherein the aqueous solution or dispersion further comprises a plasticizer and a bulking agent. 24. A dried composition with rehydration and storage stability, substantially as hereinbefore described with reference to the foregoing description, examples and accompanying drawings.

Full Text

We Claims :-
1. A dried composition with rehydration and storage stability comprising (1) alphaviruses or aiphavirus replicon particles, (2) a salt, (3) a surfactant, and (4) a hydrogen-bonding sugar, sugar alcohol or other polyol.
2. The composition of claim 1 further comprising a plasticizer.
3. A dried composition with rehydration and storage stability comprising (1) a alphaviruses or aiphavirus replicon particles, (2) a salt, (3) a surfactant, (4) a hydrogen-bonding sugar or sugar alcohol or other poiyol, and (5) a bulking agent.
4. The composition of daim 2 further comprising a plasticizer.
5. The composition of claim 1, wherein the pH of the composition prior to drying is maintained at a pH from about 7 to about 9.
6. The composition of claim 5, wherein boric acid and a pharmaceutically acceptable salt of tetraborate are used to buffer the composition prior to drying.
7. The composition of claim 1, wherein the alphaviruses or aiphavirus replicon particles are produced in Vera cell culture, CHO cell culture, BHK cell culture, or 293 cell culture.
8. The composition of claim 1, wherein tha aiphavirus is Venezuelan Equine Encephalitis Virus (VEE).
9. The composition of claim 1, wherein the salt is provided at an ionic strength sufficient to reduce, minimize or eliminate aggregation in the population of alphaviruses or aiphavirus replicon particles.
10. The composition of claim 9, wherein the salt is sodium sulfate, sodium citrate, sodium glutamate, magnesium sulfate or sodium sucrose octasulfate.
11. The composition of claim 1, wherein the surfactant is a protein, Tween 20 ™
(polyoxyethylene (20) sorbitan monolaurate), Tween 80 ™
(Polyoxyyathylanasorbitan monooleate), Brij 35 ™ (poly(ethaxethylene-23) lauryl ether), polaxamer 188 (triblock copolymer of the form poly(ethylene oxide)-poly(propyiene oxide)-poly(ethylene oxide)) or gelatin.
12. The composition of claim 11, wherein the protein is human serum albumin.
13. The composition of claim 12, wherein the human serum albumin is produced recombinantly.
14. The composition of claim 2 wherein the bulking agent if hydroxyethyl starch, dextran, mannitol, glycine, Ficoll or polyvinylpyrrolidone.
15. The composition of any of claim 1, wherein there is residual moisture content from about 0.5% to about 10%.
16. The composition of olaim 15 wherein the residual moisture content is from about 2 to about 7%.
17. The composition of claim 16, wherein the residual moisture content is from about 3 to about 5%.
18. The composition of claim 2, wherein the plasttcizer is from about 0.05% to about 2% glycerol.
19. A method for preparing the composition of claim 1 which comprises the steps of: (a) preparing an aqueous solution or dispersion comprising an alphavirus or alphavirus replicon particle, a satt, a surfactant, and a hydrogen-bonding sugar or sugar alcohol; and (b) drying the aqueous dispersion to obtain a composition wherein the alphavirus or alphavirus replicon particle is dispersed in an amorphous glassy matrix comprising the surfactant and sugar or sugar alcohol.
20. The method of claim 19 wherein the infectivity titer of the dried composition is no more than one tog less than the infectivity titer of the aqueous solution.
21. The method of claim 19, wherein the aqueous solution or dispersion further comprises a plasticizer.
22. The method of claim 20, wherein the aqueous solution or dispersion further comprises a bulking agent.
23. The method of claim 20, wherein the aqueous solution or dispersion further comprises a plasticizer and a bulking agent.
24. A dried composition with rehydration and storage stability, substantially as hereinbefore described with reference to the foregoing description, examples and accompanying drawings.

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Patent Number

270417

Indian Patent Application Number

2723/DELNP/2009

PG Journal Number

52/2015

Publication Date

25-Dec-2015

Grant Date

18-Dec-2015

Date of Filing

24-Apr-2009

Name of Patentee

ALPHAVAX, INC

Applicant Address

2 TRIANGLE DRIVE, RESEARCH TRIANGLE PARK, NC 27709-0307, U.S.A.

Inventors:

#	Inventor's Name	Inventor's Address
1	DEPAZ, ROBERTO A	2615 WINTON ROAD, DURHAM, NC 27707, U.S.A.
2	TALARICO, TODD L.	2700 CREEK CROSSING DRIVE, MCKINNEY, TX 75070, USA.

PCT International Classification Number

A61K 39/12

PCT International Application Number

PCT/US2007/083537

PCT International Filing date

2007-11-02

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/864,366	2006-11-03	U.S.A.