Methods and compositions for preserving adenoviral vectors

• US 6,225,289 B1
• Filed: 12/10/1998
• Issued: 05/01/2001
• Est. Priority Date: 12/10/1998
• Status: Expired due to Term

• Current Assignee: GenVec, Inc. (Precigen, Inc.)
• Original Assignee: GenVec, Inc. (Precigen, Inc.)
• Inventors: Ransom, Stephen C., Kovesdi, Imre
• Primary Examiner(s): TRAVERS, RUSSELL S
• Application Number:
  US09/208,666
• Time in Patent Office: 873 Days
• Field of Search: 514/777, 514/23, 424/93.2
• US Class Current: 514/23
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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 48/0091 Purification or manufacturing processes for gene therapy compositions
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10351 Methods of production or purification of viral material

Abstract

The present invention provides a method and composition for preserving an adenoviral vector. Both the method and composition involve the use of an adenoviral gene transfer vector, a pharmaceutically acceptable liquid carrier, and a stabilizing agent, which enables the adenoviral vector to be maintained at a temperature above 0° C. for at least 7 days.

Claims

1. A method for preserving an adenoviral gene transfer vector in a liquid carrier, which method comprises:

(a) preparing a pharmaceutical composition comprising an adenoviral gene transfer vector, a pharmaceutically acceptable liquid carrier, and a stabilizing agent selected from the group consisting of polysorbate 80, L-arginine, polyvinylpyrrolidone, trehalose, and combinations thereof, and

(b) maintaining said composition as a liquid at a temperature above 0°

C. for at least 7 days with a decrease in activity of said composition of about 20% or less.

2. The method of claim 1, wherein said stabilizing agent is trehalose.

3. The method of claim 2, wherein said trehalose is present in said composition in a concentration of about 2-10% (wt./vol.).

4. The method of claim 2, wherein said stabilizing agent is a mixture of trehalose and polysorbate 80.

5. The method of claim 1, wherein said pharmaceutically acceptable carrier comprises a buffer and a salt.

6. The method of claim 5, wherein said pharmaceutically acceptable carrier further comprises a saccharide other than trehalose.

7. The method of claim 2, wherein the activity of said composition decreases about 20% or less after 7 days.

8. The method of claim 7, wherein the activity of said composition remains substantially the same after 7 days.

9. The method of claim 2, wherein said composition is maintained at a temperature above 0°

C. for at least 10 weeks.

10. The method of claim 9, wherein the activity of said composition decreases about 50% or less after 10 weeks.

11. The method of claim 2, wherein said composition is maintained at a temperature of 37°

C. or higher for at least 7 days.

12. The method of claim 11, wherein the activity of said composition decreases about 50% or less after 7 days.

13. A liquid pharmaceutical composition comprising an adenoviral gene transfer vector, a pharmaceutically acceptable liquid carrier, and a stabilizing agent selected from the group consisting of polysorbate 80, L-arginine, polyvinylpyrrolidone, trehalose, and combinations thereof, wherein said composition can be maintained as a liquid at a temperature above 0°

C. for 7 days with a decrease in activity of said composition of about 20% or less.

14. The composition of claim 13, wherein said stabilizing agent is trehalose.

15. The composition of claim 14, wherein said trehalose is present in said composition in a concentration of about 2-10% (wt./vol.).

16. The composition of claim 15, wherein said trehalose is present in a concentration of about 4-6% (wt./vol.).

17. The composition of claim 13, wherein said stabilizing agent is a mixture of trehalose and polysorbate 80.

18. The composition of claim 17, wherein said trehalose is present in said composition in a concentration of about 4-6% (wt./vol.) and said polysorbate 80 is present in said composition in a concentration of about 0.001-0.01% (wt./vol.).

19. The composition of claim 13, wherein said pharmaceutically acceptable carrier comprises a buffer and a salt.

20. The composition of claim 19, wherein said pharmaceutically acceptable carrier further comprises a saccharide other than trehalose.