Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-05-31
2003-02-04
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S777000, C424S093200
Reexamination Certificate
active
06514943
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The present invention relates to methods and compositions useful in preserving viruses.
BACKGROUND OF THE INVENTION
Viruses (modified and unmodified) have several applications in modern biology wherein preservation (maintenance or storage) of the virus (for example in a virus stock or other composition comprising a virus) is desirable. Modified viruses (also referred to as viral vectors), for example, have proven convenient vector systems for investigative and therapeutic gene transfer applications. The use of viral vectors in investigative and therapeutic applications necessitates that the viral vectors be transported and stored for a period of time. During this period of storage, the viral vectors desirably are maintained without significant loss of infectivity, viability and/or the ability of the viral vector to produce a desired effect (e.g., stimulation of an immune response) or desired product, for example a viral polypeptide of interest. Unmodified viruses and other viral vectors are also useful in similar and other contexts, for example the production of an immune response to the virus, or to a component of the virus. In such contexts, preservation of the virus typically does not require retention of infectivity and/or viability of the virus, but rather the storage method can (and often seeks to) maintain (and even sometimes cause) the virus to be inactivated and/or attenuated, but stored in a manner wherein the desired property of the virus (e.g., immunogenecity of the virus or components thereof) is retained.
In the preservation of viable (active) viruses (e.g., viral vectors), it is known that viruses can be stored frozen at very low temperatures, e.g., −80° C., without significant loss of activity; however, the need for low temperature freezers, which are not widely available, limits the practicality of this approach. Lyophilization, or freeze-drying, is another known option for storage of viruses. This method has disadvantages as it is expensive, and, upon reconstitution, the virus composition is often left for extended periods of time at room temperature (i.e., 20-25° C.). In storage formulations presently known in the art, active viruses rapidly lose viability when stored at room temperature. Virus-containing compositions stored in containers in known formulations often lose viability within short periods of time. Similar problems arise when viral vectors are dried at room temperature or higher temperatures.
In view of the above, there exists a need for further methods of, and compositions useful in, the storage or preservation of viruses. In particular, there is a need for methods and compositions for storage of viruses in liquid compositions, rather than dried or frozen compositions, and in various containers. The present invention provides such methods and compositions. These and other advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.
BRIEF SUMMARY OF THE INVENTION
The present invention provides a method and composition for preserving viruses, such as viral vectors. The present invention provides a method for preserving a virus comprising preparing a liquid composition comprising a virus, a liquid carrier, and a stabilizing agent selected from the group consisting of polysorbate 80, L-arginine, polyvinylpyrrolidone, trehalose, and combinations thereof, and subsequently maintaining the liquid composition at a temperature above 0° C. for at least 1 day. The present invention also provides a liquid composition comprising a virus, a liquid carrier, and a stabilizing agent selected from the group consisting of polysorbate 80, L-arginine, polyvinylpyrrolidone, trehalose, and combinations thereof, wherein the liquid composition can be maintained at a temperature above 0° C. for about 1 day without a decrease in viral activity greater than about 20%.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method for satisfactorily preserving (i.e., storing or maintaining) a virus in a liquid composition at a temperature above 0° C. for a period of time. The method comprises preparing a liquid composition comprising a virus, a liquid carrier, and a stabilizing agent, and subsequently maintaining the liquid composition at a temperature above 0° C. for at least 1 day. The present invention also provides a liquid composition comprising a virus, a liquid carrier, and a stabilizing agent, wherein the liquid composition can be maintained at a temperature above 0° C. for 1 day without a decrease in viral activity greater than about 20%.
The present invention can be practiced with any suitable virus, which includes both wild type viruses and modified viruses (i.e., viral vectors, such as viral gene transfer vectors). Examples of suitable viruses include, but are not limited to, Adenoviruses, Arboviruses, Astroviruses, Bacteriophages, Enteroviruses, Gastroenteritis Viruses, Hantavirus, Coxsackie viruses, Hepatitis A Viruses, Hepatitis B Viruses, Hepatitis C Viruses, Herpesviruses (for example, Epstein Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV)), Influenza Viruses, Norwalk Viruses, Polio Viruses, Rhabdoviruses, Reoviruses Rhinoviruses, Rotavirus, Retroviruses (e.g., A-type retroviruses such as HIV-1, HIV-2 and FeLV), and viruses of the genuses Baculoviridae, Caliciviridae, Caulimoviridae, Coronaviridae, Filoviridae, Flaviviridae, Hepadnaviridae, Nodaviridae, Orthomyxoviridae, Paramyxoviridae, Papovaviridae, Parvoviridae, Phycodnaviridae, Picomaviridae, and Togaviridae, and modified viruses (i.e., viral vectors such as adenoviral vectors) originating from, based upon, or substantially similar to any of the foregoing or other suitable virus. Other suitable viruses are known in the art and are well characterized. Examples of such other viruses can be found in, for example, Fields et al.,
Virology
(3rd ed., Lippincott-Raven (1996)).
The present invention is particularly useful in maintaining a viral vector (as opposed to a wild type virus), e.g., a viral gene transfer vector for use in gene therapy. The viral vector can be any vector that, at least in some significant part, is (or is similar to) a wild type virus (e.g., a modified DNA vector of viral origin). Examples of suitable vectors include DNA viruses (e.g., adenoviral vectors) and RNA viral vectors (e.g., retroviral vectors). The virus preferably is an adenovirus and more preferably is an adenoviral vector. Most preferably, the virus is an adenoviral gene transfer vector (i.e., an adenovirus comprising at least one exogenous or modified gene).
The virus is maintained in a composition that is in liquid form. Preferably, the liquid composition is a pharmaceutical composition. The term “liquid” as used to describe the composition in the context of the present invention means consisting of, containing, covered with, or soaked with liquid that is not frozen solid. In other words, the composition is partially to completely liquid in nature, preferably completely liquid.
The liquid carrier can be any suitable liquid carrier, e.g., water. Preferably, the liquid carrier is a pharmaceutically acceptable liquid carrier, particularly when the liquid composition is a pharmaceutical composition. The pharmaceutically acceptable carrier can be a pharmaceutically acceptable liquid carrier that contains a buffer (e.g., a tris buffer) and a salt. Examples of suitable buffers and salts, as well as other types of pharmaceutically acceptable carriers, are well known in the art.
The stabilizing agent is selected from the group consisting of polysorbate 80, L-arginine, polyvinylpyrrolidone, &agr;-D-glucopyranosyl &agr;-D-glucopyranoside dihydrate (commonly known as trehalose), and combinations thereof. The stabilizing agent can be a single stabilizing agent or a combination of two or more stabilizing agents. Preferably, the stabilizing agent is trehalose alone, or a combination of trehalose with polysorbate 80. Of course, the liquid composition can comprise many oth
Kovesdi Imre
Ransom Stephen C.
GenVec, Inc.
Travers Russell
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