Viral vectors having reduced virulence

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

Reexamination Certificate

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C435S069100, C435S320100, C435S455000, C435S456000, C424S184100, C424S204100, C424S232100, C424S093100, C424S093200, C424S093600

Reexamination Certificate

active

06750043

ABSTRACT:

BACKGROUND OF THE INVENTION
Vaccinia virus is a member of the poxvirus family of DNA viruses. Poxviruses including vaccinia virus are extensively used as expression vectors since the recombinant viruses are relatively easy to isolate, have a wide host range, and can accommodate large amounts of DNA.
The vaccinia virus genome contains nonessential regions into which exogenous DNA can be incorporated. Exogenous DNA can be inserted into the vaccinia virus genome by well-known methods of homologous recombination. The resulting recombinant vaccinia viruses are useful as vaccines and anticancer agents.
The use of vaccinia virus recombinants as expression vectors and particularly as vaccines and anticancer agents raises safety considerations associated with introducing live recombinant viruses into the environment. Virulence of vaccinia virus recombinants in a variety of host systems has been attenuated by the deletion or inactivation of certain vaccinia virus genes that are nonessential for virus growth. However, there remains a need in the art for the development of vectors that have reduced pathogenicity while maintaining desirable properties of wild-type virus, such as host range, and active protein synthesis of a desired gene product.
SUMMARY OF THE INVENTION
The present invention provides methods of use of a recombinant vaccinia virus having a mutation in or near the region of the E3L gene that encodes a double stranded (ds)-RNA binding domain. The invention further provides an expression vector comprising the recombinant vaccinia virus and exogenous DNA.


REFERENCES:
patent: 6004777 (1999-12-01), Tartaglia et al.
patent: WO 99/55910 (1999-11-01), None
patent: 0073487 (2000-12-01), None
Beattie et al., Virus Genes, 1996, vol. 12, pp. 89-94.*
Shors et al., “Complementation of Vaccinia Virus Deleted of the E3L Gene by Mutants of E3L”, Virology 239:269-276, 1997.
Chang et al., “Indentification of a Conserved Motif That is Necessary for Binding of the Vaccinia Virus E3L Gene Products to Double-Stranded RNA”, Virology 194:537-547, 1993.
Brandt et al., “Both Carboxy- and Amino-Terminal Domains of the Vaccinia Virus Interferon Resistance Gene, E3L, Are Required for Pathogenesis in a Mouse Model”, J. Virology 75:850-856, 2001.
Kibler et al., “Double-Stranded RNA Is a Trigger for Apoptosis in Vaccinia Virus-Infected Cells”, Journal of Virology 71:1992-2003, 1997.
U.S. patent application, Ser. No. 09/837,997.
U.S. patent application Ser. No. 09/887,295, Jacobs et al., filed Jun. 22, 2001.
Beattie et al., “Reversal of the Interferon-Sensitive Phenotype of a Vaccinia Virus Lacking E3L by Expression of the Reovirus S4 Gene”, Journal of Virology, vol. 69, No. 1, Jan. 1995, pp. 499-505.

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