Onyx Pharmaceuticals, Inc.

Julie Nye

Terry Hermiston

Yuqiao Shen

David H Kirn

James R Bischoff

Lelia Ng

Angelica Williams

Sharon Horn

Adenoviral mutants are described that have single amino acid mutations in the E1B-55K protein which mutations effect the p53 binding/inactivation and the late functions of the E1B-55K protein in a manner that enhances the efficacy of such viruses for treating cancer when compared to adenoviral mutants that have the E1B-55K region deleted.

Adenovirus E1B-55K single amino acid mutants and methods of use

Provided are replication competent, recombinant adenovirus vectors containing mutations in the E1B region which permit the easy deletion of a gene or genes therein, and optionally the substitution therefore of a heterologous gene that substantially exhibits the temporal expression pattern of the E1b region gene(s) deleted. Such vectors have applications for the treatment of disease, and preferably for the treatment of neoplastic disease.

Adenovirus E1B shuttle vectors

Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Cytopathic adenoviral E1B mutated viruses for therapy and prophylaxis of

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Berkeley, CA, United States of America

Julie Nye