Avigen receives a broad patent for adeno-associated virus cancer gene therapy and a patent for adenovirus-free adeno-associated virus production.

Avigen, Inc. (Alameda, CA; 510-748-7150) announced the issuance of United States Patent 5,952,221 to Avigen covering recombinant adeno-associated virus vectors carrying therapeutic genes for the treatment of cancer, including genes encoding suicide proteins, antiangiogenic factors, interferons, lymphokines, tumor suppressors and growth factors. The patent is for a two gene system with one gene encoding a therapeutic protein and the other a "gene switch" which allows the therapy to be terminated. Scientists from Avigen developed the research underlying the patent.

"This is yet another example of Avigen's large and diverse adeno-associated virus patent estate borne from research conducted at Avigen," said Avigen's president and CEO, John Monahan, PhD. "We believe that this is a significant patent because it encompasses all types of cancers, including lung, colon, breast, prostate, liver, and glioma," he said.

One of the current obstacles for certain gene therapy applications is the ability to regulate the expression of the gene product or to terminate therapy once the therapy is completed. For hemophilia A and hemophilia B, Avigen's lead programs, gene regulation is not required because the therapy calls for continuous life-long expression of high levels of protein. For cancer, however, it is often imperative that the gene therapy be terminated or modulated after some time due either to the toxicity of the therapeutic agent or because the tumor has regressed. Avigen scientists addressed this problem by inserting two genes into a single adeno-associated virus vector. One gene encodes a therapeutic protein such as Beta-interferon, Angiostatin, Endostatin, interleukin-2, p53, or granulocyte-macrophage colony stimulating factor. These genes are typically inserted into a small fraction of the patient's tumor cells via gene therapy to stimulate an anti-tumor effect. The other gene is a "switch" which terminates the therapy in response to a pharmaceutical compound given to the patient. These genes are known as suicide genes because they will kill any cancer cell containing the suicide gene in response to a pro-drug. For example, the suicide gene thymidine kinase kills cancer cells in response to the pro-drug ganciclovir by shutting down DNA synthesis. In this way, the therapy can be allowed to continue as long as necessary, yet terminated to avoid long term toxicity.

Using this approach, Avigen and collaborators at the Nagoya University School of Medicine (Japan) have employed adeno-associated virus to transfer the thymidine kinase gene in combination with interleukin-2 to experimental gliomas in mice. Interleukin-2 is a cytokine which increases the host's immune response to the malignancy. Following six days of ganciclovir administration, histopathology results showed that tumors treated with the adeno-associated virus vector were an average of eleven times (11X) smaller than the untreated controls. Similar results were observed when the gene encoding Beta-interferon was used.

Avigen was also granted United States Patent 5,945,335 covering compositions and methods for making adeno-associated virus free of helper-viruses such as adenovirus. Using the adenovirus-free technology in the patent, undesirable adenoviral protein can be eliminated from the manufacturing process without compromising product yields.

"Avigen now has one of the largest adeno-associated virus-related patent estates," said Kenneth G. Chahine, PhD, JD, vice president of business Ddvelopment and chief patent counsel. "These patents encompass numerous significant aspects of adeno-associated virus, including manufacturing, tissue administration, vectors, and disease treatment," he added.

Avigen is a biotechnology company involved in the development of gene therapy products derived from adeno-associated virus for the treatment of inherited and acquired diseases. The company's proposed gene therapy products are designed for in vivo administration to achieve the production of therapeutic proteins within the body.