Avastin was approved by the FDA in February 2004 to be used in combination with intravenous 5-Fluorouracil-based chemotherapy as a first-line treatment for metastatic colorectal cancer and is the first FDA-approved therapy designed to inhibit angiogenesis, the process by which new blood vessels develop, which is necessary to support tumor growth and metastasis.

"The FDA approval for Avastin bulk drug production at our Vacaville facility is an important step in ensuring that there is sufficient supply available for patients who need Avastin," said David A. Ebersman, senior vice president, Product Operations. "We are pleased with the successful transfer of the Avastin process and appreciate the diligent efforts by our employees and the FDA to secure the approval of this filing."

Avastin bulk drug substance will continue to be manufactured at the company's South San Francisco facility, as well as at the Vacaville facility.

The current Vacaville site has a manufacturing capacity of 144,000 liters and was originally licensed by the FDA in April 2000. The facility is licensed to produce bulk drug substance for Avastin, Herceptin?® (Trastuzumab), Rituxan?® (Rituximab) and Xolair?® (Omalizumab).

gene

"The monkeys became extreme workaholics, as evidenced by a sustained low rate of errors in performing the experimental task, irrespective of how distant the reward might be," said Richmond. "This was conspicuously out-of-character for these animals. Like people, they tend to procrastinate when they know they will have to do more work before getting a reward."

To make sure that it was, indeed, the lack of D2 receptors that was causing the observed effect, the researchers played a similar recombinant decoy trick targeted at the gene that codes for receptors for another neurotransmitter abundant in the rhinal cortex: NMDA (N-methlD-aspartate). Three monkeys lacking the NMDA receptor in the rhinal cortex showed no impairment in reward learning, confirming that the D2 receptor is critical for learning that cues are related to reward prediction. The researchers also confirmed that the DNA treatments actually affected the targeted receptors by measuring receptor binding following the intervention in two other monkeys' brains.

"This new technique permits researchers to, in effect, measure the effects of a long-term, yet reversible, lesion of a single molecular mechanism," said Richmond. "This could lead to important discoveries that impact public health. In this case, it's worth noting that the ability to associate work with reward is disturbed in mental disorders, including schizophrenia, mood disorders and obsessive-compulsive disorder, so our finding of the pivotal role played by this gene and circuit may be of clinical interest," suggested Richmond.

"For example, people who are depressed often feel nothing is worth the work. People with OCD work incessantly; even when they get rewarded they feel they must repeat the task. In mania, people will work feverishly for rewards that aren't worth the trouble to most of us."

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