Abgenix takeover gives Amgen grasp of the humanized mouse.

Besides the promising colon cancer drug panitumumab, Amgen Inc. will get something much easier to pronounce in its $2.2 billion purchase of Abgenix Inc.

Mice--actually, a special line of genetically altered mice that have been in high demand because they now have human immune systems. As a result, antibodies can be grown in the mice and then used in humans, with less risk of rejection.

Amgen Chief Executive Kevin Sharer told analysts during a Dec. 14 conference call that the Thousand Oaks-based biotech giant was still evaluating what's being called Abgenix's XenoMouse technology. "We know there are customers who depend on that platform and we are mindful of that and respectful of it and we want to make sure that we deliver properly," Sharer said.

Might Amgen hoard the developing technology, making business tougher for its competitors?

"There are several places people can go now, but clearly taking one of the big players out of the market is going to have an impact," said RBC Capital Markets analyst Jason Kantor, adding that reduced access to XenoMouse could present an upside for smaller Abgenix competitors.

Amgen may decide to honor Abgenix's existing partnerships with about a dozen companies. Currently, those partners range from established drug giants such as Pfizer Inc. and AstraZeneca PLC, to small development firms such as Santa Monica-based Agensys Inc., whose chief scientific officer, Aya Jakobovits, led the Abgenix team that produced XenoMouse in mid- 1990's.

Unlike many young development companies with no products on the market, Abgenix has been able to supplement its funding with a small but steady royalty stream from XenoMouse--the product of years of intricate gene splicing and animal cross-breeding.

"It's like a gold mine," said Jakobovits, whose new company has a XenoMouse-developed prostate cancer drug in Phase One clinical trials with Merck and Co. Inc. as a co-development partner. "It's a well-proven technology. If you have good targets, you can produce very good antibodies with it."

Agensys' XenoMouse license is up for renewal in August, but Jakobovits hopes that small companies like hers, which often serve as farm teams for big pharmaceutical companies, will still have access to the technology.

Detecting cells

Some Abgenix shareholders filed a class action suit last month, contending that Amgen's offer of $22.50 a share is too little, given the value of the company's experimental drug portfolio and intellectual property. Fremont-based Abgenix said in a regulatory filing that the suit was without merit.

The proposed acquisition awaits approval from federal regulators and Abgenix's shareholders.

The genetically altered mice are considered important because they can offer further clues on how antibodies are used to detect and prevent microbes or viruses.

More than 25 years ago, scientists began determining how to develop antibodies that would attach to diseased cells that normally go undetected, such as many kinds of cancer. They also can attach to cells linked to arthritis and other diseases. The benefit: a treatment without the severe side-effects of radiation or pills that can weaken the liver.

Using mice to create antibodies requires genetically humanizing the mouse's immune system so that the antibodies it creates can be introduced in humans without being attacked themselves. Older drugs, such as Imclone Inc.'s cancer treatment Erbitux, were developed from mouse cells that are not as "humanized." They must be administered with other drugs that counter the side effects of the minute amount of mouse genetic matter they contain.

XenoMouse antibodies are considered among the most fully human developed to date, with panitumumab so far triggering no reported immune response in clinical trials. That kind of record has made XenoMouse, along with Princeton, N.J.-based Medarex Inc.'s UltiMab system, also used by Amgen, among the most sought after among a half dozen humanization platforms.

"An antibody produced from a XenoMouse is for all practical purposes human," said Larry Green, an Abgenix senior research fellow who was part of Jakobovits' XenoMouse development team. He noted that even an antibody originally produced from a human has the potential of being rejected by another person's immune system.

Next-generation competitors to XenoMouse are still several years off. Pasadena-based California Technology Ventures has provided seed funding for a new California Institute of Technology spin-off called Aliva Inc., which is looking to develop a humanized mouse with an even broader antibody-producing repertoire. Aliva's scientific founder, Hiroaki Shizuya, was the inventor of key technology that enabled the cloning of the human genome.

"While the Abgenix technology is excellent, we believe, theoretically, that we can build a better mouse trap," said Gary Lazar, California Technology Venture's managing partner.

Meanwhile, both Amgen and Abgenix last month applied for U.S. regulatory approval of panitumumab. A recent study found that the drug helped slow tumor growth in patients not helped by chemotherapy. Patients who got the drag were 46 percent less likely to have their cancer worsen than those who received just supportive care, exceeding the study's goal of 33 percent.