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It s Patently Clear, There Is Some Hope For Cheaper Affymetrix Microarrays

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Affymetrix last week earned yet another patent, adding to a portly portfolio of intellectual property, shedding some light into its plans for the future, and even giving researchers some hope for cheaper chips.

The company received US Patent No. 6,480,324 for “Methods involving direct write optical lithography.” The patent describes a means for doing optical lithography without using a photomask to prepare the wafers that are event ually sliced into 49 microarray chips.

The application was filed June 14, 2001. Calvin Quate and Affymetrix scientist David Stern were cited as inventors.

Quate, a professor of electrical engineering and applied physics at Stanford University, and a member of the Affymetrix scientific advisory board, told BioArray News that the innovation in the patent could mean more flexible and less expensive custom microarray chips sometime in the future.

“You could create one array for the same price as a thousand custom arrays,” Quate said. “Now, you have to make many, many chips in order to justify the cost.”

While Affymetrix’s products are regarded as the sine qua non of the microarray world, they are by no means an inexpensive product, with an entire GeneArray brand system costing $200,000 and individual chips some $600 each. The company sold 98,000 chips and 50 systems in the second quarter.

Customers buying Affymetrix’s newest product, the CustomSeq chip, have to order a minimum of 80 chips and wait eight weeks for delivery after designs are finalized.

The company is just beginning to take advantage of manufacturing tweaks that will eventually lower its costs to nil, CFO Greg Schiffman said in a recent speech to financial analysts.

The company is just beginning to take advantage of manufacturing tweaks that will eventually lower its costs to nil, CFO Greg Schiffman said in a recent speech to financial analysts.

Unmasking Arrays

Santa Clara, Calif.,-based Affymetrix has borrowed heavily from photolithography-based manufacturing methods pioneered in the semiconductor industry in Silicon Valley. This method utilizes light beamed through a mask to etch patterns onto silicon wafer to create microchips - or microarrays.

Photomasks have a predefined image pattern that permits the light used for synthesis of the polymer arrays to reach some parts of the substrate and not others. A number of masking steps are required to create the microarray.

Affymetrix says that to create an array of 20-mers requires some 70 photolithographic steps and a number of related masks.

The new patent, according to the patent application, involves a process called a Direct Write Optical Lithography System. The system uses a “spatial light modulator” that directs optical beams of predetermined intensity onto the wafer to generate a predetermined light pattern in the areas where the polymer is to be synthesized, according to the patent. The patterns of light are stored in a computer.

This Direct Write system is something that may kick in after Affymetrix has reached the limits of miniaturization on its manufacturing methods for creating polymer arrays.

The patent application says that this invention would significantly improve the cost, quality and efficiency of polymer array syntheses.

The process could also create polymer arrays of molecules such as polypeptides and carbohydrates, as well as nucleic acid chips.

Quate — who is also co-inventor of the atomic force microscope — said he couldn’t venture a guess on whether his invention could be commercialized.

“It would depend on the market for custom chips,” he said. “Affymetrix is quite saturated with that market right now.”

But Affymetrix is not alone in examining the light-based microarray synthesis technology. Light Biology of Dallas, as well as Nimblegen Systems of Madison, Wisc., and Febit of Mannheim, Germany, are also using similar technology, said Skip Garner, a biochemistry professor at the University of Texas Southwestern Medical Center and a holder of a patent assigned to Light Biology. These companies all use micromirrors to redirect light onto specific places on a substrate where synthesis is to occur.

Garner said Nimblegen and Febit may not be in a position of IP power in their micromirror microarray thrust.

“I think that they’ll certainly both have to talk to both Affymetrix about the patents from Affymetrix that dominate in this area and to us for our patent as well,” he told BioArray News. (For details on Garner’s views of this technology, see lab report, pp. 6-7.)

IP, Oh

That phone call is exactly what a company seeks when it creates a portfolio of patents. Affymetrix has some 300 patents pending and 204 granted since 1992, said Phil McGarrigle, Affymetrix chief IP counsel.

The company was, at one time, involved in four intellectual pro perty suits. Two of them were settled in the past year, giving the company’s five lawyers a much more comfortable work schedule these days.

“Four active lawsuits were fairly debilitating and distracting,” McGarrigle said.

Still, the company’s IP team’s duty is to protect the inventions the company makes. He said the company’s patent portfolio overlaps. “It’s a soup-to-nuts array,” he said. “We have patents on the array, per se We have patents on the information, how to analyze the information, on the scanner that is used.”

Affymetrix’s lawyers are not a cease-and-desist letter-writing crew, said McGarrigle. “We tend to talk to people and watch the industry to see what is going on.”

Within the company, new employees, including its lawyers, sign standard pre-employment disclosure agreements that protect what they might learn on the job and that say, “don’t take what you learned at your last job here,” he said.

Affymetrix plans to spend $70 million for the year on R&D, investing an extra $1.5 million in the fourth quarter in a ramping-up of long-term investments like the Direct Write System.

The exemplar is IBM, which produces nearly $1.7 billion a year in licensing -- 15 percent of the company’s profit.

The US Patent and Trademark Office has 3,400 examiners granting nearly 200,000 patents a year. The application process takes two years to complete.

— MOK

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