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Zyomyx Preparing to Hit Start Button On Protein Profiling Biochip Assembly Line


Zyomyx of Hayward Calif., is now leading its prized protein biochip system to the starting gates.

The company has created an assay technology based on a chip containing high-density arrays of functional proteins, which it plans to market for use in drug discovery, biomarker identification, and target validation, and sell to large pharmas, biotechs, and the academic market. Zyomyx’s lead product, the protein profiling biochip system, has been available to early-access customers of the company since the summer, and should soon be launched to the target market.

The protein array market is in its earliest stages, with no clear leader, but a cast of potential competitors includes Luminex of Austin, Texas; Molecular Staging of New Haven, Conn.; and a collaboration between Large Scale Biology of Vacaville, Calif., and Biosite Diagnostics.

The hurdles to success go beyond science to the essential financial question: Can a company manufacture a protein microarray product and create a profitable business around it?

The Zyomyx system consists of: a fluidics workstation that can process 12 chips simultaneously; a scanner; reagents; and software. Each chip can assay up to 200 proteins in six separate cells with a sample volume of 40 microliters each. The proteins will then be detected by fluorescence labeling, using a scanner developed by the company. The first product for the system will be the Human Cytokine biochip. The company is pricing the system at $150,000 and chips at $750 each. Of course, volume discounts will be available.

The chip itself is flanked by an array of patents, the last two of which Zyomyx won in November. These patents, US Patent No. 6,475,808, and 6,475,809, describe an array in which “protein immobilization regions” are spread out over the surface of a chip, and are surrounded by border regions that are resistant to nonspecific binding — chemical barriers comprised of a hydrophilic monolayer on top of a hydrophobic monolayer of alkyl chains.

In December, Zyomyx signaled its intention to begin manufacturing the product when it announced the purchase of a 903e plasma etch system from Tegal to be used in the protein chip manufacturing process, with a target date for installation set for early January.

Seeding the Field

Before beginning its first lap of the protein chip marketing race, Zyomyx already has a cast of all-star customers lined up. In August, it announced that GlaxoSmithKline would become an early-access customer for its system, chips, and subsequent chips. This deal followed the June announcement of a three-year agreement with Boston’s Partners health care system — a consortium of medical facilities that includes Harvard Medical School and its affiliated teaching hospitals, Massachusetts General Hospital and Boston’s Brigham and Women’s Hospital — to use the company’s protein chip system in clinical research. Zyomyx will provide a protein analysis system, which includes its workstation, software, and ready-to-use antibody chips. In May, the company announced that it had delivered its protein profiling biochip system to its first early access collaborator, Specialty Laboratories of Santa Monica, Calif.

Another Use For Silicon

The company bases its manufacturing process on the chip fabrication technology that is so prevalent throughout Silicon Valley, using equipment readily available, much like the way Affymetrix got it start. To make each chip, the company etches silicon, creating pillars — each 50 microns in diameter and 150 microns tall — 200 per channel and 1,200 per chip. The assay process takes place on top of the chip, enabled by a mirror image chip with wells on it, filled with the substance to array on the chip.

“We do the opposite of what DNA arrays do,” said Matthew Yoshikawa, product development manager. He said the company uses a proprietary surface chemistry.

“It’s a very classic immunoassay we are using on the surface,” Yoshikawa said. “We have a capture agent attached to the surface that will grab the analyte out of solution. Then we are coming in with a secondary detection antibody to recognize that signal. That allows for a greater degree of specificity, using two antibodies for every analyte.”

The company has designed its manufacturing process, conducted in a Class 10,000 clean room, at industrial scale, Yoshikawa said.

“We have a facility that is scalable for demand,” he said.

To make the arrays, Zyomyx has developed a PDC-dispensing robot that uses a non-contact process to spot up to 1,000 chips per day. The company’s current chip chemistry involves the biotin-streptavidin sandwich assay, co-founder Steven Nock told BioArray News in a January 2002 interview. He said at the time the company was looking at “label independent assays such as surface plasmon resonance, so we won’t have to put on the second antibody.”

In July, the company announced Series E venture capital funding led by Yasuda Enterprise Development of Japan, Alloy Ventures of Palo Alto, Credit Suisse First Boston Private Equity and including new investors Lilly BioVentures and GE Capital Life Science and Technology Finance. Founded in 1998 by four Stanford scientists, Zyomyx has collected $94 million in six rounds of investment.

Gathering Content

Zyomyx in July 2001 announced a supply and collaboration agreement with BD Biosciences of San Diego. Zyomyx received access to the BD Biosciences antibody library and the two companies agreed to collaborate on the development, manufacture, and supply of antibodies. BD Biosciences has exclusive rights to market the antibody library produced by Dyax of Cambridge, Mass., which is also a Zyomyx partner, along with Cambridge Antibody Technology, Fujirebio, and MDS Proteomics.


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