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Exploiting New Technology, CombiMatrix to Develop Customized Protein Arrays

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CombiMatrix is working to develop and commercialize a protein array, the company’s first, ProteoMonitor has learned.

The company had previously considered developing protein arrays, but found that cross-reactivity between the antibodies and the sample made it impossible to put more than 100 antibodies on the array and achieve good performance. Customers, the company believed, would not be willing to pay a premium price for these arrays.

CombiMatrix now thinks its improved technology can overcome this challenge.

“It’s starting to look like there are some niche opportunities, and we will start evaluating those market opportunities as we go forward,” said CEO Amit Kumar during the company’s fourth quarter earnings call last week in response to a private investor’s question.

Kumar told ProteoMonitor’s sister publication BioArray News that in the past CombiMatrix didn’t think customers “were willing to pay $500 for a protein array with 50 antibodies.” He said he “now … think[s] we can put together protein arrays with higher numbers of proteins, and that customers will be willing to pay significant prices for those.”

The first protein chip the company has been developing, in part with SAIC, is an antibody array that uses electrochemical detection to identify biological threats, Kumar said.

With funding from the US Department of Defense, CombiMatrix has been working with SAIC since last fall to develop DNA arrays for the detection of biothreats.

Besides offering a biothreat detection antibody array, CombiMatrix also plans to offer custom antibody arrays to researchers. These arrays could be used with either electrochemical or traditional fluorescent detection, and would have up to 12,000 sites. Customers would provide the content and decide how many antibodies of what type to put on the chip. In certain areas, the company will also provide catalog content, Kumar said.

“The main difference between our arrays [and our competitors’ arrays] is going to be the flexibility and the ability to customize them,” said Kumar. “Our partners will come to us and say, ‘We want an array with these proteins on them — will you array them for us?’”

In the future, CombiMatrix also plans to evaluate receptors and other protein types as content for the arrays, and hopes that the chips will eventually find their way into diagnostics, in addition to research.

Kumar said the biothreat arrays would be sold to the US military at the end of this year and early next year. The customized arrays would also be released early next year, Kumar added.

CombiMatrix’s move comes during a time when several other players have shown an interest in protein arrays. Last spring, Invitrogen acquired protein chip maker Protometrix (See PM 4/9/2004), and late last year licensed the patent estate of antibody array maker Zyomyx (See PM 12/3/2004). And Sigma-Aldrich said last fall it will market protein arrays from Procognia (See PM 11/12/2004), and launched a p53 array in February.

The reason that CombiMatrix had shied away from protein arrays so far, Kumar said, is that it had been impossible in the past to put more than 100 antibodies on the array and achieve good performance, due to cross-reactivity between the antibodies and the sample.

What allowed CombiMatrix to reduce, though not eliminate, cross-reactivity is proprietary surface chemistry on the chip, Kumar said. In addition, the electrochemical detection approach is more sensitive, more selective, and is believed to offer a better signal-to-noise ratio than detection by fluorescence, according to Kumar. He said this would improve the chip’s overall performance.

Making protein arrays based on its chip platform is relatively easy for CombiMatrix from a technical standpoint, according to Kumar, and manufacturing costs “will be very similar to the cost to make our DNA arrays.” The approach to put the antibodies on the chip is proprietary but takes advantage of the chip’s microelectrodes, he said.

“The question becomes what price the market will be willing to purchase those [for],” he said.

Potential competitors for the arrays are Invitrogen and BD Biosciences, “because of their size and marketing muscle,” Kumar said. “We feel our technology is superior, but we are a much smaller company than both of them.”

— JK

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