With a newly granted patent and a newly published article validating its protein binding technology, Lexington, Mass.-based Phylos is readying to attack the protein chip market.
The US patent, "Systematic Polypeptide Evolution by Reverse Translation," describes a method for developing libraries of nucleic-acid-polypeptide molecules that can serve as binding sites for target protein molecules.
This patent is among a handful that present the theoretical underpinnings of Phylos'' ProFusion technology, which links proteins to encoded mRNA, enabling PCR amplification of the protein to a detectable level, said Ashley Lawton, Phylos'' CEO.
The company is applying ProFusion as a means to find specific and strong binding molecules for target proteins on chips, which it hopes to have available in prototype form by the end of the year.
;n the article, which appeared in the June 15 issue of the Journal of Biological Chemistry, Phylos scientists present the results of experiments where they used ProFusion technology to isolate 40 specific proteins involved in apoptosis.
"This is one of several key proof-of-concept experiments we are publishing," said Lawton. "It helps to underscore the credibility of the research and the progress of the technology."
The binding technology, said Lawton, is to the point where the selection and production platform is automated, and the entire protein screening process takes place in vitro, enabling researchers to totally control the environment in which proteins interact. Furthermore, Lawton said that researchers using ProFusion can screen libraries up to 10,000 times larger than those allowed by other technologies.
The company makes these binding proteins, which mimic antibodies, from trinectin, a component of human fibronectin. The artificial binders are about one-quarter the size of regular antibodies, allowing more to be packed on a chip. According to Lawton, trinectin is more stable than conventional proteins and has a higher affinity for binding to the target protein.
"One of the issues with protein chip science is going to be the stability of the binding proteins," Lawton said. "The wild type of this molecule has a melting temperature of 110 degrees Celsius, about twice that of an antibody. This will avoid any issues with shipping these [chips] around the world."
The company has also developed a chip surface chemistry that it says minimizes non-specific binding, and orients the binding protein in a uniform way in order to maximize its performance.
Gavin MacBeath, who has developed protein chip technology at the Harvard Center for Genomics, see this technology as very promising. "In terms of generating good capture molecules for array-based profiling, Phylos is a real contender," said MacBeath. "As for the chip technology itself (surface chemistry, low non-specific binding, etc.), they appear to be as good as anyone else."
Even with this respected platform, Phylos is likely to face stiff competition once the protein chip market really heats up. Not only are there companies like Ciphergen with products on the market, and emerging partnerships like that between Biacore of Sweden and Millennium Pharmaceuticals, but Lawton said most of the major players in the DNA chip market could also present competition in the coming years.
"The Motorolas, the Agilents, the Affymetrixes of the world, those are the people that we keep a very close eye on, because they have the resources to put together something very quickly," he said.
But Lawton is not too worried about being a protein chip pioneer. With $60 million in financing ó including $25.1 million closed at the end of last yearóand 92 employees, he sees Phylos as well-situated to turn its technology into a viable product platform. And the company''s technology, he thinks, could produce thousands of new binding proteins that competitors don''t have.
"There are many companies that have declared that they are developing protein chips," he said. "But there are extremely limited sources of good quality content."
MMJ and Alison McCook