He added that the relationship with Protagen and Ruhr-University Bochum is ongoing and that the group plans on testing more drugs using the UNIchip platform. The trio is also using the platform to study samples from patients with rheumatoid diseases.
Protagen Says Study Shows Its Protein Chips Shed Light on Monoclonal Antibody Effects
Protagen last week said that a recent paper demonstrates that its protein array platform could have drug-development applications.
The study, a collaboration between the company and researchers at University Children's Hospital in Düsseldorf and Ruhr-University in Bochum, both in Germany, employed Protagen’s chips to show that three tumor necrosis factor inhibitors used to treat autoimmune diseases may bind to a significant number of proteins other than their main target [Feyen O, et al. Off-target activity of TNF-alpha inhibitors characterized by protein biochips. Analytical and Bioanalytical Chemistry. 2008 Mar 16 [Epub ahead of print]
“Although there is no direct evidence that the off-target activity we have seen leads to pathological consequences, the link [to off-target binding] can not be excluded,” the authors concluded.
For Protagen, the study is a potential launchpad for reaching pharmaceutical customers. In January the firm raised €1 million ($1.5 million) in an interim financing round to fund diagnostics R&D work and to support the firm’s goal of partnering with pharmaceutical companies. The company also opened a North American subsidiary in Chester, NJ, last year (see BAN 1/22/2008).
In their study, the researchers used Protagen’s catalog AV-400 UNIchips to investigate the protein-binding activity of three protein therapeutics for rheumatoid arthritis and juvenile idiopathic arthritis: Remicade, a chimeric monoclonal antibody sold by Johnson & Johnson; Humira, a recombinant humanized monoclonal anti-TNF antibody sold by Abbott; and Enbrel, a fusion protein sold by Amgen and Wyeth.
As the authors noted, all three drugs include a number of different side effects, such as fever and an increased risk of serious infection. The researchers incubated the UNIchip AV-400 protein biochips with the TNF-blocking agents to check their respective specificity.
Remicade was found to be the most specific antibody with no off-target activity detected on the chip. However, both Humira and Enbrel showed off-target activity, with Enbrel binding to 10 proteins with affinities greater than 20 percent of its binding affinity for the TNF inhibitors. Humira, meantime, bound 19 proteins other than the TNF blockers, though its affinity for these was lower, at only 12-18 percent of its affinity for the TNF inhibitors.
Protagen CEO Christoph Hüls told BioArray News last week that the study is a ”major application for the chips because it shows actual results and [could] help monoclonal antibody researchers make decisions.”
In some ways, though, Hüls said the application demonstrated in the study was the ideal way to show off UNIchip’s potential. “In our view, an application that looks at proteins on a surface and their interaction with antibodies is robust,” he said. “Other applications like protein-protein interaction are more difficult interactions and we will focus on that in the future.”
In addition, he said that the UNIchip is “very predictive for immunohistochemistry.” Hüls, who previously worked at Aventis, Novartis, and Hoechst, said that the process of immunohistochemistry is often a “very expensive step and bottleneck in the [drug-development] process and we can speed it up and make it more efficient.”
In general, Hüls said that Protagen is “trying to prove this product via different applications” with the hope that “drug developers will request results with [its] biochips in any case that a monoclonal antibody should be used as a drug.”
He conceded, though, that Protagen still faces some skepticism from potential pharma and biotech clients that are not yet comfortable with protein array technology. “Always when you come to market with a new technology there’s a lot of skepticism,” he said. “It takes time until we have more studies published and the scientists get acquainted with the technology and adopt it more.”
Hüls said he has noticed that over the past year there has been greater awareness of the technology and that in some ways the firm is “over this hurdle of the acceptance of a new technology.”
Tim Niehues, director of the Center for Child and Adolescent Health at the University of Düsseldorf and a co-author on the paper, said that he was skeptical about working with array technology before partnering with Protagen.
“As a clinician I always have to be very skeptical about these kinds of results,” he told BioArray News this week. “There's a danger of the over-interpretation of results leading to unnecessary conclusions for patients. On the other hand, I am interested in using new technology to be more specific in treatment of patients with rheumatic diseases.”
Niehues said he developed an interest in array technology as part of an effort to find out whether it could be used to help treat rheumatic diseases. “In the long run we need individualized therapies for patients,” he said. “A highly sophisticated chip may in the future, but definitely not now, predict which patient will respond and which patient will not respond. I think it may be a tool to tailor therapy for those patients.”