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Antibody Firm Affomix to Collaborate with U of Montreal's PGx Centre on Heart Disease Biomarkers

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By Adam Bonislawski

Proteomics reagents firm Affomix announced this week a collaboration with the University of Montreal Pharmacogenomics Centre and the Montreal Heart Institute for the study of HDL protein biomarkers linked to cardiovascular disease.

Using its automated, high-throughput monoclonal antibody selection technology, Affomix will be producing several antibodies for each protein target chosen by PGx Centre researchers, enabling them to undertake quantitative, multiplexed profiling of the putative biomarkers.

The goal is to have at least three antibodies produced for each biomarker target, Michael Phillips, director of the PGx Centre, told ProteoMonitor, the expectation being that by using multiple antibodies per target the researchers will be able to build more complex, precisely quantitative protein profiles to measure patients' responses to various anti-atherosclerotic agents.

"We've picked some targets in HDL to try to quantify the various ratios of a number of targets there. And now we're going to actually build multiple antibodies to the same target so that we're not just measuring it with one antibody, we're measuring it with multiple antibodies and probably to different antigens," Phillips said.

Assays targeting proteins with a single antibody can give researchers a "yes-no" answer as to whether or not a protein is in a sample, Phillips said, but using multiple antibodies provides a more complete picture.

"We're not just trying to say 'yes or no'. We're trying to see how much [of a protein] is around. By doing multiple measurements of the same target, we should be able to come up with a consensus and an average. And we're going to come up with an ability then to quantify the ratios of the various proteins that are in the HDLs, assuming that with disease state or exposure to specific medications it might change the composition of those proteins."

Affomix produces antibodies using a yeast two-hybrid-based technology called Y2H Express that works by excising non-specific antibodies from a library of antibodies generated in yeast cells. The process increases the specificity of the company's antibodies in yeast two-hybrid systems from the 5 percent typical with conventional methods to 30 percent, Affomix president Michael Sherman told ProteoMonitor last year (PM 04/09/2009).

"The attraction for me was their high-throughput and streamlined ability to make targeted antibodies," Phillips said. "They have a really great system for producing very specific antibodies and then titrating and picking highly precise stringencies and specificities for the antibodies."

"We started thinking, where will this technology be most useful, in what kind of applications?" John Boyce, head of business development for Affomix, told ProteoMonitor. "And one thing that's always fascinated me has been the inability of gene expression to move into point-of-care diagnostics. So we started asking, 'Who is a leader in molecular diagnostics and clinical trials in pharmacogenomics?' Michael Phillips has been doing a lot of great work on both fronts, and so we were talking and he let us know that he had a large well-phenotyped cardiovascular population in Canada that he was currently using. So we approached him and the collaboration began that way."

Affomix's antibodies also bring with them potentially interesting new readout options, Boyce said. The company is able to attach oligonucleotide backbones to its antibodies that allow the pulled-down proteins to be read via next-generation sequencing.

"In terms of actually doing this with next-generation sequencers and making the reagents to do this, this is new," Boyce said. "Generally what would happen if you tried to chemically couple an antibody to an oligonucleotide was you couldn't really delineate where on the antibody the fusion was going to take place. And so a lot of the time you would interfere with the active site of the antibody and render it useless."

Because Affomix's fusion technique doesn't involve chemical coupling, the company is able to attach oligonucleotides while maintaining the integrity of the antibodies, Boyce said.

"Hooking DNA up to these [antibodies] is definitely something that's interesting," Phillips said. "That gives us a lot of flexibility on the back end to try to do some novel stuff."

The agreement to provide the PGx Centre with antibodies for biomarker research is the second such arrangement for Affomix this year. In January the company entered into a collaboration with the City of Hope cancer center to provide antibodies to be used to create proteomic profiles for various types of cancers (PM 01/22/2010).

Ultimately the company seeks to develop what it calls the "Affome" — a comprehensive set of antibodies that can be used to detect and quantify all the proteins in the human proteome.

Both Phillips and Boyce declined to disclose the financial terms of the deal, although Boyce did allow that there was "revenue associated with [the collaboration]."

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