NEW YORK (GenomeWeb) – As it continues to pursue its goal of bringing reagent development times down to two weeks, antibody firm AxioMx has identified transcription factors as one of the main areas where it will focus building its catalog.
Specifically, the company plans to establish a library of antibodies targeting the phosphorylated forms of transcription factors for which there are good antibodies targeting their non-modified forms, Michael Weiner, company founder and CSO, told GenomeWeb.
The idea behind this decision, he said, is that, while researchers are unlikely to switch to a new antibody if they already have one they like, they might be interested in looking at phosphorylated forms of that same target.
"Its a niche [that let's the company] get into the CHiP-Seq market with the belief that anybody who has actually used someone's antibody and likes it for a particular transcription factor would want to come to us to check out the phosphorylated states of that transcription factor to see if phosphorylation makes a difference," Weiner said.
Last month AxioMx said it received a Phase I Small Business Innovation Research grant from the National Institute of Diabetes and Digestive and Kidney Diseases to fund development of these reagents. The grant is a continuation of a $218,694 SBIR award the company received in support of the effort last year.
Launched in March 2012, AxioMx offers custom recombinant antibody development with the ultimate aim of delivering antibodies on a timescale similar to oligos or DNA sequence information. Currently, it can deliver antibodies internally within 19 days and to external customers within five weeks.
The company believes that bringing antibody development time sharply down will transform the technology, Weiner said. It is "like ordering oligos in a single day. It used to be that if you ordered an oligo and it took a week it wasn't that big a deal," he said. "Nowadays, if you order an oligo and you don't get it in two days, you're a little pissed off. And we think that in the future, antibodies will be like that, too."
AxioMx is the second antibody outfit founded by Weiner in recent years. In 2008, he, along with Stanford University researcher Michael Snyder (then at Yale University), Yale researcher Sherman Weissman, and Elm Street Ventures partner Mike Sherman, launched the biotech firm Affomix, which similarly aimed to shorten antibody production timescales while increasing quality.
Affomix, which was acquired by Illumina in 2010, also explored development of antibodies for CHiP-Seq, and, Weiner noted, the presence of CHiP-Seq expert Snyder on AxioMx's scientific advisory board played a role in nudging the company in this direction.
"There's a need for good CHiP-Seq antibodies in general," Weiner said, adding that of the roughly 800 human transcription factors there are good antibodies to between 100 and 200 of them. However, he said, most antibody use revolves around a relatively small number of extensively studied targets.
"Its a chicken and egg thing with researchers. Researchers generally go after things for which a lot of information is already known so they can add to the body of literature rather than taking some of the unknown ones and blazing a new trail," he said, noting that this was not meant as a criticism. "They are going after the ones for which they already have an inkling of what they are doing inside — for example, the factors involved in oncology."
That being the case, the bulk of the CHiP-Seq antibody business focuses on a dozen or two dozen commonly studied targets, Weiner said, which suggests that chasing down antibodies to hundreds of less-studied targets might not be the best approach from a sales perspective.
Whether there will be a market for antibodies to phosphorylated forms of these popular targets remains to be seen, he said, though, obviously, AxioMx is betting on it.
"The concept is to determine if there is a market for that," he said. "The tools aren't available, so [researchers] don't do those types of studies, and the question we are asking is, 'If the tools were available, would they do it?' Our belief is that people who have already validated their transcription factor antibody from Abcam or some other antibody supply house will check out [antibodies to phosphorylated forms]."
Transcription factors are a tricky antibody target, generally, Weiner said, due to the fact that they are often part of large, highly homologous families. Additionally, the positively charged portion of these proteins that binds to DNA is an attractive epitope for antibodies, as well, but, he said, this isn't actually the portion of the protein you'd want an antibody to target.
"If you just use purified proteins, for example, a lot of your antibodies are going to go against that area, and you don't want that," he said. "So, what we have been doing is using peptides from portions of the activation domains that are unique in the family."
In addition to transcription factors, AxioMx has identified membrane-spanning proteins as another initial target group for building its library. In this case, he said, the company's antibody development will be aided by its technology that lets it screen its phage libraries against whole cells overexpressing target membrane-spanning proteins.
"The idea there is we are getting them in the proper conformation and with the proper glycosylation," he said.
In total, Weiner said, AxioMx has six SBIR grants currently running. One of these, which the company announced earlier this year, is aimed at developing a new screening technology that will be key to its goal of dramatically speeding up the development process.
As opposed to existing phage display methods that screen libraries consisting of billions of M13 phages, each displaying a different antibody against single protein or peptide antigens, to identify good antibodies to that particular target, the new screening method will screen multiple antibodies against multiple antigens.
The goal, Weiner said, is to be able to screen libraries of 10 billion antibodies against libraries of 10,000 antigens, which would in theory allow AxioMx to potentially identify antibodies to entire proteomes in a single screen.
That technology is still under development but is "progressing nicely," he said this week.