Amid cries from the research community about the sorry state of antibodies, industry and government have stepped up efforts to both bring more of them to market and improve their quality.
This week, the National Cancer Institute announced a request for proposals for the next round of its effort to raise the bar on cancer antibodies, following several recent announcements from commercial vendors related to antibody collaborations and product launches.
Two weeks ago, Sigma-Aldrich and the University of California, San Francisco, said they will be collaborating to develop monoclonal antibodies. The same day Strategic Diagnostics, the University of Oregon, and the Louisiana State University Health Science Center, New Orleans, announced an initiative to create an antibody library to study Usher syndrome.
A week earlier, LifeSpan BioSciences announced a plan to release 20,000 immunohistochemistry-validated antibodies during the next four years. And AnaSpec has continued to add new products to its growing antibody portfolio.
It’s probably just coincidence that the flurry of activity is occurring all at once. Nonetheless, it addresses a major hurdle in proteomics: the lack of high-quality antibodies.
The NCI’s RFP follows the first funding round for its antibody initiative launched last November as part of its Clinical Proteomic Technologies Initiative for Cancer program, a five-year, $104 million project to develop new proteomics tools and technologies for cancer research [See PM 11/29/07].
Early on, the NCI’s proteomics division had identified the production of highly characterized antibodies as a priority, and in the spring it awarded the first contract for antibody development to Strategic Diagnostics, which will produce three antibodies for each of 42 antigens [See PM 04/10/08].
Under this week’s RFP, awardees will be again asked to raise three antibodies against each of 42 new antigens. The antigens covered under this RFP were not included in the contract awarded to Strategic Diagnostics and include dynactin 2 (p50), fructose-bisphosphate aldolase C, and ubiquitin-conjugating enzyme E21 (UBC9 homolog yeast).
More information about the RFP is available here.
Antibodies generated as a result of the RFP will be characterized initially by the NCI’s antibody-characterization laboratory established at its Frederick, Md., site last year, then by Harvard Medical School’s Institute of Proteomics and the Royal Institute of Technology in Stockholm, Sweden, which runs the Human Protein Atlas.
According to Henry Rodriguez, director of NCI’s Clinical Proteomic Technologies for Cancer program, the institute expects to name the contract grantees in late September or October. The NCI anticipates issuing the next RFP late this year or in early 2009, he said.
“Now you need ways of measuring proteins and to do that you need universal reagents, antibodies, and it’s all about content.”
Antibodies generated from the first funding round awarded to Strategic Diagnostics are anticipated to be publicly available sometime before the end of the year through the Developmental Studies Hybridoma Bank at the University of Iowa, Rodriguez added.
Demand, Yes. Supply, No
The recent flurry of activity comes after years of complaints from proteomics researchers that the number of antibodies available and their poor quality were hindering progress in the field.
Last year, Joshua LaBaer, director of Harvard’s proteomics institute, called for greater work in antibodies and more resources from the federal government to support such work in order to help bring proteomics out of its Dark Ages [See PM 06/28/07].
Mike Snyder, a professor of molecular, cellular, and developmental biology at Yale, has also cited the low number of antibodies that have been generated against proteins as a significant barrier, saying antibody arrays have about 600 antibodies, just a minute fraction of the number of proteins found in the human proteome [See PM 11/01/07].
This spike in demand for antibodies is a recent phenomenon, those in the industry said, spurred on by the sequencing of the human genome, resulting in the identification of more than 20,000 genes, which created a need “for antibodies to recognize those gene products,” said Joseph Brown, president and CEO of LifeSpan, which has a catalog of more than 37,000 antibodies.
“Many proteins are processed by proteolysis or phosphorylation, and there are multiple applications,” said Brown. “Typically, you need two, or five, or 10 antibodies for a given gene, so there’s a need for literally hundreds of thousands of antibodies.”
While there is no shortage of companies trying to meet the need, the quality of the antibodies has often missed the mark. To address the issue, the research community has turned to itself. The Human Protein Atlas, spearheaded by Matthias Uhlen, now contains 3,014 antibodies and more than 2.9 million images. Also, ProteomeBinders, a European-US consortium, was started to catalog and eventually produce binding molecules that can detect all human proteins [See PM 03/22/07 and 12/13/07].
According to Rodriguez, part of the goal of the NCI’s antibody initiative is not only to increase the agency’s role in antibody production but to raise the stakes for everybody involved.
David Smoller, president of the research biotech business unit at Sigma-Aldrich, said commercial vendors are clearly interested in the business of antibodies as evidenced by what he sees as a growing number of companies that have joined the antibody fold. According to market analysts, the monoclonal antibody market alone is expected to triple in size from $10.3 billion in 2004 to an estimated $30 billion by 2010.
Because there are so many proteins, it’s virtually impossible for any one company to make antibodies against all of them, making the field wide open for new players, according to Smoller. In addition, “it’s a low barrier to entry,” he said. “You just need a bunny to inject with an antigen.”
Smoller’s own firm, Sigma-Aldrich, has been a busy player in the antibody market the past few months. In addition to the collaboration with UCSF, the company earlier this year reached a deal with Atlas Antibodies, the commercial arm of the Human Protein Atlas, to launch 22,000 highly characterized antibodies by 2015 [See PM 02/14/08]. Sigma-Aldrich released 1,800 antibodies in February and is scheduled to release about 1,800 additional ones in August, Smoller said.
The company also announced a licensing deal with MorphoSys in February for recombinant research antibodies. The number of antibody deals that Sigma-Aldrich has forged during the past few months is no coincidence, and more could be coming down the pike “as we move more into being a leader in functional genomics,” said Smoller. “Now you need ways of measuring proteins and to do that you need universal reagents, antibodies, and it’s all about content.”
Rodriguez of NCI’s Clinical Proteomic Technologies for Cancer program said that while he couldn’t say for sure that industry is responding to the institute’s lead, he said he is encouraged by what he is seeing so far.
“If the spirit of what [the recently announced] collaborative projects do is along the line of what NCI is doing in our program, that just raises the bar for the science community at large,” he said.