In recent months, as it has become apparent that many proteomics researchers have a strong interest in gaining access to collections of antibodies, public organizations have begun to take initial steps toward satisfying the pent-up demand. HUPO hopes to spearhead an effort to produce libraries of anti-bodies for public consumption, as has its affiliate in Germany, the German Society for Proteome Research.
But while these public-sector organizations wrangle their way through organizational and funding difficulties, several companies have quietly emerged as potential sources of antibodies suitable for use in antibody microarrays and other platforms for large-scale analysis of protein samples. One of these, Richmond, Calif.-based Milagen, claims to have put together one of the largest collections of antibodies to disease-associated proteins, although the company remains secretive as to how.
Founded in 1997 by Moncef Jendoubi, a former associate professor of immunology at the Pasteur Institute in Paris, Milagen says it has built a library of 70,000 antibodies to proteins involved in a number of diseases, including cardiovascular disease and breast and lung cancer. Although the company ultimately aims to use its antibodies in arrays as part of its own target and drug discovery pipeline, the company is open to making its library of antibodies available to partners on a “case-by-case basis,” Jendoubi told ProteoMonitor.
To build its collection of antibodies, Milagen and its academic partners have studied tissues and cell lines of various diseases in order to identify differentially-expressed proteins. To date, the company has research relationships with 16 academic groups, including those in the urology department at the University of California, San Francisco, the National Cancer Institute, and the Hôpital D'Enfants Armand Trousseau in Paris.
Producing antibodies in animals, but how?
Milagen has generated polyclonal antibodies to these proteins using a proprietary process for producing antibodies in rodents, although Jendoubi declined to say which kind. Whereas conventional approaches to generating one polyclonal antibody in mice or rabbits might take three to six months, Jendoubi said his team can produce thousands of unique high-affinity antibodies in the same time period. Within a year’s time, Jendoubi said he hopes to push the total number of antibodies in Milagen’s collection to 100,000 from 70,000 today.
Jendoubi declined to disclose any details of the patent-pending technology, except to under-score the in vivo nature of the process: “We are using animals to generate antibodies,” he said. “We are not making combinatorial antibodies or [using] in vitro immunization of any sort. This is real immunization of a real animal by a real protein.”
Although it is unclear how Milagen has become such a prolific producer of antibodies, Jendoubi said the company has plans to put its technology to good use by proceeding through a whole host of diseases, generating antibodies to thousands of proteins associated with each disease. Jendoubi said Milagen has already accomplished this feat with prostate and breast cancer, and has made progress in developing its library of antibodies to proteins differentially expressed in lung cancer. Through its academic collaborations, Milagen hopes to do the same with diabetes, obesity, cardiovascular disease, as well as skin and kidney cancer.
In fact, Jendoubi said he believes the company’s collections of antibodies will be so thorough that the same collection of antibodies could be used in an array format to probe samples associated with practically “all major diseases.” To identify protein targets linked to a specific disease, Milagen plans to use its arrays to collect data on the unique pattern of protein expression associated with each disease.
Jendoubi admitted that there are significant challenges inherent in developing an antibody array platform, but nevertheless expressed confidence that his company has solved many of them. He claimed Milagen has confirmed that its antibodies are of high specificity, and that the company has overcome the technical difficulties associated with tethering antibodies to a solid surface, although he declined to discuss the details of Milagen’s attachment chemistry.
In the near term, Milagen’s apparent progress in producing large quantities of antibodies to disease-associated proteins presents a potential opportunity for researchers willing to collaborate on the company’s terms. While the company is “always eagerly looking for collaborators,” Jendoubi said that Milagen is ideally looking for pharmaceutical company partners to share the costs of research and allow the company to secure rights to royalties from any downstream revenue.
– JSM