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PerkinElmer Enters Pattern Biomarker Screening with NCI-FDA Ovarian Study


PerkinElmer has launched a new biomarker initiative that may lead the company down the path to diagnostics and clinical development, Mary Lopez, business leader for analytical proteomics at PerkinElmer, told ProteoMonitor this week.

“PerkinElmer is a tools company, but we are moving into the area of platforms and solutions,” Lopez said. “We are developing a platform for biomarker screening, and initially it will be a research platform. Whether we go into the clinical area is still something that is under discussion, but is not off the table.”

Lopez announced at the American Society for Mass Spectrometry meeting in Nashville, Tenn. last month that PerkinElmer has embarked on an ovarian cancer study with Emanuel Petricoin and Lance Liotta of the NCI-FDA Clinical Proteomics program (see PM 5-28-04). She said at the time that the company was in the process of completing a CRADA for the collaboration, and expected everything to be signed this summer. This week, she clarified that the study “has been ongoing since November,” and that preliminary data has already started to come in.

Lopez said that Petricoin and Liotta approached PerkinElmer in October about setting up a collaboration that would be part of the pair’s ongoing efforts to develop a platform for an ovarian cancer diagnostic. The offer came at a time when PerkinElmer was looking to expand its original proteomics focus beyond gel-based differential expression proteomics, to include the exploding field of mass spec-based biomarker discovery, Lopez said. “We were already looking at applications of this type, but almost at the same time, they approached us and it really became obvious that there was a huge synergy that could happen here,” Lopez said. For PerkinElmer, it was an opportunity to develop a biomarker platform based on its MALDI proTOF mass spec. For Petricoin and Liotta, she said, it was an opportunity to test out another platform in their ongoing quest to develop an ovarian cancer diagnostic.

“The general idea [of the ovarian cancer diagnostic] is sound, but they have not been able to use the technology to date that gives them the reproducibility and robustness to be appropriate for a clinical platform,” Lopez said. Petricoin and Liotta have said in the past that they are trying out different platforms in an attempt to improve reproducibility for their test (see PM 7-18-03, 2-13-04), and the more recently released data from the NCI-FDA program combines a ProteinChip interface with an Applied Biosystems Q-STAR, as opposed to the ProteinChip-SELDI combination that they used in their original Lancet study in 2002. On their website, Petricoin and Liotta state that they are “thoroughly evaluating new platforms, bioinformatic tools and data visualization efforts” and that they will be looking at using FT-ICR in addition to TOF-based techniques. They have not announced that they are working with PerkinElmer. Petricoin and Liotta could not be reached for comment as of press time.

The PerkinElmer approach differs from that of previous ovarian cancer studies in that it hones in on applying the concept of mining “carrier proteins” — large, highly abundant sticky proteins such as albumin, said to carry smaller, potentially diagnostic peptides. This approach has been championed by Thomas Conrads, director of the mass spectrometry center at the Laboratory of Proteomics and Analytical Technologies at SAIC-Frederick, who is partnering with Petricoin and Liotta (see PM 10-17-03, 11-28-03). In addition to his work with carrier proteins, Conrads also published a paper in Clinical Proteomics this month that listed 1,444 serum proteins identified by conventional fractionation techniques (see briefs, p. 9).

The platform that Lopez’ group has developed with Petricoin and Liotta uses sample prep kits that are based on membrane chromatography technology obtained from a partnership that PerkinElmer has with Vivascience of Hannover, Germany. The kits affinity capture a variety of high abundance proteins and then elute the attached peptides through the use of a proprietary elution buffer. The eluted peptides are then spotted directly on a MALDI plate and run through PerkinElmer’s proTOF mass spec. Lopez said she is still looking for a suitable software package to add to the back-end of the workflow, but hopes to find a partner “in a matter of months”— either one with a readily available package, or one that is ready to “co-develop [software] in a very short period of time.” She said the company is in discussions with several different potential software partners. In the meantime, it is outsourcing the software analysis work.

PerkinElmer is initially looking at 400 ovarian cancer samples using this platform, first in the form of pooled samples, and then later as individual samples. Lopez’s group will eventually co-publish the results with Petricoin and Liotta, and will also release the sample prep kits — in the form of both spin columns and 96-well plates — as commercial “biomarker kits” beginning in early 2005, Lopez said.

That release will be just the first fruit of the company’s new biomarker screening effort, according to Lopez. PerkinElmer has already formed some smaller mass spec biomarker collaborations — including another on ovarian cancer with Mount Sinai School of Medicine in New York — and has begun work on applying the platform to samples from an Alzheimer’s study that it has been conducting in collaboration with the Rush Alzheimer’s Institute and the Buck Institute of Age Research (see PM 9-19-03). The Alzheimer’s study had previously focused on a gel-based differential expression platform, and initial results from that study are currently in press at Electrophoresis, Lopez said. She added that the complete study data set will be submitted to a “high profile journal” later in the year. The company also hopes to create a commercially available complete platform for pattern-based biomarker discovery — including a software solution.

But it’s not just product sales and partnerships that PerkinElmer is looking to benefit from when it comes to biomarkers. “We are interested in acquiring intellectual property in the content area — being biomarkers or other types of biological content,” Lopez said. What the company will do with that IP is not yet clear, but at the moment, nothing is being ruled out. “At this stage, we don’t foresee going into drug discovery as a business strategy for us. However, we are not unaware … that the intellectual property has value. And how we choose to utilize that value is still under consideration,” she said.


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