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Year In Review: 2003 Sees Clinical Proteomics, HUPO, Integration on Rise

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2003 was an up and down year for proteomics: Academic and clinical researchers made out well — spurred by hefty NIH funding initiatives, instrument vendors courting customers, HUPO’s expansion, and an explosion of interest in proteomics biomarker discovery — while technology start-ups continued to fumble for footing, and large instrument companies merged and reorganized their marketing strategies to stress product integration.

NIH Funding Strong

Following on the 2002 launch of 10 NHLBI centers, the NIH in September funded eight Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases at academic institutions across the country — all eight of which will include significant proteomics cores — with a total of $350 million.

Later that month, NIH director Elias Zerhouni introduced his $2.1 billion roadmap, establishing the creation of several trans-NIH initiatives. The National Academies came out in August with a report suggesting that the NIH create such initiatives, which involve the financial and administrative participation of many institutes for a single grant. The roadmap included three proteomics-focused trans-NIH initiatives, among them the establishment of two to four National Technology Centers for Networks and Pathways. The focus for these centers will be on developing technologies that can look at dynamic systems of proteins and produce quantitative, spatial, and temporal information at high resolution.

Meanwhile, an increasing number of individual NIH institutes have put out proteomics RFAs this year, several of which focus on biomarker discovery. In particular, the National Institute of Diabetes and Digestive and Kidney Disease put out two RFAs for the study of proteomics in diabetes, with particular emphasis on biomarker discovery; and the NCI renewed its four-year-old Early Detection Research Network for the discovery and validation of cancer-related biomarkers.

Not to be outdone, the Department of Energy laid out a 20-year roadmap that included up to $500 million in funding for the creation of large proteomics centers, pending congressional approval.

NIH money, at least, is not projected to run out anytime soon: despite lower growth rates in the agency’s FY 2004 budget, industry analysts expect money earmarked for proteomics technology development and proteomics-based scientific discovery to continue to grow at a healthy rate.

Biomarker Buzz

In addition to these newer initiatives, the NCI-FDA collaboration led by Emanuel Petricoin, which started the biomarker craze with the February 2002 Lancet paper on ovarian cancer proteomic patterns, continued to steam ahead. Petricoin’s gang widened its focus to breast, prostate, and lung cancer as well as ovarian cancer. The group also made the switch from Ciphergen’s SELDI mass spec to ABI’s Q-STAR for its pattern detection activities, although it continues to use the ProteinChip interface. Meanwhile, several academic researchers — in particular, Richard Caprioli at Vanderbilt University — grabbed onto the basic methodology to launch their own cancer biomarker pattern studies.

Instrument companies also enthusiastically embraced biomarkers, while stressing their desire to provide easy-to-use tools for the benchtop biologist, particularly in the area of biomarker research. After settling its lawsuit with Lumicyte in June, Ciphergen continued to advertise the popularity of its now exclusively-owned SELDI technology among academic researchers looking for biomarkers. Also, this fall, the company launched a 14-city seminar tour advertising its biomarker program, and announced a media campaign to promote biomarker discovery using SELDI technology.

In competition with Ciphergen’s seeming monopoly on do-it-yourself clinical biomarker discovery tools, Bruker Daltonics — now Bruker Biosciences — launched its ClinProt biomarker discovery system at June’s ASMS conference. The system centers around using magnetic bead technology for prepping samples in place of the ProteinChip. Bruker also launched two biomarker discovery centers this year.

Meanwhile, PerkinElmer stressed its interest in biomarkers with a talk at the October HUPO conference in Montreal describing the discovery of possible biomarkers for Alzheimer’s disease. Thermo Electron and Applied Biosystems kept more of a distance from direct involvement in biomarker discovery, but also emphasized the targeting of small biologists in marketing campaigns. SurroMed, a start-up focused entirely on biomarker discovery, also made strides with more than five research collaborations, including a December deal with Bruker.

Functional proteomics — particularly in reference to protein-protein interactions — also became a buzz-phrase in 2003. ABI announced its intentions to get involved with functional proteomics with the launch of its 8500 Affinity Chip Analyzer in September, which the company says can conduct 400 SPR experiments simultaneously on one surface. Ciphergen also launched a protein interaction offering in June with its Interaction Discovery Mapping system. Protein arrays moved along as well, with Protometrix launching its yeast proteome chip in April and Zyomyx launching its protein biochip system in February.

Mergers Morph Market

Bruker featured in this year’s M&A news, with the merger of Bruker Daltonics and Bruker AXS completed July 1. The newly configured Bruker Biosciences quickly reinvented itself as a complete proteomics solutions company, with the X-ray crystallography AXS arm serving as the “structural proteomics” part of the picture. Reports from the company’s first quarter as a fully merged company, however, indicated that this branch could be an Achilles’ heel: while Daltonics’ mass spec sales grew 22 percent in the third quarter of 2003, AXS X-ray systems sales were flat.

Still, Bruker wasn’t the only believer in structural proteomics in 2003. In April, the UK and Canada announced the formation of a $62.1 million Structural Genomics Consortium, while later that month Structural Genomix signed a deal with Eli Lilly to build an X-ray crystallography platform for the pharma company. Meanwhile, Berkeley, Calif.-based Plexxicon announced a deal in May with Genentech to provide the biotech giant with co-crystallization of targets and inhibitors.

Thermo joined Bruker in its ambitions to be an across-the-board proteomics tools provider, as well as in introducing a new FT-MS at Pittcon in March. As part of its plans for repertoire expansion, Thermo also announced a partnership in February with Amersham Biosciences to co-market mass spectrometers and to co-develop other proteomics tools. Amersham went on to make a splash in October when General Electric announced its intention to buy all of Amersham PLC for $9.5 billion. It was still unclear at year’s close what would happen to Amersham’s protein separations and proteomics divisions, which — before the acquisition announcement — Amersham Biosciences’ President Andrew Carr had said would be a particular focus for the company in the next year.

The other big takeover news of 2003 came from Oxford Glyco-sciences, which spent almost the entire first half of the year bouncing back and forth to different potential buyers at the negotiating table. OGS announced in mid-January that it would merge with Cambridge Antibody Technology. CAT said almost immediately that it would look into divesting OGS’ proteomics unit after the merger. Things seemed wrapped up for CAT until late February, when Celltech and a few other companies approached OGS to inquire about putting in possible competing bids. OGS was said to have turned away Celltech almost right away, but by the end of March the company acknowledged that it was back to the drawing board and was in talks with several potential buyers. In early April, OGS shareholders rejected Celltech’s offer, but by mid-April, Celltech had strongarmed OGS into accepting a disappointing offer of £101.4 million ($160 million). Celltech said almost immediately that it had plans to let go of the proteomics unit, and in late May the company announced it would divest proteomics almost entirely, while keeping some of the division’s resulting oncology targets. Finally, in late November, Celltech announced that it had been unable to find a buyer and closed down the proteomics services unit, just as Large Scale Biology was announcing that it was closing down its proteomics contract service business.

HUPO Lands in Montreal

While proteomics interest declined for some businesses, interest in HUPO skyrocketed this year, with all five HUPO initiatives moving forward at least into pilot phases. The Human Plasma Proteome Project made the biggest splash, with several presentations and posters at the October HUPO conference in Montreal describing progress in the project’s pilot phase. The conference had over 2,000 attendees. The initial pilot phase involved having commercial and academic research labs throughout the world test the performance of different technologies on analyzing the serum proteome of reference samples. Final data for this phase is due at the end of this month. Whether and how to remove high abundance proteins from serum before analysis was a popular debate, with Agilent’s Multiple Affinity Removal System — introduced at DDT in August — getting generally high marks for its ability to remove the six most abundant proteins from plasma.

Meanwhile, the brain proteome project got off the ground in Germany, with pilot projects on mouse and human brains scheduled to begin in January. The antibody initiative — which consists of several related initiatives under one umbrella — also moved forward, with China adding a project, the Swedes signing on with a plan for a Human Proteome Resource, and the German Society for Proteome Research getting ready to start the mass production of monoclonal antibodies in January 2004 at a new center in Croatia. The standards and liver projects were in the midst of their pilot phases at the end of 2003, with plans to publish in 2004.

HUPO President Sam Hanash also announced at the October conference that the organization’s international headquarters would be established in Montreal. This announcement coincided with the appointment of Montreal’s Jean Bergeron as the next HUPO president, effective next year.

— KAM

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