Now that the post-genomic era has begun, many large pharma and biopharmaceutical companies are scrambling to integrate tools and services for proteomics into their drug discovery platforms.

As the year 2000 came to a close, activity in proteomics began a clear move into the spotlight occupied by genomics in 1999 and early 2000. According to Cambridge Healthtech Institute’s Drug Discovery and Development Deals Database (www.discoverydeals.com), dealmaking in proteomics tripled from 1999 to 2000. The database logged 139 proteomics deals in 2000, compared with 45 in 1999, an increase of 208.9%. Additionally, dealmaking in proteomics showed an upward trend during the course of the year (see Table 1). Compared with the 41 deals initiated in this area during first half of the year, 76 were initiated during the second half, an increase of 85%.

Table 1

Quarter	Proteomics Deals
1Q00	23
2Q00	18
3Q00	45
4Q00	53
Total 2000	139

See below for a graphical representation of this data:

Although genes encode proteins, and the transcription of genes determines the manner in which proteins are expressed, proteins are the major determinants of health or disease in a cell. One well-known analogy is that proteins are the actors in the cell, while genes are behind the scenes reading the cues. And while genes can be sequenced according to a linear string of bases, the function of a protein depends not on its amino acid sequence, but upon its properly folded, three-dimensional shape.

Due to the increased complexity of proteomics studies, relatively few companies have acquired a mastery of proteomics even approaching the high-throughput capacity and speed of genomics tools. But a growing number of companies perceive the value of proteomics, either as a means of augmenting genomic information or as an alternative route of basic science inquiry or drug discovery. The year’s top dealmakers in proteomics (see Table 2) included tool-based companies offering proteomics databases and/or instrumentation, technology-based companies offering research innovation in the study of protein-protein interactions, and finally, companies developing platforms for industrial-scale proteomics-based drug discovery.

Source: Cambridge Healthtech Institute

Proteomics Database Sector: Incyte and Proteome
Providers of proteomics databases, including Incyte and Proteome, were among the top ten proteomics dealmakers of the year. Many of Incyte’s deals in 2000 involved subscriptions to the LifeExpress database. Incyte began to augment its sequence and gene expression data with proteomic data through a collaboration initiated with Oxford GlycoSciences in 1998. The companies jointly launched LifeProt software in 1999 to interrogate data from the LifeProgram, PathoProgram, and PharmacoProgram databases developed through the collaboration. In November 2000, the alliance was restructured from a profit-sharing arrangement to a non-exclusive contract payment basis.

Proteome, which closed its first round of financing in December 1999, offers an integrated database product called the BioKnowledge library, comprising data and annotations organized into "volumes" for the proteomes of human, mouse, rat, yeast, worm, and other model organisms. Subscribers to Proteome’s databases in 2000 included the Janssen Research Foundation and the R.W. Johnson Pharmaceutical Research Institute (both Johnson & Johnson member companies), and Merck. In December 2000, Incyte acquired Proteome for $77 million in cash and equity. The acquisition will result in increased proteomic annotation of Incyte’s database offerings. Proteome will continue to offer the BioKnowledge library under its own name, but the merger will bolster the curation of these databases and accelerate internet access to Proteome’s human annotation databases.

Proteomics Instrumentation Sector: Applied Biosystems, Amersham Pharmacia Biotech, Proteome Systems
Several companies developing integrated, widely-applicable benchtop-style platform proteomics technologies were also among the year’s top ten. These included industry leaders Applera’s Applied Biosystems and Amersham Pharmacia Biotech, and emerging tools company Proteome Systems.

Applied Biosystems (formerly PE Biosystems), a division of Applera, offers a wide range of instruments and other products for life sciences research with major products in the proteomics area including Proteomics Solution 1, an automated system integrating sample preparation, MALDI-TOF mass spectrometry, and software for database searches; and Voyager, a LCMS protein purification station.

Many of Applied Biosystems’ proteomics deals for the year involved the licensing of instrumentation and consumable products to companies including Geneva Proteomics, HTS Biosystems, Human Genome Sciences, Oxford GlycoSciences.

Amersham Pharmacia Biotech (APB) offers instruments, supplies, and software tools for protein expression, purification, separation, and characterization through 2D gel electrophoresis and mass spectrometry. Although APB’s proteomics expertise is primarily in the liquid chromatography (LC) area, in March 2000, the company entered into a collaboration with Analytica of Brandford for the development new leading-edge mass spectrometry systems for the characterization of proteins and peptides.

Proteome Systems, founded in January 1999, is developing instruments and consumables for arraying and characterizing proteins, and designing informatics tools and databases for high-throughput proteomics analysis. The group has several key commercial and academic agreements already, including a multiyear joint research agreement in proteomics with Dow AgroSciences, announced in 1999 and extended in February 2000, and a strategic alliance with Shimadzu for the development of high-throughput screening proteomics technology, extended in December 2000.

Protein-Protein Interaction Sector: Myriad Genetics and Hybrigenics
Companies building research platforms and compatible databases in protein interaction studies and cell mapping among the top ten included Myriad Genetics and Hybrigenics. Myriad, a genomics company focusing on the discovery of disease-related genes, has established ProNet, a program for identifying and analyzing protein-protein interactions for all human proteins. The company has developed a proprietary high-throughput system based on the yeast two-hybrid methodology, and plans to map the universe of protein-protein interactions in the next several years.

Myriad entered into a number of agreements with other companies covering the application of its ProNet technology and database during 2000, including an extension of its collaboration with Bayer in December 2000. Myriad also entered into a $26 million strategic alliance with Hitachi in May 2000, to establish a designated ProNet facility to expedite the discovery of novel protein-protein interactions for Japanese customers. And in January 2000, Myriad extended a ProNet-based target discovery collaboration with Monsanto and entered into another with Roche.

Hybrigenics, which describes itself as a functional proteomics company, has developed a high-throughput protein-protein interaction mapping technology based on screening protein fragments supported by a bioinformatics platform, called PIMRider. The company generates these protein-interaction maps (PIMs) for pathogen systems and for the cDNA of normal and diseased tissues. In September 2000, Hybrigenics entered into a collaboration with XTL Biopharmaceuticals to co-develop novel drugs against hepatitis C virus (HCV). The company also entered into a collaboration with Lynx Therapeutics to discover expressed genes and protein interactions and pathways in human obesity.

Industrial-Scale Proteomics Sector: Oxford GlycoSciences and Geneva Proteomics
Companies developing industrial-scale platforms to apply proteomics to drug and diagnostics discovery and development made up the last section of the top ten; these include Oxford GlycoSciences (OGS) and Geneva Proteomics (GeneProt). OGS has established itself as a leader in the field, while GeneProt is still very much a startup, but both companies are developing a factory-driven approach to proteomics research.

OGS’s main proteomics technologies are ProteoGraph, a high-throughput 2-D gel electrophoresis system, and ROSETTA, a proprietary bioinformatics system to track and analyze the data, which also correlates data obtained by the above techniques with other data available in public and proprietary databases.

Although OGS is applying its proteomics technology internally to discover and develop therapeutic and diagnostic products, the company has established several external proteomic collaborations with LP companies.

In December 2000, the company signed an agreement with Pfizer to apply its proteomics platform to the discovery of targets and biomarkers in Alzheimer’s disease and atherosclerosis, continuing the collaboration initiated between the two companies in April 1998. And in March 2000, OGS and Bayer entered into a multi-target research collaboration in the area of respiratory disease. OGS also entered into a biotech-biotech alliance with Medarex in September 2000, to apply Medarex’s fully human antibody technology and OGS’s proteomics technology toward high-throughput protein analysis and target validation.

Geneva Proteomics (GeneProt), a Delaware-based company founded in association with the Swiss company Geneva Bioinformatics, began operations in March 2000 and raised its first round of financing in April. The company is establishing industrial-scale proteomics "factories" in Geneva and the U.S.. These facilities will perform large-scale mass spectrometry analysis to determine protein profiles of tissues of healthy and diseased individuals. The company entered into an $84m alliance with Novartis Pharma in October 2000 to discover novel therapeutics, targets and biomarkers. Under the agreement, GeneProt will analyze the protein profile of three human diseased tissues or body fluids, selected by Novartis, in comparison with healthy samples. Novartis will have the option to develop peptides and proteins of interest identified through the research.

As is indicated by the continuing rise of dealmaking in proteomics, this technology area is beginning reach the same stage of widespread usage and progress that now characterizes genomics. Most leaders in the field of genomics-based drug discovery have shown their commitment to promptly incorporating the most advanced technologies into their platforms. Companies that have such systems, and are already involved in formulating and testing biological hypotheses through proteomic studies, will have a significant advantage over most of the rest of the pharmaceutical field, as they will be poised for the next phase of evolution of the drug discovery process—when everyone will have access to high-throughput methods for genomic inquiries, and the winners will be those with the most intelligent means of identifying ideal drug targets.