Swartz Analytical Techniques in Combinatorial Chemistry

240	Brock and Andrews

Products/technologies: Proprietary small molecule combinatorial chemistry technology, small molecule libraries, and proprietary automated chemical synthesis systems. The Multipin system technology (involving parallel synthesis of individual peptides on a solid phase support of 96 polyethylene pins arrayed in a format similar to microtiter plates) is now also being applied to libraries of small organic molecules. Multipin SPOC kits (solid phase organic chemistry) are sold through Chiron Mimotopes.

Contact: Kimberly Kraemer, Manager, Corporate Communications

Chiroscience Group plc

Cambridge Science Park, Milton Road, Cambridge CB4 4WE, UK Phone: [phone]; Fax: [phone]

E-mail: [e-mail] Internet: http:/ /www.chiroscience.com

Stock: CRO (London Stock Exchange)

Profile: Founded in 1992 to capitalize on its founders’ expertise in chiral technologies and the anticipated market growth in chiral drugs, the company acquired Darwin Molecular Corp. in December 1996. The move paved the way for Chiroscience’s entry into genomics, based on Darwin’s integrated genebased discovery platform that includes advanced bioinformatics, combinatorial chemistry, and cell-based screening capabilities. It continues to expand its technological knowledge in chiral and medicinal chemistry, drug discovery, and disease mechanisms, and has used the knowledge to build a broad drug discovery program. ChiroTech, the company’s technology services business, has developed relationships with companies in the pharmaceutical industry by solving complex chiral problems through various partnerships and collaborations.

Products/technologies: Rational drug design capabilities; chiral technology; mass spectrometry Tag technology. ChiroTech offers the ChiroChem Collection for application in combinatorial and medicinal chemistry. The collection of molecules, derived from specifically selected classes of compounds, is being launched using a phased approach. The regular supply of these structures, both novel and technically challenging in their synthesis, will complement the customer drive to establish greater structural diversity. Each new series in the collection will be accompanied by a diagram illustrating the extent of diversity achieved.

Contact: Dr. Brian Gennery, Director of Development

Commercial Resources

241

ChiroTech (See Chiroscience Group)

CombiChem

9050 Camino Santa Fe, San Diego, CA 92121, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail]

Internet: http:/ /www.combichem.com

Profile: Founded in 1994, this privately held company develops and provides integrated discovery chemistry technologies and services in collaboration with pharmaceutical, biotechnology, and fine-chemical companies to accelerate the drug discovery process. In these partnerships, the companies provide the biological capabilities and Combichem provides the chemical expertise of the discovery process. Its mission is to provide a highly efficient and successful approach to the discovery of new drug molecules.

Products/technologies: The company has proprietary technology and products in the areas of instrumentation for automated multiple-parallel synthesis, advanced chemical design software for diversity assessment and optimized chemistries. Products include the Drug Discovery Engine, which accelerates drug discovery through the integration of medicinal chemistry, small library design technology, and automation tools. Lead Generation is a process employed for novel targets with no known leads. Its proprietary Universal Informer Library generates information and launches the drug discovery cycle. With Lead Evolution, hypotheses are generated based on available data; it then matches the hypotheses against its proprietary virtual library and ultimately synthesizes alternate drug templates. Lead Optimization is a proprietary design methodology that constructs libraries around a collaborative partner’s lead to improve it before identifying it as a drug development candidate. CombiChem is collaborating with Biotage in the development of an automated parallel purification system, the CombiSynx PWS-20x, for combinatorial libraries.

Contact: Vincent Anido, Jr., Ph.D., President and CEO

ComGenex, Inc.

Hollan Erno u.5, Budapest, H-1136, Hungary

Phone: [phone]; Fax: [phone]

E-mail: [e-mail]

Internet: http:/ /www.comgenex.com

242	Brock and Andrews

Profile: The company was established in Budapest, Hungary, in November 1992 after an incubatory period of 5 years under CompuDrug Chemistry Ltd. ComGenex supplies substances for classical and high-throughput screening. The company is said to have a strong chemical background in solid and solution phase combinatorial chemistry and adapts its products and services to the ever changing and growing needs of the market. ComGenex is a sister company of RoboSynthon, Inc., which markets the MultiReactor combinatorial chemistry workstation for parallel organic synthesis manufactured by ComGenex. Offices are also located in Europe, Japan, and the United States.

Products/technologies: The company has more than 15,000 compounds in stock for high-throughput screening; this stock is dynamically changing by about 10–30% of the compounds each month. The supply of compounds is split between external suppliers and in-house synthesis, which is carried out using its Matrix Technology, a proprietary solution phase combinatorial chemistry technology. ComGenex also offers lab services; its labs are located in the Central Chemical Research Institute of the Hungarian Academy of Sciences. Additionally, it provides plant extracts, offering a collection of more than 390 extracts from the geographic region of Hungary.

Contact: Dr. Ferenc Darvas, President and CEO

Daylight Chemical Information Systems, Inc.

27401 Los Altos, Suite 370, Mission Viejo, CA, USA Phone: [phone]; Fax: [phone]

E-mail: [e-mail] Internet: http:/ /www.daylight.com

Profile: Daylight Chemical Information Systems, Inc. was incorporated in 1987 and grew from the MedChem Project at Pomona College. The invention of the SMILES language, by Dave Weininger, first at the U.S. Environmental Protection Agency in the early 1980s and then Pomona, laid the groundwork for the creation of a new chemical information system. Daylight’s mission has been to provide high-performance chemical information processing tools to chemists. New software has been developed continually and the list of available and supported software continues to grow. Emphasis has been placed on the Daylight Toolkit, a set of programming libraries constituting a chemical information infrastructure on which custom applications can be built. The Toolkit has been used both by Daylight developers to build supported applica-

Commercial Resources

243

tions and by customers to build custom in-house applications. In addition to the corporate office in Mission Viejo, the company has a research office in Santa Fe, New Mexico.

Products/technologies: Daylight Software Release 4.5 is an integrated set of programs and libraries providing high performance chemical information processing, including structural entry, display, distributed data storage, retrieval, and searching. Release 4.5 runs under Unix with user access via X-Windows (e.g., Macs, PCs). The company also provides server programs providing network services, and various toolkits (object-oriented programming libraries). Daylight’s combinatorial library toolkits are used to register, store, and search designed libraries.

Dyax Corp.

765 Concord Avenue, Cambridge, MA 02138-1044, USA Phone: [phone]; Fax: [phone]

E-mail: [e-mail] Internet: http:/ /www.dyax.com

Profile: A privately held company, Dyax was formed in 1996 with the merger of Biotage, Inc., a provider of preparative chromatography products and located in Charlottesville, VA, and Protein Engineering Corp., a Cambridge, MA, biotechnology company. Its ‘‘purification by design’’ philosophy incorporates the design and creation of a broad range of systems to effectively meet any purification challenge.

Products/technologies: The company’s proprietary Phage Display technology is used for discovery of high-affinity ligands in drug discovery, for development of custom affinity purification ligands, and for development of highly specific diagnostics. Phage display is a method for generating novel molecules with high binding affinity for virtually any target. As a part of its existing separations business, the company is exploiting this technology to develop high-value affinity separation products designed to increase the efficiency and reduce the cost of pharmaceutical purification. Dyax is also applying phage display to the discovery and development of a new generation of diagnostic imaging agents and novel pharmaceutical compounds that bind tightly and specifically to known diagnostic markers and therapeutic targets. Other products include chromatographic systems, columns, and media for the purification process; Proprep sanitary protein gradient LC systems have capacities ranging

244	Brock and Andrews

from 0.05 to 50 liters per minute; Parallex parallel purification systems, include the PFP 640 and the Parallex HPLC system, a high-throughput preparative HPLC system. See also Biotage listing.

Contact: Pamela Hay, Director of Corporate Development

Dynex Technologies

14340 Sullyfield Circle, Chantilly, VA 20151-1683, USA Phone: [phone]; Fax: [phone]

Toll-free in U.S.: [phone]

E-mail: [e-mail] Internet: http:/ /www.dynextechnologies.com

Profile: Formerly Dynatech Laboratories, the company has supplied microtiter technology products and services to research and clinical laboratories in the healthcare market for more than 30 years. Its products are marketed to scientists and researchers within universities, hospitals, and industry involved in research assays and clinical diagnostics. Dynex Technologies is a subsidiary of Thermo BioAnalysis Corporation, a Thermo Electron company.

Products/technologies: These include Microtiter Plastics (plates, strips, accessories); Microtiter plate coating systems; Microtiter detection reader systems, automated Microtiter plate immunoassay processing systems (such as the Dias immunoassay system); Microtiter plate washers; and Revelation software.

Contact: Monica Durrant, Director

EVOTEC BioSystems GmbH

Grandweg 64, D-22529 Hamburg, Germany

Phone: [phone]; Fax: [phone]

E-mail: [e-mail]

Internet: http:/ /www.evotec.de

Profile: EVOTEC was cofounded in 1993 by Nobel laureate Manfred Eigen, Ph.D., of the Max Planck Society, a pioneer in the research of molecular evolution and one of the first researchers to address molecular diversity through parallelization and miniaturization. The company’s technology originates from

Commercial Resources

245

Dr. Eigen’s work and from other Max Planck Institutes. It is also in collaboration with other researchers at academic institutions throughout Europe. Nearly half of its staff of 70 hold doctorate degrees. The company has been funded through private capital as well as government grants and early revenues from research contracts with international companies. EVOTEC makes its technologies available to third parties under product development or technology and transfer agreements.

Products/technologies: These include instrumentation and optical technology supporting ultrahigh-throughput screening. Its optical system provides accuracy and flexibility in the detection of molecular interaction. The EVOscreen instrument incorporates Evotec’s proprietary fluorescence detection technol- ogy—a technology sensitive enough to detect single molecules, even within cells, and yield important information about their interactions—with an automated, miniaturized platform designed for rapid screen configuration. Single- cell/single-bead selection techniques combine conical fluorescence scanning and single-bead/living cell retrieval systems, directed molecular evolution methods, and artificial intelligence–guided chemical synthesis of functional compounds.

Contact: Christen Hence, Ph.D., CEO

Genevac Ltd.

The Sovereign Centre, Farthing Road, Ipswich IP1 5AP, UK Phone: [phone]; Fax: [phone]

E-mail: [e-mail] Internet: http:/ /www.genevac.co.uk

Products/technologies: Atlas high-throughput evaporators are designed to meet the demands of combinatorial chemistry, parallel synthesis, natural products research, and HPLC prep. The new technology and large sample capacity allows rapid evaporation of up to 1 liter or more of even the most difficult solvents in a few hours at low or moderate sample temperatures; suitable for use with most sample formats, including microtiter plates, test tubes, and vials.

Contact: Harry Cole, Sales Manager

246	Brock and Andrews

Genelabs Technologies Inc.

505 Penobscot Drive, Redwood City, CA 94063, USA Phone: [phone]

Internet: http:/ /www.genelabs.com

Stock: GNLB (Nasdaq)

Profile: Genelabs is a biopharmaceutical company with research focused on the discovery of small-molecule drugs that act by binding to DNA or RNA to regulate gene expression or inactivate pathogens. In February 1998 the company began acquisition of directed combinatorial chemistry compounds through agreements with Tripos Inc., MDS Panlabs, and SRI International.

Products/technologies: Merlin and Viria assay systems screen combinatorial chemistry libraries for molecules and subunits of molecules that bind to segments of genetic material as small as four base pairs. The database will archive the subunits and the tiny genetic segments they disable. The database created to archive the subunits and the tiny genetic segments they disable will initially enable the rapid design of drugs to counteract pathogens employed in biological warfare; it will also have application as a database for traditional drug discovery.

Contact: Cynthia Edwards, Vice President, Research

Genome Systems Inc.

4633 World Parkway Circle, St. Louis, MO 63114, USA Phone: [phone]; Fax: [phone]

Toll-free in U.S.: [phone] E-mail: [e-mail] Internet: http:/ /www.genomesystems.com

Profile: For more than 4 years, Genome Systems has supplied researchers with genomic clones and technical support. The company makes the libraries it screens.

Products/technologies: ‘‘Do-it-yourself library screening’’ — perform library screening with ‘‘Down-to-the-Well’’ PCRable DNA pools or by using

high density colony filters.

Commercial Resources

247

Genome Therapeutics Corp.

100 Beaver Street, Waltham, MA 02154, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail] Internet: http:/ /www.cric.com

Stock: GENE (NASDAQ)

Profile: The company was founded in 1961; initial research was conducted under an SBIR grant from the National Science Foundation. The company develops proprietary gene databases and uses genomic research technologies to accelerate the development of novel therapeutics, vaccines, and diagnostics. Through alliances, the company is attempting to bridge the gap between gene discovery and drug discovery.

Products/technologies: These include proprietary high-throughput ‘‘multiplex’’ DNA sequencing; positional cloning; bioinformatics; bacterial genomics; PathoGenome sequence database.

Contact: John Richard, Vice President, Business Development

Gilson, Inc.

3000 W. Beltline Hwy., Middleton, WI 53562-0027, USA Phone: [phone]; Fax [phone]

Toll-free in U.S.: [phone] E-mail: [e-mail] Internet: http:/ /www.gilson.com

Profile: Gilson is a manufacturer of specialized analytical instrumentation for scientific research and industrial markets since the early 1950s. The company has developed software and instrumentation for HPLC, LC, and sample preparation technologies. It also produces high-precision pipettes and tips and automated instruments and systems for increasing throughput and productivity in the laboratory.

Products/technologies: Products include automated purification and analysis systems for combinatorial chromatography, including its high-throughput Combinatorial Chromatography System for HPLC purification and analysis. Additional product offerings are the UniPoint System software; automated

248	Brock and Andrews

sample preparation products; autosamplers that accept up to 10 deep well or standard microplates; dual-function autosamplers for small-scale preparative applications; and graphic sample tracking system to eliminate errors in HPLC purification of combinatorial products. Its ASPEC XL4 off-line, high capacity (108 samples/batch) SPE systems are used for purification applications using GC and LC-MS and combinatorial chemistry techniques. Other products are a chemical synthesis workstation and a high-throughput personal synthesizer system for lead generation and lead optimization libraries. Its high-throughput LC-MS Interface System is for sample preparation, injection and fraction collection.

Hewlett-Packard Co.

Centerville Road, Wilmington, DE 19808, USA

Phone: [phone]; Fax: [phone]

Toll-free in U.S.: [phone]

Internet: http:/ /www.hp.com/go/chem

Stock: HWP (NYSE)

Profile: A major manufacturer of chemical-analysis instrumentation since 1965, H-P’s core competencies are in measurement, computers, and communications. The company combines a full range of data-handling and standard networking products with HP and other vendors’ analytical instruments to provide chemists with integrated information to increase productivity. In November 1997, HP and IRORI announced an agreement to develop an integrated drug discovery platform that combines IRORI’s microchip synthesis and screening technologies with HP’s measurement and information portfolio for chemical analysis.

Products/technologies: Offers an automated combinatorial chemistry analysis system built around the HP 1100 Series HPLC, with the Gilson 233 XL sampling injector. Its GeneArray Scanner focuses a laser onto a 3- m section of a 20- m probe array on the Affymetrix chip and scans the chip in as little as 5 min. The company claims the GeneArray can read next-generation GeneChip probe arrays with up to 400,000 DNA probe sequences.

Houghten Pharmaceutials (see Trega Biosciences)

Commercial Resources

249

ICAgen, Inc.

4222 Emperor Boulevard, Suite 460, Durham, NC 27703, USA Phone: [phone]; Fax: [phone]

E-mail: [e-mail] Internet: http:/ /www.icagen.com

Profile: Founded in 1992, this privately held company is involved in the research and development of drugs that work by opening and closing ion channels. The company is currently in partnerships for the discovery of novel ion channel modulating drugs, and is the first biopharmaceutical company to integrate combinatorial biology with combinatorial chemistry focused exclusively on ion channel drug discovery and development. ICAgen has discovery programs in cardiovascular, central nervous system, and immunological disorders.

Products/technologies: These include proprietary biological targets and chemical libraries.

Contact: Kay Wagoner, Ph.D., Chief Executive Officer

IGEN International Inc.

16020 Industrial Drive, Gaithersburg, MD 20877, USA Phone: [phone]; Fax: [phone]

E-mail: [e-mail] Internet: http:/ /www.igen.com

Stock: IGEN (NASDAQ)

Profile: Founded in 1982, the company develops, manufactures, and markets diagnostic systems utilizing its patented ORIGEN technology. The technology is used in products developed by IGEN as well as its licensees. ORIGEN is based on the principle of electrochemiluminescence, which uses labels that, when attached to a biological substance and then electrochemically stimulated, emit light at a particular wavelength.

Products/technologies: These include the Origen high-throughput screening system, built around IGEN’s ECL modules (ECLMs). ECLM is expected to provide the advantages of rapid assay kinetics and improved assay range, while reducing the volume of critical reagent.

Contact: Herman Spolders, V.P., Business Development and Planning