Swartz Analytical Techniques in Combinatorial Chemistry

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Incyte Pharmaceuticals, Inc.

3174 Porter Drive, Palo Alto, CA 94304, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail]

Internet: http:/ /www.incyte.com

Stock: INCY (NASDAQ)

Profile: The company was incorporated in 1991 by a founding team of scientists and venture capitalists; in 1996, Genome Systems Inc. and Combion Inc. were acquired. Incyte designs, develops, and markets genomic databases and services to pharmaceutical companies on a nonexclusive basis. A wholly owned subsidiary, Genome Systems, Inc., is located in St. Louis, Missouri. The combined companies employ more than 500 people.

Products/technologies: Incycte designs, develops, and markets genomic databases and services to pharmaceutical companies. The company has proprietary DNA sequence, gene expression, and microbial genome databases and highthroughput full-length cloning technology. Its LifeSeq database is claimed by the company to be one of the world’s largest sources of genomic data, containing gene sequence and expression information from normal as well as diseased cells and tissues from most of the major tissues of the human body.

Contact: Lisa L. Peterson, Director, Business Development

Institute National de la Propriete Industrielle (INPI)

26 bis, rue de Saint-Petersbourg, 75800 Paris Cedex 08, France Phone: [phone]; Fax: [phone]

Internet: http:/ /www.inpi.fr

Profile: INPI is the French Patent and Trademark Office and the French Register of Commerce & Trade. INPI registers patents, trademarks, industrial designs and companies. One of its missions is to make this information more readily available by providing worldwide access to more than 35 million records of technical and business information. In December 1997, INPI and Derwent Information announced an agreement in principle to create an extensive structure searchable patent information resource for the pharmaceutical and chemical communities. Their new venture is aimed at focusing on the identification of lead compounds by shortening the time scale during the drug and chemical development life cycles. It is particularly relevant to those organiza-

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tions incorporating combinatorial chemistry methodology into their development process.

Products/technologies: It is intended that a new file will be available to customers by mid-1998 as a fast-alerting, structure-searchable on-line file. INPI and Derwent plan to extend the backfile coverage in parallel with the current coverage. Within a couple of years, they anticipate that retrospective coverage will be a full 20 years, focusing initially on pharmaceutical patents and extending coverage to all technologies later.

Institute for Scientific Information

3501 Market Street, Philadelphia, PA 19104, USA Phone: [phone]; Fax: [phone] Toll-free in U.S.: [phone]

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

Profile: ISI was founded in 1958 and is a database publisher that indexes bibliographic data, cited references, and author abstracts from scientific, technical, and medical sources. The company publishes Current Contents and the Science Citation Index . Its objective is to provide immediate desktop access to the most significant scientific literature, in its entirety, to anyone, anytime, anywhere.

Products/technologies: Index Chemicus database allows access to important reaction diagrams, full bibliographic information, full-length author abstracts, and a variety of searchable indices; published in one substructureand textsearchable database.

Irori Quantum Microchemistry

11025 North Torrey Pines Road, La Jolla, CA 92037, USA Phone: [phone]; Fax: [phone]

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

Profile: Established in 1995, the company is venture-funded. It is an earlystage development microelectronic and microchemistry company focusing on applying memory technology to solid-state matrices. Irori applies its SMART

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technology to the development of small-molecule combinatorial libraries. In November 1997, IRORI and Hewlett-Packard 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: SMART system (single or multiple, addressable, radiofrequency tags) and MEMs (memory enhanced matrices); SMART Microspheres, which are used to record information about individual chemical reactions as members of a combinatorial library are synthesized. Current microchip-based products from IRORI include a combinatorial chemistry module, a robotic sorter (AutoSortTM-10K), and a chemistry cleavage station (AccuCleaveTM-96). Initial bioassay and high-throughput screening systems are scheduled for launch during late 1998 with diagnostic/sensory industry to follow.

Contact: Michael P. Nova, M.D., President and CEO

Isco, Inc.

4700 Superior Street, Lincoln, NE 68505, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail]

Internet: http:/ /www.isco.com

Stock: ISKO (NASDAQ/NMS)

Profile: Founded in 1958, the company designs, manufactures, and markets instruments used by engineers, technicians, and scientists in the laboratory and in the field to address concerns such as research and development in chemistry and biotechnology, water pollution, process monitoring, quality control, and environmental testing.

Products/technologies: Automated flash systems for combinatorial chemistry are designed for either high-throughput or high productivity. Both highthroughput systems, the 10-channel Parallel System and the 5-channel Parallel System can be used with either a single solvent or multiple solvents. The initial 5- and 10-channel systems offer the ability to collect fractions based on time. The high productivity systems can run up to 16 or 32 columns with Isco’s sequential automated flash systems. One version is engineered for single-use columns, the other for reusable columns or cartridges. Additional products

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include LC, HPLC, optical detectors, fraction collectors, pumps, electrophoresis apparatus, SFE systems and syringe pumps.

Contact: Douglas M. Grant, President and CEO

LC Packings

80 Carolina Street, San Francisco, CA 94103, USA Phone: [phone]; Fax: [phone] Toll-free in U.S.: [phone]

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

Profile: LC Packings is a privately held company based in San Francisco, Amsterdam and Zurich. It was founded in Zurich in 1987 with the goal to develop, manufacture, and commercialize packed microcolumns for use in HPLC. The company offers a complete range of products for use in microseparation techniques such as micro, capillary and nano LC, including electrochromatography, capillary electrophoresis, and LC-MS.

Products/technologies: The mixing routine of the FAMOS microsampling HPLC workstation enables automated method development for sample handling techniques of single beads to produce combinatorial libraries; highthroughput is achieved by multiple analysis per vial.

LEAP Technologies

P. O. Box 969, Carrboro, NC 27410, USA

Phone: [phone]; Fax: [phone]

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

E-mail: [e-mail]

Internet: http:/ /www.leaptec.com

Profile: LEAP Technologies has been in the liquid sample loading business since 1989. The company provides front-end automation for chromatography (LC and GC), mass spectroscopy, elemental analysis, dissolution testing, and other analytical techniques. It specializes in applications that demand reliability, flexibility, precision, and high-throughput. LEAP works with major chromatography and mass spectroscopy companies to provide total integrated solutions for critical automation applications.

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Products/technologies: LC products include the CTC HTS PALS high throughput screening LC-MS sample loader; CTC A200LC autosampler for column-switching LC-MS; FLUX Rheos 4000 (true low-flow low-dead- volume-LC pump); FLUX compact degassers. For GC, the company offers the CTC COMBI PAL GC sampler for headspace and liquid injections, CTC A200SE GC autosampler. Products for dissolution testing include the HIDRA high-yield fiberoptic UV-Vis dissolution system; the flow-through dissolution systems (USP Apparatus #4), and the PAL automated sampling system.

Eli Lilly and Company

Lilly Corporate Center, Indianapolis, IN 46285, USA

Phone: [phone]; Fax: [phone]

Internet: http:/ /www.lilly.com

Stock: LLY (NYSE)

Profile: Founded in 1876 by Colonel Eli Lilly, the company was incorporated in 1901. It is a global research–based pharmaceutical corporation dedicated to creating and delivering innovative pharmaceutical-based healthcare solutions that enable people to live longer, healthier, and more active lives.

Products/technologies: In 1994, Eli Lilly felt they had secured a solid position in the field of combinatorial chemistry when they acquired Sphinx Pharmaceuticals, which Lilly viewed as having prominent achievements in this technology. In March 1997 the company signed a contract with Taisho Pharmaceutical Co. to introduce technology in the field of combinatorial chemistry, including the construction of a large-scale, diversified library of chemical compounds, and to efficiently synthesize derivatives.

Contact: Stephen Stitle, Vice President, Corporate Affairs

LJL BioSystems, Inc.

404 Tasman Drive, Sunnyvale, CA 94043, USA Phone: [phone]; Fax: [phone] Toll-free in U.S.: [phone]

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

Profile: A privately held company founded in 1988, LJL develops and manufactures automated assay systems for high-demand, high-throughput applica-

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tions in clinical, research, and drug discovery applications. Its plan is to develop and market systems to accelerate drug discovery and to supply instrumentation, high-value, application-specific reagents and related consumables, applications software for database management, and informatics for the acceleration of high-throughput screening (HTS). The company is a registered medical device manufacturer, operates under GMP, and is ISO 9001 certified. In 1993, LJL was ranked forty-first in the Inc. 500 list of fastest growing private companies.

Products/technologies: These include high-throughput screening systems designed to alleviate the screening bottlenecks resulting from recent advances in genomics and combinatorial chemistry; proprietary, high performance reagents, and instrumentation for a large majority of the biosassays used in the HTS market. Through a licensing agreement LJL will incorporate FluorRx’s fluorescence lifetime (FLT) sensing technology into LJL’s HTS product systems. FLT technology measures the excited state lifetime, rather than the intensity, of proprietary fluorophores by means of a robust and sensitive method

of fluorescence lifetime measurement, termed phase modulation. In September 1997 the company announced its first HTS product system, Criterion . The system consists of Analyst , an automated, multimode assay detection instru-

ment designed to seamlessly connect to existing robotics systems; a spectrum of applications-specific reagents and assay kits; assay development and application support services. Analyst is capable of performing all four major types of optical detection assays currently in use (i.e., fluorescence, fluorescence polarization, time resolved fluorescence, and luminescence assays). It reads assays in 96or smaller assay volume, 384-well microtiter plates with no loss of sensitivity or dynamic range.

Contact: William G. Burton, Ph.D., V.P. of Technology and Business Development

Lynx Therapeutics

3832 Bay Center Pl., Hayward, CA 94545, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail]

Profile: The company was founded in 1992 by the founder and former CEO and Chairman of Applied Biosystems, now a division of Perkin-Elmer. Its objective was to acquire, develop, integrate, and deploy novel molecular,

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chemical, and information technologies that provide a strong competitive advantage; and to leverage existing and future technology platforms through corporate collaborations and contracts in order to fund limited internal product development programs. Recently formed a Germany biotech startup company in Heidelberg with pharmaceutical giant BASF. According to the company, the joint venture, BASF-Lynx Bioscience AG, is a first for Germany and has the goal of serving as the launching pad for a biotech industry in Germany. It is also meant to serve as a genomics drug discovery arm for BASF and to finance the further development of Lynx’s technologies.

Products/technologies: Massively parallel signature sequencing technology has the power to examine the genetic activity of a single cell.

Contact: Sam Eletr, PhD., Chairman and CEO

MDL Information Systems, Inc.

14600 Catalina St., San Leandro, CA 94577, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail]

Internet: http:/ /www.mdli.com

Stock: MDLI (NASDAQ)

Profile: Founded in 1978, MDL supplies integrated scientific information management systems, databases, and services that are used worldwide in pharmaceutical and chemical companies and in industries that use chemical products. The company’s name was changed from Molecular Design Limited in 1993, the year it had its IPO. It is an information management software firm that has a combinatorial chemistry line of products. In late 1996 the company formed an alliance with Beckman Instruments to develop an integrated hardware and software system for high-throughput screening used in the drug discovery process. MDL is a wholly owned subsidiary of Elsevier Science.

Products/technologies: These include software programs, such as the Available Chemicals Director, which is a collection of chemical products offered by more than 200 chemical suppliers and totaling over 400,000 compounds. Other products include a line of systems for high-throughput discovery (incorporates Molecular Informatics’ BioMerge software, a genomic data management product); ISIS, a client/server system that helps researchers select diverse chemicals for discovery; MDL SCREEN, a client/server product that

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manages the process of high-throughput screening; and MDL Central Library, a client/server system for managing combinatorial chemistry libraries.

Contact: Thomas D. Jones, President and COO

MDS Panlabs

11804 North Creek Parkway South, Bothell, WA 98011-8805, USA Phone: [phone]; Fax: [phone]

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

Profile: MDS is a health and life sciences company whose products and services are used in the prevention, diagnosis, and management of illness and disease. The company has six operating divisions: MDS Laboratory Services, MDS Ingram & Bell, MDS Nordion, MDS Communicare, MDS Sciex, and MDS Pharmaceutical Services. MDS Pharmaceutical Services provides drug discovery and development services to help the pharmaceutical and biotechnology industries to speed new drugs to market. MDS Panlabs is part of this division and provides discovery of diversified R&D support services. The Pharmaceutical Services division also offers clinical trial services, contract research, and specialized research in quality control testing and analytical R&D.

Products/technologies: For product discovery assistance, the company offers high-throughput bioactivity screening for rapid identification of new drug leads; chemical and natural product libraries for drug discovery; and human DNA products from cell culture for use as disease models. In product support, MDS has PharmaScreen pharmacology profiles for early evaluation of new drug candidates; and rapid analoging for new lead molecules. Bioprocess development services include recombinant DNA microbes for fermentation manufacturing; strain, media, and process optimization studies to reduce production costs; high-yielding cultures for production of penicillin, cephalosporin, and erythromycin antibiotics; and process safety assessment and validation.

Micromass Limited

Floats Road, Wythenshawe, Manchester M23 9LZ, UK

Phone: [phone]; Fax: [phone]

E-mail: [e-mail]

Internet: http:/ /www.micromass.co.uk

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Profile: Micromass is a worldwide developer, manufacturer, and distributor of mass spectrometry (MS) instruments. In business since 1969, the company is a technology leader in the areas of magnetic sector, time-of-flight and quadrupole geometry mass spectrometers. When MS is combined with HPLC, LCMS gives scientists a powerful tool for analyzing newly synthesized compounds and measuring the metabolites of drugs under investigation. Waters Corporation, the leader in HPLC technology, acquired Micromass in September 1997. Waters trades as WAT on the NYSE.

Products/technologies: Some product offerings include systems for rapid analysis of combinatorial libraries and purification of new drug candidates. These systems are based on Waters HPLC components, Micromass Platform LC or Platform LCZ benchtop API mass spectrometer and MassLynx software with special options for combinatorial chemistry, such as OpenLynx Diversity and FractionLynx . The Waters LC-MS Solution for Drug Discovery provides a single-quadrupole solution for combinatorial analysis. Additionally, Micromass offers triple quadrupole, time-of-flight, magnetic sector, and hybrid geometry analyzers.

Contact: Mark McDowall, International Marketing Manager

Millennium Pharmaceuticals, Inc.

640 Memorial Drive, Cambridge, MA 02139-4815, USA Phone: [phone]; Fax: [phone]

E-mail: [e-mail]

Internet: http:/ /www.bio.com/companies/Millennium.html

Stock: LMNM (NASDAQ)

Profile: The company was founded in 1993. PerSeptive Biosystems is one of its principal investors. In January 1997 it was jointly announced that Millennium Pharmaceuticals would acquire privately held ChemGenics Pharmaceuticals as part of their mutual strategy to become a world leader in drug discovery. Following the merger, the combined company will employ more than 345 people. PerSeptive Biosystems is also a principal ChemGenics shareholder. In August 1997, Perkin-Elmer announced its plans to acquire PerSeptive.

Products/technologies: In addition to the technologies that ChemGenics will bring (as noted earlier in this chapter), Millennium employs large-scale genetics, genomics, and bioinformatics in an integrated, broad-based drug discovery

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program applicable to all major human diseases both independently, and in strategic alliances with leading pharmaceutical companies.

Contact: Beverly Holley, Director of Investor and Public Relations

Millipore Corporation

80 Ashby Road, Bedford, MA 01730-2271, USA Phone: [phone]; Fax: [phone] E-mail: Philip [e-mail]

Internet: http:/ /www.millipore.com

Stock: MIL (NYSE)

Profile: Millipore makes products utilizing separation technology for the analysis, identification, and purification of fluids. Products include disc and cartridge filters and housings, filter-based test kits, precision pumps, and other ancillary equipment and supplies. The company’s products are used in the pharmaceutical and biotechnology industries in sterilization, including virus reduction and sterility testing of products such as antibiotics and protein solutions; cell harvesting; and isolation of compounds from complex mixtures. Millipore, which acquired W. R. Grace’s Amicon Separation Sciences, also makes protein purification tools and semiconductor manufacturing equipment through its subsidiary, Tylan General.

Products/technologies: MultiScreen Assay Plate System is a 96-well plate configuration with membrane filters individually sealed to the bottom of each well. This allows for incubation and flow-through washes. These plates are now available with PTFE membranes and a plastic base that is solvent-resis- tant.

Contact: Philip Onigman

Molecular Devices Corporation

1311 Orleans Drive, Sunnyvale, CA 94089, USA Phone: [phone]; Fax: [phone] E-mail: [e-mail]

Internet: http:/ /www.moldev.com

Stock: NDCC (NASDAQ)