Collaborations, Agreements, Equity Participation

Company**

Company#

Type/Product Area

Terms/Details (Date)

Abgenix Inc.

Genentech Inc.

Research collaboration; use of Abgenix¿s XenoMouse technology to generate fully human monoclonal antibodies to undisclosed Genentech antigen in area of growth factor modulation

Genentech gets right to use Xeno- Mouse technology and has option on license; if it exercises option, Abgenix gets license fees, milestones and royalties; Genentech responsible for product development, manufacturing and marketing (4/98); expanded to include option on license for 2nd Genentech antigen (in cardiovascular area) (6/98)

Abgenix Inc.

Millennium Bio- Therapeutics Inc. (majority-owned subsidiary of Millennium Pharmaceuticals Inc.)

Research collaboration; use of Abgenix¿s XenoMouse technology to generate fully human antibodies to Millennium Bio¿s antigen target in area of inflammatory disease

Abgenix gets research payments, milestones and royalties; Millennium Bio will develop, manufacture and market any products (7/98); expanded to cover 2nd antigen target of Millennium Bio¿s (also for inflammatory disease) (10/98)

Abgenix Inc.

Centocor Inc.

Research collaboration; Use of Abgenix¿s XenoMouse to develop fully human antibodies to undisclosed antigen targets in area of cardiovascular diseases

Abgenix receives research payments and possible additional fees and milestone payments plus royalty payments on future sales; centocor will be responsible for product development, manufacturing and marketing (12/98)

Abgenix Inc.

Research Corporation Technologies Inc.*

Collaboration to develop antibody-based therapies for stimulating immune tolerance

Abgenix and RCT would share proceeds; Abgenix can negotiate from RCT to commercialize product candidates from the collaboration itself (12/98)

Acacia Biosciences Inc.*

Aurora Biosciences Corp.

Agreement to cross-license key genomic technologies (Aurora¿s fluorescent protein technology and Acadia¿s genome reporter matrix technology)

Companies will settle intellectual property dispute and cross-license certain elements of respective technologies; under certain conditions, companies will pay each other license fees; financial terms ND (10/98)

Acadia Pharmaceuticals Inc.*

ArQule Inc.

Collaboration to discover and develop drug candidates for undisclosed disease indications; combined use of ArQule¿s Mapping Array program with Acadia¿s cell-based screening technology, R-SAT (Receptor Selection and Amplification Technology; cell-based functional analysis of genes)

If joint research efforts identify lead compounds, companies will use ArQule¿s Directed Array program to optimize them and Acadia¿s R-SAT technology to define structure-activity relationships; companies will share ownership rights to lead compounds as well as product revenues (4/98)

Affymetrix Inc.

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE:AHP)

Expanded GeneChip supply and database agreement (dates from 11/94) on use of DNA chips for high-throughput gene expression monitoring; now, participants in Genetics Institute¿s DiscoverEase program will be able to access Affymetrix¿s GeneChip technology for expression analysis related to DiscoverEase library of secreted proteins

3-year non-exclusive agreement; Affymetrix gets $4M/year plus custom design fees and fixed per-chip fees; Genetics Institute will also build and sell access to database of gene expression patterns to its DiscoverEase subscribers (1/98)

Affymetrix Inc.

Human Genome Sciences Inc.

Agreement on use of Human Genome¿s sequence information on selected bacterial genomes to develop bacterial GeneChip probe arrays

Affymetrix gets exclusive right to use Human Genome¿s bacterial sequence information to design, manufacture and sell probe arrays; Human Genome gets royalties; Human Genome also gets access to Affymetrix¿s custom and commercial GeneChip expression arrays (6/98)

Affymetrix Inc.

Human Genome Sciences Inc.

Agreement on use of Human Genome¿s human genome database sequences in Affymetrix¿s DNA probe arrays (GeneChip)

This is 2nd agreement between the companies on use of Human Genome¿s data in GeneChips; Affymetrix gets rights to commercialize GeneChip probe arrays based on Human Genome¿s human genome sequences; it will sell those arrays to Human Genome and its database consortium members; after 2001, Affymetrix can extend agreement to all future Human Genome database subscribers (11/98)

Affymetrix Inc.

Molecular Applications Group Inc.*

Collaboration to develop bioinformatics software tools (to couple expression data from GeneChip system with information about structure and function of genes)

Companies will share any profits; other terms and details ND (9/98)

Affymetrix Inc.

Progenitor Inc.

Collaboration to identify genetic variations (polymorphisms) associated with asthma; development of custom GeneChip DNA probe arrays based on Progenitor¿s database of full-length functionally characterized genes derived from asthma patient DNA as well as single cell cDNA libraries from bronchial and inflammatory cells

Progenitor has option for exclusive rights to therapeutic and prophylactic applications of products; Affymetrix has option for diagnostics; polymorphisms identified through collaboration will be added to Affymetrix¿s database; financial terms ND (1/98)

Affymetrix Inc.

Research Genetics Inc.*

Affymetrix will sell its GeneChip technology to RGI, who will then offer screening and data analysis to third parties

Terms ND (12/98)

Affymetrix Inc.

Rosetta Inpharmatics

DNA array internal use license agreement to certain Affymatrix patents for Rosetta to make and use both mechanically spotted and ink-jet synthesized DNA arrays

Non-exclusive, three-year deal; Affymetrix is paid an undisclosed licensing fee plus an annual royalty based on number of array-based experiments performed (12/98)

Agouron Pharmaceuticals Inc.

Igen International Inc.

Expansion of 10/97 high-through-put screening agreement to include the screening of particular drug candidates of Agouron¿s with Igen¿s Origen technology (electrochemi-luminescent method for screening chemical libraries)

The expansion will double the size of the original screening project; further details ND (4/98)

AgriBioTech Inc.

Kimeragen Inc.

Licensing agreement to develop enhanced grass and forage seed products

AgriBioTech gets the exclusive license to the technology for the turf grass and forage seed applications; further details ND (12/98)

Allergy Therapeutics Ltd.* (U.K.)

Ribi ImmunoChem Research Inc.

License on Ribi¿s MPL immuno-modulator for use in allergy desensitization products

Allergy Therapeutics will use MPL in its products for allergies to pollen from grasses, trees and house dust mites (10/98)

AlphaGene Inc.*

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE:AHP)

Licensing agreement on AlphaGene¿s full-length human genes encoding secreted proteins for expression and inclusion in Genetics Institute¿s DiscoverEase protein development platform

Genetics Institute gets exclusive license to genes and proteins, which it will integrate into its DiscoverEase program and make available to participants under standard terms; AlphaGene gets payments based on number and timing of genes delivered to Genetics Institute; AlphaGene will share in milestones and royalties from products developed using its genes; further details ND (4/98)

Alza Corp.

Alkermes Inc.

Licensing agreement for Alza¿s oral drug delivery technologies RingCap and Dose Sipping Technology

Alkermes gets exclusive worldwide license to technologies; Alkermes responsible for continued R&D of products that use the technologies; Alza gets upfront payments and part of product revenues; Alza has option to acquire exclusive worldwide rights to certain products in therapeutic areas of interest to Alza (4/98)

American Biogenetic Sciences Inc.

Trevigen Inc.*

Agreement to use American Biogenetics¿ antigen-free technology to produce monoclonal antibodies for Trevigen¿s screening assays to detect DNA mutations; screening of American Biogenetics¿ neurological compounds for ability to induce apoptosis

American Biogenetic will produce 4 monoclonal antibodies for Trevigen; American Biogenetic gets payments and 5% royalty on all product sales; American Biogenetics retains manufacturing rights for monoclonals (4/98)

Aquasearch Inc.

EnzyMed Inc.

Drug discovery agreement that allows EnzyMed to potentially generate a large number of novel compounds based upon starting materials found in microalgae provided by Aquasearch

Both will share potential revenues from the commercialization of the libraries, including access fees, licensing fees, milestone payments, royalties and commercial sales (12/16)

Aronex Pharmaceuticals Inc.

Abbott Laboratories (NYSE:ABT)

Worldwide rights to Nyotran, Aronex¿s injectable, liposomal formulation of nystatin for the treatment of systemic fungal infections.

$40M to Aronex, including $2.85M upfront, followed by milestone payments, development support and royalties; Abbott purchased 837,989 shares of Aronex¿s common stock for $3M in cash; Abbott will be responsible for marketing Nyotran upon FDA approval and has an option to manufacture it; Aronex retains the rights to co-promote Nyotran in the U.S. and Canada for at least two years (11/98)

ArQule Inc.

Immunex Corp.

Collaboration on drugs for treating inflammatory disorders; use of ArQule¿s Mapping Array program to identify small-molecule therapeutics based on new chemokine gene discovered by Immunex

ArQule will use Immunex assays to identify compounds with biological activity from its Mapping Array program; once active leads identified, Immunex will elect whether to continue preclinical development with ArQule or to exclusively license leads to ArQule for clinical and commercial development (in exchange for milestones and royalties); financial terms ND (3/98)

The Automation Partnership Ltd.*

LION Bioscience AG (Denmark)

Collaboration to automate membrane filter processing and DNA hybridization

Terms ND (11/98)

Axis Genetics plc* (U.K.)

Biomira Inc. (Canada)

Research collaboration on each company¿s cancer vaccine that targets MUC-1 peptide found on common solid tumors; the 2 vaccines induce different types of immune responses

Axis will manufacture and supply its vaccine (produced in plants) to Biomira for evaluation in preclinical testing; each company will bear its own costs (11/98)

Axys Pharmaceuticals Inc.

Merck & Co.

Osteoporosis drug collaboration will focus on the development of small-molecule inhibitors of cathepsin K, a cysteine protease target

Extended collaboration until November 1999 (12/98)

Axys Pharmaceuticals Inc.

Rhone-Poulenc Rorer (RPR)

Collaboration to develop small-molecule drugs to combat inflammation; develop small molecules that inhibit cathepsin S, an enzyme

Deal could total $80M, including funding research as well as upfront licensing fees and certain milestone payments (12/98)

Axys Pharmaceuticals Inc.

Signal Pharmaceuticals Inc.*

Research collaboration; Signal will screen small molecules from Axys¿ compound libraries with its assay for signaling pathways; specific molecular targets ND

Axys gets upfront payment and milestones; Signal has option to access Axys¿ advanced chemistry capabilities (7/98)

Biogen Inc.

Genzyme Corp.

Marketing of Biogen¿s Avonex (recombinant human interferon beta-1a) for treating relapsing multiple sclerosis

Genzyme has exclusive rights to commercialize and distribute product in Japan; Genzyme responsible for clinical development and regulatory approval in Japan; financial terms ND (9/98)

Bioject Medical Technologies Inc.

GeneMedicine Inc.

Research collaboration; use of Bioject¿s needle-free jet injection devices to develop delivery systems and methods for genetic immunization (plasmid-based vaccines)

Parties will have access to each other¿s patent portfolio; Bioject will participate in GeneMedicine¿s preclinical studies; further details ND (7/98)

BioMarin Pharmaceutical Inc. (subsidiary of Glyko Biomedical Ltd.; TSE:GBL, Canada)

Genzyme Corp.

Formation of joint venture on BioMarin¿s recombinant enzyme alpha-L-iduronidase for treating lysosomal storage disorder muco-polysaccharidosis I (pivotal clinical trial initiated 1/98)

BioMarin will get $12.1M milestone payment when FDA approves product for sale; Genzyme bought $8M in Bio-Marin equity (for 5.6% stake) and will buy another $10M in stock in private placement concurrent with BioMarin¿s IPO at price to public (letter of intent 6/98; finalized 9/98)

Biomedical Photometrics Inc.* (Canada)

Allelix Biopharmaceuticals Inc. (Canada)

Genetic microarray collaboration; use of Biomedical¿s GENEscope technology (uses fluorescence to read microarrays and gene chips) in Allelix¿s drug discovery program

Allelix will evaluate a preproduction version of GENEscope instrument; Allelix will fund research project; companies will share rights to any inventions (3/98)

Biomira Inc. (Canada)

Biovector Therapeutics SA* (France)

Agreement to co-develop Biomira¿s liposomal idiotypic vaccine for B-cell lymphoma (consists of patient-specific tumor antigen combined with interleukin-2 and lipids)

Biovector will market product in North America, and manufacture and market it outside North America; Biomira retains North American manufacturing rights; Biomira gets upfront fee of $0.5M, milestones of $15.5M, plus royalties; Biomira also gets transfer fees for cost of goods; Biovector will provide most of funding for clinical trials (9/98)

Biomira Inc. (Canada)

Chiron Corp.

Expansion of 5/97 co-development agreement on Biomira¿s Theratope vaccine for metastatic breast cancer

Biomira retains marketing rights in Canada and adds exclusive rights in Latin America, Africa, the Middle East, Southeast Asia and the Pacific Rim (excluding Australia, Japan and the People¿s Republic of China); Biomira can seek other development partners in the new marketing territories; Chiron has rights in Australia and Japan; Biomira gets royalties on sales in Japan and will share upfront and milestone payments if Chiron engages 3rd party for Japanese development; each party will solely fund product development in its respective markets (6/98)

BioNative AB* (Sweden)

Maxim Pharmaceuticals Inc.

Collaboration to test Maxamine (immunomodulator) in combination with BioNative¿s natural interferon (Interferon Alfanative) and interleukin-2 in European Phase II clinical trial in renal cell carcinoma

ND (9/98)

BioStar Inc.*

Agouron Pharmaceuticals Inc.

Agreement to develop point-of-care diagnostic test (via BioStar¿s optical immunoassay technology) to assist in clinical development of Agouron¿s rhinovirus drug candidate AG7088

ND (10/98)

Briana Bio-Tech Inc. (VSE:BIA; Canada)

BioChem Pharma Inc. (Canada)

Agreement to develop and commercialize Briana¿s Second Look computerized breast cancer detection system

Briana transferred its product rights to new company, of which Briana owns 45% and BioChem Pharma 55%; new company will finance clinical trials; BioChem gets license on product and options on other applications of technology (heads of agreement 6/98; finalized 7/98)

Cadus Pharmaceutical Corp.

Genome Therapeutics Corp.

Research collaboration on G protein-coupled receptors (involved in most basic cellular functions) via Cadus¿ assays and functional genomics and Genome Therapeutics¿ sequencing and cloning of full-length genes

Companies will identify drug targets and then partner them with 3rd parties; companies will share any proceeds from these 3rd-party alliances (7/98)

Cambridge NeuroScience Inc.

Bayer Corp. (subsidiary of Bayer AG; Germany)

Development deal to develop recombinant glial growth factor 2 (GGF2) as a therapy for neurodegenerative diseases such as multiple sclerosis

Total deal worth $26M, including undisclosed upfront fees, reimbursement for research already conducted, milestone payments and royalties (12/98)

Cambridge Antibody Technology Group plc (U.K.)

Progenitor Inc.

Broad-based gene-to-clinic collaboration; use of Progenitor¿s genes as targets for Cambridge Antibody¿s antibody-based therapeutics; also use of Cambridge Antibody¿s antibody-based functional genomics tools to characterize gene discoveries from Progenitor¿s programs in asthma, inflammation, hematopoiesis and angiogenesis

Progenitor will supply set of molecular targets from its gene discovery programs; Cambridge Antibody will develop target-specific antibodies that companies will use to evaluate function and therapeutic significance; companies will bear own costs for joint research program; Cambridge Antibody has 1st rights to develop antibody-based products; Progenitor has 1st rights for other products; companies will pay each other milestones and royalties; companies also started joint program to develop and commercialize therapeutics based on Progenitor¿s leptin receptor gene discovery (3/98)

Cambridge Antibody Technology Group plc (U.K.)

Techniclone Corp.

Restructuring of 2/96 co-development agreement on tumor necrosis therapy

Techniclone wants to rapidly expand the clinical program; it will assume sole responsibility for product development; Cambridge Antibody gets royalties (5/98)

Cell GeneSys Inc.

Collateral Therapeutics Inc.

Research collaboration; Collateral will evaluate Cell GeneSys¿ 2nd-generation recombinant adenoviral vectors in preclinical studies of cardiovascular gene therapy

Details ND (12/98)

Cell Genesys Inc.

Japan Tobacco Inc.

Rights to Cell Genesys¿ GVAX cancer vaccine technology in prostate cancer and another undisclosed target

Total $152.7M deal; $12.7M upfront; $2.5M in one year; another $27.5M for half of Cell Genesys¿ development costs over there years; also $80M in milestone payments if two products are approved, plus up to $40M in loans to cover Cell Genesys¿ Phase III development costs (12/98)

Celtrix Pharmaceuticals Inc.

Genzyme Tissue Repair

Expansion of 6/94 collaboration on recombinant transforming growth factor-beta 2 (TGF-B2) to include Celtrix¿s TGF-B2 antibody and receptor technology

Genzyme Tissue is developing product as part of comprehensive approach to tissue repair and treatment of systemic disease; Genzyme Tissue gets expanded technology and territory rights (includes global commercialization rights); Celtrix gets increased revenue from future milestones and royalties (2/98)

Cepheid* Ceres*

Innogenetics NV (Belgium) Genset SA (France)

Research, development and supply agreement to develop gene-based diagnostic systems Research collaboration; use of Genset¿s mapping, sequencing and bioinformatics technologies in agricultural genetics/genomics

Innogenetics acquired 5% of Cepheid¿s shares; Innogenetics and its distributors will sell any in vitro diagnostics products (11/98) Ceres gets exclusive license to use specific aspects of Genset¿s genomics technologies in agricultural genetics; Genset retains exclusive rights to all human health applications; Genset acquired 20% stake in Ceres; Genset gets service fees and additional equity on milestones (1/98)

ChemDiv Inc.*

Amylin Pharmaceuticals Inc.

Agreement to screen ChemDiv¿s small-molecule library (TakeOneSet Library) for compounds with biological activity in area of metabolic disorders, including obesity, diabetes and dyslipidemia

Amylin gets rights to any active compounds and will control all future research, development and marketing activities for drug candidates; Amylin may seek 3rd parties for development and/or commercialization; ChemDiv gets upfront access fees, milestones and royalties (2/98)

ChemRx*

Signal Pharmaceuticals Inc.*

Chemistry-based development deal

ChemRx will develop multiple classes of compounds on a fee-for-service basis; no milestone or royalty payments (12/98)

Chiron Corp.

MedImmune Inc.

Research collaboration; use of Chiron¿s MF59 vaccine adjuvant with 2 of MedImmune¿s vaccines (against parvovirus B19 [for various indications, including anemia in AIDS and cancer]; and against Escherichia coli [for urinary tract infections])

Chiron gets upfront payment, milestones and royalties; further details ND (9/98)

Chromagen Inc.*

CombiChem Inc.

Research collaboration; use of CombiChem¿s Discovery Engine and Universal Informer Library to generate small molecules for screening in Chromagen¿s high-performance signal amplification biological assays

Chromagen gets upfront payment and screening fees; CombiChem will out-license lead drug candidates identified by screens to 3rd parties for development and commercialization (5/98)

Cobequid Life Sciences Inc. (VSE:KQR; Canada)

Qiagen NV (the Netherlands)

Two agreements to develop DNA vaccines for viral and bacterial diseases and parasitic infections in aquaculture

Cobequid gets non-exclusive access to aspects of Qiagen¿s DNA manufacturing technology for large-scale production of ultrapure DNA (for DNA vaccines and gene therapy); Cobequid also gets worldwide exclusive rights to use DNA vaccines in aquaculture (6/98)

Cognia Bioinformatics Inc.

Biobase Biological Databases/ Biologische Datenbanken GmbH*

Distribution partnership; Cognia will become the exclusive distributor of the Transfac database in the U.S. and Canada

ND (12/98)

Collagenesis Inc.*

Osiris Therapeutics Inc.*

Research collaboration; evaluation of Collagenesis¿ collagen-based tissue matrix delivery system for use in delivery of Osiris¿ mesenchymal stem cells for soft tissue regeneration (especially tendons and ligaments)

ND (9/98)

Collateral Therapeutics Inc.

Targeted Genetics Corp.

Collaboration on use of Targeted Genetics¿ recombinant adeno-associated viral vector (rAAV) for cardiovascular gene transfer (non-surgical gene therapy)

Companies will assess feasibility of this approach and have option to collaborate further on use of rAAV vector to deliver adenyl-cyclase gene into heart cells for treating congestive heart failure; financial terms ND (2/98)

CombiChem Inc.

Athena Neurosciences Inc. (wholly owned subsidiary of Elan Corp. plc; Ireland)

Expansion of 10/97 collaboration on small-molecule compounds for treating central nervous system disorders to include more targets (undisclosed)

Athena is starting work on additional project under collaboration and has taken an option on a target not covered originally; Athena will make an undisclosed cash payment to CombiChem for the option (3/98)

CombiChem Inc.

Chirotech Technology Ltd. (subsidiary of Chiroscience Group; U.K.)

Joint venture establishing ChiroChem Discovery Services Inc. to develop and market computationally designed libraries of single-isomer chiral compounds

Both funded ChiroChem Discovery Services LLC and will share profits equally (12/98)

CombiChem Inc.

Icos Corp.

Computational drug discovery agreement; use of CombiChem¿s Discovery Engine and Icos¿ small-molecule drug library and high-throughput screens to generate lead compounds for undisclosed targets

Icos gets exclusive worldwide rights to develop and market any products that result; CombiChem gets upfront payment, research support, milestones and royalties (4/98)

Compugen Ltd.

Parke-Davis (division of Warner-Lambert Co.; NYSE:WCA)

Collaboration for Compugen¿s Leads bioinformatics platform, which identifies drug targets based on the analysis of expressed sequence tag and genomic databases, pattern recognition in expression results from chips and poteomics, and mutation detection and qualification

Terms ND (11/98)

Copernicus Gene Systems Inc.*

LXR Biotechnology Inc.

Collaboration to integrate 1 of LXR¿s anticancer genes (related to control of apoptosis) into Copernicus¿ in vivo gene transfer and expression systems (which employ DNA compaction technology)

Details ND (2/98)

Copernicus Gene Systems Inc.*

Targeted Genetics Inc.

Collaboration on non-viral gene therapy vectors; use of Copernicus¿ DNA compaction technology on plasmid DNAs, which are then encapsulated in Targeted Genetics¿ LPD vectors (cationic lipid-based gene delivery systems)

Companies will work together to evaluate efficiency of gene transfer in preclinical models; companies may further collaborate to develop gene therapies for cancer and other indications; they may also seek 3rd parties for commercial product development; financial terms ND (4/98)

Corixa Corp.

CellPro Inc.

Termination of 1/96 agreement on developing ex vivo adoptive immunotherapies for oncology via Corixa¿s cancer antigens, microsphere delivery and adjuvant technologies

CellPro terminated agreement as a result of its need to conserve resources for its then ongoing patent infringement suit with Baxter et al.; all rights on Corixa¿s technology in area of adoptive immunotherapy revert to Corixa (4/98)

Corixa Corp.

Imugen Inc.*

Diagnostics collaboration; licensing of some of Corixa¿s recombinant antigens for diagnosing the tick-borne diseases Babesia microti and human granulocytic Ehrlichiosis

Imugen gets exclusive license to antigens, including right to sublicense them for reference lab testing in U.S. and Canada; Corixa gets share of revenues from sale of diagnostic kits or blood screening tests (4/98)

CpG Immuno-Pharmaceuticals Inc.*

Isis Pharmaceuticals Inc.

License agreement on Isis¿ patents covering immune stimulation by phosphorothioate oligonucleotides

CpG gets exclusive worldwide rights to methods and applications covered by patents (not including claims for antisense therapies); Isis gets license fee and part of sublicensing revenues; Isis will purchase ¿meaningful¿ equity stake in CpG (8/98)

Coulter Pharmamaceutical Inc.

SmithKline Beecham plc (NYSE:SKB; U.K.)

Joint commercialization of Bexxar, a radioactive monoclonal antibody therapy to treat non-Hodgkin¿s lymphoma

Worth up to $132M to Coulter, including a $41.5M upfront payment ($7.25M of which is in equity), plus a $15M line of credit. Both will share profits equally; SK and Coulter will jointly market Bexxar in the U.S.; SK has marketing and distribution rights worldwide except in Japan; Coulter could receive another $7M in regulatory and marketing milestones in other countries (12/98)

Creative BioMolecules Inc.

Biogen Inc.

Restructuring of 12/96 collaboration on use of Creative¿s morphogenic protein OP-1 for treating both acute and chronic kidney failure

This program is taking longer than anticipated; Biogen is reducing its role; Creative will assume primary role in developing therapy in the chronic disease setting, for which Biogen will provide $4.75M in research support; Biogen retains option through 1999 to resume product development in chronic disease setting; Creative will also assume all rights to develop product in acute disease setting, independent from Biogen (10/98)

Crescendo Pharmaceuticals Inc.

Alza Corp.

Alza exercised an option to obtain a worldwide license to OROS

Crescendo will receive payments from Alza based on worldwide sales of the product, Oxybutynin (Ditropan XL), a once-a-day treatment for overactive bladder (12/98)

CuraGen Corp.

ArQule Inc.

Collaboration to discover compounds for treating cardiovascular disease, endocrine/metabolic disorders, auto-immune disease and cancer; ArQule¿s Mapping Array libraries will be screened against thousands of biological targets via CuraGen¿s genomics-based technologies (multiplexed high-throughput screening assays including CombiGen and HitCalling database)

If leads identified through screening, companies will use ArQule¿s Directed Array program to optimize them; companies will share ownership rights to active lead compounds and will share commercial revenues (1/98)

CuraGen Corp.

Glaxo Wellcome plc (NYSE;GLX; U.K.)

Pharmacogenomics deal; Glaxo gets access to CuraGen¿s GeneCalling for the discovery of gene expression discovery and analysis and SeqCalling, a database product

Potential at least $48M over five years; $2.75M yearly, plus about $35M in milestones (11/98)

CV Therapeutics Inc.

Biogen Inc.

Amendment of terms of 3/97 agreement on CVT-124 (adenosine A1-receptor antagonist) for treating edema associated with congestive heart failure

Parties agreed to accelerate the release of a $4.5M loan to CV Therapeutics (in form of milestone payment), which will occur when Biogen gets the final report of a Phase II trial on CVT-124 (completed 5/98) (7/98)

CV Therapeutics Inc.

Incyte Pharmaceuticals Inc.

Joint research collaboration to develop prototype gene expression database in cardiovascular biology (especially atherosclerosis and restenosis)

Incyte will own any data produced; CV Therapeutics gets perpetual, non-exclusive license to use data in its internal R&D; CV Therapeutics will develop biological models of targeted disease states and supply mRNA samples to Incyte, which will generate microarray-based expression data (9/98)

Cytel Corp.

Elan Corp. plc (Ireland)

Sublicensing agreement on Cytel¿s patent covering use of antibodies that block VLA-4 integrin for treating inflammatory conditions

Elan gets exclusive sublicense to patent and has option for non-exclusive sublicense for rights to other VLA-4 blocking compounds; Elan will make $4M equity investment in Cytel; Cytel also gets milestones and royalties; transaction subject to clearance by U.S. authorities (7/98)

Cytogen Corp.

Elan Corp. plc (Ireland)

Unwinding of Targon Corp. joint venture (formed in 9/96)

Cytogen retains assets it originally contributed to Targon; Elan will pay Cytogen $4M cash ($2M of which represents new convertible note issued to Elan, which Elan has option of converting into Cytogen common stock at $2.80 per share); Elan will acquire complete ownership of Targon and all remaining assets, including opioid analgesic product Morphelan; existing $10M note from Cytogen to Elan relating to license on Morphelan is cancelled (8/98)

CytoTherapeutics Inc.

Genentech Inc.

Termination of 11/96 agreement to develop encapsulated cell technology to deliver Genentech¿s growth factor Neurturin directly to central nervous system (for treating Parkinson¿s disease)

Genentech has asked CytoTherapeutics to redeem $4M of the $8.3M in CytoTherapeutics¿ common stock it acquired as part of the agreement; the parts of the agreement pertaining to Huntington¿s disease and amyotrophic lateral sclerosis remain in effect (5/98)

Cytovia Inc.*

Aurora Biosciences Corp.

Collaboration on cell-based assays for drug discovery; use of Aurora¿s high-throughput screening, compound libraries and bioinformatics together with Cytovia¿s fluorogenic protease substrates and live-cell screening technology to identify drug leads for cancer and degenerative diseases

Cytovia gets rights to develop and commercialize any drug leads; Aurora gets fees for access to libraries and screening service, as well as milestones and royalties; Aurora will make equity investment in Cytovia (7/98)

Delsys Pharmaceutical Corp.*

Elan Corp. plc (Ireland)

Formation of joint venture on oral controlled-release drugs; combination of Delsys¿ Accudep technology (electrostatic deposition process) with Elan¿s controlled-release technologies

Elan will make $3M equity investment in Delsys (which Delsys received 9/98); further details ND (7/98)

Digene Corp.

MedImmune Inc.

Development agreement; Digene will develop DNA and mRNA expression tests for human papillomavirus

Digene will develop specific mRNA HPV tests using its Expression Analysis System based on Hybrid Capture II technology (11/98)

Draximage Inc. (subsidiary of Draxis Health Inc.; Canada)

Molecular Targeting Technology Inc.*

Strategic alliance to develop, manufacture and market imaging agents, initially Amiscan (technetium-99m glucarate) for early diagnosis of acute myocardial infarction

ND (6/98)

Dyax Corp.*

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE:AHP)

Collaboration to develop highly selective affinity ligands via Dyax¿s phage display technology for use in purifying one of Genetics Institute¿s biotherapeutic drug candidates

Genetics Institute will fund ligand discovery phase, with option for continued funding of development contingent on benchmarks; Genetics Institute has option on exclusive rights to resulting purification reagents and processes; if exercised, Dyax gets milestones and royalties (1/98)

Dyax Corp.*

Genzyme General

Drug discovery deal to develop EPI-KAL2 for chronic inflammation

Genzyme made a $3M equity investment, extended a $3M line of credit and committed an additional $25M in potential milestone payments (12/98)

Dyax Corp.*

SangStat Medical Corp.

Research collaboration; use of Dyax¿s phage display technology to screen for peptides that bind to specific component of immune cells; for use with SangStat¿s Xenoject technology in preventing transplant rejection

SangStat will fund research and pay Dyax milestones and royalties; Sang-Stat gets exclusive worldwide rights to products; further details ND (3/98)

Dynavax Technologies Corp.*

Vical Inc.

Cross-licensing agreement on patents for DNA immunization technology (administration of DNA sequences that encode versions of tumor-associated antigens to cancer patients through skin; DNA stimulates immune response by antigen-specific cytotoxic T lymphocytes)

Royalty-bearing cross-license agreement grants each company exclusive worldwide rights to combine respective DNA immunization technologies; each company retains full rights to its technology in other applications (1/98)

Electropharmacology Inc. (OTC Bulletin Board: EPHI)

Elan Corp. plc (Ireland)

Research and license agreement; development of Elan¿s flexible iontophoretic patch technology for non-cosmetic dermatology and wound care applications; also, development of flexible patch version of Electropharmacology¿s pulsed electromagnetic signal (PEMS) technology

Electropharmacology gets worldwide rights to therapeutic applications of improved PEMS product as well as combined PEMS/iontophoretic products; Elan gets upfront payment, license fees and royalties; Elan bought $7.5M in Electropharmacology convertible preferred shares and warrants; Elan may buy additional $2M in common stock (letter of intent 8/98; finalized 10/98)

Emisphere Technologies Inc.

Elan Corp. plc (Ireland)

Expansion of 11/95 joint venture on oral formulations of heparin to include initiation of clinical development of oral formulation of low-molecular-weight heparin (anti-coagulant, anti-thrombotic)

Elan will exercise all of its warrants (equal to 0.25M shares of Emisphere common stock), which it acquired when the joint venture was formed (strike price is $16.25 per share or $6.5M total), after which Elan owns 8.6% stake in Emisphere; companies are seeking 3rd party for product development and commercialization (1/98); each company contributed $5M (for $10M total) to joint venture (8/98)

Endocyte Inc.

Rhone-Poulenc Rorer GenCell (unit of Rhone-Poulenc Group; France)

Develop cancer treatments based on systemic delivery of gene therapy using Endocyte¿s vitamin-based vector technology; folate will be first vitamin employed

$40M to Endocyte; RPR gets a two-year option to expand the scope of the license to include the use of vitamins for cellular targetting and uptake; RPR gets an exclusive license under Endocyte¿s intellectual property relating to the use of folate receptors for delivery of oncology gene therapy products (12/98)

Endorex Corp.

Elan Corp. plc

Formation of joint venture, named Innovax Corp., to develop oral vaccines via Endorex¿s Orasome oral drug delivery technology (especially to reformulate injectable vaccines developed by big pharma)

Companies announced formation of joint venture in 1/98; finalized 8/98; Innovax owned 80.1% by Endorex and 19.9% by Elan; each partner will provide personnel; combined total funding of $3M for 1st year and partners will contribute $10M total to joint venture; Elan bought $10M in Endorex equity (0.31M shares of common stock at $6.50 each for $2M total and $8M in preferred stock, convertible into common at $7.50/share); Elan also got warrants to buy 0.23M shares Endorex common stock at $10 each; joint venture paid Elan $10M initial license fee; Elan may get milestones and royalties (1/98; 8/98)

Endorex Corp.

Elan Corp. plc (Ireland)

Formation of 2nd joint venture, to commercialize products using Elan¿s Medipad drug delivery system (disposable system that combines patch and infusion pump) for 2 undisclosed drugs

Companies contributed total $10.5M to joint venture, which is 80.1% owned by Endorex and 19.9% by Elan; Elan bought $8.4M in Endorex preferred stock (exchangeable for stock in joint venture or Endorex common stock at premium to market); joint venture gets exclusive worldwide rights to Medipad for use with specific drugs; Elan gets $10M license fee from joint venture as well as milestones and royalties (10/98)

EntreMed Inc.

Celgene Corp.

Sublicensing agreement for the advancement of thalidomide drug development

Celgene acquired exclusive worldwide rights to EntreMed¿s patents and technology for thalidomide as well FDA¿s orphan drug designations achieved by EntreMed further details ND (12/98)

Enzo Diagnostics (subsidiary of Enzo Biochem Inc.)

Affymetrix Inc.

Supply agreement on Enzo¿s nucleic acid labeling and detection products for use in Affymetrix¿s GeneChip expression arrays

Enzo Diagnostics will be sole supplier worldwide of specified labeling and detection kits, which Affymetrix will sell for use with its GeneChip arrays; Affymetrix also gets use of certain Enzo products and technology to optimize its existing GeneChip products and to develop new ones (5/98)

EnzyMed Inc.*

RiboGene Inc.

Joint collaboration on drugs for infectious diseases; use of RiboGene¿s infectious disease high-throughput assays to screen EnzyMed¿s small-molecule chemical libraries

Parties will jointly own and develop any compounds resulting from research (8/98)

Eos Biotechnology Inc.*

Affymetrix Inc.

Series of agreements on Affymetrix¿s custom and standard GeneChip expression arrays for use in Eos¿ molecular genomics research in cancer, inflammation and cardiovascular disease

Eos can purchase several thousand probe arrays at modified rates over next 30 months; in lieu of subscription fees, Affymetrix gets 15% stake in Eos through ownership of Series C preferred stock (5/98)

Epitope Inc.

Analytical Genetic Testing Center Inc.*

Agreement to jointly develop DNA test kits for forensic DNA testing market based on Epitope¿s OraSure oral specimen collection device

ND (1/98)

ExonHit Therapeutics

Cerep SA

Develop new methods for toxicity assessments, target validation and drug discovery

Cerep will make a $540,000 equity investment and fund expenses up to $2.32M; two year deal (11/98)

Forage Genetics* (wholly owned subsidiary of Research Seeds Inc.)

DeKalb Genetics Corp.

Research collaboration; development, evaluation and release of new alfalfa varieties with Roundup Ready trait

DeKalb will conduct product evaluation and market assessment; further details ND (7/98)

Galileo Laboratories Inc.*

Phytera Inc.*

Research agreement on drugs for treating and preventing ischemic diseases; Galileo will screen Phytera¿s ExPAND plant cell culture extracts and uMARINE microorganism extracts in its Metabolic Target Array Query assay system (detects drugs that modulate cell energy metabolism)

Companies will share equally R&D costs and commercial rights to any products; companies will seek pharmaceutical partner for development and commercialization (5/98)

GeneAsia*

CMIC Co. Ltd. (Japan)

The two will create a new generation of contract research organization services, including pharmacogenomics; the focus will be on diabetes, hypertension, arteriosclerosis and obesity as initial disease state targets

ND (12/98)

Gen-Probe Inc. (subsidiary of Chugai Pharmaceutical Co. Ltd.; Japan)

Chiron Corp.

Strategic alliance to develop, manufacture and market nucleic acid probe assay systems for blood screening and certain other diagnostic areas; initial focus on combination HIV-1/HCV assay for qualitative screening of donated blood (blood banks)

Chiron will market and sell products combining Chiron¿s HCV and HIV technology/patents with Gen-Probe¿s various nucleic acid probe technologies (7/98)

Genaissance Pharmaceuticals Inc.*

Terrapin Technologies Inc.* (name changed to Telik Inc. in 5/98)

Collaboration to validate biological targets and identify active compounds for treating estrogen-related problems in women¿s health; use of Terrapin¿s chemoinformatics technologies to identify drug candidates that modulate role of estrogen receptor variants (isogenes)

Companies will jointly seek 3rd parties to develop and commercialize drug candidates; further details ND (2/98)

Gene Logic Inc.

Procter & Gamble Co.

Expansion of gene expression deal using Gene Logic¿s READS gene expression technology

P&G is expanding its potential $75M deal, doubling the annual revenues to Gene Logic (12/98)

Genentech Inc.

Connetics Corp.

Expansion of U.S. marketing and product development agreements on Actimmune (interferon gamma-1b); agreement for treating dermatological disorders, bone disorders and infectious and respiratory diseases dates from 12/95; agreement for use in treating chronic granulomatous disease dates from 5/98 (FDA-approved in 1991 for this indication)

Connectics will assume revenue stream from Actimmune and conduct additional clinical development in its licensed fields; Genentech will continue to manufacture product; Connetics issued $2M in common stock to Genentech (with guaranteed value of $4M in 12/98); Genentech gets certain milestones and royalties (5/98)

Genetica Inc.*

Osiris Therapeutics Inc.*

Research collaboration on functional genomics of human mesenchymal stem cells; focus on discovery of genes that control growth and differentiation of these cells

Osiris gets exclusive worldwide rights to therapeutic agents and drug targets; Genetica gets royalties (10/98)

Genome Therapeutics Corp

ArQule Inc.

Genomics-based collaboration on small-molecule anti-infectives; ArQule will screen its chemical libraries against Genome Therapeutics¿ bacterial and fungal disease targets (from its Patho-Genome Database)

Once active leads are identified, companies will use ArQule¿s Directed Array technology for optimization; companies will share ownership rights to active lead compounds and will also share revenues (6/98)

Genome Therapeutics Corp.

Scriptgen Pharmaceuticals Inc.*

License agreement; use of Genome Therapeutics¿ PathoGenome microbial sequence database to identify gene targets for drugs to treat infectious diseases and drug-resistant microbes

Scriptgen gets non-exclusive license to database; Scriptgen will pay annual subscription fees and milestones, as well as royalties; Genome Therapeutics retains certain rights to use genes or gene products as therapeutics, diagnostics and vaccines (6/98)

Genometrix Inc.*

GeneMedicine Inc.

High-throughput multiplex screening agreement; use of Genometrix¿s medium density DNA microarrays for high-throughput analysis of gene expression profiles in mice treated with GeneMedicine¿s cancer gene therapy products

GeneMedicine has non-exclusive option to buy Genometrix¿s human universal cancer array product; further details ND (4/98)

Genomica Corp.*

Oxagen Ltd.* (U.K.)

License agreement; use of Genomica¿s bioinformatics software Discovery Manager (includes database of genetic information) for gene discovery and functional analysis

Multi-year agreement; terms ND (7/98)

GenQuest Inc.*

Introgen Therapeutics Inc.*

Gene therapy agreement; use of tumor suppressor gene mda-7 for gene therapy in cancer

Introgen has exclusive option to license mda-7 gene; GenQuest gets upfront payment; if Introgen exercises option, GenQuest also gets research funds, milestone payments and royalties (3/98)

Genzyme Molecular Oncology

Hexagen plc* (U.K.)

Genomics collaboration; use of Genzyme Molecular¿s SAGE technology (serial analysis of gene expression) in Hexagen¿s disease gene discovery programs, initially for Type II diabetes susceptibility genes

Hexagen gets use of SAGE technology and will pay Genzyme Molecular undisclosed user fees; Hexagen retains exclusive rights to information; Hexagen has option to license SAGE for in-house use for multiple applications (3/98)

Genzyme Molecular Oncology

Isis Pharmaceuticals Inc.

Genzyme Molecular licensed to Isis on a non-exclusive basis patent rights relating to antisense compounds that interfere with the expression of a cancer-related gene, methods for treating cancerous cells with these compounds, and the methods for identifying such compounds

Genzyme Molecular will recieve an upfront payment as well as potential milestones and royalties; further details ND (12/98)

Genzyme Molecular Oncology

Ontogeny Inc.*

Genomics collaboration; incorporation of Genzyme Molecular¿s SAGE technology (serial analysis of gene expression) in Ontogeny¿s developmental biology discovery system

Genzyme Molecular will produce SAGE libraries using RNA supplied by Ontogeny; Ontogeny will incorporate libraries into its systems; financial terms ND (2/98)

Genzyme Transgenics Corp.

Centocor Inc.

Licensing agreement to develop and produce monoclonal antibodies in the milk of transgenic goats to develop antibody-based therapeutics

Centocor will pay $3.4M during the initial phase; upon commercialization, Genzyme will supply the antibodies at a transfer price mutually agreed upon (12/98)

Genzyme Transgenics Corp.

Invitrogen Corp.*

Distribution agreement on Genzyme Transgenic¿s transgenic expression vectors (consisting of beta casein promoter and additional DNA sequences for insertion of gene of interest into fertilized ovum; expression confined to mammary gland in adult)

Invitrogen will package expression system as a kit that it will sell for research purposes (uses limited to mouse model systems); Genzyme Transgenics gets royalties (4/98)

Genzyme Transgenics Corp.

Progenics Pharmaceuticals Inc.

Collaboration to produce Progenics¿ HIV therapeutic PRO 542 (fusion protein; antibody-like molecule) in milk of transgenic goats

Following success of initial development phase, companies will enter into agreement for commercial production of product (2/98)

Human Genome Sciences Inc.

Transgene SA (France)

Gene therapy agreement; combines Human Genome¿s genomics database with Transgene¿s gene delivery systems

10-year program; Transgene has right to exclusively license and sublicense up to 10 genes from Human Genome; Transgene has rights to develop, manufacture, and commercialize any gene therapy products worldwide; if companies decide to co-develop and co-market products, Human Genome gets rights in North America, Transgene gets Europe and the companies share the rest of world; Human Genome bought 10% equity stake in Transgene¿s IPO (for $25M); Human Genome gets initial license fee; Transgene will fund research in amount equal to Human Genome¿s stock purchase; additional payments to Human Genome depend on number of genes licensed and milestones; companies will pay reciprocal royalties on co-marketed products (3/98)

Idexx Laboratories Inc.

Alpha-Beta Technology Inc.

Letter of intent to collaborate on therapeutics and diagnostics for veterinary, environmental and food markets via Alpha-Beta¿s beta-glucan immunomodulatory compounds and fungal detection products

Idexx gets exclusive marketing and distribution rights to Alpha-Beta¿s products; Alpha-Beta gets technology access fee, milestones and royalties; terms subject to definitive agreement (10/98)

Igen International Inc.

Amgen Inc.

Rights to Igen¿s Origen high-throughput drug discovery system (based on electrochemiluminescence)

Amgen will purchase Origen system and get a pre-launch production model; further details ND (5/98)

Igen International Inc.

Peptide Therapeutics Group plc (U.K.)

Rights to Igen¿s Origen high-throughput drug discovery system (based on electrochemiluminescence)

Peptide Therapeutics will purchase Origen system (pre-production) and use it as part of molecular vaccine design technology (7/98)

Igen International Inc.

ZymoGenetics Inc. (subsidiary of Novo Nordisk A/S; NYSE: NVO; Denmark)

Rights to Igen's Origen high-throughput drug discovery system (based on electrochemiluminescence)

ZymoGenetics will purchase Origen system and gets a pre-launch model; further details ND (7/98)

ImClone Systems Inc.

Merck KgaA

Cancer collaboration to commercialize C225 A monoclonal antibody, which inhibits activity of the epidermal growth factor receptor (EGFr)

Worth potentially $90M and Merck gets exclusive rights to C225 outside North America except in Japan, where both will co-develop it (12/98)

ImmGenics Pharmaceuticals Inc.* (Canada)

Corixa Corp.

Research collaboration on antibody-based immunotherapeutics and diagnostics; use of ImmGenics' selected lymphocyte antibody technology to develop antibodies to Corixa's antigens in cancer and infectious disease

ImmGenics gets R&D payments, milestones and royalties; Corixa bought $1.75M in ImmGenics preferred stock and may invest another $1.23M in 1999 (11/98)

The Immune Response Corp.

Agouron Pharmaceuticals Inc.

Collaboration on final development and commercialization of Immune Response's immune-based HIV therapy Remune (in Phase III trials)

Immune Response will manufacture commercial supplies of product; Agouron gets exclusive marketing rights in North America, Europe and certain other countries; Agouron has certain rights to terminate agreement; Immune Response gets $77M over next 2 years (license fees and milestones of $45M, development payments of $18M, and purchase of $14M in stock at premium to market); of the $77M, Agouron paid $10M initial license fee and bought $2M in stock (0.12M shares); companies will share profits equally (6/98)

Immunex Corp.

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE:AHP)

Immunex will become a participant in Genetics Institute's DiscoverEase protein development program (based on signal sequence trap technology that identifies and isolates fragments of genes coding for secreted proteins); Immunex intends to search for immune system proteins with therapeutic potential

Immunex gets access to DiscoverEase protein library, corresponding genes and relational database of associated information; Genetics Institute retains option to co-develop and co-commercialize products; if it chooses not to exercise this option, benchmarks and royalties will apply (4/98)

Immunotech SA (France; wholly owned subsidiary of Beckman Coulter Inc.; NYSE:BEC)

The Medicines Co.*

License agreement on Immunotech's drug IS-159 (highly selective 5-hydroxytriptamine [5-HT] receptor agonist) for treating acute migraines (Phase II European trials completed)

The Medicines Co. acquired exclusive worldwide rights to drug; further terms ND (8/98)

Incyte Pharmaceuticals Inc.

Xoma Corp.

License agreement on Incyte's patents and patent applications claiming use of bactericidal/ permeability-increasing protein for treating endotoxin-related disorders

Xoma gets exclusive worldwide license; Incyte gets royalties on related product sales; Xoma also granted Incyte warrants to buy 0.25M Xoma shares at $6.00 per share (7/98)

Initiatech Inc.*

Inhale Therapeutic Systems

Licensing agreement on Initiatech's protein stability formulation technology and patents (for protecting biologically active compounds in dry state); Inhale will use technology as means to stabilize dry powder aerosol formulations of peptides, proteins and other macromolecules

Inhale gets exclusive license to technology for use in area of respiratory delivery of pharmaceuticals and for any delivery form of insulin; further details ND (4/98)

Inspire Pharmaceuticals Inc.*

NeoGenesis Inc.*

Strategic alliance on drugs for respiratory disease; use of NeoGenesis' NeoMorph combinatorial chemistry libraries to discover compounds that act at the P2Y(2) receptor (regulator of mucociliary clearance from respiratory tract)

Inspire will screen NeoGenesis' compounds with its cell-based assay system (Mucosa) to identify drug candidates for lead optimization; further details ND (3/98)

Interferon Sciences Inc.

Genzyme Transgenics Corp.

Collaboration to develop transgenic versions of human interferon-alpha

Companies will form joint venture which will own product rights; each company will contribute equally to development costs and will share revenues (7/98)

Introgen Therapeutics Inc.*

LXR Biotechnology Inc.

Evaluation and option agreement; integration of LXR's Bak gene (induces apoptosis and is down-regulated in various tumors) into Introgen's gene therapy technology

Introgen will assess anti-tumor activity of Bak gene; Introgen gets option on exclusive license to gene; LXR gets upfront payment for option; if exercised, LXR gets milestones and royalties (10/98)

Introgen Therapeutics Inc.*

OncorMed Inc.

OncorMed will conduct p53 gene testing for Introgen's Phase I clinical trials of its adenoviral p53 gene therapy

OncorMed will analyze clinical tissue samples to expand knowledge of role of p53 in cancer; further details ND (4/98)

Isis Pharmaceuticals Inc.

Genelabs Technologies Inc.

Collaborative agreement under the auspices of the Defense Advanced Research Projects Agency; companies will use respective drug discovery technologies to develop countermeasures for biological warfare (especially anti-pathogens)

Research will focus on understanding properties of molecules that bind to nucleic acids (Isis to focus on RNA; Genelabs on DNA); also, Genelabs will screen Isis' library of small molecules for DNA-binding abilities (3/98)

Isis Pharmaceticals Inc.

Pantheco A/S

Sublicensing agreement; Isis sublicensed its Peptide Nucleic Acid technology to Pantheco for the creation of anti-infective drugs

Isis will receive a 24.9% equity in Pantheco (11/98)

Isis Pharmacuticals Inc.

Zeneca Pharmaceuticals Inc.

Collaboration to develop antisense-based compounds for cancer

Potential $40M including upfront access fee, annual research funding, milestone payments, plus royalties; Zeneca has exclusive worldwide rights (12/98)

Kimeragen Inc.

AgriBioTech Inc.

AgriBiotech gains an exclusive license to Kimeragen's "precise genetic surgery" technology to develop grasses and forage seed products

ND (12/98)

Layton Bioscience Inc.*

Incyte Pharmaceuticals Inc.

Licensing agreement on Layton's fundamental RNA amplification and gene expression analysis technology (including a non-PCR-based RNA amplification technology)

Incyte gets exclusive license to technology; further details ND (3/98)

Lemery SA de CV (wholly owned subsidiary of Gensia Sicor Inc.; Mexico)

Sequus Pharmaceuticals Inc.

Marketing and distribution of Amphocil (lipid-based colloidal dispersion of amphotericin B) as 2nd-line therapy for severe systemic fungal infections

Lemery gets exclusive rights to market and distribute product in Mexico and Central America for 5 years; after that, Sequus has option to co-market drug (2/98)

Lexicon Genetics Inc.*

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE: AHP)

Functional genomics research agreement for rapid engineering of custom knockout mice via homologous recombination (mice engineered to carry mutant alleles of specific genes; for drug target validation)

Multiyear agreement; Lexicon will provide up to 30 lines of knockout mice to Genetics Institute's specified gene targets; financial details ND (2/98)

Lexicon Genetics Inc.*

ZymoGenetics Inc. (unit of Novo Nordisk A/S; NYSE:NVO; Denmark)

Functional genomics agreement; use of Lexicon's gene sequence database (that corresponds to library of mutant mouse embryonic stem cell clones) to generate mouse mutants for use in ZymoGenetics' programs in gene functional analysis and drug discovery

Multiyear agreement; ZymoGenetics gets non-exclusive access to Lexicon's OmniBank library; Novo Nordisk also gets access to OmniBank information and mutant mice under the agreement; Lexicon gets annual fees for database access as well as fees for developing mutant mice and royalties on future sales (1/98)

Ligand Pharmaceuticals Inc. and its wholly owned subsidiary Glycomed Inc.

Cytel Corp.

Licensing agreement on family of Glycomed patents relating to certain carbohydrate compounds for treating acute inflammation (including Cytel's cell adhesion inhibitor Cylexin)

Cytel gets non-exclusive worldwide license on patents; Glycomed gets up-front fee of $0.9M (paid in restricted Cytel stock); Glycomed also gets $1.5M milestone on 1st FDA filing and $3.5M on 1st FDA approval of each licensed product; Cytel has option to make payments in Cytel common stock; Glycomed also gets royalties on sales of licensed or sublicensed products (2/98)

Ligand Pharmaceuticals Inc.

Elan Corp. plc (Ireland)

Strategic alliance and license on Elan's once-daily solid oral dosage form of morphine (Morphelan) for use in treating pain associated with cancer and AIDS (in Phase III trials)

Ligand will pay Elan for product rights (upfront license fees and milestones in cash or Ligand stock); companies have certain co-promotion rights in U.S., Canada and Europe; Elan bought $20M in Ligand stock ($14.9M for 1.3M shares on 9/30/98 and $5.1M for 0.44M shares on 11/9/98); Elan will also buy $110M in Ligand's zero coupon convertible senior notes due 2008 (it bought the 1st $30M in notes on 11/9/98 and will buy $80M more prior to 12/31/99); the interest-bearing notes are convertible into Ligand common stock at $14.00 per share; Elan owns 8% of Ligand after close of $20M equity purchase and initial note takedown (letter of intent 9/98; finalized 11/98)

The Liposome Co. Inc.

Amgen Inc.

Marketing of Liposome Co.'s Abelcet (amphotericin B lipid complex) for 1st-line therapy of invasive fungal disease

Amgen will market product in Australia and New Zealand; further details ND (10/98)

Maxim Pharmaceuticals Inc.

Amgen Inc.

Agreement to combine Maxamine (H2 receptor agonist) with Infergen (concensus alpha interferon) in planned clinical trial

ND (2/98)

MDS Panlabs Inc. (subsidiary of MDS Inc.; TSE:MHG.A; MHG.B; Canada)

Tripos Inc.

Restructuring of joint collaboration covering the Optiverse chemical library business (created via computer-assisted design; used to find molecular structures that interact with proteins and other cellular components)

Tripos will retain financial stake in Optiverse business; sales and distribution responsibilities will transfer to MDS Panlabs on 7/1/98; companies will continue to work together on contract R&D projects with 3rd parties (see items below) (4/98)

MDS Panlabs Inc. (subsidiary of MDS Inc.; TSE:MHG.A; MHG.B; Canada) and Tripos Inc.

Cell Pathways Inc.

Collaborative drug research agreement; use of Optiverse chemical library to screen for compounds that suppress growth of cancer cells via apoptosis, as well as to design additional compounds and synthesize custom compounds

Cell Pathways will fund research; MDS Panlabs and Tripos get royalties on future product sales; further details ND (3/98)

MDS Panlabs Inc. (subsidiary of MDS Inc.; TSE:MHG.A; MHG.B; Canada); Tripos Inc. and SRI International

Genelabs Technologies Inc.

Genelabs contracted with all 3 companies to access their combinatorial chemistry libraries for designing small-molecule compounds that bind double-stranded DNA (by displacing transcription factors from their DNA binding sites, the goal is to alter gene expression)

Tripos will design compounds via molecular modeling; MDS Panlabs will then synthesize those compounds; SRI, working independently, will use solid phase combinatorial synthesis to make molecules to Genelabs' specifications (3/98)

Medarex Inc.

Centocor Inc.

License agreement on fully human antibodies to 4 antigens created with Medarex's HuMAb-Mouse technology

Centocor exercised option from 10/97 agreement; Centocor gets exclusive license to antibodies; Centocor paid $4M for 0.9M Medarex shares (10/98)

Medarex Inc.

ErythroMed Inc.*

Research collaboration and license agreement; use of Medarex's HuMAb-Mouse technology to produce fully human antibodies for use in Erythro-Med's platform technology for treating infectious diseases

Medarex gets license fees, milestones and preclinical and clinical product manufacturing payments of $13M total, plus royalties; companies will collaborate on developing a 2nd human antibody, with shared rights (5/98)

Medarex Inc.

FibroGen Inc.*

Research collaboration and license agreement; use of Medarex's HuMAb-Mouse technology to produce fully human antibodies against FibroGen's targets for anti-fibrosis therapy (connective tissue growth factor; bone morphogenic protein)

Medarex gets license fees, R&D funds and milestones totaling $30M, plus royalties (7/98)

Medarex Inc.

Novartis Pharma AG (Switzerland)

Use of HuMAb-Mouse technology to produce high-affinity, fully human antibodies for an unlimited number of targets

Novartis will pay at least $50M plus royalties over the next 10 years; deal includes at least $6M in equity purchases. (11/98)

MedImmune Inc.

Pasteur Merieux Connaught

Licensing agreement to develop a 2nd-generation vaccine for the prevention of Lyme disease

ND (12/98)

MedImmune Inc.

Siga Pharmaceuticals Inc.

Licensing agreement on MedImmune's antibacterial technology (based on 2 key enzymes that are required for assembly of pili on Gram-negative bacteria, which allow attachment to human cells)

Siga signed agreements with MedImmune, Astra AB and Washington University-St. Louis to acquire exclusive rights to technology; MedImmune gets 0.34M shares Siga stock (5.3% stake) in exchange for exclusive rights to technology (2/98)

MicroGenics Ltd.* (U.K.)

Oxford Molecular Group plc (U.K.)

Agreement to develop screening systems for antibiotic-resistant microorganisms and to offer those services commercially

Oxford Molecular provided start-up funding to MicroGenics of $4.1M; initially, it paid $0.8M for 19.99% of common shares and $0.1M for preferred shares; Oxford will invest $1.6M over next 12 months and loan MicroGenics $1.6M; Oxford has right to buy the rest of the company between 2000 and 2003 (prices converted at rate of #0.61/US$1) (6/98)

Millennium Pharmaceuticals Inc.

Bayer AG (Germany)

Drug discovery alliance; Millennium will supply Bayer with 225 targets with relevance to cardiovascular disease, cancer, osteoporosis pain, liver fibrosis, hematology and viral infections

Bayer will pay $465M over 5 years, including $33.4 M upfront license fee and a $96.6M equity investment (14%); $388.4M consists of guaranteed funding and performance fees for drug targets identified, and a license fee for the use of Millenium's genomics technologies; Bayer will also pay royalties on developed products (9/98)

Mitotix Inc.*

Cell Genesys Inc.

Collaboration on cardiovascular gene therapy; use of Cell Genesys' 2nd generation adenoviral vector technology with Mitotix's cell cycle genes p16, p27 and p27-16 fusion (which play key roles in regulation of cell growth); Mitotix will also conduct research on cell cycle inhibitors

Cell Genesys gets exclusive worldwide license to use 3 genes for development of gene therapy products for cardiovascular disease and other indications; Cell Genesys will seek 3rd party to commercialize products; Mitotix will share in certain revenues and get milestone payments from Cell Genesys (4/98)

Molecular Dynamics Inc. (subsidiary of Amersham Pharmacia Biotech Inc.)

Clontech Laboratories Inc.*

Joint development and marketing of prefabricated cDNA expression micro-arrays (for high-throughput R&D)

Microarrays will be made broadly available to research community; early versions will be available to participants in Molecular Dynamics' microarray technology access program (9/98)

Molecular Dynamics Inc. (subsidiary of Amersham Pharmacia Biotech Inc.)

Lifecodes Corp.*

DNA microarray technology access agreement; for continued development of high-throughput microarray system (which compares levels of gene expression in normal and diseased cells)

Lifecodes will provide funding and technical expertise, while gaining early access to integrated microarray systems; Molecular Dynamics and Amersham wil supply their integrated hardware, software and chemistry system; Lifecodes will use technology to support development of improved methods of DNA-based genetic analysis (2/98)

Molecular Dynamics Inc. (subsidiary of Amersham Pharmacia Biotech Inc.)

Phase-1 Molecular Technology Inc.*

DNA microarray technology access agreement; for continued development of high-throughput microarray system (which compares levels of gene expression in normal and diseased cells)

Phase-1 will provide funding and technical expertise while gaining early access to integrated microarray systems; companies will co-develop pre-arrayed cDNA slides for toxicology testing; Molecular Dynamics will manufacture ToxArray slides and offer them preferentially to other participants in micro-array technology access program (1/98)

Molecular Simulations Inc. MorphoSys AG* (Germany)

Peptor Ltd. (Israel) LeukoSite Inc.

Drug discovery and lead optimization Research collaboration on therapeutic monoclonal antibodies for inflammatory and autoimmune disorders; use of MorphoSys' human combinatorial antibody library to screen 3 of LeukoSite's disease targets (chemokine receptors and integrins)

Peptor joined MSI's Combinatorial Chemistry Consortium (11/98) 2-year collaboration; LeukoSite gets exclusive worldwide rights to any antibody therapeutics that arise; MorphoSys gets upfront fee, milestones and royalties (8/98)

Mycogen Corp. (subsidiary of The Dow Chemical Co.; NYSE:DOW)

AgriBioTech Inc. (NASDAQ: ABTX)

Joint development program; use of Mycogen's Bt technology to develop insect-resistant alfalfa varieties

Letter of intent; Mycogen will screen its Bt gene and strain library for genes active against insect pests targeted by AgriBiotech; Mycogen will provide selected genes ready for transformation into alfalfa; AgriBioTech responsible for transformation, regeneration, breeding with its own germplasm; AgriBioTech primarily responsible for marketing, but Mycogen will also market through its channels (9/98)

Mycogen Corp. (subsidiary of The Dow Chemical Co.; NYSE:DOW)

Axis Genetics plc* (U.K.)

Licensing agreement on Mycogen's technology for genetically altering plants to produce and deliver edible vaccines

Axis gets non-exclusive license to technology for human health applications; Mycogen gets annual license fees and royalties (3/98)

Mycogen Corp. (subsidiary of The Dow Chemical Co.; NYSE:DOW)

Forage Genetics* (wholly owned subsidiary of Research Seeds Inc.) and New Mexico State University

3-way collaboration to improve forage quality of alfalfa; initially to develop transgenic alfalfa plants with modified protein composition to enhance efficiency of use by cattle and other ruminants

Mycogen and New Mexico State will contribute alfalfa transformation and gene technology; Forage Genetics will contribute alfalfa germplasm; partners will broadly license developed technology (7/98)

Myriad Genetics Inc.

Monsanto Co. (NYSE:MTC)

Monsanto will use Myriad's ProNet technology (a database of human proteins with which they interact, along with the biochemical pathways) to discover and develop therapeutics for two undisclosed disease pathways

Worth up to $15M over 12 to 15 months; includes upfront payment, option payment, license fees and milestones, plus royalties on resulting products (11/98)

NeoGenesis Pharmaceuticals Inc.*

Epix Medical Inc.

Collaboration on advanced contrast agents for magnetic resonance imaging; Epix will screen Neo-Genesis' NeoMorph combinatorial chemistry libraries for product candidates

ND (10/98)

Neurocrine Biosciences Inc.

DOV Pharmaceuticals Inc.*

License agreement on compound NBI-34060 for treating insomnia (binds differentially to gamma amino butyric acid Type I site [benzodiazepine site])

Neurocrine gets exclusive worldwide license to compound for all indications; Neurocrine responsible for development and commercialization; Neurocrine made equity investment in DOV; DOV also gets milestones and royalties (7/98)

Neurogen Corp.

Cubist Pharmaceuticals Inc.

Collaboration on anti-infective compounds active against drug-resistant microorganisms, especially life-threatening pathogens; screening of Cubist's biochemical and whole cell-based assays against part of Neurogen's combinatorial library (generated with its accelerated intelligent drug design program)

Companies will share equally in revenues resulting from future product sales; further details ND (4/98)

NeuroVir Inc.* (Canada)

Cephalon Inc.

Collaboration to create models of Huntington's disease (to evaluate potential therapeutics); involves use of NeuroVir's technologies for delivery of genes to central nervous system (vector based on outer shell of herpes simplex virus)

Cephalon will fund research and pay milestones; under certain conditions (undisclosed), Cephalon may make equity investment in NeuroVir (2/98)

NovaDx International Inc. (VSE:NVN)

Metra Biosystems Inc.

Development and joint venture agreement on NovaDx's Chondrex immunoassay and proteomics-based technologies (which identify serum proteins formed by targeted genes) for osteoporosis and arthritis diagnostics

Metra acquired worldwide rights to technology, including all available sublicensing rights; Metra also gets rights to diagnostics applications of proteomics-based technologies; Metra will buy equity in NovaDx at premium to market; NovaDx also gets upfront and milestone payments, sublicensing fees and royalties (1/98)

Novalon Pharmaceutical Corp.*

Millennium Pharmaceuticals Inc.

Evaluation and research agreement; Novalon will identify BioKeys (surrogate ligands that bind specifically to functional domains of target proteins) for limited number of Millennium's genomic targets

1-year agreement; Millennium will conduct all drug candidate screening; Novalon gets license fees, research funds, milestones and royalties (11/98)

Novavax Inc.

Cantab Pharmaceuticals plc (U.K.)

Collaboration on use of Novasome technology (lipid vesicles) as adjuvant in Cantab's TA-CIN immunotherapeutic vaccine for cervical dysplasia (vaccine composed of selected protein components of types 16 and 18 human papilloma-virus)

Cantab gets 6-month option on worldwide license to technology; Novavax will supply several different Novasome adjuvants for Cantab to test; Cantab's option is extendable for 2nd 6-month period with additional payments to Novavax; if Cantab exercises option, Novavax gets upfront license fee, additional fees, milestones and royalties (1/98); Cantab asked for and was granted a 6-month extension of its licensing option (7/98)

OncorMed Inc. (subsidiary of Gene Logic Inc.)

Affymetrix Inc.

Expansion of 9/96 collaboration on GeneChip-based genetic testing services (for cancer-associated genes); companies will co-develop gene expression database as drug development tool for 3rd-party subscribers; initial focus will be to profile selected genes against tissues from various normal and diseased organ systems

OncorMed will supply tissue samples; Affymetrix will design and supply custom and standard expression monitoring GeneChip probe arrays and related technology; OncorMed will generate high-resolution gene expression data; Affymetrix will market database; companies will share subscription revenues; OncorMed may provide GeneChip expression analysis services to 3rd-party customers (3/98)

OncorMed Inc. (subsidiary of Gene Logic Inc.)

Myriad Genetics Inc.

Settlement of infringement lawsuits on BRCA1 and BRCA2 breast and ovarian cancer patents

Myriad Genetics gets exclusive rights to OncorMed's patents for BRCA1 and BRCA2 breast and ovarian cancer genetic testing in exchange for undisclosed fees as well as exclusive license to all OncorMed's BRCA1 and BRCA2 patents (pending and current) for all genetic testing; Myriad will assume OncorMed's genetic testing business; each company will retain diagnostic and therapeutic rights for its respective patents (5/98)

OraVax Inc.

Biomerica Inc. (NASDAQ: BMRA)

Licensing agreement on OraVax's Helicobacter pylori antigen CagA for use in diagnostics for detecting virulent strains of the bacterium

Biomerica gets exclusive royalty-bearing sublicense to antigen for use in diagnostic tests (ELISA and point-of-care); OraVax retains rights to use of CagA for vaccines to treat or prevent diseases caused by H. pylori infection (4/98)

OraVax Inc.

Pasteur Merieux Connaught

Collaboration to develop a vaccine to prevent dengue fever. OraVax's ChimeriVax will be used to exploit the peculiar structure of flavi-viruses to create a host of live, attenuated viruses

Worth $23.5M plus royalties, including $1M upfront, $6M to fund research and development through the first trials; additional milestones could reach $16.5M (12/98)

Orchid Biocomputer

Motorola Inc.

Collaboration to engineer and manufacture miniaturized electronics components for Orchid's high-throughput array systems

$15M; Motorola will help build an R&D and chip-fabrication facility in Princeton, N.J. (12/98)

OSI Pharmaceuticals Inc.

Aurora Biosciences Corp.

License agreement on OSI's gene transcription patents for use in Aurora's research on small molecule gene transcription modulators

Aurora gets non-exclusive license and certain sublicensing rights to OSI's reporter gene patent and options on OSI's methods-of-modulation patent; OSI gets Aurora common stock and cash (both undisclosed) in exchange; OSI gets revenues from any sublicenses, plus annual fees, milestones and royalties (5/98)

Oxford Glyco-Sciences plc

Incyte Pharmaceuticals Inc.

Joint program in proteomics (large-scale high-throughput analysis of protein expression); companies will develop and commercialize proteomics databases for human, animal, plant and microbial organisms

4-year collaboration; Oxford Glyco-Sciences gets access to Incyte's LifeSeq and PathoSeq databases for use in its internal drug discovery programs in field of glycobiology; Incyte gets access to Oxford GlycoSciences' automated high-throughput protein expression analysis technology; companies will co-own intellectual property and share profits; Incyte will offer proteomics databases on non-exclusive basis to customers; companies will co-market satellite programs to individual customers in specific areas of interest; Incyte will make $5M equity investment in Oxford GlycoSciences (1/98)

Oxford Molecular Group plc, its Collaborative Discovery division and its associate companies, Cambridge Combinatorial Ltd. and Cambridge Drug Discovery (all U.K.)

Oxford Glyco-Sciences plc

Research agreement; use of Oxford Molecular's research and consulting services in drug design, combinatorial chemistry and high-throughput screening to design and synthesize inhibitors of carbohydrate-processing enzymes (for treating fungal infections)

5-year agreement; Oxford Glyco-Sciences will fund research and pay milestones and royalties; Oxford Glyco-Sciences retains exclusive rights to newly designed and synthesized compounds; financial details ND (2/98)

Palatin Technologies Inc.

TheraTech Inc.

Strategic collaboration to develop oral transmucosal delivery systems for several peptide products; initial focus is PT-14, Palatin's 7-amino-acid peptide (melanocortin peptidomimetic) for treating erectile dysfunction

Palatin gets certain licensing rights and will fund development costs of PT-14 delivery system; companies may also collaborate on alternate dosage forms for other Palatin peptides/peptidomimetics; TheraTech will make equity investment in Palatin (3/98)

Pangea Systems Inc.*

Isis Pharmaceuticals Inc.

Subscription to Pangea's Gene-World software and GeneThesaurus service (integrated software and related database)

ND (6/98)

Paracel Inc.*

Celera Genomics Corp. (unit of Perkin-Elmer Corp.; NYSE:PKN)

Collaboration to develop high-resolution informatics tools to analyze genomic information; focus on expressed sequence tags (DNA-and protein-level comparisons of sequence data)

Paracel will install its GeneMatcher high-performance genetic data analysis system at Celera (GeneMatcher is a massively parallel genomic data analysis engine); further details ND (9/98)

Peptimmune Inc.*

Peptide Therapeutics Group plc (U.K.)

Collaboration to design and develop orally available drugs for inhibiting cathepsin S (enzyme that plays key role in initiating immune response via antigen recognition), initially for treating asthma; use of Peptide Therapeutics' RAPiD technology (rational approach to protease inhibitor design) to generate cathepsin S inhibitors

Companies will jointly develop and own any new products; further details ND (3/98)

Pharmacopeia Inc.

Progenics Pharmaceuticals Inc.

Collaboration on small-molecule HIV therapeutics that block attachment of virus to CD4; use of Progenics' high-throughput screening methods with Pharmacopeia's combinatorial chemistry libraries of small molecules

ND (6/98)

Pharming Group NV (EASDAQ: PHAR; the Netherlands)

Genzyme Corp.

Formation of joint venture on enzyme human alpha-glucosidase for treating Pompe's disease (lysosomal storage disease); product produced in milk of transgenic rabbits

Genzyme made $14M equity investment in Pharming in 7/98; Genzyme will fund $14M in development costs; above that amount, companies will equally fund development costs; Pharming gets $7M milestone on FDA approval of product for sale (letter of intent 7/98; finalized 10/98)

Phogen Ltd. (joint venture company formed by Cantab Pharmaceuticals plc and Marie Curie Cancer Center [both U.K.])

Invitrogen Corp.*

Licensing agreement; use of Phogen's VP22-based reagents (VP22 is herpesvirus structural protein, used as intracellular delivery vehicle for peptides, proteins and DNA)

Invitrogen gets worldwide license to sell reagents to research market; Phogen gets upfront license fee and royalties on reagent sales (4/98)

Phytera Inc.*

Chiron Corp.

Research agreement; Chiron will screen Phytera's ExPAND plant cell culture extracts and uMARINE microorganism extracts in its high-throughput systems for drug leads for treating cancer and other diseases

Phytera gets upfront payment and R&D funds, as well as option and license fees based on Chiron's selection of compounds for further development; Phytera then gets milestones and royalties (6/98)

Phytera Inc.*

NeuroSearch A/S (CSE:NEUS; Denmark)

Research agreement; NeuroSearch will screen Phytera's ExPAND plant cell culture extracts and uMARINE microorganism extracts in its potassium ion channel assays for drug candidates for treating memory and attention deficit disorders, depression, asthma and diabetes

Companies will share equally costs of R&D and commercial rights to any products discovered (5/98)

PPD Inc.

Rhone-Poulenc Rorer Inc. (unit of the Rhone-Poulenc Group; France)

Development deal; PPD will search for targets using its GSX system, which isolates functional inhibitors of any gene responsible for a disease pathway; focus is on oncology, inflammation, cardiovascular disease and central nervous system disorders

PPD gets between $20M and $30M if targets in two of the four therapeutic areas are identified or validated, significant royalties on approved products, as well research and development milestones (12/98)

Protein Design Labs Inc.

Elan Corp. plc (Ireland)

License agreement on Protein Design's antibody humanization patents for use with Elan's humanized antibody Antegren (in Phase II trial for multiple sclerosis)

Elan gets non-exclusive worldwide license; Protein Design gets $1.3M license and signing fee plus "significant" milestones and royalties (5/98)

Protein Design Labs Inc.

Genentech Inc.

Cross-licensing agreement on monoclonal antibody patents

Companies granted each other rights to license particular antibodies; Genentech will pay $6M upfront fee to Protein Design for rights to license up to 6 antibodies; Protein Design will pay $1M upfront fee to Genentech for same consideration; each company can obtain non-exclusive, royalty-bearing licenses under other's patents upon payment of $1M fee per antibody (9/98)

Protein Design Labs Inc.

Genentech Inc.

License under Protein Design's antibody humanization patents for antibodies to antigen HER2, including Herceptin (FDA-approved 9/98)

Genentech gets non-exclusive license, issued under terms of 9/98 agreement (see above); Genentech paid $1M license fee; Protein Design gets royalties (11/98)

Protein Design Labs Inc.

Tanox Biosystems Inc.*

License under Protein Design's antibody humanization patents for a humanized antibody to an undisclosed target antigen

Tanox gets worldwide non-exclusive license; Protein Design gets license and signing fee of $1.5M, plus royalties (7/98)

Rapigene Inc. (subsidiary of Chiroscience Group plc, U.K.)

Gemini Research Ltd.* (U.K.)

Research collaboration; use of Gemini's Phenobase database and Rapigene's DNA analysis technologies to discover genes for obesity

Gemini will identify single nucleotide polymorphisms (SNPs) from genes selected as relevant to obesity; Rapigene will develop and perform genotyping assays on twins from Gemini's clinical database; each company will bear own costs; any intellectual property will be licensed to 3rd parties for therapeutic and diagnostic applications; companies will share income (9/98)

RiboTargets Ltd.* (U.K.)

Molecular Simulations Inc. (subsidiary of Pharmacopeia Inc.)

Collaboration to develop software specific to modeling of RNA targets and design of RNA-targeted drugs

3-year collaboration; details ND (10/98)

Roslin Bio-Med Inc.* (Scotland)

Kimeragen Inc.*

Collaboration to develop methods for precise genetic modification of livestock; use of Kimeragen's chimeraplasty technology to modify 2 genes (ovine PRP [gene associated with scrapie] and ovine alpha 1-3 gal [associated with transplant rejection of animal organs by humans])

Goal is to create animal organs that can be transplanted into humans; details ND (10/98)

Sangamo BioSciences Inc.*

Millennium Pharmaceuticals Inc.

Target validation collaboration; use of Sangamo's Universal GeneTools (rationally designed zinc finger DNA recognition proteins that selectively recognize and regulate any target gene or DNA sequence) to validate gene targets for drug discovery

Millennium will evaluate use of Gene Tools in its discovery research; Sangamo gets funding; details ND (10/98)

Scios Inc.

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE:AHP)

Scios subscribed to Genetics Institute's DiscoverEase protein development platform (based on signal sequence trap technology that identifies and isolates fragments of genes coding for secreted proteins)

Scios will use the DiscoverEase library for research in cardiorenal disorders and Alzheimer's disease; Scios gets access to library of expressed human secreted proteins, corresponding cDNAs and database (1/98)

Sepracor Inc.

ArQule Inc.

Collaboration to develop therapeutics that target resistant strains of HIV and hepatitis B virus; use of ArQule's Mapping Array program to identify lead compounds and Directed Array program to optimize them; also employs Sepracor's Anticipated Evolved Target technology for identifying resistance of viruses to drugs before this trait appears in general population

Companies will share ownership rights to any active lead compounds; they will also share revenues on commercial sales; further details ND (3/98)

Sequitur Inc.*

Inex Pharmaceuticals Corp. (TSE:IEX; Canada)

Research collaboration; combines antisense technologies to develop gene-based drugs; includes Inex's intracellular drug delivery technologies, and Sequitur's genomics and protein expression technology (PET; measures protein expression inside target cells)

Sequitur will identify one antisense lead compound for each of 5 of Inex's gene targets; Inex has option on exclusive license to Sequitur's chimeric chemistry for these compounds; Sequitur will also screen and compare alternative antisense chemistries against same 5 targets; Inex gets exclusive rights to 3 targets; companies will share equally rights to other applications of PET (5/98)

Seragen Inc. (subsidiary of Ligand Pharmaceuticals Inc.)

DiagnoCure Inc. (MSE:CUR; Canada)

Licensing agreement on Seragen's fusion protein technology for use in DiagnoCure's nanovector technology (based on nanoerythrosomes, made from red blood cells) for delivering genes or drugs to cells; initial focus on therapies for genito-urinary tract cancers

Seragen gets royalties on sales of products incorporating its technology; further details ND (2/98)

Sheffield Pharmaceuticals Inc.

Elan Corp. plc (Ireland)

Creation of wholly owned subsidiary of Sheffield to collaborate on development of systemic therapies delivered by various pulmonary drug delivery systems; initial focus on Sheffield's metered solution inhaler and Elan's unit-dose pulmonary delivery system

Elan will make $17.5M equity investment in Sheffield ($6M in common stock, for a 17% stake; and $11.5M in 7% convertible preferred stock); Elan will provide funds for acquisition of additional pulmonary drug delivery technologies; Sheffield gets license to certain of Elan's technologies; either company can market products; Elan can convert preferred stock into ownership of new subsidiary or more Sheffield stock; Sheffield gets certain marketing rights outside the collaboration (letter of intent 6/98; finalized 7/98)

SkyePharma plc (U.K.)

Sepracor Inc.

Joint development program; use of SkyePharma's metered dose aerosol technology to deliver Sepracor's chiral version of widely used drugs for asthma

SkyePharma will develop product formulation, scale up production and supply clinical trial materials; Sepracor retains commercial manufacturing rights; Sepracor will sell products under exclusive worldwide license from SkyePharma; Sepracor will fund Skye-Pharma's development costs; Skye-Pharma gets milestones and royalties (10/98)

SR Pharma (unit of Stanford Rook Holdings plc; U.K.)

Corixa Corp.

Exclusive licensing agreement; Corixa can exploit a new immunotherapeutic de-lipidated, de-glycolipidated Mycobacterium vaccae (DDMV) for psoriasis, diabetes, multiple sclerosis and rheumatoid arthritis

Corixa will be responsible for funding the product, development of DDMV in the licensed indications; SR Pharma receives a license fee, milestone payments and royalties on each commercialized indication (12/98)

Sunol Molecular Corp.*

Anergen Inc.

License agreement on Sunol's single-chain, recombinant forms of major histocompatibility complex class II (MHC-II) molecules, coupled with anti-angiogenic peptide

Anergen will evaluate Sunol's molecules for potential use in its AnergiX based program for multiple sclerosis therapies; license is result of 1997 research collaboration between the companies (9/98)

Synchem Research Inc.* (Canada)

Cell Therapeutics Inc.

Vaccine technology licensing agreement; Cell Therapeutics licensed worldwide rights to a class of compounds that are inhibitors of tumor angiogenesis

ND (12/98)

Systems Integration Drug Discovery Co. (SIDDCO)*

Aurora Biosciences Inc.

Combinatorial chemistry agreement; SIDDCO will synthesize up to 2.4M discrete compounds for use in Aurora's ultra-high-throughput screening and pharmaco-informatics programs

Multiyear collaboration; SIDDCO gets certain license and synthesis payments; Aurora will take equity stake in SIDDCO via purchase of preferred shares (4/98)

Systems Integration Drug Discovery Co. (SIDDCO)*

Cor Therapeutics Inc.

Combinatorial chemistry consortium agreement; Cor will work with SIDDCO and other consortium partners to build broad-based combinatorial chemistry technology platform

SIDDCO will integrate its combinatorial and medicinal chemistry technology into Cor's drug discovery programs; Cor will provide research funds and gets access to technology on royalty-free basis (8/98)

Tanox Biosystems Inc.*

ProCyte Corp.

Expansion of 5/98 agreement on ProCyte's wound care products Iamin Gel and OsmoCyte pillow dressings

Tanox will now distribute products in Singapore, Thailand, Malaysia, the Philippines and Indonesia (as well as the People's Republic of China, Hong Kong and Taiwan) (9/98)

Targeted Genetics Corp.

Medeva plc (U.K.)

Develop and commercialize tgAAV-CF, Medeva's cystic fibrosis drug

Total deal worth $54M; $5M in technology fees, $19M for clinical and regulatory milestone payments, a $2M loan, $3M equity investment and up to $15M in development funding over three years; plus $8.5M upfront (11/98)

Theratechnologies Inc. (ME:TH; Canada)

Genetix Pharmaceuticals Inc.*

License agreement on Theratechnologies' Vpr gene for use in Genetix's lentiviral packaging cell line (2nd-generation gene delivery system that uses Vpr gene to eliminate replication-competent retrovirus during manufacture of gene therapies)

Genetix licensed exclusive rights to gene; Theratechnologies gets upfront payment, milestones and royalties from sublicenses or product sales (4/98)

Transgene Inc.

Association Francaise Contre les Myopathies

Extended collaboration to develop a gene therapy for Duchenne's muscular dystrophy

AFM will pay $14.7M to fund research; Transgene will provide expertise in gene therapy to the effort to effectively transfer genes into the muscles of the body; AFM will also pay $11.2M in the form of a research grant and $3.5M in the form of an interest-free loan; Original deal signed in 1995; extended through June 2001 (11/98)

Trega Biosciences Inc.

Biogen Inc.

Supply agreement on Trega's Chem.Folio (small-molecule combinatorial libraries)

2-year non-exclusive agreement; Trega will supply Chem.Folio libraries to Biogen; Biogen also gets non-exclusive worldwide licenses to certain of Trega's chemical synthesis technologies; Trega gets guaranteed funding of $7.5M over 2 years plus milestones (10/98)

Trega Biosciences Inc.

Irori Inc.*

License agreement; use of Trega's Tea-Bag technology (for creating solid-phase combinatorial chemistry libraries) with Irori's AccuTag combinatorial chemistry system-based microreactors

Irori gets worldwide non-exclusive license; Trega gets upfront license fee and royalties; Trega has option to take royalty payments in Irori technology (5/98)

Tripos Inc.

Sepracor Inc.

Collaboration to co-develop new computer-aided research methods for discovering improved HIV protease inhibitors and therapies for treating drug-resistant strains of HIV

Companies will jointly develop technology and products and share profits from sales; funding comes from Small Business Innovation Research grant (2/98)

Vanguard Medica Group plc (U.K.)

Elan Corp. plc (Ireland)

License agreement on Vanguard's anti-migraine therapy frovatriptan (5HT1B/1D agonist; Phase III trials completed)

Elan gets exclusive rights in North America to sell and distribute product; Elan will buy $10M in Vanguard stock (at $6.25 per share) for a 3% stake; Vanguard also gets $50M in milestones, plus royalties; transaction subject to government approvals (10/98)

Vical Inc.

Centocor Inc.

Licensing agreement on Vical's "naked DNA" technology for use in gene-based therapeutic vaccines for treating certain cancers

Centocor licensed technology for use with certain antigens; Vical got $2M initial fee and gets additional payments and royalties (2/98)

Vyrex Corp. (OTC Bulletin Board:VYRX)

Invitrogen Corp.*

License agreement on Vyrex's reading-frame-independent epitope tagging technology and its universal DNA and antibodies that recognize the epitope

Invitrogen gets exclusive worldwide license to market line of products incorporating Vyrex's technology to research community (6/98)

Xenometrix Inc. (OTC Bulletin Board:XENO)

Affymetrix Inc.

License agreement on Xenometrix's gene expression profiling; covers collection of gene expression profiles using all methods, including high-density microarrays

Affymetrix gets non-exclusive license; companies will also collaborate on development and design of DNA arrays for toxicology applications (10/98)

Xenometrix Inc. (OTC Bulletin Board:XENO)

Aurora Biosciences Corp.

License agreement on Xenometrix's gene expression profiling; covers collection of gene profiles using methods other than high-density oligonucleotide microarrays

Aurora gets non-exclusive license and certain sublicensing rights; Xenometrix gets upfront fees, sublicensing fees and royalties (6/98)

Xenometrix Inc. (OTC Bulletin Board:XENO)

Cerep SA (Nouveau Marche: CEREP; France)

License agreement on Xenometrix's gene expression profiling; covers collection of gene expression profiles via broad array of technologies, including proteomics and high-density microarrays

Cerep gets non-exclusive license and certain sublicensing rights; Xenometrix gets upfront fees, sublicensing fees and royalties (6/98)

Xenometrix Inc. (OTC Bulletin Board:XENO)

Gene Logic Inc.

License agreement on Xenometrix's gene expression profiling; covers collection of gene expression profiles using all methods, including high-density microarrays

Gene Logic gets non-exclusive license; further details ND (10/98)

Xenometrix Inc. (OTC Bulletin Board:XENO)

Phase-1 Molecular Toxicology Inc.*

License agreement on Xenometrix's gene expression profiling; covers collection of gene expression profiles using all methods, including high-density microarrays

Phase-1 gets non-exclusive license; Xenometrix gets upfront fee and royalties (7/98)

Xoma Corp.

Diagnostic Products Corp.

License agreement; use of Xoma's lipopolysaccharide binding protein (biochemical marker of systemic exposure to bacterial endotoxin) in diagnostic tests for diseases associated with bacterial endotoxin

Diagnostic Products licensed technology; Xoma gets royalties (8/98)

Xoma Corp.

Invitrogen Corp.*

Licensing agreement on Xoma's microbial cell expression systems (AraB promoter system that controls expression of recombinant proteins in microbial cells and pelB secretion system that improves yields)

Invitrogen will incorporate technology into its plasmid vectors for DNA cloning and protein expression; Invitrogen will sell vectors and possibly recombinant proteins for research purposes; Xoma gets license fee and royalties (4/98)


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