250 APBN • Vol. 4 • No. 12 • 2000 grimm Technologies Limited of Christchurch, New Zealand is a company focusing on the research and development of products that harness the beneficial properties of natural microorganisms for use in horticulture and agriculture. A strong commitment to R&D over the last decade has led to the development of a range of plant protection products that utilize the beneficial properties of the natural soil fungus Trichoderma . These biocontrol products, some of which are registered with the regulatory authorities, control a variety of fungal diseases as well as enhancing plant growth and vigor. These products are marketed under the Trichoprotection ® brand with unique crop specific programs and are sold in several countries including New Zealand, Australia, South Africa and Turkey. Agrimm is a privately owned company, founded in 1984 by the current principals, David SJ Gale and Dr. John S Hunt, with the aim to develop effective, environmentally sustainable products for agriculture. It has four divisions including Administration, Manufacturing, Formulation and Packaging, and Research and Development. These divisions are accommodated on two sites in Christchurch. Specialist laboratories for product development and quality control are situated adjacent to Administration in Fitzgerald Avenue, four blocks from the city center. David Gale, FIMLS, Managing Director and John Hunt, Ph.D., Director of Research, head a small professional staff of ten including Bill Hartley, Production Manager, Rob Sloan, Marketing Manager and Janet McDermid, NZCS, Quality Control Manager. Specialist R&D projects and on-going collaborative research is conducted with Professor Alison Stewart at Lincoln University situated ten kilometers from Christchurch. Specialist laboratories, controlled environment growth rooms and glasshouse facilities together with a dedicated research team working on joint projects are located on the University campus. AGRIMM TECHNOLOGIES LIMITED AGRIMM TECHNOLOGIES LIMITED Trichoprotection ® is the principle of integrated crop protection using the range of biological plant protection products developed and manufactured by Agrimm Technologies Limited. The cornerstone of Trichoprotection ® is a unique range of natural and environmentally safe products that harness the properties of Trichoderma for the benefit of growing plants. The product range includes the registered bio-pesticides, Trichoject ® , Trichodowels ® and Trichoseal ® , for application to woody plants to prevent and control fungal trunk and root diseases; and the bio-inoculants, Trichopel ® , Trichoflow ™ and Trichodry ™ , for protection of the root zone against fungal wilting and root rot diseases. Crop specific programs developed for nursery, protected cropping, fine turf, orchards, vineyards and broad-acre crops are commercially available. The Trichoprotection ® Program for protected cropping includes the use of Trichodry ™ , which is incorporated with the growing media followed by the monthly application of Trichoflow ™ , a wettable powder formulation, which is applied through the fertigation water. Results from these programs have been outstanding commercially with growers reporting significantly less disease together with improved crop yields. A
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250 APBN • Vol. 4 • No. 12 • 2000
grimm Technologies Limited of Christchurch,New Zealand is a company focusing on the
research and development of products that harnessthe beneficial properties of natural microorganismsfor use in horticulture and agriculture. A strongcommitment to R&D over the last decade has ledto the development of a range of plant protectionproducts that utilize the beneficial properties ofthe natural soil fungus Trichoderma. Thesebiocontrol products, some of which are registeredwith the regulatory authorities, control a variety offungal diseases as well as enhancing plant growthand vigor.
These products are marketed under theTrichoprotection® brand with unique crop specificprograms and are sold in several countriesincluding New Zealand, Australia, South Africaand Turkey.
Agrimm is a privately owned company, founded in 1984by the current principals, David SJ Gale and Dr. John SHunt, with the aim to develop effective, environmentallysustainable products for agriculture. It has four divisionsincluding Administration, Manufacturing, Formulationand Packaging, and Research and Development. Thesedivisions are accommodated on two sites in Christchurch.Specialist laboratories for product development andquality control are situated adjacent to Administration inFitzgerald Avenue, four blocks from the city center.
David Gale, FIMLS, Managing Director and John Hunt,Ph.D., Director of Research, head a small professionalstaff of ten including Bill Hartley, Production Manager,Rob Sloan, Marketing Manager and Janet McDermid,NZCS, Quality Control Manager.
Specialist R&D projects and on-going collaborativeresearch is conducted with Professor Alison Stewartat Lincoln University situated ten kilometers fromChristchurch. Specialist laboratories, controlledenvironment growth rooms and glasshouse facilitiestogether with a dedicated research team working on jointprojects are located on the University campus.
Trichoprotection® is the principle of integratedcrop protection using the range of biological plantprotection products developed and manufactured byAgrimm Technologies Limited. The cornerstone ofTrichoprotection® is a unique range of natural andenvironmentally safe products that harness the propertiesof Trichoderma for the benefit of growing plants. Theproduct range includes the registered bio-pesticides,Trichoject®, Trichodowels® and Trichoseal®, forapplication to woody plants to prevent and control fungaltrunk and root diseases; and the bio-inoculants,Trichopel®, Trichoflow™ and Trichodry™, for protectionof the root zone against fungal wilting and root rotdiseases. Crop specific programs developed for nursery,protected cropping, fine turf, orchards, vineyards andbroad-acre crops are commercially available.
The Trichoprotection® Program for protected croppingincludes the use of Trichodry™, which is incorporated withthe growing media followed by the monthly applicationof Trichoflow™, a wettable powder formulation, whichis applied through the fertigation water. Results from theseprograms have been outstanding commercially with growersreporting significantly less disease together with improvedcrop yields.
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Apple trees
Avocado trees
Bedding plants
Turf grass
Brassicas
Conifers
Cyclamen
Grapevines
Kiwifruit vines
Lettuce
Native alpines
Ornamentals
Onions
Peas
Raspberries
Sandersonia
Strawberries
Tomatoes
Tomatoes
Tomatoes
Silverleaf 1,2
Chondrostereum purpureum
Collar rot 1
Phytophthora cactorum
Root rot 1,2
Armillaria mellea
Dying arm 1,2
Eutypa lata
Black dead arm 1,2
Botryosphaeria stevensii
Summary of Trichoprotection® Bio-pesticide Efficacy
DISEASE HOST PRODUCT RESULT
TrichodowelsTrichojectTrichoseal
TrichodowelsTrichoject
Trichoject
TrichodowelsTrichojectTrichoseal
TrichodowelsTrichojectTrichoseal
Apple, apricot,peach, cherry trees
Apple trees
Kiwifruit vines
Grapevines
Grapevines
Protectionand cureProtection
ProtectionCure
Protection
ProtectionClearanceProtection
Protectionand cureProtection
1 Field trial data 2 Field trial and commercial application
Summary of Trichoprotection Bio-inoculant Efficacy
Improved germination and growth with protection against onion
white rot (Sclerotium cepivorum) 1
Resistance to Rhizoctonia and Pythium challenge 1
Improved establishment 2
Improved growth and tuber weight with protection against
Rhizoctonia root rot 1
Earlier crop, improved yield 1
Phytophthora protection, improved crop yield 2
Fusarium wilt protection with improved crop yield 1
Fusarium wilt protection 2
1 Scientific trial data 2 Field and commercial trials
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The Trichoprotection® Program for grapevines canbe divided into two major areas of use, vine propagationand vineyard management. Trichopel®, a nutritivepellet formulation and Trichoflow® are used in themajority of vine propagation nurseries throughoutAustralasia where users report improved callusing, rootinitiation and less disease with their grafted vines.Trichoprotection® vineyard management proceduresinclude the use of Trichopel® and applications ofTrichoflow™ 2–3 times per season, for establishment ofnew vine plantings. In mature grapevines Trichoseal®
wound dressing is used annually to protect newpruning wounds from fungal invasion together withTrichodowels® and Trichoject®, which are applied forprotection and control of diseases caused by wood-invading fungi.
Agrimm Technologies has an extensive on-goingresearch and development program that stretches backthrough the last decade. This has led to thedevelopment and refinement in Trichodermaformulations and manufacturing processes, quality-assured production methods and the invention ofadvanced delivery techniques to aid the effectivenessof its products. The principals of the Company havetwo NZ patents, contribute regularly to horticulturemagazines in New Zealand and Australia and havepresented papers and posters at conferences in NewZealand, Australia and the US. Whilst Agrimm’s
primary research and development program is currentlytargeting plant protection products, the company also hasa significant interest in technology applications for animalhealth care.
A number of research projects arecurrently supported by the company throughTechnology for Business Growth (TBG)grants from the New Zealand Foundation forResearch, Science and Technology. These areconducted in collaboration with LincolnUniversity’s Soils, Plant and EcologicalSciences Division headed by Professor AlisonStewart. This research involves variousprojects to investigate the use of Trichodermaformulations for the field control ofSclerotium cepivorum onion white rot disease,Sclerotinia rots of vegetables, Botrytis diseaseof grapevines and the application ofbeneficial microorganisms for improved fieldestablishment of grapevines.
Agrimm is the commercial partnerfunding the research team working on these projects.Agrimm also co-sponsors a research project in theDepartment of Plant and Microbial Sciences at the WaiteCampus of the University of Adelaide, South Australia.
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gVax Developments Ltd. (AgVax) is aspecialist technology development
company. An autonomous subsidiary ofAgResearch and one of the world’s largestagricultural research organizations, AgVax’sexpertise is in the identification, developmentand commercialization of new technologiesarising from biological research.
In doing this, the company leverages onNew Zealand’s strategic advantage in pasture-based agricultural production. New Zealandenjoys unique status in excellent animalhealth, low environmental pollution and lowproduction costs, leading to very highproduction efficiency. It also has world leadingcapability in biological sciences which havebeen applied to agriculture in the past, butwhich will also be increasingly focused onlife sciences in the future.
Established in 1993, AgVax has grown veryfast, with consistent profitability. Thecompany’s first products were vaccines for use inagriculture, giving rise to the company name, AgVax.These products are unique and directed at particularlychallenging agricultural problems – problems which haveconsiderable economic impact on farmers, but which haveproven very difficult to elucidate. One product, Toxovaxvaccine, effective against abortion in sheep caused bytoxoplasmosis, took over 30 years to develop. This workwas performed by key researchers at WallacevilleResearch Center who now have senior positions withAgVax. Toxoplasmosis is caused by a protozoan parasiteand is increasingly also being recognized as a humanhealth issue.
AGVAX DEVELOPMENTS LIMITEDFrom Research Technology Development to Marketing
By Dr. Tony Brenton-Rule*
AgVax works at the interface between research andindustry, using a market-led approach to identifying andsourcing new technologies. The company’s strategy is toassess technologies against market demand, and then tocommit the time, energy and development funding neededto bring technologies to commercial reality. In doing this,it draws on over 100 years of biological research excellencein New Zealand, but is also prepared to back its judgement.Over 30 percent of company sales revenue is reinvested innew technology and product development.
Most R&D is outsourced to specialist providers, whileAgVax concentrates on project management. In this way,
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*Dr. Tony Brenton-Rule is CEO of AgVax Developments Ltd. and in prior roles has worked throughout Asia and the Pacific. He isalso the Vice President of the New Zealand Institute of Agricultural Science and an Executive Councillor of BIOTENZ, New Zealand’sexport-focused biotechnology council.
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resources and management are deployedto maximum effect. Product manufacture isoutsourced too, and this minimizes the need forhigh capital investment. However, productmarketing and distribution are performed byAgVax because of their strategic importance.
Future company growth is expected to comefrom new uses for existing products, newproducts and new international markets, aloneor in strategic collaboration with others.
New uses for existing products are underconstant review. An example is the Yersiniavaxvaccine, effective against yersiniosis, a deadlyscouring disease in deer. However, yersiniosisis also very important in other species, includingzoological specimens, and the company isworking with veterinarians and researchers inseveral countries on this disease.
New products based on existing technologiesare also of interest. An example is the Androvaxvaccine, which increases female sheep fertility,giving 20 percent more lambs. A similar productis under development for other livestock ofglobal economic importance.
Another example is provided by a vaccineagainst hydatids (Echinococcus granulosis).
Developed by AgResearchat Wallaceville, and theUniversity of Melbourne,the vaccine is presentlyshowing considerablesuccess in trials in thePeople’s Republic of China(PRC), in conjunctionwith the Department ofAnimal Husbandry andHealth of the Ministry ofAgriculture of PRC and theGeneral Station of AnimalHusbandry and VeterinaryScience of PRC.
AgVax is also focusedon the underlying biologyand genetics of farmanimals and their potentiallinkage to human medicalapplications. In this it drawson its parent AgResearch’s,
deep research capability in molecular biology and genomics.
AgVax actively seeks and welcomes information on marketneeds, ideas for new products and proposals for R&D projects.The company may invest itself, or assist in obtaining financefrom other sources or joint development partnering. It is alsoideally placed to assist overseas companies seeking to enter theNew Zealand market, but lacking local R&D capability andrepresentatives.
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orest Research is theprincipal supplier of
research and technologyto the forest sector in NewZealand, and is recognizedinternationally as a leader inforestry research.
The New Zealand forestindustry is facing newcompetition and challenges.The huge increase in projectedharvest volumes, the changingnature of the radiata pine resource, and dynamic marketand business environments all demand increasinglycreative technology-based solutions to ensure the long-term profitability of the industry. The new set of demandsmeans that research will become even more important, andas one of the few forest research organizations in the worldwith expertise spanning forestry science from seed to market,Forest Research is well placed to provide it.
To make the most of this capability, Forest Research isorganized into overlapping and interactive science “portfolios”which take an integrated approach to research. Guided bymarket signals, technical effort is carefully targeted so thatForest Research can provide its clients with a world-class,responsive and leading-edge service. This article describeswork within the “Future Forests” portfolio, which seeks toprovide the forest industry with a platform of genetic andpropagation technologies to improve future plantations.
GENETIC IMPROVEMENT OFRADIATA PINE
The overall goal of this project is to maintain and furtherdevelop radiata pine of superior genetic quality, tomaximize gain in profitability as well as log and woodquality. Another goal is to provide the basic genetic materialfrom which future forests will be developed, by providinga range of differentiated genotypes capable of meetingnominated requirements.
Long term aims are to provide material with improvedproperties, such as reduced spiral grain and enhanced timberstiffness, together with predictions of wood qualityperformance and other important traits for plants deployed
• providing the raw materialfor testing by other researchersinvolved in optimizingprocessing and value of endproducts,
• developing the delivery systemsthat will allow the rapiddeployment of selected genotypes.
Recent achievements include:
• Introduction of a new ranking system known asGF Plus™, to provide information for traditional traits,including growth rate, straightness, branching habit,Dothistroma resistance, wood density and spiral grain,
• A collaborative research project is in progress to developthe Juvenile Wood Index, which will concentrate on thefour main traits of wood: density, spiral grain, microfibrilangle (of cell walls) and compression wood,
• Establishment of a technique to successfully cryopreservecotyledons from embryos extracted from seed, therebyenabling the storage of genetic material while thegenotypes are being field tested.
GENETIC ENGINEERING FOR FUTUREFORESTS
Genetic engineering (GE) may provide tools tocompliment the genetic gains already made throughconventional tree breeding by manipulating endogenousgenes or by allowing the introduction of new traits, notreadily available in the breeding population. GE is alsobeing utilized to gain an understanding of fundamentaldevelopmental pathways, such as those involved in woodformation and reproductive development.
Recent achievements include:
• Development of a gene transformation technique enablingthe transfer of new genes into radiata pine. This technology
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involves the use of a “gene gun” which fires gold-coatedDNA particles into tissue. The protocol has been used tosuccessfully transfer genes into other conifer species (eg.Picea abies, Pinus taeda, Abies nordmaniana etc.),
• Regeneration and field trials of genetically engineeredtrees containing reporter genes and marker genes. Thetransgenic trees are currently undergoing further testingat regular intervals to evaluate expression of the introducedgenes,
• Pinus radiata and Picea abies were transformed forherbicide resistance. When spray tested with operationaldoses of a commercially used herbicide, only transgenicplants survived, while control (non-transformed) trees died,
• Progress has been made towards developing alternativegene transfer systems, including one that utilizesthe “natural genetic engineer” — Agrobacterium. Othertechniques under development include “Agrolistics” thatcombines Agrobacterium and biolistics; as wellas transformation of cell cultures which can be inducedto form tracheary elements (wood cells),
• Forest Research scientists provide these R&D servicesinternationally. Recently a three-year contract wassecured with Fundacion Chile to evaluate Pinus radiatalines, of Chilean origin, with a gene to improve resistanceto the pine shoot tip moth, Rhyacionia buoliana.
APPLICATIONS OF GENOMIC SCIENCE
This project’s role is to build and apply the experimentaltools needed to accelerate the genetic improvement of foresttrees. The genomics project works with both the GeneticImprovement and Genetic Engineering Projects to make thishappen, and also serves as the research arm of SignaGen™.A variety of DNA marker technologies are used in thegenomics project, but current emphasis is on developingmicrosatellite (SSR) and expressed sequence taggedpolymorphism (ESTP) markers. These new generationmarkers are used by SignaGen™ for their pine genotypingservices and are used within the Project for genome mappingand quantitative trait loci (QTL) discovery for importantwood quality traits using radiata pine as a model system.DNA marker genotype and trait phenotype data are analyzedwith advanced statistical methods and experimental designsto find optimal marker aided breeding (MAB) strategies. Tomake MAB an economic reality for forest growers, researchis also conducted to increase throughput and reduce costs ofDNA marker genotyping. The other area of emphasis in thegenomics project is in targeted gene discovery usingdifferential display and DNA sequencing of gene transcriptsfrom xylogenic (wood forming) tissues.
Recent outcomes:
• SSR markers are being developed from radiata pine usinga tripartite strategy of (1) SSR-enriched clone librariesand custom DNA sequence analysis software for highthroughput PCR primer design; (2) SSR-ESTs from publicpine EST databases; and (3) SSR markers from otherpine species,
• A novel method has been developed that can convertseventy percent of pine EST sequences into highlyinformative genetic markers that can be placed on pinegenome maps,
• A more powerful experimental design combinedwith Baysean analysis of marker-trait correlationsto accurately identify QTLs, and maximize genetic gainfrom full-sib family plantation forestry,
• Establishment and analysis of a 3000 full-sib populationfor QTL and candidate gene discovery experiments.
SignaGen™ — MOLECULAR BREEDINGSOLUTIONS
SignaGen™ is a high-throughput DNA testing centercarrying out quality control programs, parentage and paternitytesting, pine pollen contamination testing, customgenotyping, marker-assisted selection, varietal protection,transgene assays, and genetic diversity surveys. It wasestablished in 1998 specifically to provide researchers andindustry users of DNA technology with a reliable,high-quality, cost-effective DNA testing service capableof handling the high throughput needs of many programs.To meet these demands, SignaGen™ operates from apurpose-built facility housing state-of-the-art systemsfor sample tracking, DNA and genetic analyses, andelectronic transmission of results back to clients.
The technology was originally developed in response tothe New Zealand forestry sector’s rapidly growinggenotyping needs. However, the client base has quicklyexpanded to include forestry companies from around theworld and non-forestry related clients in horticulture anddairying.
THE FUTURE
Forest Research is well poised to merge new moleculartechniques with quantitative genetics and propagation toolsto develop total germplasm evaluation systems for forestryclients. The strength of the program stems from theintegration of the available technologies in a forward-thinkingpackage.
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he past six years have seen Genesis Researchand Development Corporation Limited, based in
Auckland, New Zealand, emerge and secure status asan internationally competitive biotechnology companyspecialising in genomics. Genesis has now built anoutstanding gene technology platform to identify molecularregulators of cell-to-cell communication. Commercialapplication of this technology is extended to the fullrange of life science industries including health, forestry,agriculture and horticulture.
The Genesis business strategy is topartner with biopharmaceutical,agricultural and forestry companiesto develop and market end-productsfrom the gene discovery pipeline.Corporate partnerships have provided85 percent of the Genesis research anddevelopment expenditure to date, andhave allowed the Corporation toquickly develop significant intellectualproperty.
Genesis was formed in 1994,with research focused on healthprograms in partnership with twoleading US biotechnology companies,Immunex Corporation and CorixaCorporation, both based in Seattle.These relationships remain until todayand are established cornerstones ofthe Genesis health research program.
With the foresight of the Chief Executive Officer,Dr James Watson, Genesis diversified in 1995 to includeforestry research in its portfolio, in partnership withFletcher Challenge Forestry Limited. This joint ventureinitiated the building of an expressed sequence tag(EST) database using different tissues from twoimportant forestry tree species as sources of geneticmaterial. Today, the forestry EST database is the mostcomprehensive of its kind in the world and providesGenesis with an increasing source of genomic
information from which key genes and proteins can beidentified and extracted.
The success of this venture has led directly to theexpansion of the forestry program into a joint venturewith two international leaders in forestry research andproduct development. Together with Fletcher ChallengeForests, Genesis has joined forces with International Paperand Westvaco Corporation in a new company called
ArborGen, LLC, to produce andmarket tree seedlings for theimprovement of forestry health andincreased productivity for the globalforestry market. Each partnercontributes significant strengths inmarket presence, commitment andtechnological innovation. Genesis willprovide ArborGen with intellectualproperty rights in the form of patentlicenses to use the extensive forestrygenomics database, together withongoing genomics research capabilitiesthrough a five-year contract.
Genesis is also expanding ESTdatabases to include other diversesources, for example, bacteria, andplants and mammalian tissue, to ensurethat genes of strategic importance aresecure for the subsequent candidateselection process. These databases are
selected to specifically develop a competitive advantageand a long-term research focus linked to those commercialsectors in which New Zealand primary industries are leadingthe world.
New Zealand is at the forefront of advanced technologyin the breeding of forestry trees, livestock, grasses, cropsand fruit. By harnessing this expertise with the emerginggenomics technology that Genesis is now able to provide,new collaborations to undertake animal and plantimprovement programs are being established with theagricultural and horticultural industries in New Zealand.
GENESIS RESEARCHAND DEVELOPMENT CORPORATION LIMITED
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RESEARCH PROGRAMS
Research at Genesis is mainly in two streams. The healthprogram centers around developing therapeutics basedon immune modulation. The focus is on identifyingnovel transcription regulators and cytokines involvedin development and function of the immune system andskin. Therapeutic vaccines for the inflammatoryautoimmune disorders psoriasis and asthma are in clinicaltrials and a vaccine for tuberculosis is in an initial testingphase.
The Genesis plant research programis focused on novel gene, promoterand transcription factor discoveriesleading to improvements in plantgrowth, yield and disease resistance.Initially, research involved mainlyforestry trees, targeting lignin andcellulose modification, xylogenesis,maturation and flowering control. Allof these improvements were aimedat producing a sustainable fiber crop.
The Genesis strategy has nowevolved to focus on regulatorymolecules as the most efficient meansof creating the desired improvementsin specific plants. These plantregulators fall into two basiccategories – transcription factors thatcontrol the expression of genes; andplant signaling molecules thatregulate cell-to-cell communicationin plants, and communicationbetween plants and the environment.The regulatory role of the signalingmolecules and receptors controlspecific events in plants such as the development ofleaves, flowers or fruit. They offer a powerful means ofmanipulating the growth, structure and productivity ofplants. Furthermore, their identification offers a uniqueopportunity to create value in the entire range of plantbiotechnology from pasture grasses to crop plants to foresttrees. To begin capturing this value, Genesis is nowfocusing on improving the resistance of plants to fungaland bacterial diseases.
PRODUCT CANDIDATES
Genesis has two candidates for first generation products.
Psoriasis Vaccine
Psoriasis is a flaking skin disease affecting approximately1–3 percent of the global population and for which thereis no existing long-term cure. Research in Mycobacteriumvaccae antigens at Genesis, in partnership with Corixa,has led to the development of a therapeutic vaccine forpsoriasis called PVAC™.
The efficacy of PVAC™ has been demonstrated inPhase I trials conducted in conjunction with the LeonardWood Memorial Research Center in Cebu, the Philippines.
A Phase II clinical trial IND(Investigational New Drug)application with the Food and DrugAdministration (FDA) for PVAC™was awarded in January 2000 and thetrials are being conducted in the US,Brazil and the Philippines. Thepromising results of the Phase I trialshave already attracted internationalinterest. Corixa and Genesis havesublicensed the psoriasis vaccine toZenyaku Kogyo, a privately-heldpharmaceutical company based inTokyo, to develop and market thetherapeutic in Japan.
Asthma Vaccine
Asthma is a chronic, inflammatorylung disease characterized by recurrentbreathing problems. It is a rapidlygrowing disease worldwide. Genesishas partnered with SR Pharma,United Kingdom, to develop atherapeutic asthma vaccine based onMycobacterium vaccae technology. A
vaccine candidate, called AVAC, has been testedsuccessfully in animal models. Clinical trials are beingplanned for AVAC as a therapeutic vaccine in New Zealandand the United Kingdom during 2000.
THE FUTURE
Genesis looks forward to considerable expansion in itsgenomic platform during 2000. The company aims toexpand its sequencing capabilities considerably. Thisexpansion will have a flow-through effect on the rest ofthe research programs and provide the threshold for furthergrowth in the new millennium. Genesis is also seekingnew partnerships to expand its post-genomic capabilities toextract greater value from its considerable databases.
”
“ New Zealand is
at the forefront of
advanced
technology in
the breeding of
forestry trees,
livestock, grasses,
crops and fruit.
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ollowers of the current biotechmarket are well aware of the
emphasis biotechnology companies inthe US, Canada and in Europe areplacing on the desire to translate theirdiscoveries into products or usabletechnologies ready for integration intothe drug pipeline. As a result,increased demand for productionfacilities capable of manufacturingclinical grade materials has risendramatically.
In recent years, significantinvestments have been made in contractmanufacturing facilities to meet theabove demand. Companies, such asCovance Biotechnology Services,Lonza Biologics, Bio ScienceContract Production Corp., and PPLTherapeutics, have almost exclusivelyconcentrated on protein biologics i.e.complex proteins manufactured throughcell culture, through fermentation ofrecombinant Escherichia coli/yeast orby using transgenic animals.
This, of course, has reflected theneed for satisfying the majority ofdrug types entering the pipeline.Construction of facilities formanufacturing small molecules hasalso been on the increase, e.g. SigmaAldrich and ChemSyn Laboratories,even though well over 300 contractmanufacturers worldwide arealready known to be serving thepharmaceutical industry. These havebeen primarily concerned withmaking the simpler kinds of smallmolecules easily obtainable viaorganic synthesis and not the morecomplex small molecules, e.g.secondary metabolites made bycertain types of microorganismstypically exemplified by theactinomycetes.
Contract manufacturers focusing onsecondary metabolites are remarkablyfew in number. In the US, perhapsonly Abbott stands as the best knowncontract manufacturer of cGMPsecondary metabolite clinical material.The lack of such service providersand the realization that more productsof this type will again become invogue has led Industrial Research Ltd.(IRL) in New Zealand to launch anunique cGMP biopharmaceuticalfacility. The company is well known“down under” as a contract R&Dprovider having worked in this areafor 15 years, however new businessarising out of the US over the past4–5 years convinced IRL’s directorsthat an investment in a cGMP facilitywas warranted in order to serve andcapitalize on this expanding marketsegment.
The upgrade in facilities to cGMPstandards was completed in April1999 and the first major projectutilizing the diverse capability ofthe facility has proven the invest-ment to be worthwhile. The projectinvolves the development andmanufacture of a highly toxicsecondary metabolite produced by apathogenic actinomycete for a jointventure between a US biotechcompany and one of the top tenpharmaceutical companies.
The formidable demands of theproject prompted the client toconduct a worldwide search to locatea possible contract manufacturer – onewhich could provide “under the oneroof” ability to:
• propagate a risk group 2actinomycete in viscous culture incubic meter volumes,
• process the broth with organicsolvents in a flameproof environmentto extract the vital molecule,
• handle the toxic molecule(possessing an LD50 < 0.5 mg/kg)in 100g quantities,
• manufacture the product to cGMPstandards.
Upon viewing IRL’s website (http://www.irl.cri.nz), it is recognized thatnot only could the needs of the projectbe met but that production would besupported by a fully accredited ISO9001 quality system.
While a primary focus of IRL’sbusiness lies with secondary meta-bolites, the following other recentcontracts exemplify the unusually diversecapabilities the company provides.
Over the past year IRL has:
• manufactured a C14 labeledsecondary metabolite for metabolicstudies,
• developed a process for themanufacture of a chiral intermediateusing a cross-linked enzyme crystal(CLEC) in organic solvent phase,
• manufactured the first vaccine tocombat hydatids, a parasitic wormdisease afflicting domesticatedanimals.
Current achievements along withprevious successes in addressingneeds of other North American clients(Allelix Biopharmaceuticals andAriad Pharmaceuticals) testify tothe fact that Industrial Researchintends to be a strong force in contractmanufacturing of biopharmaceuticalswell into the next millennium.
Industrial Research Ltd.
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ew Zealand Pharmaceuticals Ltd. (NZP) was formedin the early 1970s to extract and purify biochemicals
from animal by-products. Initially the company’s businesswas only in bile acids, but today NZP supplies a rangeof natural biochemicals to the pharmaceutical, cosmetic,health foods and biotechnology industries. Over 95percent of its products are exported around the world.The privately-owned company employs 70 full-time staffat its plant in Linton.
NZP’s achievements in manufacturing and exportinghave been recognized with numerous awards from theNew Zealand Government and the Manawatu BusinessDevelopment Board. Total Quality Management, whichis an integral part of the company’s culture, ensuresthat NZP’s products conform to stringent customerspecifications and comply with international regulations.In addition to holding licenses to manufacture specificmedicines, NZP is certified to manufacture activepharmaceutical ingredients according to the New Zealandcode of Good Manufacturing Practice (which is identicalto the European Union’s Pharmaceutical InspectionCode).
All the company’s products are extracted and purifiedfrom natural raw materials. The initial focus of the company
New Zealand Pharmaceuticals Ltd.New Zealand Pharmaceuticals Ltd.was the production of biochemicalsfrom meat industry by-products, butNZP is now developing a portfolioof products from plant and marineraw materials. The product rangeincludes bile acids and salts(steroids), glycosaminoglycans,proteins, protein hydrolysates, aminoacids and thymus extracts.
Bile acids and their salts havemultiple uses, which range fromdigestive aids to intermediates forthe production of corticosteroidsand gallstone dissolving drugs.Glycosaminoglycans have usesranging from blood anticoagulantsto moisturizers in cosmetics. NZP’sproteins are used in microbiologicalmedia and health foods. Taurine is
utilized in health food and infant formulae. The thymusextracts have various uses, ranging from treatment ofimmune deficiency diseases to inclusion in cosmeticcreams and haircare preparations.
NZP’s success has been due to a strong commitmentto research and development and it currently employsmore than twenty graduates with a variety of scientificdisciplines. This resource is strengthened by NZP’srelationship with major biochemical research institutes,including Massey University, Crop and Food ResearchLimited and Industrial Research Ltd.
NZP’s first commercial medicinal herb products are arange of Echinacea extracts marketed globally under thetrademark, ActiveHerb®. The second product isProenOthera®, a unique antioxidant extract developed inassociation with Industrial research Ltd. It has higheractivity than related Pine Bark and Grape Seed Extractsand was recently launched on the New Zealand dietarysupplements market. The third plant extract has thepotential to help control blood glucose levels in Type IIdiabetes. Clinical trials are underway to test the product’ssafety and efficiency. If the trials are successful, theproduct will first be sold in the dietary supplements marketin the US.
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asman Extracts manufacturesand exports New Zealand grown
products. Located in Nelson, TasmanExtracts is the country’s largestexporter of botanical extracts. TasmanExtracts supplies a wide variety ofnatural products to both national andinternational markets that include theUSA, Australia, Malaysia, Taiwan,UK and Germany.
The company specializes in thedevelopment of high quality, specialtyproducts designed for the health,nutriceutical, and food industries. Mostof the products are grown and harvestedin New Zealand. Products are processedto meet each customer’s specificspecifications and requirements.
Tasman Extracts is primarily anatural products extract ingredientsupplier. Extracts are available inpowder, liquid, tincture or paste. Theproduct can be offered encapsulatedin tablet form, in bulk or in customerdesigned retail packs.
TASMAN EXTRACTS LTD.
PRIMARY PRODUCTSSUPPLIED
The major natural products thatTasman Extracts regularly suppliesare:
Botanical Extract Products
• Echinacea Purpurea
• Valerian
• St John’s Wort
• Kavakava
• Green Tea
• Passion Flower
• Chamomile
• Hops
Animal and Sea based Products
• Deer Velvet — powders andtinctures
• New Zealand green-lipped musselpowder
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• New Zealand Shark Cartilage
• New Zealand Abalone (Paua)
• Sea Cucumber powder
All raw materials and finishedproduct are constantly tested forpotency and purity both at the in-house laboratory and independentlaborator ies. In-house test ingincludes HPLC; Mass Spectralanalysis; TLC and other specificcustomer specified assay methods.
The company’s plant is ISO 9001certified. The company has justcompleted the addition of overNZ$1 million in its new extractionand evaporation plant, significantlyexpanding production capabilitiesas well as adding new facilitiesfor blending and milling. Withthe addition of the new facilities,the company is now the largestproducer of extracts in the Southernhemisphere.
