www.asiabiotech.com

General

BIO 2006 and the Involvement of Biotech Companies in

Bird Flu R&D Dr Aldar S. Bourinbaiar

T

he 14th Annual International Convention of the Biotechnology Industry Organization (BIO) took place in Chicago in April 2006. BIO 2006, which lasted 1 week, had a record 19 479 attendees from 62 countries. BIO (www.bio.org) represents more than 1100 biotechnology companies, academic institutions, state biotechnology centers, and related organizations across the US and 31 other nations. Its members are involved in the research and development of healthcare, agricultural, industrial, and environmental biotechnology products. The exhibit hall at BIO 2006 was the largest gathering of biotechnology exhibitors, encompassing more than 1700 companies, organizations, and institutions representing every aspect of the biotechnology industry. Exhibitors from 43 states and 36 nations mingled within 176 000 net square feet of exhibit space. Almost one third of the attendees were international participants. Next year, the BIO International Convention will be held in Boston on May 6–9, 2007, with the theme “Science Converges. Business Emerges.” This year’s BIO 2006 was noted by an increasingly significant presence of companies who had products related to bird or avian flu. The type A avian influenza virus H5N1 was first discovered by Hong Kong virologists in 1997; for the first time, the bird flu virus was found to lethally infect humans. Now that the H5N1 subtype has crossed the species barrier, human-to-human transmission is a serious concern, as it could lead to a global pandemic with devastating consequences. Due to the grave concern of the disease, biotech companies have become actively involved in devising means of prevention, treatment, and diagnosis of bird flu. As of the spring of 2006, a total of 31 avian/pandemic vaccine projects from 15 manufacturers—located in Australia, Austria, Canada, France, Germany, Italy, Japan, the Netherlands, Switzerland, UK, and USA—have been registered. Of these, 11 Phase II clinical trials are either ongoing or planned for 2006. Sanofi Pasteur has at least eight different vaccine trials either recently completed or underway. Three prototype vaccines, one from Chiron/Novartis and two from GlaxoSmithKline Biologicals, have been submitted as “mock-up” dossiers for approval by the EU regulatory authority, the European Agency for the Evaluation of Medicinal Products (EMEA). Glaxo’s Dresden site, the Sächsische Serumwerk (Germany), has become the leading developer of vaccines against avian flu. APBN • Vol. 10 • No. 18 • 2006

1045

www.asiabiotech.com

General

BIO 2006 also featured small start-up companies who introduced their vaccine projects. DelSite’s (www.delsite.com) experimental H5N1 vaccine is a nasal vaccine formulated with a gel polymer, extracted and purified from an ordinary aloe vera plant. BioDiem (www.biodiem.com) is an Australian company developing LAIV, which is also an intranasal vaccine containing a live attenuated influenza virus to prevent infection from endemic and pandemic flu. BioDiem’s seasonal flu vaccine, codeveloped with the Dutch-based Nobilon company, has already been tested in Russia without any deleterious effects. Novavax’s technology platform includes virus-like particles (VLPs), as well as new vaccine adjuvants based on Novasomes (i.e. nonphospholipid vesicles and dendrimer technologies). The company is developing a pandemic flu vaccine against H5N1, H9N2, and other avian influenza viruses. Virionics (www.virionics.com) is another young vaccine company that uses VLP technology for its vaccine candidate. Using bioinformatics, Variation Biotechnologies (www.variationbiotech.com) screens thousands of viral sequences isolated from infected individuals worldwide in order to design a universal influenza vaccine that could potentially protect against many strains or variants of influenza. Protein Sciences Corporation’s (www.proteinsciences.com) influenza vaccine uses recombinant proteins from the baculovirus protein expression system in insect cells. Its vaccine consists of three recombinant hemagglutinin (HA) proteins derived from the flu strains selected by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). In addition, the Southern Research Institute of Alabama (www.sri.org) presented their work on H5N1 that they have executed for their drug- and vaccine-developing partners. On the therapeutics side, the Canadian-based Replicor’s (www.replicor.com) lead compound, REP 9, has been shown to have potent antiviral activity against the avian H5N1 influenza virus. Unlike Tamiflu, REP 9 apparently inhibits not only neuraminidase (NA), but also hemagglutinin (HA)—two viral proteins essential for influenza virus replication. ADVENTRX Pharmaceuticals (www.adventrx.com) has claimed that Thiovir, a broad-spectrum antiviral agent and nonnucleoside reverse transcriptase inhibitor (NNRTI) originally designed for HIV therapy, has an added benefit of fighting bird flu. BioCryst (www.biocryst.com) has developed peramivir, a new class of antiviral agents that inhibits influenza neuraminidase. Although the drug is not orally available, like Roche’s Tamiflu, laboratory tests showed that it retains activity against nearly all Tamifluresistant strains of influenza. In addition to vaccine and drug discovery efforts, several companies have focused on developing diagnostics of influenza viruses including H5N1. The report issued at BIO 2006 by Ernst & Young on global biotechnology announced the first avian flu virus kit developed by Vietnamese scientists. The German company Genekam Biotechnology AG (www.genekam.de) presented its product at the convention. Another German company, AJ Roboscreen (www.analytik-jena.de), has been able to double its turnover with the worldwide sales of a rapid test for the influenza virus. CombiMatrix (www. combimatrix.com), which also attended the BIO 2006 convention, has developed a microarray test to identify flu strains with HA subtypes 1–15 and NA subtypes 1–9. A similar development was reported by EraGen Biosciences (www.eragen.com), which announced the development of a MultiCode diagnostic panel to identify a range of respiratory diseases including SARS and avian flu. Rockeby Biomed (www.rockeby. com), a biotech company from Singapore, presented its main point-of-care product for use by consumers or health professionals operating outside hospitals. Vaccines and drugs against H5N1 are often featured in biotechnology news. However, available diagnostic tools, especially those that are specific for H5N1, are less known. Up-to-date information on this topic is critical, but the current information 1046

APBN • Vol. 10 • No. 18 • 2006

www.asiabiotech.com

General

available at the CDC (www.cdc.gov) and WHO (www.who.int) websites is limited. The WHO has published a guideline on the use of flu tests, including a list of countries where avian flu is confirmed or suspected. The WHO recommends that, in addition to rapid assays, a confirmatory test such as RT-PCR or viral culture must be performed on all suspected specimens. However, the CDC and WHO websites do not have allencompassing information in one place, especially concerning commercially available diagnostic tools. This is not surprising since the development process of H5N1 diagnostics has an increasingly rapid turnover, with new players emerging almost daily. Before 2004, when H5N1 first appeared outside of Hong Kong in Vietnam and Thailand, there were practically no commercially available tests on the market. A few companies had kits for the detection of influenza A and B, but there was nothing specific relating to H5N1. The only available test at that time was offered by Hong Kong DNA Chips Limited (www.hkdnachips.com), i.e. nucleic acid sequence-based amplification (NASBA)-based and reverse transcriptase–polymerase chain reaction (RT-PCR) detection kits. Most testing facilities either had custom-designed own tests or needed to send samples to influenza reference labs approved by the WHO. The current policy requires that all laboratory results for influenza A/H5N1 should be confirmed by a WHO collaborating center or by a WHO-recommended reference laboratory. However, there are very few of them: Queen Mary Hospital, University of Hong Kong; National Influenza Center, Kowloon, Hong Kong; National Institute of Infectious Diseases, Tokyo, Japan; National Institute of Medical Research, UK; Department of Infectious Diseases, Memphis, USA; and Centers for Disease Control and Prevention, Atlanta, USA. Obviously, such a referral process is slow and inefficient, but the demand for commercial testing tools has created an intensive R&D effort in this niche. The initial diagnostic products started to appear in late 2005 and early 2006. Given that many of the companies developing these products may be unknown to lay readers, I have decided to compile well-known and lesser-known companies together in Table 1 below. H5N1 first took a firm grip on poultry and wild fowl populations in 1997 in many countries across several continents including Asia, Europe, Africa, and North America. In the last 3 years, close to 240 humans in close contact with infected birds have contracted the virus and over 140 have died. This is particularly worrisome, since the fatality rate for human H5N1 infections is well over 50%. Furthermore, the H5N1 subtype shows resistance to two mainstays of influenza therapy, amantadine and rimantadine. While medications of choice currently include oseltamivir (TamifluTM) and zanamivir (RelenzaTM), there have also been reports of oseltamivir resistance. As news on avian flu evolves, local medical personnel need to identify avian flu, even if they live in unaffected countries. Thus, the key question is the availability of reliable tests to timely detect the virus. The gold standard test used to be viral culture, but results take 5 to 10 days. Typically, virus isolation by culture is done in HeP-2, RD, or MDCK cell lines, and is followed by identification with immunofluorescence assay using specific monoclonal antibody and with hemagglutination inhibition assay. Polymerase chain reaction (PCR)-based genetic tests are most sensitive, but are not widely available due to the requirements of experienced staff and adequate, often costly equipment. PCR assays typically consist of the detection of influenza-specific RNA by RT-PCR using primer sets specific for the DNA sequences of influenza A/H5 and influenza N1. Immunoassays, such as enzymelinked immunosorbent assay (ELISA) and immunofluorescence assay, are relatively simple tests, but they also need special equipment like reading machines and microscopes. The standard immunofluorescence assay is the WHO’s influenza reagent kit for the identification of the influenza A/H5 virus, which includes influenza type A/H5-specific APBN • Vol. 10 • No. 18 • 2006

1047

www.asiabiotech.com

General

monoclonal antibody pool along with influenza B, A/H1, and A/H3 subtype-specific monoclonal antibodies. The simplest and easiest of the tests are the rapid or point-of-care tests, which do not require any particular equipment or experience. They take anywhere between 15 to 30 minutes to produce results, but they are generally believed to be only 70% sensitive and 90% specific. Despite such a perceived imperfection, however, rapid tests can guide early decisions on whether to initiate antiviral therapy, isolate patients, and notify public health authorities. Laboratories, hospitals, and clinicians should have a plan in place to obtain confirmatory tests. Since it remains unclear how much of the H5N1 virus humans shed, different types of respiratory samples (nasal or throat swabs, washes, or aspirates) should be tested for multiple days. The US Food and Drug Administration (FDA) has cleared a number of rapid tests for influenza A. For example, BD Diagnostics (www.bd.com) recently announced FDA 510(k) clearance for the BD DirectigenTM EZ Flu A+B Test. In theory, any A subtype detection product can detect H5N1, but it should be emphasized that specificity and sensitivity are imperfect. Most of these tests employ immunoassay methods, while the Zstat test assesses neuraminidase activity. Since H5N1 is a subtype of influenza A, tests for influenza B will not detect it. Some of the rapid tests (Binax NOW Flu A, QuickVue, SAS, and Zstat) are Clinical Laboratory Improvement Amendments (CLIA)-waived. The CLIA law—first issued in 1988 and amended in 1992—defines waived tests as simple laboratory examinations and procedures that are cleared for home use, employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible, and pose no reasonable risk of harm to the patient if the test is performed incorrectly. Therefore, it is clear that H5N1 tests cannot be easily CLIA-waived. Indeed, on March 22, 2006, the FDA classified reagents for the detection of specific novel influenza A viruses, including H5N1, into class II (special controls); this decision was made in order to provide a reasonable assurance of safety and effectiveness of the device. However, certain kits such as Synbiotics’ (www.synbiotics.com) Flu DETECTTM and ProFLOK® AIV+ were conditionally approved by the US Department of Agriculture (USDA), since they are designed for animal (not human) use. The overwhelming majority of diagnostic companies are concentrated in the USA, despite the fact that the highly pathogenic H5N1 has yet to be detected in that country. Out of the 72 listed companies worldwide, 31 are US companies (although many of them are start-up biotechs, who have only prototype tests that are not commercially available). In second place are diagnostic manufacturers from Japan, followed by China, Singapore, and Russia. Germany is the leading country in Western Europe. Approximately half of these diagnostic companies produce rapid point-of-care detection kits. Most rapid influenza tests—such as BD’s DirectigenTM EZ Flu A+B Test, Quidel’s QuickVue Influenza A+B Test, Wampole’s Clearview Flu A/B, Thermo Electron’s FLU OIA A/B, and Remel’s Xpect® Flu A&B—can only differentiate between influenza A and influenza B subtypes, while others—like NOW® Flu A Test from Binax, Inc, and SA Scientific Ltd’s kit—can only tell whether the virus is type A. It is certain that better and more specific kits will soon be available on the market. In fact, a few companies are already claiming to have developed rapid tests that can specifically identify H5 of H5N1; among them are AgroMicron, Beijing Biochemical, World of Health Biotech, Tauns Co, Sun Biomedical, Animal Genetics, and Rockeby. This is perhaps due to 1

1048

Companies who wish to receive approval for their H5N1 test must contact Claudia Gaffey, Center for Devices and Radiological Health (HFZ–440), Food and Drug Administration, Rockville, MD 20850.

APBN • Vol. 10 • No. 18 • 2006

www.asiabiotech.com

General

the fact that H5N1-related reagents are still rare and seldom available commercially. Nevertheless, the sensitivity of some kits, e.g. Sunbiomed’s Oraline H5N1, matches pretty well with PCR-based assays. Companies producing PCR-based tests using H5N1-specific primers represent approximately one third of influenza diagnostic firms. Most kits are available in regular or real-time PCR formats. While real-time PCR is faster, it usually requires more expensive amplification machines that not every laboratory can afford. Often, real-time PCR tests come with differentiating capability, which provides an added benefit for the clinician. For example, Prodesse Inc’s real-time PCR assay can differentiate between influenza A, influenza B, and respiratory syncytial viruses. Some have configurations different from standard PCR assays. Hong Kong DNA Chips, in addition to standard and real-time RT-PCR kits, also offers NASBA-based kits for the detection of avian influenza virus H5, H7, and all other H subtypes. The sensitivity of most kits appears to be excellent. For example, Veredus Laboratories, a Singapore-based diagnostics company, announced the ability to pick up 5 femtogram (10–15 g) or as few as 1000 copies of viral RNA. Fluoresentric Inc has indicated that its one-step real-time PCR can detect under 10 copies, due to the use of sensitive SYBR dye. Speed is another significant factor to determine the choice of a product. BioMerieux’s test claims to identify the presence of both the H5 and N1 genetic targets in 90 minutes, which is significantly shorter than the usual 4-hour detection period for most kits. Futuristic chip-based multiplex assays are clearly increasingly popular. Several companies have selected the chip or microarray platform for simultaneous detection of multiple analytes. The leading company is CombiMatrix, which launched its influenza DNA array in November 2005. Some companies, like BioWarn LLC, have devoted their effort on chip assays that could detect a pathogen of interest without prior amplification procedure. Genaco Biomedical (www.genaco.com) has chosen Luminex’s proprietary multiplex bead-based xMAP assay to detect 10 separate influenza types, in addition to H5N1. Other array-based companies include Canada’s TM Bioscience, which employs Tag-It™ technology; NanoDetection Technology, with a photon detection biochip; EraGen Biosciences Inc, with an expanded genetic information system (AEGIS) technology; eGene, with an experimental multicapillary electrophoresis cartridge for genotyping H5N1; and the Australian firm Ambri, with an ion biosensor test based on ion channel switch technology. The Singaporean company Veredus recently announced the joint development of Lab-on-Chip with Geneva-based STMicroelectronics (www. st.com), using the latter’s In-CheckTM platform to identify whether a patient is infected with the avian flu (H5N1) or with a subtype of influenza A or B. Several experimental chips are currently being developed at academic institutions. For example, the recently announced FluChip was developed by researchers from the University of Colorado and the CDC. The CDC is also collaborating on the development of a DNA test with Celera Genomics (www.celera.com), which has received a US$900 000 grant from the National Institutes of Health (NIH). Moreover, a credit card-sized flu detection chip was recently developed It should be noted that some companies listed in Table 1 are not strictly in the diagnostic manufacturers category. HyTest, Biodesign, GenWay, MorphoSys, Protein Sciences, and Prosci sell antibodies and/or recombinant influenza proteins that could be used for laboratory testing, manufacturing diagnostic kits, and vaccine development. Incidentally, at least two of the firms (Protein Sciences and Denka Seiken) are working on influenza vaccine projects. Tests designed to reveal the presence of IgA, IgG, and/or IgM antibodies against influenza viruses and H5N1 could be especially useful for testing 2

An earlier PCR kit developed by CDC was approved by the FDA on February 3, 2006. APBN • Vol. 10 • No. 18 • 2006

1049

www.asiabiotech.com

General

vaccine efficacy in clinical trials. Some of these tests are available from Scimedx, Idexx SARL, World of Health Biotech, Naroo Ditech, and Animal Genetics Inc. In addition to standard rapid chromatographic immunoassays (ELISA and PCR assays), Table 1 lists unique products not available elsewhere. For example, Applied Biosystems produces a kit which is designed for the rapid and sensitive quantitation of influenza neuraminidase inhibitor resistance—a property that could be potentially useful for screening drug resistance to the two main H5N1 drugs TamifluTM and RelenzaTM. CombiMatrix’s microarray, in addition to typing influenza strains, can also identify drug-resistant strains. ZymeTx Inc is another unique company that has based its assay on the activity of neuraminidase rather than the HA antigen. A few companies have chosen other proteins of the flu virus as a target. For example, BioChek’s and ImmTech’s ELISA kits are designed for the detection of influenza NS nucleoproteins in horseradish peroxidase and alkaline phosphatase, or in chemiluminescent format. As the bird flu virus spreads from water fowl to domestic birds, it is critical to identify and localize animals carrying the virus before it spreads to humans. The availability of diagnostic tests is critical to catch the eventual epidemic in early stages, so that the relevant authorities can take measures to reduce the chances of spread by culling infected birds, disposing carcasses, as well as cleaning and disinfecting affected areas. Doctors can use appropriate antibodies and antiviral therapy on correctly diagnosed patients; prompt treatment will also reduce the possibility of antigenic shift, whereby the virus can mutate into a more virulent strain. As the influenza virus frequently mutates, it will be difficult to develop an effective vaccine to keep up with the prevailing strains of bird flu. The only real way to combat the worldwide outbreak of the disease is by continuously monitoring and screening the disease.

Contact Details: Contact Person: Aldar S. Bourinbaiar Immunitor USA Inc College Park, MD 20740 USA Tel: +1 301 474 9369 Fax: +1 775 640 6636 Email: [email protected]

1050

APBN • Vol. 10 • No. 18 • 2006

www.asiabiotech.com

General

Table 1: List of Companies Manufacturing or Developing Influenza Detection Reagents and Products No.

Company name

Country

Website and address

Description of assay

Trade or brand name

1.

AgroMicron Ltd

Singapore

www.agromicron.com 10 Anson Road #30-07 International Plaza Singapore 079903 Tel: +65 6559 3545 Fax: +65 6559 3583

RT-PCR detection kit for H5N1 combined with differential type A and B diagnosis. Rapid test for H5N1 and A/B diagnosis.

Flu VueTM

2.

AJ Roboscreen GmbH (subsidiary of Analytik Jena)

Germany

www.analytik-jena.de Konrad-Zuse-Straße 1 07745 Jena Tel: +49 3641 77-70 Fax: +49 3641 77-92

PCR-based H5N1 detection test using Analytik Jena’s SpeedCycler (rapid PCR technology)

RoboGene® Bird Flu H5N1 Test

3.

Ambri

Australia

www.ambri.com.au 1a26 Greville Street Chatswood NSW 2067 Sydney Tel: +61 2 9422 3000 Fax: +61 2 9422 3013

Experimental ion biosensor test for detection of influenza A based on ion channel switch technology.

ICSTM

4.

Amplisense

Russia

www.pcr.ru Central Epidemiology Institute 3a Novogireevskaya Street 111123, Moscow Tel: +7 495 105 05 43 Fax: +7 495 305 54 23

PCR-based fluorescent probe test for differential H5N1 and H7 diagnosis.

Amplisense Influenza Virus A H5/H7

5.

Animal Genetics Inc.

Korea

www.anigen.co.kr 404-5, Woncheon-dong Yeongtong-gu, Suwon-si Gyeonggi-do Korea 443-823 Tel : +82 31 211 0516, Fax: +82 31 211 0537

Rapid tests for avian influenza virus type A, and H5 virus antigen test. ELISA for detection of antibodies to the AIV in chicken, duck, turkey, goose, swan, guinea fowl, horse, pig. Also RT-PCR and real-time PCR kits for avian H5, H7, and H9 detection.

6.

Applied Biosystems

USA

www.appliedbiosystems.com 850 Lincoln Center Drive Foster City, CA 94404 Tel: +1-650-638-5800 Fax: +1-650-638-5884

2-hour real-time PCR kit for detection of influenza A (M and H5 genes). Influenza Neuraminidase Inhibitor Resistance Detection Kit is designed for the rapid and sensitive quantitation of influenza neuraminidase inhibitor resistance.

TaqMan® Influenza A/H5 Detection Kit v1.0

ArtusTM Influenza/H5 LC RT-PCR Kit

7.

Artus GmbH

Germany

www.artus-biotech.com Koenigstrasse 4a DE-22767 Hamburg Tel.: +49-(0)40-41 36 47 00 Fax: +49-(0)40-41 36 47 10

Real-time PCR-based tests for detection of avian H5N1 and influenza genes in human and animal samples. In collaboration with Qiagen.

8.

Asia-lion Biotechnology Co Ltd

China

www.asialionbiotech.com 4/F, Building A 48 Yinhua Road Xiangzhou, Zhuhai Tel: +86-756-2267514 Fax: +86-756-2267374

Rapid test for influenza type A and B viruses using nasal swabs in strip and card formats.

9.

BD Diagnostics

USA

www.bd.com 1 Becton Drive Franklin Lakes, NJ 07417 Tel: +1 201 847-6800 Fax: +1 877 232-8995

Two-step, rapid influenza test to differentiate between influenza A and B in 15 minutes

NA-Star® Influenza Neuraminidase Inhibitor Resistance Detection Kit

BD DirectigenTM EZ Flu A+B Test

APBN • Vol. 10 • No. 18 • 2006

1051

www.asiabiotech.com

General

10.

Beijing Chemical Import and Export Corp

China

Building 12, Jianguomeiwai, Beijing 100012 Tel: +86-10-65684516 Fax: +86-10-65682024

H5N1 antigen and antibodies in rapid and ELISA formats.

11.

Binax

USA

www.binax.com 10 Southgate Road Scarborough, ME 04074 Tel: +1 207 730-5700 Fax: +1 207 730-5710

Three rapid tests to identify and distinguish between type A and B viruses.

NOW Flu A and NOW Flu B Tests BinaxNOW® Influenza A & B Test

12.

BioChek

The Netherlands

www.biochek.com Crabethstraat 38-C 2801 AN Gouda Tel: +31 182 582 592 Fax: +31 182 599 360

ELISA kit for the presence of nucleoprotein from type A avian influenza.

13.

BIODESIGN International

USA

www.biodesign.com 60 Industrial Park Road Saco, Maine 04072 Tel: +1 207-283-6500 Fax: +1 207-283-4800

Monoclonal and polyclonal conjugated and unconjugated antibodies against influenza and H5N1.

14.

BioMerieux

France

www.biomerieux.com F-69280 Marcy l'Etoile Tel: +33 04 78 87 20 00 Fax: +33 04 78 87 20 90

Detects the presence of both the H5 and N1 genetic targets in 90 minutes.

NucliSens EasyQ® Influenza H5 and N1

15.

BioStar Inc. (Inverness Medical)

USA

www.biostar.com 331 South 104th Street Louisville, Colorado 80027 Tel: +1 303 530-3888 Fax: +1 303 530-6601

Rapid test developed in collaboration with Biota Holdings Ltd of Melbourne, Australia. CLIA-waived.

Biostar FLU OIA®

16.

BioWarn LLC

USA

www.biowarnllc.com 19632 Club House Road Suite 520, Montgomery Village MD 20886 Tel: +1 301 926-9050 Fax: +1 301 926-8432

Experimental device for influenza detection currently in development.

SmartSense

17.

CERTEST BIOTEC SL

Spain

www.certest.es Maria de Luna 11, nv 16 E-50018 Zaragoza Tel: +34 976 52 03 54 Fax: +34 976 10 62 68

Rapid chromatographic immunoassay for detection of influenza A virus in cloacal swabs and stool samples.

CerTest Avian Flu Test

18.

Charles River Laboratories

USA

www.criver.com 67 Baxter Road Storrs, CT 06268 Tel: +1 860-889-1389 Fax: +1-860-429-2572

Avian influenza antigen (CAMH/I, Turkey/Wis/66), avian influenza antiserum (T/W/66, chicken origin), and serum screening flocks for antibodies against all avian influenza types (AGID testing).

19.

Chemicon (acquired by Milipore)

USA

www.chemicon.com 28820 Single Oak Drive Temecula, CA 92590 Tel: +1 951-676-8080 Fax: +1 951-676-9209

PCR kit for detecting influenza A and B types.

LIGHT DIAGNOS-TICSTM Flu A/B Typing OligoDetect®

20.

Clonit Srl

Italy

www.clonit.it Via Bernardo Quaranta 57 20139 Milan Tel: +39-0256814413 Fax: +39-0256814515

Solid-state real-time PCR kit for H5N1 detection.

H5N1 (“nested”)

1052

APBN • Vol. 10 • No. 18 • 2006

Influenza (Type A) Antigen Detection Test Kit

www.asiabiotech.com

General

21.

CombiMatrix Corp (subsidiary of Acacia Research Corp)

USA

www.combimatrix.com 6500 Harbour Heights Parkway Suite #301 Mukilteo, WA 98275 Tel: +1 425 493-2000 Fax: +1 425 493-2010

Under 4-hour test in microarray format to identify flu strains with HA subtypes 1 through 15 and NA subtypes 1 through 9 during the posthybridization labeling step of electrochemical detection.

CombiMatrix Influenza A Microarray

22.

Coris BioConcept

Belgium

www.corisbio.com Science Park CREALYS Rue Jean Sonet 4A 5032 Gembloux Tel: +32 (0)81 719 917 Fax: +32 (0)81 719 919

Rapid (10-minute) immunochromato-graphic test for influenza A and A&B detection.

Influ-A RespiStrip

23.

Cyntegra

USA

www.cyntegra.com San Diego, California Tel: +1 619 819-5066 Fax: +1 310 861-5606

Claims combined dual rapid test for cats and dogs to detect H5N1 and H3N8. No product information is available.

Viogenix Duo

www.daiichichem.jp 13-5 Nihombashi 3-Chome Chuo-ku, Tokyo 103-0027 Tel: +81 3 3272 0691 Fax: +81 1 3275 2266

Rapid test for detection of influenza A and B.

RapidTesta FLU AB

24.

Daiichi Pure Chemicals Co

Japan

Rapid Testa FLU STICK

25.

Davidbio Biotech Co Ltd

China

www.davidbio.com 904/5, Shimao Guangchang Shantou, GD 515041 Tel: +86-754-8736059 Fax: +86-754-8736059

Rapid diagnostic kit.

26.

Denka Seiken Co Ltd

Japan

www.denka-seiken.co.jp 3-4-2, Nihonbashi Kayabacho Chuo-ku, Tokyo Tel: +81 (0)3 3669 9091 Fax: +81 (0)3 3669 9390

Differentiating influenza A and B rapid (15-minute) test. The positive result is indicated by the presence of a distinct red diamond shape. Also vaccine development R&D.

QUICK S-INFLU A/B “SEIKEN”

27.

DNA Technology A/S

Denmark

www.dna-technology.dk Gustav Wieds Vej 10A DK-8000 Aarhus C Tel: +45 87 32 30 00 Fax: +45 87 32 30 11

5-hour PCR-based kit for avian influenza type A detection.

FluAVision

28.

eGene Inc.

USA

www.egeneinc.com 17841 Fitch Irvine, CA 92614 Tel: +1 949 250-8686 Fax: +1 949 250-8833

Experimental multi-capillary electrophoresis cartridge for genotyping H5N1 DNA.

29.

Eiken Chemical Co Ltd

Japan

www.eiken.co.jp 1-33-8 Hongo, Bunkyo-ku Tokyo 113-8408 Tel: +81-3-3813-5401

Proprietary RT-loop amplification technology for detection of H5N1.

Loopamp Avian Flu H5 Primer Set

30.

EraGen Biosciences Inc.

USA

www.eragen.com 918 Deming Way Madison, WI 53717-1944 Tel: +1 608 662-9000 Fax: +1 608 662-9003

Based on proprietary AEGIS (an expanded genetic information system) technology, which allows rapid and direct DNA detection of SARS and avian flu.

MultiCode-RTx

31.

Fluoresentric Inc.

USA

www.fluoresentric.com P.O. Box 982303 Park City, Utah Tel: +1 800 808-0490 Fax: +1 435 658-1408

SYBR-based, high-sensivity (detection to >10 copies), highspecificity, 1-step real-time RT-PCR.

Avian Flu H5N1 Detection Assay—1 Step RT PCR.

APBN • Vol. 10 • No. 18 • 2006

1053

www.asiabiotech.com

General

32.

Fujirebio Inc.

Japan

www.fujirebio.co.jp 2-62-5, Nihonbashi-hamacho Chuo-ku, Tokyo 103-0007 Tel: +81-3-5695-9268 Fax: +81-3-5695-9238

Rapid test for detection of human, avian, and swine influenza viruses.

Espline Influenza A&B-N

33.

Genaco Biomedical Products

USA

www.genaco.com 2707 Artie Street Building 100, Suite 20 Huntsville, AL 35805 Tel: +1-256-704-4875 Fax: +1-256-425-0053

4-hour PCR-based multiplex test to detect 10 influenza types in addition to H5N1. Test is based on Luminex xMAP platform.

ResplexTM III

34.

Genekam Biotechnology AG

Germany

www.genekam.de Damm Str. 31-33 47119 Duisburg

Real-time PCR-based test for detection of H5N1, H9, and H7 viruses (cost: 1299 Euros).

DNA FluHunter

Tel: +49-203-555858-31 Fax: +49-203-358299 35.

GenWay Biotech Inc.

USA

www.genwaybio.com 6777 Nancy Ridge Drive San Diego, CA 92121 Tel: +1 858 458-0866 Fax: +1 858 458-0833

Hemagglutinin - Influenza A Virus H5N1 Vietnam/1203/04 (HA-Vietnam) recombinant protein (10-663-45507) from baculovirus.

36.

Hong Kong DNA Chips Limited

Hong Kong

www.hkdnachips.com 8/F Hang Tung Resources Center 18 A-Kung Ngam Vi Shau Kei Wan

NASBA-based, real-time RT-PCR detection of avian influenza virus H5, H7, and all other H subtypes.

VDS AIV, VetScreen AIV, and VetDetect for H5, H7, and H1-15

Tel: +852 2111 2123 Fax: +852 2111 9762 37.

HyTest Ltd

Finland

www.hytest.fi Intelligate, 6th floor Joukahaisenkatu 6 20520 Turku Tel: +358-2-512-0900 Fax: +358-2-512-0909

Influenza virus type A and B stock. Monoclonal and polyclonal antibodies for in vitro use.

38.

Idexx SARL

France

www.idexx.com BP 232, 95614 Cergy Pontoise Tel: +33 1 34 32 62 00 Fax: +33 1 34 30 02 08

Detects antibodies against H5N1 within 7 days postinfection.

FlockChek® Avian Influenza Antibody Test Kit

39.

ImmTech Inc

USA

www.immtech.net 206 High St, Suite 2 P.O. Box 726 New Windsor, MD 21776 Tel: +1 410-775-7060 Fax: +1 410-775-7061

ELISA kit for detection of all types of influenza nucleoproteins including H5N1 in horseradish peroxidase or in chemiluminescent format.

Influenza A Nucleoprotein Antigen Detection EIA

40.

Meridian Bioscience Inc.

USA

www.meridianbioscience.com 3471 River Hills Drive Cincinnati, OH 45244 Tel: +1 513 271-3700 Fax: +1 513 271-3762

Various rapid tests for detection of flu A and B types.

NOW® Flu A and B CLIA Waived

www.biogenesisinc.com P.O. Box 1016 Kingston, NH 03848 Tel: +1 603 642-8302 Fax: +1 603 642-8322

Various antibodies against influenza A and B.

41.

1054

MorphoSys US Inc. (Biogenesis)

USA

APBN • Vol. 10 • No. 18 • 2006

ImmunoCard STAT!® Flu A and B PLUS

www.asiabiotech.com

General

42.

NanoDetection Technology

USA

www.nanodetectiontechnology. com 2160 Lakeside Center Way Suite 250 Knoxville, TN 37922 Tel: +1 865 300-5497

Patented biochip that detects light produced as a result of a chemical reaction (DNA hybridization or protein conjugation) of a “positive” test, and that simultaneously converts the photons into an electrical signal.

Biosensor Detection System

43.

Naroo Ditech Inc.

Korea

www.narootech.co.kr #303 Jungho B/D 250-3 Yangjae Dong Seocho Gu, Seoul Tel: +82 2-578-0844 Fax: +82 2-578-0845

ELISA for influenza A and B IgA, IgG, and IgM.

44.

NCB Co Ltd

China

Xueyuanlu 20 Haidian District, Beijing Tel: +86 10 62340599 Fax: +86 10 62340599

Bird Flu Rapid Test (Avian Influenza H5N1).

45.

Nicherei Corp

Japan

www.nichirei.co.jp Nichirei Higashi-Ginza Building 6-19-20 Tsukiji, Chuo-ku Tokyo, 104-8402 Tel: +81-3-3248-2235

Rapid test for detection of A and B flu viruses.

Statmark Influenza A/B Virus Detection Reagent

46.

Orgenics (owned by Inverness)

Israel

www.orgenics.com P.O. Box 360, Yavne 70650 Tel: +972 8-9429201 Fax: +972 8-9438758

Rapid test for influenza type A.

QuickTest Influenza H5 Strip

47.

Prodesse Inc.

USA

www.prodesse.com W229 N1870 Westwood Drive Waukesha, WI 53186 Tel: +1 262 446-0700 Fax: +1 262 446-0600

Real-time PCR assay that can differentiate influenza A, influenza B, and respiratory syncytial virus.

ProFlu-1TM

48.

Prosci Inc.

USA

www.prosci-inc.com 12170 Flint Place Poway, CA 92064 Tel: +1 858-513-2638 Fax: +1 858-513-2692

Recombinant H5N1 peptides from NS1, NS2, and M1’s exportin and CRM. Also various antibodies against H5N1.

49.

Protein Sciences Corp

USA

www.proteinsciences.com 1000 Research Parkway Meriden, CT 06450 Tel: +1 203-686-0800 Fax: +1 203-686-0268

Recombinant HA and NA proteins from H1N1, H3N2, H5N1, H7N2, H6, H9, and H15 viruses for use in laboratory animals or in vitro testing.

50.

Qiagen Benelux BV

The Netherlands

www.qiagen.com Spoorstraat 50 5911 KJ Venlo

PCR-based tests for detection of avian H5N1 and influenza genes in human and animal samples. Developed with Chinese PG Biotech company.

51.

Quest Diagnostics

USA

www.questdiagnostics.com 1290 Wall Street West Lyndhurst, NJ 07071 Tel: +1 201-729-8363

Real-time RT-PCR tests targeting influenza viruses A and B; parainfluenza viruses 1, 2, and 3; and RSV.

52.

Quidel

USA

www.quidel.com 10165 McKellar Court San Diego, CA 92121 Tel:+1 858 552-1100 Fax: +1 858 455-4960

Rapid test detection of influenza A and B antigens from nasal swab, nasal wash, and/or nasal aspirate specimens (CLIAwaived).

RealArtTM Influenza LC RT PCR Kit

QuickVue Influenza A+B

APBN • Vol. 10 • No. 18 • 2006

1055

www.asiabiotech.com

General

53.

Remel Inc.

USA

www.remel.com 12076 Santa Fe Drive Lenexa, KS 66215 Tel: +1 800-255-6730 Fax: +1 913-888-0939

Rapid 15-minute test to distinguish between A and B flu viruses. Can detect avian flu strains H5N1 and H9N2.

Xpect® Flu A&B

54.

Response Biomedical Corp

Canada

www.responsebio.com 100-8900 Glenlyon Parkway Burnaby, BC V5J 5J8 Tel: +1 604 456-6010 Fax: +1 604 456-6066

Rapid influenza A type test. Signal is read with fluorescence detection machine.

RAMP Flu A

55.

Rockeby Biomed

Singapore/ Australia

www.rockeby.com 350 Orchard Road #21-01/03 Shaw House Singapore 238868 Tel: +65-6735-2368 Fax: +65-6720-0687

Rapid, one-step chromatographic immunoassay for the qualitative detection of influenza virus antigen type A in human or avian specimens.

Vet-Smart Avian Influenza Virus and Bioline Human Influenza A Test

56.

SA Scientific Ltd

USA

www.sascientific.com 4919 Golden Quail San Antonio, TX 78240 Tel: +1 210 699-8800 Fax: +1 210 699-6545

CLIA-waived rapid test for influenza A detection.

SAS Influenza A Test

57.

Scimedx Corp

USA

www.scimedx.com 400 Ford Rd Denville, NJ 07834 Tel: +1 973 625-8822 Fax: +1 973 625-8796

ELISA assays for detection of anti-influenza A and B IgG and IgM antibodies.

Anti-Influenza A IgG/M Assay

15/17 Prof. Popov Street 197376 St Petersburg Tеl: +7 812 234-62-11 Fax: +7 812 346-12-70

Rapid test for detection of influenza A and B types. Also other kits are available, e.g. ELISA RT-PCR.

58.

Anti-Influenza B IgG/M Assay

St Petersburg manufacturing plant for diagnostic devices

Russia

59.

STMicroelectro-nics

Switzerland

www.st.com 39, Chemin du Champ des Filles C. P. 21 CH 1228 Plan-Les-Ouates Geneva Tel: +41 22 929 29 29 Fax: +41 22 929 29 00

Lab-on-Chip platform to detect H5N1 and type A and B viruses simultaneously. Joint project with Veredus Labs.

In-CheckTM

60.

Sun Biomedical Laboratories Inc.

USA

www.sunbiomed.com 604 VPR Center 1001 Lower Landing Road Blackwood, NJ 08012 Tel: +1 856-401-1080 Fax: +1 856-401-1090

Rapid sensitive test for detection of H5N1 in saliva samples.

Oraline H5N1

61.

Synbiotics Corp

USA

www.synbiotics.com 11011 Via Frontera San Diego, CA 92127 Tel: +1 858 451-3771 Fax: +1 858 451-5719

Rapid 15-minute test for detection of influenza viruses, and ELISA for detection of antibodies in the serum. US FDA-approved for poultry.

Flu DETECTTM

Flu-Virotest Subtype A

ProFLOK® AIV +

62.

Sysmex Corp

Japan

www.sysmex.co.jp 1-5-1 Wakinohama-Kaigandori Chuo-ku, Kobe 651-0073 Tel: +81 78-265-0500

Rapid test for influenza A&B.

POCTEM INFLUENZA A/B

63.

Takara Bio Inc.

Japan

http://bio.takara.co.jp Seta 3-4-1, Otsu Shiga 520-2193 Tel: +81 77-543-7247 Fax: +81 77-543-9254

ELISA assay for detecting HA of influenza A virus. 96-well format.

Takara Influenza A Virus Enzyme Immunoassay Kit

1056

APBN • Vol. 10 • No. 18 • 2006

www.asiabiotech.com

64.

Tauns Co Ltd

Japan

http://www1.odn.ne.jp/tauns/ 43-3 Kozuwa, Nomazu Shizuoka 410-0872 Tel: +81 55-925-6200 Fax: +81 55-925-6161

General

Rapid test for detection of influenza A and B (sold by Nippon Beckton Dickinson).

Capilia Flu A+B

65.

Thermo Electron Corp

USA

www.thermo.com 81 Wyman Street Waltham, MA 02454 Tel: +1 781-622-1000 Fax: +1 781-622-1207

FDA-cleared rapid test which can distinguish between the two types of flu—influenza A and influenza B.

The FLU OIA A/B

66.

TIB MOLBIOL GmbH

Germany

www.tib-molbiol.com Eresburgstrasse 22-23 D-12103 Berlin Tel: +49 30 78 79 94 55 Fax: +49 30 78 79 94 99

RT-PCR mix kit for H5, N1, type M gene, and H5N1 gene detection of Asian isolates.

LightMix for Influenza A H5N1 detection

67.

TM Bioscience

Canada

www.tmbioscience.com 439 University Ave, Suite 900 Toronto, Ontario M5G 1Y8 Tel: +1 416-593-4323 Fax: +1 416-593-1066

Prototype DNA panel kit to detect respiratory syncitial virus, SARS coronavirus, parainfluenza, and influenza virus A/B (including H5N1) based on company’s Tag-ItTM technology.

Upper Respiratory Infectious Disease Panel

68.

Vector Best

Russia

www.vector-best.com 630559 Koltsovo Novosibirsk region Tel: +7 383 227-73-60 Fax: +7 383 332-81-34

ELISA and PCR tests for diagnosis of H5N1 and other influenza virus types.

69.

Veredus Laboratories

Singapore

www.vereduslabs.com 83 Science Park Drive #03-02A The Curie Singapore Science Park 1 Singapore 118258 Tel: +65 6776-3633 Fax:+65 6776-6636

Under 4-hour one-step RT-PCR kit to detect H5N1.

Avian Flu H5N1 RT-PCR Kit (1-step)

70.

Wampole Laboratories LLC (owned by Inverness)

USA

www.wampolelabs.com 2 Research Way Princeton, NJ 08540 Tel: +1 609 627-8000 Fax: +1 609 627-8013

A 15-minute test for influenza A and B on the same device. For nasal swabs, washes, and throat swabs.

Wampole Clearview Flu A/B

71.

World of Health Biotech Co Ltd

China

www.healthbiotech.net 122, No. 2 Building Xinjiekou Xicheng, Beijing 100035 Tel: +8610 66179934 Fax: +86 10 62220041

Point-of-care and ELISA tests for detection of antigens and antibodies against H5N1,

72.

ZymeTx Inc.

USA

www.zymetx.com 655 Research Parkway Suite 554 Oklahoma City, OK 73104 Tel: +1 405 271-1314 Fax: +1 405 809-1944

Point-of-care test based upon the activity of the neuraminidase. Substrate contains modified N-acetylneuraminic acid (Neu5Ac) coupled to a chromogen.

ZstatFlu®

APBN • Vol. 10 • No. 18 • 2006

1057