UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
ý ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2004
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o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Commission File Number 000-21873
BIOSITE INCORPORATED
(Exact name of registrant as specified in its charter)
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Delaware |
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33-0288606 |
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(State or other jurisdiction of |
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(I.R.S. Employer |
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11030 Roselle Street |
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92121 |
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San Diego, California |
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(Address of principal executive offices) |
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Registrant’s telephone number, including area code: (858) 455-4808 |
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Securities registered pursuant to Section 12(b) of the Act: |
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NONE |
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Securities registered pursuant to Section 12(g) of the Act: |
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Common Stock, $.01 par value |
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Preferred Stock Purchase Rights |
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(Title of Class) |
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Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports) and (2) has been subject to such filing requirements for the past 90 days. Yes ý No o
Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the best of the registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K. o
Indicate by check mark whether the registrant is an accelerated filer (as defined in Rule 12b-2 of the Securities Exchange Act of 1934. Yes ý No o
The aggregate market value of the shares of Common Stock held by non-affiliates of the Company, based upon the closing price of the Common Stock on June 30, 2004 as reported on the Nasdaq National Market, was approximately $570,000,000. Shares of Common Stock held by each executive officer and director and by each person who owned 10% or more of the outstanding Common Stock have been excluded in that such persons may be deemed to be affiliates. This determination of affiliate status is not necessarily a conclusive determination for other purposes. The determination of who was a 10% stockholder and the number of shares held by such person is based on Schedule 13G filings with the Securities and Exchange Commission, or SEC, as of June 30, 2004.
As of February 21, 2005, there were 16,790,662 shares of the Registrant’s Common Stock outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Certain information from Registrant’s Proxy Statement to be filed with the SEC in connection with the solicitation of proxies for the Registrant’s 2005 Annual Meeting of Stockholders is incorporated by reference in Part III of this Form 10-K.
BIOSITE INCORPORATED
FORM 10-K
INDEX
Biosite®, Triage®, Omniclonal® and New Dimensions in Diagnosis® are registered trademarks of Biosite Incorporated. Cardio ProfilER™, Profiler CP™, Profiler Shortness Of Breath™, MultiMarker Index™ and the Company’s logos are trademarks of Biosite Incorporated. Beckman Coulter® is a registered trademark of Beckman Coulter, Inc. This annual report on Form 10-K also contains trademarks and trade names of other companies.
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Forward-looking Statements
The matters discussed in this Annual Report on Form 10-K contain forward-looking statements that involve risks and uncertainties, including: the impact of competition, including products competitive with our Triage® BNP Tests, from companies with greater capital and resources; our ability to effectively promote our products, whether directly or through distributors, including our ability to effectively promote our products in the physician office market; our ability to successfully expand our business through direct sales in certain European countries; the outcome of ongoing litigation between us and Roche Diagnostics Corporation and others; potential contract disputes or patent conflicts; the extent to which our products and products under development are successfully developed and gain market acceptance; our ability to obtain regulatory approvals and complete other clinical and pre-market activities needed to launch new products and gain market acceptance of any new products; manufacturing inefficiencies, backlog, delays or capacity constraints; the timing of significant orders or the impact of seasonality; regulatory changes, uncertainties or delays; product recalls; dependence on third-party manufacturers and suppliers; changing market conditions and the other risks and uncertainties described under “Risk Factors” and throughout this Annual Report on Form 10-K. Actual results may differ materially from those projected. These forward-looking statements represent our judgment as of the date of the filing of this Annual Report on Form 10-K. We disclaim any intent or obligation to update these forward-looking statements.
Overview
Founded in 1988, Biosite® Incorporated is a leading [bio-medical] company commercializing proteomics discoveries for the advancement of medical diagnosis. We believe that our novel, rapid medical diagnostic products, largely evolved from an intensive study of protein biomarkers of disease, can contribute to improvements in medical care by aiding physicians in the diagnosis of critical diseases and health conditions. We have been profitable for the past 23 consecutive quarters. Our compounded annual growth rates for net product sales and diluted earnings per share over the past five years are 41% and 107%, respectively.
We believe that utilizing biotechnology to provide physicians with rapid, reliable diagnostic information is vital to improving patient outcomes and easing the tremendous cost pressures that threaten to undermine healthcare excellence. In selecting market opportunities, we primarily target highly prevalent diseases that are poorly diagnosed by existing technologies. Currently, we offer diagnostic products for drug screening, heart attack, congestive heart failure, or CHF, acute coronary syndromes, or ACS, evaluation of shortness of breath and certain bacterial and parasitic infections.
Our strategy for sustained growth is built around our unique discovery, development and commercialization platform, which is intended to ultimately produce a portfolio of proprietary, high value diagnostic products.
• To implement this concept, our technology platform includes phage display antibody discovery and production, microfluidic devices for specimen and reagent handling, and fluorescence-energy-transfer measurement systems.
• To augment our internal capabilities, we work with a growing network of proteomics and pharmaceutical companies and clinical institutions that collaborate with us in the discovery of new disease markers and in the assessment of their medical utility.
• To commercialize discoveries, our regulatory and marketing strategies are different from traditional diagnostics companies. In some cases, the novelty of our tests may require that we obtain premarket approval from the FDA, support extensive clinical studies, and provide medical education directed at the caregivers who use our products.
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We believe this innovative approach provides the potential for a competitive advantage over traditional diagnostic companies, not only because of the unique nature of our science, but also because it provides us with the basis for key patent applications. Since the medical and economic value of providing better, faster answers to pressing diagnostic questions is substantial, we believe the profit potential of our products currently in development, if successfully developed and commercialized, could parallel those of other important, proprietary medical devices.
Discovery
The recent upsurge in the understanding and utility of human biomarkers or analytes, including proteins, peptides, enzymes, hormones and other blood-borne molecules that are the biologically active components of normal and diseased physiology, has been the catalyst for our discovery effort. In most diseases, tissue damage and biological response mechanisms change the blood levels of analytes enabling them to be used as diagnostic “disease markers.” Most disease markers currently in clinical use signal disease when their concentrations rise above a defined normal cut-off point. For example, above-normal concentrations of the following markers result in a positive disease diagnosis:
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Disease |
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Glucose |
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diabetes |
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Prostate specific antigen |
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prostate cancer |
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Hepatitis surface antigen |
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hepatitis B |
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B-type natriuretic peptide, or BNP |
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Congestive heart failure, or CHF |
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Given the low returns to date, marker discovery has historically been viewed as an expensive, time consuming and risky undertaking for commercial enterprises. As a result, large diagnostic companies generally look to academic researchers for new marker validation or rely on clinically proven markers in developing testing menus.
We have developed our own internal program, Biosite Discovery, focused on screening potential protein disease markers in order to identify novel proteins or combinations of proteins that function as disease markers and have high diagnostic utility. We believe our discovery platform is significantly different from discovery methods employed by other companies. Key to Biosite Discovery is our proprietary Omniclonal® phage display antibody development technology, which enables the rapid and cost-efficient development of immunoassays that can be used to evaluate up to several hundred potential disease markers each year.
Our Biosite Discovery program encompasses a three-step process:
1. Through a variety of collaborations, we collect patient blood samples related to disease states in which we are interested. These samples include disease-specific samples, samples from patients with conditions that mimic the targeted disease, as well as samples from a normal, disease-free population. We seek to establish comprehensive sample banks, accumulating thousands of samples. Sample collection can be time intensive and subject to fluctuations in timing, therefore, our ability to establish relationships and collaborations with reliable sources of samples is essential.
2. Once samples are available, we use them for testing as we conduct “marker mining” to find markers with high diagnostic utility for a targeted disease. To do this, we use immunoassays, which require tightly binding, or high-affinity, antibodies, to test potential markers against our samples bank. Our ability to efficiently develop large quantities of high-affinity antibodies for these research immunoassays allows us to screen large numbers of markers in our efforts to identify those most suitable for a diagnostic product.
3. When data for potential markers is available, we use a proprietary software system to define the priority of the markers in terms of their importance in diagnosing the targeted disease. This enables us to determine the optimal markers for a diagnostic product. Once this decision is made, the product proceeds to development.
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We believe that our Biosite Discovery model is significantly different from discovery methods employed by other companies. Some of our differentiating qualities include:
Rapid Antibody Development: We believe we enjoy a unique position in the area of phage display antibody development. In the 1970’s, the discovery of hybridoma technology, a process for creating monoclonal antibodies, made it possible to precisely measure blood proteins at very low concentrations. Initially, we incorporated this technology into our research programs; however, the time consuming and resource intensive nature of this hybridoma technology limited the scope of research that could be performed.
In the 1990’s, we began in-licensing and refining technology for a new approach to antibody discovery and production called phage display, which creates genetically engineered, antibody-producing microorganisms. Through further advancement of this process, we were able to create Omniclonal antibody libraries, which contain thousands of gene-encoded antibodies to specific protein targets. Generally, development of antibodies may take nine months or more. Using our proprietary Omniclonal phage display antibody development technology, we can quickly create human or murine libraries in weeks. Following evaluation for clinical relevance, the useful antibodies can be economically produced.
High Throughput Capacity: Because we utilize a highly efficient antibody technology and have automated the most significant liquid handling steps, we believe we currently have a high throughput capacity to develop high affinity antibodies. With this high throughput capacity, we are able to generate antibodies to a substantial number of targets in a cost-efficient manner. This permits us to take on significant discovery endeavors, such as our stroke program, to identify, evaluate and develop novel diagnostics.
Target Validation Approach: We focus on serious health problems that are in need of improved diagnosis, prognosis and monitoring. We collaborate with commercial companies and clinical institutions to collect large numbers of protein targets and clinically documented samples that can be studied for association with selected diseases.
Proven Rapid Commercialization Capability: We have a track record of successfully moving novel diagnostics, including the Triage® BNP Test, through the development pipeline. We commercialized the first portable fluorescence-based quantitative immunoassay platform and we developed the first rapid, quantitative point-of-care immunoassays to receive U.S. Food and Drug Administration, or FDA, clearance for the measurement of cardiac markers as an aid in the diagnosis of acute myocardial infarction, of BNP as an aid in the diagnosis of CHF, and of overdosed and abused drug analytes as an aid in the identification of drug overdose.
Self-funded Program: We leverage development efficiencies to contain costs, and subsidize our discovery efforts with revenues generated from collaborations.
Development
Our on-going product development goal is to provide physicians with timely and relevant information upon which to base their diagnoses, prognoses and therapeutic strategies. The integration of several core scientific and engineering disciplines is the foundation for our research and development efforts. These include antibody development, analyte cloning and synthesis, development of highly sensitive fluorescence energy transfer dyes, microcapillary protein array technology and sample handling. More recently, however, we have enhanced our expertise in the development of test panels capable of multi-marker measurements.
Because many acute diseases and conditions, such as chest pain, stroke, sepsis and abdominal pain, have complicated causes, we are focusing a considerable portion of our development efforts on multi-marker test panels. Through Biosite Discovery, we believe we can select the optimal markers for a targeted condition. Our research has shown that discrete measurements of markers on a multi-marker panel, while sufficient, may not always provide the most useful result. Therefore, we have developed a proprietary process for reducing multiple protein concentrations to a single MultiMarker Index™ value that we believe can be more easily interpreted than multiple marker measurements and is more accurate in the clinical setting for diagnosis and prognosis.
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We anticipate that the MultiMarker Index value will be initially used in two potential products, the Triage Profiler CP Panel and the Triage Stroke Panel, pending regulatory approvals. Clinical study data collected from more than 2,000 acute coronary syndromes and non-cardiac chest pain patients demonstrated that the Triage Profiler CP™ Panel MultiMarker Index value significantly improved the overall diagnostic accuracy for the early diagnosis of acute coronary syndromes and heart attack.
An important component of our product development strategy is our approach to validating the clinical usefulness of the MultiMarker Index value. Historically, most new products in the diagnostics arena measured biomarkers or analytes, such as glucose, cholesterol and prostate specific antigen, for which clinical validity was already established. Consequently, the pre-market validation process for these tests usually focused on showing that the new product measurements correlated with diagnostic products already on the market. Manufacturers could perform this validation in their own laboratories. Many potential Biosite products lack pre-existing diagnostic models and we will be required to demonstrate that these tests provide valid diagnostic outcomes. To this end, we believe that we have developed the organizational and institutional relationships necessary to sponsor large clinical trials with the goal of obtaining data to support the diagnostic indications that we wish to claim for our products. We may also fund follow-on clinical studies once a product is launched to further validate diagnostic utility or new applications for the test. While our clinical trial process adds considerable time and expense to our development timelines, we believe it provides us with important competitive advantages and, most importantly, can help improve patient care.
We believe that our novel approach to discovering and developing new multi-marker diagnostic products for unmet applications will provide us with the best opportunity to establish and maintain broad patent protection, which may in turn support a favorable market position for our products. Many of the technologies that enable our products are already covered by issued patents or are the subject of patent filings. We have filed foundational patents covering our MultiMarker Index approach to diagnosis and prognosis, which claim both the generic algorithm used to derive a MultiMarker Index value, as well as certain combinations of proteins for specific diseases and conditions, such as stroke, sepsis, chest pain, shortness of breath, myocardial infarction, acute coronary syndromes and abdominal pain.
Commercialization
Our efforts culminate with the Total Triage Solution, a custom diagnostic system designed to fit our customers’ unique needs. With the Total Triage Solution, we seek to provide our healthcare customers with access to better, faster and more efficient and accurate diagnostic and prognostic technology backed by a comprehensive education and support network. Our products are principally sold to acute care hospitals, which number approximately 5,400 in the United States. To market our products, we utilize a direct sales team that focuses its efforts primarily on larger centers with more than 200 beds and smaller hospitals that are high volume users of our products. We also use a network of distributors both in the United States and internationally.
To commercialize MultiMarker Index products, we have developed a testing platform that can quickly and easily quantify multiple proteins using a small amount of whole-blood. The product can be used at the point-of-care, as well as in a laboratory. We have key intellectual property rights to many elements of our platform.
The Fisher HealthCare Division of the Fisher Scientific Company, or Fisher, distributes our products primarily in hospitals in the United States and supports our direct sales force, particularly in smaller hospitals. We have a distribution agreement with Fisher that extends through December 31, 2005. Sales to Fisher represented 86% and 90% of our product sales in 2004 and 2003, respectively. We utilize distributor relationships with Physician Sales & Services, or PSS, and Henry Schein, Inc., or Henry Schein, to market our products to physician office laboratories in the United States.
In international markets, we have established direct selling efforts in several countries and utilize a network of country-specific and regional distributors in other areas. During 2003 and 2004, we initiated direct sales and distribution operations in France, Germany, Belgium, Luxembourg, the United Kingdom and Italy. In the future, we may transition to direct sales and distribution of our products in additional countries. Sales to international customers in 2004, 2003, and 2002 totaled $26.0 million, $14.5 million, and $11.4 million, respectively.
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Because our products are designed to change the practice of medicine, rather than merely reduce the cost of testing, we invest substantially in education for healthcare clinicians using our diagnostic products. While diagnostic companies traditionally market their products solely to clinical laboratories, we generate demand for our products among laboratory clinicians, physicians and hospital administrators, by demonstrating the medical and economic advantages of our diagnostic products. Supporting our worldwide sales team is a field-based network that includes clinically experienced individuals providing pre- and post- sale education and training and customer and technical support resources to assist with ongoing utilization of our products. As of December 31, 2004, our worldwide sales team and our supporting field-based network consisted of 101 and 35 representatives, respectively.
Our product sales for 2004 were $240.6 million, representing a 42% increase over 2003. This growth resulted largely from increased sales of our Triage BNP Test products, which are primarily used to aid in the diagnosis of CHF. Our meter-based Triage BNP Test, launched domestically in January 2001, was the first blood test available to aid in the detection of CHF and benefited from a semi-exclusive position in the market until the entry of direct competition in June 2003. In December 2003, we received clearance from the FDA to market our Triage BNP Test for Beckman Coulter® Immunoassay Systems and began selling the product in the United States in January 2004. As a result, a customer can perform BNP testing using either our rapid, portable Triage MeterPlus system or any of Beckman Coulter Inc.’s automated immunoassay systems.
Today, our Triage BNP Test products are among several FDA-cleared products for use as an aid in the diagnosis of CHF. These include products from Bayer Healthcare, Dade Behring, Roche Diagnostics and Abbott Laboratories, which offer products based on large, centralized automated testing platforms. We have experienced, and continue to experience, competition from these companies and anticipate competition from others in the future. Our competitors may succeed in developing or marketing products that are more effective or more commercially attractive than the Triage BNP Tests. Moreover, we may not have the financial resources, technical expertise or marketing, distribution or support capabilities to compete successfully with these and other competitors in the future.
Industry Background
Testing Platforms
Generally, automated analyzers have been the preferred diagnostic testing platform in mainstream hospitals. Competition within the diagnostics industry, has traditionally centered around improvements in cost-effectiveness, throughput and the ability to precisely measure disease markers. Testing platform development within the industry usually involves relatively low technical risk, and platforms are typically marketed to clinical laboratories that run tests, rather than to the physicians who order diagnostics. There are a variety of automated analyzers for clinical laboratories to choose from and menus are typically not proprietary, therefore, competition is intense and the industry suffers from low margins compared with other medical devices. Industry leaders tend to be those companies with low cost positions and the marketing mass to succeed with commodity product lines.
Within hospitals, diagnosis is typically accomplished through a battery of testing methods including immunoassays. Historically, the majority of immunoassay testing has been accomplished through a centralized process using large automated analyzers housed in the central laboratory. These centralized immunoassay analyzers utilize automated liquid handling mechanisms and pipetting systems for reagent addition. Modern centralized immunoassay analyzers are capable of storing and selecting multiple reagents for a variety of analytes, including drugs, hormones and cancer antigens. They also provide accurate and highly sensitive test results and help to simplify the performance of immunoassays. While automated immunoassay analyzers may meet hospitals’ routine testing needs, the use of centralized automation may lead to lengthy turnaround times to accommodate transport of the sample to the testing laboratory, time-consuming sample preparation and delivery of results to the physician. Additionally, centralized immunoassay analyzers require high volumes of sample throughput to justify the investment in equipment, training, staffing and other costs required to operate and support the systems.
In recent years, rapid testing methods that can be performed in minutes with minimal training have emerged to complement centralized automated testing. Simple, rapid immunoassays are capable of detecting a single analyte marker with a color change that can be visually interpreted. Formats such as dipsticks, test tubes and membrane test
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cartridges have been used to provide fast, non-instrument read results for conditions where a single analyte marker is present in high concentrations and where a simple yes/no non-numeric answer is clinically relevant. Rapid color change test formats are widely available for drugs of abuse, pregnancy, strep throat and ovulation prediction. Many of these tests utilize compact, portable testing platforms that enable testing to occur at the point-of-care.
We believe that significant market potential exists for rapid diagnostics with novel applications that are capable of precise quantitative measurement of single or multiple analytes. Studies, including one published in the February 2004 issue of the New England Journal of Medicine, have shown that rapid testing, including point-of-care testing, may help to reduce overall healthcare delivery costs and improve patient outcomes by providing diagnosis in a reduced period of time, thereby minimizing the time to medical intervention. Patients undergoing emergency procedures can benefit from more timely and accurate testing results, both of which improve decision-making, which could limit unnecessary use of costly inpatient care. Faster diagnosis can also permit earlier and more appropriate patient management, potentially shortening the duration of illness. Furthermore, the development of new diagnostics for diseases that currently lack accurate diagnostic products could improve treatment and provide better outcomes.
We believe that rapid, point-of-care testing is optimal to significantly improve patient care and reduce healthcare costs, especially for acute conditions. However, we also recognize that diagnostic needs and objectives vary from hospital to hospital. Therefore, in addition to providing our rapid Triage BNP Test on our existing Triage MeterPlus platform, we offer a version of the product for use on a centralized automated testing platform. We have an agreement with Beckman Coulter under which it manufactures the Triage BNP Test for Beckman Coulter Immunoassay Systems for us, and we exclusively sell and market the product. The product received 510(k) Premarket Notification, or 510(k), clearance from the FDA in December 2003. We began selling the product in Europe in December 2003 and in the United States in January 2004. In the future, we may also choose to offer other products for use on centralized automated testing platforms.
Technology
Historically, we have made significant investments in research and development, exceeding traditional diagnostic industry standards. These investments have yielded several proprietary advances in the biological and physical sciences that serve as the basis for our diagnostic marker discovery platform and make practical the development and manufacture of rapid, accurate and cost-effective diagnostics. Our products integrate our expertise in several core scientific and engineering disciplines, including antibody development and engineering, analyte cloning and synthesis, signaling chemistry and microcapillary fluidics, each of which is described below. By combining research capabilities in each of these areas, we create novel single and multi-analyte diagnostics that overcome the limitations of traditional diagnostic technologies and seek to address the significant unmet need for effective, real-time diagnostic information.
Antibody Development
Traditionally, antibodies have been recognized as valuable tools for the characterization of protein targets because they can be used to localize the protein in tissues, to quantify the protein in body fluids and to modulate the biological activity of the protein by, for example, binding to the protein and blocking its natural function. Antibodies have traditionally been derived from immunization of animals and either the harvest of antiserum containing antibodies or the development of monoclonal antibodies using hybridoma technology. Antisera were generally of limited utility and monoclonal antibody technology is labor intensive and not cost-effective for the validation of large numbers of protein targets. In 1990, the phage display of antibodies was invented and over the past decade it has enabled the development of antibodies with much greater efficiency than the previous methods.
We believe that our internal antibody development capabilities allow rapid identification and development of antibodies with optimal specificity, affinity and stability characteristics. We initially utilized hybridoma technology for the selection and production of our novel antibodies. However, hybridoma technology has distinct disadvantages, including the length of time required to develop antibody candidates, higher costs associated with the use of this technology and the need to restart the antibody development process when unwanted characteristics such as cross reactivities are discovered.
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Instead, we developed a proprietary process utilizing the phage display of antibodies, which we believe enables faster and more efficient selection and production of antibodies than is possible using hybridoma technology. The technology enables the high throughput generation of custom Omniclonal antibody libraries containing genes encoding antibodies specific to the target analyte. Omniclonal antibodies produced from such libraries can contain thousands of different antibodies that bind to a target analyte with high affinity, which refers to an antibody’s ability to bind tightly to targets and is a highly desired attribute. Monoclonal antibody candidates can be rapidly selected from an Omniclonal antibody library and produced in quantities sufficient for product development. During the course of product development, unexpected antibody cross reactivities often require additional selection of antibodies to improve the assay specificity. Unlike hybridoma technology, Omniclonal antibody libraries can rapidly provide additional antibody candidates in these circumstances.
Analyte Cloning and Synthesis
Our molecular biology capabilities include the cloning and identification of specific proteins useful in the development of immunoassays. We developed proprietary expression vectors that enable the production and purification of these proteins for the development of antibodies and for use as calibrators and controls in our immunoassay products. In addition, our considerable expertise in synthetic organic chemistry allows the synthesis of targets and useful derivatives. We develop products where the targeted analyte is small (i.e., haptens, such as drugs) or large (i.e., proteins, such as cardiac enzymes). We believe that the ability to develop, stabilize and manufacture the target analyte or its analogues is key to the development of highly accurate immunoassays.
Highly Sensitive Fluorescence Energy Transfer Dyes
Immunoassays require the attachment of a detectable label to an antibody or target analyte. We developed a variety of labels for use in our products. For our qualitative products, a visual label that produces color is attached to antibodies or analytes through either non-covalent or covalent chemical methods to provide yes/no results. For our Triage MeterPlus platform products, we developed novel fluorescent dyes that are attached to antibodies or analytes using both noncovalent and covalent chemical means. Although fluorescence is a potentially powerful label for use in immunoassays, its potential has been limited by the lack of available dyes that are stable and have no sample interference, and by the requirement of a complex instrument for detection. We have invented our own proprietary dyes that satisfy four criteria:
• they are usable with complex biological samples such as serum, plasma, and whole-blood;
• they are stable for the dating period of the product;
• they utilize fluorescence energy transfer, which results in a substantial phase shift away from background fluorescence in samples; and
• they are excited at near infrared wavelengths chosen to be compatible with inexpensive solid state components.
Microcapillary/Protein Array Technology
We developed proprietary technology to design, develop and manufacture protein arrays containing microcapillaries to control the flow of fluids in immunoassay processes. The qualitative device format uses microcapillaries to draw fluids through a membrane that contains immobilized antibody zones for the detection of specific substances. The quantitative device format moves fluids through the microcapillaries in a controlled manner. When a sample is added to the quantitative assay device, a filter contained within the device separates blood cells from plasma. Then the plasma moves by capillary action into a chamber that contains dried fluorescent immunoassay reagents. Inside the chamber, the analytes that are to be measured bind to the fluorescent immunoassay reagents. After an incubation time that is determined by another microcapillary element of the array we call the time gate, the sample flows through a microcapillary path termed the protein array. The protein array is comprised of antibodies that are specific to the analytes and immobilized onto the surface of the device in discrete zones. The fluorescent reagents, which are bound to the analyte, bind to the respective zones on the protein array. The excess sample that was added to the device washes the unbound fluorescent reagents from the protein array. The binding of fluorescent reagents at the protein array is detected by our Triage MeterPlus and the fluorescence intensity at the discrete zone is related to the concentration of the substance or analyte being tested and measured in the sample. We also developed the engineering capability to design unique microcapillary structures in plastic parts and to fabricate them in commercial scale quantities using
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injection molding processes.
Sample Handling
We developed proprietary technology relating to sample handling and preparation, including technology that allows whole-blood to be passively separated into its plasma component or to be passively lysed to release the target analyte. We also developed technologies for the handling of stool samples that concentrate and purify the target analytes or organisms from solid stool materials. In addition, we developed technologies that can be used to assay urine samples.
Commercialized Products
Our products are principally sold to acute care hospitals, which number approximately 5,400 in the United States. To market our products, we utilize a direct sales team that focuses its efforts on larger centers with more than 200 beds and smaller hospitals that are high volume users of our products. Fisher distributes all of our products in U.S. hospitals and supports our direct sales force, particularly in smaller hospitals and in some U.S. physician offices. PSS and Henry Schein distribute our product to U.S. physician offices. A field-based network of clinically experienced individuals supports the sales effort by providing pre- and post- sale education and training. In international markets, we have established direct selling efforts in six European countries and utilize a network of country-specific and regional distributors in other areas.