Introduction
The emergence of real-time polymerase chain reaction (PCR) assays was much of a relief in the medical field especially given the fact that this model offers the most accurate way in the process of determining false-negative outcomes (Burggraf & Olgemoller, 2004).This ideology also finds support in the works of Nolte (2004) who asserts that, following the discovery of PCR and its application in a clinical setting, it has become possible to use nucleic acid amplification methods as transitions from research to clinical laboratories. This makes it possible to have a wide array of application in addressing issues relating to genetics, pharmacology, oncology as well as infectious diseases.
The Product
Few internal control mechanisms are commercially available. TaqMan from Applied Biosystems is the only successful commercially available internal control mechanism that distinguishes between true negatives and negatives caused by PCR inhibition. Non-commercial products include Rosenstraus et al.’s (1998) internal control nucleic acid for COBAS AMPLICOR assays, Wellinghausen et al.’s (2001) internal control mechanism using lambda phage DNA, and Danbing et al.’s (2000) internal control mechanism for PCR assays (Vickery, DePaola, & Blackstone, 2006). The product seeks to provide an internal control nucleic acid molecule which comprises of a forward binding primer, amplifiable region, and reverse primer binding sites that are randomly generated.
Product Description
The product includes a kit comprising of the following:
- Internal control nucleic acid molecule
- One or more forward primer that is complementary to the internal control nucleic acid molecule’s forward primer binding site.
- A reversed primer configured to complement the reverse primer binding site
- Methods used are pending/allowable patents. They are nucleic acid probes for concentration of nucleic acid molecules (20030082592), nucleic acid assays (6558901), PCR method (20030017482), and nucleic acid quantitative detection (WO/2000/029613).
- Tests: negative and positive control for PCR, TaqMan probe
Pending/Allowed Patent Application
Various pending and allowed patents are directed to the product. Patent application number EP20040752246 filed by Michael C. Vickery, Angelo DePaola, and George M. Blackstone on May 14, 2004 is key to the product because it is related to inventions on amplification techniques for nucleic acids. The patent, titled “Internal Control Nucleic Acid Molecular for Real-Time Polymerase Chain Reaction” was published on February 15, 2006 under publication number EP1625232 A2. The applicants were accorded the HHH patent E-213-2003/0 and US Patent 7728123. The US patent was issued on June 1, 2010 and published as US20060166232, WO2004104229A3, and WO2004104229A2 (Vickery, DePaola, & Blackstone, 2006).
Features and Potential Use
The product offers an internal control for nucleic acid molecule. This means that integral to its function is a model of eliminating false negative outcomes, especially when conducting nucleic acid amplification procedures and/or any other related methodologies of detection (Mackay, Arden, & Nitsche, 2002; Stocher & Berg, 2004; Vickery, DePaola, & Blackstone, 2006). It is equally important to note that the internal control sequence bears no significant nucleotide identity when compared to any naturally appearing or known nucleotide sequence (Vickery, DePaola, & Blackstone, 2006; Stocher & Berg, 2004).That is to say, no comparable base pair sequence exists thus far. It is also notable that the product can be tailored to a specific assay or organism such that the internal nucleic acid control mimics specific characteristics inherent to the target organism’s nucleic acid molecules. Finally, the product contains at least one probe-binding region such that the region complements the real-time PCR probe. This probe binding region will be used for DNA or RNA quantification and/ or detection (Vickery, DePaola, & Blackstone, 2006). In addition, the product will give the use the freedom to select control sizes, thermal cycling, and flourogenic detection and reporting mechanisms.
Technology Behind the Product
It is noted in the works of Picard et al. (2009) that most of the commonly applied internal control mechanisms in nucleic acid testing are less efficient. This challenge is more pronounced in verification of the extraction of nucleic acid (Picard et al., 2009). These are similar sentiments that are shared by Vickery, DePaola, and Blackstone (2006). Erudite authors and researchers like Rosenstraus et al. (1999) have made strides in constructing internal controls as a surety that clinical specimen are successfully detected and amplified (Olgemöller, 2004; Burggraf & Olgemoller, 2004; Stocher & Berg, 2004). In nucleic acid extraction, there are relatively simple procedures that are involved, which offer samples that have reasonable levels of purity thus negating the need for application of hazardous chemicals (Rosenstraus et al., 1999; Espy et al., 2006; Aliyu et al., 2004). These chemicals may result in tampering with the sample composition since they may cause extensive manipulation of the sample (Rosenstraus et al., 1999; Espy et al., 2006; Aliyu et al., 2004). In an earlier version of research, it is found that to be able to distinguish between Norovirus Genogroup I and II probes and primers, reverse transcription-polymerase chain reaction (RT-PCR) necessitated by amplified cDNA is vital for normalized data and quantified virus data (Burkhardt, Vickery, & Nordstrom, 2012). However, the need for real-time or kinetic polymerase chain reaction analysis is here (Burkhardt, Vickery, & Nordstrom, 2012; Vickery, DePaola, & Blackstone, 2006; Belak, 2001; 2005; 2007).
The product works by identifying a specific sequence and then proceeding to quantify the number of the intended nucleic acid molecules within a sample; thus negating the need for post-PCR analysis methodology (Burkhardt, Vickery, & Nordstrom, 2012; Vickery, DePaola, & Blackstone, 2006). It works by copying or amplifying DNNA sequences or cDNA template sequences from thousands to millions. Thereafter, a measurement of PCR product at each cycle is taken. These measurements help the tester to monitor the reaction and determine the target used initially with greater precision. Ethidium bromide is used as a staining agent because it helps quantify the endpoint of PCR products to prevent amplification. The product measures the DNA amount after each cycle using fluorescent markers. The markers will show that changes to the fluorescent signal are directly proportional to the quantity of the product molecules generated during reaction. The product measures changes to the fluorescent using a thermal cycling instrument with scanning functions. These changes are plotted against cycle number to create an amplification plot (Burkhardt, Vickery, & Nordstrom, 2012; Vickery, DePaola, & Blackstone, 2006).
Marketing and Commercialization
The product has ample market possibility. Take for example, the testing applications and utilities in ensuring similar results are emergent are usually marred with innumerable challenges that yield complex results. If a qualitative or quantitative research analysis is required with the current tools and models, it would be impossible to have higher levels of accuracy. This is especially when considering large volumes of the test subject regardless of whether there is utilization of internal or external control. Worth noting is that there are limited options that the market has especially on internal positive control reagents (Vickery, DePaola, & Blackstone, 2006). According to Templeton et al. (2003) and Espy et al. (2006), when a market lacks a vital product or service, the market tends to accept what is available and gets temporary satisfaction with what is available. Consequently, the market has gained temporary satisfaction from TaqMan. TaqMan®, the Applied Biosystems PCR kit, has the capability to identify only a handful of different types of negative results (Vickery, DePaola, & Blackstone, 2006). Another example of an internal control nucleic acid used in COBAS AMPLICOR test specialized on Chlamydia trachomatis, Mycobacterium tuberculosis, Neisseria gonorrhea, and human hepatitis C Virus (Vickery, DePaola, & Blackstone, 2006).
The absence of an internal control nucleic acid that can traverse through divergent application arena is what makes this product to not only be unique in its own sense, but also realistic in application and vast market potential (Vickery, DePaola, & Blackstone, 2006). The challenge in marketing the product is resistance to change (Templeton et al., 2003; Espy et al., 2006). The product bridges the dividing gap in offering high-levels of identification and isolation of false-positive or false-negative results; thus laboratory technicians across the divide are mostly the ultimate beneficiaries since their work will be made easier by internal control mechanisms that greatly reduces the changes for results falsification. In as far as fitting in the diagnostic and/or therapeutic decision tree, it is important to note that proper medical attention is heavily reliant on proper diagnosis of the ailment (Templeton et al., 2003; Espy et al., 2006). It is good to highlight the fact that, while this product is unique in its own sense, there is a higher probability that other manufacturing companies that have related products like highlighted above may make an effort to flood the market with cheaper options of their products; thus clouding the emergent product sets (Espy et al., 2006). The challenge is in the fact that these companies not only have the products already established in the market, they also have the funds and machinery to overwhelm the market with their products. Mitigating this resistance is key for the success of the product.
Competitive Landscape
There is competition from similar product line by Cepheid and TaqMan. These products are quite similar in their target although these products have their inherent limitations by virtue of their design process and targeting mechanism (Vickery, DePaola, & Blackstone, 2006). For example, in an earlier research, it is noted that the construction of an internal control sequence targeting Group B Streptococci had to be modified during application to de novo for it to become compatible with the intended target assay (Vickery, DePaola, & Blackstone, 2006). SYBR Green and TaqMan are the most common methods for real-time PCR; although TaqMan produces higher y-intercept values and is more sensitive compared to SYBR Green assays (Cao & Shockey 2012). There is also competition from companies seeking rights to sell enzymes, probes, or kits. These rights are given as enzyme supplier license, application kit manufacturing, and probe manufacturing license. License Technologies is one such competitor. The company is an exclusive licensor for real time PCR as well as well as an enzyme supplier and application kit manufacturing licensor. It produces enzymes such as AmpliTaq Gold and Platinum, and nucleic acid stains such as SYBR Green used as detection agent by the product (Life Technologies, 2013).
Sales Revenue
Assuming that 1 in 5 people go for screening at least once a year, with a population of over 800 million, it is admissible that about 50 million kits will be needed to considerably address these screenings (Belak, 2007). However, since the selling price plays a determining role in the number of items moved, it is estimated that reaching the previously mentioned figure is almost unachievable within a year. It is also realistic to point out that the level of advertisement and public enlightenment of the product is important, and it would take some time for the product to be accepted in the market (Anderson et al., 2003).
It is rational to estimate that 150,000 kits would be sold within the first year with proper campaigns and pocket-friendly pricing model used. Assuming that the kit will be up for sale for about $ 2,000, if the targeted amount of 150,000 volumes is moved within the first year, the resultant income from this sale will be $ 300,000,000. The main reason people are likely to use this product is because of its integration ability with preexisting frameworks and high accuracy level. Additionally, institutions that will be the first to use this product, and its benefit will have a competitive edge over their rivals within the industry and can use this as an advertisement arena to woo more clients to their docket.
Pending Patent Applications
The technology and proposed provides an internal control nucleic acid molecules including at least one reverse primer binding site, at least one forward primer binding site, and at least one amplifiable region, wherein all primer binding site and the amplifiable region are generated randomly. The application for the patent was filed November 2005.
That patent claims are directed towards methods of:
- An internal control nucleic acid molecule comprising of at least one forward primer binding site, at least one reverse primer site, and at least one amplifiable region, with all the primer binding and the said amplifiable region generated randomly.
The invention also comes with a kit that includes all the mentioned components, configured to complement all the components. Additionally, the invention provides methods of using the internal control nucleic acid molecules and kits of the invention.
“U.S. Patent Application No. 11/280,474 Publication No. US20060166232 A1 (published Jul. 27, 2008) (George Blackstone, Angelo DePaola, and Michael Vickery)”
Additional Work Plan
This research needs more validation for a period not less than three years with at least 10,000 clinical trials carried out to ensure safety and authentic application (Sawyer et al., 2006). Following successful clinical trials, the product will require approval from the Food and Drugs Agency (FDA) prior to being launched in the market (Sawyer et al., 2006). To be able to achieve the first milestone, an estimated $ 10million will be required since much of this will require specific factory calibration to suit the specifics required in the kit.
Cepheid Company Analysis
Company History, Product Focus and Core Competencies
Cepheid Company is the regional leader in molecular diagnostics with strong dedication to providing improved healthcare through harnessed manufacturing, development, and marketing molecular tests and their systems therein. The company provides different solutions that automate complex manual procedures such as genetic testing. Under its name Cepheid Company has manufactured the following products and technology platforms:
- Xpert® tests- Xpert C difficile, Xpert MRSA/SA SSTI, Xpert MRSA/ SA BC, and Xpert EV.
- GeneXpert® Systems – such as GeneXpert Infinity, GeneXpert I - IV
- SmartCycler® instruments (Cepheid, 2012).
Cepheid has strong distribution networks in America, Europe, Middle East, Asia and Africa. The North American market comprises 14 percent of the company sales while international market comprises 41 percent of the market (Cepheid, 2012).
Investment/Financing History
In terms of financial performance, Cepheid’s sales revenue for year 2012 was $331.2 million compared to $277.6 million the previous year (Cepheid, 2012). Clinical sales increased by 21 percent to $286.3 million by the end of 2012. The firm had a net loss of $20million in 2012 which was a deviation from $2.6 million in net income the previous year. This net loss was due to litigation settlement of $15.1 million (Cepheid, 2012). Cepheid’s current assets and liabilities as at December 31, 2012 were $219.3 million and $72.25 million respectively with a burn rate of -0.02 (Cepheid, 2012).
Business Development Strategy
Cepheid has made partnership agreements with many companies with the most recent being with The Bill and Melinda Gates Foundation and USAID on reduction of prices. The company has great growth prospects because it has the advantage of being an established name and the ability to reduce product prices through improvement of manufacturing efficiencies. This has been achieved by investment in ultramodern technologies. Additionally, Cepheid boasts of strong penetration in clinical market. Cepheid has weaknesses since it has an unstable production supply in addition to ever increasing number of competitors. Additionally, from a peek into their financial performance, it is evident that the company has been on a downward trend, consistently making huge losses.
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