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This is a guest post from the BiotechBlog Intern,  Fintan Burke. Fintan is a student at the School of Biotechnology at Dublin City University. Do you have a response to Fintan’s post? Respond in the comments section below.

One of the most overlooked but consistent problems facing many governments is waste management. Despite healthy recycling attitudes in both the US and UK, an EPA report showed US total waste production in 2010 was still around 250 million tons, while there are concerns that the UK will run out of landfill sites by 2018.

For many years, the only viable alternative to landfills was incineration. Despite its efficiency over landfill sites (incineration can reduce the waste mass by around 90%), concerns over small energy generation efficiency (estimated at 20-25%) as well as public protest over environmental impact mean incineration can never be a permanent solution.

As public and private sectors are beginning to shift their attention to cleaner, more efficient alternatives to waste disposal, one of the leading candidates is gasification.

Gasification has been with us in various forms since the 1840s. The process involves extracting combustible gases by subjecting dehydrated carbonaceous materials to intense temperatures and reacting the resulting ‘char’ with oxygen and/or steam. Originally coal and wood were used in the process and so bore little difference to incineration. Since the 1970s, however, focus has shifted from using these conventional inputs to biomass.

From this change in focus, several companies have been set up to offer biomass gasification as an effective renewable resource. One such company, Thermoselect, claims that for every 100kg of waste processed, 890kg of “pure synthesis gas” is created for energy generation. Another company, ZeroPoint Clean Tech Inc., is keen to demonstrate gasification’s use in generating renewable gas, heat, water and electricity.

This development has been embraced by both the US and UK governments, welcoming the opportunity to reduce their carbon footprint as well as municipal waste. In April 2011, the US Air Force Special Operations Command invested in a new plasma-based transportable gasification system, with the aim of reducing its waste output by 4,200 tons a year in air bases across the country. Later that year, Britain approved the first advanced gasification plant in the country, with the potential to generate 49 megawatts of renewable energy (enough to power around 8,000-16,000 US households). Some have even speculated that this new technology could be used to spark a boom in hydrogen cell powered vehicles in the future.

Not everyone has embraced the new technique, however. The proposal for a biomass gasification plant in DeKalb County, Georgia was met with protests from locals, fearing carcinogenic emissions. Furthermore, a 2009 report by The Blue Ridge Environmental Defence League warned that gasification shares many similarities with incineration, including the formation of pollutants and greenhouse gasses.

Despite these arguments, the gasification of biomass has several benefits. The high temperatures make them an ideal means of processing bio-hazardous waste from hospitals and the plants themselves occupy very little physical space. As with any emerging technology, however, uptake is cautiously slow. Many of the new plants are in trial stages and it is uncertain whether gasification will have any long-term environmental effects. Should the existent plants prove to be successful, there is no reason to doubt that gasification will become a realistic solution for environmentally sound energy generation.

 

About the author:

Fintan Burke is a student at the School of Biotechnology at Dublin City University. His main fields of interest include biomedical therapies and recombinant organisms.  Fintan may be contacted at fintan.burke2@mail.dcu.ie .

This is a guest post from Erin M. Hall. Erin is the Technical Leader at Genetica DNA Laboratories, Inc. located in Cincinnati, OH. Do you have a response to Erin’s post? Respond in the comments section below.

It is estimated that 18-36% of all actively growing cell line cultures are misidentified and/or cross-contaminated with another cell line (1).  For researchers in any field of biomedical science, this could mean that a significant amount of the experimental data published in current and past journals is of questionable value.  Every year, millions of dollars of public money are spent on potentially wasted research and this is happening not just here in the United States but around the world as well.

Cell line misidentification and cross-contamination has been around for more than 50 years.  It was finally brought to light in 1966 by Stanley Gartler, who reported that 19 supposedly independent human cell lines were in fact HeLa cells(2), which are known to be extremely robust, fast growing and able to contaminate other cultures by aerosol droplets.  There was much resistance to his findings and scientists didn’t want to admit that the research done using those contaminated cell lines may be questionable and potentially irreproducible.  Walter Nelson-Rees was one scientist who supported Gartler’s findings.  Nelson-Rees highlighted the papers and the scientists who were publishing experimental data using misidentified cell lines and for this, in 1981, he lost his contract with the National Institutes of Health (NIH) because his behavior was deemed “unscientific”(3).  From 1981 and on, misidentification went unchecked and even cell line repositories continued to distribute lines under their false names (3).

To exacerbate the problem, certain cell culture practices may be aiding cell misidentification and cross-contamination, including the practice of assessing the phenotypic characteristics, such as protein expression, as the only way to properly identify the cell population.  It has been proven that phenotypic expression can change with an increased passage number or even with changes in growth medium or other cell culture conditions(4).  The modern way of assessing the correct identity of the cell line (“cell line authentication”) is to perform short tandem repeat (STR) DNA testing.  The STR DNA profile of a human cell line is similar to a person’s fingerprint; it is unique to that individual.  STR testing is now the “gold standard” of human identification testing and is routinely used by the FBI in profiling convicted offenders (CODIS).  STR profiling is a straightforward and effective way to confirm that the cell line you think you have been using for the past 5 years, is in fact, the genuine cell line.

The reason the problem continues today is because it has not been properly brought to the attention of researchers.  Many researchers learn about the service the hard way, i.e. at the last minute when the journal requests confirmation of authentication before considering your article for publication.  In a survey that profiled 483 researchers who actively use cell cultures, only 33% authenticate their cell lines and 35% obtained their lines from other laboratories rather than a cell line repository, such as American Type Culture Collection (ATCC) (3).  We, as researchers, expect to use only the best reagents and supplies but the one aspect of the experiment that may be the most important, i.e. the cell line, is consistently and explicitly overlooked.  ATCC recommends verifying the identity of all cell lines before you start your experiments, every two months during active growth, and just prior to publication.

The NIH now officially recognizes that cell line misidentification is a serious problem in the scientific community.  They state in a formal notice issued on their website (NOT-OD-08-017) that grant applications that fail to employ acceptable experimental practices would not be looked upon favorably and would potentially not fare well in the journal review process.  The NIH encourages all peer reviewers and researchers to consider this problem carefully “in order to protect and promote the validity of the science [they] support”.  Many journals, such as those published by the American Association for Cancer Research (AACR) require a statement in the “Materials and Methods” section as to whether cells used in the submitted manuscript were authenticated.  Not properly authenticating the lines may prohibit the article from being published when peer reviewed.   To continue the advancement towards the elimination of the problem of cell line misidentification and cross-contamination, ATCC, in early 2012, released a set of guidelines written by the international Standard Development Organization (SDO) workgroup; these guidelines provide researchers with information on the use of STR DNA profiling for the purpose of cell line authentication.  In the near future, with the help of all of these influential supporters, cell line authentication will become a routine quality control check in every laboratory in the United States and around the world.

I would love to hear other thoughts and comments on this topic.  Tell us about your experiences with cell line authentication – good or bad!

(1)   Editorial – Nature 457, 935-936 (2009).
(2)   Gartler, SM. Second Decennial Review Conference on Cell Tissue and Organ Culture: 167-195 (1967).
(3)   ATCC SDO Workgroup.  Cell line misidentification: the beginning of the end: 441- 448 (2010).
(4)   Kerrigan, L.  Authentication of human cell-based products: the role of a new consensus standard: 255-260 (2011).

About the author:

Erin is the Technical Leader at Genetica DNA Laboratories, Inc. located in Cincinnati, OH. She is responsible for the technical operations of the laboratory, as well as, all aspects of the daily casework involving DNA identity sample processing and quality assurance. She received her Master’s degree in Forensic Science from PACE University in NYC and her Bachelor’s degree in Molecular Biology from the College of Mount Saint Joseph in Cincinnati, OH. For more information on Genetica, visit www.genetica.com or their website dedicated to cell line authentication, www.celllineauthentication.com .

Prior to joining Genetica, Erin worked in New York City as a laboratory manager and researcher in the Pharmacology department at Cornell University’s Medical School. She designed and executed complex experiments that examined the effects of environmental toxins on liver enzyme production utilizing HPLC, UV/vis spectroscopy, Western blotting and PCR analysis. Her work contributed to several published journal papers (under Erin Labitzke, if you want to read them!), most recently including being cited as first author on a paper related to enzymes present in mitochondria.

Erin may be contacted at erinhall@genetica.com.

This is a guest post from the BiotechBlog Intern,  Fintan Burke. Fintan is a student at the School of Biotechnology at Dublin City University. Do you have a response to Fintan’s post? Respond in the comments section below.

According to a BDO industry report, a smallUS biotech company in 2010 enjoyed average revenues of around $42m while larger firms reported average revenue of around $124m. Additionally the European biotech sector also enjoyed a sizeable success with revenues totalling €13bn the same year. Global biotechnology revenues are estimated to grow to €103bn by 2013, bolstered by the pharmaceutical market which is expected to become a trillion-dollar industry by 2014.

These high revenues can attract more than just investors; smaller companies are seeing the benefits of asserting breach of their own patents in order to attain lawsuit settlements or licensing fees. Though more well-known in the technology sector, these ‘Patent Trolls’ have started to attract attention in biotech circles.

A standout case was that of Classen Immunotherapies Inc. which brought four biotechnology companies and a medical group to court for infringing on their patent of an immunisation schedule that could curb the risk of developing chronic diseases. Although the lawsuit was first thrown out by the district court as only a mental abstract, on appeal the federal court ruled in Classen’s favour citing that Classen has a “statutory process” that allows for patent protection.

This has set a troubling precedent in biotech law; since the Classen patents were somewhat broad, there could soon be a flood of similar companies trying to claim patent infringement based in immunisation or dosage schedules.

Indeed, there is proof of some small firms already trying to build a portfolio of biotech patents. These ’non-practicing entities’ deliberately gather patents – not in order to develop products – but rather extort other companies for settlements or licensing fees. There are already specialized law firms which help companies obtain and enforce biotech-specific patents. Such companies have been known to damage stock prices, delay production and eat into revenues – all of which is completely legal.

Many identify these frivolous litigations to lie not in the vagueness of the patents, but rather in unspecific patent legislation. In Ronald I. Eisenstein’s 2006 column in The Scientist, he notes that “One size does not fit all in terms of approaching patents.” Any legislation passed to curtail the practice of ‘Trolling’ in the technology sector may inadvertently harm smaller biotech companies and universities that rely on larger companies in the FDA approval process.

In his 2008 book Intellectual Property and Biotechnology: Biological Inventions, Dr. Matthew Rimmer offers some solutions to this growing problem. “Novelty and utility are the criteria used to judge whether something is inventive or not” he writes. “It is really those doctrinal concepts that need to be tightened.”

In a 2011 Forbes article Colleen Chien also offered some advice to defend against the trolls. She notes that many trolls will use contingent fee based lawyers to manage costs. Firms that pay via successful disposal of a suit or minimise settlement costs cn likewise minimise legal fees and increase the lawyer’s incentive to defend them. Furthermore, larger firms could be better off outsourcing their defence to specialist lawyers, rather than solely relying on their own legal team.

Patent trolls remain a very real problem in the world of technology. In the most infamous case, Research In Motion (producers of the Blackberry) paid a $600m settlement to NTP Inc for infringing their wireless email patents. Fortunately steps have been taken at a federal level. The passing of the Leahy-Smith American Patents Act in September 2011 has allowed any firm threatened with infringement to petition for a patent review within 4 months of being sued. Nonetheless the biotechnology sector must begin to reassess its patent rights and monitor such changes in legislation if it is to further grow as an industry.

About the author:

Fintan Burke is a student at the School of Biotechnology at Dublin City University. His main fields of interest include biomedical therapies and recombinant organisms.  Fintan may be contacted at fintan.burke2@mail.dcu.ie .

This is a guest post by Jurgita Ashley

You are a small company ready to take a leap into the public market, whether it is for growth, liquidity or to attract greater investor interest. But, oh man, those dollar figures for IPOs would make anyone’s head spin. But wait, don’t discount it yet as a viable alternative. If done right, going public does not have to cost a fortune. Small companies can take advantage of the SEC’s relaxed reporting regime, may strategically decide to list on the Bulletin Board (the OTCBB) rather than the NYSE or NASDAQ, and can significantly limit their corporate governance-related expenses.

Your first major—and unavoidable—expense will be the preparation of a registration statement. Inevitably, it will require management’s time, preparation of audited financials and legal fees. You do not have to be charged, however, $1,000 per hour or other exorbitant fees, and your IPO team does not have to include 50 professionals. If you are a “smaller reporting company,” which is a company with a public non-affiliate common equity float of less than $75 million (or annual revenue of less than $50 million if the float cannot be calculated), your reporting requirements will be limited. Your registration statement – whether it is on a Form S-1 (involving an immediate capital raise) or a Form 10 (initial registration with the SEC to position the company for a subsequent capital raise) – will include less financial information and disclosures than is required for larger companies. In addition, this first registration statement is the “meat and bones,” so your subsequent filings will build upon this information and will involve much less drafting from scratch. This first registration statement will most likely be reviewed by the SEC, which will issue comments requiring one or more amendments. This review, however, will most likely be limited. With the Dodd-Frank and other legislative initiatives and demands on the SEC’s resources, the days of 100 plus comments are largely over. As long as your accounting is in order and your legal advice is good, you should be able to maneuver through the SEC’s comment process without excessive delays or expense.

Now, let’s say your primary goal is to obtain greater investor interest in the company and to create an avenue to sell stock. To achieve this, it is not necessary to pay the NYSE’s or NASDAQ’s listing fees or to become subject to their reporting and governance requirements. Although the OTCBB is usually not the market of first choice, it can be an effective vehicle to provide some liquidity and disseminate information about the company. To list on the OTCBB, a company only needs a market maker and to file reports with the SEC. By listing on the OTCBB, the company becomes subject to the oversight of FINRA, but there are no listing fees, no additional reporting requirements, and no special governance requirements. In addition, if down the road you are ready to transition to the NYSE or the NASDAQ, your platform will already be in place.

As a company that is listed on the OTCBB only, you are subject to limited corporate governance requirements (imposed by the SEC). Yes, some of your directors should be independent, committees should operate under board-approved charters and the company should have a code of ethics and reasonable internal controls, but all of these policies and procedures need not become all consuming. There is no need for a small company with limited financial resources to adopt all the latest “best practices” in governance or add a whole department to address the company’s new reporting obligations. Pursuant to recent SEC relief, “smaller reporting companies” also do not need to obtain—and pay for—an auditor’s report on internal control over financial reporting. Reasonable disclosure controls and procedures are important and, in some instances, improving the company’s policies and procedures is desirable and appropriate. In many cases, however, most new obligations of a small public company can be satisfied without exorbitant expense.

Nearly 50 percent of all public companies in the United States are “smaller reporting companies.”(1) Of course, not every small private company will find it desirable to go public, and for some, a full-blown—and expensive—IPO is an appropriate option. The perceived costs, however, should not discourage other companies from evaluating the option of a lower cost IPO. Access to the public markets is no longer insurmountable.

______________
Jurgita Ashley is an attorney in the Cleveland, Ohio office of Thompson Hine LLP and is a member of its Corporate Transactions and Securities practice group. Her practice is focused on public company matters, primarily securities law, corporate governance and takeover matters. She can be reached at  Jurgita.Ashley@ThompsonHine.com or through www.ThompsonHine.com. The views expressed in this article are attributable to the author and do not necessarily reflect the views of Thompson Hine LLP or its clients. The author would like to thank Derek D. Bork, a partner at Thompson Hine LLP, for his review and invaluable input on this article.

(1) Forty-eight percent of all U.S. companies filing annual reports on Form 10-K with the SEC were “smaller reporting companies” for the period from October 1, 2009 through September 30, 2010, which is the SEC’s latest fiscal year for which data is available. Proxy Disclosure Blog by Mark Borges at CompensationStandards.com (December 3, 2010), available at www.compensationstandards.com.

This is a guest post from BiotechBlog reader Jack Lundee

Technology Continues to Fight Aids

In 2008, Sub-Saharan Africa was populated with over 22 million HIV+ inhabitants, and currently there are over 5 million Southern Africans infected with the virus. Worldwide, there are upwards of 40 million people infected with HIV, a very frightening number. But with the coming of the 22nd annual World AIDS Day, it’s important to take note the progress that has been made in the fight against HIV/AIDS. At the same time, it’s very vital we familiarize ourselves with a couple great HIV research and technology investors.

Granted, there have already been major advances concerning affordable microbicides and vaccines as preventative measures against the virus. Similarly, the introduction of low-cost antiretroviral drugs has allowed people already infected to lead longer, healthier and happy lives.

This can most certainly be attributed to tremendous associations like the CGI (Clinton Global Initiative). The Clinton Global Initiative has put a tremendous amount of money into AIDS research. Known for his work in raising money for Hurricane/Tsnuami victims, former President Clinton and his close personal aide Doug Band also have great interest in tackling one of the deadliest STDs in the world, HIV/AIDS. Back in 2006, Clinton helped open people’s eyes to the severity of the disease in foreign states by traveling deep into Burma with the crew of 60 Minutes.

Before this however, he introduced CHAI (Clinton Health Access Initiative), outlined specifically as “a global health organization committed to strengthening integrated health systems in the developing world and expanding access to care and treatment for HIV/AIDS, malaria and tuberculosis.” Their main objective was to travel to these third world countries like Burma, and distribute various treatments, which weren’t currently available to sufferers. Since it’s beginning, the organization has helped more than 2 million people gain access to medicines needed for treatment. But the efforts of Former President Clinton and his close personal aide did not end there. The CGI continues to receive funding for HIV related projects in third world countries like Southern Africa.

In their latest endeavor, they’ve joined forces with HP (Hewlett Packard) to deliver technologies that will capture, manage and return early diagnosis for infants. This translates to indentifying the virus in an infant within one to two days, which is a huge improvement from previous paper based systems. How is this important? Newly borne are especially susceptible to the disease as their carriers can very easily transmit. Similarly, it’s very crucial that they begin treatment as soon as possible to ensure survival; without, they are typically unable to survive past age two. In a statement to the press, Clinton stated, “I’m pleased HP’s technology and expertise will enable the partnership with CHAI to save the lives of more than 100,000 infants in Kenya each year, and in the process, demonstrate how the private sector can and should operate in the developing world.”

Within their first year, HP is expected to return results concerning HIV testing for nearly 70,000 infants in Kenya. The technologies introduced will also allow for real-time medical data, which will be viewable to health professionals across Kenya.

Known for it’s incredibly high number of HIV+ citizens, Africa remains one of the greatest challenges for organizations like CHAI/CGI today. Recent advancements in technology combined with the help of Doug Band and Former President Clinton have helped lessen casualty rates and permitted people to live more productive lives. And although a cure remains unfound, HP and the CGI have provided great technological steps in the right direction towards eliminating the virus for good.

Jack Lundee is a writer for Everythingleft.wordpress.com and Shadesofgreen.info. With a graduates from the Newhouse School of Communications, he’s an avid supporter of all things left and progressive.

This is a guest post from Keith Bradbury, Executive Director of Drug Information at Medco Health Solutions, Inc.

Biosimilar drugs to gain greater priority as decade progresses

The Patient Protection and Affordable Care Act will heighten the degree of competition in the field of biotech drugs, a fast growing area of drug therapy that is accounting for a larger portion of drug spending. The law creates a pathway for biosimilars, which are comparable versions of biologics and are also known as “follow on biologics,” to enter the marketplace. These medicines could create a wave of lower cost competition in the biotech industry starting in 2013, leading to savings by as much as 30 percent for some of the costliest drugs.

Biologic and recombinant drugs have been instrumental in treating a variety of conditions such as cancer, diabetes, immune deficiency, metabolic disorders, and autoimmune conditions, as well as rare medical conditions such as Pompe disease, Fabry disease and Gaucher disease. The difficulty making these drugs, the absence of competition and small patient populations in which some of these drugs are used has made biologics among the most expensive drugs currently prescribed, ranging from $6,000 to more than $400,000 annually.

The Congressional Budget Office had projected $25 billion in total savings from biosimilars between 2009 and 2018. Others have estimated substantially larger savings. For employers, health plans and patients, this could represent substantial relief from the double digit growth rates of specialty drug spending. According to Medco Health Solution’s 2010 Drug Trend Report, spending on specialty drugs, a group of drugs that is mostly recombinant proteins, represented 5.6 percent of overall prescription costs in 2003, but by 2009, the figure had soared to 14.2 percent.

Biosimilars will have to undergo analytical studies to demonstrate that they’re “highly similar to the reference product notwithstanding minor differences in clinically inactive components.” The biosimilar must utilize the “same mechanisms of action” and follow the same prescribing instructions and indications as the original product. In other words, there can be no clinically meaningful differences between the biosimilar and the reference product in regards to safety, purity, and potency. The FDA will determine the level of clinical studies needed for biosimilar drugs to gain approval, but some will likely be needed. Also, cross-over studies will be needed to allow a determination of interchangeability.

There are significant protections for the makers of the original product. The law provides reference product biologic manufacturers 12 years of exclusivity for data used in the submission, starting from the date of FDA approval. That data is a necessary part of any filing for a biosimilar to gain approval under the pathway.
The marketplace for biosimilar drugs is likely to be competitive with some leading pharmaceutical makers – namely Eli Lilly, AstraZeneca, and Merck & Co. – entering the area. But biosimilars are not likely to be a significant force in the marketplace until 2014 or 2015.

The drug categories where we’re likely to see significant competition include the following:

  • Human growth hormones are likely to be among the first to face increased biosimilar competition, since they were among the first recombinant proteins to appear in the marketplace.
  • Recombinant insulins and modified recombinant insulins, such as Humulin and Novolin, are apt to be early follow-on biologics, since the reference drugs’ patents have long expired. These insulins should be relatively easily to replicate and biosimilar versions of these drugs could be introduced between 2013-2015. However, as much of the insulin use has switched to modified recombinant insulins, this may not be a large opportunity.
  • Follow-on versions of epoetin alfa, which has been sold under the brand names Epogen® and Procrit® to treat patients with kidney disease or chemotherapy-induced anemia, can have a significant effect upon specialty drug spending. However, it is not clear if cardiovascular safety data will be needed for follow-on versions of these drugs.
  • Leukine® (sagramostim), a treatment to prevent opportunistic infections, could face follow-on competition in 2014.
  • Drugs to combat neutropenia are already facing challenges to patents with Teva’s Tevagrastim seeking to compete against Neupogen® (filgrastim), which has a patent expiration in 2013.
  • Interferon-alfa based treatments were among the first biologic drugs to reach the marketplace and have found uses treating leukemia, cancer, genital warts, hepatitis and multiple sclerosis. Many patents governing these drugs have long expired. Some of the pegylated versions of interferon drugs, such as Peg-Intron (peginterferon alfa-2b) or Pegasys (peginterferon alfa-2a), gained significant extra time on their patents because the reformulation creates a different molecule that improves the efficacy of treatment.
  • Rheumatoid arthritis treatments and other biologics for autoimmune disorders are among the fastest growing drug categories, but this group is not likely to face a biosimilar competition until 2014 or 2015.

Later this decade, many treatments that gained FDA marketing approval from the year 2000 on may face greater competition from biosimilars, as well as new treatments under development. Herceptin® (trastuzumab), Avastin® (bevacizumab), Erbitux® (cetuximab) will be vulnerable to competition in the later second half of the decade, as well as some of the priciest drugs for rare enzyme disorders.

This new regulatory pathway for biosimilars could be a catalyst to greater competition in the biotechnology industry, much like the introduction of generic drugs under the Hatch-Waxman Act spurred competition among traditional small molecule drugs. Many of today’s blockbuster drugs emerged as manufacturers had to replace old revenue sources with new products. Although biosimilars are not exactly like the original products, the prospect of competition could drive the biotech industry to deliver new medicines that further improve the quality of patient care.

About the author: Keith Bradbury is Executive Director of Drug Information at Medco Health Solutions, where he has been employed for the past 14 years. Bradbury has more than 30 years experience in hospital pharmacy, managing pharmacy benefits for health plans, drug information services, developing drug formularies, and managing pharmaceutical benefits provided by a large PBM.
Bradbury also oversees Medco’s new drug pipeline management process, and is the lead author for the drug forecast section of the Medco Annual Drug Trend Report.

These papers are from the 2010 final projects in the NIH Foundation for Advanced Education in the Sciences TECH 366 — Biotechnology Management. The students were asked to tell a story based on the course lectures, and to expand with general lessons biotechnology company management:

If You Build It, Will They Come?
Derek Francis

Profitability and Orphans: The Role of Price and Incentives in Four Different Markets
Nate Hafer

Patent Analysis: A Tool for Making Strategic Business Decisions
Eric Norman

2009 final projects are posted here.

This is a student paper from the 2010 final projects in the NIH Foundation for Advanced Education in the Sciences’ TECH 366 — Biotechnology Management. The students were asked to tell a story based on the course lectures, and to expand with general lessons on biotechnology company management.

Profitability and Orphans: The Role of Price and Incentives in Four Different Markets
Nate Hafer

Drug development is long, expensive, difficult, and complex. Due to the high cost of drug development, many companies will not consider developing a drug unless there is the potential to have a “blockbuster” with $1 billion per year in sales. There are two main factors that influence a drug’s ability to get to this $1 billion threshold: market size and price. As the size of the market increases, the relative cost per drug can decrease and vice versa. Traditionally, pharmaceutical companies have tried to maximize the market size for a product while keeping prices relatively modest (1).

Many factors influence the decision to enter the market with a novel compound. Some of these factors include development costs, the competitive landscape, the present unmet medical need, the intellectual property position of the compound, and the potential market size. Over the course of the semester I became particularly interested in learning more about drug pricing and how a drug’s final price can influence the decision to enter a new market. In this paper I will review some of the basic considerations that influence the price for pharmaceuticals. Subsequently, I will consider the use of the Orphan Drug Act as a tool to incentivize drug development for rare and neglected diseases that would not be profitable under the traditional model. In particular, I will focus on four categories of drug indications and consider how novel drug pricing models and the Orphan Drug Act provide incentives to drug development. In some cases these forces work together to create profitable products with the benefits of an orphan drug designation, while in other cases drugs truly can’t reach blockbuster status but can none the less take advantage of orphan incentives.

To begin, we need to consider how price is traditionally determined for drugs and biologics. Not surprisingly, the price of a new pharmaceutical is often set by the same factors that influence the price of any consumer good. First, it is important to understand the present value of products in the market. Then, the added value of the new product over existing products is determined (2). This straightforward approach is complicated by several additional considerations. First, the health care system is unique from many other markets in that the person who receives a good or service (in this case a pharmaceutical) is usually not the payer. Instead, a third party (often an insurance company or government program such as Medicare, Medicaid, and the Department of Veterans Affairs-VA) pays the cost. In many cases the interests and willingness of the third party to accept and pay a particular price may be different than the interests of the person receiving the drug. Another consideration when pricing a drug is whether to set price based on all costs plus a margin for profit or charge as much as the market will bear. Again, the price that is reasonable to a patient may not be the same as the price a third party will consider.

Over the past few decades an alternative approach to reach $1 billion in sales has emerged. Specialized treatments, mainly for specific types of cancer and rare diseases, have come to market that offer great benefits to a small patient population. The $1 billion threshold market reality made it very difficult for many years to develop drugs for rare and neglected diseases. The Federal Government addressed this in 1983 with the passage of the Orphan Drug Act, which was designed to provide a number of incentives to encourage drug development for these indications (3). A drug is eligible for orphan status if it affects less than 200,000 people in the United States. For the most part this program has been highly successful, as the number of drugs approved for rare conditions has accelerated greatly in the years since the act was passed (4). Some of the incentives to develop orphan drugs include a 50% tax credit for clinical development costs, a seven-year market exclusivity for approved products, the waiver of licensing fees, protocol design support, and grant support. Intriguingly, some companies have been able to take advantage of these orphan incentives and have also been able to develop very profitable drugs. How is this? Companies have been able to use market pricing strategies to charge high prices for drugs that offer significant benefits. In this case the company is getting the double benefit of orphan designation and substantial revenue.

The remainder of this paper reviews four different broad drug indications that are eligible for orphan designation: therapeutics for rare diseases, targeted medicine, neglected diseases, and medical countermeasures. This review is not exhaustive, but highlights what I see as general trends for these different drug classes. I examine the market size and price potential for these products and attempt to explain why they were (or were not) able to achieve blockbuster status.

The first example is therapeutics for rare diseases. In large part, drugs for these indications have been able to enjoy the benefits of orphan drug designation and large revenues. This approach was pioneered by Genzyme, and has since been successfully followed by other companies. Since these drugs typically only affect a few thousand people in the U.S., they are eligible for orphan status. In addition, drug manufacturers have successfully charged very large amounts and have convinced insurance companies and other third party payers to cover the cost of these drugs. The reason is that in many cases these are life saving products that significantly improve patient quality of life. From a cost standpoint, it is less expensive for the third party payer to reimburse the very large price for the treatment than to pay for alternatives that would otherwise represent the standard of care. Since there are no alternatives, the company can charge $100,000-$300,000 per year for treatment and receive payment (5). By charging hundreds of thousands of dollars per treatment course for only a few thousand patients, the company is able to reach the $1billion threshold and take advantage of the additional incentives offered under the Orphan Drug Act.

The second example involves therapeutics that are selected based on specific patient criteria or clinical biomarkers. This approach has been called personalized, stratified, or targeted medicine (for clarity I will use the term targeted medicine throughout). The concept in this case is to identify a biomarker that targets therapy to a particular population that has a high likelihood of response to the therapeutic. In theory, this is an attractive option since the patient population that is most likely to respond to the drug has been pre-selected, and therefore clinical trials should be shorter, cheaper, and faster. The benefit to industry comes as the targeted therapy identifies a patient population that is significantly small enough to qualify for Orphan Drug status. Using these principles, a product can require less time to gain approval, which essentially extends patent protection while also enjoying the benefits of orphan incentives. Critics question why a company would chase down a market that is deliberately being made small as this approach runs contrary to the traditional blockbuster drug model. However, this model can be useful if it allows the drug to reach market quickly, where it can generate revenue and open the door for additional approvals for other indications.

This targeted medicine approach has been highly successful for several products. In these cases drugs reach blockbuster-type levels of sales and can enjoy the benefits of orphan drug status. Two well known examples are Novartis’s Gleevec and Amgen’s Epogen. Gleevec originally received orphan status for patients with chronic myelogenous leukemia. Over the past decade the drug has gone on to gain additional approvals and now is licensed for seven orphan indications and 10 indications overall (6). Even with these multiple indications the total patient population remains relatively small (between 50-100,000 patients), and since this drug is so effective the company is able to charge a premium (estimated $40,000/year) and third party payers are willing to pay (1, 7). Epogen follows a similar story. Originally granted orphan status and approved for anemia due to end stage renal failure and anemia associated with HIV, Epogen was later approved for anemia caused by chemotherapy, a large and lucrative market. Sales of Epogen were more than $2.5 billion for 2009 (8).
Neglected diseases represent a third group of indications that have taken advantage of orphan designation. While these diseases have a high prevalence worldwide, they are rare in the U.S. and are therefore eligible for orphan status. Unlike the previous two examples, however, the price and revenue achievements of neglected diseases have been much more modest (9). Several considerations help explain why these products can enjoy orphan incentives but generally do not charge a premium or generate large sales. Since many of the people affected by these diseases live in developing countries, the sales potential of these products is small. This is because private citizens can’t afford the products and insurance or other third party payers do not exist. Once licensed, special pricing strategies and partnerships are established in these countries to supply these drugs at no or an extremely reduced cost. From this we can see that even though the affected population is large, payers can only afford a very small price.

Recognizing this drug development challenge, the U.S. Government appears ready to take a different approach to accelerate efforts to license products for neglected diseases. Recently the National Institutes of Health (NIH) launched the Therapeutics for Rare and Neglected Diseases (TRND) program in the Office of Rare Diseases Research (10). In March 2010, this office released a Request For Information (RFI) to identify compounds that show promise for rare and neglected indications (11). NIH is particularly interested in compounds that have been halted for strategic or financial reasons. The RFI states that the Government plans to license and develop some of the most promising drug programs. This decision by the Government is essentially an admission that these indications do not present a potentially profitable market. Without sufficient market forces to drive development in these areas, the Government plans to sponsor and perform the work internally to improve the greater good. This approach is not unprecedented, since a similar governmental effort was made to develop drugs and vaccines for allied troops against tropical diseases and biological warfare agents during World War II (12). As the above examples illustrate, the potential patient population for neglected diseases, while large, generally lives in developing countries where the capacity to pay a premium for life saving drugs is very limited. As such, the price companies can charge is very low and offers little motivation for product development. Non-profit groups and governmental agencies are generally the only entities that will develop drugs for neglected diseases. In this case, orphan designation alone does not provide sufficient incentive for industry to develop these drugs.

The final category of products to consider is medical countermeasures (MCMs). These are products to be used against emerging health threats, pandemics, or chemical, biological, radiological, or nuclear terrorism threats. For the most part these indications represent very limited markets where the U.S. Government is the only buyer, and as such it is reasonable to consider these drugs for orphan designation. In fact, companies have used this approach for the approved products cyanokit (for cyanide poisoning), pyridostigmine (for Soman nerve gas), DTPA (to accelerate the removal of americium, plutonium, and curium from the body) and Prussian Blue (to accelerate the removal of cesium and thallium from the body). Sponsors have also applied for and received orphan designation for anthrax and smallpox treatments, though these products are not yet FDA approved (13).

What is the pricing situation and revenue potential for these products – are they more like targeted therapies or neglected diseases? On the surface, there is the potential that these products may be able to charge a price premium, since they fill a critical need against lethal agents. However a variety of political and economic issues make it difficult to imagine that these products will provide substantial returns due to a high price. Federal laws passed in 2004 and 2006 created a $5.6 billion fund to incentivize development of MCMs. This fund is for the procurement of MCMs that are FDA approved and demonstrates that there is a market for these products. Unfortunately the number of new MCMs has been very limited over the past 5 years and since there are few products to buy, portions of the fund have been directed for other purposes. Some experts have argued that this fund needs to be substantially increased to provide a greater incentive to industry to develop products for all of these threats (14).

I think there is little chance that this will happen for several reasons. First, the government deficit is at record levels and I believe there is little political will to substantially increase spending. In addition, the Government tends to pay the lowest price for drugs that it buys for the VA and the Center for Medicare and Medicaid Services (15, 16). Finally, there is the 2001 example of price negotiations for Ciprofloxacin (Cipro) between Bayer and the U.S. Government. Cipro is effective against anthrax, and the Government was interested in purchasing large quantities of the drug during the anthrax letter scares. Typically the Government would pay a wholesale price for Cipro. At the time, Cipro was patent protected in the U.S. but was off patent in many countries, so generic versions of the drug existed and were readily available overseas. Some members of Congress threatened to use compulsory licensing (a power the Government has to approve any drug it chooses, usually to allow it to buy a generic at a significant cost savings) to purchase generic versions of Cipro if Bayer did not agree to the lower negotiated price. In the end, the U.S. Government negotiated the price down to one-fourth the wholesale market price (17, 18). I believe the Government would use this same tactic to purchase any MCM during a public health emergency. Finally, much of the research and development costs for MCMs are being paid for by the Government as opposed to private industry. In this case, since the Government has assisted (and funded) a company to develop the MCM, an argument can be made that they should be able to purchase the final licensed product at a discounted price. For all these reasons I believe that MCMs can enjoy the incentives afforded by orphan drug designation but will not be able to generate substantial revenue by charging a premium price.

Drug pricing plays a significant role in the decision of whether or not to develop a drug. With a $1 billion per year revenue goal, companies can reach this amount based on the number of patients treated and the cost per treatment. For indications that can’t reasonably be expected to reach this $1 billion mark via a high number of patients or a high cost, other incentives such as the Orphan Drug Act have been developed to incentivize the development of rare and neglected diseases. For the most part this Act has been a great success, and in some cases companies have been able to develop products that enjoy the orphan incentives and also generate substantial revenue. These cases involve rare diseases and targeted therapies where there is a substantial benefit of the therapy and payers that can afford the high price charged. Neglected diseases and MCMs can benefit from orphan designation but are much less likely to generate significant revenues. It remains an open question if additional incentives should be considered for these indications that continue to be developed at a slow pace.

References
1. Trusheim, M. et al., Nature Reviews Drug Discovery, 6:287-293, 2007.
2. Gregson, G. et al., Nature Reviews Drug Discovery, 4: 121-130, 2005.
3. U.S. Food and Drug Administration, Orphan Drug Act, http://www.fda.gov/forindustry/developingproductsforrarediseasesconditions/overview/ucm119477.htm, accessed May 27, 2010.
4. Cote, T. et al., Nature Review Drug Discovery, 9: 84-85, 2010.
5. Friedman, Y. Building Biotechnology, 3rd Edition. Logos Press, p 157, 2008.
6. Gleevec package insert. http://www.pharma.us.novartis.com/product/pi/pdf/gleevec_tabs.pdf, accessed May 27, 2010.
7. Orphan Drug Market Catches Pharma’s Eye. Yahoo Finance, http://finance.yahoo.com/news/Orphan-Drug-Market-Catches-ibd-2653919238.html?x=0&.v=1 Accessed May 27, 2010.
8. Amgen Press Release, January 25, 2010, http://www.amgen.com/media/media_pr_detail.jsp?year=2010&releaseID=1378596 Accessed May 27, 2010.
9. Villa, S. et al. International Journal of Health Planning and Management, 24: 27-42, 2009.
10. National Institutes of Health, Therapeutics for Rare and Neglected Diseases, http://www.rarediseases.info.nih.gov/Resources.aspx?PageID=32 accessed May 27, 2010.
11. Program to Advance Development of Drug Candidates for Rare and Neglected Diseases, https://www.fbo.gov/index?s=opportunity&mode=form&id=e67390f54bc6935999963218ccf50553&tab=core&_cview=1 Accessed May 27, 2010.
12. Hoyt, K. Journal of Public Health Policy, 27: 38-57, 2006.
13. FDA Application, Search Orphan Drug Designations and Approvals, http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm Accessed May 27, 2010.
14. Matheny, J. et al. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, 5: 228-238, 2007.
15. Congressional Budget Office report, Prices for Brand-Name Drugs Under Selected Federal Programs, June 2005.
16. Government Accountability Office, Prescription Drugs: Overview of Approaches to Control Prescription Drug Spending in Federal Programs. Report GAO-09-819T, June 2009.
17. Bayer Halves Price for Cipro, but Rivals Offer Drugs Free, by Keith Bradsher, The New York Times, http://www.nytimes.com/2001/10/26/business/26CIPR.html, Originally Published October 26, 2001, Accessed May 27, 2010.
18. A Nation Challenged: The Drug; A Rush for Cipro, and the Global Ripples, The New York Times, http://www.nytimes.com/2001/10/17/world/a-nation-challenged-the-drug-a-rush-for-cipro-and-the-global-ripples.html, Originally Published October 17, 2001, Accessed May 27, 2010.

About the Author:

Nate Hafer is currently an AAAS Science and Technology Policy Fellow at NIH.  Previously he worked at the Federation of American Scientists and was a Science and Technology Policy Graduate Fellow at The National Academies.  He received his Ph.D. in molecular biology from Princeton University and his B.S. degree in biology from The Pennsylvania State University.  He can be reached at nathanielhafer@gmail.com .

This is a student paper from the 2010 final projects in the NIH Foundation for Advanced Education in the Sciences’ TECH 366 — Biotechnology Management. The students were asked to tell a story based on the course lectures, and to expand with general lessons on biotechnology company management.

If You Build It, Will They Come?
Derek Francis, PhD

Biotechnology Guru Steven Burrill is Planning to Build a Billion Dollar Biotechnology Center on an Elk Farm in Southeastern Minnesota.  Is it a Field of Dreams?

In March 2009, it was announced that a real estate development firm, Tower Investments, is teaming up with biotechnology financier Burrill & Company to build a biobusiness community on an elk farm just outside Rochester, MN[1, 2].  Elk Run, as it is to be called, will include homes, retail, schools, a recreation center, a hospital, and a biomedical research park.  When completed, the envisioned research facility will house 15 to 25 companies ranging from start-ups to publicly traded companies, employing up to 25,000 people[3, 4].  If that isn’t ambitious enough, the financier plans to raise $1B to fund the project in under a year.  The sheer size of the development, the short time frame, and the economic recession have led many to doubt the plausibility of the project.  As a native Minnesotan with interest in moving back, I was quite intrigued when I read about the proposed biotechnology center being planned in my home state.  This paper explores the current state of the biotechnology industry in Minnesota in an attempt to predict the ability of the Elk Run proposal to succeed.

Areas with thriving biotechnology industries, such as San Francisco, Boston, and San Diego, have several common characteristics.  These regions have strong local research centers with skilled laborers, willingness of the private sector to invest monetarily, and political support of the industry.  These regions with successfully established biotech industries are also the best suited to support the growth of biotech industry.  A successfully established industry attracts additional research, capital, and political support, which in turn promotes growth.  This was illustrated in a study by the Brookings Institution that found that 75% of the new biotech firms launched over the previous decade were formed in cities that ranked in the top ten in terms of established biotech[5].  Many cities and states have attempted to create a local biotechnology industry but have found that a lack of any of these crucial elements can result in failure.

The Current State of the Biotechnology Industry in Minnesota
Minnesota is home to two strong biomedical research centers, the University of Minnesota and the Mayo Clinic.  Minnesota also boasts a strong workforce, ranking #1 in high school graduation rate, #4 in the number of graduate level science and engineering students, and #1 per capita in medical technology jobs.  The state trails only California in the medical device industry, led by the world’s largest medical device company, Medtronic.  Despite having research centers and skilled labor, a 2002 study found that biotech commercialization in Minneapolis/St. Paul was well below the average of the US’s 51 largest metro areas[5].  One key factor contributing to the poor commercialization success is the lack of financial investments available in the region.  From 1995 to 2008, the state’s average share of biotech venture capital (VC) investments was roughly half the national average[6].  Not only has venture funding been poor, it is getting worse.  Recent data show that Minnesota hit a 14 year low in VC investments during Q4 of 2008[7].  Another factor contributing to the lack of financing has been the lack of government support.  The state government has refused to subsidize startup biotech companies and does not provide the tax benefits to angel investors as many other states do.  A particularly dreadful example is the Minnesota Investment Fund, which has a budget of roughly $1M per year compared to the $231M provided by Wisconsin’s Department of Commerce in 2008[8].  Politicians have in turn placed blame on the technology transfer departments within the research institutions.  The University of Minnesota built a biotech incubator called University Enterprise Laboratories (UEL) in 2004 hoping to spur commercialization of its technologies, but has yet to retain a single company using University research[9].  The Mayo Clinic has had some degree of success in commercializing its technologies, but of the 35 companies spun out of its technologies, only three have remained based in Minnesota[10].  Many of these companies are fleeing to neighboring states, such as Wisconsin, which have a more favorable funding outlook.

Elk Run Proposal
As stated earlier, the prospect of a billion dollar research center in rural Minnesota raised many eyebrows.  Many questioned how, or why, anyone would invest such a large amount of money into a completely undeveloped region.  However, the involvement of San Francisco based Burrill & Company has lent credibility to the project.  CEO Steven Burrill is a Midwest native who still has several ties to Minnesota and Wisconsin.  He was an early advisor to biotech giants Genentech and Amgen.  In 1994, he founded Burrill & Company, a venture capital firm that currently manages $950M in assets.  His annual State of the Biotech Industry report has been called “the bible for biotechnology[11].”  In 2002, he was named one of the country’s top biotech visionaries[11].  Burrill plans on securing the $1B funding from pension funds, institutional investors, and big corporations within the state such as 3M, Medronic, and Boston Scientific[4].  His company also has significant capital to invest, but it is unclear how much they are willing to personally invest.  One interesting caveat to the proposed fund is that it will be split between the biotechnology companies and the real estate development team.  $500M will provide as many as 25 companies with $20M each.  The other $500M will go towards the commercial real estate development.  The project has drawn praise from many local politicians, and state and local governments have already invested $15M to provide the infrastructure needed.  Others, however, are less than optimistic about the region’s potential to become a major biotech hotbed.  Many local venture capital firms describe Minnesota as a risk adverse state, particularly during the current recession.  Many seem to agree that raising $1B is nearly impossible, even for someone with Burrill’s credentials.  “I’m not getting a good sense that there is a workable business model here.  This thing defies gravity, in my view,” says Peter Bianco, director of the Life Science Business Development unit at Halleland Health Consulting[11].  Randy Olson, the former GM of UEL, said “There is a risk profile here that is probably off the charts[11].”  Burrill disputes claims that companies will not want to move to rural Minnesota.  Citing the troubled economy, he says “It’s a tough time to be a company, which makes this little thing that we are doing at Elk Run very, very attractive.  If I stand on a street corner at Elk Run and wave around $500M, people will come,” he said[10]. He is convinced that Minnesota has what it takes to be a national player in the biotech industry.  “Elk run is geographically and strategically positioned in a uniquely propitious way,” he said[6].  “Minnesota sits at the intersection of predictive and preventative medicine.  But there has been no catalyst to ignite it here[11].”  For example, Mayo Clinic has been collaborating with IBM’s Blue Gene supercomputer to mine Mayo’s 6 million electronic patient records for disease trends in large populations[11].  Burrill envisions that companies will soon have the ability to create computer chips that will “tell you your blood pressure is too high, your cholesterol is too high, time for you to you’re your pill, time for you to go to the doctor[3].”    Some have argued that building a biotech hub in the proximity of the Mayo clinic is insufficient to ensure that Mayo technologies will move in, citing the lack of any kind of contract between Mayo and Elk Run.  “There has to be a greater tie other than the geographic location,” says Jay Hare, who tracks VC investing[1].  Burrill counters that “there will be enormous synergy between things in Mayo that we can accelerate the development around and build companies around” and says after working with Mayo on various projects since 2005 that “I would put us in the best friends category[10].”  Mayo spokesman Adam Brase says of the project “We do support the concept of a biomedical accelerator that could create new companies and develop new therapies.  If we can have more of that in our area, the better off any medical organization is going to be[1].”

Progress and Assessment of the Future
Burrill initially declared that he would raise $1B by the end of 2009.  By July 2009, he said that he had “one big commitment”, but “no checks yet.”  In late July one prominent local investor, Vance Opperman, declared that he was not interested[12].  As the self-imposed deadline of December 2009 approached, Burrill began to express “disappointment” from the “push back” of local investors.  Unconfirmed estimates suggested that by December 2009 the fund contained anywhere from $0-250M[13].  By creating a “hybrid” investment fund mixing real estate with biotechnology, Burrill may have confused or frightened away potential investors.  When questioned about this, Burrill admitted that he was considering splitting the fund into two separate entities[13].  In February 2010, it was announced that the weak economy was forcing the developer to alter construction plans[14].  As of May 2010, no construction has begun at the site, and Tower Investments is now facing foreclosure on part of the land purchased for development.  Despite the recent troubles being faced by the Elk Run project, an interesting trend has emerged within the state.  Over the past few months, a large number of smaller venture capital funds have suddenly formed in Minnesota, each targeting early stage biotechnology companies[15-17].  One such fund, Coordinate Capital LLC, is clearly connected to Burrill & Company[15, 18].  Burrill is the chair of Coordinate’s board of advisers, and the firm lists Elk Run as an “affiliate”.  In addition to the recent increase in venture capital funding, the state also passed a five year, $50 million tax credit angel investor credit in hopes of spurring early stage investment in startup companies[19].  Additional legislation is being pushed through the state legislature that would create a stronger, more concentrated high-tech economic development authority[20].  The local governments are also advertising financial assistance in the form of grants, bonds, and seed funding.  Additionally, the University of Minnesota has revamped its Office of Technology Commercialization and is planning construction of a 60,000 square foot building as a first step in creating a planned $750M Minnesota Science Park that it hopes will rival Research Triangle Park in North Carolina[21].  This commercialization center would likely compete with Elk Run for a variety of resources.

Conclusion
It remains to be seen whether or not Elk Run will succeed, or even launch for that matter.  Minnesota has historically lacked the financial and political support needed to give rise to a prominent biotech industry, and even the infusion of a billion dollars would not be sufficient to create an industry overnight.  It seems, however, that by simply declaring his intention to invest in the region, Steve Burrill may have provided the spark necessary for these things to change.  The past year has seen the state of Minnesota begin to position itself to build a significant biotechnology industry.  Perhaps Burrill’s assertion that Minnesota will become the next big thing in biotechnology will become a self-fulfilling prophecy, with or without Elk Run.

Citations
1.    Lee, T. 2009. Developer, investor OK Elk Run biosciences project. In Star Tribune, Minneapolis.
2.    Stachura, S. 2009. Officials announce $1 billion Elk Run Project. In Minnesota Public Radio.
3.    April 10, 2010. Elk Run Investor Hopes to Redefine Medicine. In WCCO.
4.    Lee, T. 2009. Elk Run investor raising $1 billion. In Star Tribune, Minneapolis.
5.    Mayer, J. C. a. H. 2002. Signs of Life: The growth of biotechnology Centers in the US. Brookings Institution Center on Urban and Metropolitan Policy.
6.    Lee, T. 2009. Developer, investor OK Elk Run biosciences project. In Star Tribune, Minneapolis.
7.    Lee, T. 2009. Venture capital spigot taps out to 14-year low in 4th quarter. In Star Tribune, Minneapolis.
8.    Lee, T. 2010. Former Pawlenty aide now university champion.  Not as weird as you think. In MedCity News.
9.    Stubbe, G. 2009. UEL still finding its feet. In Star Tribune, Minneapolis.
10.    Grayson, K. 2009. Burrill seeking $1B for Elk Run, but “no checks yet”. Minneapolis St Paul Business Journal.
11.    Lee, T. 2009. Can biotech boom in state? In Star Tribune, Minneapolis.
12.    Lee, T. 2009. Opperman to Burrill: Good luck but no thanks. In Star Tribune, Minneapolis.
13.    Lee, T. December 21, 2009. Wanted: Money for $1 billion Bioscience Project.  Contact Steven Burrill. In Medcity News.
14.    Lee, T. 2010. Bad economy forces Elk Run developer to alter biotech plans. In MedCity News.
15.    Lee, T. January 18, 2010. New Minnesota biotech fund seeks $25 million with a little help from Steve Burrill and yours truly. In MedCity News.
16.    Lee, T. February 18, 2010. Affinity Capital and Triathlon Medical Ventures plan new $10M early stage fund in Minnesota. In MedCity News.
17.    Lee, T. March 2, 2010. Upwind Medical Partners to create $8 million early stage fund. In MedCity News.
18.    Lee, T. 2010. New Minnesota biotech fund seeks $25 million with a little help from Steve Burrill and yours truly. In MedCity News.
19.    Lee, T. 2010. Minnesota Legislature passes historic angel tax credit. In MedCity News.
20.    Lee, T. 2010. Minnesota seeks its own “Third Frontier”. In MedCity News.
21.    Lee, T. 2010. University of Minnesota and developers plan $20M venture fund to anchor major science park.

About the author:
Derek Francis is a post-doctoral research scientist at the National Institutes of Health with an interest in all aspects of biotechnology.  He may be reached at francisd3@ninds.nih.gov.

This is a student paper from the 2010 final projects in the NIH Foundation for Advanced Education in the Sciences’ TECH 366 — Biotechnology Management. The students were asked to tell a story based on the course lectures, and to expand with general lessons on biotechnology company management.

Patent Analysis: A Tool for Making Strategic Business Decisions
Eric Norman

It takes 10-15 years and over a billion dollars to develop a drug and get it to market. Once in the market, only 2 out 10 drugs generate revenues that match or exceed its research and development costs[1]. Of the drugs reaching the commercial market less than a third become blockbusters, drugs that earn or exceed a billion dollars in revenues. These are the numbers for the success stories; in the pharmaceutical industry 1 out of 10,000 chemical compounds discovered are found beneficial and safe for commercialization[2].  In the face of these numbers, can a company truly grow big enough and diversify enough through mergers and acquisitions to ensure stability and future profits? I believe that a change is needed and that change is minimization, focus, and partnerships. This idea is not new for it has been made in a 2004 Businessweek article[3]. However, as with all big things, changing directions is slow and costly. In the eventual necessity of this change there will be a greater need for market analysis and strategic decision making for new drug development as a way of minimizing invested research and development dollars and subsequently, risk. Since innovation drives the market and innovation rests on intellectual property rights predominantly secured by patents, I believe that patent analysis can become the cornerstone for market analysis and strategic business decisions.

As a way of emphasizing patent analysis as a marketing and business strategy tool I have devised a flow chart comprising an integrative model of the resource base-view and Porter’s five forces, both of which are commonly used for assessing risk and potential value of new businesses and drug development.  Although patent analysis does not address all issues that are encompassed by this business model, patent analysis serves as an economical approach to determine a focused marketing area, risk of new drug development, and potential value of a drug by addressing the following questions: What are my resources (IP)? How can I best use my IP? How does my innovation differ from that of my rivals? Who are my rivals? What are the potential markets? How crowded are these markets? Who are the innovators, leaders and laggards in these markets? Are there IP barriers to entry into this market? What is the likely direction of the market? What will it take to stay competitive in this market?

Figure 1: Resource-based view(7): Overview of resource-based view and Porter’s five forces that are predominantly used for market analysis.

Patent analysis begins with a patentability and freedom to operate search. These two searches will provide relevant “prior art” that determines whether your innovation is patentable and has no IP impedance to commercialization. Next, based on the prior art a series of relevant patents can be collected and Patent Citation analysis can be done. Ocean Tomo, the leading Intellectual Capital Merchant Bank, has been innovators in patent analysis since 2003 and has devised various unique ways of using Patent Citation analysis[4,5]. In particular, Ocean Tomo has used Patent citation analysis as a way of determining the relatedness of patents for assessing potential litigation issues. However, modifications of this analysis can bring forth a list of potential markets that your innovation may have a use and potential partners to build collaborations to exploit those markets. In essence, through exploring the relationship between your patent and other patents there is a potential to generate additional revenues and/or diversification through: licensing part of your technologies to non-competitors, setting-up research partnerships to exploit an open market, or in-licensing a particular technology that would allow you to expand your market base or create additional IP barriers to prevent others from entering into the market. An additional use of Patent citation analysis, also utilized by Ocean Tomo, is to create categories of ‘hot topics’ and ‘next generation’ patents (figure 2). Hot topic patents are generally older patents that have a large number of citations by patents that expand a variety of technologies. They tend to be patents that lead to industry standards, disruptive technologies, and/or made a substantial impact across various industries. The ‘next generation’ of patents cites two or more of these ‘hot topic’ patents. The ‘next generation’ patents should represent patents that are improving and innovating upon an industry standard, suggesting that market adoption should be quicker with these technologies as oppose to the actual disruptive technology. Secondly, this analysis provides insight into potential market direction and who the innovators are for a particular technology group.  These analyses should be substantiated through Patent Count Analysis[5]. Patent count analysis adds up the number of published (public) patents pending, issued, and abandoned for a technology group to assess the market drive/pull in a given industry; The greater the number of patents being filed and maintained in a particular industry the greater the probability that there is a profitable and growing market to support the investments being made in those intellectual properties. Furthermore, subdividing patent counts by ownerships gives an idea of the market leaders and how aggressively they are in using patents to prevent others from entering into the market. Pending on the analysis, the best business strategy may be to license your technology to the more aggressive company or seek a partnership with one of the rival companies that have approximately equal market size. Opposite to this, a large number of abandoned patents suggest that there is not enough money being made in the industry to justify continuing with the patent process and incurring additional fees or paying patent maintenance fees.  Under these circumstances it may be better to forgo the patenting of the technology and either license the technology cheaper than it would cost to replicate the technology or make the technology available to everyone as ‘good will’ expense.

Figure 2: From presentation by Ocean Tomo.

A final benefit of patent analysis is the valuation of your intangible properties for merger and acquisition, litigation, and/or taxes. The analyses discussed above can also be used to address three issues that underlie the valuation of intellectual properties: potential litigation issues, potential value of the technology (substitutable, ‘next generation’ technology, hot market area, and potential to be implemented in multiple markets), and the potential value of the market (market competitors, competitor market size, and a growing market). By addressing these issues you can have a clear idea of risk involved in the drug development and/or business development and can better utilized a more appropriate discount rate for calculated values determined by traditional market-base, asset-base, or income-base approach for valuation. In summary, product value is influenced by its scarcity and alternative uses. Patent analysis reflects scarcity and alternative uses of a product by outlining market availability, market need, market size, and market competitors.

In conclusion, through regular use of patent analysis you will be able to bring your drug development, IP portfolio management, business strategy, and business development groups together, using an integrative approach to minimizing research and development spending through targeted research projects and/or partnerships. As a single group, they can collectively use patent analysis to better position the company for the future through innovation and innovative strategies.

References

1.    (Pharmaceutical Research and Manufacturers of America, Pharmaceutical Industry Profile 2010 (Washington, DC: PhRMA, March 2010)

2.    (Davidson, L and Greblov G. The Pharmaceutical industry in the Global Economy (2005) Indiana University Kelley School of Business )

3.    Arnst C, Barrett A, and Arndt M (2004) The Waning of The Blockbuster Drug. BussinessWeek  Oct. 18 (http://www.businessweek.com/magazine/content/04_42/b3904034_mz011.htm)

4.    Malackowski J.E., Barney J.A., Cardoza K, Walker M.D., and Gray C., (2006) Innovation Measurement: The Economic Impact of Patent Value: Business Submission at Ocean Tomo, LLC and Ocean Tomo Federal Services, LLC. Contact jmalackowski@oceantomo.com or 312-327-4400.

5.    Malackowski J.E. and Barney J (2009) Patent Attributions To Equity Returns. Business Submission at Ocean Tomo, LLC and Ocean Tomo Federal Services, LLC. Contact jmalackowski@oceantomo.com or 312-327-4400.

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About the author

Eric Norman received his Ph.D. in neuroscience from the University of Pittsburgh. Eric has spent many years conducting scientific research and has gained a broad knowledge of neurophysiology that culminated in a series of scientific articles. Currently working at NIH’s Office of Technology Transfer (OTT), Eric brings his scientific knowledge and critical thinking skills to the development of marketing campaigns aimed at promoting early stage technologies available at NIH and FDA. As a strong interest and personal passion, Eric studies the use of patent analysis and how it may be used in business development.