Intellectual property and nutrigenomics.

Introduction

Evidence for the connection between good nutritional regimens and healthy living comes from many quarters: personal testimony, folk wisdom, cross-cultural comparisons, dietetics, naturopathy and other health care modalities, and clinical epidemiology. On the face of it, recommendations to eat fruits and vegetables each day, but not eat a daily pound of butter, are over-determined by available evidence. Yet this might just be literally on the face of it, since many of the strongest associations between diet and heath are based on contestable food recall data paired with phenotypic information drawn from memories, retrospective studies and secondary uses of clinical data. During the short histories of evidence-based medicine and the nutritional sciences this is how it has been: in a sense everyone knows about healthy eating, but explaining what that means in scientific terms has been difficult to achieve.

Two methodological advances in the biological and medical sciences have, since the f950s, dramatically changed the evidence base for understanding diet-health interactions. The first is that the biological and medical sciences have become increasingly experimental, and the second is the shift to a molecular focus. The result is the development of molecular, experimental nutritional sciences, (1) and the advent of the Human Genome Project and molecular genetics. (2) One can now begin to point to causal explanations about the underlying mechanisms that make some diets appear to be healthier than others. More significantly, human genomics and genetics are beginning to reveal how diet and health are linked not only through the physiological activity of nutrients, but that nutrients are involved in the cascade of events beginning with gene regulation and expression.

Nutrigenomics lies at the crossroads of these major developments in the nutritional sciences and human genomics and genetics, and it is also developing at a time when the commercialization of research is an expected outcome of research funding. Technology transfer of bench science to publicly accessible applications is a high priority for universities and their funders who coordinate with private sector companies and investors to bring new products and services to market. Nutrigenomics is a growing field of innovative research and development, it has opened a new field of environmental genomics research, (3) and represents a novel and potentially high-value proposition recognized already by private sector interests. Accordingly, proprietary interest in nutrigenomics has resulted in a number of patents being issued, or existing patents being licensed for use in nutrigenomics applications.

The purpose of this paper is to give an overview of the status of intellectual property rights, particularly patents, in the emerging field of nutrigenomics. It is not a formal and exhaustive review of all nutrigenomics patents, licensing activity, and estimation of market capitalization. Rather, the approach taken here involves the characterization of a few representative patents in nutrigenomics to shed light on the kind of patenting activity in the field. Next follows a discussion about the role of patents in genomics and biotechnology innovation, and highlights some of the claims made about the impact that patents have on innovation and markets. These considerations lead to a short discussion of the impact of patents in nutrigenomics. In recognition of the criticism directed toward patenting in genomics and genetics, this paper concludes with a preliminary evaluation of effects of strategic patent uses in nutrigenomics.

Patenting Activity in Nutrigenomics

There are three main types of conventional patenting activity and one wild-card type that are of interest in nutrigenomics. The three conventional types are: patents on genes, gene variants or methods of detecting gene variants; patents for bioactive food compounds; and patents on proprietary methods for analyzing gene-nutrient associations using computer supported algorithms. The wild-card patenting situation involves a patent on so-called junkDNA, which is having an impact throughout genomics and biotechnology including nutrigenomics. Before describing these patent types, it should be pointed out that with the exception of the wild-card situation, the three kinds of patent activity to be discussed are considered conventional because they are cornerstones in the business plans of companies already offering services to the public. The patents involve the identification of genetic variation from nutrient-gene association studies, methods for detecting the genetic variation, and techniques for extracting biological information from the presence of the gene variant in combination with lifestyle information. In practice, nutrigenomic services offered to the public typically involve the consumer submitting a cheek cell sample and completed lifestyle assessment questionnaire to the company, which then performs a genetic test to see if the client has variants for genes believed to be associated with nutrigenetic effects, such as increased susceptibility to chronic diseases like cardiovascular disease (CVD).

Nutrigenomics is often illustrated by CVD examples of nutrient-gene assocations. One frequently mentioned gene codes for an enzyme, methelenetetrahydrofolate reductase (MTHFR). This enzyme uses folate to reduce blood homocysteine to methionine, and is believed to be a contributor to maintaining healthy cardiovascular function. There are two variants of the gene that lower the kinetics of the enzyme, leading to higher levels of homocysteine which has been implicated in CVD. (4) Intellectual property rights in MTHFR are held by McGill University in Canada, which is the assignee on several MTHFR patents filed with the United States Patent and Trademark Office. For example, in a patent filed under the Patent Cooperation Treaty May 25, 1995 and with the USPTO on February 12, 1997, inventors Rozen and Goyette claimed the invention of a cDNA probe for MTHFR. (5) A subsequent filing on March 1, 1999 was for a method to detect the MTHFR allelic variants, particularly the fairly common variant 677C, so that reduced MTHFR activity could be detected and treated. (6) A year later, on September 13, 2000, another patent was filed by the same inventors, with McGill University as the assignee, which extended the scope of the diagnostic and therapeutic methods for MTHFR. (7) Another, more recent patent, also filed in 1999 and awarded May 1, 2006, is for the methods by which methionine synthase reductase, which is in the same pathway as MTHFR and is also a cause of hyperhomocysteinemia. (8) This patent, like the others held on MTHFR, provides methods for identifying and potentially treating elevated homocysteine levels, in anticipation that control of hyperhomocysteinemia will reduce CVD risk.

Unlike the MTHFR example, in which a university-owned patent is licensed to researchers and to the private sector, many gene patents are filed by principals of nutrigenomics companies. In many cases, these inventors might also have university affiliations that would require the intellectual property rights to be assigned to the university if the invention arose from federal research funding. In many other cases, inventors might already be involved in a separate company. Since the companies involved in nutrigenomics are mainly privately-held and small-to-medium enterprises, they do not have large patent portfolios. Consequently, whatever intellectual property rights they hold tend to be foundational to the overall corporate plan, and hence represent the most important intangible assets giving firm equity. A case in point would be the nutrigenomics company Interleukin Genetics. (9) This company focused on genes that control inflammatory pathways implicated in heightened CVD risk. These genes are thought to be associated with certain nutrient regimes, making possible the attenuation of risk through dietary modification. An early entrant into the field of nutrigenomics, Interleukin Genetics, became the assignee of two important patents in the genetics of inflammation-related heart disease. One patent, filed March 10,1997 and awarded April 3, 2001, disclosed a method by which variants in genes for IL-1 could be identified, relative risk to carriers identified, all in an effort to disclose "presymptomatic risk" to patients. Another two patents, filed November 1, 1999 and May 24, 2000 and awarded February 23, 2003 and April 13, 2004 respectively, described a kit, method and therapeutic regimens that could be used to diagnose and treat cardiovascular disorders arising from IL-1 genetic variations.

The second type of patenting activity in nutrigenomics involves patents associated with bioactive food components and their method of detection. Patents held for nutraceuticals and their detection are the logical counterparts to gene patents and methods of detecting genetic variation. Two related examples of nutraceutical patents have been filed by the principals of WellGen, a self-described wellness company. (10) WellGen does not appear to have a stake in the genetics aspects of nutrigenomics, but instead has patented a process, assigned to Rutgers University, by which nutraceuticals useful in nutrigenomics can be detected and isolated. (11) This patent, which was filed June 20, 1996 and awarded September 21, 1999, described a method for identifying and isolating non-nutrient, food and food substances that are involved in modulating the expression of genes implicated in cancer tumour growth. This patent is related to a subsequent patent for a bioactive found in black tea called TF2. (12) Filed on June 17, 2004, and awarded July 2, 2007, this patent was again assigned to Rutgers University but filed by the principals of WellGen. The patent is for a compound, WG0401, marketed by WellGen as a nutraceutical, that inhibits the expression of COX-2 and IL-10, thereby inhibiting cancer cell growth. WellGen's focus appears to be on nutraceuticals supplement research and development, but that does not preclude another firm from offering the relevant genetic test and offering personalized advice regarding supplement regimens.

One of the founders of Interleukin Genetics, Kenneth Kornmann, is an inventor on many of the patents assigned to Interleukin. Kornmann had also been active in filing patents, not for single genes and their known variants, but for integrated systems models. These computer-based models would be useful in diagnosing and generating therapeutic plans for patients, it was claimed, because they would integrate the biological hierarchies into a consolidated cell model useful for in vitro drug targeting. (13) Generating a system capable of capturing biological complexity and narrowing it down to patient-specific needs is the central idea behind personalized medicine. Practical applications of nutrigenomics share a similar premise, insofar as nutrition can replace drugs as potential therapeutics, or play a role in reducing a person's susceptibility to disease. This idea was captured in a patent filed by Sciona Limited, (14) which like Interleukin Genetics was an early entrant in the field of nutrigenomics. The Sciona patent, which was filed January 30, 2001 and awarded May 30, 2006 to Sciona Limited, is a utility patent for a "Computer-assisted means for assessing lifestyle risk factors." (15) It claims a computer algorithm by which the results of a genetic test and a lifestyle questionnaire can be combined to give personalized advice, as the patent abstract says:

  The present invention relates to methods of assessing disease
  susceptibility associated with dietary and lifestyle risk factors. The
  invention provides for analysis of alleles at loci of genes associated
  with lifestyle risk factors, and the disease susceptibility profile of
  an individual is determined by reference to datasets which further
  match the risk factor with lifestyle recommendations in order to
  produce a personalized lifestyle advice plan. (16)

This patent has utility, it ought to be pointed out, so long as the number of genes with known nutrient associations is large enough to make a testable portfolio. Since many of these genes might have been patented along the lines of MTHFR or IL-1, the Sciona patent is contingent on there being other, licensable genes for use.

Licensing in nutrigenomics presents an interesting wild card for companies working in the field. Amidst controversy, Genetic Technologies Limited (GTG) (17) has acquired nearly 30 patents in total in several jurisdictions (18) for non-coding regions of DNA. These patents are important because licensed genetic technologies almost all use some so-called junk DNA, meaning that GTG has a legally legitimate stake in these licensed technologies. Although there has been some discussion about whether this patent could be successfully challenged, or whether reforms to the patent system are called for in light of the GTG patents, (19) for small-to-medium enterprises the expense of mounting a patent challenge is prohibitive and would distract from core operations. The other option, one chosen by the Austrian genetic diagnostics and preventative medicine firm, Genosense Diagnostics, (20) and Sciona Limited, is to license GTG's non-coding patents directly. (21) By taking this course of action, these firms are able to combine licenses for genetic variants with non-exclusive but negotiated licenses with GTG, thus stacking licenses to achieve advantage over competitors. In other sectors, similar stacking of licenses has had to occur, but this is perhaps the first of its kind in nutrigenomics.

Divergent Views about Intellectual Property in Genomics and Biotechnology Innovation

Proportionate growth exists between the number of genes that have been discovered, the number of patents on genes, and the number of articles in the academic literature commenting on gene patenting. The reason for the latter is attributable to the novelty of gene patents, which continue to raise important issues about the role of intellectual property rights in biotechnology innovation, the systemic and distributional effects of intellectual property rights, particularly patents, and our capacity to understand, analyze and make thoughtful recommendations about required policy changes. (22)

The role patents play in driving biotechnology innovation is an open question. (23) The conventional view is that inventors take risks, and without a patent system in place, they would have no basis in law to seek their rewards. A trade-off exists between providing the incentive, in the form of limited term rights over the invention, for innovators to take risks, and disclosing the invention to the public. The conundrum facing researchers and policy makers is that, so-described, the patent systems appear to work because there are inventions being disclosed, innovation systems that add value, products and services that reach markets, and patent protection all along the way. Generating independent evidence that without patents invention disclosures would speed up, or slow down, or perhaps commercialization would be radically changed, is perhaps an impossibility. It is tantalizing as a thought experiment, but not possible in practice to test. Consequently, an alternative approach has arisen, which is to suggest that the system works, but not because the incentive-access paradigm works, but because the patent system solves a social coordination problem in large markets between inventors and users of inventions. (24) In this respect, there is perhaps convergence on the view that patents are an important, if not necessary, requirement for bridging the invention-innovation gap. As it stands, the reality is that patents are important for commercialization, and there are two theoretical accounts about why this is so.

Although there are unresolved issues about the role patents play in the commercialization of research, including whether or not they are necessary for commercialization, the potential for negative effects of patents on commercialization have garnered considerable attention. These come in two main types: systemic effects and distributional effects. The systemic effects can be divided among those who are interested in anti-commons issues, and those who are interested in the linkages between knowledge and economics. The former group's concern centre on the potential for patents to disrupt normal movement of knowledge between inventors and innovators by creating an anti-commons effect where knowledge becomes more valuable to a smaller number of people but access to it diminishes. (25) Not everyone, however, is convinced that anti-commons effects can be attributed to biotechnology patent licensing. (26) Because a wide variety of licensing practices exist according to different objectives of licensing, it is often difficult to make generalized statements about effects of gene patenting. (27) Murray and Stern found a modest anti-commons effect in one of the few papers with empirical data looking into the effect. (28) Nevertheless, the idea of anti-commons effects of biotechnology patenting has influence those interested in alternatives to conventional licensing arrangements, including open source. (29) Open source is also part of the other major grouping of concerns about the relationship between knowledge and economics, for it presents a possible escape route from knowledge-based economic activity that resembles feudalism at one level, (30) and the potential for the worst form of trade piracy in bilateral negotiations on another level. (31)

The distributional effects of patents in biotechnology are often said to arise from the two classes of systemic problems, and therefore are often the chief arguments put forward for reform to patent systems. One source of distributional inequity that is widely discussed concerns the effects on patents with respect to accessing inventions that are useful tools in research. (32) The other major distributional issue concerns the effect that patents, because of their licensing requirements, have on access to new technologies for end users. The idea is that in patent-free commercialization, technologies would be cheaper because the costs of research tool licenses, as well as end-user licenses, would drop away. The problem of elevated end-user costs is attributed to costs of accessing agricultural biotechnologies (33) as well as medical biotechnologies:

  Today's high drug prices are a consequence of intellectual property
  enforcement mechanisms that are designed to pay for the R & D done by
  drugs companies and stop the "free rider" effect, whereby companies
  manufacture and sell copies of drugs that other companies spent large
  amounts of money developing. These mechanisms have the unpleasant side
  effect of making it the primary responsibility of pharmaceutical
  companies to maximise return on investment, which inflates drugs
  prices beyond what many people can pay. (34)

Behind these concerns about distributional effects of patents in biotechnology is that the gold rush of patenting activity has proceeded in advance of sober reflection about gene patents and their potential to distort a market for genetic technologies. As one commentator has put it, extensive gene patenting--since 2005 more than 4,000 genes have been patented--represents a "land grab" in which the finite number of genes is being snapped up as quickly as possible by investors interested in owning and exploiting this resource. (35)

Discussion

Patents have been awarded for the three central activities that comprise commercial applications of nutrigenomics. There are patents for gene variants and their detection, patents for bioactive food components and their detection, and a patent for a method of combining personal genetic and lifestyle information such that personalized dietary guidelines can be generated. This breadth of patenting in nutrigenomics is to be expected of a new field recognized as having commercial potential in which high value-added products and services can be offered to consumers. At the same time, it must be pointed out that the patenting activity in nutrigenomics is not qua nutrigenomics or its cognate terms like nutritional genomics or personalized nutrition. Nutrigenomics is a relatively new field both for research and for commercial activity, and many of the characteristic patents discussed above were filed before 'nutrigenomics' became the term of art that it is now.

What are the effects of patenting activity in nutrigenomics? The short answer is that it is too soon to say anything definitive. To the extent that there might be systemic and distributional effects of patenting in nutrigenomics just because these effects prevail elsewhere in genetic and biotechnology patents is simply to locate nutrigenomics as a member of a class. That said, however, it is worth considering whether or not there is direct evidence of the effects attributed to patents already apparent in the field of nutrigenomics. In this respect, it is fair to say that McGill University has attempted to make the most of a good thing--MTHFR is considered an important gene for CVD risk management and has been studied extensively around the world. There does not appear to be any evidence that MTHFR licenses have impeded research; similarly there do not appear to be demands for licensing exemptions for MTHFR. Moreover, it may be the case that nutrigenomics contributes to a general anti-commons problem in genetics and biotechnology, but since anti-commons are theoretically possible but are neither empirically confirmed nor disconfirmed, agnosticism about anti-commons effects arising from nutrigenomic patents is currently the only option.

Evaluation of the distributional effects is a somewhat different matter, in the sense that commercial products and services offered by companies like WellGen, Interleukin Genetics and Sciona are based on technologies that require licensing, for example use of McGill's MTHFR patents or GTG's non-coding DNA patents. Consumers wishing to use services of these companies or buy products will indirectly pay for licensing, and the products and services are not inexpensive. As the Institute for the Future had determined in its assessment of the early adopters of nutrigenomics, price was not likely to be a significant barrier. For everyone else who is not a well-educated, middle-aged professional, one can speculate in the absence of good, publicly available marketing data, that access might be a barrier. For public health delivery of nutrigenomics, and for uptake in developing countries, the ramification might be delayed or denied access. (36) How much barriers to access can be attributed to patents in the field would require subtle health economics research, and probably a great deal more public uptake of nutrigenomics to give the robust data needed to say anything conclusive about barriers to access.

That said, the privately held nutrigenomics companies discussed above are pursuing a strategy of leveraging the most value from their patented technologies. For example, Interleukin Genetics was well positioned in 2006 to purchase the Alan James Group, a healthcare consumer products company, because its major investor, Alticor, was able to backstop the $30 million (USD) transaction. (37) In a similar vein, Sciona Limited has been able to attract major venture capital -$21 million (USD)--from DSM Venturing (38) and BASF Venture Capital GmbH. (39) The patent portfolios of these companies is obviously of interest to their investors. Perhaps this trend will worry critics of genetic and biotechnology patents the most: by leveraging assets and adding value to their innovations, small-to-medium sized nutrigenomics companies deliberately tighten the connection between knowledge and economics. Patents are proxies for cash in this private system of exchange. No one should expect the fruits of the revolutions in nutritional sciences and human genetics to come for free, or even all that cheaply, but the translation of research that has its origins in public investments via private companies does raise questions about the impact of commercial interests on access to potentially valuable biotechnologies.

David Castle is Canada Research Chair in Science and Society, University of Ottawa. Contact: [e-mail]. Funding support is acknowledged from the Network of Centres of Excellence for Advanced Foods & Materials (www.afmnet.ca).

1. K.J. Carpenter, "A Short History of Nutritional Science: Part 1 (1785-1885)" (2003) 133 Journal of Nutrition 638; K.J. Carpenter, "A Short History of Nutritional Science: Part 2 (1885-1912)" (2003) 133 Journal of Nutrition 975; K.J. Carpenter, "A Short History of Nutritional Science: Part 3 (1912-1944)" (2003) 133 Journal of Nutrition 3023; and K.J. Carpenter, "A Short History of Nutritional Science: Part 4 (1945-1985)" (2003) 133 Journal of Nutrition 3331.

2. J. Craig Venter et al., "The Sequence of the Human Genome" (2001) 291 Science 1304; E.S. Lander et al., "Initial Sequencing and Analysis of the Human Genome" (2001) 409 Nature 860.

3. Peter J. Gillies, "Nutrigenomics: The Rubicon of Molecular Nutrition" (2003) 103S Journal of the American Dietetic Association S50. See also Jim Kaput & Raymond L. Rodriquez, "Nutritional Genomics: The Next Frontier in the Postgenomic Era" (2004) 16 Physiological Genomics 166.

4. Raymond Meleady et al., "Thermolabile Methylenetetrahydrofolate Reductase, Homocysteine, and Cardiovascular Disease Risk: The European Concerted Action Project" (2003) 77 American Journal of Clinical Nutrition 63. See also Pauline A.J. Ashfield-Watt et al., "Methylenetetrahydrofolate Reductase 677C[right arrow]T Genotype Modulates Homocysteine Responses to a Folate-Rich Diet or a Low-Dose Folic Acid Supplement: A Randomized Controlled Trial" (2002) 76 American Journal of Clinical Nutrition 180.

5. Rima Rozen & Philippe Goyette, "CDNA for human methylenetetrahydrofolate reductase" U.S. Patent 6,074,821, issued June 13, 2000.

6. Rima Rozen & Philippe Goyette, "Methods for detecting methylene tetrahydrofolate reductase allelic variants" U.S. Patent 6,218,120, issued, April 17, 2001.

7. Rima Rozen & Philippe Goyette, "Methods for detecting methylene tetrahydrofolate reductase allelic variants" U.S. Patent 6,528,259, issued March 4, 2003.

8. Roy A. Gravel et al., "Human methionine synthase reductase: cloning, and methods for evaluating risk of neural tube defects, cardiovascular disease, and cancer" U.S. Patent 7,045,612, issued May 16, 2006.

9. Interleukin Genetics, <http://www.ilgenetics.com/>.

10. Wellgen, <http://www.wellgen.com>.

11. Geetha Ghai et al., "Methods of screening foods for nutraceuticals" U.S. Patent 5,955,269, issued Sept. 21, 1999.

12. Kuang Yu Chen et al., "Black tea extract for prevention of disease" U.S. Patent 7,238,376, issued July 3, 2007.

13. Pamela K. Fink & Kenney S. Kornman, "Hierarchical biological modelling system and method" U.S. Patent 5,657,255, issued Aug. 12, 1997 and Pamela K. Fink & Kenney S. Kornman, "Hierarchical biological modelling system and method" U.S. Patent 5,808,918, issued Sept. 15, 1998.

14. Sciona Limited, <http://sciona.com>.

15. Rosalynn D. Gill-Garrison, Christopher J. Martin & Manuel V. Sanchez-Felix, "Computer-assisted means for assessing lifestyle risk factors" U.S. Patent 7,054,758, issued May 30, 2006.

16. Ibid.

17. Genetic Technologies Limited, <http://www.gtg.com.au>.

18. Genetic Technologies Limited, Genetic Technologies Patent List--June 2006 (2006), online: <http://www.gtg.com.au/imhome/attachment_stream.asp?ID=274&FootprintID=0&ProcessID=0>.

19. Dianne Nicol, "Balancing Innovation and Access to Healthcare through the Patent System: An Australian Perspective" (2005) 8 Community Genetics 228.

20. Genosense Diagnostics, <http://www.genosense.com/EN/Index.html>.

21. Jess Holiday, "Sciona gains license to explore Asian nutrigenomics potential" Nutralngredients.com (March 14 2007), online: Nutralngedients.com <http://www.nutraingredients.com/news/ng.asp?n=74962-sciona-gtg-personlised-nutrition-nutrigenomics>.

22. E.R. Gold et al., "The Unexamined Assumptions of Intellectual Property: Adopting an Evaluative Approach to Patenting Biotechnological Innovation" (2004) 18 Public Affairs Quarterly 299; E.R. Gold et al., "Needed: Models of Biotechnology Intellectual Property" (2002) 20 Trends in Biotechnology 327.

23. David Castle, ed., The Role of Intellectual Property Rights in Biotechnology Innovation (Gloucestershire, UK: Edward Elgar, forthcoming 2008).

24. F. Scott Kieff, "On the Comparative Institutional Economics of Intellectual Property in Biotechnology" in Castle, ed., supra note 22.

25. M.A. Heller & R.S. Eisenberg, "Can Patents Deter Innovation? The Anticommons in Biomedical Research" (1998) 280 Science 698. See also A.K. Rai & R. Eisenberg, "Bayh-Dole Reform and the Progress of Biomedicine" (2003) 66 Law & Contemp. Probs. 289.

26. F. Scott Kieff, "Facilitating Scientific Research: Intellectual Property Rights and the Norms of Science--A Response to Rai & Eisenberg" (1999) 95 Nw. U.L. Rev. 691. See also H.H. Ramirez, "Defending the Privatization of Research Tools: An Examination of the "Tragedy of the Anticommons" in Biotechnology Research and Development" (2004) 54 Emory L.J. 359; and M.S. Mireles, "An Examination of Patents, Licensing, Research Tools and the Tragedy of the Commons in Biotechology Innovation" (2004) 38 U. Mich. J.L. Ref. 141.

27. Lori Pressman et al., "The Licensing of DNA Patents by US Academic Institutions an Empirical Survey" (2006) 24 Nature Biotechnology 31.

28. Fiona Murray & Scott Stern, Do Formal Intellectual Property Rights Hinder the Free Flow of Scientific Knowledge? An Empirical Test of the Anti-Commons Hypothesis, NBER Working Paper 11465 (Cambridge, Mass.: National Bureau of Economic Research, 2005), online: National Bureau of Economic Research <http://www.nber.org/papers/w11465>.

29. Stephen M. Maurer, "New Institutions for Doing Science: From Databases to Open Source Biology" (Paper presented to the European Policy for Intellectual Property Conference on Copyright and Database Protection, Patents and Research Tools, and Other Challenges to the Intellectual Property System, University of Maastricht, The Netherlands, November 24-25 2003), online: <http://www.merit.unimaas.nl/epip/papers/maurer_paper.pdf>. See also Amy Kapczynski et al., "Addressing Global Health Inequities: An Open Licensing Approach for University Innovations" (2005) 20 Berkeley Tech. L.J. 1031.

30. P. Drahos & J. Braithwaite, Information Feudalism: Who Owns the Knowledge Economy? (New York: The New Press, 2002).

31. G. Dutfield, Intellectual Property Rights, Trade and Biodiversity (London: International Union for Conservation of Nature and Natural Resources, 2000).

32. B.E. Arnold & E. Ogielska-Zei, "Patenting Genes and Genetic Research Tools: Good or Bad for Innovation" (2002) 3 Annual Review of Genomics and Human Genetics 415.

33. A.L. Brewster, A.R. Chapman & S.A. Hansen, "Facilitating Humanitarian Access to Pharmaceutical and Agricultural Innovation" (2005) 1 Innovation Strategy Today 203.

34. T. Hubbard & J. Love, "Medicines Without Barriers" (2003) 2399 New Scientist 29.

35. Kyle Jensen & Fiona Murray, "Intellectual Property Landscape of the Human Genome" (2005) 310 Science 239.

36. David Castle et al., Science, Society and the Supermarket: The Opportunities and Challenges of Nutrigenomics (New Jersey: John Wiley & Sons, 2007).

37. "Interleukin Genetics Acquires Alan James Group and Secures $30 Million in New Financing" (17 August 2006), online: Interleukin Genetics <http://www.ilgenetics.com/content/about-interleukin/newsDetail.jsp/q/news-id/88>.

38. http://www.dsm.com/en_US/html/venturing/home.htm

39. http://www2.basf.de/en/venturecapital/?id=V00-YycGsBTRgbw2.iF