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BINF 705Research Ethics

Does the promise of new drug therapies justify exclusive proprietary access to

genetic information?

Intellectual Property

Ryosuke Kadoi John J. Kopecky

April 3, 2007

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Topics to be discussedIssue of DNA Patents

Background on patent law

Ethical issues related to DNA patents

History of Life-form patents

What has / is being patented

Property rights related to tissue samples, or “Who owns your body parts after they’re gone?”

Property rights to USG funded research, or “Haven’t I paid for this already?”

The Bird Flu Deal, orYou Don’t Get What You Deserve, You Get What You Negotiate”

Drug Company Advertising, or“Should Drug Ads be Tax Deductible”

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Intellectual PropertyIn law, intellectual property (IP) is an umbrella term for various legal entitlements which attach to certain names, written and recorded media, and inventions. The holders of these legal entitlements are generally entitled to exercise various exclusive rights in relation to the subject matter of the IP. The term intellectual property reflects the idea that this subject matter is the product of the mind or the intellect, though the term is a matter of some controversy.

Intellectual property laws and enforcement vary widely from jurisdiction to jurisdiction. There are inter-governmental efforts to harmonize them through international treaties such as the 1994 World Trade Organization (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPs), while other treaties may facilitate registration in more than one jurisdiction at a time. Enforcement of copyright, as well as disagreements over medical and software patents, have so far prevented the emergence of a cohesive international system.

http://en.wikipedia.org/wiki/Intellectual_property

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Grand Challenge I-5 Develop policy options that facilitate the widespread use of genome

information in both research and clinical settings

Realization of the opportunities provided by genomics depends on effective access to the information (such as data about genes, gene variants, haplotypes, protein structures, small molecules and computational models) by a wide range of potential users, including researchers, commercial enterprises, health-care providers, patients and the public. Researchers themselves need maximum access to the data as soon as possible (see 'Data release', below). Use of the information for the development of therapeutic and other products necessarily entails consideration of the complex issues of intellectual property (for example, patenting and licensing) and commercialization. The intellectual property practices, laws and regulations that affect genomics must adhere to the principle of maximizing public benefit, but must also be consistent with more general and longer-established intellectual property principles. Further, because genome research is global, international treaties, laws, regulations, practices, belief systems and cultures also come into play.

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Grand Challenge I-5 Develop policy options that facilitate the widespread use of genome

information in both research and clinical settings

Without commercialization, most diagnostic and therapeutic advances will not reach the clinical setting, where they can benefit patients. Thus, we need to develop policy options for data access and for patenting, licensing and other intellectual property issues to facilitate the dissemination of genomics data.

Francis S. Collins, Eric D. Green, Alan E. Guttmacher and Mark S. Guyer“A vision for the future of genomics research: A blueprint for the genomic era” Nature, Vol. 422, No. 6934, April 24, 2003, p. 835-847.http://www.nature.com/nature/journal/v422/n6934/full/nature01626.html

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Four Uses to Which DNA Sequences Can Be Put:

• Diagnostic Tests

• Research Tools

• Gene Therapy

• Therapeutic Proteins

The ethics of patenting DNA: A discussion paperNuffield Council on Bioethics2002

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To get a patent one needs to meet three legal requirements:

1. Novelty - meaning that the technology is not "anticipated" or identical to an invention disclosed in a single piece of prior art.

2. Non-Obviousness (Inventiveness) - meaning that the technology must be different enough from the prior art so as to not be obvious in view of the prior art.

3. Utility (Industrial Applicability) - meaning that the invention must have a useful purpose.

Under U.S. law, a patent must be applied for within one year of the first offer for sale, public use, or publication of the invention. Patent applications have become increasingly complex, so high-quality examination takes time. If an application seems to be borderline patentable, it is quicker for officers to grant it rather than to accumulate the necessary evidence that may justify rejection.

What are the criteria for granting a patent?

http://www.patentsearchexpress.com/patent-an-invention.htmlhttp://www.nature.com/news/2006/060501/full/060501-11.html

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What Rights Does a Patent Convey?

A patent grants the owner the right to exclude [for up to 20 years] others from making, using, offering to sell, selling or importing the invention into the U.S.   For example, if a patent owner discovers that an unauthorized individual is making and selling his or her patented invention, the owner may sue in an infringement case. 

In the event that you are granted a patent, you will need to fully disclose all the secrets of your invention.  Not only that, but all these secrets will be fully and freely available to the public.  Everyone and anyone will have access to your invention once it is patented. 

The advantage is that once your invention is patented, no one will be allowed to make, use, offer to sell, sell or import your invention into the U.S. other than you during your patent's term.  You will essentially be granted a monopoly on it.  You will control the production and sales of your invention, and therefore, you will make the profits

http://www.patentlawportal.com/information/patentbasics/what-are-the-rights-granted-by-a-patent.html

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What Rights Does a Patent Not Convey?

A patent does not give the patentee any right of ownership of the invention being patented: all a patent does is give the patentee the right to stop others commercially benefiting from the invention.

Therefore, a patent does not grant some right of ownership of the DNA which physically constitutes a gene; rather a patent merely arms the patentee with certain limited rights to stop others commercially benefiting from the invention

The BioIndustry Association The patenting of Genes - Factsheet

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1. The laws of nature, physical phenomena, and abstract ideas. 2. A new mineral or a new plant found in the wild. 3. Inventions intended solely for use in special nuclear material or atomic

energy for weapons. 4. A machine that does not serve a useful purpose. 5. Methods of doing business. 6. Printed matter. 7. In the case of mixtures of ingredients, such as medicines, a patent cannot

be granted unless the effect of the mixture is greater than the effect of its components.

8. Human beings. 9. Mere substitution of one material for another or changes in size to a

previously known useful invention without "novelty," or newness.

http://science.enotes.com/science-fact-finder/general-science-technology/what-cannot-patented

What Cannot Be Patented

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Some Ethical Concerns Raised Related to Patents of DNA Sequences

• Patents that assert rights over DNA sequences, in particular human DNA sequences, should not be allowed by virtue of the special status or nature of DNA;

• Patents that assert rights over DNA sequences should not be allowed because they do not meet the legal criteria for patenting;

• Patents that assert rights over DNA sequences should not be allowed by virtue of the possible deleterious consequences for healthcare and healthcare research.

The ethics of patenting DNA: A discussion paperNuffield Council on Bioethics2002

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Patenting Life

by Michael Crichton (2/13/07, The New York Times)

Gene patents are used to halt research, prevent medical testing and keep vital information from you and your doctor. A test for breast cancer that could be done for $1,000 now costs $3,000. The holder of the gene patent can charge whatever he wants, and does. Your breast cancer gene is now private property. The patent holder blocks any competitor’s test. He owns the gene and nobody else can test for it. The owner of the Hepatitis C genome is paid millions by researchers to study this disease. When SARS came out across the globe, scientists hesitated to study it due to patent concerns. Much of the pressure of liberalize European gene patenting laws has come from the US. The French president Jacques Chirac mentioned that gene patenting should NOT be permitted. For years we’ve been promised the coming era of personalized medicine but gene patents destroy that dream.

http://historical-debates.oireachtas.ie/D/0526/D.0526.200011160005.html

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Patent singles out Ashkenazi Jewish womenJuly 9, 2005

WOMEN in Europe who happen to be of Ashkenazi Jewish descent may want to keep that fact from their doctor when being tested for breast cancer genes.Myriad Genetics of Salt Lake City won a European patent on 1 July covering a specific mutation in the BRCA2 gene, which increases the risk of breast cancer. The mutation is found in 1 in 100 women of Ashkenazi Jewish descent. The ruling means that doctors offering tests for BRCA2 mutations are now legally obliged to ask women if they are Ashkenazi Jews. If they say they are, doctors must pay a license fee to Myriad. No fee is due if a patient says she does not know."We believe there is something fundamentally wrong if one ethnic group can be singled out by patenting," says Gert Matthijs of the Catholic University of Leuven (KUL) in Belgium, a member of the European Society of Human Genetics. “It means that someone is exploring the limits of what is acceptable legally and ethically.”But the society is delighted that two years of legal battles have so weakened Myriad's major European patents on BRCA1 and BRCA2 that no license fees have to be paid for breast cancer tests in Europe except those involving Ashkenazi Jewish women.

http://www.newscientist.com/channel/health/mg18725073.300-patent-singles-out-ashkenazi-jewish-women.html

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You Can’t Own a GeneEnclosing the Genome

What the Squabbles over Genetic Patents Could Teach Us by James Boyle (2003)

Because it would be against the tenets of my faith (The Sacred).

Because it would be immoral; some things should be outside of the property system; if they become commodified the market seeps into aspects of our lives that should be free from market logic (The Uncommodifiable).

To do so is to embrace a system in which nature, even our own nature, is to be manipulated, traded and commodified (The Environmental Ethic).

Because the genome belongs to all of us (The Common Heritage of Mankind).

You can’t own ‘this’ gene because I owned it first. My gene information is my property. You gene sequences came originally from a source and the source’s claims should be recognized, either instead of or as well as, the person seeking the patent (The Rights of Sources).

Because you can’t patent it; it doesn’t satisfy the basic requirements of the patent law and the constitution (Patentable Subject Matter).

If you did so, it would actually hurt research and innovation, the very things you are trying to encourage (Innovation Policy).

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Short History of Life-Form Patents

• Prior to 1980 several US cases upheld that “products of nature were non-patentable.

• 1980 Standford University received a “Process” patent issued for the use of plasmids for gene-splicing but not for the transformed bacteria.

• In 1980 the US Supreme Court, in Diamond v. Chakrabarty, held that genetically altered organisms could qualify as new “manufactured” or “compositions of matter”. And further that “the fact that micro-organisms are alive is without legal significance for purposes of the patent law." In this case the altered organism was an “oil-eating” microbe.

• 1984 Stanford received a “Product” patent on the transformed E. coli bacteria based on the the Chakrabarty decision which allowed the patenting of novel lifeforms.

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Short History of Life-Form Patents

• In 1987 the USPTO announced it would allow patents on non-human multicellular living organisms.

• In April 1988 U.S. Patent 4,736,866 was awarded to Harvard University for any non-human mammal transgenetically engineered to incorporate in its genome an oncogene. The first example was the Harvard Oncomouse. No U.S. courts were called on to decide the validity of the patent.

• Between 1987 and 1991 efforts were made by animal rights activists, and several religious groups to overturn the USPTOs policy. These efforts resulted in court cases, congressional hearings, but no legislation was passed and the USPTO policy remains in force.

• In 1992 European Patent EP 0169672 was issued to Harvard after a failed court challenge. In 1993 Further challenges resulted in limiting it to mice.

• In 2002 the Canadian Supreme Court rejected the patent application.

• As of 2002 17 countries allowed the patent.

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What Has Been Patented?

• SNPs: Have been patented.

• Gene Tests: These tests are usually patented and licensed by the owners of the disease gene patent.

• Proteins: Protein patents have been around for a century.

• Stem Cells: Patents for stem cells from monkeys and other organisms already have been issued. • Genes and Gene Fragments (ESTS): USPTO has issued patents for gene fragments. Patent applications for such gene fragments have sparked controversy among scientists, many of whom urged the USPTO not to grant broad patents in this early stage of human genome research to applicants who have neither characterized the genes nor determined their functions and uses. In 2001 USPTO issued new rules tightening the rules on these patents to require that the claimed utility be “specific, substantial, and credible”.

http://www.ornl.gov/sci/techresources/Human_Genome/elsi/patents.shtml#1

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USPTO Position on Gene PatentsUtility Examination Guidelines

DEPARTMENT OF COMMERCEUnited States Patent and Trademark Office

[Docket No. 991027289-0263-02]

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USPTO Position on Gene PatentsUtility Examination Guidelines

DEPARTMENT OF COMMERCEUnited States Patent and Trademark Office

[Docket No. 991027289-0263-02]

Arguments:1. A gene is not a new composition of matter because it exists in nature 2. Naturally occurring DNAs are part of our heritage and are not inventions 3. Concern that a person whose body includes a patented gene could be guilty of

patent infringementResponses:1. An excised gene is eligible for a patent as a composition of matter or as an

article of manufacture because that DNA molecule does not occur in that isolated form in nature,

2. Synthetic DNA preparations are eligible for patents because their purified state is different from the naturally occurring compound.

3. A patent on a gene covers the isolated and purified gene but does not cover the gene as it occurs in nature. The body does not contain the patented, isolated and purified gene because genes in the body are not in the patented, isolated and purified form. When the patent [was] issued for purified adrenaline about one hundred years ago, people did not infringe the patent merely because their bodies naturally included unpurified adrenaline.

http://www.mindfully.org/GE/Utility-Examination-Guidelines.htm

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Property Rights Related to Patents Derived From a Patient’s Genetic Material*

Rights of persons whose genetic material is used to develop a patentable invention.

In 1976 tissue from a patient was used as source material for a patent awarded to UCLA in 1984. The patient John Moore, sued for a share of the expected profits from exploiting the patent. In 1990 the California Supreme Court found that the patient had no property rights in the cells taken from his body, and further there were strong policy reasons for not awarding such rights since it might impede the free flow of biological material among researchers who might be concerned as to whether the donors were property holders.

In 1997 a patent was issued to the Miami Children’s Hospital on the gene that causes Canavan’s disease, a congenital neurological disorder that results in death during childhood. The parents of children with the disease who supported the research and donated their children’s tissue to allow the gene to be identified were appalled when the hospital began to seek royalties on the invention and sued the hospital based on its use of the children's blood and tissue, without consent, to secure a gene patent and develop a commercial test. They lost the case.

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Property Rights Related to Patents Derived from Genetic Material*

As a result of these and other cases patient groups are now pre-negotiating their rights to the tissues they donate by requiring researchers who want to use donated materials to agree to joint possession of any intellectual property that might result from the research, with the usual goal of making any tests or treatments based on the research accessible and affordable.

Thus while US law still does not give patients rights over their donated tissues individuals and groups of patients have stared negotiating such rights as a condition of their donation of research material.

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Property Rights From USG-Funded Research*

In 1963 President Kennedy issued a memorandum stating that the USG would hold patents that resulted from research that was federally funded.

However, there was belief that this resulted in government-owned inventions not being developed by the private sector since they might not be able to get an adaquate return on their investment.

Thus in 1980 the Bayh-Dole Act was passed which gave nonprofit organization contractors or grantees the right to retain patents from government funded research with some limitations on how the royalties could be applied, and the USG retained the right to require sublicensing based on health needs. In 1983 President Reagan expanded this to include nearly all contractors and grantees.

In 1980 the Stephenson-Wylder Act was passed which gave federal agencies the power to offer exclusive and non-exclusive licenses to private organizations to develop inventions made in federal labs.

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Property Rights From USG-Funded Research*

In 1986 this was amended to create Cooperative Research and Development Agreements (CRADAs) that allowed USG personnel and equipment to be co-mingled with private sector investment

In 1986 this was amended to create Cooperative Research and Development Agreements (CRADAs) that allowed USG personnel and equipment to be co-mingled with private sector investment, and allow the for the private sector participant to receive exclusive or non-exclusive licenses on inventions discovered by federal employees working under these agreements.

* Baruch BrodyIntellectual Property and Biotechnology:The U.S. Internal Experience—Part IKennedy Institute of Ethics Journal Vol. 16, No. 1, 1–37 © 2006

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Bird Flu Vaccine IssueGlaxoSmithKline (GSK), Britain’s largest drugs company, is in talks with the World Health Organisation (WHO) about a proposal for a subsidised mass vaccination programme against avian flu for developing countries, The Times has learnt.

Jean-Pierre Garnier, GSK’s chief executive, will meet Margaret Chan, the WHO’s director-general, on Friday to discuss proposals to provide low-cost vaccines against the H5N1 virus to countries such as Indonesia, which has suffered the highest number of deaths from avian flu so far.

The negotiations come after concern that poorer countries, particularly in the Far East, are likely to be at the forefront of any human outbreak of pandemic flu but could be unable to afford to buy the vaccines being developed by big Western drug companies.

In protest, Indonesia temporarily halted the supply of its bird flu strains to the WHO because it said that they were being used commercially to create products that the country could not afford.

http://business.timesonline.co.uk/tol/business/industry_sectors/health/article1599720.

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Drug Advertising: The Drug Companies’ Perspective

Advertising raises a product’s cost (to recoup the initial investment) but lowers the cost in the long run.

How one advertises drug products: a form of speech. Not what you say but how you say it.

The government already undermines market forces and thereby raises the cost of medicine w/ existing programs such as Medicare & Medicaid. New or expanded programs would only make things worse.

http://www.capmag.com/article.asp?ID=4902

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Table I. 2000 Direct-to-consumer spending with drugs ranked in terms of year 2000 spending adapted from NIH Report available at (http://www.nihcm.org/DTCbrief2001.pdf)

NIH Report on Drug Company Direct-to-Consumer (DTC) Advertising

Total for all drugs in 2000 was $2.25 Billion

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107th U.S. Congress: 2001-2002

H.R. 4821 [107th]: Fair Advertising and Increased Research (FAIR) Act

H. R. 4821 2D SESSION

To amend the Internal Revenue Code of 1986 to limit the deduction for advertising of FDA approved prescription drugs by the manufacturer of such drugs to the level of such manufacturer's research and development expenditures, and for other purposes.

The bill was referred to the House Committee on Ways and Means, and was never heard from again.

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ConclusionIndustrialized countries obtain patents on inventions based on genetic resources and traditional knowledge from the developing world, while the developing world is saddled with the cost of preserving biodiversity and yet deprived of the opportunity to share in its benefits. The term IP is a matter of some controversy since is a unique creation of the human mind and needs to be defined thoughtfully at each court in a given context. The definition changes from time to time and the arguments vary importantly depending on the subject matter of the patent. However, James Boyle stated that for a variety of reasons the embrace of the logic of enclosure to justify the expansion of IP across so many fields and so many dimensions was a probably mistake. a.) overestimates the applicability of the general logic of enclosure to the special case of intellectual material.b.) undervalues the importance of the public domain and the commons to intellectual production, thusc.) focusing only on the very real arguments in favor of private property while neglecting the role of the raw materials out of which future innovation is constructed.

The resulting policies also:d.) overestimate the potential threats and underestimates the potential benefits of the technologies of cheap copying to existing IP rights and e.) fail to take seriously enough the important potential for various types of distributed production, which require a rather different IP environment in order to flourish.

Boyle, James (2003), “Enclosing the Genome: What the Squabbles over Genetic Patents Could Teach Us.”

McManis, Charles R. (2002) “Intellectual Property, Genetic Resources and Traditional …”